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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
#1
Dannel Yeo, Phoebe Phillips, Graham S Baldwin, Hong He, Mehrdad Nikfarjam
Pancreatic cancer remains one of the most lethal of all solid tumours. 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 a modified outgrowth method. The effect of inhibiting PAK1 with a group 1 PAK inhibitor, FRAX597, on cell proliferation and apoptosis in vitro was measured by thymidine incorporation and annexin V assays, respectively...
January 21, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28108630/macropinocytosis-of-nab-paclitaxel-drives-macrophage-activation-in-pancreatic-cancer
#2
Jane E Cullis, Despina Siolas, Antonina Avanzi, Sugata Barui, Anirban Maitra, Dafna Bar-Sagi
Pancreatic cancer is a devastating disease that is largely refractory to currently available treatment strategies. Therapeutic resistance is partially attributed to the dense stromal reaction of PDAC tumors that includes a pervasive infiltration of immunosuppressive (M2) macrophages. Nab-paclitaxel (trade name Abraxane) is a nanoparticle albumin-bound formulation of paclitaxel that, in combination with gemcitabine, is currently the first line treatment for pancreatic cancer. Here, we show that macrophages internalized nab-paclitaxel via macropinocytosis...
January 20, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28108627/oncogenic-kras-targets-muc16-ca125-in-pancreatic-ductal-adenocarcinoma
#3
Chen Liang, Yi Qin, Bo Zhang, Shunrong Ji, Si Shi, Wenyan Xu, Jiang Liu, Jinfeng Xiang, Dingkong Liang, Qiangsheng Hu, Quanxing Ni, Jin Xu, Xianjun Yu
: Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with the 5-year survival rate less than 6%. Previous results indicated that serum levels of CA125 (encoded by MUC16) could be used to predict which groups of pancreatic cancer patients may benefit from surgery. However, the underlying mechanism remains elusive. Herein, using the Cancer Genome Atlas and clinicopathologic data obtained from our center, we demonstrate that high CA125 serum levels and expression levels of MUC16 are predictive of poor prognosis...
January 20, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28108468/metabolic-biomarker-signature-to-differentiate-pancreatic-ductal-adenocarcinoma-from-chronic-pancreatitis
#4
Julia Mayerle, Holger Kalthoff, Regina Reszka, Beate Kamlage, Erik Peter, Bodo Schniewind, Sandra González Maldonado, Christian Pilarsky, Claus-Dieter Heidecke, Philipp Schatz, Marius Distler, Jonas A Scheiber, Ujjwal M Mahajan, F Ulrich Weiss, Robert Grützmann, Markus M Lerch
OBJECTIVE: Current non-invasive diagnostic tests can distinguish between pancreatic cancer (pancreatic ductal adenocarcinoma (PDAC)) and chronic pancreatitis (CP) in only about two thirds of patients. We have searched for blood-derived metabolite biomarkers for this diagnostic purpose. DESIGN: For a case-control study in three tertiary referral centres, 914 subjects were prospectively recruited with PDAC (n=271), CP (n=282), liver cirrhosis (n=100) or healthy as well as non-pancreatic disease controls (n=261) in three consecutive studies...
January 20, 2017: Gut
https://www.readbyqxmd.com/read/28107421/peroxiporin-expression-is-an-important-factor-for-cancer-cell-susceptibility-to-therapeutic-h2o2-implications-for-pharmacological-ascorbate-therapy
#5
Dieanira Erudaitius, Andrew Huang, Sarah Kazmi, Garry R Buettner, Victor G J Rodgers
Cancer cell toxicity to therapeutic H2O2 varies widely depending on cell type. Interestingly, it has been observed that different cancer cell types have varying peroxiporin expression. We hypothesize that variation in peroxiporin expression can alter cell susceptibility to therapeutic H2O2 concentrations. Here, we silence peroxiporin aquaporin-3 (AQP3) on the pancreatic cancer cell line MIA PaCa-2 and compare clonogenic survival response to the wild-type. The results showed a significantly higher surviving fraction in the clonogenic response for siAQP3 MIA PaCa-2 cells at therapeutic H2O2 doses (P < 0...
2017: PloS One
https://www.readbyqxmd.com/read/28106883/pten-deficiency-permits-the-formation-of-pancreatic-cancer-in-the-absence-of-autophagy
#6
Mathias T Rosenfeldt, Jim O'Prey, Lucia Flossbach, Colin Nixon, Jennifer P Morton, Owen J Sansom, Kevin M Ryan
No abstract text is available yet for this article.
January 20, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28106782/from-clinical-standards-to-translating-next-generation-sequencing-research-into-patient-care-improvement-for-hepatobiliary-and-pancreatic-cancers
#7
REVIEW
Ioannis D Kyrochristos, Georgios K Glantzounis, Demosthenes E Ziogas, Ioannis Gizas, Dimitrios Schizas, Efstathios G Lykoudis, Evangelos Felekouras, Anastasios Machairas, Christos Katsios, Theodoros Liakakos, William C Cho, Dimitrios H Roukos
Hepatobiliary and pancreatic (HBP) cancers are associated with high cancer-related death rates. Surgery aiming for complete tumor resection (R0) remains the cornerstone of the treatment for HBP cancers. The current progress in the adjuvant treatment is quite slow, with gemcitabine chemotherapy available only for pancreatic ductal adenocarcinoma (PDA). In the advanced and metastatic setting, only two targeted drugs have been approved by the Food & Drug Administration (FDA), which are sorafenib for hepatocellular carcinoma and erlotinib for PDA...
January 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28106283/therapeutic-potential-of-curcumin-in-treatment-of-pancreatic-cancer-current-status-and-future-perspectives
#8
Mina Hosseini, Seyed Mahdi Hassanian, Elham Mohamamdazade, Soodabeh ShahidSales, Mina Maftouh, Hasan Fayazbakhsh, Majid Khazaei, Amir Avan
Pancreatic cancer is among the leading cause of deaths due to cancer with extremely poor prognosis. Gemcitabine is being used in the treatment of patient with pancreatic ductal adenocarcinoma (PDAC), although, the response rate is bellow 12%. A recent phase III trial revealed that FOLFIRINOX could be an option for the treatment of metastatic PDAC patients, although it is associated with increased toxicity. Therefore, identification of novel agents that either improves gemcitabine activity, within novel combinatorial approaches, or with a better efficacy than gemcitabine is warranted...
January 20, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28106227/can-ngal-be-employed-as-prognostic-and-diagnostic-biomarker-in-human-cancers-a-systematic-review-of-current-evidence
#9
Laura Roli, Valentina Pecoraro, Tommaso Trenti
BACKGROUND: Some studies have reported differentially altered neutrophil gelatinase-associated lipocalin (NGAL) levels in several malignancies. We evaluated NGAL measured in plasma or urine as both prognostic and diagnostic marker for different types of human tumors. METHODS: We performed systematic electronic searches in Medline, Embase and CRDTAS. Studies were included if they evaluated NGAL as a prognostic or diagnostic marker for human cancers. The selection of the studies, screening of the full texts and data extraction were conducted independently by 2 authors...
January 16, 2017: International Journal of Biological Markers
https://www.readbyqxmd.com/read/28105537/procedures-and-recommended-times-in-the-care-process-of-the-patient-with-pancreatic-cancer-pan-time-consensus-between-scientific-societies
#10
R Vera, A Ferrández, C J Ferrer, C Flores, C Joaquín, S López, T Martín, E Martín, M Marzo, A Sarrión, E Vaquero, A Zapatero, J Aparicio
PURPOSE: Pancreatic cancer (PC) is a disease with bad prognosis. It is usually diagnosed at advanced stages and its treatment is complex. The aim of this consensus document was to provide recommendations by experts that would ameliorate PC diagnosis, reduce the time to treatment, and optimize PC management by interdisciplinary teams. METHODS: As a consensus method, we followed the modified Delphi methodology. A scientific committee of experts provided 40 statements that were submitted in two rounds to a panel of 87 specialists of 12 scientific societies...
January 19, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28105356/conversion-therapy-for-pancreatic-cancer-with-peritoneal-metastases-using-intravenous-and-intraperitoneal-paclitaxel-with-s-1
#11
Hiromitsu Kitayama, Yasushi Tsuji, Tomohiro Kondo, Junko Sugiyama, Michiaki Hirayama, Kazuyuki Yamamoto, You Kawarada, Yumiko Oyamada, Satoshi Hirano
Combination chemotherapy consisting of systemic and intraperitoneal agents against peritoneal metastases from several types of cancer has shown promising results. We herein report a case in which combination therapy with intravenous and intraperitoneal paclitaxel with S-1 converted an unresectable pancreatic cancer with peritoneal metastases into a resectable one. The patient was a 65-year old woman with recurrent pancreatitis for 5 months. Endoscopic ultrasonography-guided fine-needle aspiration revealed minute epithelial masses composed of cells with irregular nuclei in the pancreatic body...
December 2016: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28105213/wogonin-induces-beclin-1-pi3k-and-reactive-oxygen-species-mediated-autophagy-in-human-pancreatic-cancer-cells
#12
Shao-Jun Li, Shi-Jie Sun, Jie Gao, Fu-Bo Sun
Wogonin is considered to be an inhibitor of myeloid cell leukemia 1 and B-cell lymphoma 2, and a potential antitumor drug due to its ability to induce apoptosis in certain cancer cells; however, few previous studies have reported on wogonin-induced autophagy. The aim of the present study was to investigate the influence of wogonin on autophagy in human pancreatic cancer cells (HPCCs), elucidate its mechanism, and identify strategies to increase its effectiveness as an anti-cancer treatment. HPCCs were treated with wogonin and autophagy was detected in the cells...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28105181/activator-protein-1-promotes-gemcitabine-induced-apoptosis-in-pancreatic-cancer-by-upregulating-its-downstream-target-bim
#13
Xiaoxia Ren, Wenjing Zhao, Yongxing Du, Taiping Zhang, Lei You, Yupei Zhao
Gemcitabine is a commonly used chemotherapy drug in pancreatic cancer. The function of activator protein 1 (AP-1) is cell-specific, and its function depends on the expression of other complex members. In the present study, we added gemcitabine to the media of Panc-1 and SW1990 cells at clinically achieved concentrations (10 µM). Compared with constitutive c-Fos expression, c-Jun expression increased in a dose-dependent manner upon gemcitabine treatment. c-Jun overexpression increased gemcitabine-induced apoptosis through Bim activation, while cell apoptosis and Bim expression decreased following c-Jun knockdown...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28105175/analysis-of-transcription-profile-to-reveal-altered-signaling-pathways-following-the-overexpression-of-human-desumoylating-isopeptidase-2-in-pancreatic-cancer-cells
#14
Yu-Yin Fu, Yu-Huan Kang, Cong-Cong Shen, Rui-Xue Wang, Lin Yu, Xin-Yue Li, Dan-Dan Cui, Jin-Liang Yang, Yu-Qin Yao, Lan-Tu Gou
Human desumoylating isopeptidase 2 (DESI-2) is a member of the DESI family and contains a conserved PPPDE1 domain. Previous studies have demonstrated that DESI-2 overexpression may induce cell apoptosis. In the present study, differentially expressed genes were analyzed using a transcription microarray in DESI-2 overexpressing PANC-1 pancreatic cancer cells. A total of 45,033 genes were examined by microarray, which identified 1,766 upregulated and 1,643 downregulated genes. A series of altered signaling pathways were analyzed, in which certain essential signaling factors, including retinoid X receptor (RXR), BH3 interacting-domain death agonist, Ras homolog gene family member A (RhoA) and Rho-associated protein kinase, were further investigated at the protein level...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28105159/small-bowel-metastasis-from-pancreatic-cancer-in-a-long-term-survival-patient-with-synchronous-advanced-malignant-pleural-mesothelioma-a-case-report-and-literature-review
#15
Morena Fasano, Carminia Maria Della Corte, Giovanni Vicidomini, Valerio Scotti, Pier Francesco Rambaldi, Alfonso Fiorelli, Marina Accardo, Ferdinando De Vita, Mario Santini, Fortunato Ciardiello, Floriana Morgillo
Diffuse malignant pleural mesothelioma (MPM) is an aggressive tumor that originates from the surface of the pleura. Approximately 70% of cases are associated with chronic asbestos exposure. MPM is regarded as an incurable disease, with a median survival of ~2 years following intensive multimodality treatment. Pancreatic cancer is a malignancy also associated with a poor prognosis, with only 2% of patients surviving for 5 years. The majority of patients with pancreatic cancer are diagnosed with an advanced stage of disease and experience a poor response to therapy...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28105157/prognostic-impact-of-the-tumor-infiltrating-regulatory-t-cell-foxp3-activated-cytotoxic-t-lymphocyte-granzyme-b-ratio-on-resected-left-sided-pancreatic-cancer
#16
Ho Kyoung Hwang, Hyoung-Il Kim, Se Hoon Kim, Junjeong Choi, Chang Moo Kang, Kyung Sik Kim, Woo Jung Lee
Among the subsets of tumor-infiltrating lymphocytes (TILs), activated cytotoxic T lymphocytes (granzyme B(+)) have an antitumor effect, while regulatory T lymphocytes [forkhead box P3 (Foxp3)(+)] suppress the antitumor immune response. The aim of the present study was to investigate the possible associations between TIL subsets and survival outcomes in patients with left-sided pancreatic ductal adenocarcinoma (PDAC). From January 2000 to December 2008, 30 patients who underwent curative distal pancreatectomy without neoadjuvant chemoradiotherapy due to left-sided PDAC were enrolled in the present study...
December 2016: Oncology Letters
https://www.readbyqxmd.com/read/28104621/high-prevalence-of-mutant-kras-in-circulating-exosome-derived-dna-from-early-stage-pancreatic-cancer-patients
#17
K Allenson, J Castillo, F A San Lucas, G Scelo, D U Kim, V Bernard, G Davis, T Kumar, M Katz, M J Overman, L Foretova, E Fabianova, I Holcatova, V Janout, F Meric-Bernstam, P Gascoyne, I Wistuba, G Varadhachary, P Brennan, S Hanash, D Li, A Maitra, H Alvarez
BACKGROUND: Exosomes arise from viable cancer cells and may reflect a different biology than circulating cell-free DNA (cfDNA) shed from dying tissues. We compare exosome-derived DNA (exoDNA) to cfDNA in liquid biopsies of patients with pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: Patient samples were obtained between 2003 and 2010, with clinically annotated follow up to 2015. Droplet digital PCR (ddPCR) was performed on exoDNA and cfDNA for sensitive detection of KRAS mutants at codons 12/13...
January 18, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28104298/kr%C3%A3-pple-like-factor-10-regulates-radio-sensitivity-of-pancreatic-cancer-via-uv-radiation-resistance-associated-gene
#18
Vincent Hung-Shu Chang, Yi-Chih Tsai, Ya-Li Tsai, Shu-Ling Peng, Su-Liang Chen, Tsung Ming Chang, Winston Chun-Yuan Yu, Hui-Ju Ch'ang
BACKGROUND AND PURPOSE: Krüpple-like factor 10 (Klf10), an early response gene of TGFβ, was reported to be a prognostic biomarker for pancreatic cancer survival. The role of Klf10 in predicting tumor response to cancer treatment is unknown. MATERIALS AND METHODS: Genetically manipulated MiaPaCa and Panc-1 cells were established to evaluate clonogenic survival, autophagy, apoptosis and DNA repair after radiation. The interaction between Klf10 and UV radiation resistance-associated gene (UVRAG) was demonstrated by ChiP-PCR and luciferase reporter assay...
January 16, 2017: Radiotherapy and Oncology: Journal of the European Society for Therapeutic Radiology and Oncology
https://www.readbyqxmd.com/read/28103577/association-of-rab5-overexpression-in-pancreatic-cancer-with-cancer-progression-and-poor-prognosis-via-e-cadherin-suppression
#19
Takamichi Igarashi, Kenichiro Araki, Takehiko Yokobori, Bolag Altan, Takahiro Yamanaka, Norihiro Ishii, Mariko Tsukagoshi, Akira Watanabe, Norio Kubo, Tadashi Handa, Yasuo Hosouchi, Masahiko Nishiyama, Tetsunari Oyama, Ken Shirabe, Hiroyuki Kuwano
Pancreatic cancer is a common type of cancer with poor prognosis worldwide. Postoperative survival depends on the existence of metastasis. Elucidation of the mechanism underlying cancer progression is important to improve prognosis. The RAS-associated protein RAB5 activates intracellular membrane trafficking, and RAB5 expression is correlated to progression and epithelial mesenchymal transition in various cancers.The expression of RAB5 and E-cadherin in 111 pancreatic cancer samples was investigated by immunohistochemical staining, and the relationship among RAB5 expression, clinicopathological factors, and E-cadherin expression was assessed...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28102193/tumour-derived-interleukin-35-promotes-pancreatic-ductal-adenocarcinoma-cell-extravasation-and-metastasis-by-inducing-icam1-expression
#20
Chongbiao Huang, Na Li, Zengxun Li, Antao Chang, Yanan Chen, Tiansuo Zhao, Yang Li, Xiuchao Wang, Wei Zhang, Zhimin Wang, Lin Luo, Jingjing Shi, Shengyu Yang, He Ren, Jihui Hao
Interleukin 35 (IL-35) is a novel member of the IL-12 family, consisting of an EBV-induced gene 3 (EBI3) subunit and a P35 subunit. IL-35 is an immune-suppressive cytokine mainly produced by regulatory T cells. However, the role of IL-35 in cancer metastasis and progression is not well understood. Here we demonstrate that IL-35 is overexpressed in human pancreatic ductal adenocarcinoma (PDAC) tissues, and that IL-35 overexpression is associated with poor prognosis in PDAC patients. IL-35 has critical roles in PDAC cell extravasation and metastasis by facilitating the adhesion to endothelial cells and transendothelial extravasation...
January 19, 2017: Nature Communications
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