Review
Oncology
Wenting Du, Marina Pasca di Magliano, Yaqing Zhang
Summary: The stroma-rich, immunosuppressive microenvironment in PDA is characterized by interactions between tumor cells and other cellular components, leading to immune evasion and contributing to cancer cell phenotypes. Therapeutic approaches targeting the stroma and re-programming the tumor microenvironment may improve clinical outcomes for pancreatic cancer patients.
FRONTIERS IN ONCOLOGY
(2021)
Review
Oncology
Kendelle J. Murphy, Cecilia R. Chambers, David Herrmann, Paul Timpson, Brooke A. Pereira
Summary: PDAC is a highly lethal solid malignancy with a low five-year survival rate of around 10%. The interactions between tumor and stromal or immune cells in the pancreatic tumor microenvironment play a critical role in both promoting and restraining the development and progression of PDAC. Understanding the role of the extracellular matrix and stromal cells like cancer-associated fibroblasts (CAFs) is vital for developing effective treatment strategies for this aggressive disease.
Article
Materials Science, Biomaterials
Viola Sgarminato, Simone Luigi Marasso, Matteo Cocuzza, Giorgio Scordo, Alberto Ballesio, Gianluca Ciardelli, Chiara Tonda-Turo
Summary: This article introduces a microfluidic in vitro model that recreates the interaction between pancreatic ductal adenocarcinoma (PDAC) and the stromal microenvironment, for validation of innovative therapies. The model allows for the control of interactions between PDAC cells and pancreatic stellate cells (PSCs), and analysis of their effects on cell behavior. The model validation shows that stromal cells are activated and secrete more cytokines under co-culture conditions. This microfluidic system enables drug efficacy evaluation and provides insights into the early evolution steps of PDAC.
BIOMATERIALS SCIENCE
(2022)
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.
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.
Review
Immunology
Claire Lamaison, Karin Tarte
Summary: Stromal cells in bone marrow and lymphoid organs function to regulate B cell behavior, with follicular lymphoma being a prime example of a B-cell neoplasia dependent on a specific tumor microenvironment that includes cancer-associated fibroblasts (CAFs). This interaction between malignant B cells and stromal cells contributes to the complexity of the tumor microenvironment and highlights the need for further research into signaling pathways and molecular mechanisms for potential therapeutic targets.
IMMUNOLOGICAL REVIEWS
(2021)
Article
Medicine, Research & Experimental
Hongquan Qin, Jiali Chen, Katia Bouchekioua-Bouzaghou, Ya-Ming Meng, Jordi Bach Griera, Xue Jiang, Xiangzhan Kong, Minghui Wang, Qiuping Xu, Ping-Pui Wong
Summary: The study found that MAGEA regulates tumor-stromal crosstalk in PDAC, with high expression correlating with poor chemotherapeutic response and prognosis in multiple cancers. The mechanism includes inhibition of gemcitabine-induced cancer cell apoptosis and activation of GDF15 secretion to enhance gemcitabine resistance. Targeting MAGEA-mediated paracrine regulation of chemoresistance by immunotherapy could be a promising strategy for pancreatic cancer treatment.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Article
Oncology
Mira Stadler, Karoline Pudelko, Alexander Biermeier, Natalie Walterskirchen, Anthoula Gaigneaux, Claudia Weindorfer, Nathalie Harrer, Hagen Klett, Markus Hengstschlaeger, Julia Schueler, Wolfgang Sommergruber, Rudolf Oehler, Michael Bergmann, Elisabeth Letellier, Helmut Dolznig
Summary: Colorectal cancer is influenced by the tumor microenvironment, where cancer-associated fibroblasts and tumor-associated macrophages play crucial roles. The molecular crosstalk between tumor cells, fibroblasts, and macrophages affects monocyte recruitment and their differentiation into immunosuppressive macrophages. Cytokine profiling shows that fibroblasts induce specific cytokine secretion in co-culture with macrophages, contributing to tumor cell invasion.
Review
Biochemistry & Molecular Biology
Xiangyu Chu, Yinmo Yang, Xiaodong Tian
Summary: This article reviews the mechanism of exosomal miRNAs in the crosstalk between PDAC cells and cancer-associated fibroblasts (CAFs) in the tumor microenvironment, aiming to improve the understanding of TME regulation and provide evidence for designing diagnostic and therapeutic targets against exosomal miRNA in human PDAC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
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
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)
Review
Biotechnology & Applied Microbiology
Ying Li, Wenjing Zhao, Yanli Wang, Haiyan Wang, Shanglong Liu
Summary: Pancreatic cancer interacts closely with the tumor microenvironment, and extracellular vesicles play a key role in this interaction. Understanding the selective packaging and mechanistic impact of these vesicles is important for understanding cancer biology. This review summarizes recent findings on the interactions between pancreatic cancer and stromal cells, as well as the mechanisms involved in immune response and chemoresistance. It also identifies extracellular vesicles as potential diagnostic biomarkers and therapeutic targets for pancreatic cancer.
JOURNAL OF NANOBIOTECHNOLOGY
(2022)
Review
Immunology
Giovanni Monteleone, Claudia Maresca, Marco Colella, Teresa Pacifico, Daniele Congiu, Edoardo Troncone, Irene Marafini
Summary: This article reviews the current understanding of the involvement of interleukin-34 (IL-34) and its receptor, macrophage colony-stimulating factor-1 receptor (MCSF-1R), in colorectal cancer (CRC). It highlights the role of the IL-34/MCSF-1R axis in controlling tumor-associated macrophages (TAMs) and promoting cancer resistance to chemotherapy and immunotherapy. The findings suggest that targeting IL-34/MCSF-1R could be a potential therapeutic intervention in CRC.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, Research & Experimental
Zhiwei Peng, Manping Ye, Huiming Ding, Zhenyou Feng, Kongwang Hu
Summary: This study investigated the role of tumor-associated fibroblasts (CAFs) in colorectal cancer and their interaction with the tumor microenvironment. Two distinct types of CAFs were identified, one associated with myofibroblast-like cells and the other related to immune inflammation. Functional analysis revealed a significant crosstalk between immune inflammation-related CAFs and stromal components in the tumor microenvironment, promoting tumor progression and metastasis. Additionally, these CAFs were found to influence immune cells and lipid metabolism in patients undergoing chemotherapy. Furthermore, a correlation between immune inflammation-related CAFs and poor prognosis was identified through public databases.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Oncology
Yasuyuki Okada, Fuduan Peng, Jose Perea, Luis Corchete, Luis Bujanda, Wei Li, Ajay Goel
Summary: A novel methylation signature risk-scoring model was developed to reliably identify patients with synchronous colorectal cancer (SyCRC), which has the potential to improve the diagnosis and management of colorectal cancer (CRC) patients.
BRITISH JOURNAL OF CANCER
(2023)
Article
Oncology
Keisuke Okuno, Shuichi Watanabe, Souvick Roy, Mitsuro Kanda, Masanori Tokunaga, Yasuhiro Kodera, Yusuke Kinugasa, Ajay Goel
Summary: We established a miRNA-based liquid biopsy signature that can reliably predict early recurrence in gastric cancer patients by analyzing miRNA expression profiling. Additionally, a model combining the miRNA signature, microsatellite instability (MSI) status, and tumor size exhibited better predictive performance and was successfully validated in another independent cohort. Finally, we translated the miRNA signature into a liquid biopsy assay and demonstrated its independence as a predictor for early recurrence.
BRITISH JOURNAL OF CANCER
(2023)
Letter
Gastroenterology & Hepatology
Kota Nakamura, Ajay Goel
Article
Genetics & Heredity
Divya Sahu, Chen-Ching Lin, Ajay Goel
Summary: This study identified eRNA panels that can predict tumor recurrence in patients with colorectal cancer. These panels outperformed TNM staging in predicting recurrence and showed excellent accuracy. The findings of this study have the potential to improve risk stratification and guide precision oncology treatments for colorectal cancer patients.
Article
Biochemistry & Molecular Biology
Keisuke Okuno, Caiming Xu, Silvia Pascual-Sabater, Masanori Tokunaga, Tetsuji Takayama, Haiyong Han, Cristina Fillat, Yusuke Kinugasa, Ajay Goel
Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer due to its resistance to chemotherapy, including Gemcitabine (Gem). This study aimed to investigate whether the natural botanical Andrographis (Andro) can reverse Gem resistance in PDAC cells. The findings suggest that Andro can enhance the anti-cancer potential of Gem by regulating the ERBB3 and calcium signaling pathways.
Article
Oncology
Keisuke Okuno, Muhammad Yogi Pratama, Jiang Li, Masanori Tokunaga, Xin Wang, Yusuke Kinugasa, Ajay Goel
Summary: This cell culture-based study demonstrated that Ginseng has the potential to fight against colorectal cancer by regulating cellular apoptosis and reversing the methylation status of silenced genes.
Review
Endocrinology & Metabolism
Amir Reza Moravejolahkami, Mehdi Shakibaei, Andrea Mary Fairley, Manoj Sharma
Summary: Dysbiosis in the gut has been linked to T1DM, and this review analyzed the effects of probiotics, prebiotics, and synbiotics on T1DM patients. After evaluating 258 entries, five trials were included, showing that probiotic supplementation decreased fasting blood glucose but had no significant effect on HbA1c, C-peptide, and insulin requirements. Probiotics may serve as a complementary therapeutic strategy for T1DM, but more trials are needed.
DIABETES-METABOLISM RESEARCH AND REVIEWS
(2023)
Editorial Material
Gastroenterology & Hepatology
Keisuke Okuno, Masanori Tokunaga, Daniel Von Hoff, Yusuke Kinugasa, Ajay Goel
Article
Biochemistry & Molecular Biology
Aranka Brockmueller, Sosmitha Girisa, Ajaikumar B. B. Kunnumakkara, Mehdi Shakibaei
Summary: Resveratrol can enhance the sensitivity of colorectal cancer cells to 5-FU by regulating the beta 1-integrin/HIF-1α signaling axis, leading to suppression of cancer cell growth and invasion, inhibition of inflammation and cancer stem cell production. These findings highlight the potential application of resveratrol in the treatment of colorectal cancer by overcoming chemoresistance to 5-FU.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Medicine, Research & Experimental
Aranka Brockmueller, Samson Mathews Samuel, Alena Mazurakova, Dietrich Busselberg, Peter Kubatka, Mehdi Shakibaei
Summary: Colorectal cancer (CRC) is a major global malignant disease often resistant to chemotherapy drugs. Two polyphenolic turmeric ingredients, calebin A and curcumin, show anti-inflammatory and anticancer effects, including the ability to sensitize CRC cells to chemotherapy drugs. They modulate inflammation, proliferation, cell cycle, cancer stem cells, and apoptotic signaling to convert chemoresistant CRC cells into non-chemoresistant cells. Further studies and clinical trials are needed to test their effectiveness in overcoming cancer chemoresistance.
Article
Genetics & Heredity
Julyann Perez-Mayoral, Maria Gonzalez-Pons, Hilmaris Centeno-Girona, Ingrid M. Montes-Rodriguez, Marievelisse Soto-Salgado, Belisa Suarez, Natalia Rodriguez, Giancarlo Colon, Javier Sevilla, Daphne Jorge, Xavier Llor, Rosa M. Xicola, Doris H. Toro, Luis Tous-Lopez, Marla Torres-Torres, Jose S. Reyes, Nicolas Lopez-Acevedo, Ajay Goel, Segundo Rodriguez-Quilichini, Marcia Cruz-Correa
Summary: This study analyzed the molecular markers and clinicopathologic features of colorectal tumors from Puerto Rico to better understand the molecular pathways leading to colorectal cancer in this Hispanic subpopulation. The results showed distinct differences in the prevalence of molecular markers among tumors from Puerto Rico compared to other racial/ethnic groups, suggesting a unique molecular carcinogenic pathway among Hispanics.
Article
Cell Biology
Katsuki Miyazaki, Yuji Morine, Caiming Xu, Chiharu Nakasu, Yuma Wada, Hiroki Teraoku, Shinichiro Yamada, Yu Saito, Tetsuya Ikemoto, Mitsuo Shimada, Ajay Goel
Summary: This study demonstrates that the combination of Curcumin and Lenvatinib exhibits synergistic anti-tumor efficacy in Lenvatinib-resistant HCC cell lines. Curcumin reverses Lenvatinib resistance through inhibition of the EGFR pathway. These findings suggest that the combination therapy has potential clinical application for adjunctive treatment in HCC.
Article
Chemistry, Medicinal
Katsuki Miyazaki, Caiming Xu, Mitsuo Shimada, Ajay Goel
Summary: Colorectal cancer (CRC) is a major cause of cancer-related deaths worldwide. Limitations of current CRC chemotherapeutic drugs include toxicity, side effects, and high costs. In this study, a combination of curcumin and andrographis showed superior anti-tumor effects in CRC cells by inhibiting cell proliferation, invasion, colony formation, and inducing apoptosis. The combination treatment also activated the ferroptosis pathway and downregulated the expression of GPX-4 and FSP-1, leading to accumulation of reactive oxygen species and lipid peroxides in CRC cells.
Editorial Material
Biochemistry & Molecular Biology
Patrick K. T. Shiu, Mirolyuba Ilieva, Anja Holm, Shizuka Uchida, Johanna K. DiStefano, Agnieszka Bronisz, Ling Yang, Yoh Asahi, Ajay Goel, Liuqing Yang, Ashok Nuthanakanti, Alexander Serganov, Suresh K. Alahari, Chunru Lin, Barbara Pardini, Alessio Naccarati, Jing Jin, Beshoy Armanios, Xiao-bo Zhong, Nikolaos Sideris, Salih Bayraktar, Leandro Castellano, Andre P. Gerber, He Lin, Simon J. Conn, Doha Magdy Mostafa Sleem, Lisa Timmons
Article
Oncology
Koldo Garcia-Etxebarria, Ane Etxart, Maialen Barrero, Beatriz Nafria, Nerea Miren Segues Merino, Irati Romero-Garmendia, Ajay Goel, Andre Franke, Mauro D'Amato, Luis Bujanda
Summary: This study found that some genetic polymorphisms (SNPs), when combined with clinical data, can be used as predictors for colorectal cancer (CRC) outcomes. Additionally, new SNPs associated with CRC outcomes were detected and may serve as feasible markers.
