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https://www.readbyqxmd.com/read/29155449/baicalein-inhibits-acinar-to-ductal-metaplasia-of-pancreatic-acinal-cell-ar42j-via-improving-the-inflammatory-microenvironment
#1
Wei-Ling Pu, Ying-Ying Luo, Ru-Yu Bai, Ao-Wei Guo, Kun Zhou, Yun-Sha Zhang, Lin Miao, Curzio Rüegg, Micheal O Hottiger, Xiu-Mei Gao, Li-Kang Sun
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers. Recent research has demonstrated that chronic pancreatitis (CP) is associated with an increased risk of PDAC, partly due to acinar-to-ductal metaplasia (ADM). Baicalein has been shown to exert anti-inflammatory and anti-tumor effects for CP or PDAC, respectively. The aim of our study was to investigate the effect of baicalein, and the putative underlying mechanism, on inflammatory cytokines-induced ADM of rat pancreatic acinar cell line AR42J...
November 20, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29151366/the-150-most-important-questions-in-cancer-research-and-clinical-oncology-series-questions-76-85-edited-by-chinese-journal-of-cancer
#2
EDITORIAL
(no author information available yet)
Since the beginning of 2017, Chinese Journal of Cancer has published a series of important questions in cancer research and clinical oncology to promote cancer research and accelerate collaborations. In this article, 10 questions are presented as followed. Question 76. How to develop effective therapeutics for cancer cachexia? Question 77. How can we develop preclinical animal models to recapitulate clinical situations of cancer patients for more effective anti-cancer drug development? Question 78. How can we develop novel effective therapeutics for pancreatic cancer and hepatocellular carcinoma? Question 79...
November 20, 2017: Chinese Journal of Cancer
https://www.readbyqxmd.com/read/29149107/treponema-denticola-chymotrypsin-like-proteinase-may-contribute-to-orodigestive-carcinogenesis-through-immunomodulation
#3
Mikko T Nieminen, Dyah Listyarifah, Jaana Hagström, Caj Haglund, Daniel Grenier, Dan Nordström, Veli-Jukka Uitto, Marcela Hernandez, Tülay Yucel-Lindberg, Taina Tervahartiala, Mari Ainola, Timo Sorsa
BACKGROUND: Periodontal pathogens have been linked to oral and gastrointestinal (orodigestive) carcinogenesis. However, the exact mechanisms remain unknown. Treponema denticola (Td) is associated with severe periodontitis, a chronic inflammatory disease leading to tooth loss. The anaerobic spirochete Td is an invasive bacteria due to its major virulence factor chymotrypsin-like proteinase. Here we aimed to investigate the presence of Td chymotrypsin-like proteinase (Td-CTLP) in major orodigestive tumours and to elucidate potential mechanisms for Td to contribute to carcinogenesis...
November 16, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29143898/the-multidisciplinary-approach-to-localized-pancreatic-adenocarcinoma
#4
REVIEW
Hiral D Parekh, Jason Starr, Thomas J George
Pancreatic adenocarcinoma 2030 (PCa) is predicted to be the second leading cause of cancer death in USA by 2030. To date, attempts at early detection have been unsuccessful. Therapies for resectable PCa include surgery followed by adjuvant chemotherapy with or without radiotherapy. Unfortunately, most patients with PCa present with advanced disease and thus only 20% of patients are potentially resectable upon presentation. Improved surgical techniques along with adjuvant combination chemotherapy have improved outcomes for patients with resectable disease...
November 16, 2017: Current Treatment Options in Oncology
https://www.readbyqxmd.com/read/29138370/-development-of-holistic-cancer-treatment-centering-cancer-patients-from-the-standpoint-of-hypoxia-and-hedgehog-signaling
#5
Hideya Onishi, Toshitatsu Ogino, Takashi Morisaki, Mitsuo Katano
Recently, hypoxia that is one of cancer microenvironments, takes much attention. Because circumstance that we usually perform experiment is 20% O2 condition, it is likely that different signaling pathways may be activated in vivo cancer. We focused Hedgehog(Hh)signaling as one of activated pathways under hypoxia. It has been shown that Hh signaling is activated under hypoxia, followed by inducing malignant phenotypes in pancreatic cancer. Therefore, Hh signaling inhibitor should elicit anti-tumor effect. However, if we consider "whole-person therapy" we should confirm how Hh signaling affects the function of immune cells...
November 2017: Gan to Kagaku Ryoho. Cancer & Chemotherapy
https://www.readbyqxmd.com/read/29121972/long-noncoding-rna-norad-a-novel-competing-endogenous-rna-enhances-the-hypoxia-induced-epithelial-mesenchymal-transition-to-promote-metastasis-in-pancreatic-cancer
#6
Hongzhe Li, Xinjing Wang, Chenlei Wen, Zhen Huo, Weishen Wang, Qian Zhan, Dongfeng Cheng, Hao Chen, Xiaxing Deng, Chenghong Peng, Baiyong Shen
BACKGROUND: Pancreatic cancer, one of the top two most fatal cancers, is characterized by a desmoplastic reaction that creates a dense microenvironment, promoting hypoxia and inducing the epithelial-to-mesenchymal transition (EMT) to facilitate invasion and metastasis. Recent evidence indicates that the long noncoding RNA NORAD may be a potential oncogenic gene and that this lncRNA is significantly upregulated during hypoxia. However, the overall biological role and clinical significance of NORAD remains largely unknown...
November 9, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/29115428/inhibition-of-p21-activated-kinase-enhances-tumour-immune-response-and-sensitizes-pancreatic-cancer-to-gemcitabine
#7
Kai Wang, Nhi Huynh, Xiao Wang, Graham Baldwin, Mehrdad Nikfarjam, Hong He
Pancreatic ductal adenocarcinoma (PDA) is one of the major types of cancer that exhibit high mortality worldwide because of the late diagnosis and the lack of effective treatment. Immunotherapy appears to be ineffective in PDA treatment due to the existence of a unique immune-suppressive microenvironment in PDA. Gemcitabine-based therapy is still the most commonly used chemotherapy to treat PDA patients with only marginal increased survival rates. This prompted us to continue the search for more effective therapy for PDA treatment...
November 7, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29111329/exosomes-derived-from-pancreatic-cancer-cells-induce-activation-and-profibrogenic-activities-in-pancreatic-stellate-cells
#8
Atsushi Masamune, Naoki Yoshida, Shin Hamada, Tetsuya Takikawa, Tatsuhide Nabeshima, Tooru Shimosegawa
Pancreatic cancer cells (PCCs) interact with pancreatic stellate cells (PSCs), which play a pivotal role in pancreatic fibrogenesis, to develop the cancer-conditioned tumor microenvironment. Exosomes are membrane-enclosed nanovesicles, and have been increasingly recognized as important mediators of cell-to-cell communications. The aim of this study was to clarify the effects of PCC-derived exosomes on cell functions in PSCs. Exosomes were isolated from the conditioned medium of Panc-1 and SUIT-2 PCCs. Human primary PSCs were treated with PCC-derived exosomes...
October 27, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29108266/the-systemic-tumor-response-to-rnase-a-treatment-affects-the-expression-of-genes-involved-in-maintaining-cell-malignancy
#9
Nadezhda Mironova, Olga Patutina, Evgenyi Brenner, Alexander Kurilshikov, Valentin Vlassov, Marina Zenkova
Recently, pancreatic RNase A was shown to inhibit tumor and metastasis growth that accompanied by global alteration of miRNA profiles in the blood and tumor tissue (Mironova et al., 2013). Here, we performed a whole transcriptome analysis of murine Lewis lung carcinoma (LLC) after treatment of tumor-bearing mice with RNase A. We identified 966 differentially expressed transcripts in LLC tumors, of which 322 were upregulated and 644 were downregulated after RNase A treatment. Many of these genes are involved in signaling pathways that regulate energy metabolism, cell-growth promoting and transforming activity, modulation of the cancer microenvironment and extracellular matrix components, and cellular proliferation and differentiation...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29107216/pharmacological-effects-and-potential-therapeutic-targets-of-dt-13
#10
REVIEW
Ghulam Jilany Khan, Mohsin Rizwan, Muhammad Abbas, Muhammad Naveed, Yu Boyang, Muhammad Ahsan Naeem, Sara Khan, Shengtao Yuan, Mirza Muhammad Faran Ashraf Baig, Li Sun
DT-13 is an isolated compound from Dwarf lillytruf tuber and currently among active research drugs by National Natural Science foundation of China for its several potential effects. The drug has been reported for its multiple pharmacological actions however no thorough review studies are available on it. Our present study is highlighting the pros and cons of DT-13 focusing on its potential pharmacological actions, therapeutic utilization and further exploration for novel targets. The drug possesses very low toxicity profile, quick onset and long duration of action with slow elimination that combinely makes it favorable for the clinical studies...
October 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29092903/gpr68-a-proton-sensing-gpcr-mediates-interaction-of-cancer-associated-fibroblasts-and-cancer-cells
#11
Shu Z Wiley, Krishna Sriram, Wenjing Liang, Sarah E Chang, Randall French, Thalia McCann, Jason Sicklick, Hiroshi Nishihara, Andrew M Lowy, Paul A Insel
The microenvironment of pancreatic ductal adenocarcinoma (PDAC) is characterized by a dense fibrotic stroma (desmoplasia) generated by pancreatic cancer-associated fibroblasts (CAFs) derived from pancreatic stellate cells (PSCs) and pancreatic fibroblasts (PFs). Using an unbiased GPCRomic array approach, we identified 82 G-protein-coupled receptors (GPCRs) commonly expressed by CAFs derived from 5 primary PDAC tumors. Compared with PSCs and PFs, CAFs have increased expression of GPR68 (a proton-sensing GPCR), with the results confirmed by immunoblotting, The Cancer Genome Atlas data, and immunohistochemistry of PDAC tumors...
November 1, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29075790/differential-contribution-of-tissue-factor-and-factor%C3%A2-xii-to-thrombin-generation-triggered-by-breast-and-pancreatic-cancer-cells
#12
Aurélie Rousseau, Annette K Larsen, Patrick Van Dreden, Michele Sabbah, Ismail Elalamy, Grigoris T Gerotziafas
Most cancer cells trigger thrombin generation (TG) to various extent. In the present study, we dissected the mechanisms responsible for the procoagulant activity of pancreatic adenocarcinoma cells (BXPC3), a highly thrombogenic cancer type, and breast cancer cells (MCF7), a less thombogenic tumor type. TG of normal plasma was assessed by the Thrombinoscope (CAT®) in the presence or absence of cancer cells. TG was also assessed in plasma depleted of clotting factors, in plasma spiked with tissue factor (TF) and/or procoagulant phospholipids, in plasma spiked with an anti-TF monoclonal antibody or with corn trypsin inhibitor (CTI)...
October 20, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29074407/adaptation-of-vectors-and-drug-inducible-systems-for-controlled-expression-of-transgenes-in-the-tumor-microenvironment
#13
Joanna Poutou, Maria Bunuales, Manuela Gonzalez-Aparicio, Beatriz German, Ines Zugasti, Ruben Hernandez-Alcoceba
Biological therapies based on recombinant proteins such as antibodies or cytokines are continuously improving the repertoire of treatments against cancer. However, safety and efficacy of this approach is often limited by inappropriate biodistribution and pharmacokinetics of the proteins when they are administered systemically. Local administration of gene therapy vectors encoding these proteins would be a feasible alternative if they could mediate long-term and controlled expression of the transgene after a single intratumoral administration...
October 24, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29059164/fam49b-a-novel-regulator-of-mitochondrial-function-and-integrity-that-suppresses-tumor-metastasis
#14
M S Chattaragada, C Riganti, M Sassoe, M Principe, M M Santamorena, C Roux, C Curcio, A Evangelista, P Allavena, R Salvia, B Rusev, A Scarpa, P Cappello, F Novelli
Mitochondrial dysregulation plays a central role in cancers and drives reactive oxygen species (ROS)-dependent tumor progression. We investigated the pro-tumoral roles of mitochondrial dynamics and altered intracellular ROS levels in pancreatic ductal adenocarcinoma (PDAC). We identified 'family with sequence similarity 49 member B' (FAM49B) as a mitochondria-localized protein that regulates mitochondrial fission and cancer progression. Silencing FAM49B in PDAC cells resulted in increased fission and mitochondrial ROS generation, which enhanced PDAC cell proliferation and invasion...
October 23, 2017: Oncogene
https://www.readbyqxmd.com/read/29056077/halo-109-301-a-phase-iii-trial-of-pegph20-with-gemcitabine-and-nab-paclitaxel-in-hyaluronic-acid-high-stage-iv-pancreatic-cancer
#15
Gary J Doherty, Margaret Tempero, Pippa G Corrie
The outlook for patients with advanced pancreatic cancer remains poor, despite significant advances in our understanding of pancreatic tumor biology. One emerging theme highlights the distinct composition of the pancreatic tumor microenvironment. Hyaluronic acid is a hydrophilic glycosaminoglycan whose production within the tumor leads to increased interstitial tumor pressure, thereby limiting the access of potentially effective circulating anticancer drugs via reduced tumor perfusion. PEGylated rHuPH20 is a multiply PEGylated recombinant human hyaluronidase that has shown promising efficacy in preclinical models and early phase clinical trials in pancreatic cancer patients...
October 23, 2017: Future Oncology
https://www.readbyqxmd.com/read/29053398/the-involvement-of-lncrnas-in-the-development-and-progression-of-pancreatic-cancer
#16
Li Duguang, He Jin, Qian Xiaowei, Xu Peng, Wang Xiaodong, Li Zhennan, Qian Jianjun, Yao Jie
Pancreatic cancer is one of the most malignant tumors that are difficult to diagnose at its early stage and there is no effective therapy. Recent studies uncovered that many non-protein-coding RNAs including the class of long noncoding RNAs (lncRNAs) are differentially expressed in various types of tumors and they are potent regulators of tumor progression and metastasis. LncRNA can mediate tumor initiation, proliferation, migration and metastasis through modulating epigenetic modification, alternative splicing, transcription, and protein translation...
October 20, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29048660/canonical-and-non-canonical-wnt-signaling-in-cancer-stem-cells-and-their-niches-cellular-heterogeneity-omics-reprogramming-targeted-therapy-and-tumor-plasticity-review
#17
Masaru Katoh
Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49)...
September 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29043413/cholecystokinin-receptor-antagonist-alters-pancreatic-cancer-microenvironment-and-increases-efficacy-of-immune-checkpoint-antibody-therapy-in-mice
#18
Jill P Smith, Shangzi Wang, Sandeep Nadella, Sandra A Jablonski, Louis M Weiner
Advanced pancreatic ductal adenocarcinoma (PDAC) has typically been resistant to chemotherapy and immunotherapy; therefore, novel strategies are needed to enhance therapeutic response. Cholecystokinin (CCK) has been shown to stimulate growth of pancreatic cancer. CCK receptors (CCKRs) are present on pancreatic cancer cells, fibroblasts, and lymphocytes. We hypothesized that CCKR blockade would improve response to immune checkpoint antibodies by promoting influx of tumor-infiltrating lymphocytes (TILs) and reducing fibrosis...
October 17, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29042665/gdc-0449-improves-the-antitumor-activity-of-nano-doxorubicin-in-pancreatic-cancer-in-a-fibroblast-enriched-microenvironment
#19
Quan Zhou, Yongcun Zhou, Xiangrui Liu, Youqing Shen
Pancreatic cancer is one of the most lethal human cancers that currently does not have effective therapies. Novel treatments including nanomedicines and combination therapies are thus urgently needed for these types of deadly diseases. A key feature of pancreatic cancer is its tumor protective dense stroma, which is generated by cancer-associated fibroblasts (CAFs). The interaction between CAFs and pancreatic cancer cells abnormally activates sonic hedgehog (SHH) signaling and facilitates tumor growth, metastasis, and drug resistance...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29021221/cancer-associated-fibroblasts-promote-directional-cancer-cell-migration-by-aligning-fibronectin
#20
Begum Erdogan, Mingfang Ao, Lauren M White, Anna L Means, Bryson M Brewer, Lijie Yang, M Kay Washington, Chanjuan Shi, Omar E Franco, Alissa M Weaver, Simon W Hayward, Deyu Li, Donna J Webb
Cancer-associated fibroblasts (CAFs) are major components of the carcinoma microenvironment that promote tumor progression. However, the mechanisms by which CAFs regulate cancer cell migration are poorly understood. In this study, we show that fibronectin (Fn) assembled by CAFs mediates CAF-cancer cell association and directional migration. Compared with normal fibroblasts, CAFs produce an Fn-rich extracellular matrix with anisotropic fiber orientation, which guides the cancer cells to migrate directionally...
November 6, 2017: Journal of Cell Biology
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