Review
Oncology
Manoj Amrutkar, Ivar P. Gladhaug
Summary: PDAC, a type of cancer with poor prognosis and drug resistance, is closely related to activated pancreatic stellate cells (PSCs) and metabolic reprogramming. PSCs play a crucial role in the growth and metastasis of PDAC, aiding in metabolic reprogramming and gemcitabine chemoresistance.
Article
Biochemistry & Molecular Biology
Stefania Forciniti, Elisa Dalla Pozza, Maria Raffaella Greco, Tiago Miguel Amaral Carvalho, Barbara Rolando, Giulia Ambrosini, Cristian Andres Carmona-Carmona, Raffaella Pacchiana, Daria Di Molfetta, Massimo Donadelli, Silvia Arpicco, Marta Palmieri, Stephan Joel Reshkin, Ilaria Dando, Rosa Angela Cardone
Summary: The study utilized a new potential therapeutic prodrug C18GEM to treat PDAC, showing that PDAC CSCs were more sensitive to C18GEM, especially on collagen I. The mechanism of action of C18GEM was mainly through intracellular uptake via membrane nucleoside transporters and CD36, inducing more cell death and protective autophagy in the cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Concetta Panebianco, Nadia Trivieri, Annacandida Villani, Fulvia Terracciano, Tiziana Pia Latiano, Adele Potenza, Francesco Perri, Elena Binda, Valerio Pazienza
Summary: miR-217 enhances the sensitivity of pancreatic cancer cells to gemcitabine by impairing cell cycle progression, as shown in this study.
Article
Biochemistry & Molecular Biology
Ella Rimmer, Sadaf Rashid, Igor Kraev, Francesc Miralles, Androulla Elia
Summary: Pancreatic cancer cells release extracellular vesicles that confer resistance to gemcitabine and TRAIL treatment. Removal of these vesicles during treatment may improve the response of pancreatic cancer cells to gemcitabine and TRAIL.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Cell Biology
Faizah Farooq, Asif Amin, Umer Majeed Wani, Asif Lone, Raies A. Qadri
Summary: Resistance to chemotherapy and targeted therapies is a common feature in most cancers and is a major factor in tumor relapse and metastasis. Fibronectin, a glycoprotein abundant in the extracellular matrix, has long been believed to play an important role in the pathobiology of cancer. Recent research has revealed the role of Fibronectin in the development of chemoresistance against various anticancer drugs. This review summarizes the role of Fibronectin in mediating drug resistance and discusses how aberrant expression of Fibronectin drives oncogenic signaling pathways leading to drug resistance through inhibition of apoptosis and promotion of cancer cell growth and proliferation.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Review
Cell Biology
Alica K. Beutel, Christopher J. Halbrook
Summary: Pancreatic ductal adenocarcinoma (PDA) is a leading cause of cancer-related deaths worldwide and its treatment is challenging due to a lack of durable responses to standard-of-care chemotherapies. Gemcitabine, a cornerstone in PDA treatment, faces resistance mechanisms that have not yet been overcome in patient care.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Oncology
Ananya Chakraborty, Bithika Halder, Souravi Mondal, Amanda Barrett, Wenbo Zhi, Gabor Csanyi, E. Sabbatini
Summary: Patients with chronic pancreatitis (CP) have a higher risk of pancreatic ductal adenocarcinoma (PDAC). Activated pancreatic stellate cells (PaSCs) in CP contribute to the progression of non-invasive pancreatic intraepithelial neoplasia (PanIN) lesions to invasive PDAC. In this study, we found that NADPH oxidase 1 (Nox1) in activated PaSCs from a mouse model of CP promotes the growth of pancreatic cancer cells by up-regulating Twist1/MMP-9 expression and causing changes in the extracellular matrix composition. Inhibiting Nox1 signaling in activated PaSCs can ameliorate the progression of PDAC in patients with CP.
AMERICAN JOURNAL OF CANCER RESEARCH
(2023)
Article
Oncology
Ananya Chakraborty, Bithika Halder, Souravi Mondal, Amanda Barrett, Wenbo Zhi, Gabor Csanyi, Maria E. Sabbatini
Summary: Patients with chronic pancreatitis (CP) are at higher risk of pancreatic ductal adenocarcinoma (PDAC) compared to the general population. Activated pancreatic stellate cells (PaSCs) in CP play a role in the progression of non-invasive pancreatic intraepithelial neoplasia (PanIN) to invasive PDAC. In this study, we investigated the role of NADPH oxidase 1 (Nox1) in CP-activated PaSCs and found that Nox1 enhances the growth and invasion of pancreatic cancer cells through Twist1/MMP-9 expression and changes in the extracellular matrix composition. Blocking Nox1 signaling in CP-activated PaSCs can potentially reduce extracellular matrix reorganization and protect neoplastic cells from cellular stresses, thereby ameliorating the progression of PDAC.
AMERICAN JOURNAL OF CANCER RESEARCH
(2023)
Article
Medicine, Research & Experimental
Jing Cui, Yao Guo, Tao Yin, Shanmiao Gou, Jiongxin Xiong, Xueyi Liang, Chong Lu, Tao Peng
Summary: In this study, we found that the expression of ubiquitin-specific protease 8 (USP8) was increased in pancreatic cancer patients and was associated with Gem chemotherapy recurrence. USP8 was found to promote Gem resistance by regulating cell viability and apoptosis. Additionally, USP8 enhanced Nrf2 signaling activation, which was dependent on its deubiquitinase ability. Furthermore, we demonstrated that USP8 interacted directly with Nrf2 and deubiquitinated K48-linked polyubiquitin chains from Nrf2, stabilizing its expression.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Multidisciplinary Sciences
Chen Chen, Binfeng Wu, Mingge Wang, Jinghua Chen, Zhaohui Huang, Jin-Song Shi
Summary: Our findings suggest that GABRP may serve as a downstream target of CD44s to diminish gemcitabine resistance in pancreatic cancer, and both CD44s and GABRP molecules have the potential to become prognostic biomarkers for PDAC patients with gemcitabine resistance.
Article
Biochemistry & Molecular Biology
Chonghui Hu, Renpeng Xia, Xiang Zhang, Tingting Li, Yuancheng Ye, Guolin Li, Rihua He, Zhihua Li, Qing Lin, Shangyou Zheng, Rufu Chen
Summary: This study found that the CAF-specific circRNA circFARP1 plays a critical role in pancreatic ductal adenocarcinoma (PDAC), and is associated with gemcitabine resistance and poor patient survival. Mechanistically, circFARP1 regulates the interaction between CAV1, ZNRF1, and LIF, influencing the development of tumor cell stemness and drug resistance. Additionally, high levels of circFARP1 are associated with elevated serum LIF levels and poor patient survival in PDAC.
Article
Pharmacology & Pharmacy
Ying Tan, Xuanna Li, Zhenfeng Tian, Shangxiang Chen, Jinmao Zou, Guoda Lian, Shaojie Chen, Kaihong Huang, Yinting Chen
Summary: The study revealed that TIMP1 is highly expressed in PDAC and correlated with poorer overall survival. Down-regulation of TIMP1 can enhance sensitivity of PDAC cells to GEM and reverse chemoresistance.
BIOCHEMICAL PHARMACOLOGY
(2021)
Review
Oncology
Sadegh Safaei, Roya Sajed, Ahmad Shariftabrizi, Shima Dorafshan, Leili Saeednejad Zanjani, Masoumeh Dehghan Manshadi, Zahra Madjd, Roya Ghods
Summary: Matrix stiffness is a mechanical characteristic of the extracellular matrix (ECM) that increases from the tumor core to the tumor periphery in a gradient pattern in a variety of solid tumors and can promote proliferation, invasion, metastasis, drug resistance, and recurrence. Cancer stem cells (CSCs) are a rare subpopulation of tumor cells with self-renewal, asymmetric cell division, and differentiation capabilities. Evidence suggests that matrix stiffness can activate receptors and mechanosensor/mechanoregulator proteins such as integrin, FAK, and YAP, modulating the characteristics of tumor cells as well as CSCs through different molecular signaling pathways. A deeper understanding of the effect of matrix stiffness on CSCs characteristics could lead to development of innovative cancer therapies.
CANCER CELL INTERNATIONAL
(2023)
Article
Pharmacology & Pharmacy
Yongmei Zhao, Yuanlin Zheng, Yan Zhu, Yi Zhang, Hongyan Zhu, Tianqing Liu
Summary: This study developed a specific drug delivery system based on M1 macrophage-derived exosomes for pancreatic cancer with chemoresistance. The nanoformulation combining GEM and DFX in M1Exo significantly enhanced therapeutic efficacy against GEM-resistant cancer cells.
Article
Oncology
Zongting Gu, Yongxing Du, Xueping Zhao, Chengfeng Wang
Summary: PDAC is a solid malignant tumor with a low operative rate and poor prognosis, with gemcitabine chemotherapy being one of the main treatment options. However, the efficacy of gemcitabine therapy is limited due to gemcitabine resistance, which may be influenced by the fibrotic tumor microenvironment and metabolic remodeling in PDAC. Targeting the tumor microenvironment may be a key strategy to overcome gemcitabine resistance and improve patient outcomes.
Article
Endocrinology & Metabolism
Urszula Chursa, Esther Nunez-Duran, Emmelie Cansby, Manoj Amrutkar, Silva Sutt, Marcus Stahlman, Britt-Marie Olsson, Jan Boren, Maria E. Johansson, Fredrik Backhed, Bengt R. Johansson, Carina Sihlbom, Margit Mahlapuu
Meeting Abstract
Gastroenterology & Hepatology
M. Mahlapuu, M. Amrutkar, U. Chursa, E. Nunez-Duran, J. Boren, B. R. Johansson, H. -U. Marschall, M. Blueher, E. Cansby
JOURNAL OF HEPATOLOGY
(2017)
Review
Oncology
Manoj Amrutkar, Ivar P. Gladhaug
Article
Hematology
Emmelie Cansby, Elin Magnusson, Esther Nunez-Duran, Manoj Amrutkar, Matteo Pedrelli, Paolo Parini, Jenny Hoffmann, Marcus Stahlman, Brian W. Howell, Hanns-Ulrich Marschall, Jan Boren, Margit Mahlapuu
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2018)
Article
Endocrinology & Metabolism
Silva Sutt, Emmelie Cansby, Alexandra Paul, Manoj Amrutkar, Esther Nunez-Duran, Nagaraj M. Kulkarni, Marcus Stahlman, Jan Boren, Jurga Laurencikiene, Brian W. Howell, Sven Enerback, Margit Mahlapuu
JOURNAL OF ENDOCRINOLOGY
(2018)
Article
Cell Biology
Daniela Lenggenhager, Manoj Amrutkar, Petra Santha, Monica Aasrum, Johannes-Matthias Lohr, Ivar P. Gladhaug, Caroline S. Verbeke
Article
Cell Biology
Manoj Amrutkar, Emma Kristine Larsen, Monica Aasrum, Anette Vefferstad Finstadsveen, Per Arne Andresen, Caroline S. Verbeke, Ivar P. Gladhaug
Article
Oncology
Manoj Amrutkar, Nils Tore Vethe, Caroline S. Verbeke, Monica Aasrum, Anette Vefferstad Finstadsveen, Petra Santha, Ivar P. Gladhaug
Review
Oncology
Manoj Amrutkar, Ivar P. Gladhaug
Summary: PDAC, a type of cancer with poor prognosis and drug resistance, is closely related to activated pancreatic stellate cells (PSCs) and metabolic reprogramming. PSCs play a crucial role in the growth and metastasis of PDAC, aiding in metabolic reprogramming and gemcitabine chemoresistance.
Article
Oncology
Petra Santha, Daniela Lenggenhager, Anette Finstadsveen, Linda Dorg, Kristin Tondel, Manoj Amrutkar, Ivar P. Gladhaug, Caroline Verbeke
Summary: Pancreatic cancer has a poor prognosis mainly due to resistance to treatment, with tumor heterogeneity being a known cause for treatment failure. This study demonstrates that morphological heterogeneity in pancreatic cancer reflects structural and functional diversity, allowing for prediction of morphological patterns and potentially providing clinically relevant information. Histopathology has the potential to inform on the operationality of key biological processes in individual tumors.
Article
Biochemistry & Molecular Biology
Mara Caputo, Yeshwant Kurhe, Sima Kumari, Emmelie Cansby, Manoj Amrutkar, Eli Scandalis, Sheri L. Booten, Marcus Stahlman, Jan Boren, Hanns-Ulrich Marschall, Mariam Aghajan, Margit Mahlapuu
Summary: This study identifies MST3 as a critical regulator of ectopic fat accumulation in human hepatocytes and shows that targeting MST3 signaling with ASOs can effectively mitigate NAFLD progression in obese mice. MST3 ASOs suppress lipogenic gene expression, reduce lipotoxicity-mediated oxidative and endoplasmic reticulum stress, and correlate with NAFLD severity in human liver biopsies. These findings suggest that MST3 inhibitors may offer a new strategy for treating NAFLD patients.
Article
Oncology
Manoj Amrutkar, Caroline S. S. Verbeke, Anette Vefferstad Finstadsveen, Linda Dorg, Knut Jorgen Labori, Ivar P. P. Gladhaug
Summary: This study examines the effects of neoadjuvant chemotherapy (NAT) on the tumor and systemic metabolism in pancreatic ductal adenocarcinoma (PDAC), using comparative proteomic profiling. NAT-treated tumors showed lower expression of metabolic proteins, and patients who underwent NAT had reduced serum lactate and high-density lipoprotein-cholesterol. Furthermore, chemoresistant cancer cells expressed higher cancer stem cell markers, both in vivo and in vitro.
MOLECULAR ONCOLOGY
(2023)
Article
Gastroenterology & Hepatology
Emmelie Cansby, Esther Nunez-Duran, Elin Magnusson, Manoj Amrutkar, Sheri L. Booten, Nagaraj M. Kulkarni, L. Thomas Svensson, Jan Boren, Hanns-Ulrich Marschall, Mariam Aghajan, Margit Mahlapuu
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2019)
Article
Gastroenterology & Hepatology
Esther Nunez-Duran, Mariam Aghajan, Manoj Amrutkar, Silva Sutt, Emmelie Cansby, Sheri L. Booten, Andrew Watt, Marcus Stahlman, Norbert Stefan, Hans-Ulrich Haering, Harald Staiger, Jan Boren, Hanns-Ulrich Marschall, Margit Mahlapuu
HEPATOLOGY COMMUNICATIONS
(2018)