記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/sj.onc.1207960

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1002/path.1282

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1097/00000478-200108000-00007

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1038/modpathol.3880180

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語  

DOI： 10.1111/cas.16409

PubMed

記述言語：英語   出版者・発行元：Journal of Experimental and Clinical Cancer Research  

Background: Tumor-associated neutrophils (TANs) constitute an abundant component among tumor-infiltrating immune cells and have recently emerged as a critical player in pancreatic ductal adenocarcinoma (PDAC) progression. This study aimed to elucidate the pro-tumor mechanisms of TAN and identify a novel target for effective immunotherapy against PDAC. Methods: Microarray and cytokine array analyses were performed to identify the mechanisms underlying the function of TANs. Human and mouse TANs were obtained from differentiated HL-60 cells and orthotopically transplanted PDAC tumors, respectively. The interactions of TANs with cancer and cytotoxic T-cells were evaluated through in vitro co-culture and in vivo orthotopic or subcutaneous models. Single-cell transcriptomes from patients with PDAC were analyzed to validate the cellular findings. Results: Increased neutrophil infiltration in the tumor microenvironment was associated with poor survival in patients with PDAC. TANs secreted abundant amounts of chemokine ligand 5 (CCL5), subsequently enhancing cancer cell migration and invasion. TANs subpopulations negatively correlated with cytotoxic CD8+ T-cell infiltration in PDAC and promoted T-cell dysfunction. TANs upregulated the membranous expression of Nectin2, which contributed to CD8+ T-cell exhaustion. Blocking Nectin2 improved CD8+ T-cell function and suppressed tumor progression in the mouse model. Single-cell analysis of human PDAC revealed two immunosuppressive TANs phenotypes: Nectin2+ TANs and OLR1+ TANs. Endoplasmic reticulum stress regulated the protumor activities in TANs. Conclusions: TANs enhance PDAC progression by secreting CCL5 and upregulating Nectin2. Targeting the immune checkpoint Nectin2 could represent a novel strategy to enhance immunotherapy efficacy in PDAC.

DOI： 10.1186/s13046-024-03178-6

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PubMed

記述言語：英語   出版者・発行元：npj Precision Oncology  

Prognosis after neoadjuvant chemotherapy (NAC) for osteosarcoma is generally predicted using manual necrosis-rate assessments; however, necrosis rates obtained in these assessments are not reproducible and do not adequately reflect individual cell responses. We aimed to investigate whether viable tumor cell density assessed using a deep-learning model (DLM) reflects the prognosis of osteosarcoma. Seventy-one patients were included in this study. Initially, the DLM was trained to detect viable tumor cells, following which it calculated their density. Patients were stratified into high and low-viable tumor cell density groups based on DLM measurements, and survival analysis was performed to evaluate disease-specific survival and metastasis-free survival (DSS and MFS). The high viable tumor cell density group exhibited worse DSS (p = 0.023) and MFS (p = 0.033). DLM-evaluated viable density showed correct stratification of prognosis groups. Therefore, this evaluation method may enable precise stratification of the prognosis in osteosarcoma patients treated with NAC.

DOI： 10.1038/s41698-024-00515-y

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PubMed

出版者・発行元：eBioMedicine  

Background: Emergence of SARS-CoV-2 variants that escape neutralising antibodies hampers the development of vaccines and therapeutic antibodies against SARS-CoV-2. IGHV3-53/3-66-derived public antibodies, which are generally specific to the prototype virus and are frequently induced in infected or vaccinated individuals, show minimal affinity maturation and high potency against prototype SARS-CoV-2. Methods: Monoclonal antibodies isolated from a Delta breakthrough infection case were analysed for cross-neutralising activities against SARS-CoV-2 variants. The broadly neutralising antibody K4-66 was further analysed in a hamster model, and the effect of somatic hypermutations was assessed using the inferred germline precursor. Findings: Antibodies derived from IGHV3-53/3-66 showed broader neutralising activity than antibodies derived from IGHV1-69 and other IGHV genes. IGHV3-53/3-66 antibodies neutralised the Delta variant better than the IGHV1-69 antibodies, suggesting that the IGHV3-53/3-66 antibodies were further maturated by Delta breakthrough infection. One IGHV3-53/3-66 antibody, K4-66, neutralised all Omicron subvariants tested, including EG.5.1, BA.2.86, and JN.1, and decreased the viral load in the lungs of hamsters infected with Omicron subvariant XBB.1.5. The importance of somatic hypermutations was demonstrated by the loss of neutralising activity of the inferred germline precursor of K4-66 against Beta and Omicron variants. Interpretation: Broadly neutralising IGHV3-53/3-66 antibodies have potential as a target for the development of effective vaccines and therapeutic antibodies against newly emerging SARS-CoV-2 variants. Funding: This work was supported by grants fromAMED (JP23ym0126048,JP22ym0126048,JP21ym0126048,JP23wm0125002,JP233fa627001,JP223fa627009,JP24jf0126002, andJP22fk0108572), and theJSPS (JP21H02970,JK23K20041, andJPJSCCA20240006).

DOI： 10.1016/j.ebiom.2024.105439

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記述言語：英語   出版者・発行元：Skeletal Radiology  

Low-grade central osteosarcoma (LGCOS), which arises from the intramedullary cavity of the metaphysis of long bones, occasionally exhibits extraosseous spread. Approximately 10–30% of patients with LGCOS exhibit dedifferentiation, but it is rare to experience a primary tumor with a dedifferentiated component. A 38-year-old female patient presented with right knee pain for two months. Imaging studies revealed a bone mass with extraosseous involvement. Wide resection was performed, and pathologic examination led to the diagnosis of LGCOS with a dedifferentiated extraosseous lesion. A single defect in the bone cortex constituted the boundary between the low- and high-grade components. The extraosseous high-grade component included more tumor cells with p53 overexpression and more murine double minute 2 (MDM2) copies compared with the low-grade component. These genetic mutations and copy number alterations can be associated with malignant transformation of LGCOS.

DOI： 10.1007/s00256-024-04647-x

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PubMed

出版者・発行元：Scientific Reports  

The ongoing vaccination efforts and exposure to endemic and emerging coronaviruses can shape the population's immunity against this group of viruses. In this study, we investigated neutralizing immunity against endemic and emerging coronaviruses in 200 Tanzanian frontline healthcare workers (HCWs). Despite low vaccination rates (19.5%), we found a high SARS-CoV-2 seroprevalence (94.0%), indicating high exposure in these HCWs. Next, we determined the neutralization capacity of antisera against human coronavirus NL63, and 229E, SARS-CoV-1, MERS-CoV and SARS-CoV-2 (including Omicron subvariants: BA.1, BQ.1.1 and XBB.1.5) using pseudovirus neutralization assay. We observed a broad range of neutralizing activity in HCWs, but no neutralization activity detected against MERS-CoV. We also observed a strong correlation between neutralizing antibody titers for SARS-CoV-2 and SARS-CoV-1, but not between other coronaviruses. Cross-neutralization titers against the newer Omicron subvariants, BQ.1.1 and XBB.1.5, was significantly reduced compared to BA.1 and BA.2 subvariants. On the other hand, the exposed vaccinated HCWs showed relatively higher median cross-neutralization titers against both the newer Omicron subvariants and SARS-CoV-1, but did not reach statistical significance. In summary, our findings suggest a broad range of neutralizing potency against coronaviruses in Tanzanian HCWs with detectable neutralizing immunity against SARS-CoV-1 resulting from SARS-CoV-2 exposure.

DOI： 10.1038/s41598-024-55989-4

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記述言語：英語   出版者・発行元：Scientific Reports  

PRAME (PReferentially expressed Antigen in MElanoma) was first identified as a malignant melanoma-specific antigen. Recently, a few cases of fibrosarcomatous dermatofibrosarcoma protuberans (FS-DFSP) were shown to have positivity for PRAME, while conventional dermatofibrosarcoma protuberans (C-DFSP) was negative. Because PRAME may be of diagnostic utility in FS-DFSP and is raising expectations as a new immunotherapy target, we examined the positivity of PRAME in FS-DFSP. Twenty-one cases of FS-DFSP and age/sex/location-matched cases of C-DFSP as a control group were examined by immunohistochemistry for CD34 and PRAME. The results were then evaluated by H-score, which was objectively and semi-quantitatively calculated using the open-source bioimaging analysis software QuPath. The results revealed that the PRAME H-score in FS-DFSP was significantly higher than that in C-DFSP (p = 0.0137). As for CD34, the H-score in FS-DFSP was significantly lower than that in C-DFSP (p < 0.001). Using these two immunohistochemical analyses in combination, the sensitivity and specificity for the diagnosis of FS-DFSP were 86% and 90%, respectively. Double staining of CD34 and PRAME revealed that PRAME-positive and CD34-positive areas did not overlap. This is the largest study to examine PRAME expression in FS-DFSP, and it confirmed the usefulness of PRAME in diagnosing this condition.

DOI： 10.1038/s41598-024-74556-5

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PubMed

記述言語：英語   出版者・発行元：Nature Communications  

Despite the success of immune checkpoint blockade (ICB) therapy for esophageal squamous cell cancer, the key immune cell populations that affect ICB efficacy remain unclear. Here, imaging mass cytometry of tumor tissues from ICB-treated patients identifies a distinct cell population of CD39+PD-1+CD8+ T cells, specifically the TCF1+ subset, precursor exhausted T (CD39+ Tpex) cells, which positively correlate with ICB benefit. CD39+ Tpex cells are predominantly in the stroma, while differentiated CD39+ exhausted T cells are abundantly and proximally within the parenchyma. Notably, CD39+ Tpex cells are concentrated within and around tertiary lymphoid structure (TLS). Accordingly, tumors harboring TLSs have more of these cells in tumor areas than tumors lacking TLSs, suggesting Tpex cell recruitment from TLSs to tumors. In addition, circulating CD39+ Tpex cells are also increased in responders following ICB therapy. Our findings show that this unique subpopulation of CD39+PD-1+CD8+ T cells is crucial for ICB benefit, and suggest a key role in TLS-mediated immune responses against tumors.

DOI： 10.1038/s41467-024-53262-w

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PubMed

記述言語：英語   出版者・発行元：Nature Communications  

Circulation of SARS-CoV-2 Omicron XBB has resulted in the emergence of XBB.1.5, a new Variant of Interest. Our phylogenetic analysis suggests that XBB.1.5 evolved from XBB.1 by acquiring the S486P spike (S) mutation, subsequent to the acquisition of a nonsense mutation in ORF8. Neutralization assays showed similar abilities of immune escape between XBB.1.5 and XBB.1. We determine the structural basis for the interaction between human ACE2 and the S protein of XBB.1.5, showing similar overall structures between the S proteins of XBB.1 and XBB.1.5. We provide the intrinsic pathogenicity of XBB.1 and XBB.1.5 in hamsters. Importantly, we find that the ORF8 nonsense mutation of XBB.1.5 resulted in impairment of MHC suppression. In vivo experiments using recombinant viruses reveal that the XBB.1.5 mutations are involved with reduced virulence of XBB.1.5. Together, our study identifies the two viral functions defined the difference between XBB.1 and XBB.1.5.

DOI： 10.1038/s41467-024-45274-3

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PubMed

記述言語：英語   出版者・発行元：Scientific Reports  

Extramammary Paget disease (EMPD) is a rare skin cancer that primarily affects older individuals predominantly in areas with apocrine sweat glands. Although most early EMPD lesions are indolent, patients with metastatic EMPD have a poor prognosis due to the lack of effective systemic treatment. In this study, we investigated the role of forkhead box M1 (FOXM1), a potent transcription factor, in EMPD and assessed the potential of FOXM1 as a therapeutic target. Immunohistochemistry of 112 primary and 17 metastatic EMPD samples revealed that FOXM1 expression increased with tumor progression. Patients in whom FOXM1 was expressed in more than 10% of tumor cells had significantly shorter disease-specific survival than the other patients (p = 0.0397). In in vitro studies using our newly established EMPD cell line, KS-EMPD-1, we found high expression of FOXM1. Knockdown of FOXM1 impaired tumor cell viability, migration, and invasion. Inhibition of FOXM1 using thiostrepton also reduced tumor cell viability in a dose-dependent manner. These findings suggest that FOXM1 is a promising therapeutic target for patients with EMPD.

DOI： 10.1038/s41598-024-54773-8

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PubMed

記述言語：英語   出版者・発行元：Journal of Experimental and Clinical Cancer Research  

Background: Although immune checkpoint blockade (ICB) therapy has proven to be extremely effective at managing certain cancers, its efficacy in treating pancreatic ductal adenocarcinoma (PDAC) has been limited. Therefore, enhancing the effect of ICB could improve the prognosis of PDAC. In this study, we focused on the histamine receptor H1 (HRH1) and investigated its impact on ICB therapy for PDAC. Methods: We assessed HRH1 expression in pancreatic cancer cell (PCC) specimens from PDAC patients through public data analysis and immunohistochemical (IHC) staining. The impact of HRH1 in PCCs was evaluated using HRH1 antagonists and small hairpin RNA (shRNA). Techniques including Western blot, flow cytometry, quantitative reverse transcription polymerase chain reaction (RT-PCR), and microarray analyses were performed to identify the relationships between HRH1 and major histocompatibility complex class I (MHC-I) expression in cancer cells. We combined HRH1 antagonism or knockdown with anti-programmed death receptor 1 (αPD-1) therapy in orthotopic models, employing IHC, immunofluorescence, and hematoxylin and eosin staining for assessment. Results: HRH1 expression in cancer cells was negatively correlated with HLA-ABC expression, CD8+ T cells, and cytotoxic CD8+ T cells. Our findings indicate that HRH1 blockade upregulates MHC-I expression in PCCs via cholesterol biosynthesis signaling. In the orthotopic model, the combined inhibition of HRH1 and αPD-1 blockade enhanced cytotoxic CD8+ T cell penetration and efficacy, overcoming resistance to ICB therapy. Conclusions: HRH1 plays an immunosuppressive role in cancer cells. Consequently, HRH1 intervention may be a promising method to amplify the responsiveness of PDAC to immunotherapy.

DOI： 10.1186/s13046-024-03060-5

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PubMed

記述言語：英語   出版者・発行元：Cardio-Oncology  

The advent of immune checkpoint inhibitors (ICIs) has significantly improved cancer treatment. With the increasing use of ICIs, ICI-related myocarditis has been recognized. However, an evidence-based therapeutic strategy has not been established because of the limited knowledge on ICI-related myocarditis. Here, we present four cases of ICI-related fulminant myocarditis (FM). Three of the four cases resulted in fatal outcomes despite aggressive treatment with mechanical circulatory support and immunosuppressive therapy with corticosteroids. Given the poor prognosis of ICI-FM, the establishment of rapid and adequate therapeutic interventions on the basis of clinical and pathological evaluation is imperative.

DOI： 10.1186/s40959-024-00288-0

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PubMed

記述言語：英語   出版者・発行元：Journal of Experimental and Clinical Cancer Research  

Background: Pancreatic ductal adenocarcinoma tumors exhibit resistance to chemotherapy, targeted therapies, and even immunotherapy. Dendritic cells use glucose to support their effector functions and play a key role in anti-tumor immunity by promoting cytotoxic CD8+ T cell activity. However, the effects of glucose and lactate levels on dendritic cells in pancreatic ductal adenocarcinoma are unclear. In this study, we aimed to clarify how glucose and lactate can impact the dendritic cell antigen-presenting function and elucidate the relevant mechanisms. Methods: Glycolytic activity and immune cell infiltration in pancreatic ductal adenocarcinoma were evaluated using patient-derived organoids and resected specimens. Cell lines with increased or decreased glycolysis were established from KPC mice. Flow cytometry and single-cell RNA sequencing were used to evaluate the impacts on the tumor microenvironment. The effects of glucose and lactate on the bone marrow-derived dendritic cell antigen-presenting function were detected by flow cytometry. Results: The pancreatic ductal adenocarcinoma tumor microenvironment exhibited low glucose and high lactate concentrations from varying levels of glycolytic activity in cancer cells. In mouse transplantation models, tumors with increased glycolysis showed enhanced myeloid-derived suppressor cell infiltration and reduced dendritic cell and CD8+ T cell infiltration, whereas tumors with decreased glycolysis displayed the opposite trends. In three-dimensional co-culture, increased glycolysis in cancer cells suppressed the antigen-presenting function of bone marrow-derived dendritic cells. In addition, low-glucose and high-lactate media inhibited the antigen-presenting and mitochondrial functions of bone marrow-derived dendritic cells. Conclusions: Our study demonstrates the impact of dynamic glycolytic reprogramming on the composition of immune cells in the tumor microenvironment of pancreatic ductal adenocarcinoma, especially on the antigen-presenting function of dendritic cells.

DOI： 10.1186/s13046-024-03192-8

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PubMed

記述言語：英語  

DOI： 10.1007/s10147-024-02666-1

PubMed

記述言語：英語  

DOI： 10.1093/jjco/hyae160

PubMed

記述言語：英語   出版者・発行元：Skeletal Radiology  

A glomus tumor is a benign mesenchymal tumor comprised of cells that resemble the perivascular modified smooth muscle cells of the glomus body. Glomus tumors typically appear in the superficial lesions of the soft tissue in the extremities, such as the subungual region. However, their occurrence in the bone is rare, with only about 30 cases reported to date. Half of these cases involved the distal phalanges of the fingers or toes, with only three reported cases involving the long bones. Here, we present the first case, a primary glomus tumor in the humerus of a 14-year-old female. An osteolytic and cystic lesion was detected after a pathological fracture occurred during exercise. Despite the tumor’s large size, no pathological findings indicated malignancy. The fracture healed through conservative treatment, while the tumor was effectively managed with curettage. Appropriate medical care can be provided to patients by focusing on pathological findings.

DOI： 10.1007/s00256-024-04604-8

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PubMed

記述言語：英語  

DOI： 10.1016/j.prp.2024.155642

PubMed

記述言語：英語  

DOI： 10.1186/s40792-024-02033-2

PubMed

出版者・発行元：mBio  

Due to the incessant emergence of various SARS-CoV-2 variants with enhanced fitness in the human population, controlling the COVID-19 pandemic has been challenging. Understanding how the virus enhances its fitness during a pandemic could offer valuable insights for more effective control of viral epidemics. In this manuscript, we review the evolution of SARS-CoV-2 from early 2022 to the end of 2023—from Omicron BA.2 to XBB descendants. Focusing on viral evolution during this period, we provide concrete examples that SARS-CoV-2 has increased its fitness by enhancing several functions of the spike (S) protein, including its binding affinity to the ACE2 receptor and its ability to evade humoral immunity. Furthermore, we explore how specific mutations modify these functions of the S protein through structural alterations. This review provides evolutionary, molecular, and structural insights into how SARS-CoV-2 has increased its fitness and repeatedly caused epidemic surges during the pandemic.

DOI： 10.1128/mbio.03220-23

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記述言語：英語   出版者・発行元：Experimental Dermatology  

Cutaneous squamous cell carcinoma (cSCC) is a common form of skin cancer, but treatments for advanced cases have limited efficacy. Trophoblast cell-surface antigen 2 (TROP2) is a cell-surface protein that is widely expressed in various tumours, where it exerts significant influence over critical processes such as tumour cell growth, apoptosis, migration, invasion and metastasis. Sacituzumab govitecan, an antibody-drug conjugate (ADC) targeting TROP2, is emerging as a promising strategy for anticancer therapy. In this study, we investigated TROP2 expression in cSCC tissues from 51 patients and evaluated its function in the A431 human SCC cell line. Immunohistochemical analysis revealed TROP2 expression on the plasma membrane of cSCC tissues and A431 cells. A431 cells showed sensitivity to sacituzumab govitecan with a significant concentration-dependent decrease in viable cell number. In addition, Knockdown of TROP2 resulted in decreased expression of cyclin D1 and BCL-2, along with reduced cell viability. Knockdown of TROP2 also resulted in decreased expression of vimentin, along with reduced migratory capacity. These findings suggest that TROP2 plays a crucial role in cSCC cell proliferation and migration, and highlight the potential of sacituzumab govitecan as a promising therapeutic option for cSCC.

DOI： 10.1111/exd.15196

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PubMed

記述言語：英語   出版者・発行元：Anticancer Research  

Background/Aim: The benefit of neoadjuvant chemotherapy (NAC) in the treatment of head and neck squamous cell carcinoma (HNSCC) remains unclear. Patients and Methods: We retrospectively collected 30 patients with HNSCC who had undergone radical resection after NAC. We pathologically evaluated the therapeutic response to NAC, and classified the residual tumor patterns. In addition, we compared the maximum horizontal diameter on pathology with imaging. Results: The residual patterns were categorized as follows: 10 cases of shrunken type, 11 cases of mixed type, and seven cases of fragmented type. The majority of underestimation cases – those cases in which the maximum horizontal diameter measured on post-NAC imaging was less than the pathological size after resection – were multifocal residual lesions, with a tendency for more frequent “positive” or “close” surgical margins. Conclusion: The strategy of performing NAC to reduce resection volume is not appropriate, and resection margins should be based on the assessment before NAC.

DOI： 10.21873/anticanres.17289

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PubMed

記述言語：英語   出版者・発行元：Neuropathology  

The hypothalamus is the region of the brain that integrates the neuroendocrine system and whole-body metabolism. Patients with Alzheimer's disease (AD) have been reported to exhibit pathological changes in the hypothalamus, such as neurofibrillary tangles (NFTs) and amyloid plaques (APs). However, few studies have investigated whether hypothalamic AD pathology is associated with clinical factors. We investigated the association between AD-related pathological changes in the hypothalamus and clinical pictures using autopsied brain samples obtained from deceased residents of a Japanese community. A total of 85 autopsied brain samples were semi-quantitatively analyzed for AD pathology, including NFTs and APs. Our histopathological studies showed that several hypothalamic nuclei, such as the tuberomammillary nucleus (TBM) and lateral hypothalamic area (LHA), are vulnerable to AD pathologies. NFTs are observed in various neuropathological states, including normal cognitive cases, whereas APs are predominantly observed in AD. Regarding the association between hypothalamic AD pathologies and clinical factors, the degree of APs in the TBM and LHA was associated with a lower body mass index while alive, after adjusting for sex and age at death. However, we found no significant association between hypothalamic AD pathology and the prevalence of hypertension, diabetes, or dyslipidemia. Our study showed that a lower BMI, which is a poor prognostic factor of AD, might be associated with hypothalamic AP pathology and highlighted new insights regarding the disruption of the brain–whole body axis in AD.

DOI： 10.1111/neup.12974

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記述言語：英語  

DOI： 10.1007/s13691-024-00713-2

PubMed

記述言語：英語  

DOI： 10.1186/s40792-024-02023-4

PubMed

記述言語：英語  

DOI： 10.1016/j.esmoop.2024.103726

PubMed

記述言語：英語  

DOI： 10.1158/0008-5472.CAN-24-0830

PubMed

記述言語：英語  

DOI： 10.1158/1078-0432.CCR-24-1004

PubMed

記述言語：英語   出版者・発行元：Annals of Surgical Oncology  

Background: Signal-regulatory protein alpha (SIRPα) is an immune checkpoint molecule expressed on macrophages that functions to inhibit phagocytosis by binding to CD47 expressed on tumor cells. SIRPα has attracted increasing attention as a novel target for cancer immunotherapy; however, the expression and immune function of SIRPα in lung squamous cell carcinoma (LUSC) remain unclear. Therefore, this study aimed to identify the clinical importance of SIRPα expression in LUSC and to explore the factors that elevate SIRPα expression. Patients and Methods: Primary LUSC specimens surgically resected from 172 patients underwent immunohistochemical evaluation of the association of SIRPα expression on tumor-associated macrophages with clinicopathological features and clinical outcomes. Furthermore, we analyzed the association of SIRPα expression with tumor-infiltrating lymphocytes and the expression of programmed cell death ligand 1 (PD-L1). In vitro, monocytes were treated with cytokines, and SIRPα protein expression was assessed by flow cytometry. Results: There were no differences in SIRPα expression and clinicopathological factors. High SIRPα expression was significantly associated with PD-L1-positive expression, and high CD8, PD-1, and CD163 expression. The high SIRPα expression group showed significantly shorter recurrence-free survival (RFS) and overall survival (OS). On multivariate analysis, high SIRPα expression was an independent poor prognostic factor for RFS and OS. The expression of SIRPα protein in monocytes was upregulated by treatment with IFNγ. Conclusion: Our analysis revealed that high SIRPα expression significantly predicts poor prognosis in patients with surgically resected LUSC.

DOI： 10.1245/s10434-024-15649-3

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PubMed

記述言語：英語   出版者・発行元：Microbiology and Immunology  

In middle to late 2023, a sublineage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron XBB, EG.5.1 (a progeny of XBB.1.9.2), is spreading rapidly around the world. We performed multiscale investigations, including phylogenetic analysis, epidemic dynamics modeling, infection experiments using pseudoviruses, clinical isolates, and recombinant viruses in cell cultures and experimental animals, and the use of human sera and antiviral compounds, to reveal the virological features of the newly emerging EG.5.1 variant. Our phylogenetic analysis and epidemic dynamics modeling suggested that two hallmark substitutions of EG.5.1, S:F456L and ORF9b:I5T are critical to its increased viral fitness. Experimental investigations on the growth kinetics, sensitivity to clinically available antivirals, fusogenicity, and pathogenicity of EG.5.1 suggested that the virological features of EG.5.1 are comparable to those of XBB.1.5. However, cryo-electron microscopy revealed structural differences between the spike proteins of EG.5.1 and XBB.1.5. We further assessed the impact of ORF9b:I5T on viral features, but it was almost negligible in our experimental setup. Our multiscale investigations provide knowledge for understanding the evolutionary traits of newly emerging pathogenic viruses, including EG.5.1, in the human population.

DOI： 10.1111/1348-0421.13165

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PubMed

記述言語：英語   出版者・発行元：一般社団法人 日本動脈硬化学会  

Aims: Vascular calcification is observed in advanced atherosclerotic lesions. Vascular calcification is considered to increase the risk of intraplaque hemorrhage and subsequent plaque destabilization; however, there is limited pathohistoological evidence of the association between vascular calcification and intraplaque hemorrhage. The aim of this study was to investigate the association between vascular calcification and intraplaque hemorrhage in the coronary arteries. Methods: We examined 374 coronary arteries obtained from the autopsy samples of 126 deceased individuals. The vascular calcification levels of each artery were categorized into no calcification and quintiles of calcification area size among the arteries with calcification. Macrophage infiltration and neovascularization were also evaluated. The association of the calcification area, macrophage area, or number of vessels with the presence of intraplaque hemorrhage in the coronary arteries was estimated using a logistic regression analysis.Results: Calcification lesions were observed in 149 coronary arteries. Arteries in the fourth quintile of calcification area size had a significantly greater likelihood of intraplaque hemorrhage than the arteries without calcification, after adjusting for confounders: odds ratio 13.13 (95% confidence interval: 2.97–58.16). After evaluating the influence of macrophage infiltration, the highest odds ratio of intraplaque hemorrhage was associated with the combination of large macrophage area and moderately sized calicification areas. The odds ratio of intraplaque hemorrhage additively increased with the combination of calcification and the number of vessels. Conclusions: The present findings suggest that vascular calcification is significantly associated with intraplaque hemorrhage. The association between vascular calcification and intraplaque hemorrhage may decrease above a certain size of the calcification area.

DOI： 10.5551/jat.64394

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CiNii Research

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.5551/jat.64394.

記述言語：英語   出版者・発行元：Laboratory Investigation  

Epithelioid sarcoma (ES) is a rare aggressive sarcoma that, unlike most soft-tissue sarcomas, shows a tendency toward local recurrence and lymph node metastasis. Novel antitumor agents are needed for ES patients. Forkhead box transcription factor 1 (FOXM1) is a member of the Forkhead transcription factor family and is associated with multiple oncogenic functions; FOXM1 is known to be overexpressed and correlated with pathogenesis in various malignancies. In this study, we immunohistochemically analyzed FOXM1 expression levels and their clinical, clinicopathologic, and prognostic significance in 38 ES specimens. In addition, to investigate potential correlations between FOXM1 downregulation and oncologic characteristics, we treated ES cell lines with thiostrepton, a naturally occurring antibiotic that inhibits both small interfering RNA (siRNA) and FOXM1. In the analyses using ES samples, all 38 specimens were diagnosed as positive for FOXM1 by immunohistochemistry. We separated specimens into high (n = 19) and low (n = 19) FOXM1–protein expression groups by staining index score, and into large (n = 12), small (n = 25), and unknown (n = 1) tumor-size groups using a cutoff of 5 cm maximum diameter. Although there were significantly more samples with high FOXM1 expression in the large tumor group (P = .013), there were no significant differences with respect to age (P = 1.00), gender (P = .51), primary site of origin (P = .74), histologic subtypes (P = 1.00), depth (P = .74), or survival rate (P = .288) between the high and low FOXM1–protein expression groups. In the in vitro experiments using ES cell lines, FOXM1 siRNA and thiostrepton successfully downregulated FOXM1 mRNA and protein expression. Furthermore, downregulation of FOXM1 inhibited cell proliferation, drug resistance against chemotherapeutic agents, migration, and invasion and caused cell cycle arrest in the ES cell lines. Finally, cDNA microarray analysis data showed that FOXM1 regulated cIAP2, which is one of the apoptosis inhibitors activated by the TNFα-mediated NF-κB pathway. In conclusion, the FOXM1 gene may be a promising therapeutic target for ES.

DOI： 10.1016/j.labinv.2024.102093

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PubMed

記述言語：英語   出版者・発行元：Virchows Archiv  

In papillary renal neoplasm with reverse polarity (PRNRP), the status of chromosomal copy number alterations, especially chromosomes 7/17 gain and chromosome Y loss, has remained controversial. In the literatures, there is a discrepancy among the results of chromosomal alteration in PRNRP depending on the analytical methods. Here, we comprehensively analyzed the status of chromosomal abnormalities in PRNRP. Nineteen PRNRP cases were analyzed by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), five of which were additionally subjected to array-based comparative genomic hybridization (aCGH) analysis. Fifteen cases of PRCC were used as controls. From the aCGH results, no genome copy number abnormalities were found in the five PRNRP cases. By FISH, numbers of nuclei with abnormal chromosomal signals in PRNRP (centromere 7 gain: 11–21% of nuclei, centromere 17 gain: 11% of nuclei, centromere Y loss: 14–31% of nuclei) were similar to those in non-neoplastic tubular cells (centromere 7 gain: 11–15% of nuclei, centromere 17 gain: 12–15% of nuclei, centromere Y loss: 13–45% of nuclei). c-MET immunohistochemical overexpression, a substitute marker for chromosome 7 trisomy, was observed in 0 of 19 PRNRP cases, consistent with the analyses by aCGH and NGS regarding chromosome 7 gain. Taken together, the frequency of chromosomal alterations in PRNRP is similar to that in non-neoplastic tubular cells, and lower than that in PRCC. Our data suggest that PRNRP has a different tumorigenesis and is a distinct entity from PRCC.

DOI： 10.1007/s00428-024-03840-6

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記述言語：英語   出版者・発行元：Clinical Journal of Gastroenterology  

Pancreatic acinar cell carcinoma (PACC) is a very rare subtype of pancreatic cancer. Due to small number of patients, no standard chemotherapy protocol has been established. We experienced an extremely rare case of PACC with liver metastasis that showed a pathological complete response after modified FOLFIRINOX (mFFX) therapy. A 42-year-old man who underwent distal pancreatectomy for an 80 mm tumor at the pancreatic tail 3 years ago was referred to our hospital in September 2017 for the treatment of a recurrent liver tumor. Percutaneous biopsy revealed an acinar-neuroendocrine carcinoma, similar to the surgical specimen. He received eight cycles of irinotecan plus cisplatin chemotherapy. However, the tumor increased in size, and treatment was switched to mFFX therapy. The tumor in the liver shrank remarkably after nine cycles of mFFX therapy. Conversion surgery was selected, and the patient underwent hepatic left and caudate lobectomy 8 months after administration of mFFX. The resected specimen showed no viable tumor cells, indicating a pathological complete response. The histological diagnosis was reconsidered, and PACC was finally diagnosed via an additional immunohistological review. The patient has remained well with no recurrence for 6 years after surgery. This study is the first to report a case of pathological complete response with mFFX therapy for the recurrence of PACC.

DOI： 10.1007/s12328-024-01983-2

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記述言語：英語   出版者・発行元：シュプリンガー・ジャパン(株)  

記述言語：英語  

DOI： 10.1093/jjco/hyae095

PubMed

記述言語：英語   出版者・発行元：Journal of Immunology  

Immune checkpoint blockade therapies are widely used for cancer treatment, including advanced renal cell carcinoma (RCC). This study aimed to investigate the impact of zygosity in HLA genes and individual HLA genotypes on the efficacy of an anti-PD-1 Ab, nivolumab, in treating advanced RCC. Patient enrollment was conducted across 23 institutions in Japan from August 19, 2019, to September 30, 2020, with follow-up concluding on March 31, 2021. HLA genotype imputation of HLA-A, B, and C, DQB1, and DRB1 loci was performed. Among 222 patients, the presence of at least one homozygosity of the HLA-II allele significantly improved the best objective response (hazard ratio, 0.34; 95% confidence interval, 0.21-0.96; p 5 0.042). The HLA evolutionary divergence (HED) of the HLA-A and HLA-B loci was higher than the HLA-C (p < 0.0001 and p < 0.0001, respectively), with high HED of the HLA-B locus correlating to clinical benefits in nivolumab treatment (hazard ratio, 0.44; 95% confidence interval, 0.21-0.90; p 5 0.024) and improving cancer-specific survival compared with the low group (p 5 0.0202). Additionally, high HED of the HLA-B locus was correlated with the number of infiltrated CD8+ cells in the tumor microenvironment (correlation coefficient, 0.4042). These findings indicate that the diversity of the HLA-B locus plays a significant role in the anti-tumor effect of nivolumab treatment in advanced RCC, potentially offering insights for improved risk stratification in nivolumab treatment and leading to better medical management of advanced RCC. The Journal of Immunology, 2024, 213: 23-28.

DOI： 10.4049/jimmunol.2300308

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PubMed

記述言語：英語   出版者・発行元：American Journal of Surgical Pathology  

Isolated hypoganglionosis (IHG) is histologically characterized by small numbers of myenteric ganglion cells and small myenteric ganglia; however, no numerical diagnostic criteria for IHG have been established. Therefore, this study aimed to develop quantitative pathologic criteria for IHG. We evaluated 160 resected intestinal tissue specimens from 29 pediatric autopsies and 10 IHG cases. These specimens were obtained from the jejunum, ileum, ascending colon, transverse colon, and rectum. Morphologic features of the myenteric ganglion cells and myenteric ganglia were quantified and analyzed in digitized HuC/HuD-immunostained and CD56-immunostained sections, respectively. Quantitative criteria were developed with a scoring system that used parameters with the area under the receiver operating characteristic curve (AUC) values > 0.7 and sensitivity and specificity exceeding 70%. The selected parameters were the number of myenteric ganglion cells per cm and the number of myenteric ganglia with an area > 2500 µm2per cm. The score for each parameter ranged from −1 to 2, and the total score of the scoring system ranged from −2 to 4. With a cutoff value of ≥ 2 (AUC, 0.98; 95% CI: 0.96-1.00), the scoring system had a sensitivity of 96% (95% CI: 0.82-1.00) and a specificity of 99% (95% CI: 0.95-1.00). We devised a novel pathologic criterion based on the quantification of the number of myenteric ganglion cells and ganglia. Furthermore, this criterion showed high diagnostic accuracy and could lead to a definitive diagnosis of IHG in clinical practice.

DOI： 10.1097/PAS.0000000000002243

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記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   出版者・発行元：Annals of Surgical Oncology  

Background: Glutathione peroxidase 2 (GPX2) is an antioxidant enzyme with an important role in tumor progression in various cancers. However, the clinical significance of GPX2 in lung adenocarcinoma has not been clarified. Methods: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to analyze GPX2 mRNA expression. Then, we conducted immunohistochemistry (IHC) to assess GPX2 expression in specimens acquired from 351 patients with lung adenocarcinoma who underwent surgery at Kyushu University from 2003 to 2012. We investigated the association between GPX2 expression and clinicopathological characteristics and further analyzed the prognostic relevance. Results: qRT-PCR revealed that GPX2 mRNA expression was notably higher in tumor cells than in normal tissues. IHC revealed that high GPX2 expression (n = 175, 49.9%) was significantly correlated with male sex, smoking, advanced pathological stage, and the presence of pleural, lymphatic, and vascular invasion. Patients with high GPX2 expression exhibited significantly shorter recurrence-free survival (RFS) and overall survival. Multivariate analysis identified high GPX2 expression as an independent prognostic factor of RFS. Conclusions: GPX2 expression was significantly associated with pathological malignancy. It is conceivable that high GPX2 expression reflects tumor malignancy. Therefore, high GPX2 expression is a significant prognostic factor of poor prognosis for completely resected lung adenocarcinoma.

DOI： 10.1245/s10434-024-15116-z

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記述言語：英語   出版者・発行元：Japanese Journal of Clinical Oncology  

Background: Soft tissue sarcoma (STS) has various histological types and is rare, making it difficult to evaluate the malignancy of each histological type. Thus, comprehensive histological grading is most important in the pathological examination of STS. The Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grading system is most commonly used in daily pathological analysis of STS. Among the FNCLCC grading system parameters, mitotic count is a key morphological parameter reflecting the proliferative activity of tumor cells, although its reproducibility may be lacking. Here, we compared the prognostic utility of the conventional and modified FNCLCC grading systems in JCOG1306. Methods: We analyzed 140 patients with non-small round cell sarcoma. We performed Ki-67 immunostaining using open biopsy specimens before preoperative chemotherapy in all patients. We assessed histological grade in individual cases by conventional FNCLCC grading (tumor differentiation, mitotic count, and necrosis) and modified FNCLCC grading using the Ki-67 labeling index instead of mitotic count. We conducted univariable and multivariable Cox regression analyses to investigate the influence of grade on overall survival. Results: In univariable analysis, prognosis was worse for patients with conventional FNCLCC Grade 3 tumors compared with Grade 1 or 2 tumors (hazard ratio [HR] 4.21, 95% confidence interval [CI] 1.47-12.05, P = 0.008). Moreover, prognosis was worse in patients with modified FNCLCC Grade 3 tumors compared with Grade 1 or 2 tumors (HR 4.90, 95% CI 1.64-14.65, P = 0.004). In multivariable analysis including both conventional and modified FNCLCC grading, the modified grading more strongly affected overall survival (HR 6.70, 95% CI 1.58-28.40, P = 0.010). Conclusions: The modified FNCLCC grading system was superior to the conventional system in predicting the prognosis of patients with non-small round cell sarcoma according to this supplementary analysis of data from the randomized controlled trial JCOG1306.

DOI： 10.1093/jjco/hyae020

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/his.15169.

記述言語：英語   出版者・発行元：Histopathology  

Aims: p16 is a sensitive surrogate marker for transcriptionally active high-risk human papillomavirus (HR-HPV) infection in endocervical adenocarcinoma (ECA); however, its specificity is not perfect. Methods and results: We examined p16 and Rb expressions by immunohistochemistry (IHC) and the transcriptionally active HR-HPV infection by mRNA in-situ hybridisation (ISH) with histological review in 108 ECA cases. Thirteen adenocarcinomas of endometrial or equivocal origin (six endometrioid and seven serous carcinomas) were compared as the control group. HR-HPV was detected in 83 of 108 ECA cases (77%), including five HPV-associated adenocarcinomas in situ and 78 invasive HPV-associated adenocarcinomas. All 83 HPV-positive cases showed consistent morphology, p16 positivity and partial loss pattern of Rb. Among the 25 cases of HPV-independent adenocarcinoma, four (16%) were positive for p16, and of these four cases, three of 14 (21%) were gastric type adenocarcinomas and one of 10 (10%) was a clear cell type adenocarcinoma. All 25 HPV-independent adenocarcinomas showed preserved expression of Rb irrespective of the p16 status. Similarly, all 13 cases of the control group were negative for HR-HPV with preserved expression of Rb, even though six of 13 (46%) cases were positive for p16. Compared with p16 alone, the combination of p16 overexpression and Rb partial loss pattern showed equally excellent sensitivity (each 100%) and improved specificity (100 versus 73.6%) and positive predictive values (100 versus 89.2%) in the ECA and control groups. Furthermore, HR-HPV infection correlated with better prognosis among invasive ECAs. Conclusions: The results suggest that the combined use of p16 and Rb IHC could be a reliable method to predict HR-HPV infection in primary ECAs and mimics. This finding may contribute to prognostic prediction and therapeutic strategy.

DOI： 10.1111/his.15169

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記述言語：英語   出版者・発行元：Pathology Research and Practice  

Hepatoblastoma (HB) is the most common malignant liver tumor in childhood. Although pre-operative cisplatin (CDDP)-based chemotherapy is often used in cases of HB, about 20％ of HB patients exhibit resistance to CDDP. Forkhead box protein M1 (FOXM1) and chromo-domain-helicase-DNA-binding protein 4 (CHD4) have been associated with CDDP resistance in various tumors. We here analyzed the immunohistochemical expression of FOXM1 and CHD4 in HB specimens of 33 patients (mean age: 20 months) post-chemotherapy. The differentiation of specimens was assessed using the digital pathology software QuPath®, and then the relation between the FOXM1 or CHD4 expression and the differentiation and various other clinicopathological parameters was investigated. The histological type was epithelial in 19 cases (57.6%) and mixed epithelial and mesenchymal in 14 cases (42.4%). Nine cases had only a fetal component, 1 case had only an embryonal component, 22 cases had both fetal and embryonal components, and 1 case had no viable tumor. Both the FOXM1 and CHD4 immunoexpressions were found significantly more frequently in the embryonal than fetal components (p<0.0001 and p<0.0001, respectively). Regarding chemotherapy efficacy, the alpha-fetoprotein (AFP) level after chemotherapy was correlated with both the imaging shrinkage rate (R=-0.52) and histological residual rate (the percentage of the viable tumors of HB after chemotherapy)(R=0.62). High FOXM1 score was correlated with a high-postoperative AFP value (p<0.01) and a low AFP attenuation rate (p<0.05), but the FOXM1 score was not correlated with the imaging shrinkage rate (p=0.4418) or histological residual rate (p=0.4418). High CHD4 score showed a nonsignificant trend toward correlation with high postoperative AFP value (p=0.0849) and was not significantly correlated with the other parameters. Collectively, our results showed that FOXM1 expression may be useful in evaluating the response to CDDP-based chemotherapeutic regimens. Accurate measurement of FOXM1 expression by our scoring system using QuPath® is important in cases with mixed HB components of various differentiation levels.

DOI： 10.1016/j.prp.2024.155348

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記述言語：英語   出版者・発行元：Cancer Letters  

Familial adenomatous polyposis (FAP) is a heritable disease that increases the risk of colorectal cancer (CRC) development because of heterozygous mutations in APC. Little is known about the microenvironment of FAP. Here, single-cell RNA sequencing was performed on matched normal tissues, adenomas, and carcinomas from four patients with FAP. We analyzed the transcriptomes of 56,225 unsorted single cells, revealing the heterogeneity of each cell type, and compared gene expression among tissues. Then we compared the gene expression with that of sporadic CRC. Furthermore, we analyzed specimens of 26 FAP patients and 40 sporadic CRC patients by immunohistochemistry. Immunosuppressiveness of myeloid cells, fibroblasts, and regulatory T cells was upregulated even in the early stages of carcinogenesis. CD8+ T cells became exhausted only in carcinoma, although the cytotoxicity of CD8+ T cells was gradually increased according to the carcinogenic step. When compared with those in the sporadic CRC microenvironment, the composition and function of each cell type in the FAP-derived CRC microenvironment had differences. Our findings indicate that an immunosuppressive microenvironment is constructed from a precancerous stage in FAP.

DOI： 10.1016/j.canlet.2024.216822

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s10120-024-01474-w

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1186/s13046-024-03060-5.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.molmet.2024.101954

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s00535-024-02104-z

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s00535-024-02088-w

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.ebiom.2024.105102

記述言語：英語   出版者・発行元：Oncology Letters  

Ovarian high-grade serous carcinoma (OHGSC) is the most common type of ovarian cancer worldwide. Genome sequencing has identified mutations in chromatin remodeling factors (CRFs) in gynecological cancer, such as clear cell carcinoma, endometrioid carcinoma and endometrial serous carcinoma. However, to the best of our knowledge, the asso- ciation between CRFs and OHGSC remains unexplored. The present study aimed to investigate the clinicopathological and molecular characteristics of CRF dysfunction in OHGSC. CRF alterations were analyzed through numerous methods, including the analysis of public next-generation sequencing (NGS) data from 585 ovarian serous carcinoma cases from The Cancer Genome Atlas (TCGA), immunohistochemistry (IHC), and DNA copy number assays, which were performed on 203 surgically resected OHGSC samples. In the public NGS dataset, the most frequent genetic alteration was actin-like protein 6A (ACTL6A) amplification at 19.5%. Switch/sucrose non-fermentable related, matrix associated, actin dependent regulator of chromatin subfamily c member 2 (SMARCC2) amplification (3.1%) was associated with significantly decreased overall survival (OS). In addition, chromodo- main-helicase-DNA-binding protein 4 (CHD4) amplification (5.7%) exhibited unfavorable outcome trends, although not statistically significant. IHC revealed the protein expression loss of ARID1A (2.5%), SMARCA2 (2.5%) and SMARCA4 (3.9%). The protein expression levels of ACTL6A, SMARCC2 and CHD4 were evaluated using H-score. Patients with low protein expression levels of ACTL6A showed a significantly decreased OS. Copy number gain or gene amplification was demonstrated in ACTL6A (66.2%) and SMARCC2 (33.5%), while shallow deletion or deep deletion was demonstrated in CHD4 (70.7%). However, there was no statistically significant difference in protein levels of these CRFs, between the different copy number alterations (CNAs). Overall, OHGSC exhibited CNAs and protein loss, indicating possible gene alterations in CRFs. Moreover, there was a significant association between the protein expression levels of ACTL6A and poor prognosis. Based on these findings, it is suggested that CRFs could serve as prognostic markers for OHGSC.

DOI： 10.3892/ol.2024.14329

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記述言語：英語   出版者・発行元：eBioMedicine  

Background: The human adrenal cortex consists of three functionally and structurally distinct layers; zona glomerulosa, zona fasciculata (zF), and zona reticularis (zR), and produces adrenal steroid hormones in a layer-specific manner; aldosterone, cortisol, and adrenal androgens, respectively. Cortisol-producing adenomas (CPAs) occur mostly as a result of somatic mutations associated with the protein kinase A pathway. However, how CPAs develop after adrenocortical cells acquire genetic mutations, remains poorly understood. Methods: We conducted integrated approaches combining the detailed histopathologic studies with genetic, RNA-sequencing, and spatially resolved transcriptome (SRT) analyses for the adrenal cortices adjacent to human adrenocortical tumours. Findings: Histopathological analysis revealed an adrenocortical nodular structure that exhibits the two-layered zF- and zR-like structure. The nodular structures harbour GNAS somatic mutations, known as a driver mutation of CPAs, and confer cell proliferative and autonomous steroidogenic capacities, which we termed steroids-producing nodules (SPNs). RNA-sequencing coupled with SRT analysis suggests that the expansion of the zF-like structure contributes to the formation of CPAs, whereas the zR-like structure is characterised by a macrophage-mediated immune response. Interpretation: We postulate that CPAs arise from a precursor lesion, SPNs, where two distinct cell populations might contribute differently to adrenocortical tumorigenesis. Our data also provide clues to the molecular mechanisms underlying the layered structures of human adrenocortical tissues. Funding: KAKENHI, The Uehara Memorial Foundation, Daiwa Securities Health Foundation, Kaibara Morikazu Medical Science Promotion Foundation, Secom Science and Technology Foundation, ONO Medical Research Foundation, and Japan Foundation for Applied Enzymology.

DOI： 10.1016/j.ebiom.2024.105087

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記述言語：英語   出版者・発行元：Journal of Gastroenterology  

Background: Achalasia is an esophageal motility disorder with an unknown etiology. We aimed to determine the pathogenesis of achalasia by studying alterations in esophageal smooth muscle contraction and the associated inflammatory response, and evaluate the role of esophageal microbiota in achalasia development. Methods: We analyzed esophageal mucosa and lower esophageal sphincter (LES) samples, obtained from patients with type II achalasia who underwent peroral endoscopic myotomy. Esophageal conditioned media obtained from patients were transferred into the mouse esophagus to determine whether the esophageal intraluminal environment is associated with achalasia. Results: Approximately 30% of 20-kDa myosin light chains (LC20) was phosphorylated in LES from the control group under resting and stimulated conditions, whereas less than 10% of LC20 phosphorylation was detected in achalasia under all conditions. The hypophosphorylation of LC20 in achalasia was associated with the downregulation of the myosin phosphatase-inhibitor protein CPI-17. Th17-related cytokines, including IL-17A, IL-17F, IL-22, and IL-23A, were significantly upregulated in achalasia. α-Diversity index of esophageal microbiota and the proportion of several microbes, including Actinomyces and Dialister, increased in achalasia. Actinomyces levels positively correlated with IL-23A levels, whereas Dialister levels were positively associated with IL-17A, IL-17F, and IL-22 levels. Esophageal IL-17F levels increased in mice after oral administration of the conditioned media. Conclusions: In LES of patients with achalasia, hypophosphorylation of LC20, a possible cause of impaired contractility, was associated with CPI-17 downregulation and an increased Th17-related immune response. The esophageal intraluminal environment, represented by the esophageal microbiota, could be associated with the development and exacerbation of achalasia.

DOI： 10.1007/s00535-024-02088-w

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記述言語：英語   出版者・発行元：Thoracic Cancer  

Tracheomediastinal fistula is a rare but life-threatening complication of cancer. We report a case of tracheomediastinal fistula induced by concurrent chemoradiotherapy in limited stage small cell lung cancer. Despite the treatment response, the metastatic paratracheal lymph node increased gradually during concurrent chemoradiotherapy, resulting in the occurrence of tracheomediastinal fistula and mediastinitis. Without any surgical intervention, the patient achieved successful recovery from mediastinitis through antibiotic treatment, although the tracheomediastinal fistula remained open. In this report, we also review previous studies of tracheomediastinal and bronchomediastinal fistulas and summarize the clinical features.

DOI： 10.1111/1759-7714.15270

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記述言語：英語   出版者・発行元：Gastric Cancer  

Background: In gastric solid-type poorly differentiated adenocarcinoma (PDA), the role of microsatellite instability and immune escape mechanism remains unclear. The current study aimed to elucidate the clinical significance of mismatch repair (MMR) status, genome profile, C-X-C motif chemokine receptor 2 (CXCR2) expression, and myeloid-derived suppressor cell (MDSC) infiltration in solid-type PDA. Methods: In total, 102 primary solid-type PDA cases were retrieved, and classified into 46 deficient-MMR (dMMR) and 56 proficient-MMR (pMMR) cases based on immunohistochemistry (IHC) and polymerase chain reaction-based molecular testing results. The mRNA expression profiles (NanoString nCounter Assay) of stage-matched dMMR (n = 6) and pMMR (n = 6) cases were examined. The CXCR2 expression and MDSC infiltration (CD11b- and CD33-positive cells) were investigated via IHC in all solid-type PDA cases. Results: mRNA analysis revealed several differentially expressed genes and differences in biological behavior between the dMMR (n = 46) and pMMR (n = 56) groups. In the multivariate analysis, the dMMR status was significantly associated with a longer disease-free survival (hazard ratio = 5.152, p = 0.002) and overall survival (OS) (hazard ratio = 5.050, p = 0.005). CXCR2-high expression was significantly correlated with a shorter OS in the dMMR group (p = 0.018). A high infiltration of CD11b- and CD33-positive cells was significantly correlated with a shorter OS in the pMMR group (p = 0.022, 0.016, respectively). Conclusions: dMMR status can be a useful prognostic predictor, and CXCR2 and MDSCs can be novel therapeutic targets in patients with solid-type PDA.

DOI： 10.1007/s10120-024-01474-w

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記述言語：英語   出版者・発行元：British Journal of Cancer  

Background: Leiomyosarcomas are among the most common histological types of soft tissue sarcoma (STS), with no effective treatment available for advanced patients. Lung metastasis, the most common site of distant metastasis, is the primary prognostic factor. We analysed the immune environment targeting lung metastasis of STS to explore new targets for immunotherapy. Methods: We analysed the immune environment of primary and lung metastases in 38 patients with STS using immunohistochemistry. Next, we performed gene expression analyses on primary and lung metastatic tissues from six patients with leiomyosarcoma. Using human leiomyosarcoma cell lines, the effects of the identified genes on immune cells were assessed in vitro. Results: Immunohistochemistry showed a significant decrease in CD8+ cells in the lung metastases of leiomyosarcoma. Among the genes upregulated in lung metastases, epithelial cellular adhesion molecule (EPCAM) showed the strongest negative correlation with the number of CD8+ cells. Transwell assay results showed that the migration of CD8+ T cells was significantly increased in the conditioned media obtained after inhibition or knock down of EPCAM. Conclusions: EPCAM was upregulated in lung metastases of leiomyosarcoma, suggesting inhibition of CD8+ T cell migration. Our findings suggest that EPCAM could serve as a potential novel therapeutic target for leiomyosarcoma.

DOI： 10.1038/s41416-024-02576-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1038/s41416-024-02576-z.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/neup.12974.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/liv.15839.

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Journal of Gastroenterology  

Background: Recently, two molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) have been proposed: the “Classical” and “Basal-like” subtypes, with the former showing better clinical outcomes than the latter. However, the “molecular” classification has not been applied in real-world clinical practice. This study aimed to establish patient-derived organoids (PDOs) for PDAC and evaluate their application in subtype classification and clinical outcome prediction. Methods: We utilized tumor samples acquired through endoscopic ultrasound-guided fine-needle biopsy and established a PDO library for subsequent use in morphological assessments, RNA-seq analyses, and in vitro drug response assays. We also conducted a prospective clinical study to evaluate whether analysis using PDOs can predict treatment response and prognosis. Results: PDOs of PDAC were established at a high efficiency (> 70%) with at least 100,000 live cells. Morphologically, PDOs were classified as gland-like structures (GL type) and densely proliferating inside (DP type) less than 2 weeks after tissue sampling. RNA-seq analysis revealed that the “morphological” subtype (GL vs. DP) corresponded to the “molecular” subtype (“Classical” vs. “Basal-like”). The “morphological” classification predicted the clinical treatment response and prognosis; the median overall survival of patients with GL type was significantly longer than that with DP type (P < 0.005). The GL type showed a better response to gemcitabine than the DP type in vitro, whereas the drug response of the DP type was improved by the combination of ERK inhibitor and chloroquine. Conclusions: PDAC PDOs help in subtype determination and clinical outcome prediction, thereby facilitating the bench-to-bedside precision medicine for PDAC.

DOI： 10.1007/s00535-024-02103-0

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記述言語：英語   出版者・発行元：International Journal of Urology  

Objectives: Excellent anticancer effect for solid tumors with microsatellite instability (MSI)-high by anti-PD-1 antibody has been reported. In this study, we investigated the clinical impact of MSI status in bladder cancer. Methods: This study included 205 Japanese patients who underwent transurethral resection for bladder cancer between 2005 and 2021. The prevalence rates of microsatellite stable (MSS), MSI-low (MSI-L), and MSI-high (MSI-H) were determined using molecular testing. We examined the association of MSI status (MSS versus MSI-L/H) with clinicopathological characteristics and oncological outcomes. Results: MSI-L/H tumors were associated with higher T-category in non-muscle invasive bladder cancer (NMIBC). Additionally, MSI-L/H tumors were associated with a higher risk of intravesical recurrence in NMIBC patients treated with intravesical bacillus Calmette-Guérin (BCG) but not with non-BCG therapy. Conclusions: This study suggested that the MSI status might serve as a predictive marker for intravesical recurrence after BCG intravesical therapy in NMIBC and highlighted an unmet need for an alternative treatment in patients with MSI-L/H tumors.

DOI： 10.1111/iju.15370

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記述言語：英語   出版者・発行元：Liver International  

Background & Aims: Recently, the association between hepatocellular carcinoma (HCC) and ferroptosis has been the focus of much attention. The expression of long chain fatty acyl-CoA ligase 4 (ACSL4), a marker of ferroptosis, in tumour tissue is related to better prognosis in various cancers. In HCC, ACSL4 expression indicates poor prognosis and is related to high malignancy. However, the mechanism remains to be fully understood. Methods: We retrospectively enrolled 358 patients with HCC who had undergone hepatic resection. Immunohistochemistry (IHC) for ACSL4 was performed. Factors associated with ASCL4 expression were investigated by spatial transcriptome analysis, and the relationships were investigated by IHC. The association between ACSL4 and the tumour immune microenvironment was examined in a public dataset and investigated by IHC. Results: Patients were divided into ACSL4-positive (n = 72, 20.1%) and ACSL4-negative (n = 286, 79.9%) groups. ACSL4 positivity was significantly correlated with higher α-fetoprotein (p =.0180) and more histological liver fibrosis (p =.0014). In multivariate analysis, ACSL4 positivity was an independent prognostic factor (p <.0001). Spatial transcriptome analysis showed a positive correlation between ACSL4 and cancer-associated fibroblasts; this relationship was confirmed by IHC. Evaluation of a public dataset showed the correlation between ACSL4 and exhausted tumour immune microenvironment; this relationship was also confirmed by IHC. Conclusion: ACSL4 is a prognostic factor in HCC patients and its expression was associated with cancer-associated fibroblasts and anti-tumour immunity.

DOI： 10.1111/liv.15839

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PubMed

記述言語：英語   出版者・発行元：DEN Open  

Background: Pancreatic ductal adenocarcinoma (PDAC) has a high mortality rate owing to its late diagnosis and aggression. In addition, there are relatively few minimally invasive screening methods for the early detection of PDAC, making the identification of biomarkers for this disease a critical priority. Recent studies have reported that microRNAs in extracellular vesicles (EV-miRs) from bodily fluids can be useful for the diagnosis of PDACs. Given this, we designed this study to evaluate the utility of cancer EVs extracted from duodenal fluid (DF) and their resident EV-miRs as potential biomarkers for the detection of PDAC. Methods: EV-miRs were evaluated and identified in the supernatants of various pancreatic cancer cell lines (Panc-1, SUIT2, and MIAPaca2), human pancreatic duct epithelial cells, and the DF from patients with PDAC and healthy controls. EVs were extracted using ultracentrifugation and the relative expression of EV-miR-20a was quantified. Results: We collected a total of 34 DF samples (27 PDAC patients and seven controls) for evaluation and our data suggest that the relative expression levels of EV-miR-20a were significantly higher in patients with PDAC than in controls (p = 0.0025). In addition, EV-miR-20a expression could discriminate PDAC from control patients regardless of the location of the tumor with an area under the curve values of 0.88 and 0.88, respectively. Conclusions: We confirmed the presence of EVs in the DF and suggest that the expression of EV-miR-20a in these samples may act as a potential diagnostic biomarker for PDAC.

DOI： 10.1002/deo2.333

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記述言語：英語   出版者・発行元：Clinical Journal of Gastroenterology  

Pancreatic neuroendocrine tumors (PanNETs) are rare malignant tumors that occur in the pancreas. They are divided into functioning and non-functioning tumors based on the presence or absence of their specific hormonal hyper-expression symptoms. Adrenocorticotropic hormone (ACTH)-producing PanNETs are rare, functional tumors, and their clinical characteristics and outcomes have not been well reported. Here, we report the cases of two patients with PanNETs who presented with ectopic ACTH syndrome (EAS) during the course of their disease. Case 1 involved a non-functioning PanNET at the time of surgery. During treatment for recurrent liver metastases, the patient presented with EAS and tumor-associated hypercalcemia, probably due to ACTH and parathyroid hormone-related peptide (PTHrP) production from the liver tumor. Case 2 was a gastrinoma, and similar to Case 1, this patient presented with EAS during the treatment of recurrent liver metastases. It is not uncommon for patients with PanNETs to have multiple hormones and develop secondary hormone secretion during their disease course, although tumor phenotypes differ between primary and metastatic sites. In patients with functioning PanNETs, symptom control with anti-hormonal therapy is essential, in addition to anti-tumor therapy, especially for EAS, which is an endocrine emergency disease that requires prompt diagnosis and treatment.

DOI： 10.1007/s12328-023-01908-5

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記述言語：英語  

DOI： 10.1007/s13691-024-00659-5

PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/cas.16060.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1016/j.humpath.2024.02.007.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1245/s10434-024-15116-z

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.ebiom.2024.105087.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s00428-024-03796-7.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s10120-023-01456-4.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1002/deo2.333.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s00234-024-03288-0.

記述言語：英語   出版者・発行元：International Journal of Molecular Sciences  

Severe obesity in young children prompts for a differential diagnosis that includes syndromic conditions. Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) syndrome is a potentially fatal disorder characterized by rapid-onset obesity associated with hypoventilation, neural crest tumors, and endocrine and behavioral abnormalities. The etiology of ROHHAD syndrome remains to be established, but recent research has been focusing on autoimmunity. We report on a 2-year-old girl with rapid-onset obesity during the first year of life who progressed to hypoventilation and encephalitis in less than four months since the start of accelerated weight gain. The patient had a high titer of anti-ZSCAN1 antibodies (348; reference range < 40), and the increased values did not decline after acute phase treatment. Other encephalitis-related antibodies, such as the anti-NDMA antibody, were not detected. The rapid progression from obesity onset to central hypoventilation with encephalitis warns about the severe consequences of early-onset ROHHAD syndrome. These data indicate that serial measurements of anti-ZSCAN1 antibodies might be useful for the diagnosis and estimation of disease severity. Further research is needed to determine whether it can predict the clinical course of ROHHAD syndrome and whether there is any difference in antibody production between patients with and without tumors.

DOI： 10.3390/ijms25052820

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記述言語：英語   出版者・発行元：Cancer Science  

Preoperative treatment is commonly carried out for borderline resectable pancreatic ductal adenocarcinoma (PDAC). However, the relationship between the combination of immune cells in the tumor microenvironment and their intratumoral heterogeneity along with their association with histological findings remains unclear, especially in patients receiving preoperative chemotherapy. We aimed to explore the therapeutic strategies for patients with PDAC with poor prognosis after receiving chemotherapy based on histological and immunological microenvironmental classifications. We investigated the correlation between the prognosis and histological immune microenvironmental factors of patients who initially underwent surgery (n = 100) and were receiving gemcitabine plus nab-paclitaxel (GEM + nabPTX) as preoperative chemotherapy (n = 103). Immune profiles were generated based on immune cell infiltration into the tumor, and their correlation with patient outcomes and histological features was analyzed. Tumor-infiltrating neutrophils (TINs) were identified as independent poor prognostic factors using multivariate analysis in both surgery-first and preoperative chemotherapy groups. The patients were further classified into four groups based on immune cell infiltration into the tumor. Patients with high CD15 infiltration into the tumor and immature stroma at the cancer margins showed the worst prognosis in the preoperative chemotherapy group. The analysis of mRNA expression and immunohistochemical features revealed that CXCR2, the receptor for CXCL8, was correlated with disease-free and overall survival. We inferred that patients with immature stroma at the margins and high infiltration of CD15+ neutrophils within the tumor showed the worst prognosis and they could particularly benefit from treatment with inhibitors targeting CXCR2 or CXCL8.

DOI： 10.1111/cas.16060

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記述言語：英語   出版者・発行元：Annals of Gastroenterological Surgery  

Aim: Immune checkpoint inhibitors (ICIs) are less effective in mismatch repair (MMR)-proficient (pMMR) colorectal cancers (CRCs) than in MMR-deficient CRCs. Here, we investigated changes in the tumor microenvironment after neoadjuvant chemotherapy (NAC) without radiotherapy in locally advanced rectal cancer (LARC) and the potential of ICIs as therapeutic agents for pMMR CRCs. Methods: This was an ad hoc analysis of a KSCC1301 randomized phase II trial in which patients with untreated resectable LARC were randomly assigned to receive S-1 and oxaliplatin or folinic acid, 5-fluorouracil, and oxaliplatin as NAC. Forty-nine patients were studied in this ad hoc analysis. As a reference cohort, we assessed 25 rectal cancer patients who underwent surgery without NAC outside the randomized trial. Immune checkpoint molecules (ICMs; PD-1, PD-L1, CTLA-4, LAG3), tumor-infiltrating lymphocytes (TILs; CD8, FOXP3), and other related proteins were evaluated by immunohistochemistry. Next-generation sequencing (NGS) using Oncomine™ Comprehensive Assay version 3 was conducted in 23 patients. Results: The expression levels of PD-1, CTLA-4, and LAG3 in the NAC group were significantly higher than in reference patients (p < 0.001). Additionally, the infiltration of CD8+ and FOXP3+ T cells, and the CD8/FOXP3 ratio were significantly higher in the NAC group than in reference patients (p < 0.0001). NGS analysis revealed no specific gene alteration related to TILs or ICMs. Conclusion: We demonstrated changes in the tumor immune microenvironment after NAC in pMMR rectal cancer. NAC was associated with increased expression of ICMs and TILs. Rectal cancer could be susceptible to combined immunotherapy with chemotherapy.

DOI： 10.1002/ags3.12730

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記述言語：英語   出版者・発行元：Gastric Cancer  

Background: Gastric cancer (GC) is characterized by an immunosuppressive and treatment-resistant tumor immune microenvironment (TIME). Here, we investigated the roles of different immunosuppressive cell types in the development of the GC TIME. Methods: Single-cell RNA sequencing (scRNA-seq) and multiplex immunostaining of samples from untreated or immune checkpoint inhibitor (ICI)-resistant GC patients were used to examine the correlation between certain immunosuppressive cells and the prognosis of GC patients. Results: The results of the scRNA-seq analysis revealed that tumor-infiltrating monocytic myeloid-derived suppressor cells (TI-M-MDSCs) expressed higher levels of genes with immunosuppressive functions than other immunosuppressive cell types. Additionally, M-MDSCs in GC tissues expressed significantly higher levels of these markers than adjacent normal tissues. The M-MDSCs were most enriched in GC tissues relative to adjacent normal tissues. Among the immunosuppressive cell types assessed, the M-MDSCs were most enriched in GC tissues relative to adjacent normal tissues; moreover, their presence was most strongly associated with a poor prognosis. Immediate early response 3 (IER3), which we identified as a differentially expressed gene between M-MDSCs of GC and adjacent normal tissues, was an independent poor prognostic factor in GC patients (P = 0.0003). IER3+ M-MDSCs expressed higher levels of genes with immunosuppressive functions than IER3− M-MDSCs and were abundant in treatment-resistant GC patients. Conclusions: The present study suggests that TI-M-MDSCs, especially IER3+ ones, may play a predominant role in the development of the immunosuppressive and ICI-resistant GC TIME.

DOI： 10.1007/s10120-023-01456-4

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記述言語：英語   出版者・発行元：Human Pathology  

Several high-grade pleomorphic sarcoma cases that cannot be classified into any existing established categories have been reported. These cases were provisionally classified into undifferentiated pleomorphic sarcoma (UPS). Some dedifferentiated liposarcoma (DDLS) cases may also have been classified into the UPS category due to the absence of MDM2 amplification or an atypical lipomatous tumor/well-differentiated liposarcoma component. We retrieved and reviewed 77 high-grade pleomorphic sarcoma cases, initially diagnosed as UPS in 66 cases and DDLS in 11 cases. Fluorescence in situ hybridization (FISH) analyses of DDIT3 and MDM2 were performed for available cases. Of the cases successfully subjected to DDIT3 FISH (n = 56), nine (7 UPS and 2 DDLS) showed DDIT3 amplification but no MDM2 amplification. Two UPS cases showed both telomeric (5′) and centromeric (3′) amplification of DDIT3 or low polysomy of chromosome 12, whereas 5 UPS and 2 DDLS cases showed 5′-predominant DDIT3 amplification. Histopathologically, all cases showed UPS-like proliferation of atypical pleomorphic tumor cells. Immunohistochemically, only one case showed focal nuclear positivity for DDIT3, supporting the previous finding that DDIT3 expression was not correlated with DDIT3 amplification. All three cases with focal MDM2 expression involved 5′-predominant amplification, two of which showed DDLS-like histological features. The majority of cases (7/9) showed decreased expression in p53 staining, suggesting that DDIT3 amplification regulates the expression of TP53 like MDM2. From a clinicopathological perspective, we hypothesize that DDIT3-amplified sarcoma, especially with 5′-predominant amplification, can be reclassified out of the UPS category.

DOI： 10.1016/j.humpath.2024.02.007

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記述言語：英語   出版者・発行元：Annals of Plastic Surgery  

Klippel-Trenaunay syndrome (KTS) is characterized by port-wine stains, mixed vascular malformations, and soft tissue and bone hypertrophy. Klippel-Trenaunay syndrome is occasionally complicated by chyluria, for which there is no effective treatment currently. We report a case of KTS complicated by intractable chyluria and hematuria due to a lymphatic-ureteral fistula. The patient was successfully treated with multiple lymphaticovenular anastomoses (LVAs). A 66-year-old woman with an enlarged left lower extremity since childhood was diagnosed with KTS. At 60 years of age, she developed chyluria (urine albumin, 2224 μg/mL) and hematuria. Lymphoscintigraphy showed a lymphatic-ureteral fistula near the ureterovesical junction. Conservative treatment was ineffective. She also developed left lower extremity lymphedema, which gradually worsened. Leg cellulitis and purulent pericarditis developed because of hypoalbuminemia (minimum serum albumin level, 1.3 g/dL). We performed 14 LVAs in 2 surgeries to reduce lymphatic fluid flow through the lymphatic-ureteral fistula. The chyluria and hematuria resolved soon after the second operation, and the urine albumin level decreased (3 μg/mL). After 28 months, she had no chyluria or hematuria recurrence and her serum albumin level improved (3.9 g/dL). Multiple LVAs can definitively treat chyluria caused by a lymphatic-ureteral fistula in patients with KTS.

DOI： 10.1097/SAP.0000000000003744

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1093/jjco/hyae020

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Abdominal Radiology  

Purpose: To elucidate how precisely microvascular invasion (MVI) in hepatocellular carcinoma (HCC) can be predicted using multiparametric assessment of gadoxetic acid-enhanced MRI. Methods: In this retrospective single-center study, patients who underwent liver resection or transplantation of HCC were evaluated. Data obtained in patients who underwent liver resection were used as the training set. Nine kinds of MR findings for predicting MVI were compared between HCCs with and without MVI by univariate analysis, followed by multiple logistic regression analysis. Using significant findings, a predictive formula for diagnosing MVI was obtained. The diagnostic performance of the formula was investigated in patients who underwent liver resection (validation set 1) and in patients who underwent liver transplantation (validation set 2) using a receiver operating characteristic curve analysis. The area under the curves (AUCs) of these three groups were compared. Results: A total of 345 patients with 356 HCCs were selected for analysis. Tumor diameter (D) (P = 0.021), tumor washout (TW) (P < 0.01), and peritumoral hypointensity in the hepatobiliary phase (PHH) (P < 0.01) were significantly associated with MVI after multivariate analysis. The AUCs for predicting MVI of the predictive formula were as follows: training set, 0.88 (95% confidence interval (CI) 0.82,0.93); validation set 1, 0.81 (95% CI 0.73,0.87); validation set 2, 0.67 (95% CI 0.51,0.80). The AUCs were not significantly different among three groups (training set vs validation set 1; P = 0.15, training set vs validation set 2; P = 0.09, validation set 1 vs validation set 2; P = 0.29, respectively). Conclusion: Our multiparametric assessment of gadoxetic acid-enhanced MRI performed quite precisely and with good reproducibility for predicting MVI. Graphical abstract: (Figure presented.)

DOI： 10.1007/s00261-023-04179-3

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s13691-024-00659-5.

記述言語：英語   出版者・発行元：Journal of Obstetrics and Gynaecology Research  

A 25-year-old female Carney complex patient with a PRKAR1A mutation who had undergone surgery to remove teratomas visited our dermatology department. She was suspected of having a malignant melanoma in a teratoma. On clinical examination, a black nodule was found within the cyst. On histopathological examination, the black lesion was composed of heavily pigmented round cells with vesicular nuclei and single prominent nucleoli. Additionally, there were large cells with irregularly shaped nuclei. Upon immunohistochemical examination, the large, irregularly shaped cells were positively stained with Melan A, HMB45, S-100 protein, SOX10, CD10 (focally), and BRAFV600E, but negatively stained with PRAME. Based on the histopathological features, we diagnosed the patient with pigmented epithelioid melanocytoma (PEM) in a teratoma of a Carney complex patient. This is the first case of PEM developing from a teratoma. Since PEM lesions may spread to regional lymph nodes, careful follow-up is necessary.

DOI： 10.1111/jog.15832

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記述言語：英語   出版者・発行元：Journal of Clinical Pathology  

Aims Collecting duct carcinoma (CDC) and fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) have similar histological morphologies and both show a poor prognosis. Programmed death ligand 1 (PD-L1) inhibitor has been approved for the treatment of RCC. However, tumour-infiltrating neutrophils stimulated by interleukin-8 (IL-8) interfere with PD-L1 inhibitors. Here, we retrospectively analysed PD-L1 and IL-8 expression, and examined its relationship with infiltrating immune cells. Methods Nine cases of CDC and seven cases of FH-deficient RCC were selected. We defined PD-L1 and IL-8 expression by the Tumour Proportion Score and Combined Positive Score (CPS). We counted the numbers of CD8 +, CXCR2 +, CD11b +, CD66b + and CD33 + immune cells located in the tumour components. Results A number of CXCR2 + (p=0.0058), CD11b + (p=0.0070) and CD66b + (p=0.0067) immune cells infiltrating into CDC were significantly higher than those infiltrating into FH-deficient RCC. In CDC, PD-L1 expression was correlated with a high density of CD8 + lymphocytes (p=0.0389), but was not in FH-deficient RCC (p=0.6985). IL-8 CPS was significantly higher in CDC than in FH-deficient RCC (p=0.0069). In addition, among the CDC cases, IL-8 CPS showed significant positive correlations with CXCR2 +, CD11b + and CD66b + immune cell densities (p=0.0250, p=0.0104 and p=0.0374, respectively), whereas FH-deficient RCC showed no significant correlations between IL-8 CPS and immune cell densities. Conclusions Our results suggest the difference of each tumour microenvironment between CDC and FH-deficient RCC, and IL-8 is a potential therapeutic target for treating CDC, but not FH-deficient RCC.

DOI： 10.1136/jcp-2022-208589

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1136/jcp-2022-208589.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1038/s41698-024-00515-y.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/cas.15981.

記述言語：英語   出版者・発行元：Cancer Science  

TP53-induced glycolysis and apoptosis regulator (TIGAR) is an important gene that encodes a regulatory enzyme of glycolysis and reactive oxygen species (ROS) detoxification and is associated with worse prognosis in various cancers. Ferroptosis is a recently identified type of programmed cell death that is triggered by iron-dependent lipid peroxidation. There are no reports on the prognostic impact of TIGAR on intrahepatic cholangiocarcinoma (ICC), and its role in ferroptosis is unclear. Ninety ICC patients who had undergone hepatic resection were enrolled. Immunohistochemical staining for TIGAR was performed. The regulation of malignant activity by TIGAR and the association between ferroptosis and TIGAR were investigated in vitro. Twenty-two (24.4%) patients were categorized into TIGAR-high and -low groups by immunohistochemical staining. There were no noticeable differences in background factors between the two groups, but TIGAR positivity was an independent prognostic factor in disease-free survival (hazard ratio [HR], 2.00; 95% confidence interval [CI], 1.04–3.85, p = 0.0378) and overall survival (HR, 2.10; 95% CI, 1.03–4.30, p = 0.00422) in a multivariate analysis. In vitro, TIGAR knockdown (KD) decreased cell motility (cell proliferation/migration/invasion/colony-forming capabilities) and elevated ROS and lipid peroxidation. This indicated that TIGAR KD induced ferroptosis. TIGAR KD-induced ferroptosis was suppressed using liproxstatin. TIGAR KD decreased the expression of glutathione peroxidase 4, known as factor-suppressing ferroptosis. The combination of TIGAR KD with cisplatin significantly induced more ferroptosis. In conclusion, TIGAR is associated with poor outcomes in ICC patients and resistance to ferroptosis.

DOI： 10.1111/cas.15981

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記述言語：英語   出版者・発行元：Annals of Gastroenterological Surgery  

Background: There is limited published information regarding the expression of mechanistic target of rapamycin (mTOR) in vessels that encapsulate tumor cluster (VETC)-positive hepatocellular carcinoma (HCC). The mTOR inhibitor, everolimus, has been approved as an immunosuppressant for use in HCC patients after living donor liver transplantation (LDLT). Methods: Using a database of 214 patients who underwent LDLT for HCC, we examined the mTOR protein and angiopoietin-2 (Ang-2) in VETC-positive HCC by immunohistochemical staining. The presence of VETC and mTOR expression were evaluated in both primary and recurrent HCC lesions. Results: Forty-three of the 214 patients (20.1%) were VETC-positive, and 29 of these 43 patients (67.4%) expressed mTOR. Relative Ang-2 expression was significantly higher in the mTOR-positive than in the mTOR-negative group (p = 0.037). Thirty-four of the 214 patients experienced HCC recurrence after LDLT; 20 of these were operable. The primary lesions of six of these 20 patients were VETC-positive; five of these six patients also had VETC-positive recurrent lesions (p < 0.001). The expression of mTOR was significantly higher in the VETC-positive lesions (p = 0.0018). Conclusions: We showed that mTOR expression was higher in the VETC-positive primary and recurrent lesions than in the VETC-negative ones.

DOI： 10.1002/ags3.12735

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記述言語：英語   出版者・発行元：International Journal of Surgical Pathology  

Myxoid pleomorphic liposarcoma (MPLS) is an extremely rare tumor listed in the fifth edition of the WHO classification (2020). Histologically, it mainly comprises a mixture of myxoid and pleomorphic liposarcoma-like components. Genetically, it lacks FUS/EWSR1::DDIT3 fusion and MDM2 amplification. Herein, we describe an example of MPLS with rhabdoid cells in a 10-year-old girl who presented with a growing mass in the right inguinal region. The specimen from the wide excision measured 68 mm × 55 mm × 43 mm, and a circumscribed and lobulated mass was observed in the subcutaneous tissue. Histologically, oval-to-short, spindle-shaped, proliferating tumor cells with moderate nuclear atypia and mesh-like capillaries against a myxoid background were noted. Adipocytes were observed focally, while rhabdoid cells were observed multifocally. Immunohistochemically, the tumor showed inconsistent reactivity for desmin but was negative for MYOD1, myogenin, MDM2, and CDK4. Fluorescence in situ hybridization revealed no DDIT3 rearrangement. Despite adjuvant chemotherapy, the tumor metastasized to the thoracic cavity 24 months after excision. The metastatic lesions contained abundant lipoblasts rather than rhabdoid cells, and we concluded this tumor was a MPLS. The presence of rhabdoid cells could be a diagnostic pitfall, and recognizing such a variation in histology would help improve diagnostic accuracy.

DOI： 10.1177/10668969241226695

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記述言語：英語   出版者・発行元：Annals of Surgical Oncology  

Background: Ferroptosis is a cell death caused by iron-dependent accumulation of lipid peroxidation. Transferrin receptor (TFR) is a ferroptosis-related protein responsible for iron transport. The detailed biologic role of TFR in intrahepatic cholangiocarcinoma (ICC) is not fully elucidated. Methods: The study enrolled 92 ICC patients who had undergone hepatic resection. Immunohistochemistry (IHC) assays were performed for TFR protein expression. The regulation of malignant activity and the effect on sensitivity to the ferroptosis-inducer artesunate by TFR were investigated in vitro. Results: Using IHC staining, 23 patients were categorized as TFR-positive. The TFR-positive group had a significantly larger tumor size and more microscopic vascular invasion. In the multivariate analysis, TFR positivity was an independent poor prognostic factor. In vitro TFR-knockdown (KD) significantly decreased the intracellular iron levels and the cell proliferation, migration, and invasion rates. Artesunate treatment significantly decreased cell viability, whereas cisplatin promoted ferroptosis. When iron transport into cells was inhibited by TFR-KD, ferroptosis was significantly suppressed. Expression of PD-L1 was induced by cisplatin, with a further increase observed when artesunate and cisplatin were used in combination. Conclusions: Transferrin receptor is a poor prognostic factor for ICC and contributes to sensitivity to ferroptosis.

DOI： 10.1245/s10434-024-16065-3

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記述言語：英語   出版者・発行元：International Journal of Clinical Oncology  

Background: Failure-free survival (FFS) rates of low-risk patients with rhabdomyosarcoma improved in Intergroup Rhabdomyosarcoma Study IV after the escalation of cyclophosphamide total dose to 26.4 g/m2. However, this dose may increase the risk of adverse events, including infertility, in some patients. The JRS-I LRA0401 and LRB0402 protocols aimed to reduce the cyclophosphamide dose to 9.6 g/m2 and 17.6 g/m2, respectively, without decreasing the FFS rates. Methods: Subgroup-A patients received eight cycles (24 weeks) of vincristine, actinomycin D, and 1.2 g/m2/cycle cyclophosphamide. Subgroup-B patients received eight cycles (24 weeks) of vincristine, actinomycin D, and 2.2 g/m2/cycle cyclophosphamide, followed by six cycles (24 weeks) of vincristine and actinomycin D. Group II/III patients in both subgroups received radiotherapy. Results: In subgroup A (n = 12), the 3-year FFS rate was 83% (95% confidence interval [CI], 48–96), and the 3-year overall survival (OS) rate was 100%. Only one isolated local recurrence was observed (8.3%). There were no unexpected grade-4 toxicities and no deaths. In subgroup B (n = 16), the 3-year FFS and OS rates were 88% (95% CI, 59–97) and 94% (95% CI, 63–99), respectively. There were no unexpected grade 4 toxicities and no deaths. Conclusions: Shorter duration therapy using vincristine, actinomycin D, and lower dose cyclophosphamide with or without radiotherapy for patients with low-risk subgroup A rhabdomyosarcoma (JRS-I LRA0401 protocol) and moderate reduction of cyclophosphamide dose for patients with low-risk subgroup B rhabdomyosarcoma (JRS-I LRB0402 protocol) did not compromise FFS.

DOI： 10.1007/s10147-024-02608-x

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記述言語：英語   出版者・発行元：Cancer Cytopathology  

Background: A standardized reporting system for bone and soft tissue tumor cytopathology has not yet been established. The objective of this study was to explore the potential utility of a classification modified from the Milan System for Salivary Gland Cytopathology and compared it with the upcoming World Health Organization (WHO) system for fine-needle aspiration of soft tissue lesions. Methods: The authors reviewed 285 cytology cases of bone/joint (n = 173) and soft tissue (n = 112) lesions, scoring each within diagnostic categories. The results were compared with histologic diagnoses and the risk of malignancy (ROM) for each category, and diagnostic reliability was analyzed. Results: All 285 cases were successfully classified into one of the following categories: nondiagnostic (6.3%), non-neoplastic (11.9%), atypia of uncertain significance (11.9%), benign neoplasm (5.6%), bone and soft tissue neoplasm of uncertain malignant potential (25.3%), suspicious for malignancy (1.4%), and malignant (37.5%). The ROM was 44.4% (eight of /18 cases) in nondiagnostic, 0% (zero of 34 cases) in non-neoplastic, 32.4% (11 of 34 cases) in atypia of uncertain significance, 0% (zero of 16 cases) in benign neoplasm, 16.7% (12 of 72 cases) in bone and soft tissue neoplasm of uncertain malignant potential, 75.0% (three of four cases) in suspicious for malignancy, and 100% (107 of 107 cases) in malignant categories. Using the WHO system, the proportion and ROM of the benign category (non-neoplastic and benign neoplasm) was 17.5% and 0%, respectively. Among benign and malignant lesions, the diagnostic accuracy, sensitivity, and specificity for detecting malignancy were 99.4%, 100%, and 98.0%, respectively. Conclusions: The modified Milan system as well as the WHO system may be a useful cytopathologic classification tool for both bone and soft tissue lesions.

DOI： 10.1002/cncy.22888

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PubMed

記述言語：英語   出版者・発行元：Annals of Thoracic Surgery  

Background: Cluster of differentiation (CD) 155 is a transmembrane protein that belongs to the nectin-like molecule family, which is widely overexpressed in several types of cancer. However, the clinical significance of CD155 in pathologic stage I lung adenocarcinoma remains poorly understood. Methods: We analyzed 320 patients diagnosed with pathologic stage I lung adenocarcinoma who underwent surgical treatment at Kyushu University Hospital between 2006 and 2015. The number of tumor cells expressing CD155 was assessed by immunohistochemistry, and patients were categorized into high and low CD155 expression groups. We compared the clinical and pathologic characteristics and clinical outcomes between these groups. Results: Mutation status of the epidermal growth factor receptor gene (EGFR) was determined in 237 patients. A total of 106 patients (33.1%) had EGFR wild-type, and 131 patients (40.9%) had EGFR mutant-type. CD155 expression was classified as high in 77 patients (24.1%) and as low in 243 (75.9%) as low. Multivariate analysis identified pleural invasion and EGFR wild-type as independent predictors of high CD155 expression. The Kaplan-Meier plot demonstrated significantly poorer recurrence-free survival and overall survival in the high CD155 group compared with the low CD155 group. Multivariate analysis showed high CD155 expression was an independent poor prognostic factor for recurrence-free and overall survival. Subgroup analyses revealed that a prognostic difference related to CD155 expression was observed only in patients with EGFR wild-type but not in those with EGFR mutant-type. Conclusions: Our findings suggest that high expression of CD155 is associated with EGFR wild-type and could serve as a valuable prognostic marker in pathologic stage I lung adenocarcinoma, particularly in cases without EGFR mutation.

DOI： 10.1016/j.athoracsur.2024.05.042

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PubMed

記述言語：英語   出版者・発行元：一般社団法人 日本内科学会  

DOI： 10.2169/internalmedicine.3743-24

PubMed

CiNii Research

記述言語：英語   出版者・発行元：Virchows Archiv  

Currently, it is difficult to predict the prognosis of myxoid liposarcoma (MLS) in biopsy specimens. In this study, we determined whether nuclear morphology may be used to predict the prognosis of MLS in primary biopsy specimens. Two pathologists evaluated nuclear morphology using the modified WHO/ISUP and Fuhrman grades. Survival analyses were performed by grouping nuclear high- and low-grades. We examined 53 MLS cases, which included 29 (54.7%) male and 24 (45.3%) female patients with a median age of 46 years (interquartile range, 37 − 60). In total, 7 (13.2%) and 16 (30.2%) cases were assigned to the high nuclear grade group based on the modified WHO/ISUP and Fuhrman gradings, respectively. Survival analyses revealed a significantly worse disease-free survival in the high-grade group (hazard ratio (HR), 7.51; 95% confidence interval (CI), 2.67–21.1, p < 0.001 by the modified WHO/ISUP grading; HR, 4.45; 95% CI, 1.63–12.1, p = 0.001 by the modified Fuhrman grading). Moreover, the modified WHO/ISUP grade showed a significantly worse overall survival in the high-grade group (HR, 4.39; 95% CI, 1.04–18.6, p = 0.028), and the modified Fuhrman grade exhibited a similar, but not significant, trend. Our results indicate that nuclear morphology grading is a good predictor of patient prognosis at the time of biopsy in MLS. Even when cell density is sparse, treatment strategies should be carefully considered when individual tumor cells exhibit atypical nuclei.

DOI： 10.1007/s00428-024-03796-7

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PubMed

記述言語：英語   出版者・発行元：Skeletal Radiology  

Synovial chondrosarcoma (CHS) is a rare malignant tumor arising from the synovial tissue and is often associated with synovial chondromatosis. Herein, we present a unique case of primary synovial CHS in the shoulder joint without evidence of synovial chondromatosis. A 60-year-old man presented to our hospital with a complain of left shoulder pain that persisted for 6 years, which was initially misdiagnosed as synovitis. Radiography revealed an osteolytic lesion involving the humerus and the scapula. Histologically, the tumor exhibited features of grade 2 synovial CHS, infiltrating the trabecular bones and intra-articular space. Wide resection led to a 9-year recurrence-free survival. This case underscores the challenges in diagnosing and managing synovial CHS, particularly in cases with atypical presentations lacking synovial chondromatosis, necessitating careful follow-up and adequate surgical intervention.

DOI： 10.1007/s00256-024-04811-3

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PubMed

記述言語：英語   出版者・発行元：Gastric Cancer  

Background: Hepatoid adenocarcinoma of the stomach (HAS), a subtype of gastric cancer (GC), includes multiple tumor components, such as enteroblastic and tubular adenocarcinoma components. However, which component mostly contributes to the aggressive behavior of HAS remains unclear. Moreover, the role of tumor-associated macrophages (TAMs) has not been explored in HAS. This study evaluated the clinical significance of the proportion of the hepatoid component within the tumor, CD163 + macrophages, and macrophage colony-stimulating factor-1 (CSF-1) in HAS. Methods: In total, 56 cases of primary HAS were analyzed. In each case, hepatoid (HC), enteroblastic (EC), and tubular (TC) components were identified, and the ratio of HC to the entire tumor (hepatoid component ratio, HCR) was assessed to examine the correlation between HCR and clinicopathological features. Immunohistochemical staining for CD163 and CSF-1 was performed, and differences in immunohistochemical results among the three tumor components were analyzed. In each tumor component, the prognostic impact of CD163 and CSF-1 was examined. Results: A high HCR was associated with worse overall survival (OS). CD163 + TAMs and CSF-1 immunoreactivity score in HC were significantly higher than those in the other components. High infiltration of CD163 + TAMs and a high CSF-1 immunoreactivity score in HC were associated with an aggressive course and worse OS. Multivariate analysis revealed the proportion of HC in HAS as an independent prognostic factor (HR = 3.176, p = 0.006). Conclusions: The HCR and CD163 + TAMs may be useful prognostic predictors, and TAMs may be novel therapeutic targets of HAS.

DOI： 10.1007/s10120-024-01562-x

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PubMed

記述言語：英語   出版者・発行元：International Journal of Clinical Oncology  

Background: Cluster of differentiation 155 (CD155) is expressed in many tumor types. CD155 is involved in the immune avoidance of tumor cells and contributes to tumor development and progression. Therefore, CD155 is a novel target for cancer immunotherapy. The clinical significance of CD155 expression in lung squamous cell carcinoma (LUSC) has not been fully elucidated. Materials and methods: We performed a retrospective analysis of 264 patients with surgically resected LUSC. Immunohistochemistry was used to evaluate CD155 expression. The association of CD155 expression with clinicopathological features and clinical outcomes was assessed. We also analyzed the relationship between CD155 expression and programmed cell death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes. Results: Among the 264 patients, 137 patients (51.9%) were classified in the high CD155 expression group. High CD155 expression was significantly associated with pleural invasion, vascular invasion, PD-L1 positivity, and high CD3, CD4, and CD8 expressions. In multivariate analysis, the presence of pleural invasion and PD-L1 positivity were independent predictors of high CD155 expression. Kaplan–Meier curve analysis showed that high CD155 expression was significantly associated with shorter disease-free survival and overall survival. In multivariate analysis, high CD155 expression was an independent poor prognostic factor for overall survival, but not for disease-free survival. Subgroup analyses revealed that the prognostic effect of CD155 expression was observed in the PD-L1 positive group but not the PD-L1 negative group. Conclusion: Our analysis revealed that high CD155 expression significantly predicted poor prognosis in patients with surgically resected LUSC, especially in patients with PD-L1-positive tumors.

DOI： 10.1007/s10147-024-02640-x

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PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1245/s10434-023-14053-7.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s11748-023-01938-3.

出版者・発行元：Communications Biology  

The unremitting emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants necessitates ongoing control measures. Given its rapid spread, the new Omicron subvariant BA.5 requires urgent characterization. Here, we comprehensively analyzed BA.5 with the other Omicron variants BA.1, BA.2, and ancestral B.1.1. Although in vitro growth kinetics of BA.5 was comparable among the Omicron subvariants, BA.5 was much more fusogenic than BA.1 and BA.2. Airway-on-a-chip analysis showed that, among Omicron subvariants, BA.5 had enhanced ability to disrupt the respiratory epithelial and endothelial barriers. Furthermore, in our hamster model, in vivo pathogenicity of BA.5 was slightly higher than that of the other Omicron variants and less than that of ancestral B.1.1. Notably, BA.5 gains efficient virus spread compared with BA.1 and BA.2, leading to prompt immune responses. Our findings suggest that BA.5 has low pathogenicity compared with the ancestral strain but enhanced virus spread /inflammation compared with earlier Omicron subvariants.

DOI： 10.1038/s42003-023-05081-w

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記述言語：英語   出版者・発行元：The Japan Society for Respiratory Endoscopy  

<p>The case involves a 57-year-old man with a history of laryngeal and lung cancers. He underwent a laryngectomy and right upper lobectomy and developed tracheal methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) colonization. He also underwent endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to diagnose right mediastinal lymph node adenopathy. His recovery was complicated by a mediastinal infection caused by MRSA five days post-procedure. Combining triple antibiotics comprising MEPM, DAP, and VCM for three weeks gradually improved the mediastinal infection. To our knowledge, this is the first report of mediastinal infection caused by MRSA after EBUS-TBNA. Our successful treatment of EBUS-TBNA-related infectious complications gives us information regarding rare complications management caused by EBUS-TBNA.</p>

DOI： 10.58585/respend.2023-0007

CiNii Research

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s00262-023-03505-4.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.3390/cancers15235608.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1245/s10434-023-14085-z.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/cas.15921.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1186/s12885-023-11528-4.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1038/s41416-023-02396-7

記述言語：英語   出版者・発行元：Asian Journal of Endoscopic Surgery  

Pagetoid spread (PS) of anorectal cancer is relatively rare and associated with poor prognosis. While a primary tumorous lesion is usually obvious in most PS cases, we experienced two cases of nonmass-forming type anorectal cancer with PS. It remains challenging to decide strategies. In both cases, histological findings of a perianal skin biopsy showed proliferation of atypical cells that were positive for cytokeratin (CK) 7, CK20, and caudal type homeobox 2 and negative for Gross cystic disease fluid protein 15, suggesting PS. Abdominoperineal resection (APR) with extensive anal skin resection was performed in both patients. The pathological diagnosis in each was nonmass-forming type anorectal cancer with PS. Neither has experienced recurrence in postoperative courses. Even nonmass-forming type anorectal cancer with PS could have high malignant potentials. APR with lymph nodes dissection and wide skin excision and regular surveillance might be necessary.

DOI： 10.1111/ases.13217

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記述言語：英語   出版者・発行元：シュプリンガー・ジャパン(株)  

症例は55歳女性。腹痛を主訴に受診し、上部消化管内視鏡検査で十二指腸第3部にBorrmann 2型腫瘍が認められ、生検により高頻度マイクロサテライト不安定性(MSI-H)と高分化型から中分化型の腺癌が明らかになった。上部消化管造影とCTでも十二指腸に腫瘍が認められ、ステージIV十二指腸腺癌と診断した。腫瘍は左腎静脈に近接しており、小腸の腸間膜リンパ節転移も認められたため、ペムブロリズマブによる術前治療を開始した。2コース終了後に十二指腸狭窄のため緊急入院となり、上部消化管内視鏡検査で十二指腸内腔に微小な穴が認められた。CTでは、腫瘍の著しい退縮と十二指腸狭窄が認められた。リンパ節も著明に縮小していたことから、根治切除が可能であると判断し、腹腔鏡下十二指腸部分切除術とリンパ節郭清を行った。術後経過は順調で、病理学的完全奏効を達成した。生検でMSI-Hが検出されたこと、子宮癌の既往があること、近親者に癌の既往があることから、Lynch症候群(LS)が疑われた。患者の末梢血を用いて遺伝子検査を行ったところ、MSH2遺伝子のNM_000251.3:c.211+1G>Cに変異が認められ、LSと診断した。

記述言語：英語   出版者・発行元：Pathobiology  

Rapid advances are being made in cancer drug therapy. Since molecularly targeted therapy has been introduced, personalized medicine is being practiced, pathological tissue from malignant tumors obtained during routine practice is frequently used for genomic testing. Whereas cytological specimens fixed mainly in alcohol are considered to be more advantageous in terms of preservation of the nucleic acid quality and quantity. This article is aimed to share the information for the proper handling of cytological specimens in practice for genomic medicine based on the findings established in "Guidelines for Handling of Cytological Specimens in Cancer Genomic Medicine (in Japanese)"published by the Japanese Society of Clinical Cytology in 2021. The three-part practical guidelines are based on empirical data analyses; Part 1 describes general remarks on the use of cytological specimens in cancer genomic medicine, then Part 2 describes proper handling of cytological specimens, and Part 3 describes the empirical data related to handling of cytological specimens. The guidelines indicated proper handling of specimens in each fixation, preparation, and evaluation.

DOI： 10.1159/000528346

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PubMed

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1097/PAS.0000000000002086.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.3389/fimmu.2023.1276014.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.3390/cancers15184456.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.modpat.2023.100336

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/cas.15901.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1097/PAS.0000000000002089.

記述言語：英語   出版者・発行元：Cancer Science  

Intratumor bacteria modify the tumor immune microenvironment and influence outcomes of various tumors. Periodontal pathogen Fusobacterium nucleatum has been detected in pancreatic cancer tissues and is associated with poor prognosis. However, it remains unclear how F. nucleatum affects pancreatic cancer. Here, we compared clinical features with F. nucleatum colonization in pancreatic cancer tissues. F. nucleatum was detected in 15.5% (13/84) of pancreatic cancer patients. The tumor size was significantly larger in the F. nucleatum-positive group than in the negative group. To clarify the biological effect of intratumor F. nucleatum on pancreatic cancer progression, we performed migration/invasion assays and cytokine array analysis of cancer cells cocultured with F. nucleatum. F. nucleatum promoted CXCL1 secretion from pancreatic cancer cells, leading to cancer progression through autocrine signaling. Intratumor F. nucleatum suppressed tumor-infiltrating CD8+ T cells by recruiting myeloid-derived suppressor cells (MDSCs) to the tumor in an F. nucleatum-injected subcutaneous pancreatic cancer mouse model, resulting in tumor progression. Furthermore, tumor growth accelerated by F. nucleatum was suppressed by MDSC depletion or cytokine inhibitors. Intratumor F. nucleatum promoted pancreatic cancer progression through autocrine and paracrine mechanisms of the CXCL1-CXCR2 axis. Blockade of the CXCL1-CXCR2 axis may be a novel therapeutic approach for patients with intratumor F. nucleatum-positive pancreatic cancer.

DOI： 10.1111/cas.15901

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PubMed

記述言語：英語   出版者・発行元：Cell Reports  

Small cell lung cancer (SCLC) is one of the deadliest human cancers, with a 5-year survival rate of ∼7%. Here, we performed a targeted proteomics analysis of human SCLC samples and thereby identified hypoxanthine phosphoribosyltransferase 1 (HPRT1) in the salvage purine synthesis pathway as a factor that contributes to SCLC malignancy by promoting cell survival in a glutamine-starved environment. Inhibition of HPRT1 by 6-mercaptopurine (6-MP) in combination with methotrexate (MTX), which blocks the de novo purine synthesis pathway, attenuated the growth of SCLC in mouse xenograft models. Moreover, modulation of host glutamine anabolism with the glutamine synthetase inhibitor methionine sulfoximine (MSO) in combination with 6-MP and MTX treatment resulted in marked tumor suppression and prolongation of host survival. Our results thus suggest that modulation of host glutamine anabolism combined with simultaneous inhibition of the de novo and salvage purine synthesis pathways may be of therapeutic benefit for SCLC.

DOI： 10.1016/j.celrep.2023.112899

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出版者・発行元：AIP Conference Proceedings  

JA DEMO is a steady-state tokamak which produces several hundreds of MW of electric power. Electron cyclotron heating and current drive (ECH/CD) system is one of the major components of JA DEMO tokamak, and it is expected to play an important role in its plasma operation scenario. Design activities for JA DEMO ECH/CD are in progress regarding both physics and engineering. Analysis of ECCD physics for current drive efficiency improvement shows that an upper-side injection can produce sufficient driven current by avoiding absorption at second harmonic resonance. RF power for ECCD operation of JA DEMO is expected to be 100 MW at the frequency of >200 GHz range. The conceptual design of the RF power plant represents the location and scale of the building for the RF power plant. The transmission Line (TL) for RF power delivery from the RF power plant to the tokamak exceeds 200 m, and studies of TL components for highly efficient RF transmission are in progress. The concept of the launcher, which combines remote steering technology and phased array, is evaluated by a simulation. A low-power experiment and preliminary results demonstrate that the large oblique angle injection necessary for ECCD operation is possible.

DOI： 10.1063/5.0162701

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.modpat.2023.100181.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1002/ags3.12730

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1002/ags3.12735

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.celrep.2023.112899.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/1759-7714.15014.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s00432-022-04554-5.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1136/jclinpath-2022-208158.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1038/s41598-023-40050-7.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s10147-023-02358-2.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/hepr.13902.

記述言語：英語   出版者・発行元：Modern Pathology  

Mixed-type ampullary carcinoma is a subtype that combines intestinal-type (I-type) and pancreatobiliary-type (PB-type) lesions, but few studies have examined its clinicopathologic features and genetic alterations. The differences in genetic alterations between mixed type and other subtypes, as well as the genetic differences between I-type and PB-type lesions in the mixed type, remain unclear. In this study, we compared the clinicopathologic features and prognosis of 110 ampullary carcinomas classified by hematoxylin and eosin and immunohistochemical staining as follows: 63 PB-type, 35 I-type, and 12 mixed-type carcinomas. A comparative analysis of genetic mutations by targeted sequencing of 24 genes was also performed in 3 I-type cases, 9 PB-type cases, and I and PB-type lesions of 6 mixed-type cases. The mixed subtype had a poorer prognosis than the other subtypes, and there was also a similar tendency in the adjuvant group (n = 22). A total of 49 genetic mutations were detected in all 18 lesions for which genetic alteration was analyzed. No genetic mutations specific to the mixed type were found, and it was not possible to determine genetically whether the mixed type had originally been I or PB type. However, 5 of 6 cases had mutations common to both I and PB-type lesions, and additional mutations were found only in either I or PB-type lesions. In support of this, the mixed type more frequently exhibited genetic heterogeneity intratumorally than the other subtypes. Mixed-type tumors are histologically, immunohistochemically, and genetically heterogeneous, and this heterogeneity is associated with poor prognosis and may affect treatment resistance.

DOI： 10.1016/j.modpat.2023.100181

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記述言語：英語   出版者・発行元：Communications Biology  

Postnatal cell fate is postulated to be primarily determined by the local tissue microenvironment. Here, we find that Mediator 1 (Med1) dependent epigenetic mechanisms dictate tissue-specific lineage commitment and progression of dental epithelia. Deletion of Med1, a key component of the Mediator complex linking enhancer activities to gene transcription, provokes a tissue extrinsic lineage shift, causing hair generation in incisors. Med1 deficiency gives rise to unusual hair growth via primitive cellular aggregates. Mechanistically, we find that MED1 establishes super-enhancers that control enamel lineage transcription factors in dental stem cells and their progenies. However, Med1 deficiency reshapes the enhancer landscape and causes a switch from the dental transcriptional program towards hair and epidermis on incisors in vivo, and in dental epithelial stem cells in vitro. Med1 loss also provokes an increase in the number and size of enhancers. Interestingly, control dental epithelia already exhibit enhancers for hair and epidermal key transcription factors; these transform into super-enhancers upon Med1 loss suggesting that these epigenetic mechanisms cause the shift towards epidermal and hair lineages. Thus, we propose a role for Med1 in safeguarding lineage specific enhancers, highlight the central role of enhancer accessibility in lineage reprogramming and provide insights into ectodermal regeneration.

DOI： 10.1038/s42003-023-05105-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.jpedsurg.2023.01.050.

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s00428-023-03572-z.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s00432-022-04078-y.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.21873/anticanres.16462.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/1759-7714.14910.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1245/s10434-022-13058-y.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s00262-022-03353-8.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1245/s10434-022-12926-x.

DOI： 10.1245/s10434-022-12974-3

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記述言語：英語   出版者・発行元：Journal of Clinical Pathology  

Aims: Liposarcoma is a malignant soft tissue tumour with adipocytic differentiation. Dedifferentiated liposarcoma (DDLS) and myxoid liposarcoma (MLS) are classified as high-grade liposarcomas. Lipid droplet-associated protein (also known as perilipin 1 (PLIN1)) is the predominant perilipin and has utility as a specific marker of adipogenic differentiation. Adipose differentiation-related protein (also known as adipophilin (ADRP)) is ubiquitously expressed in a range of tissues. High ADRP expression is reportedly a poor prognostic factor in several cancer types. However, no previous studies have examined the association between PLIN1 or ADRP expression and prognosis in sarcoma. This study therefore aimed to evaluate the association between PLIN1 or ADRP expression and prognosis in liposarcoma. Methods: In total, 97 primary resection specimens (53 MLS and 44 DDLS) were examined in this study. PLIN1 and ADRP expression was evaluated by immunohistochemistry. Survival analyses were performed for MLS and DDLS. Results: Of the 53 MLS specimens, 15 (28.3%) exhibited high PLIN1 expression. PLIN1 expression was not observed in DDLS specimens. High PLIN1 expression was significantly associated with increased disease-free survival (DFS) among patients with MLS (p=0.045). Distinct ADRP expression was observed in 13 of 53 (24.5%) MLS specimens and 5 of 44 (11.4%) DDLS specimens. High ADRP expression was associated with shorter overall survival (OS) in MLS (p=0.042) and DFS and shorter OS in DDLS (p=0.024 and p<0.001, respectively). Conclusions: PLIN1 and ADRP expression is associated with poor prognosis in high-grade liposarcoma.

DOI： 10.1136/jcp-2023-208814

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記述言語：英語   出版者・発行元：Nature Communications  

In late 2022, SARS-CoV-2 Omicron subvariants have become highly diversified, and XBB is spreading rapidly around the world. Our phylogenetic analyses suggested that XBB emerged through the recombination of two cocirculating BA.2 lineages, BJ.1 and BM.1.1.1 (a progeny of BA.2.75), during the summer of 2022. XBB.1 is the variant most profoundly resistant to BA.2/5 breakthrough infection sera to date and is more fusogenic than BA.2.75. The recombination breakpoint is located in the receptor-binding domain of spike, and each region of the recombinant spike confers immune evasion and increases fusogenicity. We further provide the structural basis for the interaction between XBB.1 spike and human ACE2. Finally, the intrinsic pathogenicity of XBB.1 in male hamsters is comparable to or even lower than that of BA.2.75. Our multiscale investigation provides evidence suggesting that XBB is the first observed SARS-CoV-2 variant to increase its fitness through recombination rather than substitutions.

DOI： 10.1038/s41467-023-38435-3

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記述言語：英語   出版者・発行元：Nature Communications  

In late 2022, various Omicron subvariants emerged and cocirculated worldwide. These variants convergently acquired amino acid substitutions at critical residues in the spike protein, including residues R346, K444, L452, N460, and F486. Here, we characterize the convergent evolution of Omicron subvariants and the properties of one recent lineage of concern, BQ.1.1. Our phylogenetic analysis suggests that these five substitutions are recurrently acquired, particularly in younger Omicron lineages. Epidemic dynamics modelling suggests that the five substitutions increase viral fitness, and a large proportion of the fitness variation within Omicron lineages can be explained by these substitutions. Compared to BA.5, BQ.1.1 evades breakthrough BA.2 and BA.5 infection sera more efficiently, as demonstrated by neutralization assays. The pathogenicity of BQ.1.1 in hamsters is lower than that of BA.5. Our multiscale investigations illuminate the evolutionary rules governing the convergent evolution for known Omicron lineages as of 2022.

DOI： 10.1038/s41467-023-38188-z

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/cas.15729.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1136/jcp-2023-208814.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/hepr.13875.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.ejrad.2023.110756.

記述言語：英語   出版者・発行元：Hepatology Research  

Aims: The fibroblast growth factor receptor 2 (FGFR2) fusion gene is frequently found as a genetic abnormality in the FGFR pathway in patients with intrahepatic cholangiocarcinoma (ICC). The FGFR fusion protein, produced from the FGFR fusion gene, is thought to cause tumor cell growth. To date, there have been few reports on the relationship between pathologic FGFR2 expression and prognosis in patients who have undergone hepatectomy for ICC, and on the relationship between FGFR2 and tumor-infiltrating lymphocytes (TILs). Methods and Results: We enrolled 92 patients who underwent hepatectomy for ICC and performed immunohistochemical staining for FGFR2 and cluster of differentiation 8, and hematoxylin and eosin staining for evaluating TILSs. The relationships between the FGFR2 and clinicopathological characteristics and outcomes were analyzed, and patients were classified into positive (n = 18) and negative (n = 74) FGFR2 groups. The FGFR2-positive group contained more men (p < 0.0001) and had lower serum albumin (p = 0.0355) and higher carcinoembryonic antigen (p = 0.0099). Furthermore, multivariable analyses revealed that the FGFR2-positive group had worse disease-free survival (DFS) (p = 0.0002). Multivariate analysis showed that the independent prognostic factors for DFS were maximum tumor size (≥5 cm) (p = 0.0011), tumor localization (perihilar type) (p = 0.0180), and FGFR2 positivity (p = 0.0029). There was no significant difference in TILs count between the two groups. Conclusion: We showed that FGFR2 high expression was an independent prognostic factor for recurrence of resected ICC.

DOI： 10.1111/hepr.13875

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.prp.2023.154384.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1159/000525013.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/iju.15119.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.prp.2023.154423.

記述言語：英語   出版者・発行元：Pediatric Blood and Cancer  

DOI： 10.1002/pbc.30155

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記述言語：英語  

DOI： 10.1007/s13691-022-00592-5

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記述言語：英語   出版者・発行元：American Journal of Case Reports  

Objective: Background: Case Report: Conclusions: Rare disease Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal disease caused by the change of prion protein (PrP). Affected patients present with rapidly progressive cognitive dysfunction, myoclonus, or akinetic mutism. Diagnosing the Heidenhain variant of sCJD, which initially causes various visual symptoms, can be particularly difficult. A 72-year-old woman presented with a 2-to 3-month history of photophobia, blurring vision in both eyes. Seven days previously, she showed visual impairment of 20/2000 in both eyes. Left homonymous hemianopia and restricted downward movement of the left eye were observed with an intact pupillary light reflex and normal fundoscopy. On admission, her visual acuity was light perception. Cranial magnetic resonance imaging revealed no abnormality, and electroencephalography showed no periodic synchronous discharges. Cerebrospinal fluid examination on the sixth hospital day revealed tau and 14-3-3 protein with a positive result of real-time quak-ing-induced conversion. She thereafter developed myoclonus and akinetic mutism and died. Autopsy revealed thinning and spongiform change of the cerebral cortex of the right occipital lobe. Immunostaining showed syn-aptic-type deposits of abnormal PrP and hypertrophic astrocytes. Consequently, she was diagnosed with the Heidenhain variant of sCJD with both methionine/methionine type 1 and type 2 cortical form based on the western blot of cerebral tissue and PrP gene codon 129 polymorphism. When a patient presents with various progressive visual symptoms, even without typical findings of electro-encephalography or cranial magnetic resonance imaging, it is essential to suspect the Heidenhain variant of sCJD and perform appropriate cerebrospinal fluid tests.

DOI： 10.12659/AJCR.938654

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s00428-023-03497-7.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1186/s12885-023-10693-w.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.isci.2023.106480.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/cas.15644.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.prp.2023.154313.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： 10.1007/s10616-022-00559-7.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1038/s41420-023-01358-5.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s11605-023-05591-2.

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記述言語：英語   出版者・発行元：Cytotechnology  

The standard treatment for non-muscle-invasive bladder cancer is intravesical Bacillus Calmette–Guérin (BCG) therapy, which is considered the only intravesical therapy that reduces the risk of progression to muscle-invasive cancer. BCG unresponsiveness, in which intravesical BCG therapy is ineffective, has become a problem. It is thus important to evaluate the effectiveness of BCG treatment for patients as soon as possible in order to identify the optimal therapy. Urine cytology is a noninvasive, easy, and cost-effective method that has been used during BCG treatment, but primarily only to determine benign or malignant status; findings concerning the efficacy of BCG treatment based on urine cytology have not been reported. We investigated the relationship between BCG exposure and nuclear an important criterion in urine cytology, i.e., nuclear chromatin patterns. We used three types of cultured cells to evaluate nuclear chromatin patterns and the cell cycle, and we used T24 cells to evaluate the phosphorylation of retinoblastoma protein (pRb) in six-times of BCG exposures. The results revealed that after the second BCG exposure, (i) nuclear chromatin is distributed predominantly at the nuclear periphery and (ii) the dephosphorylation of threonine-821/826 in pRb occurs. This is the first report of a dynamic change in the nuclear chromatin pattern induced by exposure to BCG. Molecular findings also suggested a relationship between this phenomenon and cell-cycle proteins. Although these results are preliminary, they contribute to our understanding of the cytomorphological changes that occur with BCG exposure.

DOI： 10.1007/s10616-022-00559-7

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記述言語：英語   出版者・発行元：Cell Reports  

The cellular interactions in the tumor microenvironment of colorectal cancer (CRC) are poorly understood, hindering patient treatment. In the current study, we investigate whether events occurring at the invasion front are of particular importance for CRC treatment strategies. To this end, we analyze CRC tissues by combining spatial transcriptomics from patients with a public single-cell transcriptomic atlas to determine cell-cell interactions at the invasion front. We show that CRC cells are localized specifically at the invasion front. These cells induce human leukocyte antigen G (HLA-G) to produce secreted phosphoprotein 1 (SPP1)+ macrophages while conferring CRC cells with anti-tumor immunity, as well as proliferative and invasive properties. Taken together, these findings highlight the signaling between CRC cell populations and stromal cell populations at the cellular level.

DOI： 10.1016/j.celrep.2022.111929

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.prp.2022.154239.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.7150/jca.78993.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.22603/ssrr.2022-0063.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.2340/actadv.v103.4407.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.celrep.2022.111929.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1002/ctm2.1181.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.7150/jca.78993.

出版者・発行元：Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)  

Various applications of lip-reading technology are considered, and it is an important issue. In recent years, lip-reading research on sentences has attracted attention. However, most of the published datasets are English-talking scenes, and there are few datasets other than English. Therefore, in this research, we are researching Japanese sentence-level lip-reading. In this paper, we construct Japanese sentence utterance scene datasets ITA and ROHAN4600 and propose the Conformer-based lip-reading method. Recognition experiments were conducted using the Transformer model as a conventional method. As a result, it was confirmed that the Conformer model obtained high recognition accuracy both at the phoneme and the mora levels.

DOI： 10.1007/978-3-031-25825-1_34

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s00428-022-03403-7.

出版者・発行元：Comparative Clinical Pathology  

Immaturity of ganglia (IG), is a rare entity of an allied disorder of Hirschsprung’s disease. We reviewed our IG cases to provide further pathological insight into IG. The clinical data and pathological findings of IG cases in our department from 2011 to 2020 were examined. Hematoxylin and eosin (HE) staining and immunostaining for HuC/D, BCL-2, SOX10, and CD56 were performed on full-thickness specimens. Sufficient clinical data and pathological specimens were available in five cases during the study period. The patient profiles were as follows: four term infants and one preterm infant with initial symptoms of abdominal distension or vomiting; all cases underwent ileostomy at a median age of 2 days and stoma closure at a median age of 5 months. Although the interpretation of HE staining was difficult, immunostaining for HuC/D and SOX10 clearly distinguished ganglion cells from glial cells. The number of ganglion cells in the IG group was significantly greater than that in the control group (p < 0.05), while the number of enteric glial cells and total area of the myenteric nerve plexus did not differ. The finding of the increased number of ganglion cells in a normal-size myenteric plexus is a novel feature of IG that contributes to its accurate diagnosis.

DOI： 10.1007/s00580-022-03390-w

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記述言語：英語   出版者・発行元：Virchows Archiv  

Solitary fibrous tumors (SFTs) are rare mesenchymal tumors that can occur at any location. Since the identification of specific NAB2-STAT6 fusion in SFTs, the fusion gene variants, NAB2 exon 4-STAT6 exon 2/3 and NAB2 exon 5/6/7-STAT6 exon 16/17/18, have been reported to be associated with clinicopathological features, and the latter variant is predominant in meningeal SFTs. SFTs developing in the salivary glands are rare, and more rarely, those involving ectopic salivary glands (ESGs) have been reported in the cerebellopontine angle (CPA); however, their characteristics remain not well understood. In this study, we performed a clinicopathological and molecular analysis of 3 cases of meningeal SFT with ESGs. All cases presented with an extra-axial mass in the CPA, which is a rarer location for intracranial ESGs compared to the sellar region. Histologically, except for the presence of ESGs, there was no significant difference between current cases and ordinary SFTs. The ESGs demonstrated no cellular atypia, and although the spindle tumor cells were immunopositive for STAT6, the ESGs were negative in all cases, supporting that the ESGs are non-neoplastic components. In 1 case, ESGs were found only in the primary tumor and disappeared in recurrence/dissemination. Of note, molecular analysis identified NAB2 exon 4-STAT6 exon 2 in all cases. In conclusion, our results suggest that ESGs particularly in the CPA may be associated with SFTs and that meningeal SFTs with ESGs may be associated with the minor fusion variant of NAB2-STAT6 in the intracranial lesions.

DOI： 10.1007/s00428-022-03403-7

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s00432-021-03860-8.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.21037/tlcr-22-393.

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記述言語：英語   出版者・発行元：Pancreatology  

Figures in this paper contained western blots where the same membrane was probed repeatedly by the indicated antibodies, occasionally resulting in similar band shapes among the individual panels. Moreover, in Figure 5, results from the same membrane were presented in two columns with the panels for the α-SMA and β-actin blots shown twice for easier comparison. We apologize for any misunderstanding this may have caused.

DOI： 10.1016/j.pan.2022.08.013

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記述言語：英語   出版者・発行元：Cell  

After the global spread of the SARS-CoV-2 Omicron BA.2, some BA.2 subvariants, including BA.2.9.1, BA.2.11, BA.2.12.1, BA.4, and BA.5, emerged in multiple countries. Our statistical analysis showed that the effective reproduction numbers of these BA.2 subvariants are greater than that of the original BA.2. Neutralization experiments revealed that the immunity induced by BA.1/2 infections is less effective against BA.4/5. Cell culture experiments showed that BA.2.12.1 and BA.4/5 replicate more efficiently in human alveolar epithelial cells than BA.2, and particularly, BA.4/5 is more fusogenic than BA.2. We further provided the structure of the BA.4/5 spike receptor-binding domain that binds to human ACE2 and considered how the substitutions in the BA.4/5 spike play roles in ACE2 binding and immune evasion. Moreover, experiments using hamsters suggested that BA.4/5 is more pathogenic than BA.2. Our multiscale investigations suggest that the risk of BA.2 subvariants, particularly BA.4/5, to global health is greater than that of original BA.2.

DOI： 10.1016/j.cell.2022.09.018

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記述言語：英語   出版者・発行元：Science Advances  

Natural systems, composite materials, and thin-film devices adsorb macromolecules in different phases onto their surfaces. In general, polymer chains form interfacial layers where their aggregation states and thermal molecular motions differ from the bulk. Here, we visualize well-defined double-stranded DNAs (dsDNAs) using atomic force microscopy and molecular dynamics simulations to clarify the adsorption mechanism of polymer chains onto solid surfaces. Initially, short and long dsDNAs are individually and cooperatively adsorbed, respectively. Cooperative adsorption involves intertwining of multiple chains. The dependence of adsorption on the chain affects the formation of the interfacial layer, realizing different mechanical properties of DNA/filler bulk composites. These findings will contribute to the development of light and durable polymer composites and films for various industrial, biomedical, and environmental applications.

DOI： 10.1126/sciadv.abn6349

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記述言語：英語  

DOI： 10.1093/jscr/rjac478

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.ejrad.2022.110461.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1093/jnen/nlac078.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.prp.2022.154125.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.prp.2022.154124.

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記述言語：英語   出版者・発行元：Cell Host and Microbe  

The SARS-CoV-2 Omicron BA.2.75 variant emerged in May 2022. BA.2.75 is a BA.2 descendant but is phylogenetically distinct from BA.5, the currently predominant BA.2 descendant. Here, we show that BA.2.75 has a greater effective reproduction number and different immunogenicity profile than BA.5. We determined the sensitivity of BA.2.75 to vaccinee and convalescent sera as well as a panel of clinically available antiviral drugs and antibodies. Antiviral drugs largely retained potency, but antibody sensitivity varied depending on several key BA.2.75-specific substitutions. The BA.2.75 spike exhibited a profoundly higher affinity for its human receptor, ACE2. Additionally, the fusogenicity, growth efficiency in human alveolar epithelial cells, and intrinsic pathogenicity in hamsters of BA.2.75 were greater than those of BA.2. Our multilevel investigations suggest that BA.2.75 acquired virological properties independent of BA.5, and the potential risk of BA.2.75 to global health is greater than that of BA.5.

DOI： 10.1016/j.chom.2022.10.003

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s00795-022-00323-y.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.molmet.2022.101599.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： DOI: 10.3892/ol.2022.13457

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi:10.21873/anticanres.15934

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s10120-022-01307-8.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/his.14703.

記述言語：英語   出版者・発行元：Histopathology  

Hamartomas in the pancreas are rare and are often histologically and morphologically similar to solitary fibrous tumours (SFTs). We examined the differences between hamartomas and SFTs at the molecular level. Methods and results: Thirteen patients histopathologically diagnosed with pancreatic hamartoma were included in the study. We also performed STAT6 immunohistochemistry (IHC), which is used in the diagnosis of SFT. Furthermore, for the three cases in which RNA was extracted, reverse transcription polymerase chain reaction to search for NAB2::STAT6 fusions was used. Macroscopically, 13 patients had well-demarcated tumour lesions. Histologically, no islets of Langerhans were observed in the lesions, acinar tissue and ducts were unevenly distributed and elastic fibres were not observed around the ducts by Elastica van Gieson staining. One case contained a lipomatous hamartoma composed mainly of adipose tissue. Seven of the 13 cases demonstrated expression of STAT6 in the nuclei of intervening spindle cells. NAB2::STAT6 fusions were observed in two of the three cases in which RNA was extracted. These two cases also demonstrated STAT6 expression in spindle cells using STAT6 IHC. In one case of lipomatous hamartoma, we did not confirm NAB2::STAT6 fusion or STAT6 expression in STAT6 IHC. Conclusion: Of the 13 patients histopathologically diagnosed with hamartoma, two demonstrated NAB2::STAT6 fusions, suggesting the existence of pancreatic hamartomas with molecular-level components identical to those of SFT.

DOI： 10.1111/his.14703

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記述言語：英語   出版者・発行元：American Journal of Ophthalmology Case Reports  

Purpose: This article presents a case of panuveitis that occurred after unrelated allogeneic hematopoietic stem cell transplantation (allo-HSCT) in a patient with lymphoma-type human T-cell leukemia virus type-1 (HTLV-1)-associated adult T-cell leukemia (ATL). Observations: A 45-year-old man developed unilateral panuveitis 18 months after undergoing allo-HSCT. He underwent vitrectomy, and depositions of grey-white granules localized on the retinal artery were observed in the eye. Cytological examination of the vitreous aspirates showed that the atypical lymphoid cells stained positive for CD3 and CD8, but negative for CD4, B-cell markers, and cytomegalovirus antigen. Interphase fluorescence in situ hybridization using X‐ and Y‐chromosome probes revealed complete donor chimerism in CD8+ T cells in the vitreous aspirates. Conclusions and importance: Donor-derived CD8+ T lymphocytes can induce panuveitis like HTLV-1-assiciated uveitis after allo-HSCT in patients with ATL. Pathological diagnosis of vitreous infiltration by vitrectomy is helpful in patients with ATL. Donor-derived CD8+ T lymphocytes-induced panuveitis is recurrent but susceptible to regional corticosteroid treatment.

DOI： 10.1016/j.ajoc.2022.101673

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1038/s41598-022-17728-5.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s00428-022-03327-2.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/1759-7714.14524

記述言語：英語   出版者・発行元：Journal of Gastroenterology  

Background: This is the first report from a multicenter prospective cohort study of colorectal neuroendocrine tumor (NET), the C-NET STUDY, conducted to assess the long-term outcomes of the enrolled patients. This report aimed to elucidate the clinicopathological features of the enrolled patients and lesions. Methods: Colorectal NET patients aged 20–74 years were consecutively enrolled and followed up at 50 institutions. The baseline characteristics and clinicopathological findings at enrollment and treatment were assessed. Results: A total of 495 patients with 500 colorectal NETs were included. The median patient age was 54 years, and 85.3% were asymptomatic. The most frequent lesion location was the lower rectum (88.0%); 99.4% of the lesions were clinically diagnosed to be devoid of metastatic findings, and 95.4% were treated with endoscopic resection. Lesions < 10 mm comprised 87.0% of the total, 96.6% had not invaded the muscularis propria, and 92.6% were classified as WHO NET grade 1. Positive lymphovascular involvement was found in 29.2% of the lesions. Its prevalence was high even in small NETs with immunohistochemical/special staining for pathological assessment (26.4% and 40.9% in lesions sized < 5 mm and 5–9 mm, respectively). Among 70 patients who underwent radical surgery primarily or secondarily, 18 showed positive lymph node metastasis. Conclusions: The characteristics of real-world colorectal NET patients and lesions are elucidated. The high positivity of lymphovascular involvement in small NETs highlights the necessity of assessing the clinical significance of positive lymphovascular involvement based on long-term outcomes, which will be examined in later stages of the C-NET STUDY. Trial registration number: UMIN000025215.

DOI： 10.1007/s00535-022-01877-5

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1097/PAS.0000000000001857.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1093/biomethods/bpac014.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.prp.2022.153920.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.jpedsurg.2022.02.035.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1259/bjr.20211066.

記述言語：英語   出版者・発行元：American Journal of Surgical Pathology  

High-risk human papillomavirus (HPV) infection in conjunctival and lacrimal sac squamous cell carcinomas (SCCs) has been sporadically reported; however, its prevalence, clinicopathologic significance and surrogate markers have not been fully elucidated. Here, we attempted to clarify these questions in Japanese patients with conjunctiva and lacrimal sac SCCs. We retrospectively collected 51 conjunctival SCC and 7 lacrimal sac SCC samples and analyzed them for (1) transcriptionally active high-risk HPV infection using messenger RNA in situ hybridization and (2) protein expressions of p16 and Rb using immunohistochemistry (IHC). Among a total of 58 cases, 25 (43.1%) and 16 (27.6%) tumors were positive for p16-IHC and HPV in situ hybridization, respectively. Ten (19.6%) of the 51 conjunctival SCCs, especially in the palpebral conjunctiva, and 6 (85.7%) of the 7 lacrimal sac SCCs were positive for high-risk HPV. High-risk HPV infection was significantly associated with younger patients, nonkeratinizing SCC histology, p16-positivity and partial loss of Rb expression, but not with recurrence risk. Notably, p16-IHC was not a perfect surrogate marker for high-risk HPV infection; only 64% (16/25) of p16-positive tumors were positive for high-risk HPV. In contrast, the p16+/Rb partial loss pattern was exclusively correlated with high-risk HPV-positivity. The results suggest that the combination of p16 and Rb expression patterns by IHC could be a useful method to predict high-risk HPV infection in conjunctival and lacrimal sac SCCs. HPV infection may be of less prognostic value in this field of cancers.

DOI： 10.1097/PAS.0000000000001857

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.humpath.2022.03.002.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.crad.2022.03.001.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.3892/mco.2022.2564.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1136/jclinpath-2020-207311.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1089/end.2021.0483.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s00428-022-03277-9.

記述言語：英語   出版者・発行元：Clinical Radiology  

AIM: To determine whether the pathological response to preoperative chemotherapy for pancreatic ductal adenocarcinoma (PDAC) can be predicted using 2-[18F]-fluoro-2-deoxy-D-glucose positron-emission tomography (F-18 FDG-PET). MATERIALS AND METHODS: Twenty-eight patients with PDAC who underwent only neoadjuvant chemotherapy (NAC) before surgery were enrolled in the study. All patients had F-18 FDG-PET examinations before NAC. The resected specimen was pathologically evaluated according to the Classification of Pancreatic Carcinoma (7th edn). Patients were categorised into a non-response group and a response group based on the pathological findings. The non-response group (Grades 1a and 1b) showed ≤50% necrosis in the specimen, while the specimens of the response group (Grades 2–3) showed >50% necrosis. The maximum standardised uptake values (SUVmax) of the tumours on F-18 FDG-PET were measured. The mean values of SUVmax were compared between the two groups. The diagnostic performance of SUVmax in distinguishing the two groups was also evaluated using receiver operating characteristic analysis. RESULTS: The mean SUVmax of the response group was higher than that of the non-response group (9.00 ± 1.78 versus 4.26 ± 2.35; p<0.001). The optimal cut-off value of SUVmax was 9.28 for distinguishing the two groups. The sensitivity, specificity, and accuracy for the prediction in the response group were 80%, 95.7%, and 92.9%, respectively. CONCLUSIONS: SUVmax on F-18 FDG-PET may be useful as a biomarker to predict the pathological response to NAC in patients with PDAC.

DOI： 10.1016/j.crad.2022.03.001

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記述言語：英語   出版者・発行元：Virchows Archiv  

Mucinous cystic neoplasm (MCN) of the pancreas rarely progresses to invasive carcinoma, but few studies have analyzed genomic alterations involved in its malignant transformation. The relationships of ring finger protein 43 (RNF43) mutations with cytological atypia, RNF43 protein expression, and Wnt signaling proteins in MCN remain unclear. This study included 106 MCN cases, classified into 89 low-grade dysplasia (LG), 9 high-grade dysplasia (HG), and 8 invasive carcinoma (INV). We analyzed HG/INV and LG lesions of 9 HG/INV cases and LG lesions of 9 LG cases using targeted sequencing and confirmed the protein expression of RNF43 and β-catenin. The frequency of RNF43 mutations was significantly higher in HG/INV cases than in LG cases. Furthermore, HG/INV lesions (56%) and LG lesions (33%) of HG/INV cases possessed RNF43 mutation, whereas no such mutation was detected in any LG cases. The expression of RNF43 was reduced in 71% of HG/INV cases and significantly correlated with histological grade and aberrant expression of β-catenin. In 3 of 5 RNF43-mutated cases, the expression of RNF43 was reduced, but there was no significant correlation between RNF43 mutation and protein expression. MCNs frequently harbored KRAS mutations, at rates of 100% in HG/INV lesions and 50% in LG lesions of HG/INV and LG cases. There was no significant difference in mutation frequency in LG lesions between HG/INV and LG cases. These results suggest that RNF43 mutations may be involved in and predictive of malignant transformation from an early stage of MCN.

DOI： 10.1007/s00428-022-03277-9

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1038/s41379-021-00972-x.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1038/s41598-022-12528-3.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/pin.13222.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s00428-021-03261-9.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1038/s41416-021-01695-1.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1002/hep4.1838.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1684/ejd.2022.4241.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1038/s41598-022-10077-3.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.3390/jcm11072062.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.5217/ir.2021.00124.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s00428-022-03293-9.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.ygyno.2022.01.031.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1159/000521504.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1159/000521426.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1136/jclinpath-2022-208158.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.3892/ol.2022.13213.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1038/s41598-022-07727-x.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1186/s13046-022-02301-9.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1002/cam4.4537.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.humpath.2021.12.010.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1002/pros.24278.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/and.14307.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/his.14588.

記述言語：英語   出版者・発行元：Andrologia  

This study aimed to investigate the significance of HSD3B1 gene status including germline polymorphism and somatic alterations in prostate cancer. Patients with prostate cancer treated with androgen-deprivation therapy, as well as tissues from metastatic prostate cancer, were included. Genomic DNA was extracted from cancer tissues and whole blood samples, and HSD3B1 (rs1047303, 1245C) was genotyped by Sanger sequencing. The association of HSD3B1 genotype with progression-free survival according to metastatic volume was examined. Copy number alteration and gene expression of HSD3B1 were examined in prostate cancer cells and public datasets. Among 194 patients, 121 and 73 patients were categorized into low- and high-volume diseases respectively. In multivariate analysis, the adrenal-permissive genotype (AC/CC) was significantly associated with increased risk of progression compared with the adrenal-restrictive genotype (AA) in low volume, but not high-volume diseases. Somatic mutation in HSD3B1 was detected at least in two cases of castration-resistant prostate cancer tissues. HSD3B1 amplification and overexpression were detected in castration-resistant prostate cancer cells and tissues. The current findings suggest that both germline and somatic alterations of HSD3B1 may cooperatively promote castration resistance in prostate cancer and HSD3B1 as a promising biomarker for precision medicine, warranting further investigations.

DOI： 10.1111/and.14307

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記述言語：英語   出版者・発行元：Metabolites  

In mass spectrometry-based metabolomics, the differences in the analytical results from different laboratories/machines are an issue to be considered because various types of machines are used in each laboratory. Moreover, the analytical methods are unique to each laboratory. It is important to understand the reality of inter-laboratory differences in metabolomics. Therefore, we have evaluated whether the differences in analytical methods, with the exception sample pretreatment and including metabolite extraction, are involved in the inter-laboratory differences or not. In this study, nine facilities are evaluated for inter-laboratory comparisons of metabolomic analysis. Identical dried samples prepared from human and mouse plasma are distributed to each laboratory, and the metabolites are measured without the pretreatment that is unique to each laboratory. In these measurements, hydrophilic and hydrophobic metabolites are analyzed using 11 and 7 analytical methods, respectively. The metabolomic data acquired at each laboratory are integrated, and the differences in the metabolomic data from the laboratories are evaluated. No substantial difference in the relative quantitative data (human/mouse) for a little less than 50% of the detected metabolites is observed, and the hydrophilic metabolites have fewer differences between the laboratories compared with hydrophobic metabolites. From evaluating selected quantitatively guaranteed metabolites, the proportion of metabolites without the inter-laboratory differences is observed to be slightly high. It is difficult to resolve the inter-laboratory differences in metabolomics because all laboratories cannot prepare the same analytical environments. However, the results from this study indicate that the inter-laboratory differences in metabolomic data are due to measurement and data analysis rather than sample preparation, which will facilitate the understanding of the problems in metabolomics studies involving multiple laboratories.

DOI： 10.3390/metabo12020135

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.pan.2021.09.012.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/ped.15228.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.3390/jcm11030607.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1186/s12885-022-09195-y.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/cas.15187.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1159/000521382.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1002/cnr2.1420.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/bpa.13014

記述言語：英語   出版者・発行元：Surgical Neurology International  

Background: Angiolipomas are benign mesenchymal tumors comprising mature adipocytes and abnormal blood vessels, commonly found in the subcutaneous tissue of the trunk and rarely in the skull. Furthermore, sporadic cases of angiolipoma with arteriovenous fistula (AVF) have been reported. Case Description: We reported the case of a 72-year-old woman who presented with head swelling, seizures, and cognitive dysfunction. Computed tomography and magnetic resonance imaging revealed a right frontal bone tumor exceeding a sagittal suture of up to 10.7 cm. Angiography revealed AVF and varices formation. Endovascular embolization was performed to treat the AVF and reduce blood loss during surgical resection. Two days after the embolization, a craniotomy was performed; however, uncontrollable bleeding was observed at the time of tumor resection. Postoperatively, the patient was symptom-free and has been stable for 2 years without recurrence. Conclusion: Despite careful preoperative evaluation and treatment planning, the patient in this case report was difficult to treat. Such cases require adequate preparation.

DOI： 10.25259/SNI_422_2022

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s00428-021-03189-0.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1038/s41379-021-00868-w.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1245/s10434-021-10209-5.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/his.14400.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1186/s13287-021-02652-8.

リポジトリ公開URL： https://hdl.handle.net/2324/7172586

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/pin.13170.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1038/s41379-021-00868-w.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1038/s41598-021-94022-w.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s10147-021-01962-4.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s10147-021-01985-x.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.prp.2021.153635.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.ekir.2021.09.007.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.jjcc.2021.03.014.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.cell.2021.07.020.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s10120-021-01194-5.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1097/SLA.0000000000005001

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.humpath.2021.05.001.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.21873/anticanres.15217.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1101/mcs.a006102.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.lungcan.2021.05.023.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/cas.14971.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s00432-021-03616-4.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.3390/ijms22147706.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.3389/fonc.2021.710378.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.humpath.2021.03.009.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1038/s41598-021-91358-1.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.humpath.2021.03.001.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1002/cam4.3828.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/his.14393.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1097/PAS.0000000000001672.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1002/hep4.1659.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1038/s41379-020-00702-9.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1038/s41598-021-87748-0.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s00432-020-03390-9.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1002/hep4.1715.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1038/s41598-021-85186-6.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.3390/biomedicines9040355.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1002/ijc.33322.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.3892/or.2021.7947.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1016/j.humpath.2020.11.017.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1007/s00432-020-03438-w.

記述言語：英語   掲載種別：研究論文（学術雑誌）  

DOI： doi: 10.1111/his.14357. Online ahead of print.