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Pancreatic cancer

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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/28108766/immunosuppressive-myeloid-derived-suppressor-cells-are-increased-in-splenocytes-from-cancer-patients
#2
Kimberly R Jordan, Puja Kapoor, Eric Spongberg, Richard P Tobin, Dexiang Gao, Virginia F Borges, Martin D McCarter
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of myeloid cells that are increased in the peripheral blood of cancer patients and limit productive immune responses against tumors. Immunosuppressive MDSCs are well characterized in murine splenic tissue and are found at higher frequencies in spleens of tumor-bearing mice. However, no studies have yet analyzed these cells in parallel human spleens. We hypothesized that MDSCs would be increased in the spleens of human cancer patients, similar to tumor-bearing mice...
January 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28108630/macropinocytosis-of-nab-paclitaxel-drives-macrophage-activation-in-pancreatic-cancer
#3
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
#4
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
#5
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/28107977/ultrasensitive-detection-of-mucin-1-biomarker-by-immuno-loop-mediated-isothermal-amplification
#6
Hongmei Cao, Xueen Fang, Haipeng Li, Hua Li, Jilie Kong
Mucin 1 (MUC-1), a glycoprotein over-expressed on most malignant epithelial cell surfaces, such as colorectal, lung, prostate, pancreatic, ovarian, and bladder carcinomas, has been confirmed as a useful biomarker for the diagnosis of early cancers. Therefore, it is very important for early cancer diagnoses to develop the sensitive and specific detection approach of MUC-1. In this paper, we report a novel technique of aptamer-based Immuno-Loop-Mediated Isothermal Amplification (Im-LAMP) for the quantitative detection of MUC-1 by MUC-1 aptamer with high affinity for MUC-1...
March 1, 2017: Talanta
https://www.readbyqxmd.com/read/28107421/peroxiporin-expression-is-an-important-factor-for-cancer-cell-susceptibility-to-therapeutic-h2o2-implications-for-pharmacological-ascorbate-therapy
#7
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/28107195/a-new-hdac-inhibitor-cinnamoylphenazine-shows-antitumor-activity-in-association-with-intensive-macropinocytosis
#8
Bing-Yan Zhu, Bo-Yang Shang, Yue Du, Yi Li, Liang Li, Xian-Dong Xu, Yong-Su Zhen
Previous studies have shown that intensive macropinocytosis occurs in cancer cells and neutral red (NR) is noted for its capability to enter into the cell massively through a process mimetic to macropinocytosis. In addition, trans-cinnamic acid (tCA) has been found to be an inhibitor of histone deacetylase (HDAC). In the present study, cinnamoylphenazine (CA-PZ) that consists of NR and tCA moieties was synthesized and evaluated. As shown, CA-PZ massively entered into colon carcinoma HT-29 cells and pancreatic carcinoma MIA PaCa-2 cells and this entry was blocked by 5-(N-ethyl-N-isopropyl) amiloride (EIPA, an inhibitor of macropinocytosis), indicating a macropinocytosis-mediated uptake...
January 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28106883/pten-deficiency-permits-the-formation-of-pancreatic-cancer-in-the-absence-of-autophagy
#9
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
#10
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
#11
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
#12
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/28105634/does-radiologic-response-correlate-to-pathologic-response-in-patients-undergoing-neoadjuvant-therapy-for-borderline-resectable-pancreatic-malignancy
#13
Brent T Xia, Baojin Fu, Jiang Wang, Young Kim, S Ameen Ahmad, Vikrom K Dhar, Nick C Levinsky, Dennis J Hanseman, David A Habib, Gregory C Wilson, Milton Smith, Olugbenga O Olowokure, Jordan Kharofa, Ali H Al Humaidi, Kyuran A Choe, Daniel E Abbott, Syed A Ahmad
BACKGROUND AND OBJECTIVES: In patients with borderline resectable pancreas cancers, clinicians frequently consider radiographic response as the primary driver of whether patients should be offered surgical intervention following neoadjuvant therapy (NT). We sought to determine any correlation between radiographic and pathologic response rates following NT. METHODS: Between 2005 and 2015, 38 patients at a tertiary care referral center underwent NT followed by pancreaticoduodenectomy for borderline resectable pancreas cancer...
January 20, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28105582/-control-of-opisthorchis-viverrini-infection-for-cholangiocarcinoma-prevention
#14
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/28105537/procedures-and-recommended-times-in-the-care-process-of-the-patient-with-pancreatic-cancer-pan-time-consensus-between-scientific-societies
#15
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/28105371/unfolding-anti-tumor-immunity-er-stress-responses-sculpt-tolerogenic-myeloid-cells-in-cancer
#16
REVIEW
Juan R Cubillos-Ruiz, Eslam Mohamed, Paulo C Rodriguez
Established tumors build a stressful and hostile microenvironment that blocks the development of protective innate and adaptive immune responses. Different subsets of immunoregulatory myeloid populations, including dendritic cells, myeloid-derived suppressor cells (MDSCs) and macrophages, accumulate in the stressed tumor milieu and represent a major impediment to the success of various forms of cancer immunotherapy. Specific conditions and factors within tumor masses, including hypoxia, nutrient starvation, low pH, and increased levels of free radicals, provoke a state of "endoplasmic reticulum (ER) stress" in both malignant cells and infiltrating myeloid cells...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28105356/conversion-therapy-for-pancreatic-cancer-with-peritoneal-metastases-using-intravenous-and-intraperitoneal-paclitaxel-with-s-1
#17
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
#18
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
#19
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
#20
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
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