Review
Physiology
Keigo Machida
Summary: This article reviews the links between HCV-associated HCC and TICs, discussing how HCV promotes the genesis of TICs and the development of HCC, and how this process can be utilized as a novel therapeutic target for HCC treatment. Additionally, it introduces the ten hall marks of TIC oncogenesis and HCC development as targets for novel therapeutic modalities.
FRONTIERS IN PHYSIOLOGY
(2022)
Review
Oncology
Keigo Machida, Stanley M. Tahara
Summary: This review discusses the pharmacological and immune therapeutic targeting for hepatocellular carcinoma (HCC) and cholangiocarcinoma, as well as the role of immunotherapies and microbiota in tumor-initiating stem-like cells (TICs). Gut dysbiosis inhibits the efficacy of immunotherapies, and personalized medicine approaches targeting TIC/metastasis-initiating cells may be potential targets for HCC immunotherapy and microbiota modulation therapy.
Article
Chemistry, Multidisciplinary
Chia-Lin Chen, Juan Carlos Hernandez, Dinesh Babu Uthaya Kumar, Tatsuya Machida, Stanley M. Tahara, Anthony El-Khoueiry, Meng Li, Vasu Punj, Suresh Kumar Swaminathan, Ameya Kirtane, Yibu Chen, Jayanth Panyam, Keigo Machida
Summary: The improvement of drug selectivity, toxicity, and reduced recurrence of tumors from tumor-initiating stem-like cells is essential for effective cancer therapy. Through high-throughput screens, a combination of histone deacetylase (HDAC) inhibitor(s) and all-trans retinoic acid (ATRA) has been found to effectively inhibit TIC growth. This combined treatment reduces Toll-like receptors (TLR) and stemness genes, leading to loss of self-renewal property of TICs.
Article
Oncology
Mamatha Kakarla, Sathyavathi ChallaSivaKanaka, Mary F. Dufficy, Victoria Gil, Yana Filipovich, Renee Vickman, Susan E. Crawford, Simon W. Hayward, Omar E. Franco
Summary: The increase of EFNB ligands in CAF in the TME of PCa plays a crucial role in promoting tumor growth and modulating the tumor environment. Activation of EFNB by Src family kinases transforms normal fibroblasts into CAF that affect PCa progression by secreting factors that enhance tumor growth and invasion. Through stromal-epithelial interactions, CAF contribute significantly to the tumorigenicity of PCa cells.
Editorial Material
Cell Biology
Jenny A. Rudnick, Jayanta Debnath
Summary: Growing evidence suggests that autophagy in the host stroma plays a crucial role in influencing the tumor microenvironment, particularly in promoting mammary tumor progression. Loss of fibroblast autophagy hinders the secretion of type 1 collagen, leading to an impairment in the development of a stiff tissue matrix conducive to mammary tumor growth. Therefore, targeting autophagy in stromal fibroblasts could be a potential strategy to inhibit the desmoplastic response required for cancer progression.
Article
Oncology
Ilaria Giusti, Marianna Di Francesco, Giuseppina Poppa, Letizia Esposito, Sandra D'Ascenzo, Vincenza Dolo
Summary: Fibroblasts in the tumor microenvironment can be activated by cancer cells to become cancer-associated fibroblasts (CAFs), which promote tumor progression by remodeling the tumor stroma. Extracellular vesicles (EVs), including exosomes (EXOs) and microvesicles (MVs), play a crucial role in the communication between cancer cells and fibroblasts. Different subpopulations of EVs have different effects on fibroblasts, and the secretome of activated fibroblasts can modulate the response of bystander cells, indicating the important role of EVs in the mutual cross-talk between tumor cells and CAFs.
FRONTIERS IN ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Noemi Eiro, Maria Fraile, Silvia Fernandez-Francos, Rosario Sanchez, Luis A. Costa, Francisco J. Vizoso
Summary: MSCs play a crucial role in the tumor microenvironment, with their effects on tumors depending on their source and the type of tumor. MSCs from reproductive tissues show potent anti-tumor effects.
CELL AND BIOSCIENCE
(2021)
Article
Genetics & Heredity
Kevin Nee, Dennis Ma, Quy H. Nguyen, Maren Pein, Nicholas Pervolarakis, Jacob Insua-Rodriguez, Yanwen Gong, Grace Hernandez, Hamad Alshetaiwi, Justice Williams, Maha Rauf, Kushal Rajiv Dave, Keerti Boyapati, Aliza Hasnain, Christian Calderon, Anush Markaryan, Robert Edwards, Erin Lin, Ritesh Parajuli, Peijie Zhou, Qing Nie, Sundus Shalabi, Mark A. LaBarge, Kai Kessenbrock
Summary: Premalignant stromal cells from women with germline BRCA1 mutations have increased expression of secreted factors regulating epithelial homeostasis, promoting premalignant epithelial changes and increased breast cancer risk. The stromal niche in BRCA1-driven tumor initiation promotes epithelial proliferation and mutant BRCA1-driven tumorigenesis through paracrine signals, such as matrix metalloproteinase 3 (MMP3), produced by pre-cancer-associated fibroblasts (pre-CAFs). This study highlights the importance of precancerous stroma in BRCA1(+/mut) in elevating breast cancer risk.
Article
Oncology
Lucie M. Frerichs, Bastian Frerichs, Patrick Petzsch, Karl Koehrer, Joachim Windolf, Bernd Bittersohl, Michele J. Hoffmann, Vera Grotheer
Summary: Patients with muscle-invasive bladder cancer have a poor prognosis. The tumor microenvironment plays a key role in tumor development and therapy resistance. This study found that mesenchymal stromal cells and fibroblasts have tumor-promoting effects on bladder cancer cells and increase chemoresistance.
FRONTIERS IN ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Shinichiro Takashima, Soichiro Usui, Oto Inoue, Chiaki Goten, Kosei Yamaguchi, Yusuke Takeda, Shihe Cui, Yoshio Sakai, Kenshi Hayashi, Kenji Sakata, Masa-aki Kawashiri, Masayuki Takamura
Summary: The study found that the adipose tissue-derived stromal vascular fraction (Ad-SVF) from adult mice can be transdifferentiated into beating cardiomyocyte-like cells through a simple culture method. These beating cardiomyocytes exhibit characteristics of cardiomyocytes and show synchronized oscillation of intracellular calcium concentration on day 28 of culture. The research identified key transcription factors, such as myocyte-specific enhancer 2c (Mef2c), that play a role in this transdifferentiation process.
SCIENTIFIC REPORTS
(2021)
Review
Pharmacology & Pharmacy
Leon Jia Wei Tang, Ayshath Zaseela, Clarissa Chin Min Toh, Christabella Adine, Abdullah Omer Aydar, N. Gopalakrishna Iyer, Eliza Li Shan Fong
Summary: Advancements in single-cell technologies have increased our understanding of stromal heterogeneity, leading to the incorporation of this knowledge in tumor modeling for drug development and personalized drug testing. This approach may result in the development of more precise drugs targeting specific stromal cell subpopulations and improved recapitulation of patient tumors in vitro for personalized drug testing.
ADVANCED DRUG DELIVERY REVIEWS
(2021)
Article
Cell Biology
Jenny A. Rudnick, Teresa Monkkonen, Florie A. Mar, James M. Barnes, Hanna Starobinets, Juliet Goldsmith, Srirupa Roy, Sofia Bustamante Eguiguren, Valerie M. Weaver, Jayanta Debnath
Summary: Autophagy inhibitors are being explored for cancer treatment due to their ability to hinder tumor cell survival, while researchers are increasingly interested in how modulating autophagy in the host stroma affects tumorigenesis. Fibroblasts play key roles in cancer progression by promoting desmoplasia, with autophagy in stromal fibroblasts found to be crucial for mammary tumor growth.
GENES & DEVELOPMENT
(2021)
Article
Oncology
Tao Lu, Lisa Oomens, Leon W. M. M. Terstappen, Jai Prakash
Summary: Cancer-associated fibroblasts (CAFs) are important drivers in the tumor microenvironment and facilitate the growth and survival of tumor cells, as well as metastasis formation. In this study, we aimed to study circulating CAFs (cCAFs) and circulating tumor cells (CTCs) in a preclinical breast tumor model in mice in order to understand the effect of chemotherapy on cCAFs and CTC formation. We found that tumors with CAFs grew faster than tumors without CAFs. Furthermore, chemotherapy may exacerbate the formation of cCAFs and CTCs, which may eventually support the formation of a metastasis niche in breast cancer.
Article
Oncology
Laura Gomez-Cuadrado, Esme Bullock, Zeanap Mabruk, Hong Zhao, Margarita Souleimanova, Pernille Rimmer Noer, Arran K. Turnbull, Claus Oxvig, Nicholas Bertos, Adam Byron, J. Michael Dixon, Morag Park, Syed Haider, Rachael Natrajan, Andrew H. Sims, Valerie G. Brunton
Summary: This study demonstrates the molecular differences in the tumor microenvironment (TME) between invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC), identifying differences in matrix organization and growth factor signaling pathways. These differences are associated with the long-term survival outcomes in ILC.
Review
Cell Biology
Deepshikha Mishra, Debabrata Banerjee
Summary: The cancer secretome is a collection of proteins released by cancer cells, which provides important information for cancer diagnosis and treatment. While previous studies have focused on the secretome of cancer cells, the contribution of stromal cells, particularly cancer-associated fibroblasts (CAFs), needs to be further explored. Investigating the secretome of CAFs can lead to the discovery of novel biomarkers and potential therapeutic targets, and enhance our understanding of personalized cancer treatment.
Article
Oncology
Dadasaheb Akolkar, Darshana Patil, Timothy Crook, Sewanti Limaye, Raymond Page, Vineet Datta, Revati Patil, Cynthe Sims, Anantbhushan Ranade, Pradeep Fulmali, Pooja Fulmali, Navin Srivastava, Pradip Devhare, Sachin Apurwa, Shoeb Patel, Sanket Patil, Archana Adhav, Sushant Pawar, Akshay Ainwale, Rohit Chougule, Madhavi Apastamb, Ajay Srinivasan, Rajan Datar
INTERNATIONAL JOURNAL OF CANCER
(2020)
Article
Multidisciplinary Sciences
Dadasaheb Akolkar, Darshana Patil, Navin Srivastava, Revati Patil, Vineet Datta, Sachin Apurwa, Nitin Yashwante, Raja Dhasarathan, Rahul Gosavi, Jinumary John, Shabishta Khan, Ninad Jadhav, Priti Mene, Dhanashri Ahire, Sushant Pawar, Harshal Bodke, Subhraline Sahoo, Arun Nile, Dinesh Saindane, Harshal Darokar, Pradip Devhare, Ajay Srinivasan, Rajan Datar
Summary: The CellDx multigene variant profiling assay demonstrates high specificity, sensitivity, accuracy, and reproducibility, making it suitable for guiding selection of targeted and immunotherapy agents in patients with solid organ tumors.
Review
Biochemistry & Molecular Biology
Pradip Devhare, Mridula Madiyal, Chiranjay Mukhopadhyay, Shiran Shetty, Shamee Shastry
Summary: HEV infection can lead to high mortality in pregnant women and chronic disease in immunocompromised individuals. Extrahepatic manifestations like neuronal and renal diseases can also occur during HEV infection, but the mechanism of pathogenesis is poorly understood.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Reina Sasaki-Tanaka, Kalyan C. Nagulapalli Venkata, Hiroaki Okamoto, Mitsuhiko Moriyama, Tatsuo Kanda
Summary: Hepatitis A virus (HAV) infection is a major cause of acute hepatitis worldwide, and the prevalence of HAV vaccination is not adequate in some countries. The development of new anti-HAV therapeutic options has been motivated, and in silico and in vitro studies have identified potential inhibitors for HAV replication.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Reina Sasaki-Tanaka, Toshikatsu Shibata, Hiroaki Okamoto, Mitsuhiko Moriyama, Tatsuo Kanda
Summary: In this study, several novel therapeutic drugs were investigated through a drug repositioning approach, with favipiravir identified as a potential antiviral against hepatitis A virus (HAV) infection. The study examined the replication of HAV and introduced nucleotide mutations in the HAV genome using different drugs. Favipiravir showed inhibitory effects on HAV replication and introduced more nucleotide mutations compared to ribavirin. Further in vivo experiments are needed to confirm the efficacy of favipiravir in treating severe HAV infection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Ryota Masuzaki, Tatsuo Kanda, Reina Sasaki, Naoki Matsumoto, Kazushige Nirei, Masahiro Ogawa, Seth J. Karp, Mitsuhiko Moriyama, Hirofumi Kogure
Summary: Hepatocellular carcinoma (HCC) is a common malignancy worldwide and the SOCS family proteins play an important role in HCC development and liver regeneration. By negatively regulating cytokine signaling, SOCS proteins can modulate cellular growth, differentiation, and immune response. In HCC treatment, SOCS proteins may be potential targets for controlling cell proliferation and immune response.
Editorial Material
Biochemistry & Molecular Biology
Tatsuo Kanda, Reina Sasaki-Tanaka, Shingo Nakamoto
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Medicine, General & Internal
Tatsuo Kanda, Reina Sasaki-Tanaka, Tomotaka Ishii, Hayato Abe, Masahiro Ogawa, Hirayuki Enomoto
JOURNAL OF CLINICAL MEDICINE
(2022)
Review
Biochemistry & Molecular Biology
Reina Sasaki-Tanaka, Ranjit Ray, Mitsuhiko Moriyama, Ratna B. Ray, Tatsuo Kanda
Summary: Alcohol is a major cause of liver diseases, such as liver cirrhosis and hepatocellular carcinoma. This is due to the conversion of alcohol to acetaldehyde in hepatocytes, leading to various liver damage, as well as the production of toxins from intestinal bacteria aggravating inflammation. Genetic factors also play a role in this process.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Reina Sasaki-Tanaka, Toshikatsu Shibata, Mitsuhiko Moriyama, Hirofumi Kogure, Asuka Hirai-Yuki, Hiroaki Okamoto, Tatsuo Kanda
Summary: In this study, HuhT7-HAV/Luc cells were established as a suitable model for anti-HAV drug screening. Masitinib, a tyrosine kinase inhibitor, was found to reduce HAV replication and internal ribosomal entry-site (IRES) activity. It may be a potential treatment for severe HAV infection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Tatsuo Kanda, Ryota Masuzaki, Reina Sasaki-Tanaka, Hirofumi Kogure, Mitsuhiko Moriyama
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Shini Kanezawa, Mitsuhiko Moriyama, Tatsuo Kanda, Akiko Fukushima, Ryota Masuzaki, Reina Sasaki-Tanaka, Akiko Tsunemi, Takahiro Ueno, Noboru Fukuda, Hirofumi Kogure
Summary: Metabolic-dysfunction-associated fatty-liver disease (MAFLD) is the leading cause of liver disease worldwide. Nonalcoholic steatohepatitis (NASH) patients have a higher prevalence of small-intestinal bacterial overgrowth (SIBO). In this study, we investigated the differences in gut microbiota between stroke-prone spontaneously hypertensive-5 rats (SHRSP5) fed a normal diet (ND) or a high-fat- and high-cholesterol-containing diet (HFCD). We found an association between MAFLD and gut microbiota alteration, suggesting that targeting gut microbiota may be a potential therapeutic approach for MAFLD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, General & Internal
Tatsuo Kanda, Naoki Matsumoto, Tomotaka Ishii, Shuhei Arima, Shinji Shibuya, Masayuki Honda, Reina Sasaki-Tanaka, Ryota Masuzaki, Shini Kanezawa, Masahiro Ogawa, Shintaro Yamazaki, Osamu Aramaki, Hirofumi Kogure, Yukiyasu Okamura
Summary: Through living-donor liver transplantation (LDLT) from a HLA-matched sibling donor, the use of immunosuppressants can potentially be stopped. The prognosis of liver transplantation may be affected by acute and chronic rejection reactions mediated by anti-HLA antibodies and T cells, as well as the underlying liver disease of the recipient. This case report highlights the importance of initiating direct-acting antiviral (DAA) therapy immediately after LDLT for hepatitis C virus (HCV) infection, in order to improve the prognosis of the recipients.
Article
Medicine, General & Internal
Tomotaka Ishii, Keijiro Hoshino, Masayuki Honda, Yoichiro Yamana, Reina Sasaki-Tanaka, Mariko Kumagawa, Shini Kanezawa, Taku Mizutani, Naoki Matsumoto, Ryota Masuzaki, Kazushige Nirei, Hiroaki Yamagami, Mitsuhiko Moriyama, Tatsuo Kanda
Summary: This article describes a case of liver injury induced by benzbromarone in a male patient, emphasizing the importance of regular monitoring of liver function tests in patients taking benzbromarone.
Meeting Abstract
Oncology
Pradip Devhare, Revati Patil, Dadasaheb B. Akolkar, Darshana Patil, Navin Srivastava, Pooja Fulmali, Shoeb Patel, Pradyumna Shejwalkar, Vineet Datta, Cynthe Sims, Ajay Srinivasan, Rajan Datar
JOURNAL OF CLINICAL ONCOLOGY
(2020)