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pancreatic cancer fibrosis

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https://www.readbyqxmd.com/read/28414765/validation-of-full-field-optical-coherence-tomography-in-distinguishing-malignant-and-benign-tissue-in-resected-pancreatic-cancer-specimens
#1
Labrinus van Manen, Paulien L Stegehuis, Arantza Fariña-Sarasqueta, Lorraine M de Haan, Jeroen Eggermont, Bert A Bonsing, Hans Morreau, Boudewijn P F Lelieveldt, Cornelis J H van de Velde, Alexander L Vahrmeijer, Jouke Dijkstra, J Sven D Mieog
BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer-related mortality in the United States. The minority of patients can undergo curative-intended surgical therapy due to progressive disease stage at time of diagnosis. Nonetheless, tumor involvement of surgical margins is seen in up to 70% of resections, being a strong negative prognostic factor. Real-time intraoperative imaging modalities may aid surgeons to obtain tumor-free resection margins. Full-field optical coherence tomography (FF-OCT) is a promising diagnostic tool using high-resolution white-light interference microscopy without tissue processing...
2017: PloS One
https://www.readbyqxmd.com/read/28407685/extra-pancreatic-invasion-induces-lipolytic-and-fibrotic-changes-in-the-adipose-microenvironment-with-released-fatty-acids-enhancing-the-invasiveness-of-pancreatic-cancer-cells
#2
Takashi Okumura, Kenoki Ohuchida, Masafumi Sada, Toshiya Abe, Sho Endo, Kazuhiro Koikawa, Chika Iwamoto, Daisuke Miura, Yusuke Mizuuchi, Taiki Moriyama, Kohei Nakata, Yoshihiro Miyasaka, Tatsuya Manabe, Takao Ohtsuka, Eishi Nagai, Kazuhiro Mizumoto, Yoshinao Oda, Makoto Hashizume, Masafumi Nakamura
Pancreatic cancer progression involves components of the tumor microenvironment, including stellate cells, immune cells, endothelial cells, and the extracellular matrix. Although peripancreatic fat is the main stromal component involved in extra-pancreatic invasion, its roles in local invasion and metastasis of pancreatic cancer remain unclear. This study investigated the role of adipose tissue in pancreatic cancer progression using genetically engineered mice (Pdx1-Cre; LSL-KrasG12D; Trp53R172H/+) and an in vitro model of organotypic fat invasion...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404095/type-3c-pancreatogenic-diabetes-mellitus-secondary-to-chronic-pancreatitis-and-pancreatic-cancer
#3
REVIEW
Phil A Hart, Melena D Bellin, Dana K Andersen, David Bradley, Zobeida Cruz-Monserrate, Christopher E Forsmark, Mark O Goodarzi, Aida Habtezion, Murray Korc, Yogish C Kudva, Stephen J Pandol, Dhiraj Yadav, Suresh T Chari
Diabetes mellitus is a group of diseases defined by persistent hyperglycaemia. Type 2 diabetes, the most prevalent form, is characterised initially by impaired insulin sensitivity and subsequently by an inadequate compensatory insulin response. Diabetes can also develop as a direct consequence of other diseases, including diseases of the exocrine pancreas. Historically, diabetes due to diseases of the exocrine pancreas was described as pancreatogenic or pancreatogenous diabetes mellitus, but recent literature refers to it as type 3c diabetes...
November 2016: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28390098/noninvasive-characterization-of-pancreatic-tumor-mouse-models-using-magnetic-resonance-imaging
#4
Navid Farr, Yak-Nam Wang, Samantha D'Andrea, Kayla M Gravelle, Joo Ha Hwang, Donghoon Lee
The preclinical models of pancreatic adenocarcinoma provide an alternative means for determining the mechanisms of malignancy and possibilities for treatments, thus representing a resource of immense potential for cancer treatment in medicine. To evaluate different tumor models, quantifiable magnetic resonance imaging (MRI) techniques can play a significant role in identifying valuable in vivo biomarkers of tumor characteristics. We characterized three models of pancreatic cancer with multiparametric MRI techniques...
April 7, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28365915/autoimmune-pancreatitis
#5
REVIEW
Shounak Majumder, Naoki Takahashi, Suresh T Chari
Autoimmune pancreatitis (AIP) is a chronic fibroinflammatory disease of the pancreas that belongs to the spectrum of immunoglobulin G-subclass4-related diseases (IgG4-RD) and typically presents with obstructive jaundice. Idiopathic duct-centric pancreatitis (IDCP) is a closely related but distinct disease that mimics AIP radiologically but manifests clinically most commonly as recurrent acute pancreatitis in young individuals with concurrent inflammatory bowel disease. IgG4 levels are often elevated in AIP and normal in IDCP...
April 1, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28337946/up-regulation-of-cxcr4-expression-contributes-to-persistent-abdominal-pain-in-rats-with-chronic-pancreatitis
#6
Hong-Yan Zhu, Xuelian Liu, Xiuhua Miao, Di Li, Shusheng Wang, Guang-Yin Xu
Background Pain in patients with chronic pancreatitis is critical hallmark that accompanied inflammation, fibrosis, and destruction of glandular pancreas. Many researchers have demonstrated that stromal cell-derived factor 1 (also named as CXCL12) and its cognate receptor C-X-C chemokine receptor type 4 (CXCR4) involved in mediating neuropathic and bone cancer pain. However, their roles in chronic pancreatic pain remain largely unclear. Methods Chronic pancreatitis was induced by intraductal injection of trinitrobenzene sulfonic acid to the pancreas...
January 2017: Molecular Pain
https://www.readbyqxmd.com/read/28286044/preoperative-fecal-elastase-1-is-a-useful-prognostic-marker-following-curative-resection-of-pancreatic-cancer
#7
Jin Hong Lim, Joon Seong Park, Dong Sup Yoon
BACKGROUND: The clinical relevance of fibrosis with regard to tumor progression is supported by the correlation between fibrosis and poor outcomes. Fecal elastase-1 (FE-1) level has been used to assess exocrine dysfunction of the pancreas and to predict pancreas fibrosis. The aim of this study was to assess the impact of FE-1 on the survival of pancreatic cancer patients. METHODS: Between January 2006 and December 2014, 136 patients with pancreatic adenocarcinoma underwent R0 resection at Gangnam Severance Hospital, Korea...
March 9, 2017: HPB: the Official Journal of the International Hepato Pancreato Biliary Association
https://www.readbyqxmd.com/read/28281184/tgf-%C3%AE-1-mir-200a-pten-induces-epithelial-mesenchymal-transition-and-fibrosis-of-pancreatic-stellate-cells
#8
Min Xu, Guoying Wang, Hailang Zhou, Jing Cai, Ping Li, Meng Zhou, Ying Lu, Xiaomeng Jiang, Hongmei Huang, Youli Zhang, Aihua Gong
Although the function of miR-200a has been discussed in many cancers and fibrotic diseases, its role in pancreatic fibrosis is still poorly understood. In this study, we for the first time confirm that miR-200a attenuates TGF-β1-induced pancreatic stellate cells activation and extracellular matrix formation. First, we find that TGF-β1 induces activation and extracellular matrix (ECM) formation in PSCs, and the effects are blocked by the inhibitor of PI3K (LY294002). Furthermore, we identify that miR-200a is down-regulated in TGF-β1-activated PSCs, and up-regulation of miR-200a inhibits PSCs activation induced by TGF-β1...
March 9, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28281169/complications-of-chronic-pancreatitis
#9
REVIEW
Mitchell L Ramsey, Darwin L Conwell, Phil A Hart
Chronic pancreatitis is a disease that leads to irreversible changes in the pancreatic morphology and function. The loss of function can lead to diabetes mellitus and exocrine pancreatic insufficiency. The inflammation and fibrosis can also lead to other complications including a chronic abdominal pain syndrome, metabolic bone disease, and pancretic cancer. This article reviews our current understanding of the mechanisms and management of these complications of chronic pancreatitis.
March 9, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28278438/diagnosis-of-autoimmune-pancreatitis-with-cholesterol-granuloma-mimicking-intraductal-papillary-mucinous-carcinoma-a-case-report
#10
Yusuke Takahashi, Naoyuki Yokoyama, Daisuke Sato, Tetsuya Otani, Koko Mitsuma, Hideki Hashidate
INTRODUCTION: Pancreatic cysts are often observed incidentally on abdominal computed tomography (CT). For cysts involving intracystic nodules, malignant neoplasms such as intraductal papillary-mucinous carcinoma (IPMC) should be suspected. In contrast, cholesterol granuloma (CG) rarely occurs in the pancreas, and CG-associated autoimmune pancreatitis (AIP) has not yet been reported. To our knowledge, this is the first reported case of AIP with CG mimicking IPMC. PRESENTATION OF CASE: A 56-year-old woman underwent abdominal CT for preoperative breast cancer screening...
March 1, 2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/28217371/pathogenic-mechanisms-of-pancreatitis
#11
REVIEW
Murli Manohar, Alok Kumar Verma, Sathisha Upparahalli Venkateshaiah, Nathan L Sanders, Anil Mishra
Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancreatitis with acute inflammatory responses and; chronic pancreatitis characterized by marked stroma formation with a high number of infiltrating granulocytes (such as neutrophils, eosinophils), monocytes, macrophages and pancreatic stellate cells (PSCs). These inflammatory cells are known to play a central role in initiating and promoting inflammation including pancreatic fibrosis, i...
February 6, 2017: World Journal of Gastrointestinal Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28210075/pancreatic-stellate-cell-pandora-s-box-for-pancreatic-disease-biology
#12
REVIEW
Ratnakar R Bynigeri, Aparna Jakkampudi, Ramaiah Jangala, Chivukula Subramanyam, Mitnala Sasikala, G Venkat Rao, D Nageshwar Reddy, Rupjyoti Talukdar
Pancreatic stellate cells (PSCs) were identified in the early 1980s, but received much attention after 1998 when the methods to isolate and culture them from murine and human sources were developed. PSCs contribute to a small proportion of all pancreatic cells under physiological condition, but are essential for maintaining the normal pancreatic architecture. Quiescent PSCs are characterized by the presence of vitamin A laden lipid droplets. Upon PSC activation, these perinuclear lipid droplets disappear from the cytosol, attain a myofibroblast like phenotype and expresses the activation marker, alpha smooth muscle actin...
January 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28194432/bet-inhibitors-block-pancreatic-stellate-cell-collagen-i-production-and-attenuate-fibrosis-in-vivo
#13
Krishan Kumar, Brian T DeCant, Paul J Grippo, Rosa F Hwang, David J Bentrem, Kazumi Ebine, Hidayatullah G Munshi
The fibrotic reaction, which can account for over 70%-80% of the tumor mass, is a characteristic feature of human pancreatic ductal adenocarcinoma (PDAC) tumors. It is associated with activation and proliferation of pancreatic stellate cells (PSCs), which are key regulators of collagen I production and fibrosis in vivo. In this report, we show that members of the bromodomain and extraterminal (BET) family of proteins are expressed in primary PSCs isolated from human PDAC tumors, with BRD4 positively regulating, and BRD2 and BRD3 negatively regulating, collagen I expression in primary cancer-associated PSCs...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28133225/-a-case-of-curative-resection-for-advanced-pancreatic-acinar-cell-carcinoma-with-liver-metastasis-and-involvement-of-the-superior-mesenteric-artery-after-chemoradiotherapy-following-systemic-chemotherapy
#14
Hiroko Toda, Hiroshi Kurahara, Kosei Maemura, Yuko Mataki, Yota Kawasaki, Masahiko Sakoda, Satoshi Iino, Shinichi Ueno, Hiroyuki Shinchi, Kanro Makisumi, Shoji Natsugoe
A 52-year-old man was initially diagnosed with an unresectable acinar cell carcinoma of the pancreas with liver metastasis and involvement of the superior mesenteric artery. After 5 courses of systemic chemotherapy(gemcitabine and S-1), the size of the pancreatic tumor had decreased from 31mm to 19mm and the liver metastasis had disappeared. We initiated chemoradiotherapy( CRT: S-1+56 Gy)for further local treatment. After CRT the size of the pancreatic tumor decreased to 13mm and his serum CA 19-9 level decreased from 677...
November 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/28126348/autophagy-is-required-for-activation-of-pancreatic-stellate-cells-associated-with-pancreatic-cancer-progression-and-promotes-growth-of-pancreatic-tumors-in-mice
#15
Sho Endo, Kohei Nakata, Kenoki Ohuchida, Shin Takesue, Hiromichi Nakayama, Toshiya Abe, Kazuhiro Koikawa, Takashi Okumura, Masafumi Sada, Kohei Horioka, Biao Zheng, Yusuke Mizuuchi, Chika Iwamoto, Masaharu Murata, Taiki Moriyama, Yoshihiro Miyasaka, Takao Ohtsuka, Kazuhiro Mizumoto, Yoshinao Oda, Makoto Hashizume, Masafumi Nakamura
BACKGROUND & AIMS: Pancreatic stellate cells (PSCs) change from a quiescent to activated state in the tumor environment and secrete extracellular matrix (ECM) molecules and cytokines to increase the aggressiveness of tumors. However, it is not clear how PSCs are activated to produce these factors, or whether this process can be inhibited. PSCs have morphological and functional similarities to hepatic stellate cells, which undergo autophagy to promote fibrosis and tumor growth. We investigated whether autophagy activates PSCs, which promotes development of the tumor stroma and growth of pancreatic tumors in mice...
January 23, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28109008/inhibition-of-group-1-p21-activated-kinases-suppresses-pancreatic-stellate-cell-activation-and-increases-survival-of-mice-with-pancreatic-cancer
#16
Dannel Yeo, Phoebe Phillips, Graham S Baldwin, Hong He, Mehrdad Nikfarjam
Pancreatic cancer remains one of the most lethal of all solid tumors. Pancreatic stellate cells (PSCs) are primarily responsible for the fibrosis that constitutes the stroma and p21-activated kinase 1 (PAK1) may have a role in signalling pathways involving PSCs. This study aimed to examine the role of PAK1 in PSCs and in the interaction of PSCs with pancreatic cancer cells. Human PSCs were isolated using the modified outgrowth method. The effect of inhibiting PAK1 with group 1 PAK inhibitor, FRAX597, on cell proliferation and apoptosis in vitro was measured by thymidine incorporation and annexin V assays, respectively...
May 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28105582/-control-of-opisthorchis-viverrini-infection-for-cholangiocarcinoma-prevention
#17
Y Buisson
The International Agency for Research on Cancer (IARC) has classified two liver flukes as carcinogenic to humans (Group 1): Opisthorchis viverrini in 1994 and Clonorchis sinensis in 2009. This review is focused on O. viverrini, the most studied of these two trematodes, which infects nearly 10 million people in Southeast Asia. The life cycle involves two intermediate hosts living in fresh water: a snail of the genus Bithynia and a ciprinid fish. The definitive hosts (human, cat, dog) become infected by ingesting raw fish containing metacercariae, the infective stage of the parasite...
January 19, 2017: Bulletin de la Société de Pathologie Exotique
https://www.readbyqxmd.com/read/28093281/kindlin-2-in-pancreatic-stellate-cells-promotes-the-progression-of-pancreatic-cancer
#18
Naoki Yoshida, Atsushi Masamune, Shin Hamada, Kazuhiro Kikuta, Tetsuya Takikawa, Fuyuhiko Motoi, Michiaki Unno, Tooru Shimosegawa
Pancreatic stellate cells (PSCs) play a pivotal role in pancreatic fibrosis associated with pancreatic ductal adenocarcinoma (PDAC). Kindlin-2 is a focal adhesion protein that regulates the activation of integrins. This study aimed to clarify the role of kindlin-2 in PSCs in pancreatic cancer. Kindlin-2 expression in 79 resected pancreatic cancer tissues was examined by immunohistochemical staining. Kindlin-2-knockdown immortalized human PSCs were established using small interfering RNA. Pancreatic cancer cells were treated with conditioned media of PSCs, and the cell proliferation and migration were examined...
April 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28091744/prediction-of-pancreatic-fistula-after-distal-pancreatectomy-based-on-cross-sectional-images
#19
Ye Rim Chang, Jae Seung Kang, Jin-Young Jang, Woo Hyun Jung, Mee Joo Kang, Kyung Bun Lee, Sun-Whe Kim
BACKGROUND: Postoperative pancreatic fistula (POPF) is one of the most common and clinically relevant complications after distal pancreatectomy (DP), occurring in 5-40% of patients. Determining risk factors for this complication may aid in its prevention. This study sought to predict the development of POPF after DP preoperatively and objectively based on radiologic findings. METHODS: This study included 60 patients who underwent DP using a stapler for pancreatic division between June 2011 and January 2013...
January 13, 2017: World Journal of Surgery
https://www.readbyqxmd.com/read/28067794/the-tgf-%C3%AE-smad4-signaling-pathway-in-pancreatic-carcinogenesis-and-its-clinical-significance
#20
REVIEW
Sunjida Ahmed, Azore-Dee Bradshaw, Shweta Gera, M Zahidunnabi Dewan, Ruliang Xu
Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal human cancers due to its complicated genomic instability. PDAC frequently presents at an advanced stage with extensive metastasis, which portends a poor prognosis. The known risk factors associated with PDAC include advanced age, smoking, long-standing chronic pancreatitis, obesity, and diabetes. Its association with genomic and somatic mutations is the most important factor for its aggressiveness. The most common gene mutations associated with PDAC include KRas2, p16, TP53, and Smad4...
January 5, 2017: Journal of Clinical Medicine
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