Kyushu University Academic Staff Educational and Research Activities Database
List of Reports
Eishi Baba Last modified date:2023.09.28

Professor / Department of Oncology and Social Medicine / Center for Cohort Studies / Faculty of Medical Sciences


Reports
1. 固形がんの免疫・抗体療法 II.基礎研究の進歩と展望 抗体療法 抗体療法の現状と開発動向.
2. Course for Medical Oncologist : Prep test for medical oncologist(36)answer and explanation.
3. Kyoko Inadomi, Hozumi Kumagai, Shuji Arita, Kotoe Takayoshi, Hiroshi Uchi, Hidetaka Yamamoto, Hiroshi Ariyama, Hitoshi Kusaba, Koichi Akashi, Eishi Baba, Primary malignant melanoma of the esophagus successfully treated with nivolumab: A case report, ANNALS OF ONCOLOGY, Vol.26, pp.125-126, 2015.11.
4. 難治がん 治療標的の同定と創薬への展望 胃組織幹細胞と印環細胞癌発癌モデルマウス.
5. 有山 寛, 早河 翼, 馬場 英司, 赤司 浩一, Wang Timothy, 胃印環細胞癌発癌マウスモデルの構築(Establishment of mouse model of diffuse type gastric cancer), 日本胃癌学会総会記事, Vol.89回, p.232, 2017.03.
6. 有山 寛, 早河 翼, 馬場 英司, 赤司 浩一, Wang Timothy, 新たなステージに入ったがん幹細胞研究 胃印環細胞癌における癌幹細胞とニッチ, 日本癌学会総会記事, Vol.76回, pp.CS4-2, 2017.09.
7. 【胃癌治療ガイドライン最新版を読み解く-改定のポイントとその背景】 ガイドラインにみる胃癌化学療法 補助化学療法
<文献概要>ポイント ◆胃癌術後補助化学療法の標準治療はS-1あるいはCapeOXである.今後はS-1+ドセタキセルも含め,各レジメンの使い分けが必要である.◆術後補助化学療法後早期の再発に対する化学療法は,少なくとも薬剤を変更して行うことが適切と考えられる.◆SP療法による術前化学療法は,高度リンパ節転移を有する症例において有効と考えられるが,今後さらなるエビデンスの蓄積が必要である..
8. 【胃癌のすべて】 薬物療法 切除不能進行・再発胃癌の二次・三次化学療法の開発
わが国を中心とした臨床試験の結果から、パクリタキセルやイリノテカンなどの殺細胞性抗がん薬の二次治療、三次治療におけるポジションが確立されていった。また、HER2陽性胃癌に対するトラスツズマブの一次治療での有効性が確認され、血管新生阻害薬であるラムシルマブも二次治療においてパクリタキセル(PTX)との併用で生存期間の延長を示した。さらにニボルマブも三次治療における標準治療となり、ほかのがん種と同様に胃癌化学療法における免疫チェックポイント阻害薬の開発が進んでいる。その一方で多くの分子標的薬が有効性を示すことができておらず、トラスツズマブの継続投与の有効性も明らかでない。殺細胞性抗がん薬に加えて、分子標的薬の一次耐性・二次耐性機序を解明しバイオマーカーを同定することが今後ますます重要となり、これらの耐性メカニズムを踏まえた有効な薬剤の選択が求められる。(著者抄録).
9. 【知っておきたい感染によるがん診療の知識】 トピックス EBVと胃がん、免疫チェックポイント療法.
10. 【2020年代に向けた胃がん化学療法】 どの患者に、どのレジメンを、どう用いるか 二次治療のレジメン選択は?
<View Points!>▼ヒト型抗VEGFR-2モノクローナル抗体ラムシルマブ(RAM)とパクリタキセル(PAC)の併用療法が推奨されるレジメンである。▼PAC(毎週法)、ドセタキセル、イリノテカン、RAMも条件付きで推奨されるレジメンである。▼ABSOLUTE試験の結果から、ナブパクリタキセル(nab-PAC)(毎週法)も条件付きで推奨されるレジメンである。▼nab-PACは特に腹水や腹膜播種症例に対して、従来のPACと比較して高い有効性が示唆されているが、RAMとの併用では骨髄抑制に注意が必要である。▼HER2陽性胃がんに対する二次治療のトラスツズマブ(Tamb)の効果は明らかになっていない。PAC(毎週法)へのTmabの上乗せ効果を検討するWJOG7112G試験が進行中である。(著者抄録).
11. 【分子標的薬の最適な治療シーケンス】 分子標的薬の最適な治療シーケンス 胃がん
がんの分子生物学的特性の理解が深まるにつれ、胃がんにおいても分子標的薬の開発が進んでいる。現在、切除不能進行・再発胃がんに対する分子標的薬の治療シーケンスとしては、HER2陽性胃がんに対しては1次治療としてトラスツズマブを使用することが推奨される。2次治療においては血管新生阻害薬であるラムシルマブの有効性が確認され、3次治療においては抗PD-1抗体であるニボルマブが使用可能となった。これらの分子標的薬については今後胃がんにおける不均質性の克服や治療効果を予測するバイオマーカーの同定が必要であり、その結果precision medicineがますます加速していくものと考えられる。このように個々の病態に応じて適切な治療法を選択することで、胃がんの治療成績がさらに向上していくことが期待される。(著者抄録).
12. 山本 雄介, 馬場 英司, 腫瘍生物学におけるエクソソーム研究の現状と展望(The Exosome Biology in Cancer: Current Topics and Perspectives), 日本癌学会総会記事, Vol.77回, p.874, 2018.09.
13. Kyoko Yamaguchi, Kenji Tsuchihashi, Kunihiro Tsuji, Yosuke Kito, Kenro Tanoue, Hirofumi Ohmura, Mamoru Ito, Taichi Isobe, Hiroshi Ariyama, Hitoshi Kusaba, Koichi Akashi, Eishi Baba, Prominent PD-L1-positive M2 macrophage infiltration in gastric cancer with hyper-progression after anti-PD-1 therapy, Medicine, 10.1097/md.0000000000025773, Vol.100, No.19, p.e25773, 2021.05, RATIONALE: Anti-PD-1 antibody is the standard therapy for treatment-resistant gastric cancer, but only a limited number of patients respond. Additionally, cases of hyper-progressive disease (HPD) in which tumor growth accelerates after anti-PD-1 antibody administration have been reported; however, the biological mechanism has not been elucidated. PATIENT CONCERNS: In the present case, metastatic gastric cancer was treated with the anti-PD-1 antibody, nivolumab, as third-line treatment. DIAGNOSIS: After the initiation of nivolumab therapy, a rapidly enlarging para-aortic lymph nodes were observed leading to the diagnosis of HPD. INTERVENTIONS: Multiplex immunohistochemistry was used to examine immune cells infiltrating in the primary tumor and in liver metastasis which were obtained before nivolumab treatment, and in lymph node metastasis which presented with HPD after nivolumab therapy. OUTCOMES: In the primary tumor, helper T (Th) cells, cytotoxic T lymphocytes (CTLs), regulatory T (Treg) cells, and PD-L1-negative macrophages were observed. On the other hand, in metastatic lymph nodes presenting with HPD, PD-L1-positive macrophages prominently increased, while Treg cells, CTLs, and Th cells decreased. PD-L1 expression was not observed in gastric cancer cells among the three specimens. LESSONS: The findings suggest the possibility that PD-L1-positive M2 macrophage might contribute to acceleration of tumor growth with anti-PD-1 therapy in the present case..
14. Dedifferentiation process driven by TGF-beta signaling enhances stem cell properties in human colorectal cancer..
15. 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., The oncologist, 10.1634/theoncologist.2018-0119, Vol.24, No.3, pp.327-337, 2019.03, 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..
16. Efficacy and safety of ramucirumab plus modified FOLFIRI for metastatic colorectal cancer..
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, 10.1007/s10120-019-00930-2, 2019.09, 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. Shiho Kawagoe, Masahiro Nakano, Keita Uchino, Kohei Arimizu, Tatsuhiro Kajitani, Hozumi Shimokawa, Tetsuya Kusumoto, Koji Ikejiri, Eishi Baba, Analysis of response evaluation criteria in solid tumors reduction ratio of primary chemotherapy in unresectable advanced or recurrent colorectal cancer, 10.3892/mco.2019.1894, 2019.09, Response Evaluation Criteria in Solid Tumors (RECIST) is used to assess the objective response of solid tumors to treatment. However, it remains unclear to what extent the response rate assessed by RECIST reflects a reduction of tumor size in multiple organs in patients with unresectable advanced or recurrent colorectal cancer (CRC) with multiple organ metastases. It is also unclear whether the management of liver metastases with systemic chemotherapy in CRC patients with multiple organ metastases improves their prognosis, although surgical resection has been shown to be the most effective treatment approach to CRC cases with liver metastases. A total of 38 CRC patients who underwent systemic chemotherapy in Kyushu Medical Center Hospital between January 2013 and April 2016 were examined. The patients had measurable lesions in multiple organs, including the liver, and did not undergo curative surgery for metastatic lesions after initiation of chemotherapy. The association between the total reduction ratio (TRR) of all lesions and liver lesion reduction ratio (LRR) was retrospectively analyzed. A total of 18 patients (47%) had H3 liver metastases, and the median liver lesion occupancy rate in the sum of the measured lesions with RECIST was 76%. TRR and LRR were strongly correlated, regardless of the volume of the liver metastases. Although a TRR of >30% was significantly associated with improved overall survival (OS), this improvement was not observed in patients with H3 liver metastases. TRR was correlated with LRR and was associated with a better OS. CRC patients with both multiple organ and H3 liver metastases exhibited poor survival, even with a high reduction ratio by chemotherapy..
19. Kyoko Yamaguchi, Mamoru Ito, Hirofumi Ohmura, Fumiyasu Hanamura, Michitaka Nakano, Kenji Tsuchihashi, Shuntaro Nagai, Hiroshi Ariyama, Hitoshi Kusaba, Hidetaka Yamamoto, Yoshinao Oda, Masafumi Nakamura, Koichi Akashi, Eishi Baba, Helper T cell-dominant tertiary lymphoid structures are associated with disease relapse of advanced colorectal cancer, OncoImmunology, 10.1080/2162402X.2020.1724763, 2020.01, Tertiary lymphoid structures (TLSs), clusters of immune cells found around tumor tissue, have been shown to be associated with anti-tumor immunity, but the cellular composition within each TLS and whether the cellular composition of a TLS affects a patient’s prognosis are poorly understood. In the present study, each TLS was categorized according to its cellular composition determined by a system of multiplex immunohistochemical staining and quantitative analysis, and the correlation between the category and prognosis was examined. Sixty-seven patients with curatively resected stage II/III colorectal cancer (CRC) were enrolled. A TLS, consisting of germinal center B cells, follicular dendritic cells, T helper (Th) cells, B cells, cytotoxic T cells, and macrophages, was confirmed in the tumor tissue of 58 patients (87%). The densities of Th cells and macrophages were significantly higher in relapsed patients than in not-relapsed patients (p = .043 and p = .0076). A higher ratio of Th cells was the most significant independent risk factor for disease relapse on multivariate analysis. The subset increasing in Th cells was GATA3+ Th2. A total of 353 TLSs was divided into five clusters according to immune cell composition. Among them, the Th-rich type TLS was significantly increased (p = .0009) in relapsed patients. These data suggest the possibility that Th cell-dominant composition might disturb the anti-tumor immune response, and the function of each TLS might differ depending on its composition..
20. Saori Mishima, Hiroya Taniguchi, Kiwamu Akagi, Eishi Baba, Yutaka Fujiwara, Akira Hirasawa, Masafumi Ikeda, Osamu Maeda, Kei Muro, Hiroshi Nishihara, Hiroyki Nishiyama, Tadao Takano, Katsuya Tsuchihara, Yasushi Yatabe, Yasuhiro Kodera, Takayuki Yoshino, Japan Society of Clinical Oncology provisional clinical opinion for the diagnosis and use of immunotherapy in patients with deficient DNA mismatch repair tumors, cooperated by Japanese Society of Medical Oncology, First Edition., International journal of clinical oncology, 10.1007/s10147-019-01498-8, Vol.25, No.2, pp.217-239, 2020.02, BACKGROUND: Novel therapeutic agents have improved survival outcomes in patients with advanced solid tumors. In parallel, the development of predictive biomarkers to identify patients who are likely to benefit from a certain treatment has also contributed to the improvement of survival. Recently, clinical trials have reported the efficacy of immune checkpoint inhibitors in the treatment of mismatch repair-deficient (dMMR) advanced solid tumors. In Japan, a PD-1 inhibitor for dMMR advanced solid tumors, regardless of the primary tumor site, has been approved. However, there are some issues related to administering immune checkpoint inhibitors in the clinical practice setting, making it necessary to develop the guidelines. METHODS: Clinical questions (CQs) regarding medical care were formulated for patients with dMMR advanced solid tumors, and evidence to the CQs was collected by manual search to prepare recommendations. Then, the committee members voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other factors. RESULTS: The current guideline, which we consider a provisional clinical opinion at this point, describes the 11 requirements to be considered in terms of patients for whom dMMR testing is recommended, the timing and methods of dMMR testing, and clinical care systems required to perform dMMR testing properly and to administer immune checkpoint inhibitors safely. CONCLUSION: This provisional clinical opinion proposes the requirements for performing dMMR testing properly to select patients who are likely to benefit from immune checkpoint inhibitors and administering them safely..
21. Takanobu Nobori, Masumi Kawamura, Ryosuke Yoshida, Taisei Joichi, Kenta Kamino, Akihiro Kishimura, Eishi Baba, Takeshi Mori, Yoshiki Katayama, Fluorescence Signal Amplification by Using β-Galactosidase for Flow Cytometry; Advantages of an Endogenous Activity-Free Enzyme., Analytical chemistry, 10.1021/acs.analchem.9b04471, Vol.92, No.4, pp.3069-3076, 2020.02, We previously proposed using a hydrolysis enzyme for fluorescent signal amplification in flow cytometric detection of antigen proteins, which was named the catalyzed reporter penetration (CARP) method. In this method, antigen proteins are labeled with enzyme-modified antibodies, and then fluorophore-modified substrates stain cells by penetrating the cell membrane upon hydrolysis of the substrate. We proved the concept by using alkaline phosphatase (AP) as the hydrolysis enzyme. However, a required prior inactivation process of endogenous AP activity on the cell surface risked disrupting recognition of antigen proteins by antibodies. In this report, the CARP method was extended to β-galactosidase (β-gal) as an amplification enzyme, which circumvented the requirement of an initial inactivation process because endogenous β-gal activity on the surface of examined cells was found to be negligible. The substrate structure for β-gal was optimized and used for the CARP method. The CARP method showed significantly higher fluorescent signals than a conventional method using fluorophore-modified antibodies. Moreover, the degree of amplification of the fluorescence signal was higher for antigens with low expression levels, showing that the CARP method is a suitable signal amplification method over current conventional approaches..
22. Hirofumi Ohmura, Kyoko Yamaguchi, Fumiyasu Hanamura, Mamoru Ito, Akitaka Makiyama, Keita Uchino, Hozumi Shimokawa, Shingo Tamura, Taito Esaki, Kenji Mitsugi, Yoshihiro Shibata, Hisanobu Oda, Kenji Tsuchihashi, Hiroshi Ariyama, Hitoshi Kusaba, Yoshinao Oda, Koichi Akashi, Eishi Baba, OX40 and LAG3 are associated with better prognosis in advanced gastric cancer patients treated with anti-programmed death-1 antibody., British journal of cancer, 10.1038/s41416-020-0810-1, Vol.122, No.10, pp.1507-1517, 2020.05, BACKGROUND: Anti-PD-1 monoclonal antibody, nivolumab, has shown efficacy for advanced gastric cancer (AGC). However, the specific immune cell subsets predominantly activated during the period of anti-PD-1 therapy for AGC have not been clarified. METHODS: Peripheral blood of 30 AGC patients treated with nivolumab was prospectively obtained before the initial and second administrations and at the time of progressive disease (PD). The proportions of immune cell subsets and the serum concentrations of cytokines were systematically analysed by flow cytometry. Associations of subsets and serum cytokines with therapeutic effects were evaluated. RESULTS: After the initial administration, significant increases in activated central/effector memory, activated effector T cells, and activated T-helper 1 subsets were observed. At the time of PD, activated regulatory T cells, LAG3-positive CD4+/CD8+ T cells, and TIM3-positive CD4+/CD8+ T cells increased significantly. Significant positive correlations were shown between progression-free survival and proportions of LAG3-positive CD4+/CD8+ T cells and of OX40-positive CD4+/CD8+ T cells (log-rank p = 0.0008, 0.0003, 0.0035 and 0.0040). CONCLUSIONS: Nivolumab therapy enhances activation of central/effector memory and effector subsets of CD4+/CD8+ T cells. The expression levels of LAG-3 and OX40 on T cells correlated with the efficacy of nivolumab therapy and could be reasonable biomarkers for anti-PD-1 therapy..