Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/sj.onc.1207960

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/path.1282

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1097/00000478-200108000-00007

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/modpathol.3880180

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：Scientific Reports  

Extramammary Paget disease (EMPD) is a rare skin cancer that typically occurs in the anogenital area of older people. Since efficacy of treatments for metastatic or unresectable EMPD remains poor, development of a novel therapeutic approach is strongly desired. However, the lack of EMPD models has hampered investigation of EMPD. Here we investigated whether trophoblast cell surface antigen 2 (TROP2) could be a promising therapeutic target for EMPD. We retrospectively collected 108 samples from 54 patients with primary and metastatic EMPD from 10 Japanese institutions, and compared TROP2 expression between primary and metastatic lesions of each paired sample. In vitro assays were performed using a newly established EMPD cell line, KS-EMPD-1. TROP2 was strongly and homogeneously expressed in patient tissues, regardless of primary or metastatic lesions. The KS-EMPD-1 cells were treated with a TROP2-targeted antibody–drug conjugate (ADC), sacituzumab govitecan, and it significantly reduced cell viability in a dose-dependent manner compared with that of the cells treated with sacituzumab alone. Knockdown of TROP2 reduced cell viability and cell migration, and caused slight upregulation of the apoptosis-related factors, together with downregulation of the epithelial-to-mesenchymal transition-related factors. These findings suggest that a TROP2-targeted ADC may be a promising treatment option for unresectable EMPD.

DOI： 10.1038/s41598-024-84566-y

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Language：English   Publisher：Pediatric Blood and Cancer  

Programs allowing access to investigational drugs and off-label drug use for serious diseases have often been applied to pediatric cancers. A clinical study conducted under the Japanese “Patient-Proposed Healthcare Services” evaluated the efficacy and safety of dabrafenib plus trametinib in children with BRAF V600 mutant glioma (jRCTs071210071). This study successfully provided unapproved and off-label medications to four enrolled patients, two with low-grade glioma and two with high-grade glioma (median age: 10.5 years), until regulatory approval. The timeframe and data collection from such access programs need to be optimized for pediatric patients in accordance with the healthcare system of each nation.

DOI： 10.1002/pbc.31510

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Language：English   Publisher：Cancer Letters  

Therapies targeting HER2 are the standard treatment for HER2-positive gastric cancer (GC). Trastuzumab, a monoclonal antibody against HER2, exerts anti-tumor activity through cell growth regulation and antibody-dependent cellular cytotoxicity (ADCC). ADCC is induced by the binding of trastuzumab to Fcγ receptor III (CD16) in natural killer (NK) cells. However, the relationship between immune checkpoint (IC) molecules of NK cells and trastuzumab-induced ADCC is poorly understood. We performed single-cell RNA sequencing (scRNA-seq) and immunohistochemistry to identify IC molecules associated with CD16 expression in NK cells of GC patients. Additionally, we conducted in vitro assays with HER2-transfected GC cells and in vivo experiments using a mouse HER2-positive GC model to assess expression changes in IC molecules in NK cells and their ligands during trastuzumab treatment. In GC patients, the expression of TIM3, an IC molecule, was strongly correlated with that of CD16 in NK cells. In vitro assays showed that ADCC with trastuzumab increased TIM3 expression in NK cells. scRNA-seq analysis revealed that TIM3 expression of cytotoxic NK cells was elevated in HER2-positive GC patients treated with trastuzumab. HMGB1, a TIM3 ligand, was expressed at higher levels in HER2-transfected GC cells than in controls. Furthermore, HMGB1 expression was higher in HER2-positive GC patients treated with trastuzumab compared to untreated HER2-positive GC patients. In the mouse HER2-positive GC model, anti-TIM3 antibodies and trastuzumab demonstrated synergistic anti-tumor effects without toxicity. This study suggests the combined anti-TIM3 antibody and trastuzumab therapy may have potential as a new treatment strategy for HER2-positive GC.

DOI： 10.1016/j.canlet.2024.217412

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DOI： 10.1111/cas.70018

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DOI： 10.1007/s10147-024-02666-1

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DOI： 10.1111/cas.16409

PubMed

Language：English   Publisher：Journal of Cancer Research and Clinical Oncology  

Purpose: Congenital mesoblastic nephromas (CMN) are histologically classified into classical, cellular, and mixed subtypes. Most cellular CMNs harbor ETV6-NTRK3 gene fusions, and classic and mixed CMNs harbor EGFR internal tandem duplications (EGFR-ITDs). Classic CMNs are considered benign, whereas recurrent or metastatic diseases occur in the cellular subtypes. Direct identification of mutations is desirable for an accurate diagnosis. However, molecular genetic analyses cannot be performed in a number of histopathology laboratories. This study aimed to investigate a surrogate marker for the accurate histological classification of CMN. Methods: Overall, 11 CMN cases diagnosed at our institute were included in this study. Reverse transcription-polymerase chain reaction was performed for the NTRK gene fusion and EGFR-ITDs in all cases. Comprehensive mRNA analysis was performed using the nCounter® Gene Expression Assay. Principal component analysis (PCA) was performed based on the gene expression levels. Immunohistochemical evaluation was conducted for the expression of p-Mek1/2, p-Erk1/2, and EGFR. Results: PCA revealed differences in mutation patterns between the EGFR-ITDs and NTRK fusion tumor groups. Gene ontology analysis of the highly expressed genes in the EGFR-ITDs tumor group revealed enrichment related to the mitogen-activated protein kinase (MAPK) signaling pathway. p-Mek1/2 and p-Erk1/2 immunoreactivity was significantly increased in the EGFR-ITDs tumor group (p = 0.018 and p = 0.017, respectively). EGFR immunoreactivity is not a useful marker for CMN with EGFR-ITD. Conclusion: p-Mek1/2 and p-Erk1/2 immunoreactivity may be useful markers for EGFR-ITDs. Thus, MEK1/2 inhibitors possess the potential to be used as a targeted therapy for CMN with EGFR-ITDs.

DOI： 10.1007/s00432-025-06116-x

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Language：English   Publisher：Journal of Cancer Research and Clinical Oncology  

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is considered a “cold” tumor because the tumor immune microenvironment (TIME) exhibits poor intratumoral T-cell infiltration. This study aimed to identify the marker genes associated with induction of cold TIME in PDAC cells. Methods: We orthotopically transplanted 10 primary cultures of PDAC derived from KrasG12D/+; Trp53R172H/+; Pdx-1-Cre (KPC) mice into immunocompetent mice and evaluated TIME by immunohistochemistry (IHC) staining of CD8. We divided primary cultures into two groups: cold TIME group with low CD8+ T-cell infiltration and a hot TIME group with high infiltration. RNA sequencing was performed to identify specific genes in the cold TIME group, and single-cell RNA sequencing (scRNA-seq) data was used for validation. IHC was performed to evaluate expressions in human PDAC samples. Results: We identified six genes specific in PDAC cells to the cold TIME group by RNA sequencing; these were defined as “cold tumor induction–related genes”. Human PDAC scRNA-seq data revealed that cold tumor induction–related genes were significantly and negatively correlated with the number of CD8+ T-cells (p = 0.0341). These genes included protocadherin 7 (PCDH7). High expression of PCDH7 significantly and negatively correlated with the number of CD8+ T-cells in scRNA-seq (p = 0.0474) and IHC (p = 0.0110) data using human PDAC samples. PCDH7 was an independent factor for poor prognosis in PDAC (overall survival: hazard ratio = 2.07, p = 0.0367). Conclusion: PCDH7 is a prognostic marker associated with CD8+ T-cell infiltration for PDAC patients.

DOI： 10.1007/s00432-025-06095-z

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Language：English  

DOI： 10.1038/s44276-024-00120-3

PubMed

Language：English   Publisher：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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Language：English   Publisher：Journal of Orthopaedic Science  

Background: In Japan, there are currently no general guidelines for the treatment of primary malignant bone tumors. Therefore, the Japanese Orthopaedic Association established a committee to develop guidelines for the appropriate diagnosis and treatment of primary malignant bone tumors for medical professionals in clinical practice. Methods: The guidelines were developed in accordance with “Minds Clinical Practice Guideline Development Handbook 2014″ and “Minds Clinical Practice Guideline Development Manual 2017". The Japanese Orthopaedic Association's Bone and Soft Tissue Tumor Committee established guideline development and systematic review committees, drawing members from orthopedic specialists leading the diagnosis and treatment of bone and soft tissue tumors. Pediatricians, radiologists, and diagnostic pathologists were added to both committees because of the importance of multidisciplinary treatment. Based on the diagnosis and treatment algorithm for primary malignant bone tumors, important decision-making points were selected, and clinical questions (CQ) were determined. The strength of recommendation was rated on two levels and the strength of evidence was rated on four levels. The recommendations published were selected based on agreement by 70% or more of the voters. Results: The guideline development committee examined the important clinical issues in the clinical algorithm and selected 22 CQs. The systematic review committee reviewed the evidence concerning each CQ and a clinical value judgment was added by experts. Eventually, 25 questions were published and the text of each recommendation was determined. Conclusion: Since primary malignant bone tumors are rare, there is a dearth of strong evidence based on randomized controlled trials, and recommendations cannot be applied to all the patients. In clinical practice, appropriate treatment of patients with primary malignant bone tumors should be based on the histopathological diagnosis and degree of progression of each case, using these guidelines as a reference.

DOI： 10.1016/j.jos.2023.11.007

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Language：English   Publisher：Asian Journal of Endoscopic Surgery  

Introduction: This study examined factors that affected sentinel lymph node (SLN) identification of patients with endometrial cancer having a preoperative estimation of low recurrent risk. Methods: This study included 97 patients with endometrial cancer who attempted to identify SLN using a uterine cervical injection of technetium-99 m phytate under laparoscopic or robotic-assisted surgery at our institute. A preoperative single photon emission computed tomography (SPECT) and intraoperative gamma probe were used to detect hot nodes. Multiple clinical factors, including age, body mass index (BMI), and so on, were investigated for their association with SLN mapping failure. Results: Among 97 cases, SPECT failed to detect SLN unilaterally in 38 cases (39%) and on both sides in 9 cases (9%). Meanwhile, the gamma probe failed to detect SLN unilaterally in 23 cases (24%) and on both sides in 3 cases (3%). While only age was significantly associated with SLN detection failure using the SPECT detection system, both age and BMI were significantly associated with SLN detection failure using the gamma probe detection system. When limiting to the preoperative SLN detection failure cohort of 47 cases, there was a strong association between intraoperative SLN detection failure and BMI, but not age. Conclusion: The SLN biopsy system was effectively applied to patients with endometrial cancer who underwent minimally invasive surgery (MIS). Attempts to improve SLN identification in older patients and those with obesity are warranted to obtain maximum benefits of MIS for low- or medium-risk cases.

DOI： 10.1111/ases.70015

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Language：English   Publisher：Annals of Surgical Oncology  

Background: Tumor microvasculature is an important component of the tumor microenvironment (TME), and it has been reported that tumor microvasculature induces TME to become immunosuppressive via vascular endothelial growth factor. However, the significance of this in adenocarcinoma with epidermal growth factor receptor (EGFR) common mutations has not been fully investigated. Methods: We analyzed 262 patients with adenocarcinoma harboring EGFR common mutations who underwent surgery at Kyushu University Hospital between 2006 and 2021. Microvessel density (MVD) was calculated by CD34 immunohistochemistry. Patients were categorized into high and low MVD status, which was compared with the clinicopathological characteristics. Results: A total of 136 (51.9%) patients had L858R mutation, and 126 (48.1%) had Exon 19 Del. Regarding MVD status; 133 patients (50.8%) were classified as high and 129 (49.2%) as low. Fisher’s exact test revealed a significant association of high MVD status with high CD8+ tumor infiltrating lymphocytes (TILs) (p = 0.0187), low GZMB+ TILs (p = 0.0019), and high Foxp3+ TILs (p = 0.0003). On multivariate analysis, MVD status was significantly associated with Foxp3+ TILs and GZMB+ TILs. Fisher’s exact test also revealed that tumors with L858R mutation had a high MVD status (p = 0.0136) compared with tumors with deletions of exon 19 (Exon 19 Del), and multivariate analysis revealed that L858R mutation was significantly associated with high MVD status. Conclusions: In adenocarcinomas harboring EGFR common mutations, abundant tumor microvasculature might induce the TME to be immunosuppressive. Tumors with L858R mutation compared with Exon 19 Del might be more likely to form an immunosuppressive TME owing to the abundance of tumor microvasculature.

DOI： 10.1245/s10434-024-16806-4

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Language：English   Publisher：Gastric Cancer  

Background: The role of janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling remains unclear in gastric solid-type poorly differentiated adenocarcinoma. The present study investigates the clinicopathological significance of JAK2, STAT3, and STAT4 expression in solid-type poorly differentiated adenocarcinoma. Methods: We retrospectively enrolled 102 participants with primary solid-type poorly differentiated adenocarcinoma. We categorized participants according to deficient or proficient mismatch repair status (46 and 56 participants, respectively). Expression of phosphorylated JAK2 (pJAK2), phosphorylated STAT3 (pSTAT3), and STAT4 were analyzed via immunohistochemistry. We analyzed differences in protein expression in relation to mismatch repair status, and associations of high/low protein expression with clinicopathological characteristics and prognoses. Results: Deficient mismatch repair was found to be associated with high pJAK2 (p = 0.038) and STAT4 (p = 0.023) expression in contrast to proficient mismatch repair. Log-rank analysis revealed high pSTAT3 and low STAT4 expression to be significantly correlated with reduced overall survival (p = 0.001). Multivariate analysis revealed high pSTAT3 and low STAT4 expression to be independent indicators of unfavorable prognosis (hazard ratio = 2.751, p = 0.030), as was proficient mismatch repair status (hazard ratio = 3.819, p = 0.012). Conclusions: High expression of pJAK2 and STAT4 is more frequent in deficient compared with proficient mismatch repair in solid-type poorly differentiated adenocarcinoma. High pSTAT3 and low STAT4 expression could be a useful prognostic indicator in solid-type poorly differentiated adenocarcinoma.

DOI： 10.1007/s10120-025-01589-8

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DOI： 10.1093/icvts/ivae181

PubMed

Language：English   Publisher：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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Language：English   Publisher：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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Language：English   Publisher：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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Language：English   Publisher：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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DOI： 10.1093/ehjimp/qyae141

Language：English  

DOI： 10.1093/jjco/hyae160

PubMed

Language：English   Publisher：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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Language：English   Publisher：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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Language：English   Publisher：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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Language：English  

DOI： 10.1016/j.prp.2024.155642

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Language：English   Publisher：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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Language：English   Publisher：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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DOI： 10.1016/j.esmoop.2024.103726

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DOI： 10.1158/0008-5472.CAN-24-0830

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DOI： 10.1158/1078-0432.CCR-24-1004

PubMed

Language：English   Publisher：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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DOI： 10.1136/jcp-2023-208814

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PubMed

Language：English   Publisher：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

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.5551/jat.64394.

Language：English   Publisher：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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PubMed

Language：English   Publisher：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

Language：English  

DOI： 10.1093/jjco/hyae095

PubMed

Language：English   Publisher：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

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publisher：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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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/his.15169.

Language：English   Publisher：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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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1007/s10120-024-01474-w

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.molmet.2024.101954

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00535-024-02104-z

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1007/s00535-024-02088-w

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.ebiom.2024.105102

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/neup.12974.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/liv.15839.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00535-024-02103-0

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41416-024-02576-z.

Language：English   Publisher：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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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/cas.16060.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.humpath.2024.02.007.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.ebiom.2024.105087.

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00428-024-03796-7.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s10120-023-01456-4.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/deo2.333.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00234-024-03288-0.

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1093/jjco/hyae020

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00261-023-04179-3

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1136/jcp-2022-208589.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41698-024-00515-y.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/cas.15981.

DOI： 10.1111/cas.15981

Language：English   Publisher：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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PubMed

Language：English   Publisher：Cancer Science  

Ovarian carcinosarcoma (OCS) is a rare and aggressive tumor, and the development of its sarcomatous component is believed to be due to epithelial–mesenchymal transition (EMT). The SWIch/sucrose nonfermentable chromatin remodeling factor (CRF) is closely related to EMT; however, the relationship between CRF and EMT in OCS remains unclear. In this study, we analyzed the protein expression of CRFs, including ARID1A and SMARCA4, and their downstream mRNA expression in 28 OCS cases, two fallopian tube CS cases, and one peritoneal CS case. ARID1A and SMARCA4 exhibited a histological type-specific loss of protein expression in 5 of 11 (45%) endometrioid cases and all 5 serous/homologous OCS cases, respectively. The mRNA analysis suggested that sarcomatogenesis is induced by the transforming growth factor-β and Hippo signaling pathways, both of which regulate YAP1. Immunostaining for YAP1 suggested YAP1-associated sarcomatogenesis in the CRF-retained group, whereas YAP1-unassociated sarcomatogenesis was suggested in the CRF-reduced group. High-grade serous carcinoma cell line experiments showed that the transcriptome of the SMARCA4-knockdown group showed lower expression of the epithelial gene CDH1 and higher expression of mesenchymal genes such as VIM, ZEB1, and SNAI1 than the control group. Moreover, cell adhesion disappeared and cell morphology changed to a spindle shape, indicating sarcomatogenesis. In conclusion, this study reveals a mechanism for sarcoma development in OCS and provides novel therapeutic possibilities.

DOI： 10.1111/cas.16423

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PubMed

Language：English   Publisher：Gastric Cancer  

Background: Gastric cancer (GC) shows limited response to immune checkpoint inhibitors due to its complex tumor immune microenvironment (TIME). This study explores the functions of various immune cells in the complex TIME in GC. Methods: We assessed CD8 + T-cell infiltration of GC tissues by immunohistochemistry, and performed single-cell RNA sequencing (scRNA-seq) of tumor and normal tissues from 34 patients with GC. Results: We categorized 157 GC patients into LOW, MID, and HIGH groups based on their CD8 + T-cell infiltration. Overall survival was notably lower for the HIGH and LOW groups compared with the MID group. Our scRNA-seq data analysis showed that CD8 + T-cell activity markers in the HIGH group were expressed at lower levels than in normal tissue, but the T-cell-attracting chemokine CCL5 was expressed at a higher level. Notably, CD8 + T-cells in the HIGH group displayed lower PD1 expression and higher CTLA4 expression. TCR repertoire analysis using only Epstein–Barr virus-negative cases showed that CD8 + T-cell receptor clonality was lower in the HIGH group than in the MID group. Furthermore, in the HIGH group, the antigen-presenting capacity of type 1 conventional dendritic cells was lower, the immunosuppressive capacity of myeloid-derived suppressor cells was higher, and the expression of CTLA4 in regulatory T-cells was higher. Conclusion: The present data suggest that the infiltration of inactive CD8 + T-cells with low clonality is induced by chemotaxis in the HIGH group, possibly leading to a poor prognosis for patients with GC.

DOI： 10.1007/s10120-024-01577-4

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PubMed

Language：English   Publisher：The Japanese Society of Internal Medicine  

<p>A 75-year-old man diagnosed with esophageal cancer and lung metastasis received a combination of fluorouracil, cisplatin, and pembrolizumab. During pembrolizumab maintenance therapy, lymphoproliferative lesions at the lips and mouth and multiple lymph node swellings appeared. Histologically, Epstein-Barr virus (EBV)-encoded RNA was positive, and EBV-DNA was detected in the blood. The patient was diagnosed with other iatrogenic immunodeficiency-associated lymph proliferative disorders (OIIA-LPDs) related to EBV activation induced by pembrolizumab. Rituximab was administered, resulting in the improvement of the OIIA-LPD. The emergence of an OIIA-LPD merits close attention in patients receiving immune checkpoint inhibitors. </p>

DOI： 10.2169/internalmedicine.3743-24

PubMed

CiNii Research

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1007/s11748-023-01938-3.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1245/s10434-023-14053-7.

Publisher：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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Language：English   Publisher：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

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.3390/cancers15235608.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1245/s10434-023-14085-z.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1007/s00262-023-03505-4.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1111/cas.15921.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1186/s12885-023-11528-4.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1038/s41416-023-02396-7

Language：English   Publisher：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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PubMed

Language：English   Publisher：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。

Language：English   Publisher：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

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.3389/fimmu.2023.1276014.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.3390/cancers15184456.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1016/j.modpat.2023.100336

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1111/cas.15901.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1097/PAS.0000000000002089.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1097/PAS.0000000000002086.

Language：English   Publisher：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

Language：English   Publisher：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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PubMed

Publisher：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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Language：English   Publishing type：Research paper (scientific journal)  

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

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1002/ags3.12730

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1002/ags3.12735

Language：English   Publishing type：Research paper (scientific journal)  

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

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1111/1759-7714.15014.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1007/s00432-022-04554-5.

Language：English   Publishing type：Research paper (scientific journal)  

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

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1038/s41598-023-40050-7.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1007/s10147-023-02358-2.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1111/hepr.13902.

Language：English   Publisher：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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Language：English   Publisher：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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Language：English   Publisher：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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Language：English   Publisher：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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DOI： doi: 10.1016/j.jpedsurg.2023.01.050.

Language：Japanese   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1007/s00428-023-03572-z.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1007/s00432-022-04078-y.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.21873/anticanres.16462.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1111/1759-7714.14910.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1245/s10434-022-13058-y.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1007/s00262-022-03353-8.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1245/s10434-022-12926-x.

DOI： 10.1245/s10434-022-12974-3

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Language：English   Publisher：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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Language：English   Publisher：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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Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1111/cas.15729.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1111/hepr.13875.

Language：English   Publishing type：Research paper (scientific journal)  

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

Language：English   Publisher：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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Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1016/j.prp.2023.154384.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1159/000525013.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1111/iju.15119.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1016/j.prp.2023.154423.

Language：English   Publisher：Pediatric Blood and Cancer  

DOI： 10.1002/pbc.30155

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DOI： 10.1007/s13691-022-00592-5

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Language：English   Publisher：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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Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1007/s00428-023-03497-7.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1016/j.isci.2023.106480.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1111/cas.15644.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1186/s12885-023-10693-w.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1016/j.prp.2023.154313.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s10616-022-00559-7.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1038/s41420-023-01358-5.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1007/s11605-023-05591-2.

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Language：English   Publisher：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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Language：English   Publisher：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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Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1016/j.prp.2022.154239.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.7150/jca.78993.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.22603/ssrr.2022-0063.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.2340/actadv.v103.4407.

Language：English   Publishing type：Research paper (scientific journal)  

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

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1002/ctm2.1181.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.7150/jca.78993.

Publisher：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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Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1007/s00428-022-03403-7.

Publisher：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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Language：English   Publisher：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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Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1007/s00432-021-03860-8.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.21037/tlcr-22-393.

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Language：English   Publisher：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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Language：English   Publisher：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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Language：English   Publisher：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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DOI： 10.1093/jscr/rjac478

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Language：English   Publishing type：Research paper (scientific journal)  

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

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1093/jnen/nlac078.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1016/j.prp.2022.154125.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1016/j.prp.2022.154124.

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Language：English   Publisher：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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DOI： doi: 10.1007/s00795-022-00323-y.

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

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

Language：English   Publishing type：Research paper (scientific journal)  

DOI： DOI: 10.3892/ol.2022.13457

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi:10.21873/anticanres.15934

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1007/s10120-022-01307-8.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1111/his.14703.

Language：English   Publisher：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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Language：English   Publisher：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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Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1038/s41598-022-17728-5.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1007/s00428-022-03327-2.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1111/1759-7714.14524

Language：English   Publisher：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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Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1097/PAS.0000000000001857.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1093/biomethods/bpac014.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1016/j.prp.2022.153920.

Language：English   Publishing type：Research paper (scientific journal)  

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

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1259/bjr.20211066.

Language：English   Publisher：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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Language：English   Publishing type：Research paper (scientific journal)  

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

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1016/j.crad.2022.03.001.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.3892/mco.2022.2564.

Language：English   Publishing type：Research paper (scientific journal)  

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

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1089/end.2021.0483.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1007/s00428-022-03277-9.

Language：English   Publisher：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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Language：English   Publisher：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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Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1038/s41379-021-00972-x.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1038/s41598-022-12528-3.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1111/pin.13222.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1007/s00428-021-03261-9.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1038/s41416-021-01695-1.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1002/hep4.1838.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1684/ejd.2022.4241.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1038/s41598-022-10077-3.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.3390/jcm11072062.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.5217/ir.2021.00124.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1007/s00428-022-03293-9.

Language：English   Publishing type：Research paper (scientific journal)  

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

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1159/000521504.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1159/000521426.

Language：English   Publishing type：Research paper (scientific journal)  

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

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.3892/ol.2022.13213.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1038/s41598-022-07727-x.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1186/s13046-022-02301-9.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1002/cam4.4537.

Language：English   Publishing type：Research paper (scientific journal)  

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

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1002/pros.24278.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1111/and.14307.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1111/his.14588.

Language：English   Publisher：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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Language：English   Publisher：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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Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1016/j.pan.2021.09.012.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1111/ped.15228.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.3390/jcm11030607.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1186/s12885-022-09195-y.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1111/cas.15187.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1159/000521382.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1002/cnr2.1420.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1111/bpa.13014

Language：English   Publisher：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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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1007/s00428-021-03189-0.

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1038/s41379-021-00868-w.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1245/s10434-021-10209-5.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1111/his.14400.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1186/s13287-021-02652-8.

Repository Public URL： https://hdl.handle.net/2324/7172586

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1111/pin.13170.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1038/s41379-021-00868-w.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1038/s41598-021-94022-w.

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1007/s10147-021-01962-4.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1007/s10147-021-01985-x.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1016/j.prp.2021.153635.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1016/j.ekir.2021.09.007.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1016/j.jjcc.2021.03.014.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1016/j.cell.2021.07.020.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1007/s10120-021-01194-5.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1097/SLA.0000000000005001

Language：English   Publishing type：Research paper (scientific journal)  

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

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.21873/anticanres.15217.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1101/mcs.a006102.

Language：English   Publishing type：Research paper (scientific journal)  

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

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1111/cas.14971.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1007/s00432-021-03616-4.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.3390/ijms22147706.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.3389/fonc.2021.710378.

Language：English   Publishing type：Research paper (scientific journal)  

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

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1038/s41598-021-91358-1.

Language：English   Publishing type：Research paper (scientific journal)  

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

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1002/cam4.3828.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1111/his.14393.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1097/PAS.0000000000001672.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1002/hep4.1659.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1038/s41379-020-00702-9.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1038/s41598-021-87748-0.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1007/s00432-020-03390-9.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1002/hep4.1715.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1038/s41598-021-85186-6.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.3390/biomedicines9040355.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1002/ijc.33322.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.3892/or.2021.7947.

Language：English   Publishing type：Research paper (scientific journal)  

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

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1007/s00432-020-03438-w.

Language：English   Publishing type：Research paper (scientific journal)  

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

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1002/hep4.1643.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1016/j.ejso.2020.08.002.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1097/PAS.0000000000001566.

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1002/gcc.22899.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.21873/anticanres.14752.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1111/cas.14790.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1002/cam4.3619.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1002/cam4.3713. Online ahead of print.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1186/s13287-020-02113-8.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1111/ped.14596. Online ahead of print.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1111/cas.14695.

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1007/s00262-020-02659-9.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： DOI: 10.22541/au.159863177.79676202

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1111/his.14337. Online ahead of print.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.3892/or.2020.7837.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1007/s00428-020-02844-2.

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1158/1541-7786.MCR-20-0186.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.21873/anticanres.14642.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1002/hep4.1643.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1002/jhbp.819.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1371/journal.pone.0241580.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1016/j.mri.2020.08.018. Epub 2020 Aug 27.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1007/s00428-020-02839-z.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.21873/anticanres.14579.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1016/j.humpath.2020.09.004.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1038/s41598-020-72962-z.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1016/j.pan.2020.07.011. Epub 2020 Jul 25.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.3390/jcm9103133.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1111/pin.12952.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1016/j.humpath.2020.04.003.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1016/j.transproceed.2020.01.164.

Language：English  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi: 10.1111/cas.14515.

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00428-019-02741-3

Language：English  

Language：English   Publishing type：Research paper (scientific journal)  

DOI： DOI: 10.1002/ags3.12340

Language：English   Publishing type：Research paper (scientific journal)  

DOI： doi:10.1097/SLA.0000000000003060

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DOI： 10.1007/s00432-020-03242-6

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00432-020-03250-6

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/hepr.13484

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s41416-020-0810-1

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s00262-020-02508-9

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.lungcan.2020.04.034

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1007/s12282-019-01043-5

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DOI： 10.1007/s00432-020-03146-5

Language：English  

Language：English   Publishing type：Research paper (scientific journal)