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pancreatic cancer fibrosis

Elisabetta Fenocchio, Ilaria Depetris, Delia Campanella, Lucia Garetto, Fabrizio Carnevale Schianca, Danilo Galizia, Giovanni Grignani, Massimo Aglietta, Francesco Leone
BACKGROUND: Gemcitabine is currently the standard chemotherapy for the adjuvant treatment of pancreatic cancer. This chemotherapeutic agent is generally well-tolerated, myelosuppression and gastrointestinal toxicity being common side effects. Nevertheless, gemcitabine-induced pulmonary toxicity has been rarely reported. Despite its low incidence, the spectrum of pulmonary injury is wide, including potentially fatal conditions. We report a case of acute interstitial pneumonia related to gemcitabine, completely solved with Imatinib Mesylate (IM)...
October 12, 2016: BMC Cancer
Sangeetha N Kalimuthu, Stefano Serra, Neesha Dhani, Sara Hafezi-Bakhtiari, Eva Szentgyorgyi, Rajkumar Vajpeyi, Runjan Chetty
AIM: Several regression grading systems have been proposed for neoadjuvant chemoradiation-treated pancreatic ductal adenocarcinoma (PDAC). This study aimed to examine the utility, reproducibility and level of concordance of three most frequently used grading systems. METHODS: Four gastrointestinal pathologists used the College of American Pathologists (CAP), Evans, MD Anderson Cancer Centre (MDA) regression grading systems to grade 14 selected cases (7-20 slides from each case) of neoadjuvant chemoradiation-treated PDAC...
September 28, 2016: Journal of Clinical Pathology
Benedikt Fels, Nikolaj Nielsen, Albrecht Schwab
The tumor environment contributes importantly to tumor cell behavior and cancer progression. Aside from biochemical constituents, physical factors of the environment also influence the tumor. Growing evidence suggests that mechanics [e.g., tumor (stroma) elasticity, tissue pressure] are critical players of cancer progression. Underlying mechanobiological mechanisms involve among others the regulation of focal adhesion molecules, cytoskeletal modifications, and mechanosensitive (MS) ion channels of cancer- and tumor-associated cells...
October 2016: European Biophysics Journal: EBJ
Yuichi Waragai, Rei Suzuki, Tadayuki Takagi, Mitsuru Sugimoto, Hiroyuki Asama, Ko Watanabe, Hitomi Kikuchi, Takuto Hikichi, Atsushi Masamune, Ya'an Kang, Jason B Fleming, Hiromasa Ohira
BACKGROUND: Wisteria floribunda agglutinin-positive mac-2 binding protein (WFA(+)-M2BP) is an excellent biomarker for predicting hepatic fibrosis. We hypothesized WFA(+)-M2BP might be a serum biomarker for the diagnosis of chronic pancreatitis (CP) and pancreatic ductal adenocarcinoma (PDAC) with dense fibrosis. METHODS: In this study, we included 16 CP and 24 PDAC patients. Serum levels of WFA(+)-M2BP (cut-off index [COI]) were compared between the 2 groups. To confirm the cellular production of WFA(+)-M2BP, we investigated the presence of WFA(+)-M2BP in HEK293 cells, 3 established human PDAC cell lines and a recently generated human PDAC cell line derived from a liver metastasis (MDA-PATC53)...
September 7, 2016: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
Misako Sato-Matsubara, Norifumi Kawada
Nielsen SR, Quaranta V, Linford A, et al.(1) (Macrophage-secreted granulin supports pancreatic cancer metastasis by inducing liver fibrosis. Nat Cell Biol. 2016;18:549-60) recently described a new mechanism for the tumor-stromal interaction in the metastatic progression of pancreatic ductal adenocarcinoma (PDAC) in the liver via granulin that is secreted by metastasis-associated macrophages (MAMs).(1) MAM-derived granulin transactivates hepatic stellate cells (hStCs), which leads to the production of periostin and extracellular matrix (ECM) at the metastatic site...
September 19, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Matthew J Ware, Vazrik Keshishian, Justin J Law, Jason C Ho, Carlos A Favela, Paul Rees, Billie Smith, Sayeeduddin Mohammad, Rosa F Hwang, Kimal Rajapakshe, Cristian Coarfa, Shixia Huang, Dean P Edwards, Stuart J Corr, Biana Godin, Steven A Curley
Pancreatic ductal adenocarcinoma (PDAC) is characterized by a prominent desmoplastic/stromal reaction, which contributes to the poor clinical outcome of this disease. Therefore, greater understanding of the stroma development and tumor-stroma interactions is highly required. Pancreatic stellate cells (PSC) are myofibroblast-like cells located in exocrine areas of the pancreas, which as a result of inflammation produced by PDAC migrate and accumulate in the tumor mass, secreting extracellular matrix components and producing the dense PDAC stroma...
November 2016: Biomaterials
Inge Ubink, Elisha R Verhaar, Onno Kranenburg, Roel Goldschmeding
CCN2, also known as connective tissue growth factor (CTGF) is a transcriptional target of TGF-β signaling. Unlike its original name ("CTGF") suggested, CCN2 is not an actual growth factor but a matricellular protein that plays an important role in fibrosis, inflammation and connective tissue remodeling in a variety of diseases, including cancer. In pancreatic ductal adenocarcinoma, CCN2 signaling induces stromal infiltration and facilitates a strong tumor-stromal interaction. In many types of cancer, CCN2 overexpression has been associated with poor outcome...
September 2016: Journal of Cell Communication and Signaling
Yoshikuni Yonenaga, Fumiki Kushihata, Jota Watanabe, Taiji Tohyama, Hitoshi Inoue, Atsuro Sugita, Yasutsugu Takada
Autoimmune pancreatitis (AIP) is a unique form of pancreatitis, histopathologically characterized by dense lymphoplasmacytic infiltration and fibrosis of the pancreas with obliterative phlebitis. AIP is associated with a good response to steroid therapy. Differentiation between AIP and pancreatic cancer to determine a preoperative diagnosis is often challenging, despite the use of various diagnostic modalities, including computed tomography (CT), magnetic resonance imaging and endoscopic retrograde cholangiopancreatography...
September 2016: Oncology Letters
Pratiek N Matkar, Krishna Kumar Singh, Dmitriy Rudenko, Yu Jin Kim, Michael A Kuliszewski, Gerald J Prud'homme, David W Hedley, Howard Leong-Poi
Pancreatic ductal adenocarcinoma (PDAC) is characterized by an intense fibrotic reaction termed tumor desmoplasia, which is in part responsible for its aggressiveness. Endothelial cells have been shown to display cellular plasticity in the form of endothelial-to-mesenchymal transition (EndMT) that serves as an important source of fibroblasts in pathological disorders, including cancer. Angiogenic co-receptor, neuropilin-1 (NRP- 1) actively binds TGFβ1, the primary mediator of EndMT and is involved in oncogenic processes like epithelial-to-mesenchymal transition (EMT)...
August 4, 2016: Oncotarget
Qian Xiao, Donger Zhou, Agnieszka A Rucki, Jamila Williams, Jiaojiao Zhou, Guanglan Mo, Adrian Murphy, Kenji Fujiwara, Jennifer Kleponis, Bulent Salman, Christopher L Wolfgang, Robert A Anders, Shu Zheng, Elizabeth M Jaffee, Lei Zheng
Stromal fibrosis is a prominent histologic characteristic of pancreatic ductal adenocarcinoma (PDAC), but how stromal fibroblasts are regulated in the tumor microenvironment (TME) to support tumor growth is largely unknown. Here we show that PDAC cells can induce DNA methylation in cancer-associated fibroblasts (CAF). Upon direct contact with PDAC cells, DNA methylation of SOCS1 and other genes is induced in mesenchymal stem cells or in CAF that lack SOCS1 methylation at baseline. Silencing or decitabine treatment to block the DNA methylation enzyme DNMT1 inhibited methylation of SOCS1...
September 15, 2016: Cancer Research
Monika A Jakubowska, Pawel E Ferdek, Oleg V Gerasimenko, Julia V Gerasimenko, Ole H Petersen
The mammalian diffuse stellate cell system comprises retinoid-storing cells capable of remarkable transformations from a quiescent to an activated myofibroblast-like phenotype. Activated pancreatic stellate cells (PSCs) attract attention owing to the pivotal role they play in development of tissue fibrosis in chronic pancreatitis and pancreatic cancer. However, little is known about the actual role of PSCs in the normal pancreas. These enigmatic cells have recently been shown to respond to physiological stimuli in a manner that is markedly different from their neighbouring pancreatic acinar cells (PACs)...
August 2016: Open Biology
Masaki Yoshida, Yoshihiro Miyasaka, Kenoki Ohuchida, Takashi Okumura, Biao Zheng, Nobuhiro Torata, Hayato Fujita, Toshinaga Nabae, Tatsuya Manabe, Masaya Shimamoto, Takao Ohtsuka, Kazuhiro Mizumoto, Masafumi Nakamura
Desmoplasia contributes to the aggressive behavior of pancreatic cancer. However, recent clinical trials testing several anti-fibrotic agents on pancreatic cancer have not shown clear efficacy. Therefore, further investigation of desmoplasia-targeting anti-fibrotic agents by another mechanism is needed. Calpeptin, an inhibitor of calpains, suppressed fibroblast function and inhibited fibrosis. In this study, we investigated the anticancer effects of calpeptin on pancreatic cancer. We investigated whether calpeptin inhibited tumor progression using a mouse xenograft model...
August 3, 2016: Cancer Science
Cole R Drifka, Agnes G Loeffler, Kara Mathewson, Guneet Mehta, Adib Keikhosravi, Yuming Liu, Stephanie Lemancik, William A Ricke, Sharon M Weber, W John Kao, Kevin W Eliceiri
Stromal collagen alignment has been shown to have clinical significance in a variety of cancers and in other diseases accompanied by fibrosis. While much of the biological and clinical importance of collagen changes has been demonstrated using second harmonic generation (SHG) imaging in experimental settings, implementation into routine clinical pathology practice is currently prohibitive. To translate the assessment of collagen organization into routine pathology workflow, a surrogate visualization method needs to be examined...
September 2016: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
Xiaoqing He, Emily Despeaux, Todd A Stueckle, Alexander Chi, Vincent Castranova, Cerasela Zoica Dinu, Liying Wang, Yon Rojanasakul
Carbon nanotubes (CNTs) have been likened to asbestos in terms of morphology and toxicity. CNT exposure can lead to pulmonary fibrosis and promotion of tumorigenesis. However, the mechanisms underlying CNT-induced carcinogenesis are not well defined. Mesothelin (MSLN) is overexpressed in many human tumors, including mesotheliomas and pancreatic and ovarian carcinomas. In this study, the role of MSLN in the carcinogenic transformation of human bronchial epithelial cells chronically exposed to single-walled CNT (BSW) was investigated...
September 1, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Eiji Miyoshi, Yoshihiro Kamada
The prognosis of pancreatic cancer is extremely poor compared to that of other cancers. One of the reasons for this is the difficulty of early diagnosis. Surveillance using cancer biomarkers and image diagnosis can enable early detection and has improved the prognosis of hepatocellular carcinoma in Japan. However, it is very difficult to detect pancreatic cancer at an early stage using cancer biomarkers and image diagnosis alone. Fucosylation is one of the most important types of glycosylation involved in cancer and inflammation...
July 14, 2016: Cancer Science
Thomas Payen, Carmine F Palermo, Stephen A Sastra, Hong Chen, Yang Han, Kenneth P Olive, Elisa E Konofagou
Recently, ultrasonic imaging of soft tissue mechanics has been increasingly studied to image otherwise undetectable pathologies. However, many underlying mechanisms of tissue stiffening remain unknown, requiring small animal studies and adapted elasticity mapping techniques. Harmonic motion imaging (HMI) assesses tissue viscoelasticity by inducing localized oscillation from a periodic acoustic radiation force. The objective of this study was to evaluate the feasibility of HMI for in vivo elasticity mapping of abdominal organs in small animals...
August 7, 2016: Physics in Medicine and Biology
Hong Jiang, Samarth Hegde, Brett L Knolhoff, Yu Zhu, John M Herndon, Melissa A Meyer, Timothy M Nywening, William G Hawkins, Irina M Shapiro, David T Weaver, Jonathan A Pachter, Andrea Wang-Gillam, David G DeNardo
Single-agent immunotherapy has achieved limited clinical benefit to date in patients with pancreatic ductal adenocarcinoma (PDAC). This may be a result of the presence of a uniquely immunosuppressive tumor microenvironment (TME). Critical obstacles to immunotherapy in PDAC tumors include a high number of tumor-associated immunosuppressive cells and a uniquely desmoplastic stroma that functions as a barrier to T cell infiltration. We identified hyperactivated focal adhesion kinase (FAK) activity in neoplastic PDAC cells as an important regulator of the fibrotic and immunosuppressive TME...
August 2016: Nature Medicine
Neus Martínez-Bosch, Pedro Enrique Guerrero, Mireia Moreno, Anabel José, Mar Iglesias, Jessica Munné-Collado, Héctor Anta, Joan Gibert, Carlos Alberto Orozco, Judith Vinaixa, Cristina Fillat, Francesc Viñals, Pilar Navarro
Current treatments for pancreatic ductal adenocarcinoma (PDA) are ineffective, making this the 4th leading cause of cancer deaths. Sunitinib is a broad-spectrum inhibitor of tyrosine kinase receptors mostly known for its anti-angiogenic effects. We tested the therapeutic effects of sunitinib in pancreatic cancer using the Ela-myc transgenic mouse model. We showed that Ela-myc pancreatic tumors express PDGFR and VEGFR in blood vessels and epithelial cells, rendering these tumors sensitive to sunitinib by more than only its anti-angiogenic activity...
June 21, 2016: Oncotarget
Kazumi Ebine, Christina R Chow, Brian T DeCant, Holly Z Hattaway, Paul J Grippo, Krishan Kumar, Hidayatullah G Munshi
Cells in the pancreas that have undergone acinar-ductal metaplasia (ADM) can transform into premalignant cells that can eventually become cancerous. Although the epithelial-mesenchymal transition regulator Snail (Snai1) can cooperate with Kras in acinar cells to enhance ADM development, the contribution of Snail-related protein Slug (Snai2) to ADM development is not known. Thus, transgenic mice expressing Slug and Kras in acinar cells were generated. Surprisingly, Slug attenuated Kras-induced ADM development, ERK1/2 phosphorylation and proliferation...
2016: Scientific Reports
Yuichi Takano, Masatsugu Nagahama, Eiichi Yamamura, Naotaka Maruoka, Kazuaki Yokomizo, Hiroki Mizukami, Jun-Ichi Tanaka, Nobuyuki Ohike
The case patient was a previously healthy 82-year-old male. Abdominal ultrasound during a medical check-up revealed a dilatation of the main pancreatic duct, and the patient was referred to our hospital for closer examination. Contrast-enhanced computed tomography (CT) revealed a low-density mass of 20 mm in the pancreatic head-body transitional area. Magnetic resonance cholangiopancreatography (MRCP) revealed marked dilatation of the main pancreatic duct and branches in the body-tail. On endoscopic ultrasonography (EUS), a hypoechoic mass with irregular shape was detected, which was consistent with the area of pancreatic duct stenosis...
August 2016: Clinical Journal of Gastroenterology
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