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Clinical pathways and cancer

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https://www.readbyqxmd.com/read/28538690/dysregulation-of-mirna-expression-in-cancer-associated-fibroblasts-cafs-and-its-consequences-on-the-tumor-microenvironment
#1
REVIEW
Maren Schoepp, Anda Jana Ströse, Jörg Haier
The tumor microenvironment, including cancer-associated fibroblasts (CAF), has developed as an important target for understanding tumor progression, clinical prognosis and treatment responses of cancer. Cancer cells appear to transform normal fibroblasts (NF) into CAFs involving direct cell-cell communication and epigenetic regulations. This review summarizes the current understanding on miR involvement in cancer cell-tumor environment/stroma communication, transformation of NFs into CAFs, their involved targets and signaling pathways in these interactions; and clinical relevance of CAF-related miR expression profiles...
May 24, 2017: Cancers
https://www.readbyqxmd.com/read/28537889/immune-signature-of-metastatic-breast-cancer-identifying-predictive-markers-of-immunotherapy-response
#2
Ji-Yeon Kim, Eunjin Lee, Kyunghee Park, Woong-Yang Park, Hae Hyun Jung, Jin Seok Ahn, Young-Hyuck Im, Yeon Hee Park
In breast cancer (BC), up to 10-20% patients were known to have clinical benefit with immune checkpoint inhibitors, and biomarkers are needed for optimal use of this multi-potential therapeutic strategy. Accordingly, we conducted an experiment to identify expression of genes associated with immune checkpoints that represent potential targets of cancer immunotherapy. We performed whole-transcriptome sequencing and whole-exome sequencing using 37 refractory BC specimens. In the immune pathway gene set expression analysis, we found that HER2 expression and previous taxane treatment were positively correlated with high expression of immune gene set expression (p = 0...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537888/high-expression-of-mir-493-5p-positively-correlates-with-clinical-prognosis-of-non-small-cell-lung-cancer-by-targeting-oncogene-itgb1
#3
Zhu Liang, Rui Kong, Zhan He, Li-Yao Lin, Shan-Shan Qin, Chun-Yuan Chen, Zhan-Qiang Xie, Fei Yu, Guo-Qian Sun, Chun-Guang Li, Da Fu, Geng-Xi Jiang, Jie Chen, Yu-Shui Ma
Increasing evidence supports that microRNA (miRNA)-mediated gene regulation plays a significant functional role in cancer progression. To investigate the expression and clinical significance of ITGB1 in non small cell lung cancer (NSCLC), the expression levels of ITGB1 in NSCLC tissues and human normal lung tissues were analyzed in silico using genes microarray, KEGG pathway and hierarchical clustering analysis followed by validation with quantitative RT-PCR. Our results showed that ITGB1 was upregulated in NSCLC tissues when compared with normal lung tissues...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537885/identifying-cpg-sites-with-different-differential-methylation-frequencies-in-colorectal-cancer-tissues-based-on-individualized-differential-methylation-analysis
#4
Haidan Yan, Jun He, Qingzhou Guan, Hao Cai, Lin Zhang, Weicheng Zheng, Lishuang Qi, Suyun Zhang, Huaping Liu, Hongdong Li, Wenyuan Zhao, Sheng Yang, Zheng Guo
A big challenge to clinical diagnosis and therapy of colorectal cancer (CRC) is its extreme heterogeneity, and thus it would be of special importance if we could find common biomarkers besides subtype-specific biomarkers for CRC. Here, with DNA methylation data produced by different laboratories, we firstly revealed that the relative methylation-level orderings (RMOs) of CpG sites within colorectal normal tissues are highly stable but widely disrupted in the CRC tissues. This finding provides the basis for using the RankComp algorithm to identify differentially methylated (DM) CpG sites in every individual CRC sample through comparing the RMOs within the individual sample with the stable RMOs predetermined in normal tissues...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537878/biological-characterization-of-sn32976-a-selective-inhibitor-of-pi3k-and-mtor-with-preferential-activity-to-pi3k%C3%AE-in-comparison-to-established-pan-pi3k-inhibitors
#5
Gordon W Rewcastle, Sharada Kolekar, Christina M Buchanan, Swarna A Gamage, Anna C Giddens, Kit Y Tsang, Jackie D Kendall, Ripudaman Singh, Woo-Jeong Lee, Greg C Smith, Weiping Han, David J Matthews, William A Denny, Peter R Shepherd, Stephen M F Jamieson
Multiple therapeutic agents have been developed to target the phosphatidylinositol 3-kinase (PI3K) signaling pathway, which is frequently dysregulated in cancer promoting tumor growth and survival. These include pan PI3K inhibitors, which target class Ia PI3K isoforms and have largely shown limited single agent activity with narrow therapeutic windows in clinical trials. Here, we characterize SN32976, a novel pan PI3K inhibitor, for its biochemical potency against PI3K isoforms and mTOR, kinase selectivity, cellular activity, pharmacokinetics, pharmacodynamics and antitumor efficacy relative to five clinically-evaluated pan PI3K inhibitors: buparlisib, dactolisib, pictilisib, omipalisib and ZSTK474...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537875/n-myc-downstream-regulated-gene-1-promotes-oxaliplatin-triggered-apoptosis-in-colorectal-cancer-cells-via-enhancing-the-ubiquitination-of-bcl-2
#6
Xiao Yang, Fan Zhu, Chaoran Yu, Jiaoyang Lu, Luyang Zhang, Yanfeng Lv, Jing Sun, Minhua Zheng
N-myc downstream-regulated gene1 (NDRG1) has been identified as a potent tumor suppressor gene. The molecular mechanisms of anti-tumor activity of NDRG1 involve its suppressive effects on a variety of tumorigenic signaling pathways. The purpose of this study was to investigate the role of NDRG1 in the apoptosis of colorectal cancer (CRC) cells. We first collected the clinical data of locally advanced rectal cancer (LARC) patients receiving oxaliplatin-based neoadjuvant chemotherapy in our medical center. Correlation analysis revealed that NDRG1 positively associated with the downstaging rates and prognosis of patients...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28537764/gefitinib-and-egfr-gene-copy-number-aberrations-in-esophageal-cancer
#7
Russell D Petty, Asa Dahle-Smith, David A J Stevenson, Aileen Osborne, Doreen Massie, Caroline Clark, Graeme I Murray, Susan J Dutton, Corran Roberts, Irene Y Chong, Wasat Mansoor, Joyce Thompson, Mark Harrison, Anirban Chatterjee, Stephen J Falk, Sean Elyan, Angel Garcia-Alonso, David Walter Fyfe, Jonathan Wadsley, Ian Chau, David R Ferry, Zosia Miedzybrodzka
Purpose The Cancer Esophagus Gefitinib trial demonstrated improved progression-free survival with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib relative to placebo in patients with advanced esophageal cancer who had disease progression after chemotherapy. Rapid and durable responses were observed in a minority of patients. We hypothesized that genetic aberration of the EGFR pathway would identify patients benefitting from gefitinib. Methods A prespecified, blinded molecular analysis of Cancer Esophagus Gefitinib trial tumors was conducted to compare efficacy of gefitinib with that of placebo according to EGFR copy number gain (CNG) and EGFR, KRAS, BRAF, and PIK3CA mutation status...
May 24, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28535511/capn4-enhances-osteopontin-expression-through-activation-of-the-wnt-%C3%AE-catenin-pathway-to-promote-epithelial-ovarian-carcinoma-metastasis
#8
Xiaoming Yang, Jing Sun, Dandan Xia, Xupei Can, Lei Liu, Jing Zhang, Huali Xu, Na Du, Wenxue Liu, Fangqian Shen, Zhenbo Zhang, Yunyan Sun, Xiaowei Xi
BACKGROUND AND AIM: Increasing evidence shows that the calpain regulatory subunit Capn4 can modulate the proliferation and metastasis of cancer cells, and plays an important role in the development of malignant tumors. However, there is no information on the clinical significance of Capn4 in epithelial ovarian carcinoma (EOC) or the molecular mechanisms by which Capn4 promotes the growth and metastasis of EOC. Therefore, the aim of this study was to clarify the role of Capn4 in EOC. METHODS: We evaluated Capn4 and osteopontin (OPN) expression in EOC cell lines and tissues from patients with ovarian cancer by western blotting and immunohistochemical analysis...
May 25, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28535102/why-value-framework-assessments-arrive-at-different-conclusions-a-multiple-myeloma-case-study
#9
Kimberly Westrich, Lisabeth Buelt, Robert W Dubois
As the United States transitions from a volume-based health care system to one that rewards value, new frameworks are emerging to help patients, providers, and payers assess the value of medical services and biopharmaceutical products. These value assessment frameworks are intended to support various types of health care decision making. They have the potential to substantially affect patients, whether as tools for shared decision making with their doctors, as an input to care pathways used by providers, or through payer use of the frameworks to make coverage or reimbursement decisions...
June 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28534986/overexpression-of-sox4-promotes-cell-migration-and-invasion-of-renal-cell-carcinoma-by-inducing-epithelial-mesenchymal-transition
#10
Hailong Ruan, Hongmei Yang, Haibin Wei, Wen Xiao, Ning Lou, Bin Qiu, Guanghua Xu, Zhengshuai Song, Haibin Xiao, Lei Liu, Yali Zhou, Wenjun Hu, Ke Chen, Xuanyu Chen, Xiaoping Zhang
Incomplete understanding remains in the molecular mechanisms underlying progression and metastasis of renal cancer. The transcription factor SOX4 is upregulated in various human malignancies, including renal cancer, indicating it may be involved in renal tumorigenesis. In this study, we explored this hypothesis by loss-of-function and gain-of-function assays of SOX4 in renal cancer cell lines and renal epithelial cell line. We found that specific knockdown of SOX4 in renal cancer cell lines significantly suppressed the migration and invasion of cancer cells; specific overexpression of SOX4 in renal epithelial cell line markedly promoted the migration and invasion of the cell line...
May 17, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28534969/the-cdc2-cdk1-inhibitor-purvalanol-a-enhances-the-cytotoxic-effects-of-taxol-through-op18-stathmin-in-non-small-cell-lung-cancer-cells-in%C3%A2-vitro
#11
Xian Chen, Ying Liao, Dan Long, Ting Yu, Fang Shen, Xuechi Lin
Purvalanol A is a highly selective inhibitor of Cdc2 [also known as cyclin-dependent kinase 1 (CDK1)]. Taxol is an anti-tumor chemotherapeutic drug which is widely used clinically. In this study, the CDK1 inhibitor, purvalanol A was applied to explore the relevance of Cdc2 signaling and taxol sensitivity through analyses, such as cellular proliferation and apoptosis assays, ELISA, western blot analysis and immunoprecipitation. We demonstrated that purvalanol A effectively enhanced the taxol-induced apoptosis of NCI-H1299 cells, as well as its inhibitory effects on cellular proliferation and colony formation...
May 15, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28534966/microrna-92a-promotes-epithelial-mesenchymal-transition-through-activation-of-pten-pi3k-akt-signaling-pathway-in-non-small-cell-lung-cancer-metastasis
#12
Chaojing Lu, Zhengxiang Shan, Jiang Hong, Lixin Yang
MicroRNAs (miRNAs) have important roles in various cancers, including non-small cell lung cancer (NSCLC). Although several miRNAs have reported to be involved in the development of NSCLC, understanding the regulatory roles of other miRNAs in NSCLC is essential. Therefore, the aim of the current study was to explore the roles and mechanisms of screened miRNAs in NSCLC. First, the differentially expressed miRNAs that were screened based on GSE29248 microarray data retrieved from Gene Expression Omnibus (GEO)...
May 16, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28534366/assessing-the-clinical-utility-of-wnt-pathway-markers-in-colorectal-cancer
#13
Georgios Veloudis, Apostolos Pappas, Stavros Gourgiotis, Evangelos Falidas, Nikoletta Dimitriou, Ioannis Karavokiros, Anastasios Aggelou, Vasileios Komborozos, Constantina Petraki, Panagiotis Menounos, Ioannis Bramis, Elias Bastounis, Emmanouel Pikoulis
PURPOSE: β-catenin and AXIN2 play an important role in the Wnt signaling pathway. The aim of this study was to investigate β-catenin and AXIN2 expression in colorectal cancer (CRC) and relate these findings with patients' clinicopathological features and prognosis. METHODS: 57 consecutive patients with surgically treated CRC were included in this study. Quantitative PCR and immunohistochemistry (IHC) analyses were performed to characterize the expression of the aforementioned markers in CRC tissues...
March 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/28534323/-era-of-enhanced-recovery-after-surgery-and-robotic-gastric-cancer-surgery
#14
Yanbing Zhou
Enhanced recovery after surgery (ERAS) has been rapidly developing by combining several techniques with evidence-based adjustments, including preoperative education, preoperative carbohydrate loading, epidural or regional anesthesia, early initiation of enteral nutrition, ambulation and multi-modal pain management. The core part of ERAS is to reduce and reverse surgical stress and therefore greatly improve clinical outcome. Under the guidance of ERAS, perioperative management of robotic gastric cancer operation should follow the basic principles of ERAS and clinical pathway to maximize the advantages of the robotic surgery...
May 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/28534024/cancer-immunoprevention-and-public-health
#15
REVIEW
Sandeep K Singh, Mehmet Tevfik Dorak
The power of cancer immune surveillance has been documented beyond doubt, and the successful exploitation of immune response to cancer has started a new era in the war against cancer. Cancer biologists have recognized immunoevasion as an emerging hallmark in addition to the six hallmarks of cancer. Besides the natural connection between the immune system and cancer development, most established environmental risk factors are now known to interfere with immune surveillance mechanisms. Genetic variations regulating immunity may also modulate cancer susceptibility, but evidence for this is currently limited...
2017: Frontiers in Public Health
https://www.readbyqxmd.com/read/28533754/the-ace2-angiotensin-1-7-mas-receptor-axis-pleiotropic-roles-in-cancer
#16
REVIEW
Juanjuan Xu, Jinshuo Fan, Feng Wu, Qi Huang, Mengfei Guo, Zhilei Lv, Jieli Han, Limin Duan, Guorong Hu, Lian Chen, Tingting Liao, Wanli Ma, Xiaonan Tao, Yang Jin
Cancer remains one of the most common causes of death and disability and represents a major economic burden in industrialized nations. The renin-angiotensin system (RAS) has been well-recognized as one of the most important regulators of both normal and pathological physiological processes in the brain, kidney, heart, and blood vessels. The activation of the angiotensin-converting enzyme 2/angiotensin-(1-7)/mitochondrial assembly receptor [ACE2/Ang-(1-7)/MasR] axis, which is one component of the RAS, has recently been identified as a critical component of pulmonary systems, gastric mucosa, and cancer...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28533502/clinical-value-and-prospective-pathway-signaling-of-microrna-375-in-lung-adenocarcinoma-a-study-based-on-the-cancer-genome-atlas-tcga-gene-expression-omnibus-geo-and-bioinformatics-analysis
#17
Ting-Qing Gan, Wen-Jie Chen, Hui Qin, Su-Ning Huang, Li-Hua Yang, Ye-Ying Fang, Lin-Jiang Pan, Zu-Yun Li, Gang Chen
BACKGROUND Lung adenocarcinoma (LUAD) is the most frequent lung cancer. MicroRNAs (miRNAs) are believed to have fundamental roles in tumorigenesis of LUAD. Although miRNAs are broadly recognized in LUAD, the role of microRNA-375 in LUAD is still not fully elucidated. MATERIAL AND METHODS We evaluated the significance of miR-375 expression in LUAD by using analysis of a public dataset from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database and a literature review. Furthermore, we investigated the biological function of miR-375 by gene ontology enrichment and target prediction analysis...
May 23, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28533437/metformin-inhibits-cellular-proliferation-and-bioenergetics-in-colorectal-cancer-patient-derived-xenografts
#18
Nur-Afidah Mohamed Suhaimi, Wai Min Phyo, Hao Yun Yap, Sharon Heng Yee Choy, Xiaona Wei, Yukti Choudhury, Wai Jin Tan, Luke Anthony Peng Yee Tan, Roger Sik Yin Foo, Suzanne Hui San Tan, Zenia Tiang, Chin Fong Wong, Poh Koon Koh, Min-Han Tan
There is increasing pre-clinical evidence suggesting that metformin, an anti-diabetic drug, has anti-cancer properties against various malignancies including colorectal cancer (CRC). However, majority of evidence which were derived from cancer cell lines and xenografts are likely to overestimate the benefit of metformin since these models are inadequate and require supraphysiological levels of metformin. Here, we generated patient-derived xenografts (PDX) lines from 2 CRC patients to assess the properties of metformin and 5-fluorouracil (5-FU), the first-line drug treatment for CRC...
May 22, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28533273/akt-signaling-is-sustained-by-a-cd44-splice-isoform-mediated-positive-feedback-loop
#19
Sali Liu, Chonghui Cheng
Tumor cells nearly invariably evolve sustained PI3K/Akt signaling as an effective means to circumvent apoptosis and maintain survival. However, for those tumor cells that do not acquire PI3K/Akt mutations to achieve this end the underlying mechanisms have remained obscure. Here we describe the discovery of a splice isoform-dependent positive feedback loop that is essential to sustain PI3K/Akt signaling in breast cancer. Splice isoform CD44s promoted expression of the hyaluronan synthase HAS2 by activating the Akt signaling cascade...
May 22, 2017: Cancer Research
https://www.readbyqxmd.com/read/28533224/microrna-196b-5p-regulates-colorectal-cancer-cell-migration-and-metastases-through-interaction-of-hoxb7-and-galnt5
#20
Verena Stiegelbauer, Petra Vychytilova-Faltejskova, Michael Karbiener, Anna-Maria Pehserl, Andreas Reicher, Margit Resel, Ellen Heitzer, Cristina Ivan, Marc D Bullock, Hui Ling, Alexander Ja Deutsch, Annika Wulf-Goldenberg, Jan Basri Adiprasito, Herbert Stöger, Johannes Haybaeck, Marek Svoboda, Michael Stotz, Gerald Höfler, Ondrej Slaby, George A Calin, Armin Gerger, Martin Pichler
Purpose: MicroRNA-196b-5p (miR-196b-5p) has been previously implicated in malignant transformation, however, its role in colorectal cancer (CRC) has not been fully explored. In the current study, we examine the clinical and biological relevance of miR-196b-5p, and the molecular pathways regulated by miR-196b-5p in CRC. <p>Experimental design: MiR-196b-5p expression was quantitated by qRT-PCR in two independent cohorts comprised of 292 CRC patients in total, to explore its biomarker potential. Transient and stable gain and loss of function experiments were conducted in a panel of CRC cell lines and mice, to evaluate the impact of miR-196b-5p on proliferation, chemo-sensitivity, migration/invasion and metastases formation in vitro and in vivo The molecular pathways influenced by miR-196b-5p were characterized using whole transcriptome profiling, in-silico target prediction tools, luciferase-interaction assays, and pheno-copy/rescue gene knock-down experiments...
May 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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