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Cancer Biology & Therapy

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https://www.readbyqxmd.com/read/28532298/ctbp-an-emerging-oncogene-and-novel-small-molecule-drug-target-advances-in-the-understanding-of-its-oncogenic-action-and-identification-of-therapeutic-inhibitors
#1
M Michael Dcona, Benjamin L Morris, Keith C Ellis, Steven R Grossman
C-terminal Binding Proteins (CtBP) 1 and 2 are oncogenic transcriptional co-regulators overexpressed in many cancer types, with their expression level correlating to worse prognostic outcomes and aggressive tumor features. CtBP negatively regulates the expression of many tumor suppressor genes, while coactivating genes that promote proliferation, epithelial-mesenchymal transition, and cancer stem cell self-renewal activity. In light of this evidence, the development of novel inhibitors that mitigate CtBP function may provide clinically actionable therapeutic tools...
May 22, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28513320/crispr-cas9-based-pten-knock-out-and-sleeping-beauty-transposon-mediated-nras-knock-in-induces-hepatocellular-carcinoma-and-hepatic-lipid-accumulation-in-mice
#2
Mingming Gao, Dexi Liu
Both Pten and Nras are downstream mediators of receptor tyrosine kinase activation that plays important roles in controlling cell survival and proliferation. Here, we investigated whether and how Pten loss cross-talks with Nras activation in driving liver cancer development in mice. Somatic disruption of hepatic Pten and overexpression of Nras were achieved in out-bred immunocompetent CD-1 mice through a hydrodynamic delivery of plasmids carrying Sleeping Beauty transposon-based integration of Nras and the CRISPR/Cas9-mediated Pten knock-out system...
May 17, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28513269/immune-surveillance-in-melanoma-from-immune-attack-to-melanoma-escape-and-even-counterattack
#3
Fade Mahmoud, Bradley Shields, Issam Makhoul, Nathan Avaritt, Henry K Wong, Laura F Hutchins, Sara Shalin, Alan J Tackett
Pharmacologic inhibition of the cytotoxic T lymphocyte antigen 4 (CTLA4) and the programmed death receptor-1 (PD1) has resulted in unprecedented durable responses in metastatic melanoma. However, resistance to immunotherapy remains a major challenge. Effective immune surveillance against melanoma requires four essential steps: activation of the T lymphocytes, homing of the activated T lymphocytes to the melanoma microenvironment, identification and attack of melanoma cells by activated T lymphocytes, and the sensitivity of melanoma cells to apoptosis...
May 17, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28506198/naturally-occurring-benzoic-acid-derivatives-retard-cancer-cell-growth-by-inhibiting-histone-deacetylases-hdac
#4
Preethi G Anantharaju, Bandi Deepa Reddy, Mahesh A Padukudru, Ch M Kumari Chitturi, Manjunath G Vimalambike, SubbaRao V Madhunapantula
Histone deacetylases (HDACs), which modulate the expression of genes, are potential therapeutic targets in several cancers. Targeted inhibition of HDAC prevents the expression of oncogenes thereby help in the treatment of cancers. Hence, several pharmaceutical companies developed inhibitors of HDAC and tested them in preclinical models and in clinical trials. SAHA (suberanilohydroxamic acid) is one such HDAC inhibitor developed for treating breast and colorectal carcinomas. However, due to poor efficacy in clinical trials the utility of SAHA for treating cancers was discouraged...
May 16, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28498028/mir-337-can-be-a-key-negative-regulator-in-melanoma
#5
Wanan Xiao, Enyang Yao, Wei Zheng, Feng Tian, Lijie Tian
Incidence of melanoma is increasing annually worldwide. There remains a lack of suitable treatment methods which can significantly improve the five-year survival rates of patients. It is established that micro RNAs (miRNAs) have important roles in the diagnosis and treatment of cancer. MiR-337 had been reported to regulate the development of variety of cancers, as a cancer suppressive factor. In our research we found that miR-337 had a lower expression in melanoma than adjacent tissues. The patients who had a lower miR-337 also got a worse survival...
May 12, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28494188/depletion-of-signal-recognition-particle-72kda-increases-radiosensitivity
#6
Remko Prevo, Gaganpreet S Tiwana, Timothy S Maughan, Francesca M Buffa, W Gillies McKenna, Geoff S Higgins
The identification of genetic determinants that underpin tumor radioresistance can help the development of targeted radiosensitizers or aid personalization of radiotherapy treatment. Here we identify signal recognition particle 72 kDa (SRP72) as a novel gene involved in radioresistance. Knockdown of SRP72 resulted in significant radiosensitization of HeLa (cervical), PSN-1 (pancreatic), and T24 (bladder), BT-549 (breast) and MCF7 (breast) tumor lines as measured by colony formation assays. SRP72 depletion also resulted in the radiosensitization of normal lung fibroblast cell lines (HFL1 and MRC-5), demonstrating that the effect is not restricted to tumor cells...
May 11, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28494187/the-screening-of-the-functional-microrna-binding-site-snps-in-sporadic-colorectal-cancer-genes
#7
Hongjuan He, Lei Lei, Erfei Chen, Xiaona Xu, Lili Wang, Junqiang Pan, Fangfang Yang, Min Wang, Jing Dong, Jin Yang
Sporadic colorectal cancer (sCRC) is one of the most commonly diagnosed cancers worldwide, but few genetic markers have been identified and utilized for its early detection. MicroRNAs are diverse cellular regulators in cancer pathogenesis that bind to the 3'-untranslated region (3'-UTR) of their target mRNAs, and variants within the miRNA target sites on sCRC-related genes may influence its pathogenesis. To investigate this possibility, we used a bioinformatical method to screen SNPs for putative changes in miRNA recognition sites within the 3'-UTR of sCRC-related genes...
May 11, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28494185/functional-analysis-of-rare-variants-in-mismatch-repair-proteins-augments-results-from-computation-based-predictive-methods
#8
Sanjeevani Arora, Peter J Huwe, Rahmat Sikder, Manali Shah, Amanda J Browne, Randy Lesh, Emmanuelle Nicolas, Sanat Deshpande, Michael J Hall, Roland L Dunbrack, Erica A Golemis
The cancer-predisposing Lynch Syndrome (LS) arises from germline mutations in DNA mismatch repair (MMR) genes, predominantly MLH1, MSH2, MSH6,and PMS2. A major challenge for clinical diagnosis of LS is the frequent identification of variants of uncertain significance (VUS) in these genes, as it is often difficult to determine variant pathogenicity, particularly for missense variants. Generic programs such as SIFT and PolyPhen-2, and MMR gene-specific programs such as PON-MMR and MAPP-MMR, are often used to predict deleterious or neutral effects of VUS in MMR genes...
May 11, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28494184/current-status-of-research-and-treatment-for-non-small-cell-lung-cancer-in-never-smoking-females
#9
Shin Saito, Fernando Espinoza-Mercado, Hui Liu, Naohiro Sata, Xiaojiang Cui, Harmik J Soukiasian
Lung cancer is the leading cause of cancer-related deaths worldwide with over 1 million deaths each year. The overall prognosis of lung cancer patients remains unsatisfactory, with a 5-year overall survival rate of less than 15%. Although most lung cancers are a result of smoking, approximately 25% of lung cancer cases worldwide are not attributable to tobacco use. Notably, more than half of the lung cancer cases in women occur in non-smokers. Among non-small-cell lung cancer (NSCLC) cases, cigarette-smokers have a greater association with squamous cell carcinoma than adenocarcinoma, which is more common in non-smokers...
May 11, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28494179/predictive-biomarkers-for-triple-negative-breast-cancer-treated-with-platinum-based-chemotherapy
#10
Juan Jin, Wenwen Zhang, Wenfei Ji, Fang Yang, Xiaoxiang Guan
Treatment of triple negative breast cancer (TNBC) has been a big challenge since it is defined. To date, platinum-based chemotherapy has played a significant role in the treatment of TNBC patients. However, some patients do not respond to platinum salts or gradually develop chemoresistance, resulting in little effect, or even some adverse effects. Here, we review numerous preclinical and clinical investigations to summarize possible mechanisms and potential predictive biomarkers of platinum in TNBC. The homologous recombination deficiency (HRD) resulting from the loss of BRCA function is the main rationale of platinum efficacy in TNBC...
May 11, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28494176/comparative-analysis-of-the-effects-of-a-sphingosine-kinase-inhibitor-to-temozolomide-and-radiation-treatment-on-glioblastoma-cell-lines
#11
Liliana R Oancea-Castillo, Carmen Klein, Amir Abdollahi, Klaus-Josef Weber, Anne Régnier-Vigouroux, Ivana Dokic
Glioblastoma multiforme (GBM) exhibits high resistance to the standard treatment of temozolomide (TMZ) combined with radiotherapy, due to its remarkable cell heterogeneity. Accordingly, there is a need to target alternative molecules enhancing specific GBM autocrine or paracrine mechanisms and amplifying the effect of standard treatment. Sphingosine 1-phosphate (S1P) is such a lipid target molecule with an important role in cell invasion and proliferation. Sphingosine kinase inhibitors (SKI) prevent S1P formation and induce increased production of reactive oxygen species (ROS), which may potentiate radiation cytotoxicity...
May 11, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28494171/zinc-oxide-nanoparticles-antagonize-the-effect-of-cetuximab-on-head-and-neck-squamous-cell-carcinoma-in-vitro
#12
Thomas Gehrke, Agmal Scherzad, Pascal Ickrath, Philipp Schendzielorz, Rudolf Hagen, Norbert Kleinsasser, Stephan Hackenberg
Zinc oxide nanoparticles (ZnO-NPs) are being used in many cosmetic products and have been shown to induce tumor-selective cell death in human head and neck squamous cell carcinoma (HNSCC) in vitro. Cetuximab is a monoclonal antibody directed against the epidermal growth factor receptor (EGFR), whose effectiveness for HNSCC, alone or in combination with cytostatic drugs, has been demonstrated intensively in the last decades. Nanoparticles are known to interact with protein structures and thus may influence their functionality...
May 11, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28485999/igf2-mrna-binding-protein-3-imp3-mediated-regulation-of-transcriptome-and-translatome-in-glioma-cells
#13
Shruti Bhargava, Vikas Patil, Riyaz Ahmad Shah, Kumaravel Somasundaram
RNA binding proteins mediate global regulation at the level of transcriptome and translatome of a cell. We studied the global level expression changes regulated by IMP3 in transcriptome and translatome by performing microarray using total cellular RNA and heavy polysome derived RNA of IMP3 silenced glioma cells respectively. Differentially regulated transcripts at the transcriptome level (n = 2388) and at the level of translatome (n = 479) were identified. Further, these transcripts were classified as direct and indirect targets on the basis of presence of IMP3 binding site...
May 9, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28475454/impact-of-perineural-invasion-on-survival-in-node-negative-colon-cancer
#14
Katelin A Mirkin, Christopher S Hollenbeak, Ali Mohamed, Yuxia Jia, Wafik S El-Deiry, Evangelos Messaris
Perineural invasion (PNI) has been implicated as a poor prognostic indicator in many cancers. The National Comprehensive Cancer Network recommends consideration of observation or adjuvant therapy in the presence of PNI in early colon cancer. These recommendations are based on single institutional studies that fail to evaluate PNI within the context of adjuvant chemotherapy. The US National Cancer Database (2004-2012) was reviewed for patients with node negative colon cancer, and stratified by PNI and receipt of chemotherapy...
May 5, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28475408/vandetanib-and-cabozantinib-potentiate-mitochondria-targeted-agents-to-suppress-medullary-thyroid-carcinoma-cells
#15
Dmytro Starenki, Seung-Keun Hong, Pui-Kei Wu, Jong-In Park
Although the FDA-approved receptor tyrosine kinases inhibitors, vandetanib and cabozantinib, are used to treat surgically inoperable progressive medullary thyroid carcinoma (MTC), not all patients are responsive while the disease sometimes progresses after an initial response. To better understand MTC drug resistance at molecular and biochemical levels, we have generated drug-resistant subpopulations of the human MTC cell lines, TT and MZ-CRC-1, via prolonged exposure to vandetanib and cabozantinib. These drug-resistant progenies exhibited substantial cross-resistance to vandetanib and cabozantinib, suggesting that these inhibitors may invoke an overlapping resistance mechanism(s) in MTC cells...
May 5, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28475407/diagnosis-staging-and-risk-stratification-in-prostate-cancer-utilizing-diagnostic-tools-to-avoid-unnecessary-therapies-and-side-effects
#16
Louis Rodgers, Cody J Peer, William D Figg
A lack of appropriate diagnostic tools for prostate cancer has led to overdiagnosis and over treatment. In a recent publication in the New England Journal of Medicine, Hamdy et al showed no difference in the outcomes of patients that had undergone either radical prostatectomy, radiotherapy, or active monitoring. In an effort to enhance clinical stratification, the development of improved, more accurate diagnostic tools is actively being pursued. Herein, we explore recent advances in prostate cancer screening, including biomarker assays, genetic testing, and specialized fields, such as mathematical oncology...
May 5, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28475405/the-codon-72-polymorphism-of-p53-influences-cell-fate-following-nutrient-deprivation
#17
Che-Pei Kung, Qin Liu, Maureen E Murphy
The TP53 gene is distinguished as the most frequently mutated gene in cancer. Unlike most cancer-relevant genes, the TP53 gene is also distinguished by the existence of coding region polymorphisms that alter p53 sequence, and in some cases, also alter p53 function. A common coding region variant at amino acid 72 of p53 encodes either proline (P72) or arginine (R72). P72 is the ancestral variant and is most common in populations near the equator. The frequency of the R72 variant increases in a linear manner with latitude...
May 5, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28475402/dna-repair-genes-paxip1-and-tp53bp1-expression-is-associated-with-breast-cancer-prognosis
#18
Giuliana De Gregoriis, Juliene Antonio Ramos, Priscila Valverde Fernandes, Giselle Maria Vignal, Rafael Canfield Brianese, Dirce Maria Carraro, Alvaro N Monteiro, Claudio Struchiner, Guilherme Suarez-Kurtz, Rosane Vianna-Jorge, Marcelo Alex de Carvalho
Despite remarkable advances in diagnosis, prognosis and treatment, advanced or recurrent breast tumors have limited therapeutic approaches. Many treatment strategies try to explore the limitations of DNA damage response (DDR) in tumor cells to selectively eliminate them. BRCT (BRCA1 Carboxy-Terminal) domains are present in a superfamily of proteins involved in cell cycle checkpoints and the DDR. Tandem BRCT domains (tBRCT) represent a distinct class of these domains. We investigated the expression profile of seven tBRCT genes (BARD1, BRCA1, LIG4, ECT2, MDC1, PAXIP1/PTIP and TP53BP1) in breast cancer specimens and observed a high correlation between PAXIP1 and TP53BP1 gene expression in tumor samples...
May 5, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28475401/cellular-identity-crisis-antiandrogen-resistance-by-lineage-plasticity
#19
Daniel Tuerff, Tristan Sissung, William D Figg
A recent publication in Science demonstrates the ability of prostate cancer cells to switch lineages from one that is dependent on androgen signaling to a cell type that is not. Known as lineage plasticity, this phenomenon is driven by the transcription factor SOX2 in RB1 and TP53-deficient prostate cancer. SOX2 is a potential prognostic marker and therapeutic target in castration resistant prostate cancer.
May 5, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28453394/expression-of-mir-23a-by-apoptotic-regulators-in-human-cancer-a-review
#20
Rabih Roufayel, Seifedine Kadry
MicroRNAs play fundamental roles in mammalian development, differentiation and cellular homeostasis by regulating essential processes such as proliferation, migration, metabolism, migration and cell death. These small non-coding RNAs are also responsible in RNA silencing, and in many developmental and pathological processes. Not surprisingly, miR-23a misexpression contributes to numerous diseases including cancer where certain miRNA genes have been classified as either oncogenes or tumor suppressor genes. Since a single microRNA is capable of targeting a large number of mRNA sequences, de-regulated miRNA expression has the ability to alter various transcripts and activate a wide range of cancer-related pathways...
April 28, 2017: Cancer Biology & Therapy
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