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Clinical pathways and cancer

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https://www.readbyqxmd.com/read/29150944/toll-like-receptor-signaling-pathway-as-a-potential-therapeutic-target-in-colorectal-cancer
#1
REVIEW
Reyhaneh Moradi-Marjaneh, Seyed Mahdi Hassanian, Hamid Fiuji, Saman Soleimanpour, Gordon A Ferns, Amir Avan, Majid Khazaei
Toll like receptor (TLR) signaling is involved in activating innate and adaptive immune responses and plays a critical role in inflammation-induced diseases such as colorectal cancer (CRC). Dysregulation of this signaling pathway can result in disturbance of epithelial layer hemostasis, chronic inflammatory, excessive repair responses and development of CRC. There is now substantial evidence for the benefit of targeting of this pathway in cancer treatment, and several agents have been approved, such as BCG (Bacillus Calmette Guérin), MPL (monophosphoryl lipid A) and imiquimod...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150934/the-current-status-and-perspectives-regarding-the-clinical-implication-of-intracellular-calcium-in-breast-cancer
#2
REVIEW
Amir Tajbakhsh, Alireza Pasdar, Mehdi Rezaee, Mostafa Fazeli, Saman Soleimanpour, Seyed Mahdi Hassanian, Zahra FarshchiyanYazdi, Tayebe Younesi Rad, Gordon A Ferns, Amir Avan
Calcium ions (Ca(2+) ) act as second messengers in intracellular signaling. Ca(2+) pumps, channels, sensors, and calcium binding proteins, regulate the concentrations of intracellular Ca(2+) as a key regulator of important cellular processes such as gene expression, proliferation, differentiation, DNA repair, apoptosis, metastasis, and hormone secretion. Intracellular Ca(2+) also influences the functions of several organelles, that include: the endoplasmic reticulum, mitochondria, the Golgi, and cell membrane both in normal and breast cancer cells...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150921/tgf-%C3%AE-and-hepatocellular-carcinoma-when-a-friend-becomes-an-enemy
#3
Marco Arrese, Daniel Cabrera, Alejandra Hernandez, Luis Astete, Lisbell Estrada, Claudio Cabello-Verrugio
Hepatocellular carcinoma (HCC) is the second most common cause of cancer death worldwide accounting for more than 700 thousand deaths per year. Most of the HCC develops in a cirrhotic liver, a microenvironment where fibrotic tissue replaces parenchymal cells. Thus, there is a close connection between fibrosis and HCC development. Understanding the cellular and molecular mechanisms involved in this process is a crucial step to advance in novel therapeutic or pharmacological strategies to prevent or improve the course of this malignancy...
November 16, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/29149600/repair-of-uv-induced-dna-damage-independent-of-nucleotide-excision-repair-is-masked-by-mutyh
#4
Abdelghani Mazouzi, Federica Battistini, Sarah C Moser, Joana Ferreira da Silva, Marc Wiedner, Michel Owusu, Charles-Hugues Lardeau, Anna Ringler, Beatrix Weil, Jürgen Neesen, Modesto Orozco, Stefan Kubicek, Joanna I Loizou
DNA lesions caused by UV damage are thought to be repaired solely by the nucleotide excision repair (NER) pathway in human cells. Patients carrying mutations within genes functioning in this pathway display a range of pathologies, including an increased susceptibility to cancer, premature aging, and neurological defects. There are currently no curative therapies available. Here we performed a high-throughput chemical screen for agents that could alleviate the cellular sensitivity of NER-deficient cells to UV-induced DNA damage...
November 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29149451/transcriptional-alterations-in-hereditary-and-sporadic-nonfunctioning-pancreatic-neuroendocrine-tumors-according-to-genotype
#5
Xavier M Keutgen, Suresh Kumar, Sudheer Gara, Myriem Boufraqech, Sunita Agarwal, Ralph H Hruban, Naris Nilubol, Martha Quezado, Richard Finney, Maggie Cam, Electron Kebebew
BACKGROUND: Nonfunctioning pancreatic neuroendocrine tumors (NFPanNETs) may be sporadic or inherited because of germline mutations associated with von Hippel-Lindau disease (VHL) or multiple endocrine neoplasia type 1 (MEN1). The clinical behavior of NFPanNETs is difficult to predict, even in tumors of the same stage and grade. The authors analyzed genotype-specific patterns of transcriptional messenger RNA (mRNA) levels of NFPanNETs to understand the molecular features that determine PanNET phenotype...
November 17, 2017: Cancer
https://www.readbyqxmd.com/read/29147602/gdnf-secreted-by-nerves-enhances-pd-l1-expression-via-jak2-stat1-signaling-activation-in-hnscc
#6
Chengzhong Lin, Wei Cao, Zhenhu Ren, Yu Tang, Chunye Zhang, Rong Yang, Yiming Chen, Zheqi Liu, Canbang Peng, Lizhen Wang, Xu Wang, Tong Ji
Programmed death ligand 1 (PD-L1) functions as a key immune inhibitory factor by binding with its receptor, programmed death 1 (PD-1), to induce immune cell dysfunction and escape of the immune system. However, the mechanisms of PD-L1 expression under growth factor stimulation are not well characterized. Here, we demonstrate a novel role for glial cell line-derived neurotrophic factor (GDNF) in upregulating PD-L1 expression in head and neck squamous cell carcinoma (HNSCC). The expression and correlation of PD-L1, GDNF and perineural invasion (PNI) status were evaluated by bioinformatics analysis of TCGA database and IHC assays from 145 HNSCC patients...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29147491/augmented-expression-levels-of-lncrnas-eccebpa-and-uca1-in-gastric-cancer-tissues-and-their-clinical-significance
#7
Mojdeh Nasrollahzadeh-Khakiani, Modjtaba Emadi-Baygi, Parvaneh Nikpour
Objectives: As the second cause of cancer death, gastric cancer (GC) is one of the eminent dilemmas all over the world, therefore investigating the molecular mechanisms involved in this cancer is pivotal. Unrestricted proliferation is one of the characteristics of cancerous cells, which is due to deficiency in cell regulatory systems. Long non-coding RNAs (lncRNAs) have emerged as critical regulators of the epigenome. lncRNA extra coding CEBPA (ecCEBPA) is involved in DNA methylation...
October 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29146938/computational-investigation-of-homologous-recombination-dna-repair-deficiency-in-sporadic-breast-cancer
#8
Yue Wang, Matthew H Ung, Sharon Cantor, Chao Cheng
BRCAness has important implications in the management and treatment of patients with breast and ovarian cancer. In this study, we propose a computational framework to measure the BRCAness of breast and ovarian tumor samples based on their gene expression profiles. We define a characteristic profile for BRCAness by comparing gene expression differences between BRCA1/2 mutant familial tumors and sporadic breast cancer tumors while adjusting for relevant clinical factors. With this BRCAness profile, our framework calculates sample-specific BRCA scores, which indicates homologous recombination (HR)-mediated DNA repair pathway activity of samples...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29146569/found-in-translation-how-preclinical-research-is-guiding-the-clinical-development-of-the-bcl2-selective-inhibitor-venetoclax
#9
REVIEW
Joel D Leverson, Deepak Sampath, Andrew J Souers, Saul H Rosenberg, Wayne J Fairbrother, Martine Amiot, Marina Konopleva, Anthony Letai
Since the discovery of apoptosis as a form of programmed cell death, targeting the apoptosis pathway to induce cancer cell death has been a high-priority goal for cancer therapy. After decades of effort, drug-discovery scientists have succeeded in generating small-molecule inhibitors of antiapoptotic BCL2 family proteins. Innovative medicinal chemistry and structure-based drug design, coupled with a strong fundamental understanding of BCL2 biology, were essential to the development of BH3 mimetics such as the BCL2-selective inhibitor venetoclax...
November 16, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29146545/werner-syndrome-wrn-gene-variants-and-their-association-with-altered-function-and-age-associated-diseases
#10
REVIEW
Michel Lebel, Raymond J Monnat
Werner syndrome (WS) is a heritable autosomal recessive human disorder characterized by the premature onset of several age-associated pathologies including cancer. The protein defective in WS patients, WRN, is encoded by a member of the human RECQ gene family that contains both a DNA exonuclease and a helicase domain. WRN has been shown to participate in several DNA metabolic pathways including DNA replication, recombination and repair, as well as telomere maintenance and transcription modulation. Here we review base pair-level genetic variation that has been documented in WRN, with an emphasis on non-synonymous coding single nucleotide polymorphisms (SNPs) and their associations with anthropomorphic features, longevity and disease risk...
November 13, 2017: Ageing Research Reviews
https://www.readbyqxmd.com/read/29145973/tak-ing-aim-at-chemoresistance-the-emerging-role-of-map3k7-as-a-target-for-cancer-therapy
#11
Raffaela Santoro, Carmine Carbone, Geny Piro, Paul J Chiao, Davide Melisi
Cellular drug resistance remains the main obstacle to the clinical efficacy of cancer chemotherapy. Alterations in key pathways regulating cell cycle checkpoints, apoptosis and Epithelial to Mesenchymal Transition (EMT), such as the Mitogen-activated protein kinase (MAPK) pathway, appear to be closely associated to cancer chemoresistance. Transforming growth factor-β (TGF-β)- activated kinase 1 (TAK1, also known as MAP3K7) is a serine/threonine kinase in the mitogen-activated protein kinase (MAP3K) family...
November 2017: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/29145892/association-between-plasma-phospholipid-saturated-fatty-acids-and-metabolic-markers-of-lipid-hepatic-inflammation-and-glycaemic-pathways-in-eight-european-countries-a-cross-sectional-analysis-in-the-epic-interact-study
#12
Ju-Sheng Zheng, Stephen J Sharp, Fumiaki Imamura, Albert Koulman, Matthias B Schulze, Zheng Ye, Jules Griffin, Marcela Guevara, José María Huerta, Janine Kröger, Ivonne Sluijs, Antonio Agudo, Aurelio Barricarte, Heiner Boeing, Sandra Colorado-Yohar, Courtney Dow, Miren Dorronsoro, Pia T Dinesen, Guy Fagherazzi, Paul W Franks, Edith J M Feskens, Tilman Kühn, Verena Andrea Katzke, Timothy J Key, Kay-Tee Khaw, Maria Santucci de Magistris, Francesca Romana Mancini, Elena Molina-Portillo, Peter M Nilsson, Anja Olsen, Kim Overvad, Domenico Palli, Jose Ramón Quirós, Olov Rolandsson, Fulvio Ricceri, Annemieke M W Spijkerman, Nadia Slimani, Giovanna Tagliabue, Anne Tjonneland, Rosario Tumino, Yvonne T van der Schouw, Claudia Langenberg, Elio Riboli, Nita G Forouhi, Nicholas J Wareham
BACKGROUND: Accumulating evidence suggests that individual circulating saturated fatty acids (SFAs) are heterogeneous in their associations with cardio-metabolic diseases, but evidence about associations of SFAs with metabolic markers of different pathogenic pathways is limited. We aimed to examine the associations between plasma phospholipid SFAs and the metabolic markers of lipid, hepatic, glycaemic and inflammation pathways. METHODS: We measured nine individual plasma phospholipid SFAs and derived three SFA groups (odd-chain: C15:0 + C17:0, even-chain: C14:0 + C16:0 + C18:0, and very-long-chain: C20:0 + C22:0 + C23:0 + C24:0) in individuals from the subcohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study across eight European countries...
November 17, 2017: BMC Medicine
https://www.readbyqxmd.com/read/29145164/long-noncoding-rna-hnf1a-as1-indicates-a-poor-prognosis-of-colorectal-cancer-and-promotes-carcinogenesis-via-activation-of-the-wnt-%C3%AE-catenin-signaling-pathway
#13
Xin Zhang, Yumin Xiong, Fengying Tang, Ying Bian, Yanhui Chen, Fengli Zhang
Long non-coding RNAs (lncRNAs) have been identified to play critical roles in tumorigenesis. LncRNA HNF1A-AS1 has been suggested to act as an oncogene and serves as a novel prognostic biomarker for various cancer. However, the biological role and clinical significance of lncRNA HNF1A-AS1 in colorectal cancer (CRC) have yet to be fully elusive. Therefore, the present study was designed to determine the expression of lncRNA HNF1A-AS1 in patients with CRC, the role of lncRNA HNF1A-AS1 in CRC cells, as well as the underlying regulatory mechanisms...
October 24, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29144791/is-there-a-role-for-programmed-death-ligand-1-testing-and-immunotherapy-in-colorectal-cancer-with-microsatellite-instability-part-i-colorectal-cancer-microsatellite-instability-testing-and-clinical-implications
#14
Esmeralda Celia Marginean, Barbara Melosky
CONTEXT: - Colorectal cancer (CRC) represents the third most-common cancer in developed countries and is a leading cause of cancer deaths worldwide. Two recognized pathways contribute to CRC development: a more-common chromosomal instability pathway and, in 15% of cases, a deficient mismatch repair or microsatellite instability-high (MSI-H) pathway. The MSI-H CRC can be associated with somatic or germline mutations. Microsatellite status has been recognized as a prognostic and predictive biomarker...
November 16, 2017: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29144412/pancreatic-cancer-chemoresistance-to-gemcitabine
#15
REVIEW
Manoj Amrutkar, Ivar P Gladhaug
Pancreatic ductal adenocarcinoma (PDAC), commonly referred to as pancreatic cancer, ranks among the leading causes of cancer-related deaths in the Western world due to disease presentation at an advanced stage, early metastasis and generally a very limited response to chemotherapy or radiotherapy. Gemcitabine remains a cornerstone of PDAC treatment in all stages of the disease despite suboptimal clinical effects primarily caused by molecular mechanisms limiting its cellular uptake and activation and overall efficacy, as well as the development of chemoresistance within weeks of treatment initiation...
November 16, 2017: Cancers
https://www.readbyqxmd.com/read/29142802/metastatic-her2-breast-cancer-a-potentially-curable-disease
#16
Lisa Prior, Marvin Lim, Cian Ward, Hannah Featherstone, Hazel Murray, Clare D'Arcy, John Crown, Giuseppe Gullo
The advent of trastuzumab and other human epidermal growth factor receptor 2 (HER2)-directed therapies has revolutionized the treatment of metastatic HER2-positive breast cancer, leading to prolonged survival and appreciable clinical benefit for a substantial subset of patients. Previously, in a retrospective study at our institution, we observed that nearly 10% of patients achieved a durable complete remission (DCR) following a combination of HER2-directed therapy and cytotoxic chemotherapy. We are currently expanding this study to include patients who were treated since the initial introduction of trastuzumab...
September 5, 2017: Curēus
https://www.readbyqxmd.com/read/29142107/is-inflammatory-micronucleation-the-key-to-a-successful-anti-mitotic-cancer-drug
#17
REVIEW
T J Mitchison, J Pineda, J Shi, S Florian
Paclitaxel is a successful anti-cancer drug that kills cancer cells in two-dimensional culture through perturbation of mitosis, but whether it causes tumour regression by anti-mitotic actions is controversial. Drug candidates that specifically target mitosis, including inhibitors of kinesin-5, AurkA, AurkB and Plk1, disappointed in the clinic. Current explanations for this discrepancy include pharmacokinetic differences and hypothetical interphase actions of paclitaxel. Here, we discuss post-mitotic micronucleation as a special activity of taxanes that might explain their higher activity in solid tumours...
November 2017: Open Biology
https://www.readbyqxmd.com/read/29141970/natural-forms-of-vitamin-e-as-effective-agents-for-cancer-prevention-and-therapy
#18
REVIEW
Qing Jiang
Initial research on vitamin E and cancer has focused on α-tocopherol (αT), but recent clinical studies on cancer-preventive effects of αT supplementation have shown disappointing results, which has led to doubts about the role of vitamin E, including different vitamin E forms, in cancer prevention. However, accumulating mechanistic and preclinical animal studies show that other forms of vitamin E, such as γ-tocopherol (γT), δ-tocopherol (δT), γ-tocotrienol (γTE), and δ-tocotrienol (δTE), have far superior cancer-preventive activities than does αT...
November 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/29141914/proteotranscriptomics-reveal-signaling-networks-in-the-ovarian-cancer-microenvironment
#19
Thomas Worzfeld, Florian Finkernagel, Silke Reinartz, Anne Konzer, Till Adhikary, Andrea Nist, Thorsten Stiewe, Uwe Wagner, Mario Looso, Johannes Graumann, Rolf Müller
Ovarian cancer is characterized by early transcoelomic metastatic spread via the peritoneal fluid, where tumor cell spheroids (TU), tumor-associated T cells (TAT), and macrophages (TAM) create a unique microenvironment promoting cancer progression, chemoresistance and immuno-suppression. However, the underlying signaling mechanisms remain largely obscure.  To chart these signaling networks, we performed comprehensive proteomic and transcriptomic analyses of TU, TAT and TAM from ascites of ovarian cancer patients...
November 15, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/29141899/atypical-g-protein-%C3%AE-5-promotes-cardiac-oxidative-stress-apoptosis-and-fibrotic-remodeling-in-response-to-multiple-cancer-chemotherapeutics
#20
Biswanath Maity, Sreemoyee Chakraborti, Arnab Pramanick, Sudipta Saha, Somnath Singha Roy, Arnab Ray Chaudhuri, Madhusudan Das, Sujoy Ghosh, Adele Stewart
The clinical use of multiple classes of cancer chemotherapeutics is limited by irreversible, dose-dependent, and sometimes life-threatening cardiotoxicity. We report here that, though distinct in their mechanisms of action, doxorubicin, paclitaxel, and 5-FU all induce rapid and robust upregulation of atypical G protein Gβ5 in the myocardium, correlating with oxidative stress, myocyte apoptosis, and the accumulation of pro-inflammatory and pro-fibrotic cytokines. In ventricular cardiac myocytes (VCM), Gβ5 deficiency provided substantial protection against the cytotoxic actions of chemotherapeutics, including reductions in oxidative stress and simultaneous attenuation of ROS-dependent activation of the ATM and CaMKII pro-apoptotic signaling cascades...
November 15, 2017: Cancer Research
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