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cancer pathway

Yue Guo, Renyi Wu, John M Gaspar, Davit Sargsyan, Zheng-Yuan Su, Chengyue Zhang, Linbo Gao, David Cheng, Wenji Li, Chao Wang, Ran Yin, Mingzhu Fang, Michael P Verzi, Ronald P Hart, Ah-Ng Kong
Inflammation is highly associated with colon carcinogenesis. Epigenetic mechanisms could play an important role in the initiation and progression of colon cancer. Curcumin, a dietary phytochemical, shows promising effects in suppressing colitis-associated colon cancer in AOM-DSS mice. However, the potential epigenetic mechanisms of curcumin in colon cancer remain unknown. In this study, the anti-cancer effect of curcumin in suppressing colon cancer in an 18-week AOM-DSS colon cancer mouse model was confirmed...
March 14, 2018: Carcinogenesis
Asmaa E Kassab, Ehab M Gedawy
As we are interested in synthetizing biologically active leads with dual anticancer and antibacterial activity, we adopted biology oriented drug synthesis (BIODS) strategy to synthesize a series of novel ciprofloxacin (CP) hybrids. The National Cancer Institute (USA) selected seventeen newly synthesized compounds for anticancer evaluation against 59 different human tumor cell lines. Five compounds 3e, 3f, 3h, 3o and 3p were further studied through determination of IC50 values against the most sensitive cancer cell lines...
March 9, 2018: European Journal of Medicinal Chemistry
Peng Liu, Teng-Fei Zhou, Bao-An Qiu, Ying-Xiang Yang, Yong-Jian Zhu, Yang An, Wen-Chao Zhao, Yin-Tao Wu, Peng-Fei Ma, Jing-Bo Li, Nian-Xin Xia
Cholangiocarcinoma (CCA) is one of the most common hepatic and biliary malignancies, accounting for about 3% of all gastrointestinal tumors. GATA5 is a transcription factor capable of suppressing the development of various human cancer types. Transcriptional inactivation and CpG island (CGI) methylation of GATA3 and GATA5, two members of the GATA family of transcription factors, have been observed in some human cancers. But whether high-density CGI methylation of GATA5 is associated with the clinical course of CCA patients has not been clarified...
March 13, 2018: Translational Oncology
Ruiting Lin, Siyuan Xia, Changliang Shan, Dong Chen, Yijie Liu, Xue Gao, Mei Wang, Hee-Bum Kang, Yaozhu Pan, Shuangping Liu, Young Rock Chung, Omar Abdel-Wahab, Taha Merghoub, Michael Rossi, Ragini R Kudchadkar, David H Lawson, Fadlo R Khuri, Sagar Lonial, Jing Chen
Dietary supplements such as vitamins and minerals are widely used in the hope of improving health but may have unidentified risks and side effects. In particular, a pathogenic link between dietary supplements and specific oncogenes remains unknown. Here we report that chondroitin-4-sulfate (CHSA), a natural glycosaminoglycan approved as a dietary supplement used for osteoarthritis, selectively promotes the tumor growth potential of BRAF V600E-expressing human melanoma cells in patient- and cell line-derived xenograft mice and confers resistance to BRAF inhibitors...
March 15, 2018: Molecular Cell
Jared T Hammill, Daniel C Scott, Jaeki Min, Michele C Connelly, Gloria Holbrook, Fangyi Zhu, Amy Matheny, Lei Yang, Bhuvanesh Singh, Brenda A Schulman, R Kiplin Guy
We previously discovered and validated a class of piperidinyl ureas that regulate defective in cullin neddylation 1 (DCN1)-dependent neddylation of cullins. Here, we report preliminary structure-activity relationship studies aimed at advancing our high-throughput screen hit into a tractable tool compound for dissecting the effects of acute DCN1-UBE2M inhibition on the NEDD8/cullin pathway. Structure-enabled optimization led to a 100-fold increase in biochemical potency and modestly increased solubility and permeability as compared to our initial hit...
March 16, 2018: Journal of Medicinal Chemistry
Petra Bachour, Stephen T Sonis
PURPOSE OF REVIEW: The goals of this review are to describe the complexity of factors influencing the risk of cancer regimen-related mucosal injury (CRRMI), to evaluate the contribution of the innate immune response to CRRMI risk, to compare the concordance of genome analytics in describing mechanism and risk, and to determine if common biological pathways are noted when CRRMI is compared to a disease with a similar phenotype. RECENT FINDINGS: The pathogenesis of and risk for CRRMI are complex and influenced by multiple intrinsic and extrinsic factors...
March 14, 2018: Current Opinion in Supportive and Palliative Care
J Russell Hoverman, Marcus A Neubauer, Melissa Jameson, Jad E Hayes, Kathryn J Eagye, Mitra Abdullahpour, Wendy J Haydon, Maria Sipala, Amy Supraner, Michael A Kolodziej, Diana K Verrilli
PURPOSE: Reform of cancer care delivery seeks to control costs while improving quality. Texas Oncology collaborated with Aetna to conduct a payer-sponsored program that used evidence-based treatment pathways, a disease management call center, and an introduction to advance care planning to improve patient care and reduce total costs. METHODS: From June 1, 2013, to May 31, 2016, 746 Medicare Advantage patients with nine common cancer diagnoses were enrolled. Patients electing for patient support services were telephoned by oncology nurses who assessed symptoms and quality of life and introduced advance care planning...
March 16, 2018: Journal of Oncology Practice
Ziling Fang, Bo Cao, Jun-Ming Liao, Jun Deng, Kevin D Plummer, Peng Liao, Tao Liu, Wensheng Zhang, Kun Zhang, Li Li, David Margolin, Shelya X Zeng, Jianping Xiong, Hua Lu
Ribosomal proteins (RPs) play important roles in modulating the MDM2-p53 pathway. However, less is known about the upstream regulators of the RPs. Here we identify SPIN1 (Spindlin 1) as a novel binding partner of human RPL5/uL18 that is important for this pathway. SPIN1 ablation activates p53, suppresses cell growth, reduces clonogenic ability, and induces apoptosis of human cancer cells. Mechanistically, SPIN1 sequesters uL18 in the nucleolus, preventing it from interacting with MDM2, and thereby alleviating uL18-mediated inhibition of MDM2 ubiquitin ligase activity towards p53...
March 16, 2018: ELife
Hironori Aoki, Eiichiro Yamamoto, Hiro-O Yamano, Tamotsu Sugai, Tomoaki Kimura, Yoshihito Tanaka, Hiro-O Matsushita, Kenjiro Yoshikawa, Ryo Takagi, Eiji Harada, Michiko Nakaoka, Yuko Yoshida, Taku Harada, Gota Sudo, Makoto Eizuka, Akira Yorozu, Hiroshi Kitajima, Takeshi Niinuma, Masahiro Kai, Masanori Nojima, Hiromu Suzuki, Hiroshi Nakase
BACKGROUND: Colorectal serrated lesions (SLs) are important premalignant lesions whose clinical and biological features are not fully understood. AIMS: We aimed to establish accurate colonoscopic diagnosis and treatment of SLs through evaluation of associations among the morphological, pathological, and molecular characteristics of SLs. METHODS: A total of 388 premalignant and 18 malignant colorectal lesions were studied. Using magnifying colonoscopy, microsurface structures were assessed based on Kudo's pit pattern classification system, and the Type II pit pattern was subcategorized into classical Type II, Type II-Open (Type II-O) and Type II-Long (Type II-L)...
March 15, 2018: Digestive Diseases and Sciences
Mаhmoud Youns, Abeer ElKhoely, Rehab Kamel
Pancreatic cancer, the fourth most common cause of cancer-related deaths, is one of the most aggressive and devastating human malignancies with increasing incidence worldwide. To date, surgical resection is the only potentially curative therapy available for pancreatic cancer patients. Early diagnosis of pancreatic tumors is difficult, and hence, nearly 80% of patients cannot receive surgical resection. Natural products have always been a vital source for novel compounds for cancer treatment. The naturally occurring prenylated xanthone, gambogic acid, has been previously shown to exert potent anticancer, anti-inflammatory, apoptotic, antiangiogenic, and antioxidant activities...
March 15, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
H Zhao, J Wang, D Fang, O Lee, R T Chatterton, V Stearns, S A Khan, S E Bulun
Obesity is associated with increased risk of breast cancer in postmenopausal but not in premenopausal women. Many factors may be responsible for this difference. The aim of this study was to determine the mechanisms by which the genes related to the AMPK pathway, inflammation, and estrogen actions are affected by adiposity in breast tissue with the objective of identifying differences that may explain the different breast cancer risk in premenopausal and postmenopausal women. Random fine needle aspirates (rFNAs) of breast tissue were collected from 57 premenopausal and 55 postmenopausal women and were classified as normal weight, overweight, or obese...
March 15, 2018: Hormones & Cancer
Xiangfeng Wang, Hu Fang, Yong Cheng, Lin Li, Xiaohui Sun, Tao Fu, Peide Huang, Anping Zhang, Zhimin Feng, Chunxue Li, Xuanlin Huang, Guangyan Li, Peina Du, Huanming Yang, Xiaodong Fang, Fan Li, Qiang Gao, Baohua Liu
Synchronous colorectal cancers (syCRCs), which present two or more lesions at diagnosis, are rare and pose a great challenge for clinical management. Although some predisposing factors associated with syCRCs have been studied with limited accession, the full repertoire of genomic events among the lesions within an individual and the causes of syCRCs remain unclear. We performed whole-exome sequencing of 40 surgical tumour samples of paired lesions from 20 patients to characterize the genetic alterations. Lesions from same patient showed distinct landscapes of somatic aberrations and shared few mutations, which suggests that they originate and develop independently although they shared the similar genetic background...
March 13, 2018: Carcinogenesis
Yanlan Li, Xiaodan Liu, Pengchao Gong, Xin Tian
Bufalin, a key active ingredient of the Chinese medicine Chan Su, inhibits breast cancer tumorigenesis in vitro and in vivo. Here we found that the pan-caspase inhibitor zVAD-fmk failed to inhibit bufalin-induced cell death in MCF-7 and MDA-MB-231 human breast cancer cells, confirming that the cell death induced by bufalin is caspase-independent. Instead, bufalin increased the expression of the necroptosis mediators RIP1 and RIP3. Bufalin-induced cell death was prevented by small molecule inhibitors of RIP1 and poly (ADP-ribose) polymerase-1 (PARP-1) or genetic knockdown of RIP3 by shRNA transfection...
March 13, 2018: Carcinogenesis
Hua Zhou, Abdul Mondal, Aleksandra Dakic, Lama Alhawas, Xuefeng Liu, Zhixu He
The roles of protection of telomeres 1 (POT1) in human ovarian cancer have not been fully elucidated. Here, we investigated the impact of POT1 knockdown (POT1-KD) on in vitro cell proliferation, tumorigenesis, and histone deacetylase inhibitor (HDACi) response in human ovarian cancer-derived SK-OV3 cells. The POT1 gene was knocked down by infection with POT1 lenti-shRNA. POT1, c-Myc, and hTERT mRNA levels and relative telomere length were determined by qRT-PCR; POT1 protein levels were determined by western blot...
2018: BioMed Research International
Wan-Angkan Poolsri, Phornpun Phokrai, Somrudee Suwankulanan, Narinthorn Phakdeeto, Pattamaphorn Phunsomboon, Dumrongsak Pekthong, Lysiane Richert, Sutatip Pongcharoen, Piyarat Srisawang
Increased expression levels of both mitochondrial citrate transporter (CTP) and plasma membrane citrate transporter (PMCT) proteins have been found in various cancers. The transported citrates by these two transporter proteins provide acetyl-CoA precursors for the de novo lipogenesis (DNL) pathway to support a high rate of cancer cell viability and development. Inhibition of the DNL pathway promotes cancer cell apoptosis without apparent cytotoxic to normal cells, leading to the representation of selective and powerful targets for cancer therapy...
2018: BioMed Research International
Muhammad Khairi Ahmad, Nur Ainina Abdollah, Nurul Husna Shafie, Narazah Mohd Yusof, Siti Razila Abdul Razak
Mitogen-activated protein kinases (MAPKs) are the main regulators of cellular proliferation, growth, and survival in physiological or pathological conditions. Aberrant MAPK signaling plays a pivotal role in carcinogenesis, which leads to development and progression of human cancer. Dual-specificity phosphatase 6 (DUSP6), a member of the MAPK phosphatase family, interacts with specifically targeted extracellular signal-regulated kinase 1/2 via negative feedback regulation in the MAPK pathway of mammalian cells...
February 2018: Cancer Biology & Medicine
Caroline K Søgaard, Siver A Moestue, Morten B Rye, Jana Kim, Anala Nepal, Nina-Beate Liabakk, Siri Bachke, Tone F Bathen, Marit Otterlei, Deborah K Hill
Docetaxel is the chemotherapeutic choice for metastatic hormone-refractory prostate cancer, however, it only marginally improves the survival rate. The purpose of the present study was to examine if a peptide targeting the cellular scaffold protein PCNA could improve docetaxel's efficacy. We found that docetaxel given in combination with a cell penetrating peptide containing the AlkB homolog 2 PCNA interacting motif (APIM-peptide), reduced the prostate volume and limited prostate cancer regrowth in vivo in the immunocompetent transgenic adenocarcinoma model of prostate cancer (TRAMP)...
February 20, 2018: Oncotarget
Muhammad Mosaraf Hossain, David Barua, Vahid Arabkari, Nahidul Islam, Ananya Gupta, Sanjeev Gupta
Nuclear receptor coactivators (NCOAs) function as coactivators for nuclear receptors as well as several other transcription factors and potentiate their transcriptional activity. NCOAs play an important role in biology of hormone-dependent and -independent cancers. MCB-613 is a recently described, small molecule stimulator of NCOAs and anti-neoplastic compound that leads to the death of tumour cells due to increased cellular stress. In the present study we investigated the molecular mechanism of MCB-613-induced cell death...
February 20, 2018: Oncotarget
Ali Ben Djoudi Ouadda, Yi He, Viviane Calabrese, Hidetaka Ishii, Rony Chidiac, Jean-Philippe Gratton, Philippe P Roux, Nathalie Lamarche-Vane
Cdc42 GTPase-activating protein (CdGAP, also named ARHGAP31) is a negative regulator of the GTPases Rac1 and Cdc42. Associated with the rare developmental disorder Adams-Oliver Syndrome (AOS), CdGAP is critical for embryonic vascular development and VEGF-mediated angiogenesis. Moreover, CdGAP is an essential component in the synergistic interaction between TGFβ and ErbB-2 signaling pathways during breast cancer cell migration and invasion, and is a novel E-cadherin transcriptional co-repressor with Zeb2 in breast cancer...
February 20, 2018: Oncotarget
Francesca Vena, Ruochen Jia, Arman Esfandiari, Juan J Garcia-Gomez, Manuel Rodriguez-Justo, Jianguo Ma, Sakeena Syed, Lindsey Crowley, Brian Elenbaas, Samantha Goodstal, John A Hartley, Daniel Hochhauser
Targeting the DNA damage response (DDR) in tumors with defective DNA repair is a clinically successful strategy. The RAS/RAF/MEK/ERK signalling pathway is frequently deregulated in human cancers. In this study, we explored the effects of MEK inhibition on the homologous recombination pathway and explored the potential for combination therapy of MEK inhibitors with DDR inhibitors and a hypoxia-activated prodrug. We studied effects of combining pimasertib, a selective allosteric inhibitor of MEK1/2, with olaparib, a small molecule inhibitor of poly (adenosine diphosphate [ADP]-ribose) polymerases (PARP), and with the hypoxia-activated prodrug evofosfamide in ovarian and pancreatic cancer cell lines...
February 20, 2018: Oncotarget
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