Article
Oncology
Tomohiko Shinkawa, Kenoki Ohuchida, Yuki Mochida, Kukiko Sakihama, Chika Iwamoto, Toshiya Abe, Noboru Ideno, Yusuke Mizuuchi, Koji Shindo, Naoki Ikenaga, Taiki Moriyama, Kohei Nakata, Yoshinao Oda, Masafumi Nakamura
Summary: The presence of abundant stroma in pancreatic ductal adenocarcinoma (PDAC) can define the PDAC phenotype and induce distinct therapeutic responses. Cancer-associated fibroblasts (CAFs) maintain the differentiated PDAC phenotype through secreting niche factors and induce different drug responses.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Multidisciplinary Sciences
Hua Su, Fei Yang, Rao Fu, Brittney Trinh, Nina Sun, Junlai Liu, Avi Kumar, Jacopo Baglieri, Jeremy Siruno, Michelle Le, Yuhan Li, Stephen Dozier, Ajay Nair, Aveline Filliol, Nachanok Sinchai, Sara Brin Rosenthal, Jennifer Santini, Christian M. Metallo, Anthony Molina, Robert F. Schwabe, Andrew M. Lowy, David Brenner, Beicheng Sun, Michael Karin
Summary: This study reveals the opposing effects of intact and cleaved collagen I (Col I) in regulating the bioenergetics, tumor growth, and metastasis of pancreatic ductal adenocarcinoma (PDAC) through the tumor microenvironment. Intact Col I inhibits tumor growth, while cleaved Col I promotes tumor growth. Patients with tumors enriched in intact Col I and low levels of related signaling molecules have a longer median survival. These findings shed light on the complex mechanisms of the tumor microenvironment in PDAC and provide new therapeutic targets.
Article
Gastroenterology & Hepatology
Koelina Ganguly, Jesse L. Cox, Dario Ghersi, Paul M. Grandgenett, Michael A. Hollingsworth, Maneesh Jain, Sushil Kumar, Surinder K. Batra
Summary: The secretion of MUC5AC in pancreatic cancer is associated with tumor progression and increased migration of AD-MSCs, leading to stromal heterogeneity in pancreatic tumors.
Review
Biochemistry & Molecular Biology
Nicholas Willumsen, Christina Jensen, George Green, Neel Nissen, Jaclyn Neely, David M. Nelson, Rasmus S. Pedersen, Peder Frederiksen, Inna M. Chen, Mogens K. Boisen, Astrid Z. Johansen, Daniel H. Madsen, Inge Marie Svane, Allan Lipton, Kim Leitzel, Suhail M. Ali, Janine T. Erler, Daan P. Hurkmans, Ron H. J. Mathijssen, Joachim Aerts, Mohammed Eslam, Jacob George, Claus Christiansen, Mina J. Bissel, Morten A. Karsdal
Summary: Due to fibroblast activation into cancer-associated fibroblasts, there is increased tumor fibrosis. Measuring collagen deposition can predict prognosis and guide future drug development.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Review
Oncology
Anna Brichkina, Pierfrancesco Polo, Shrey Dharamvir Sharma, Nico Visestamkul, Matthias Lauth
Summary: Pancreatic cancer is characterized by a significant fibrotic reaction caused by activated cancer-associated fibroblasts (CAFs) that contribute to the extracellular matrix deposition in the tumor microenvironment. CAFs are not a singular cellular entity but consist of multiple potentially dynamic subgroups that have diverse effects on tumor biology. This review aims to provide an overview of CAF heterogeneity, including the phenotypic, functional, and therapeutic distinctions among different stromal subpopulations.
Review
Pathology
Mara H. Sherman, Gregory L. Beatty
Summary: Pancreatic ductal adenocarcinoma (PDAC) has a diverse stromal microenvironment that plays a significant role in disease biology and treatment resistance. Recent advancements in imaging, single-cell analytics, and disease modeling have provided insights into the complexity of PDAC tumors. Understanding the functional and spatial dependencies between cancer cells and extracellular matrix components can reveal therapeutic vulnerabilities.
ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE
(2023)
Article
Oncology
Jiahong Jiang, Yaping Xu, Lianpeng Chang, Guoqing Ru, Xuefeng Xia, Ling Yang, Xin Yi, Zheling Chen, Dong-Sheng Huang, Liu Yang
Summary: This study revealed the presence of driver gene mutations in PDAC stroma, indicating that the genomic features of stromal components may serve as prognostic biomarkers in resectable PDAC and may help guide a more precise treatment paradigm in therapeutic options.
FRONTIERS IN ONCOLOGY
(2021)
Review
Oncology
Yohei Masugi
Summary: Pancreatic cancer is a highly malignant disease with a complex desmoplastic stroma playing crucial roles in its pathobiology. Recent technologies have highlighted the complexity of the stroma in pancreatic cancer and the potential therapeutic opportunities it presents. Abundant desmoplastic stroma is a histological hallmark of pancreatic ductal adenocarcinoma.
Article
Immunology
Yuning Wang, Yun Chen, Yinping Xiao, Jingyao Ruan, Qi Tian, Qi Cheng, Kaikai Chang, Xiaofang Yi
Summary: This study revealed the heterogeneity of endometriosis (EMs) ectopic lesions and identified two distinct subtypes: stroma-enriched (S1) and immune-enriched (S2). S1 was associated with fibroblast activation and extracellular matrix remodeling, while S2 was characterized by immune pathway upregulation and a positive correlation with immunotherapy response. Furthermore, S2 was strongly associated with hormone therapy failure/intolerance.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Engineering, Biomedical
Andreas Stylianou, Chrysovalantis Voutouri, Fotios Mpekris, Triantafyllos Stylianopoulos
Summary: Cancer progression is closely associated with changes in the tumor microenvironment (TME) structure and mechanical properties. Desmoplasia, mainly caused by collagen overproduction, leads to tumor stiffness and hinders drug delivery. Understanding the mechanisms involved in desmoplasia and identifying nanomechanical and collagen-based properties can lead to the development of diagnostic and prognostic biomarkers. In this study, in vitro experiments using pancreatic cell lines and orthotopic tumor models demonstrated that invasive cells are softer with elongated shapes and aligned stress fibers. The study also found distinct nanomechanical and collagen-based optical properties in pancreatic cancer, which can be potential biomarkers for monitoring tumor progression and treatment outcomes.
ANNALS OF BIOMEDICAL ENGINEERING
(2023)
Review
Cell Biology
Parniyan Maneshi, James Mason, Mitesh Dongre, Daniel Ohlund
Summary: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis due to late diagnosis and lack of effective treatments. The tumor microenvironment plays a pivotal role in tumor progression and drug resistance with collagen being a key component. Experimental models are available to study tumor-stromal interactions and potential therapeutic targets within the stroma are being discussed.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Oncology
Ulrike Heger, Anna Martens, Lisa Schillings, Britta Walter, Domenic Hartmann, Ulf Hinz, Thomas Pausch, Nathalia Giese, Christoph W. Michalski, Thilo Hackert
Summary: This study analyzed the role of pancreatic cancer stroma in treatment response and prognosis. The findings suggest that treatment with gemcitabine + nab-paclitaxel reduces collagen content, while FOLFIRINOX has no quantitative effect. Additionally, a higher number of activated fibroblasts after chemotherapy is beneficial for prognosis. These findings contribute to a better understanding of the mechanisms of response and chemoresistance in pancreatic cancer, and may help to stratify patients for different treatment approaches.
Article
Engineering, Biomedical
Nicole L. Habbit, Benjamin Anbiah, Luke Anderson, Joshita Suresh, Iman Hassani, Matthew Eggert, Andrew Brannen, Joshua Davis, Yuan Tian, Balabhaskar Prabhakarpandian, Peter Panizzi, Robert D. Arnold, Elizabeth A. Lipke
Summary: In this study, a three-dimensional in vitro prostate cancer tissue model was established and characterized based on xenograft tumor stiffness. The model can mimic the progression of prostate cancer and provide a foundation for future studies on cancer progression and drug development.
ACTA BIOMATERIALIA
(2022)
Article
Medicine, Research & Experimental
Yifan Liu, Yansha Sun, Peng Wang, Songling Li, Yiwei Dong, Min Zhou, Bizhi Shi, Hua Jiang, Ruixin Sun, Zonghai Li
Summary: In this study, the combined antitumor activity of FAP-targeted and CLDN18.2-targeted CAR-T cells against PDAC was explored. The results showed that prior infusion of FAP-targeted CAR-T cells could eliminate CAFs and enhance the anti-PDAC efficacy of subsequently infused CLDN18.2-targeted CAR-T cells. Moreover, FAP-targeted CAR-T cells could suppress the recruitment of MDSCs and promote the survival of CD8(+) T cells and CAR-T cells in tumor tissue.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Oncology
Eva-Maria Kamionka, Baifeng Qian, Wolfgang Gross, Frank Bergmann, Thilo Hackert, Carlo A. Beretta, Nicolas Dross, Eduard Ryschich
Summary: Excessive desmoplasia is a hallmark of human pancreatic cancer and does not significantly impact T-cell migration or distribution in the tumor. The study found no correlation between collagen organization and T-cell distribution, suggesting that remodeling stroma collagen may not improve T-cell-tumor cell contact.
Article
Anesthesiology
Yukino Oshima, Makoto Sano, Ichie Kajiwara, Yoshimi Ichimaru, Tomoaki Itaya, Tomoya Kuramochi, Emiko Hayashi, Jinsuk Kim, Osamu Kitajima, Yohei Masugi, Atsushi Masamune, Hideaki Ijichi, Yukimoto Ishii, Takahiro Suzuki
Summary: In this study, we found that midazolam can inhibit the proliferation and inflammatory response of pancreatic ductal adenocarcinoma, thereby slowing down its progression. This drug also has analgesic effects on cancer-associated pain.
BRITISH JOURNAL OF ANAESTHESIA
(2022)
Letter
Oncology
Yohei Masugi, Tokiya Abe, Ken Yamazaki, Akihisa Ueno, Michiie Sakamoto
CLINICAL CANCER RESEARCH
(2022)
Article
Gastroenterology & Hepatology
Yutaka Kurebayashi, Kosuke Matsuda, Akihisa Ueno, Hanako Tsujikawa, Ken Yamazaki, Yohei Masugi, Wit Thun Kwa, Kathryn Effendi, Yasushi Hasegawa, Hiroshi Yagi, Yuta Abe, Minoru Kitago, Hidenori Ojima, Michiie Sakamoto
Summary: HCC can be categorized into four distinct immunovascular subtypes (IH/AS, IM/AM, IL/AG, and IL/AL) reflecting the reciprocal interaction between the antitumor immune microenvironment and tumor angiogenesis. The different subtypes are associated with decreasing lymphocytic infiltration, increasing angiogenic factor expression, and VETC/MTM positivity. IL/AG subtype is characterized by CTNNB1 mutation and Wnt/beta-catenin pathway activation, while IL/AL subtype is not associated with increased lymphocyte infiltration or angiogenic factor expression.
Article
Nutrition & Dietetics
Takamasa Mizota, Takako Hishiki, Masahiro Shinoda, Yoshiko Naito, Kazuya Hirukawa, Yohei Masugi, Osamu Itano, Hideaki Obara, Minoru Kitago, Hiroshi Yagi, Yuta Abe, Kentaro Matsubara, Makoto Suematsu, Yuko Kitagawa
Summary: This study found that in acute liver failure, there is a decrease in metabolites related to glycolysis and pentose phosphate pathways, as well as high-energy phosphornucleotides, while methionine and its metabolites are increased. Furthermore, the increase in hypotaurine and taurine coincides with a decrease in total glutathione, suggesting a potential role of the hypotaurine-taurine pathway in oxidative stress protection.
JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION
(2022)
Review
Medicine, Research & Experimental
Iori Kisu, Kouji Banno, Yusuke Matoba, Yohei Yamada, Katsura Emoto, Yohei Masugi, Kentaro Matsubara, Hideaki Obara, Daisuke Aoki
Summary: Uterus transplantation is a potential option for women with uterine factor infertility, but it is still in the experimental stage. Japan has conducted extensive research and exploration, preparing for future clinical applications.
KEIO JOURNAL OF MEDICINE
(2022)
Article
Oncology
Tatsunori Suzuki, Yohei Masugi, Yosuke Inoue, Tsuyoshi Hamada, Mariko Tanaka, Manabu Takamatsu, Junichi Arita, Tomotaka Kato, Yoshikuni Kawaguchi, Akiko Kunita, Yousuke Nakai, Yutaka Nakano, Yoshihiro Ono, Naoki Sasahira, Tsuyoshi Takeda, Keisuke Tateishi, Sho Uemura, Kazuhiko Koike, Tetsuo Ushiku, Kengo Takeuchi, Michiie Sakamoto, Kiyoshi Hasegawa, Minoru Kitago, Yu Takahashi, Mitsuhiro Fujishiro
Summary: In this study, we detected KRAS mutations in pancreatic cancer patients using ddPCR and analyzed their association with prognosis. The results showed that KRAS mutations were present in a high proportion of patients, but mutation positivity was not associated with prognosis. However, KRAS variant allele frequency was inversely associated with survival in pancreatic cancer patients.
Review
Oncology
Yohei Masugi
Summary: Pancreatic cancer is a highly malignant disease with a complex desmoplastic stroma playing crucial roles in its pathobiology. Recent technologies have highlighted the complexity of the stroma in pancreatic cancer and the potential therapeutic opportunities it presents. Abundant desmoplastic stroma is a histological hallmark of pancreatic ductal adenocarcinoma.
Article
Biochemistry & Molecular Biology
Akiko Kubo, Yohei Masugi, Takeshi Hase, Kengo Nagashima, Yuko Kawai, Minako Takizawa, Takako Hishiki, Megumi Shiota, Masatoshi Wakui, Yuko Kitagawa, Yasuaki Kabe, Michiie Sakamoto, Ayako Yachie, Tetsu Hayashida, Makoto Suematsu
Summary: Pathological examination of FFPE needle-biopsied samples is the gold standard for differential diagnosis between DCIS and IBC, but marker metabolite information is lost. Infrared laser-scanning SERS enables visualization of metabolites in fresh-frozen needle-biopsied samples with spatial matching. SERS-derived biochemical fingerprints serve as a useful method for precision diagnosis in breast cancer.
Review
Surgery
K. Abe, M. Kitago, S. Matsuda, M. Shinoda, H. Yagi, Y. Abe, G. Oshima, S. Hori, Y. Endo, T. Yokose, E. Miura, N. Kubota, A. Ueno, Y. Masugi, H. Ojima, M. Sakamoto, Y. Kitagawa
Summary: The inflammatory pseudotumor variant of follicular dendritic cell sarcoma is a tumor associated with Epstein-Barr virus and has a favorable prognosis when treated with surgical resection. It predominantly occurs in the liver or spleen, with no symptoms, and is more common in middle-aged Asian women. Pathologically, it is characterized by spindle cells mixed with inflammatory cells, and shows variable expression of follicular dendritic cell markers and Epstein-Barr virus-encoded RNA. Genetic analysis suggests that it is associated with latent Epstein-Barr virus type 2 infection.
SURGICAL CASE REPORTS
(2022)
Article
Pathology
Yohei Masugi, Manabu Takamatsu, Mariko Tanaka, Kensuke Hara, Yosuke Inoue, Tsuyoshi Hamada, Tatsunori Suzuki, Junichi Arita, Yuki Hirose, Yoshikuni Kawaguchi, Yousuke Nakai, Atsushi Oba, Naoki Sasahira, Gaku Shimane, Tsuyoshi Takeda, Keisuke Tateishi, Sho Uemura, Mitsuhiro Fujishiro, Kiyoshi Hasegawa, Minoru Kitago, Yu Takahashi, Tetsuo Ushiku, Kengo Takeuchi, Michiie Sakamoto
Summary: Alterations in KRAS, CDKN2A, TP53, and SMAD4 genes are major drivers of pancreatic carcinogenesis. Loss of SMAD4 expression and an increasing number of altered genes are associated with unfavorable outcomes in pancreatic cancer patients, including shorter disease-free survival and overall survival, as well as higher risk of liver metastasis.
JOURNAL OF PATHOLOGY CLINICAL RESEARCH
(2023)
Meeting Abstract
Oncology
Tomotaka Ugai, Takashi Shimizu, Hidetaka Kawamura, Yasutoshi Takashima, Juha P. Vayrynen, Seyed Mostafa Mousavi Kahaki, Kazuo Okadome, Yohei Masugi, Annacarolina da Silva, Xuehong Zhang, Andrew T. Chan, Molin Wang, Jeffrey A. Meyerhardt, Jonathan A. Nowak, Mingyang Song, Marios Giannakis, Shuji Ogino
Proceedings Paper
Computer Science, Information Systems
Yusuke Murayama, Tohru Sugiyama, Yoshihiko Ogino, Hiroki Furuta, Takaaki Kambara, Koi Kamisono, Tokiya Abe, Katsura Emoto, Akinori Hashiguchi, Yoichi Kajimura, Michiie Sakamoto
Summary: This report describes a method for solving the problem of different color images shown when using different cameras and displays in the shot and display of one subject. Researchers have developed a color chart and a tool to create an International Color Consortium profile, and verified the color correction accuracy in actual stained pathological specimens.
MEDICAL IMAGING 2022: DIGITAL AND COMPUTATIONAL PATHOLOGY
(2022)
Article
Endocrinology & Metabolism
Tami Tsuchiya, Yoshifumi Saisho, Jun Inaishi, Hironobu Sasaki, Midori Sato, Masaru Nishikawa, Yohei Masugi, Taketo Yamada, Hiroshi Itoh
Summary: The alpha to beta cell mass ratio is increased in patients with pancreatic cancer, which may contribute to worsened glucose metabolism. Further studies are needed to elucidate the mechanisms behind the increased alpha to beta cell mass in these patients.
Meeting Abstract
Critical Care Medicine
T. Asakura, K. Okuda, G. Chen, T. Kato, Y. Mikami, G. C. Rodney, S. Barbosa Cardenas, M. Chua, Y. Masugi, P. G. Noone, C. P. Ribeiro, C. M. Doerschuk, K. N. Olivier, N. Hasegawa, S. H. Randell, W. K. O'Neal, R. C. Boucher
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Meeting Abstract
Oncology
Yohei Masugi, Tokiya Abe, Ken Yamazaki, Akihisa Ueno, Yoko Nishimura, Minoru Kitago, Michiie Sakamoto