|馬場 英司（ばば えいし）||データ更新日：2019.07.03|
教授 ／ 医学研究院 附属総合コホートセンター 社会環境医学講座 連携社会医学分野
|1.||Toshikazu Moriwaki, Shota Fukuoka, Hiroya Taniguchi, Atsuo Takashima, Yusuke Kumekawa, Takeshi Kajiwara, Kentaro Yamazaki, Taito Esaki, Chinatsu Makiyama, Tadamichi Denda, Hironaga Satake, Takeshi Suto, Naotoshi Sugimoto, Masanobu Enomoto, Toshiaki Ishikawa, Tomomi Kashiwada, Masahiko Sugiyama, Yoshito Komatsu, Hiroyuki Okuyama, Eishi Baba, Daisuke Sakai, Tomoki Watanabe, Takao Tamura, Kimihiro Yamashita, Masahiko Gosho, Yasuhiro Shimada, Propensity Score Analysis of Regorafenib Versus Trifluridine/Tipiracil in Patients with Metastatic Colorectal Cancer Refractory to Standard Chemotherapy (REGOTAS)
A Japanese Society for Cancer of the Colon and Rectum Multicenter Observational Study, Oncologist, 10.1634/theoncologist.2017-0275, 23, 1, 7-15, 2018.01, [URL], Background: This study compared the efficacy of regorafenib and trifluridine/tipiracil (TFTD) in patients with metastatic colorectal cancer (mCRC) who are refractory to standard chemotherapy, because despite their clinical approval, it still remains unclear which of these two drugs should be used as initial treatment. Materials and Methods: The clinical data of patients with mCRC who were treated with regorafenib or TFTD and those of drug-naive patients, between June 2014 and September 2015, were retrospectively collected from 24 institutions in Japan. Overall survival (OS) was evaluated using the Cox's proportional hazard models based on propensity score adjustment for baseline characteristics. Results: A total of 550 patients (223 patients in the regorafenib group and 327 patients in the TFTD group) met all criteria. The median OS was 7.9 months (95% confidence interval [CI], 6.8–9.2) in the regorafenib group and 7.4 months (95% CI, 6.6–8.3) in the TFTD group. The propensity score adjusted analysis showed that OS was similar between the two groups (adjusted hazard ratio [HR], 0.96; 95% CI, 0.78–1.18). In the subgroup analysis, a significant interaction with age was observed. Regorafenib showed favorable survival in patients aged <65 years (HR, 1.29; 95% CI, 0.98–1.69), whereas TFTD was favored in patients aged ≥65 years (HR, 0.78; 95% CI, 0.59–1.03). Conclusion: No significant difference in OS between regorafenib and TFTD was observed in patients with mCRC. Although the choice of the drug by age might affect survival, a clearly predictive biomarker to distinguish the two drugs should be identified in further studies. Implications for Practice: Previous studies of patients with metastatic colorectal cancer refractory to standard chemotherapy had demonstrated that both regorafenib and trifluridine/tipiracil could result in increased overall survival compared with placebo, but there are no head-to-head trials. This large, multicenter, observational study retrospectively compared the efficacy of regorafenib and trifluridine/tipiracil in 550 patients with metastatic colorectal cancer refractory to standard chemotherapy who had access to both drugs. Although no difference in overall survival was found between the two drugs in adjusted analysis using propensity score, regorafenib showed favorable survival in patients aged <65 years, whereas trifluridine/tipiracil was favored in patients aged ≥65 years in the subgroup analysis..
|2.||Takanobu Nobori, Kenta Tosaka, Akira Kawamura, Taisei Joichi, Kenta Kamino, Akihiro Kishimura, Eishi Baba, Takeshi Mori, Yoshiki Katayama, Alkaline Phosphatase-Catalyzed Amplification of a Fluorescence Signal for Flow Cytometry, Analytical Chemistry, 10.1021/acs.analchem.7b03893, 90, 2, 1059-1062, 2018.01, [URL], Despite the expanding use of flow cytometry, its detection limit is not satisfactory for many antigen proteins with low copy numbers. Herein, we describe an alkaline phosphatase (AP)-based technique to amplify the fluorescence signal for cell staining applications. We designed a fluorescent substrate that acquires membrane permeability upon dephosphorylation by AP. By using the substrate, the fluorescence signal of cells in flow cytometry could be successfully amplified to give a much stronger signal than the cells labeled using a conventional fluorophore-modified antibody..|
|3.||Kotoe Takayoshi, Goro Doi, Nobuhiro Tsuruta, Tomoyasu Yoshihiro, Kenta Nio, Kenji Tsuchihashi, hiroshi ariyama, Jun Odawara, Shinji Shimoda, Kenichi Kouhashi, Yoshinao Oda, shinji itoh, Norifumi Harimoto, Yoshihiko Maehara, Hitoshi Kusaba, Koichi Akashi, Eishi Baba, Successful chemotherapeutic treatment for metastatic littoral cell angioma
A case report, Medicine (United States), 10.1097/MD.0000000000010378, 97, 15, 2018.04, [URL], Rationale:Metastatic littoral cell angioma (LCA) is extremely rare. No standard therapeutic strategy has been established, and the impact of chemotherapy has not yet been evaluated.Patient concerns:A 61-year-old woman was admitted because of bicytopenia. She had a splenectomy for LCA of the spleen 10 years earlier. Bone marrow aspiration was normal, and a computed tomography (CT) scan showed hepatomegaly with multiple liver tumors. Diagnoses:Liver biopsy samples showed macrophage-like cell infiltration in the hepatic sinusoids. Metastatic LCA was diagnosed based on immunohistochemistry, imaging tests, and the clinical course.Interventions:Immunosuppressive agents, such as prednisolone and cyclosporine, were ineffective. Next, cytotoxic agents, such as etoposide, paclitaxel, and vincristine, were administered.Outcomes:Cytotoxic agents showed a prominent effect against LCA. CT showed improvement of the hepatomegaly, and fluoro-deoxyglucose (FDG) uptake decreased markedly at a follow-up FDG- positron emission tomography (PET) scan.Lessons:Chemotherapeutic treatment based on hemophagocytic syndrome or angiosarcoma might have anti-tumor activity against metastatic LCA. Analysis of the molecular characteristics of this tumor is needed to develop better treatment options..
|4.||Akitaka Makiyama, Kohei Arimizu, Gen Hirano, Chinatsu Makiyama, Yuzo Matsushita, Tsuyoshi Shirakawa, Hirofumi Ohmura, Masato Komoda, Keita Uchino, Kyoko Inadomi, Shuji Arita, hiroshi ariyama, Hitoshi Kusaba, Yudai Shinohara, Miyuki Kuwayama, Tatsuhiro Kajitani, Hisanobu Oda, Taito Esaki, Koichi Akashi, Eishi Baba, Irinotecan monotherapy as third-line or later treatment in advanced gastric cancer, Gastric Cancer, 10.1007/s10120-017-0759-9, 21, 3, 464-472, 2018.05, [URL], Background: Patients with advanced gastric cancer (AGC) are often treated with irinotecan monotherapy as salvage-line therapy. However, the survival benefit of this therapy remains to be elucidated. Methods: Medical records of AGC patients who were treated with irinotecan monotherapy as salvage-line treatment in six institutions from 2007 to 2014 were reviewed. Results: A total of 146 patients had prior fluoropyrimidine and taxane therapies, and 75.3% had prior platinum therapy. The median age was 66 (range 27–81) years, and 102 males (69.9%) were included. Performance status (PS) was 0/1/2/3 in 53/70/19/4 patients. Eighty-nine patients (61.0%) had two or more metastatic sites. Irinotecan monotherapy as 3rd-/4th-line therapy was performed in 135/11 (92.5%/7.5%). The median number of administrations was 4 (range 1–62). Forty-six patients (31.5%) required initial dose reduction at the physician’s discretion. The overall response rate was 6.8%, and the disease control rate was 43.1%. The median PFS was 3.19 months [95% confidence interval (CI) 2.30–4.08 months], and the median OS was 6.61 months (95% CI 5.94–7.28 months). Grade 3/4 adverse events were hematological toxicity (46 patients, 31.5%) and non-hematological toxicity (50 patients, 34.2%). Hospitalization due to adverse events was required in 31 patients (21.2%). Patients with relative dose intensity (RDI) less than 80% showed similar survival to those with RDI 80% or higher. Conclusions: Irinotecan monotherapy was relatively safely performed as salvage-line treatment for AGC in Japanese clinical practice. Careful patient selection and intensive modification of the dose of irinotecan might possibly be associated with favorable survival..|
|5.||Hozumi Kumagai, Hitoshi Kusaba, Takeharu Yamanaka, Kenta Nio, Kyoko Inadomi, Kotoe Takayoshi, Mamoru Ito, Shingo Tamura, Akitaka Makiyama, Chinatsu Makiyama, Gen Hirano, Yoshihiro Shibata, Tsuyoshi Shirakawa, Kenji Mitsugi, hiroshi ariyama, Taito Esaki, Koichi Akashi, Eishi Baba, A phase 2 study of fosaprepitant combined with high-dose dexamethasone for Japanese cancer patients receiving highly emetogenic chemotherapy, Medicine (United States), 10.1097/MD.0000000000011042, 97, 25, 2018.06, [URL], Purpose: Combination therapy of fosaprepitant, dexamethasone (DEX) and a serotonin (5-HT 3) receptor antagonist is a standard antiemetic prophylaxis for patients receiving highly emetogenic chemotherapy (HEC). However, the appropriate dose of DEX has not been established in Japan. This study determined the efficacy and safety of triplet antiemetic prophylaxis in Japanese patients receiving HEC when administered the same doses of DEX as those given in a previous international phase 3 study on this drug. Methods: To assess the efficacy and safety of a sufficient dose of DEX (12mg on day 1, 8mg on day 2, 16mg on days 3 and 4) in combination with intravenous fosaprepitant and granisetron, we prospectively examined patients receiving HEC including cisplatin (≥50mg/m 2). The primary endpoint was to determine the percentage of patients who had achieved a complete response (CR), which was defined as no vomiting and no rescue therapy during the entire treatment course. Results: Between February 2013 and January 2015, 44 patients were enrolled with a median age of 65 years (range, 30-75). There were 34 males (77.3%) in the study. Most of the patients had upper gastrointestinal cancers. The CR rate during the treatment course was 70% (95% confidence interval [CI]: 55%-83%) in the overall phase and 91% (95% CI: 78%-97%) in the acute phase and 70% (95% CI: 55%-83%) in the delayed phase. Appreciable severe toxicities related to the antiemetic therapy were not observed. Conclusions: These results suggest that a sufficient dose of DEX in combination with fosaprepitant and granisetron is optimal as an antiemetic prophylaxis for Japanese patients receiving HEC..|
|6.||Shingo Tamura, Taichi Isobe, hiroshi ariyama, Michitaka Nakano, Yoshikane Kikushige, Shigeo Takaishi, Hitoshi Kusaba, Katsuto Takenaka, Takashi Ueki, Masafumi Nakamura, Koichi Akashi, Eishi Baba, E-cadherin regulates proliferation of colorectal cancer stem cells through NANOG, Oncology reports, 10.3892/or.2018.6464, 40, 2, 693-703, 2018.08, [URL], Cancer stem cells (CSCs) possess a self-renewal ability and display tumorigenic potential in immunodeficient mice. Colorectal CSCs are thought to be a uniform population and no functionally distinct subpopulations have been identified. Because E-cadherin is an essential molecule for self-renewal of embryonic stem cells, we examined E-cadherin expression, which may play a role in maintaining the properties of CSCs, in EpCAMhigh/CD44+ colorectal CSCs from human primary colorectal cancers. We obtained 18 surgical specimens of human primary colorectal cancer. CD44, EpCAM, and E-cadherin expression were analyzed by fluorescence-activated cell sorting. Sorted EpCAMhigh/CD44+ colorectal CSCs were injected into immunodeficient mice to estimate the tumorigenic potential. Genetic profiles were analyzed by cDNA microarray. Notably, colorectal CSCs could be divided into two populations based on the E-cadherin expression status, and they exhibited different pathological characteristics. Compared to E-cadherin-negative colorectal CSCs, E-cadherin-positive (EC+) colorectal CSCs demonstrated higher tumor growth potential in vivo. EC+ colorectal CSCs revealed a higher expression of the pluripotency factor NANOG, which contributed to the higher tumor growth potential of EC+ colorectal CSCs through control of cyclin D1 expression. These findings are the first demonstration of functionally distinct subpopulations of colorectal CSCs in human clinical samples..|
|7.||Michitaka Nakano, Mamoru Ito, Risa Tanaka, Kyoko Yamaguchi, hiroshi ariyama, Kenji Mitsugi, Tomoyasu Yoshihiro, Hirofumi Ohmura, Nobuhiro Tsuruta, Fumiyasu Hanamura, Kosuke Sagara, Yuta Okumura, Kenta Nio, Kenji Tsuchihashi, Shuji Arita, Hitoshi Kusaba, Koichi Akashi, Eishi Baba, PD-1+ TIM-3+ T cells in malignant ascites predict prognosis of gastrointestinal cancer, Cancer Science, 10.1111/cas.13723, 109, 9, 2986-2992, 2018.09, [URL], The liquid biopsy of ascites fluid could be an excellent source of tumor and microenvironment for the study of prognostic biomarkers because of its accessibility. Tumor-infiltrating lymphocytes (TILs) can predict prognosis in multiple malignancies, including the response to immune checkpoint inhibitors, a breakthrough cancer therapy. However, TILs’ profiles from malignant ascites have not been extensively studied. Using flow cytometric analysis, we quantified the proportion of exhausted T cells and memory/naive/effector T-cell subsets, among the CD4+ and CD8+ T-cell populations of paired TILs and peripheral blood T cell samples (n = 22). The correlation between CD4+ and CD8+ subset profiles suggested that the combined analysis of CD4+ and CD8+ cells in malignant ascites was clinically significant. We found that cells positive for the exhaustion markers programmed cell death-1 (PD-1), and T-cell immunoglobulin and mucin domain 3 (TIM-3), and cells coexpressing PD-1 and TIM-3 abundantly exist among malignant ascites TILs. Furthermore, patients with high frequency of PD-1+ TIM-3+ cells among the CD4+ and CD8+ T-cell population showed worse clinical outcome in multivariate analysis (n = 27). We propose that exhausted ascites TILs represent a clinically significant prognostic biomarker in advanced gastrointestinal cancer and represent an important target for immune checkpoint inhibitors..|
|8.||Akitaka Makiyama, Kenji Kunieda, Masaaki Noguchi, Takeshi Kajiwara, Takao Tamura, Koji Takeda, Junko Sugiyama, Keiko Minashi, Toshikazu Moriwaki, Naotoshi Sugimoto, Michitaka Nagase, Yuji Negoro, Takashi Tsuda, Hideki Shimodaira, Naohiro Okano, Akihito Tsuji, Daisuke Sakai, Kazuhiro Yanagihara, Shinya Ueda, Shingo Tamura, Satoshi Otsu, Takuya Honda, Yuzo Matsushita, Tatsuya Okuno, Tomomi Kashiwada, Akira Nozaki, Masahide Ebi, Hiroyuki Okuda, Mototsugu Shimokawa, Shuichi Hironaka, Ichinosuke Hyodo, Eishi Baba, Narikazu Boku, Kei Muro, Taito Esaki, First-line chemotherapy with S-1 alone or S-1 plus cisplatin for elderly patients with advanced gastric cancer
a multicenter propensity score matched study, Gastric Cancer, 10.1007/s10120-018-0797-y, 21, 5, 792-801, 2018.09, [URL], Background: Fluoropyrimidine and platinum combination is the standard treatment for advanced or recurrent gastric cancer (AGC). However, fluoropyrimidine monotherapy is commonly used for elderly patients with AGC because of its good tolerability. Methods: In this multicenter retrospective study, we collected clinical data of AGC patients aged 70 years or older, treated with S-1 alone or S-1 plus cisplatin (SP) as the first-line treatment between January 2009 and December 2011. Propensity score matched cohorts (PSMC) were used for reducing the confounding effects to compare efficacy and safety between the two treatment groups. Cox regression analysis was performed to clarify the prognostic factors. Results: PSMC (n = 109 in each group) were selected from among 444 eligible patients (S-1 group, 210; SP group, 234); the S-1 group included more patients deemed unfit for intensive chemotherapy than the SP group (e.g., higher age, poorer PS, poor renal function). In the PSMC, patients’ characteristics were comparable between groups, except the male ratio (S-1 group, 64.2%; SP group, 77.1%; p = 0.04). No significant differences were observed in either overall survival [hazard ratio (HR) 0.93, p = 0.63] or progression-free survival (HR 1.09, p = 0.61). Severe adverse events (AEs) and hospitalization due to AEs were more frequent in the SP group than in the S-1 group (p < 0.001 each). Conclusion: Our findings do not support the survival benefit of SP over S-1 in elderly patients with AGC. We are now conducting a prospective comparative study to optimize treatment strategy and explore applicability of the geriatric assessment for these patients..
|9.||Kyoko Yamaguchi, Hitoshi Kusaba, Akitaka Makiyama, Kenji Mitsugi, Keita Uchino, Shingo Tamura, Yoshihiro Shibata, Taito Esaki, Mamoru Ito, Kotoe Takayoshi, Kenji Tsuchihashi, Shuji Arita, hiroshi ariyama, Koichi Akashi, Eishi Baba, The risk factors for oxaliplatin-induced peripheral sensory neuropathy and thrombocytopenia in advanced gastric cancer, Cancer chemotherapy and pharmacology, 10.1007/s00280-018-3652-2, 82, 4, 625-633, 2018.10, [URL], Purpose: Peripheral sensory neuropathy (PSN) and thrombocytopenia are the main dose-limiting toxicities of oxaliplatin for the treatment of advanced gastric cancer (AGC). Because the risk factors for those toxicities in practice have not been clarified, we conducted this prospective study. Methods: AGC patients who received oxaliplatin-based therapy at any of seven institutions participating in the Kyushu Medical Oncology Group were assessed after we obtained written informed consent. Results: A total of 60 patients including 39 males and 21 females were examined. The median age was 66 years. The numbers of patients receiving oxaliplatin as the first, second, or third and later lines of therapy were 39, 16, and 5, respectively. An initial dose of 130, 100, or < 100 mg/m
oxaliplatin was administered to 12, 39, and 9 patients, respectively. S-1 or capecitabine as a concomitant drug was administered in 54 and 6 patients, respectively. In multivariate analysis, the comorbidity of diabetes mellitus was associated with ≥ grade 2 thrombocytopenia (p = 0.035). No significant risk factor was associated with ≥ grade 2 PSN. However, the accumulated dose of oxaliplatin exhibited a strong correlation with ≥ grade 2 PSN (p = 0.0043), and the predicted accumulated dose of oxaliplatin in which 10% of patients developed ≥ grade 2 PSN was 800 mg/m
. The frequency of PSN in subsequent paclitaxel therapy in patients with ≥ grade 2 or worse PSN in oxaliplatin-based chemotherapy did not increase compared to those with none or grade 1 PSN in oxaliplatin. Conclusion: Thrombocytopenia in AGC patients with diabetes mellitus should be carefully monitored during oxaliplatin-based therapy..
|10.||Kenji Tsuchihashi, Shuji Arita, Minako Fujiwara, Kazuhide Iwasaki, Atsushi Hirano, Tomoyasu Yoshihiro, Kenta Nio, Yutaka Koga, Motohiro Esaki, hiroshi ariyama, Hitoshi Kusaba, Taiki Moriyama, Kenoki Ouchida, Eishi Nagai, Masafumi Nakamura, Yoshinao Oda, Koichi Akashi, Eishi Baba, Metastatic esophageal carcinosarcoma comprising neuroendocrine carcinoma, squamous cell carcinoma, and sarcoma A case report, Medicine (United States), 10.1097/MD.0000000000012796, 97, 41, 2018.10, [URL], Rationale: Esophageal carcinosarcoma generally comprises 2 histological components: squamous cell carcinoma (SqCC) and sarcoma. Esophageal carcinosarcoma comprising 3 components is extremely rare and no reports have described therapeutic effects for this disease with metastasis. Patient concerns: A 76-year-old man with dysphagia presented to a local clinic. Gastrointestinal endoscopy revealed a polypoid tumor in the middle esophagus and he was referred to our hospital. Diagnosis and Interventions: Thoracoscopic esophagectomy with super-extended (D3) nodal dissection and gastric tube reconstitution was performed, which resulted in carcinosarcoma comprising neuroendocrine carcinoma (NEC), SqCC, and sarcoma. Pathological stage was T1bN1M0 stage IIB according to the TNM Classification of Malignant Tumors-7th edition. The NEC component was observed in lymph node. At 47 days after surgery, lymph nodes, liver, and bone metastasis appeared, and tumor markers such as ProGRP and NSE were elevated. Combination chemotherapy with cisplatin and etoposide (EP) adapted to NEC was performed. Outcomes: The patient showed complete response within 4 cycles of chemotherapy. However, the disease recurred 5.5 months after the final course of EP chemotherapy. Lessons: A therapeutic strategy based on assessment of which component caused metastasis might be important for metastatic carcinosarcoma comprising 3 components, although more accumulation of data about the efficacy of chemotherapy is necessary. Moreover, elucidation of the mechanisms underlying generation of carcinosarcoma is expected in the future..|
|11.||Kyoko Yamaguchi, Koji Mishima, Hirofumi Ohmura, Fumiyasu Hanamura, Mamoru Ito, Michitaka Nakano, Kenji Tsuchihashi, Shun Ichiro Ota, Naoko Wada, Uchi Hiroshi, hiroshi ariyama, Hitoshi Kusaba, Hiroaki Niiro, Koichi Akashi, Eishi Baba, Activation of central/effector memory T cells and T-helper 1 polarization in malignant melanoma patients treated with anti-programmed death-1 antibody, Cancer Science, 10.1111/cas.13758, 109, 10, 3032-3042, 2018.10, [URL], Human anti-programmed death-1 (PD-1) antibody possesses the capability to revitalize host T cells and has been an effective therapy for metastatic malignant melanoma (MM). The precise subsets of T cells predominantly activated by anti-PD-1, however, have not yet been clarified. In this study, peripheral blood mononuclear cells obtained from MM patients scheduled to receive anti-PD-1 (nivolumab) therapy, and healthy subjects (HS), were systematically examined on flow cytometry to identify changes in the proportion of immune cell subsets. Compared with HS, MM patients prior to therapy had an increased proportion of activated CD8+ T cells with effector memory phenotypes (Tem), and PD-1 positive subsets of CD4+ central memory T cells (Tcm) and T-helper (Th)17 cells. After a single course of anti-PD-1 therapy, MM patients had an increase in activated Tem and Tcm subsets of CD4+ and CD8+ T cells, and activated Th1 plus T-helper follicular 1 cells. There was no consistent change in the proportion of Tfh cells, B cells, natural killer cells, or dendritic cells. The observed activated phenotypes were attenuated during the course of therapy, but regulatory T cells belonging to the CD3+CD4+CD45RO+CD25high fraction increased at disease progression. Taken together, anti-PD-1 therapy modulates systemic immune reactions and exerts anti-tumor effects, not only by revitalizing Tem and Tcm of CD4+ and CD8+ T cells, but also via a shift to a Th1 phenotype..|
|12.||Michitaka Nakano, Mamoru Ito, Risa Tanaka, hiroshi ariyama, Kenji Mitsugi, Akitaka Makiyama, Keita Uchino, Taito Esaki, Nobuhiro Tsuruta, Fumiyasu Hanamura, Kyoko Yamaguchi, Yuta Okumura, Kosuke Sagara, Kotoe Takayoshi, Kenta Nio, Kenji Tsuchihashi, Shingo Tamura, Hozumi Shimokawa, Shuji Arita, Kohta Miyawaki, Hitoshi Kusaba, Koichi Akashi, Eishi Baba, Epithelial-mesenchymal transition is activated in CD44-positive malignant ascites tumor cells of gastrointestinal cancer, Cancer Science, 10.1111/cas.13777, 109, 11, 3461-3470, 2018.11, [URL], Disseminated cancer cells in malignant ascites possess unique properties that differ from primary tumors. However, the biological features of ascites tumor cells (ATC) have not been fully investigated. By analyzing ascites fluid from 65 gastrointestinal cancer patients, the distinguishing characteristics of ATC were identified. High frequency of CD44+ cells was observed in ATC using flow cytometry (n = 48). Multiplex quantitative PCR (n = 15) showed higher gene expression of epithelial-mesenchymal transition (EMT)-related genes and transforming growth factor beta (TGF-beta)-related genes in ATC than in the primary tissues. Immunohistochemistry (n = 10) showed that ATC also had much higher expression of phosphorylated SMAD2 than that in the corresponding primary tissues. TGF-beta 1 was detected in all cases of malignant ascites by enzyme-linked immunoassay (n = 38), suggesting the possible interaction of ATC and the ascites microenvironment. In vitro experiments revealed that these ATC properties were maintained by TGF-beta 1 in cultured ATC(n = 3). Here, we showed that ATCrevealed high frequencies of CD44 and possessed distinct EMT features from primary tissues that were mainly maintained by TGF-beta 1 in the ascites..|
|13.||Kenji Tsuchihashi, Mamoru Ito, Toshikazu Moriwaki, Shota Fukuoka, Hiroya Taniguchi, Atsuo Takashima, Yosuke Kumekawa, Takeshi Kajiwara, Kentaro Yamazaki, Taito Esaki, Akitaka Makiyama, Tadamichi Denda, Hironaga Satake, Takeshi Suto, Naotoshi Sugimoto, Kenji Katsumata, Toshiaki Ishikawa, Tomomi Kashiwada, Eiji Oki, Yoshito Komatsu, Hiroyuki Okuyama, Daisuke Sakai, Hideki Ueno, Takao Tamura, Kimihiro Yamashita, Junji Kishimoto, Yasuhiro Shimada, Eishi Baba, Role of Predictive Value of the Modified Glasgow Prognostic Score for Later-line Chemotherapy in Patients With Metastatic Colorectal Cancer, Clinical Colorectal Cancer, 10.1016/j.clcc.2018.07.004, 17, 4, e687-e697, 2018.12, [URL], The survival and safety of patients with metastatic colorectal cancer treated with trifluridine/tipiracil or regorafenib as later-line chemotherapy were retrospectively examined according to the modified Glasgow Prognostic Score (mGPS). Overall and progression-free survival were strongly correlated with mGPS in all patients. The frequency of adverse events was generally similar in each mGPS group. Background: Assessment of patient factors is essential for selecting later-line chemotherapy in patients with metastatic colorectal cancer (mCRC). The efficacy, prognosis, and safety of each treatment regimen according to nutritional and inflammatory status still remain to be elucidated. Patients and Methods: A total of 550 patients with mCRC who were registered in the REGOTAS study (Regorafenib versus TAS-102 as Salvage-line in patients with colorectal cancer refractory to standard chemotherapies: a multicenter observational study, UMIN 000020416) and treated with trifluridine/tipiracil (TFTD) or regorafenib as a later-line therapy were retrospectively stratified according to the modified Glasgow Prognostic Score (mGPS), which divided patients into mGPS 0 to 2 by serum albumin and C-reactive protein, and compared. Results: The median overall survival (OS) of patients with mGPS 0, 1, and 2 was 10.0 months (95% confidence interval [CI], 9.2-11.6 months), 6.5 months (95% CI, 5.3-7.1 months), and 3.9 months (95% CI, 3.3-4.9 months), respectively. The median progression-free survival (PFS) with mGPS 0, 1, and 2 was 2.5 months (95% CI, 2.1-3.0 months), 2.0 months (95% CI, 1.9-2.3 months), and 1.7 months (95% CI, 1.4-1.9 months), respectively. There were significant differences by mGPS in both OS and PFS (all P <.001). No significant differences in OS and PFS were observed between the patient groups treated with TFTD and regorafenib in each mGPS group. In patients aged ≥ 65 years with mGPS 2, the OS and PFS were worse with regorafenib than with TFTD (OS: hazard ratio, 1.45; 95% CI, 0.93-2.25; P =.097; PFS: hazard ratio, 1.57, 95% CI, 1.01-2.44; P =.047), but there were no consistent trends observed as mGPS increased. The frequency of grade 3 and more adverse events was generally similar in each mGPS group. The multivariate analyses showed that mGPS was the strongest predictive factor for OS. Conclusions: The mGPS before later-line chemotherapy is strongly correlated with survival in patients with mCRC..|
|14.||Kentaro Suina, Kenji Tsuchihashi, Juntaro Yamasaki, Shohei Kamenori, Subaru Shintani, Yuki Hirata, Shogo Okazaki, Oltea Sampetrean, Eishi Baba, Koichi Akashi, Yoichiro Mitsuishi, Fumiyuki Takahashi, Kazuhisa Takahashi, Hideyuki Saya, Osamu Nagano, Epidermal growth factor receptor promotes glioma progression by regulating xCT and GluN2B-containing N-methyl-d-aspartate–sensitive glutamate receptor signaling, Cancer Science, 10.1111/cas.13826, 109, 12, 3874-3882, 2018.12, [URL], Autocrine and paracrine factors, including glutamate and epidermal growth factor (EGF), are potent inducers of brain tumor cell invasion, a pathological hallmark of malignant gliomas. System xc(–) consists of xCT and CD98hc subunits and functions as a plasma membrane antiporter for the uptake of extracellular cystine in exchange for intracellular glutamate. We previously showed that the EGF receptor (EGFR) interacts with xCT and thereby promotes the activity of system xc(–) in a kinase-independent manner, resulting in enhanced glutamate release in glioma cells. However, the molecular mechanism underlying EGFR-mediated glioma progression in a glutamate-rich microenvironment has remained unclear. Here we show that the GluN2B subunit of the N-methyl-d-aspartate–sensitive glutamate receptor (NMDAR) is a substrate of EGFR in glioma cells. In response to EGF stimulation, EGFR phosphorylated the COOH-terminal domain of GluN2B and thereby enhanced glutamate-NMDAR signaling and consequent cell migration in EGFR-overexpressing glioma cells. Treatment with the NMDAR inhibitor MK-801 or the system xc(–) inhibitor sulfasalazine suppressed EGF-elicited glioma cell migration. The administration of sulfasalazine and MK-801 also synergistically suppressed the growth of subcutaneous tumors formed by EGFR-overexpressing glioma cells. Furthermore, shRNA-mediated knockdown of xCT and GluN2B cooperatively prolonged the survival of mice injected intracerebrally with such glioma cells. Our findings thus establish a central role for EGFR in the signaling crosstalk between xCT and GluN2B-containing NMDAR in glioma cells..|
|15.||K. Muro, F. Lordick, T. Tsushima, G. Pentheroudakis, Eishi Baba, Z. Lu, B. C. Cho, I. M. Nor, M. Ng, L. T. Chen, K. Kato, J. Li, M. H. Ryu, W. I. Wan Zamaniah, W. P. Yong, K. H. Yeh, T. E. Nakajima, K. Shitara, H. Kawakami, Y. Narita, T. Yoshino, E. Van Cutsem, E. Martinelli, E. C. Smyth, D. Arnold, H. Minami, J. Tabernero, J. Y. Douillard, Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with metastatic oesophageal cancer
A JSMO-ESMO initiative endorsed by CSCO, KSMO, MOS, SSO and TOS, Annals of Oncology, 10.1093/annonc/mdy498, 30, 1, 34-43, 2019.01, [URL], The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of oesophageal cancer was published in 2016, and covered the management and treatment of local/ locoregional disease, limited disease, locally advanced disease and the management of advanced/metastatic disease. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and the Japanese Society of Medical Oncology (JSMO) to convene a special guidelines meeting immediately after the JSMO Annual Meeting in 2018. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic oesophageal cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic oesophageal cancer representing the oncological societies of Japan (JSMO), China (CSCO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices and the drug availability and reimbursement situations in the individual participating Asian countries..
|16.||K. Muro, E. Van Cutsem, Y. Narita, G. Pentheroudakis, Eishi Baba, J. Li, M. H. Ryu, W. I. Wan Zamaniah, W. P. Yong, K. H. Yeh, K. Kato, Z. Lu, B. C. Cho, I. M. Nor, M. Ng, L. T. Chen, T. E. Nakajima, K. Shitara, H. Kawakami, T. Tsushima, T. Yoshino, F. Lordick, E. Martinelli, E. C. Smyth, D. Arnold, H. Minami, J. Tabernero, J. Y. Douillard, Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with metastatic gastric cancer
A JSMO-ESMO initiative endorsed by CSCO, KSMO, MOS, SSO and TOS, Annals of Oncology, 10.1093/annonc/mdy502, 30, 1, 19-33, 2019.01, [URL], The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of gastric cancer (GC) was published in 2016, and covered the management and treatment of local, locoregional, locally advanced and metastatic disease. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and The Japanese Society of Medical Oncology (JSMO) to convene a special guidelines meeting immediately after the JSMO Annual Meeting in 2018. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic GC in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic GC representing the oncological societies of Japan (JSMO), China (CSCO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of both the current treatment practices and the drug availability and reimbursement situations in the individual participating Asian countries..
|17.||Kotoe Takayoshi, Hitoshi Kusaba, Tomomi Aikawa, Sakuya Koreishi, Kosuke Sagara, Michitaka Nakano, Masato Komoda, Mihoko Kono, Mitsuhiro Fukata, Takeshi Arita, Taito Esaki, Koichi Akashi, Eishi Baba, Hypoalbuminemia for the prediction of venous thromboembolism and treatment of direct oral anticoagulants in metastatic gastric cancer patients, Gastric Cancer, 10.1007/s10120-019-00930-2, 2019.01, [URL], Background: Venous thromboembolism (VTE) is highly associated with advanced gastric cancer (AGC) and is sometimes lethal. Predictors of VTE have not been identified, and the efficacy and safety of direct oral anticoagulants (DOACs) for AGC-associated VTE remain to be clarified. Methods: A total of 188 AGC patients who started chemotherapy during the period from January 2014 to December 2017 in our institutions were retrospectively examined for the incidence of VTE, risk factors for VTE, and the efficacy and safety of DOAC-based anticoagulant therapy for VTE. Results: Thirty-four patients (18%) were diagnosed with VTE at the start or during the course of chemotherapy (VTE group). More VTE group patients had a history of abdominal surgery and had moderate–severe ascites (32% versus 17%, 32% versus 14%, respectively) than non-VTE group patients (NVTE group). The mean serum albumin concentrations in the VTE group were significantly lower than NVTE group (3.38 mg/dL vs 3.65 mg/dL, respectively). Multivariate analysis showed that hypoalbuminemia was significantly correlated with VTE (P = 0.012). In the VTE group, 29 patients (85%) received anticoagulant therapy, including 24 patients treated with DOACs. No lethal VTE was observed in any patients. Thirteen patients (45%) terminated DOACs because of anemia or bleeding events, of whom eleven developed major bleeding. Median overall survivals of the VTE and NVTE groups were 9.63 months and 11.5 months, respectively (P = 0.262). Conclusion: Hypoalbuminemia appears to be a risk factor for AGC-associated VTE. DOACs are effective to AGC-associated VTE, but careful observation of bleeding events is required..|
|18.||Michitaka Nakano, Yoshikane Kikushige, Kohta Miyawaki, Yuya Kunisaki, Shinichi Mizuno, Katsuto Takenaka, Shingo Tamura, Yuta Okumura, Mamoru Ito, hiroshi ariyama, Hitoshi Kusaba, Masafumi Nakamura, Takahiro Maeda, Eishi Baba, Koichi Akashi, Dedifferentiation process driven by TGF-beta signaling enhances stem cell properties in human colorectal cancer, Oncogene, 10.1038/s41388-018-0480-0, 38, 6, 780-793, 2019.02, [URL], Cancer stem cells (CSCs) possess the capacity for self-renewal and the potential to differentiate into non-CSCs. The recent discoveries of dynamic equilibrium between CSCs and non-CSCs revealed the significance of acquiring CSC-like properties in non-CSCs as an important process in progression of cancer. The mechanism underlying acquisition of CSC-like properties has mainly been investigated in the context of epithelial–mesenchymal transition. Here, we demonstrate the dedifferentiation process may be an alternative mechanism in acquisition of CSC-like properties in human colorectal cancer cells. By exploring the single-cell gene expression analysis of organoids developed from CD44
CSCs, we identified TWIST1 as a key molecule for maintaining the undifferentiated state of cancer cells. Consistent with the finding, we found that TGF-beta signaling pathway, a regulator of TWIST1, was specifically activated in the undifferentiated CD44
CSCs in human colorectal cancer using microarray-based gene expression analysis and quantitative pathology imaging system. Furthermore, we showed that external stimulation with TGF-beta and the induction of TWIST1 converted CD44
non-CSCs into the undifferentiated CD44
CSCs, leading to the significant increment of CSCs in xenograft models. This study strongly suggests dedifferentiation driven by TGF-beta signaling enhances stem cell properties in human colorectal cancer..
|19.||Yoshihiko Fujita, Masataka Taguri, Kentaro Yamazaki, Junji Tsurutani, Kazuko Sakai, Takahiro Tsushima, Michitaka Nagase, Hiroshi Tamagawa, Shinya Ueda, Takao Tamura, Yasushi Tsuji, Kohei Murata, Koichi Taira, Tadamichi Denda, Toshikazu Moriwaki, Sadao Funai, Takako Eguchi Nakajima, Kei Muro, Akihito Tsuji, Motoki Yoshida, Koichi Suyama, Takuya Kurimoto, Naotoshi Sugimoto, Eishi Baba, Nobuhiko Seki, Mikio Sato, Takaya Shimura, Narikazu Boku, Ichinosuke Hyodo, Takeharu Yamanaka, Kazuto Nishio, aCGH Analysis of Predictive Biomarkers for Response to Bevacizumab plus Oxaliplatin- or Irinotecan-Based Chemotherapy in Patients with Metastatic Colorectal Cancer, Oncologist, 10.1634/theoncologist.2018-0119, 24, 3, 327-337, 2019.03, [URL], Background: The randomized phase III study (WJOG4407G) showed equivalent efficacy between FOLFOX and FOLFIRI in combination with bevacizumab as the first-line treatment for metastatic colorectal cancer (mCRC). We studied whole genome copy number profiles using array-based comparative genomic hybridization (aCGH) analysis of tumor tissue samples obtained in this study. The aim of this study was to identify gene copy number alterations that could aid in selecting either FOLFOX or FOLFIRI in combination with bevacizumab for patients with mCRC. Materials and Methods: DNA was purified from 154 pretreatment formalin-fixed paraffin-embedded tissue samples (75 from the FOLFOX arm and 79 from the FOLFIRI arm) of 395 patients enrolled in the WJOG4407G trial and analyzed by aCGH. Genomic regions greater than 1.2-fold were regarded as copy number gain (CNG). Results: Patient characteristics between the treatment arms were well balanced except for tumor laterality (left side; 64% in FOLFOX arm and 80% in FOLFIRI arm, p =.07). FOLFIRI showed a trend toward better response rate (RR), progression-free survival (PFS) and overall survival (OS) than FOLFOX in the patients with CNG of chromosome 8q24.1 (Fisher's exact test, p =.134 for RR; interaction test, p =.102 for PFS and p =.003 for OS) and 8q24.2 (Fisher's exact test, p =.179 for RR; interaction test, p =.144 for PFS and p =.002 for OS). Conclusion: Chromosome 8q24.1–q24.2 may contain genes that could potentially serve as predictive markers for selecting either FOLFOX or FOLFIRI in combination with bevacizumab for treatment of patients with mCRC. Implications for Practice: Bevacizumab has been used as a standard first-line treatment for patients with metastatic colorectal cancer (mCRC) in combination with either oxaliplatin-based or irinotecan-based chemotherapy. Until now, there has been no predictive marker to choose between the two combination chemotherapies. This array-based comparative genomic hybridization analysis revealed that the difference in therapeutic effect between the two combination chemotherapies is prominent in patients with mCRC with gene copy number gain in chromosome 8p24.1–p24.2. Such patients showed more favorable response and survival when treated with irinotecan-based combination chemotherapy. Overlapping genes commonly found in this region may be predictive biomarkers of the efficacy of the combination chemotherapy with bevacizumab..|
|20.||Tomoyasu Yoshihiro, Hitoshi Kusaba, Akitaka Makiyama, Kazuma Kobayashi, Masato Uenomachi, Mamoru Ito, Yasuhiro Doi, Kenji Mitsugi, Tomomi Aikawa, Kotoe Takayoshi, Taito Esaki, Hozumi Shimokawa, Kenji Tsuchihashi, hiroshi ariyama, Koichi Akashi, Eishi Baba, Efficacy and safety of ramucirumab plus modified FOLFIRI for metastatic colorectal cancer, International Journal of Clinical Oncology, 10.1007/s10147-018-01391-w, 24, 5, 508-515, 2019.05, [URL], Background: Dose modification of chemotherapy for metastatic colorectal cancer (MCRC) is often needed, especially in second-line and later-line treatments due to adverse events of previous treatment and poor patient condition. No study has focused on ramucirumab plus modified dose of FOLFIRI for MCRC, and whether low relative dose intensity (RDI) affects treatment efficacy has not been clarified. Methods: MCRC patients who received ramucirumab plus FOLFIRI, which consisted of 150 mg/m
of irinotecan, at six institutions were retrospectively analyzed. Results: A total of 43 patients were assessed. Median age was 63 years, and 22 patients (51%) were women. Twenty-six patients (60%) were given ramucirumab plus FOLFIRI as second-line therapy, and 17 (40%) as third or later-line. The median relative dose intensity (RDI) of irinotecan was 60.6%, which is lower than that in the pivotal phase 3 study (RAISE), and other agents showed the same trend. Median progression-free survival was 4.8 [95% confidence interval (CI) 3.2–5.7] months for all patients, 5.4 (95% CI 3.5–7.2) months for second-line patients, and 2.8 (95% CI 1.6–5.8) months for third or later-line patients. Median overall survival was 17.3 (95% CI 11.5–22.4) months for all patients. Patients with irinotecan RDI less than 60% showed similar treatment efficacy. Hematological toxicities of grade 3 or worse were observed in 21 patients, but all were manageable. Conclusion: Low RDI did not compromise the treatment efficacy of ramucirumab plus modified FOLFIRI for MCRC patients..
|21.||Eishi Baba, Human Nanog pseudogene8 promotes the proliferation of gastrointestinal cancer cells., Exp Cell Res, 318, 1799-1807, 2012.09.|
|22.||Eishi Baba, Human Nanog pseudogene8 promotes the proliferation of gastrointestinal cancer cells., Exp Cell Res, 318, 1799-1807, 2012.09.|
|23.||Baba E, Fujishima H, Makiyama A, Uchino K, Tanaka R, Esaki T, Kusaba H, Mitsugi K, Nakano S, Akashi K, Phase II Study of Modified CPT-11 and Bolus 5-FU/l-Leucovorin in Japanese Metastatic Colorectal Cancer Patients., Advances in Therapy, 29, 287-96, 2012.03.|
|24.||Baba E, Fujishima H, Makiyama A, Uchino K, Tanaka R, Esaki T, Kusaba H, Mitsugi K, Nakano S, Akashi K, Phase II Study of Modified CPT-11 and Bolus 5-FU/l-Leucovorin in Japanese Metastatic Colorectal Cancer Patients., Advances in Therapy, 29, 287-96, 2012.01.|
|25.||Uchino K, Kusaba H, Kishimoto J, Mitsuyasu H, Kawasaki H, Baba E, Akashi K:, Validation of hospital anxiety and depression scale as a screening tool for psychological distress in advanced cancer patients undergoing chemotherapy., Palliative Care Research, 6, 150-157, 2011.12.|
|26.||Baba E, Esaki T, Ariyama H, Mitsugi K, Morikita T, Fujishima H, Kusaba H, Nakano S, Akashi K, Phase II study of sequential treatment with S-1 and cisplatin for metastatic gastric cancer, Cancer Chemother Pharmacol, 68, 611-7, 2011.05.|
|27.||Isobe T, Baba E, Arita S, Komoda M, Tamura S, Shirakawa T, Ariyama H, Takaishi S, Kusaba H, Ueki T, Akashi K: , Human STEAP3 maintains tumor growth under hypoferric condition., Exp Cell Re, 317, 2582-91, 2011.05.|
|28.||Kusaba H, Esaki T, Futami K, Tanaka S, Fujishima H, Mitsugi K, Sakai K, Ariyama H, Tanaka R, Kinugawa N, Ueki T, Mibu R, Baba E, Nakano S, Akashi K., Phase I/II study of a 3-week cycle of irinotecan and S-1 in patients with advanced colorectal cancer., Cancer Sci, 101, 2591, 2010.12.|
|29.||Baba E, Esaki T, Ariyama H, Mitsugi K, Morikita T, Fujishima H, Kusaba H, Nakano S, Akashi K., Phase II study of sequential treatment with S-1 and cisplatin for metastatic gastric cancer., Cancer Chemother Pharmacol, 10.1007/s00280-010-1529-0, 2010.11.|
|30.||Shibata Y, Ariyama H, Baba E, Takii Y, Esaki T, Mitsugi K, Tsuchiya T, Kusaba H, Akashi K, Nakano S, Oxaliplatin-induced allergic reaction in patients with colorectal cancer in Japan, Int J Clin Oncol, 2009 in Press, 2009.12.|
|31.||Baba E, Fujishima H, Kusaba H, Esaki T, Ariyama H, Kato K, Tanaka R, Mitsugi K, Shibata Y, Harada M, Nakano S, Phase I Study of the Sequential Administration of S-1 and Cisplatin for Metastatic Gastric Cancer, Anticancer Res, 29(5), 1727-32, 2009, 2009.06.|
|32.||Tabrizi SJ, Niiro H, Masui M, Yoshimoto G, Iino T, Kikushige Y, Wakasaki T, Baba E, Shimoda S, Miyamoto T, Hara T, Akashi K, T cell leukemia/lymphoma 1 and galectin-1 regulate survival/cell death pathways in human naive and IgM+ memory B cells through altering balances in Bcl-2 family proteins, J Immunol 182(3): 1490-1499, 2009, 2009.02.|
|33.||Makiyama A, Qin B, Uchino K, Shibata Y, Arita S, Isobe T, Hirano G, Kusaba H, Baba E, Akashi K, Nakano S, Schedule-dependent synergistic interaction between gemcitabine and oxaliplatin in human gallbladder adenocarcinoma cell lines, Anticancer Drugs, 20(2),123-30,2009, 2009.02.|
|34.||Tomiyama N, Higashiuesato Y, Oda T, Baba E, Harada M, Azuma M, Yamashita T, Uehara K, Miyazato A, Hatta K, Ohya Y, Iseki K, Jinno Y, Takishita S, MEFV mutation analysis of familial Mediterranean fever in Japan, Clin Exp Rheumatol , 26(1): 13-17, 2008, 2008.06.|
|35.||Kanda Y, Omuro Y, Baba E, Oshima K, Nagafuji K, Heike Y, Takaue Y, Sasaki T, Sakamaki H, Harada M, Allo-SCT using reduced-intensity conditioning against advanced pancreatic cancer: a Japanese survey, Bone Marrow Transplant , 42(2): 99-103, 2008, 2008.06.|
|36.||Arita S, Baba E, Shibata Y, Niiro H, Shimoda S, Isobe T, Kusaba H, Nakano S, Harada M, B cell activation regulates exosomal HLA production, Eur J Immunol , 38(5): 1423-1434, 2008, 2008.06.|
|37.||Ariyama H, Qin B, Baba E, Tanaka R, Mitsugi K, Harada M, Nakano S. , Gefitinib, a selective EGFR tyrosine kinase inhibitor, induces apoptosis through activation of Bax in human gallbladder adenocarcinoma cells. , J Cell Biochem, 97:724-34, 2006.12.|
|38.||Baoli Q, Kato K, Mitsugi K, Nakamura M, Tanaka R, Baba E, Ariyama H, Kuroiwa T, Harada M, Nakano S, Baoli Q, Kato K, Mitsugi K, Nakamura M, Tanaka R, Baba E, Ariyama H, Kuroiwa T, Harada M, Nakano S. Feasibility study of ambulatory continuous infusion of 5-fluorouracil followed by cisplatin through hepatic artery for metastatic colorectal cancer. , . Cancer Chemother Pharmacol. , 57(1):114-119, 2006.01.|
|39.||Mitsugi K, Nakamura T, Kashiwabara N, Ariyama H, Tanaka R, Baba E, Nakamura M, Harada M, Nakano S., Protection against methotrexate toxicity by a soybean protein- and omega-3 fatty acid-containing diet: comparative study with a casein-containing diet., Oncol Rep., 12, 1, 41-45, 12(1):41-5., 2004.07.|
|40.||Onishi H, Kuroki H, Matsumoto K, Baba E, Sasaki N, Kuga H, Tanaka M, Katano M, Morisaki T., Monocyte-derived dendritic cells that capture dead tumor cells secrete IL-12 and TNF-alpha through IL-12/TNF-alpha/NF-kappaB autocrine loop, Cancer Immunol Immunother., 10.1007/s00262-004-0568-y, 53, 12, 1093-1100, 2004.06.|
|41.||Fujishima H, Kikuchi I, Miyanaga O, Ueda A, Baba E, Mitsugi K, Harada M, Nakano S., Phase I study of CPT-11 and bolus 5-FU/ l-leucovorin in patients with metastatic colorectal cancer., Int J Clin Oncol., 9(2):92-7., 2004.04.|
|42.||Tasaki A, Yamanaka N, Kubo M, Matsumoto K, Kuroki H, Nakamura K, Nakahara C, Onishi H, Kuga H, Baba E, Tanaka M, Morisaki T, Katano M., Three-dimensional two-layer collagen matrix gel culture model for evaluating complex biological functions of monocyte-derived dendritic cells., J Immunol Methods., 10.1016/j.jim.2004.01.014, 287, 1-2, 79-90, 287(1-2):79-90., 2004.04.|
|43.||Morisaki T, Matsumoto K, Kuroki H, Kubo M, Baba E, Onishi H, Tasaki A, Nakamura M, Inaba S, Katano M., Combined immunotherapy with intracavital injection of activated lymphocytes, monocyte-derived dendritic cells and low-dose OK-432 in patients with malignant effusion., Anticancer Res., 23, 6A, 4459-4465, 23(6a):4459-65., 2003.11.|