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pancreatic cancer fibrosis

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https://www.readbyqxmd.com/read/29706374/risk-of-gastrointestinal-cancers-in-patients-with-cystic-fibrosis-a-systematic-review-and-meta-analysis
#1
Akihiro Yamada, Yuga Komaki, Fukiko Komaki, Dejan Micic, Samantha Zullow, Atsushi Sakuraba
BACKGROUND: The management and life expectancy of patients with cystic fibrosis have improved substantially in the past three decades, which has resulted in an increased number of these patients being diagnosed with malignancies. Our aim was to assess the risk of gastrointestinal cancers in patients with cystic fibrosis. METHODS: In this systematic review and meta-analysis, we searched PubMed, MEDLINE, Google Scholar, Scopus, Embase, and Cochrane databases with no language restrictions for studies published from inception of the databases to Aug 1, 2017, assessing the risk of gastrointestinal cancers in patients with cystic fibrosis...
April 26, 2018: Lancet Oncology
https://www.readbyqxmd.com/read/29671537/chronic-pancreatitis-diagnosis-and-treatment
#2
Kathleen Barry
Chronic pancreatitis is an irreversible and progressive disorder of the pancreas characterized by inflammation, fibrosis, and scarring. Exocrine and endocrine functions are lost, often leading to chronic pain. The etiology is multifactorial, although alcoholism is the most significant risk factor in adults. The average age at diagnosis is 35 to 55 years. If chronic pancreatitis is suspected, contrast-enhanced computed tomography is the best imaging modality for diagnosis. Computed tomography may be inconclusive in early stages of the disease, so other modalities such as magnetic resonance imaging, magnetic resonance cholangiopancreatography, or endoscopic ultrasonography with or without biopsy may be used...
March 15, 2018: American Family Physician
https://www.readbyqxmd.com/read/29660164/high-grade-panin-presenting-with-localized-stricture-of-the-main-pancreatic-duct-a-clinicopathological-and-molecular-study-of-10-cases-suggests-a-clue-for-the-early-detection-of-pancreatic-cancer
#3
Masataka Yokode, Masayuki Akita, Kohei Fujikura, Mi-Ju Kim, Yukiko Morinaga, Seiichi Yoshikawa, Takuro Terada, Hiroshi Matsukiyo, Takuma Tajiri, Shiho Abe-Suzuki, Tomoo Itoh, Seung-Mo Hong, Yoh Zen
AIMS: This study aimed to identify the pathological features of high-grade PanIN that presents with imaging-detectable abnormalities. METHODS AND RESULTS: Ten cases of isolated, main-duct, high-grade PanIN as the primary clinical presentation were identified. All patients presented with stenosis of the main pancreatic duct, with 2 being associated with extensive upstream duct dilatation (>5 mm in diameter). Pancreatic juice cytology suggested adenocarcinoma in all 7 cases examined...
April 16, 2018: Histopathology
https://www.readbyqxmd.com/read/29611542/complex-roles-of-the-stroma-in-the-intrinsic-resistance-to-gemcitabine-in-pancreatic-cancer-where-we-are-and-where-we-are-going
#4
REVIEW
Chen Liang, Si Shi, Qingcai Meng, Dingkong Liang, Shunrong Ji, Bo Zhang, Yi Qin, Jin Xu, Quanxing Ni, Xianjun Yu
Pancreatic ductal adenocarcinoma (PDAC) is among the most devastating human malignancies. The poor clinical outcome in PDAC is partly attributed to a growth-permissive tumor microenvironment. In the PDAC microenvironment, the stroma is characterized by the development of extensive fibrosis, with stromal components outnumbering pancreatic cancer cells. Each of the components within the stroma has a distinct role in conferring chemoresistance to PDAC, and intrinsic chemoresistance has further worsened this pessimistic prognosis...
December 1, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29555876/identification-and-characterization-of-novel-receptor-interacting-serine-threonine-protein-kinase-2-ripk2-inhibitors-using-structural-similarity-analysis
#5
Mohamed Salla, Rodrigo Aguayo-Ortiz, Danmaliki Gaddafi Ibrahim, Alaa Zare, Ahmed Said, Jack Moore, Vrajeshkumar Pandya, Robin Manaloor, Sunny Fong, Anna R Blankstein, Spencer Gibson, Laura Ramos Garcia, Pascal Meier, Khushwant S Bhullar, Basil P Hubbard, Yahya Fiteh, Harissios Vliagoftis, Ing Swie Goping, Dion Brocks, Peter Hwang, Jose Carlos A Martinez Velazquez, Shairaz Baksh
Receptor interacting protein kinase 2 (RIP2 or RICK herein referred to as RIPK2) is linked to the pathogen pathway that activates NFkB and autophagic activation. Using molecular modeling (docking) and chemoinformatics analyses we utilized the RIPK2/ponatinib crystal structure and searched in chemical databases for small molecules exerting binding interactions similar to those exerted by ponatinib. The identified RIPK2 inhibitors potently inhibited the proliferation of cancer cells by > 70% as well as inhibition of NFkB activity...
March 19, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29477748/transforming-growth-factor-%C3%AE-modulates-pancreatic-cancer-associated-fibroblasts-cell-shape-stiffness-and-invasion
#6
Andreas Stylianou, Vasiliki Gkretsi, Triantafyllos Stylianopoulos
BACKGROUND: Tumor microenvironment consists of the extracellular matrix (ECM), stromal cells, such as fibroblasts (FBs) and cancer associated fibroblasts (CAFs), and a myriad of soluble factors. In many tumor types, including pancreatic tumors, the interplay between stromal cells and the other tumor microenvironment components leads to desmoplasia, a cancer-specific type of fibrosis that hinders treatment. Transforming growth factor beta (TGF-β) and CAFs are thought to play a crucial role in this tumor desmoplastic reaction, although the involved mechanisms are unknown...
March 12, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29467550/translational-pancreatic-cancer-research-a-comparative-study-on-patient-derived-xenograft-models
#7
Mercedes Rubio-Manzanares Dorado, Luis Miguel Marín Gómez, Daniel Aparicio Sánchez, Sheila Pereira Arenas, Juan Manuel Praena-Fernández, Juan Jose Borrero Martín, Francisco Farfán López, Miguel Ángel Gómez Bravo, Jordi Muntané Relat, Javier Padillo Ruiz
AIM: To assess the viability of orthotopic and heterotopic patient-derived pancreatic cancer xenografts implanted into nude mice. METHODS: This study presents a prospective experimental analytical follow-up of the development of tumours in mice upon implantation of human pancreatic adenocarcinoma samples. Specimens were obtained surgically from patients with a pathological diagnosis of pancreatic adenocarcinoma. Tumour samples from pancreatic cancer patients were transplanted into nude mice in three different locations (intraperitoneal, subcutaneous and pancreatic)...
February 21, 2018: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29465558/analysis-of-clinical-characteristics-and-treatment-of-immunoglobulin-g4-associated-cholangitis-a-retrospective-cohort-study-of-39-iac-patients
#8
Jianchun Xiao, Peiran Xu, Binglu Li, Tao Hong, Wei Liu, Xiaodong He, Chaoji Zheng, Yupei Zhao
Immunoglobulin (Ig)G4-associated cholangitis (IAC) is one of the common organ manifestations of IgG4-related systemic disease (ISD). IAC and autoimmune pancreatitis (AIP) may mimic sclerosing cholangitis, cholangiocarcinoma, or pancreatic carcinoma. Diagnosis is based on a combination of clinical, biochemical, radiological, and histological findings.To study the clinical presentation of and treatment strategy for IAC, we reviewed clinical, serologic, and imaging characteristics, as well as treatment response, in 39 patients with IAC...
February 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29435115/fibrosis-related-mirnas-as-serum-biomarkers-for-pancreatic-ductal-adenocarcinoma
#9
Rei Suzuki, Hiroyuki Asama, Yuichi Waragai, Tadayuki Takagi, Takuto Hikichi, Mitsuru Sugimoto, Naoki Konno, Ko Watanabe, Jun Nakamura, Hitomi Kikuchi, Yuki Sato, Shigeru Marubashi, Atsushi Masamune, Hiromasa Ohira
We investigated whether serum microRNAs (miRNAs) could be diagnostic or prognostic markers in pancreatic ductal adenocarcinoma (PDAC). We first identified miRNAs showing altered expression in human pancreatic stellate cells (hPSCs) co-cultured with PDAC cells (Panc-1 and BxPC-3) as compared to hPSCs cultured alone. Among the miRNAs with altered expression, let-7d exhibited reduced expression in an in silico analysis of The Cancer Genome Atlas data. Inhibition of let-7d resulted in enhanced expression of fibrosis-related genes...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29408203/reprogramming-tumor-stroma-using-an-endogenous-lipid-lipoxin-a4-to-treat-pancreatic-cancer
#10
Jonas Schnittert, Marcel A Heinrich, Praneeth R Kuninty, Gert Storm, Jai Prakash
Pancreatic stellate cells (PSCs) are the precursors of cancer-associated fibroblasts (CAFs), which potentiate pancreatic tumor growth and progression. In this study, we investigated whether Lipoxin A4 (LXA4), an endogenous bioactive lipid, can inhibit the differentiation of human PSCs (hPSCs) into CAF-like myofibroblasts and thereby hPSC-induced pro-tumorigenic effects. LXA4 significantly inhibited TGF-β-mediated differentiation of hPSCs by inhibiting pSmad2/3 signalling. Furthermore, treatment with LXA4 abolished the paracrine effects (proliferation and migration of Panc-1 tumor cells) of hPSCs in vitro...
April 28, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29405509/introduction-and-practical-approach-to-exocrine-pancreatic-insufficiency-for-the-practicing-clinician
#11
REVIEW
Mohamed O Othman, Diala Harb, Jodie A Barkin
AIMS: In exocrine pancreatic insufficiency (EPI), the quantity and/or activity of pancreatic digestive enzymes are below the levels required for normal digestion, leading to maldigestion and malabsorption. Diagnosis of EPI is often challenging because the characteristic signs and symptoms overlap with those of other gastrointestinal conditions. Additionally, there is no single convenient, or specific diagnostic test for EPI. The aim of this review is to provide a framework for differential diagnosis of EPI vs other malabsorptive conditions...
February 2018: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/29363544/tumor-stroma-il1%C3%AE-irak4-feedforward-circuitry-drives-tumor-fibrosis-chemoresistance-and-poor-prognosis-in-pancreatic-cancer
#12
Daoxiang Zhang, Lin Li, Hongmei Jiang, Qiong Li, Andrea Wang-Gillam, Jinsheng Yu, Richard Head, Jingxia Liu, Marianna B Ruzinova, Kian-Huat Lim
Targeting the desmoplastic stroma of pancreatic ductal adenocarcinoma (PDAC) holds promise to augment the effect of chemotherapy, but success in the clinic has thus far been limited. Preclinical mouse models suggest that near-depletion of cancer-associated fibroblasts (CAF) carries a risk of accelerating PDAC progression, underscoring the need to concurrently target key signaling mechanisms that drive the malignant attributes of both CAF and PDAC cells. We previously reported that inhibition of IL1 receptor-associated kinase 4 (IRAK4) suppresses NFκB activity and promotes response to chemotherapy in PDAC cells...
April 1, 2018: Cancer Research
https://www.readbyqxmd.com/read/29349096/safety-and-efficacy-of-aav-retrograde-pancreatic-ductal-gene-delivery-in-normal-and-pancreatic-cancer-mice
#13
Kayla A Quirin, Jason J Kwon, Arafat Alioufi, Tricia Factora, Constance J Temm, Max Jacobsen, George E Sandusky, Kim Shontz, Louis G Chicoine, K Reed Clark, Joshua T Mendell, Murray Korc, Janaiah Kota
Recombinant adeno-associated virus (rAAV)-mediated gene delivery shows promise to transduce the pancreas, but safety/efficacy in a neoplastic context is not well established. To identify an ideal AAV serotype, route, and vector dose and assess safety, we have investigated the use of three AAV serotypes (6, 8, and 9) expressing GFP in a self-complementary (sc) AAV vector under an EF1α promoter (scAAV.GFP) following systemic or retrograde pancreatic intraductal delivery. Systemic delivery of scAAV9.GFP transduced the pancreas with high efficiency, but gene expression did not exceed >45% with the highest dose, 5 × 1012 viral genomes (vg)...
March 16, 2018: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29329392/risk-of-pancreatic-cancer-associated-with-family-history-of-cancer-and-other-medical-conditions-by-accounting-for-smoking-among-relatives
#14
E Molina-Montes, P Gomez-Rubio, M Márquez, M Rava, M Löhr, C W Michalski, X Molero, A Farré, J Perea, W Greenhalf, L Ilzarbe, M O'Rorke, A Tardón, T Gress, V M Barberà, T Crnogorac-Jurcevic, E Domínguez-Muñoz, L Muñoz-Bellvís, J Balsells, E Costello, J Huang, M Iglesias, J Kleeff, Bo Kong, J Mora, L Murray, D O'Driscoll, I Poves, A Scarpa, W Ye, M Hidalgo, L Sharp, A Carrato, F X Real, N Malats
Background: Family history (FH) of pancreatic cancer (PC) has been associated with an increased risk of PC, but little is known regarding the role of inherited/environmental factors or that of FH of other comorbidities in PC risk. We aimed to address these issues using multiple methodological approaches. Methods: Case-control study including 1431 PC cases and 1090 controls and a reconstructed-cohort study (N = 16 747) made up of their first-degree relatives (FDR)...
January 10, 2018: International Journal of Epidemiology
https://www.readbyqxmd.com/read/29328490/galectin-1-expression-in-activated-pancreatic-satellite-cells-promotes-fibrosis-in-chronic-pancreatitis-pancreatic-cancer-via-the-tgf-%C3%AE-1-smad-pathway
#15
Dong Tang, Qi Wu, Jingqiu Zhang, Hongpeng Zhang, Zhongxu Yuan, Jiaming Xu, Yang Chong, Yuqin Huang, Qingquan Xiong, Sen Wang, Ying Tian, Yongdie Lu, Xiao Ge, Wenjing Shen, Daorong Wang
Chronic pancreatitis/pancreatic cancer (CP/PC) is characterized by fibrous connective tissue proliferation induced by activated pancreatic stellate cells (PSCs). Galectin-1 is upregulated in activated PSCs and is important for the continuing activation of PSCs. The aim of this study was to evaluate the effect of galectin-1 derived from activated PSCs on the progression of fibrosis in CP/PC. To this end, the expression of desmin, α-SMA, galectin-1, fibronectin and collagen type I in normal pancreatic, CP and PC tissues, as well as quiescent/activated PSCs, was investigated...
March 2018: Oncology Reports
https://www.readbyqxmd.com/read/29305893/randomized-trial-comparing-the-franseen-and-fork-tip-needles-for-eus-guided-fine-needle-biopsy-sampling-of-solid-pancreatic-mass-lesions
#16
Ji Young Bang, Shantel Hebert-Magee, Udayakumar Navaneethan, Muhammad K Hasan, Robert Hawes, Shyam Varadarajulu
BACKGROUND AND AIMS: Recently, a 3-plane symmetric needle with Franseen geometry and a Fork-tip biopsy needle have been developed for histologic tissue procurement. We compared 22-gauge Franseen and 22-gauge Fork-tip needles in patients undergoing EUS-guided sampling of pancreatic masses. METHODS: Fifty patients underwent sampling using both 22-gauge Franseen and 22-gauge Fork-tip needles, with randomization of needle order. Two dedicated passes were performed using both needles for cell block...
January 3, 2018: Gastrointestinal Endoscopy
https://www.readbyqxmd.com/read/29304760/regulation-of-pancreatic-stellate-cell-activation-by-notch3
#17
Haiyan Song, Yuxiang Zhang
BACKGROUND: Activated pancreatic stellate cells (PaSCs) are the key cellular source of cancer-associated fibroblasts in the pancreatic stroma of patients with pancreatic ductal adenocarcinoma (PDAC), however, the activation mechanism of PaSCs is not yet known. The Notch signaling pathway, components of which are expressed in stromal cells, is involved in the fibrosis of several organs, including the lung and liver. In the current study, we investigated whether Notch signal transduction is involved in PaSC activation in PDAC...
January 5, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29213026/-case-of-protein-plug-in-the-pancreatic-duct-mimicking-pancreatic-cancer-concomitant-with-branch-type-intraductal-papillary-mucinous-neoplasm
#18
Ken Ichikawa, Kana Hattori, Tomoki Kusafuka, Takao Omori, Yasuo Ohkura, Takashi Hamada, Hiroki Taoka, Hiroki Tanaka, Shimpei Matsusaki, Youichirou Baba
A 65-year-old male was referred to our hospital 2 years ago for a multilocular cyst accompanied with a protein plug in the pancreas tail. He was diagnosed as having branch duct-type intraductal papillary mucinous neoplasm and was followed-up. Two years later, endoscopic ultrasonography revealed a hypoechoic lesion, 10mm in diameter, near the cyst-like lesion. Finally, he was diagnosed with small pancreatic adenocarcinoma concomitant with intraductal papillary mucinous neoplasm and underwent radical distal pancreatectomy with splenectomy...
2017: Nihon Shokakibyo Gakkai Zasshi, the Japanese Journal of Gastro-enterology
https://www.readbyqxmd.com/read/29211796/reprogramming-pancreatic-stellate-cells-via-p53-activation-a-putative-target-for-pancreatic-cancer-therapy
#19
Maya Saison-Ridinger, Kathleen E DelGiorno, Tejia Zhang, Annabelle Kraus, Randall French, Dawn Jaquish, Crystal Tsui, Galina Erikson, Benjamin T Spike, Maxim N Shokhirev, Christopher Liddle, Ruth T Yu, Michael Downes, Ronald M Evans, Alan Saghatelian, Andrew M Lowy, Geoffrey M Wahl
Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extremely dense fibrotic stroma, which contributes to tumor growth, metastasis, and drug resistance. During tumorigenesis, quiescent pancreatic stellate cells (PSCs) are activated and become major contributors to fibrosis, by increasing growth factor signaling and extracellular matrix deposition. The p53 tumor suppressor is known to restrict tumor initiation and progression through cell autonomous mechanisms including apoptosis, cell cycle arrest, and senescence...
2017: PloS One
https://www.readbyqxmd.com/read/29155423/experimental-models-of-pancreatic-cancer-desmoplasia
#20
Sujit Suklabaidya, Pujarini Dash, Biswajit Das, Voddu Suresh, Prakash K Sasmal, Shantibhusan Senapati
Desmoplasia is a fibro-inflammatory process and a well-established feature of pancreatic cancer. A key contributor to pancreatic cancer desmoplasia is the pancreatic stellate cell. Various in vitro and in vivo methods have emerged for the isolation, characterization, and use of pancreatic stellate cells in models of cancer-associated fibrosis. In addition to cell culture models, genetically engineered animal models have been established that spontaneously develop pancreatic cancer with desmoplasia. These animal models are currently being used for the study of pancreatic cancer pathogenesis and for evaluating therapeutics against pancreatic cancer...
January 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
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