Annual Report 2023
Division of Biomarker Discovery (Kashiwa Campus)
Shuichi Mitsunaga, Tomofumi Miura, Hidetaka Suzuki, Michiko Hamamoto, Reiko Nakamura
Introduction
Our research mission involves the elucidation of the tumor-driven abnormal responses of normal tissues from a perspective of clinical symptoms and the development of the ways to control them. We are investigating new treatments and biomarkers to facilitate the clinical benefits for patients, especially with pancreatic cancer.
The Team and What We Do
Tumor-driven abnormal responses of normal tissues are estimated on the basis of the interpretation of clinical symptoms and various Omics data from clinical samples. The pathophysiology is elucidated through developing and investigating the tumor-bearing murine model reproducible for the features of tumor-driven abnormal responses in non-cancerous tissues. A collaboration with an external research institute and a drug discovery company is welcomed for testing the efficacies of a new drug or biomarker in our murine model.
Research Activities
Suppression of intracellular signals of the inflammatory cytokine interleukin-6 (IL-6) enhanced the antitumor efficacy of gemcitabine + nab-paclitaxel, a standard chemotherapy regimen for advanced pancreatic cancer, in pancreatic cancer from a genetically engineered mouse model. These data encouraged us to conduct an investigator-initiated phase I study of gemcitabine + nab-paclitaxel in combination with anti-IL-6 receptor antibody for patients with advanced pancreatic cancer who have become refractory to gemcitabine + nab-paclitaxel therapy. We found good antitumor effects and revealed a suppression of cancer-associated fibroblast and an increase of intratumoral drug infiltration using paired biopsy samples, whose data were published.
Our research using clinical samples and the murine model of cancer cachexia revealed that skeletal muscle loss in pancreatic cancer was characterized by the elevation of hepatic branched-chain α-keto acid dehydrogenase inactive form and the high plasma level of malonylcarnitine. Those had the predictive values of the unfavorable clinical course including poor prognosis, malnutrition and loss of skeletal muscle mass, which were patented through industry-academia collaboration.
We identified a fragment of CD276 protein that was specifically detected in the urine of pancreatic cancer patients. The urinary CD276 fragment had the diagnostic value of detecting pancreatic cancer, which was patented. A company obtained an exclusive license to use the patent.
Education
We supervise one graduate student and one university student.
Future Prospects
We will continue our activities to provide academic support for IL-6 signal inhibition therapy and the development of new biomarkers, as well as explore new seeds through reverse translational research.
List of papers published in 2023
Journal
1. Kadono T, Ishiki H, Yokomichi N, Ito T, Maeda I, Hatano Y, Miura T, Hamano J, Yamaguchi T, Ishikawa A, Suzuki Y, Arakawa S, Amano K, Satomi E, Mori M. Malignancy-related ascites in palliative care units: prognostic factor analysis. BMJ supportive & palliative care, 13:e1292-e1299, 2024
2. Amano K, Okamura S, Baracos V, Mori N, Sakaguchi T, Uneno Y, Hiratsuka Y, Hamano J, Miura T, Ishiki H, Yokomichi N, Hatano Y, Morita T, Mori M. Fluid retention and weight loss in refractory cancer cachexia. BMJ supportive & palliative care, spcare-2024-004820, 2024
3. Tsuno T, Kawaguchi T, Yanaizumi R, Kondo J, Kojima K, Igarashi T, Inoue M, Miura T, Miyasato A, Azuma K, Hamada H, Saeki T, Mawatari H, Ogura H, Kotani A, Yamaguchi T, Hakamata H. Psychological Barriers to the Use of Opioid Analgesics for Treating Pain in Patients With Advanced Recurrent Cancer: A Multicenter Cohort Study. Palliative medicine reports, 5:43-52, 2024
4. Noda S, Yamaguchi J, Kosugi K, Ishida A, Harada M, Ishizuka K, Inoue Y, Kubo E, Miura T. Peppermint Inhalation Therapy for Persistent Hiccups in Terminally Ill Cancer Patient: A Case Study. Journal of pain and symptom management, 67:e503-e505, 2024
5. Amano K, Baracos VE, Mori N, Okamura S, Yamada T, Miura T, Tatara R, Kessoku T, Matsuda Y, Tagami K, Otani H, Mori M, Taniyama T, Nakajima N, Nakanishi E, Kako J, Morita T, Miyashita M. Associations of nutrition impact symptoms with dietary intake and eating-related distress in patients with advanced cancer. Clinical nutrition ESPEN, 60:313-319, 2024
6. Amano K, Okamura S, Baracos VE, Mori N, Sakaguchi T, Uneno Y, Hiratsuka Y, Hamano J, Miura T, Ishiki H, Yokomichi N, Hatano Y, Morita T, Mori M. Impacts of fluid retention on prognostic abilities of cachexia diagnostic criteria in cancer patients with refractory cachexia. Clinical nutrition ESPEN, 60:373-381, 2024
7. Maeda S, Morita T, Yokomichi N, Imai K, Tsuneto S, Maeda I, Miura T, Ishiki H, Otani H, Hatano Y, Mori M. Continuous Deep Sedation for Psycho-Existential Suffering: A Multicenter Nationwide Study. Journal of palliative medicine, 26:1501-1509, 2023
8. Shiraishi R, Kizawa Y, Mori M, Maeda I, Hatano Y, Ishiki H, Miura T, Yokomichi N, Kodama M, Inoue K, Otomo S, Yamaguchi T, Hamano J. Comparison of Symptom Severity and Progression in Advanced Cancer Patients Among Different Care Settings: A Secondary Analysis. Palliative medicine reports, 4:139-149, 2023
9. Amano K, Baracos V, Okamura S, Yamada T, Maeda I, Otani H, Ishiki H, Miura T, Hamano J, Hatano Y, Morita T, Mori M. Low serum creatinine as a prognostic marker in advanced cancer. BMJ supportive & palliative care, spcare-2023-004646, 2023
10. Habu T, Kumanishi R, Ogata T, Fujisawa T, Mishima S, Kotani D, Kadowaki S, Nakamura M, Hojo H, Fujiwara H, Kumagai S, Koyama S, Fujita T, Kinoshita T, Nishikawa H, Yano T, Tajika M, Muro K, Mitsunaga S, Kojima T, Bando H. Complete response to definitive chemoradiotherapy in unresectable locally advanced esophageal squamous cell carcinoma. Esophagus, 20:533-540, 2023
11. Satake T, Shibuki T, Watanabe K, Sasaki M, Imaoka H, Mitsunaga S, Kojima M, Ikeda M. Case Report: Atezolizumab plus bevacizumab for combined hepatocellular-cholangiocarcinoma. Frontiers in oncology, 13:1234113, 2023
12. Mitsunaga S, Ikeda M, Imaoka H, Sasaki M, Watanabe K, Sato A, Aoki K, Ochiai A, Makikawa M, Nishidate M, Yamaguchi K, Terao K, Sawada N, Fujitomo T, Fujii E, Kato A, Tsunoda H. Fibroblast inhibition by tocilizumab enabled gemcitabine/nab-paclitaxel rechallenge for pancreatic cancer. Cancer science, 114:4006-4019, 2023
13. Shibuki T, Sasaki M, Yamaguchi S, Inoue K, Taira T, Satake T, Watanabe K, Imaoka H, Mitsunaga S, Fujisawa T, Tomizawa K, Oyoshi H, Nakamura M, Hojo H, Ikeda M. Palliative radiotherapy for tumor bleeding in patients with unresectable pancreatic cancer: a single-center retrospective study. Radiation oncology (London, England), 18:178, 2023
14. Otani H, Amano K, Morita T, Miura T, Mori N, Tatara R, Kessoku T, Tokoro A, Tagami K, Mori M, Taniyama T, Nakajima N, Nakanishi E, Kako J, Miyashita M. Difficulty swallowing and food bolus obstruction in advanced cancer: association with the cachexia-related quality of life. Annals of palliative medicine, 12:717-728, 2023
15. Kubo E, Harada M, Ishizuka K, Umetsu K, Inoue Y, Kosugi K, Miura T. Letter to the Editor: Three Cases of Pain Treatment in Cancer Patients Using an Alternating Magnetic Field Therapy Device. Journal of palliative medicine, 26:1444-1445, 2023
16. Shibuki T, Sasaki M, Yamaguchi S, Inoue K, Taira T, Satake T, Watanabe K, Imaoka H, Mitsunaga S, Fujisawa T, Tomizawa K, Oyoshi H, Nakamura M, Hojo H, Ikeda M. Correction: Palliative radiotherapy for tumor bleeding in patients with unresectable pancreatic cancer: a single-center retrospective study. Radiation oncology (London, England), 18:199, 2023