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Hallmarks, cancer

Xi Chen, Chun Xie, Xing-Xing Fan, Ze-Bo Jiang, Vincent Kam-Wai Wong, Jia-Hui Xu, Xiao-Jun Yao, Liang Liu, Elaine Lai-Han Leung
Drug resistance is becoming an obstacle in anti-cancer therapies. For target-based therapy of lung cancer, gefitinib, as the first generation of tyrosine kinase inhibitors (TKIs), demonstrated good initial response to the non-small cell lung cancer (NSCLC) patients whom harbors epidermal growth factor receptor (EGFR) mutation. However, within one year, additional EGFR mutation occurred, leading to eventual gefitinib-resistance. Therefore, it is urgently to discover novel effective small molecule inhibitors for those patients...
November 10, 2017: Oncotarget
Smruthi Vijayaraghavan, Stacy Moulder, Khandan Keyomarsi, Rachel M Layman
Cell cycle dysregulation is a hallmark of all cancers, resulting in uncontrolled proliferation. Cyclin dependent kinases (CDKs), a family of proteins that are involved in the regulation of the cell cycle, are frequently overexpressed or mutated in cancer. Hence, CDK-inhibiting drugs have been developed and evaluated as cancer therapeutics. Clinical trials have shown CDK4/6 inhibitors (CDK4/6i) to be relatively safe and effective, and these are now standard of care treatment for advanced hormone receptor positive breast cancer...
December 7, 2017: Targeted Oncology
Milica Momcilovic, David B Shackelford
It is widely accepted that altered metabolism contributes to cancer growth and has been described as a hallmark of cancer. Our view and understanding of cancer metabolism has expanded at a rapid pace, however, there remains a need to study metabolic dependencies of human cancer in vivo. Recent studies have sought to utilize multi-modality imaging (MMI) techniques in order to build a more detailed and comprehensive understanding of cancer metabolism. MMI combines several in vivo techniques that can provide complementary information related to cancer metabolism...
December 7, 2017: Biomolecules & Therapeutics
Michael L Neugent, Justin Goodwin, Ishwarya Sankaranarayanan, Celal Emre Yetkin, Meng-Hsiung Hsieh, Jung-Whan Kim
Tumors are dynamic metabolic systems which highly augmented metabolic fluxes and nutrient needs to support cellular proliferation and physiological function. For many years, a central hallmark of tumor metabolism has emphasized a uniformly elevated aerobic glycolysis as a critical feature of tumorigenecity. This led to extensive efforts of targeting glycolysis in human cancers. However, clinical attempts to target glycolysis and glucose metabolism have proven to be challenging. Recent advancements revealing a high degree of metabolic heterogeneity and plasticity embedded among various human cancers may paint a new picture of metabolic targeting for cancer therapies with a renewed interest in glucose metabolism...
December 7, 2017: Biomolecules & Therapeutics
Lili Zhao, Bingrong Liu
Accumulating evidence suggested that long non-coding RNAs (lncRNAs) can function as competing endogenous RNAs (ceRNAs) to interact with other RNA transcripts and ceRNAs perturbation play important roles in cancer initiation and progression including pancreatic adenocarcinoma (PAAD). In this study, we constructed a PAAD-specific hallmark gene-related ceRNA network (HceNet) using paired genome-wide expression profiles of mRNA, lncRNA and miRNA and regulatory relationships between them. Based on "ceRNA hypothesis", we analyzed the characteristics of HceNet and identified a ceRNA module comprising of 29 genes (12 lncRNAs, two miRNAs and 15 mRNAs) as potential prognostic biomarkers related to overall survival of patients with PAAD...
November 7, 2017: Oncotarget
Yi-Rong Li, Shiming Li, Chi-Chien Lin
Over the past years, several studies have found that foods rich in polyphenols protect against age-related disease, such as atherosclerosis, cardiovascular disease, cancer, arthritis, cataracts, osteoporosis, type 2 diabetes (T2D), hypertension and Alzheimer's disease. Resveratrol and pterostilbene, the polyphenol found in grape and blueberries, have beneficial effects as anti-aging compounds through modulating the hallmarks of aging, including oxidative damage, inflammation, telomere attrition and cell senescence...
December 6, 2017: BioFactors
Mahmoud Chaker, Audrey Minden, Suzie Chen, Robert H Weiss, Eduardo N Chini, Amit Mahipal, Asfar S Azmi
Sustained proliferative signaling and de-regulated cellular bioenergetics are two of the chief hallmarks of cancer. Alterations in the Ras pathway and its downstream effectors are among the major drivers for uncontrolled cell growth in many cancers. The GTPases are one of the signaling molecules that activate crucial signal transducing pathways downstream of Ras through several effector proteins. The GTPases (GTP bound) interact with several effectors and modulate a number of different biological pathways including those that regulate cytoskeleton, cellular motility, cytokinesis, proliferation, apoptosis, transcription and nuclear signaling...
December 6, 2017: Expert Opinion on Therapeutic Targets
G Ruffenach, S Bonnet, S Rousseaux, S Khochbin, S Provencher, F Perros
Pulmonary arterial hypertension (PAH) shares many hallmarks with cancer. Cancer cells acquire their hallmarks by a pathological Darwinian evolution process built on the so-called cancer cell "identity crisis." Here we demonstrate that PAH shares the most striking features of the cancer identity crisis: the ectopic expression of normally silent tissue-specific genes.
January 2018: Pulmonary Circulation
Anna Konstorum, John S Lowengrub
The tumor microenvironment is an integral component in promoting tumor development. Cancer-associated fibroblasts (CAFs), which reside in the tumor stroma, produce Hepatocyte Growth Factor (HGF), an important trigger for invasive and metastatic tumor behavior. HGF contributes to a pro-tumorigenic environment by activating its cognate receptor, c-Met, on tumor cells. Tumor cells, in turn, secrete growth factors that upregulate HGF production in CAFs, thereby establishing a dynamic tumor-host signaling program...
December 1, 2017: Journal of Theoretical Biology
Sabina Davidsson, Jessica Carlsson, Paula Mölling, Natyra Gashi, Ove Andrén, Swen-Olof Andersson, Elzbieta Brzuszkiewicz, Anja Poehlein, Munir A Al-Zeer, Volker Brinkmann, Carsten Scavenius, Seven Nazipi, Bo Söderquist, Holger Brüggemann
Inflammation is one of the hallmarks of prostate cancer. The origin of inflammation is unknown, but microbial infections are suspected to play a role. In previous studies, the Gram-positive, low virulent bacterium Cutibacterium (formerly Propionibacterium) acnes was frequently isolated from prostatic tissue. It is unclear if the presence of the bacterium represents a true infection or a contamination. Here we investigated Cutibacterium acnes type II, also called subspecies defendens, which is the most prevalent type among prostatic C...
2017: Frontiers in Microbiology
Mehmet G Badur, Christian M Metallo
Metabolic dysfunction has reemerged as an essential hallmark of tumorigenesis, and metabolic phenotypes are increasingly being integrated into pre-clinical models of disease. The complexity of these metabolic networks requires systems-level interrogation, and metabolic flux analysis (MFA) with stable isotope tracing present a suitable conceptual framework for such systems. Here we review efforts to elucidate mechanisms through which metabolism influences tumor growth and survival, with an emphasis on applications using stable isotope tracing and MFA...
November 30, 2017: Metabolic Engineering
Peter J Burke
Until recently, the dual roles of mitochondria in ATP production (bioenergetics) and apoptosis (cell life/death decision) were thought to be separate. New evidence points to a more intimate link between these two functions, mediated by the remodeling of the mitochondrial ultrastructure during apoptosis. While most of the key molecular players that regulate this process have been identified (primarily membrane proteins), the exact mechanisms by which they function are not yet understood. Because resistance to apoptosis is a hallmark of cancer, and because ultimately all chemotherapies are believed to result directly or indirectly in induction of apoptosis, a better understanding of the biophysical processes involved may lead to new avenues for therapy...
December 2017: Trends in Cancer
M Winkle, J L Kluiver, A Diepstra, A van den Berg
Long noncoding (lnc)RNAs have emerged as essential mediators of cellular biology, differentiation and malignant transformation. LncRNAs have a broad range of possible functions at the transcriptional, posttranscriptional and protein level and their aberrant expression significantly contributes to the hallmarks of cancer cell biology. In addition, their high tissue- and cell-type specificity makes lncRNAs especially interesting as biomarkers, prognostic factors or specific therapeutic targets. Here, we review current knowledge on lncRNA expression changes during normal B-cell development, indicating essential functions in the differentiation process...
December 2017: Critical Reviews in Oncology/hematology
Emily L Rossi, Subreen A Khatib, Steven S Doerstling, Laura W Bowers, Melissa Pruski, Nikki A Ford, Randolph D Glickman, Mengmeng Niu, Peiying Yang, Zhengrong Cui, John DiGiovanni, Stephen D Hursting
Adipose tissue dysregulation, a hallmark of obesity, contributes to a chronic state of low-grade inflammation and is associated with increased risk and progression of several breast cancer subtypes, including claudin-low breast tumors. Unfortunately, mechanistic targets for breaking the links between obesity-associated adipose tissue dysfunction, inflammation, and claudin-low breast cancer growth have not been elucidated. Ovariectomized female C57BL/6 mice were randomized (n = 15/group) to receive a control diet, a diet-induced obesity (DIO) diet, or a DIO + resveratrol (0...
November 20, 2017: Molecular Carcinogenesis
Yosuke Inoue, Kazumasa Moriwaki, Yasuhiro Ueda, Toshihisa Takeuchi, Kazuhide Higuchi, Michio Asahi
O-GlcNAcylation is a dynamic post-translational modification of cytonuclear proteins for intracellular signaling. Elevated O-GlcNAcylation is a general feature of cancer and contributes to cancer progression, and recent studies indicate the contribution to increasing incidence of various types of cancer in diabetic patients. However, the role of O-GlcNAcylation in tumor progression is not fully elucidated. Forkhead box M1 (FOXM1), a master mitotic transcription factor, has been implicated in all major hallmarks of cancer, and is wildly expressed in solid tumors...
November 28, 2017: Biochemical and Biophysical Research Communications
Jayant Dewangan, Shweta Kaushik, Srikanta Kumar Rath, Anil K Balapure
AIMS: Angiogenesis is a recognized hallmark of cancer which promotes cancer cell progression and metastasis. Inhibition of angiogenesis to attenuate cancer growth is becoming desirable strategy for breast cancer management. The present study is aimed to investigate the antiangiogenic efficacy of a novel selective estrogen receptor modulator Centchroman (CC) on human breast cancer cells. MAIN METHODS: Effect of CC on cell viability was evaluated using Sulforhodamine B assay...
November 28, 2017: Life Sciences
Danyi Wu, Carol Prives
In response to varying stress signals, the p53 tumor suppressor is able to promote repair, survival, or elimination of damaged cells - processes that have great relevance to organismal aging. Although the link between p53 and cancer is well established, the contribution of p53 to the aging process is less clear. Delineating how p53 regulates distinct aging hallmarks such as cellular senescence, genomic instability, mitochondrial dysfunction, and altered metabolic pathways will be critical. Mouse models have further revealed the centrality and complexity of the p53 network in aging processes...
December 1, 2017: Cell Death and Differentiation
Hugues de Thé
The concept of differentiation therapy emerged from the fact that hormones or cytokines may promote differentiation ex vivo, thereby irreversibly changing the phenotype of cancer cells. Its hallmark success has been the treatment of acute promyelocytic leukaemia (APL), a condition that is now highly curable by the combination of retinoic acid (RA) and arsenic. Recently, drugs that trigger differentiation in a variety of primary tumour cells have been identified, suggesting that they are clinically useful. This Opinion article analyses the basis for the clinical successes of RA or arsenic in APL by assessing the respective roles of terminal maturation and loss of self-renewal...
December 1, 2017: Nature Reviews. Cancer
Emanuel Gonçalves, Marco Sciacovelli, Ana S H Costa, Maxine Gia Binh Tran, Timothy Isaac Johnson, Daniel Machado, Christian Frezza, Julio Saez-Rodriguez
Deregulated signal transduction and energy metabolism are hallmarks of cancer and both play a fundamental role in tumorigenesis. While it is increasingly recognised that signalling and metabolism are highly interconnected, the underpinning mechanisms of their co-regulation are still largely unknown. Here we designed and acquired proteomics, phosphoproteomics, and metabolomics experiments in fumarate hydratase (FH) deficient cells and developed a computational modelling approach to identify putative regulatory phosphorylation-sites of metabolic enzymes...
November 27, 2017: Metabolic Engineering
Jay H Lo, Thomas T Chen
E-peptide of the pro-Insulin-like growth factor-I (pro-IGF-I) is produced from pre-pro-IGF-I by proteolytic cleavage in the post-translational processing. The human Eb-peptide (hEb-peptide), derived from the E domain of pro-IGF-IB isoform, is a bioactive molecule whose exact physiological role remains elusive. Accumulated evidence reported from our laboratory indicated that hEb-peptide possesses activity against multiple hallmark characteristics of solid tumor in different cancer cell types. In human breast carcinoma cells (MDA-MB-231), it was demonstrated that hEb-peptide can promote cell attachment to substratum, inhibit colony formation in a semisolid medium, reduce cancer cell invasion, and inhibit cancer-induced angiogenesis...
November 27, 2017: Experimental Cell Research
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