Chronic heart failure is characterized by altered mitochondrial function and structure in circulating leucocytes.
Authors: Coluccia R, Raffa S, Ranieri D, Micaloni A, Valente S, Salerno G, Scrofani C, Testa M, Gallo G, Pagannone E, Torrisi MR, Volpe M, Rubattu S Abstract Oxidative stress is currently viewed as a key factor in the genesis and progression of Heart Failure (HF). The aim of this study was to characterize the mitochondrial changes linked to oxidative stress generation in circulating peripheral blood mononuclear cells isolated from chronic HF patients (HF_PBMCs) in order to highlight the involvement of mitochondrial dysfunction in the pathophysiology of HF. To assess the production of reactive oxygen species (ROS), ...
Source: Oncotarget - November 13, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Molecular analysis of the dual targeting of the epidermal growth factor receptor and the O6-methylguanine-DNA methyltransferase with a double arm hybrid molecule.
Authors: Rupp M, Mouhri ZS, Williams C, Jean-Claude BJ Abstract Disordered expression of the epidermal growth factor receptor (EGFR) has been associated with induction of DNA repair genes (e.g. XRCC1, ERCC1) and resistance to radiation and genotoxic drugs. However, our previous work showed that EGFR inhibition did not affect O6-methylguanine-DNA methyltransferase (MGMT)-mediated resistance. In order to block uncoupled events associated with EGFR and MGMT, we designed MR30, a single molecule termed "combi-molecule" that contains a quinazoline arm targeted to EGFR and an O6-benzylguanine (O6-BG) moiety to b...
Source: Oncotarget - November 13, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Predictive values of two frailty screening tools in older patients with solid cancer: a comparison of SAOP2 and G8.
Authors: Russo C, Giannotti C, Signori A, Cea M, Murialdo R, Ballestrero A, Scabini S, Romairone E, Odetti P, Nencioni A, Monacelli F Abstract Objectives: Comprehensive Geriatric Assessment (CGA), the gold standard for detecting frailty in elderly cancer patients, is time-consuming and hard to apply in routine clinical practice. Here we compared the performance of two screening tools for frailty, G8 and SAOP2 for their accuracy in identifying vulnerable patients. Material and Methods: We tested G8 and SAOP2 in 282 patients aged 65 or older with a diagnosis of solid cancer and candidate to undergo surgical, medi...
Source: Oncotarget - November 13, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

The Cockayne syndrome protein B is involved in the repair of 5-AZA-2'-deoxycytidine-induced DNA lesions.
Authors: Burgos-Morón E, Calderón-Montaño JM, Pastor N, Höglund A, Ruiz-Castizo Á, Domínguez I, López-Lázaro M, Hajji N, Helleday T, Mateos S, Orta ML Abstract The Cockayne Syndrome Protein B (CSB) plays an essential role in Transcription-Coupled Nucleotide Excision Repair (TC-NER) by recruiting repair proteins once transcription is blocked with a DNA lesion. In fact, CSB-deficient cells are unable to recover from transcription-blocking DNA lesions. 5-Aza-2'-deoxycytidine (5-azadC) is a nucleoside analogue that covalently traps DNA methyltransferases (DNMTs) ont...
Source: Oncotarget - November 13, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

LncRNAs as novel players in hepatocellular carcinoma recurrence.
Authors: Gramantieri L, Baglioni M, Fornari F, Laginestra MA, Ferracin M, Indio V, Ravaioli M, Cescon M, De Pace V, Leoni S, Coadă CA, Negrini M, Bolondi L, Giovannini C Abstract Long non-coding RNAs (lncRNAs) are ncRNAs more than 200 nucleotides long that participate to a wide range of biological functions. However, their role in cancer is poorly known. By using an NGS-based approach we analyzed the intragenic and poliA-lncRNAs in hepatocellular carcinoma (HCC) and we assayed the relationships between their deregulated expression and clinical-pathological characteristics. The expression profile of lncRNAs was stu...
Source: Oncotarget - November 13, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

IDH1R132H is intrinsically tumor-suppressive but functionally attenuated by the glutamate-rich cerebral environment.
In this study, we report that IDH1R132H is intrinsically tumor-suppressive but the activity can be attenuated by glutamate-the cerebral neurotransmitter. We observed that IDH1R132H was highly suppressive of subcutaneous tumor growth driven by platelet-derived growth factor B (PDGFB), but IDH1R132H tumor growth and glioma penetrance were virtually indistinguishable from those of IDH1-wildtype tumors in orthotopic models. In vitro, addition of glutamate compromised IDH1R132H inhibition of neurosphere genesis, indicating glutamate promotion of oncogenic dominance. Furthermore, we observed that IDH1R132H expression was markedl...
Source: Oncotarget - November 13, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

MicroRNA expression profile during different conditions of hypoxia.
Conclusions: Intermittent hypoxia induces the expression of some miRNAs more than chronic hypoxia. These miRNAs may play an important role in the development of different diseases usually associated with OSA such as cardiovascular disease. In addition, mechanisms involved in cancer progression may be induced in the presence of chronic and more often intermittent hypoxia. PMID: 30416683 [PubMed] (Source: Oncotarget)
Source: Oncotarget - November 13, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

CXCR4- and BCR-triggered integrin activation in B-cell chronic lymphocytic leukemia cells depends on JAK2-activated Bruton's tyrosine kinase.
In this study, we investigated, in normal versus CLL B-lymphocytes, the role of BTK in signal transduction activated by the CXCL12-CXCR4 signaling axis and its involvement in rapid integrin activation. We show that BTK is rapidly activated by CXCL12 in healthy as well as CLL B-lymphocytes, with a kinetic of tyr-phosphorylation coherent with rapid adhesion triggering. BTK inhibition prevents CXCL12-induced triggering of lymphocyte function-associated antigen-1 (LFA-1) and very late antigen-4 (VLA-4) integrins. Furthermore, BTK inhibition blocks the activation of the small GTP-binding protein RhoA, controlling integrin affin...
Source: Oncotarget - November 13, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Antitumor profile of the PI3K inhibitor ZSTK474 in human sarcoma cell lines.
Authors: Namatame N, Tamaki N, Yoshizawa Y, Okamura M, Nishimura Y, Yamazaki K, Tanaka M, Nakamura T, Semba K, Yamori T, Yaguchi SI, Dan S Abstract Treatment of patients with advanced sarcoma remains challenging due to lack of effective medicine, with the development of novel drugs being of keen interest. A pan-PI3K inhibitor, ZSTK474, has been evaluated in clinical trials against a range of advanced solid tumors, with clinical benefit shown in sarcoma patients. In the present study, we developed a panel of 14 human sarcoma cell lines and investigated the antitumor effect of 24 anticancer agents including ZSTK474, ...
Source: Oncotarget - November 13, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Transcriptomic and genomic profiling of early-stage ovarian carcinomas associated with histotype and overall survival.
Authors: Engqvist H, Parris TZ, Rönnerman EW, Söderberg EMV, Biermann J, Mateoiu C, Sundfeldt K, Kovács A, Karlsson P, Helou K Abstract Ovarian cancer is the most lethal gynecological malignancy in the western world. Despite recent efforts to characterize ovarian cancer using molecular profiling, few targeted treatment options are currently available. Here, we examined genetic variants, fusion transcripts, SNP genotyping, and gene expression patterns for early-stage (I and II) ovarian carcinomas (n=96) in relation to clinicopathological characteristics and clinical outcome, thereby identifying nove...
Source: Oncotarget - November 13, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Brain metastases in ALK-positive NSCLC - time to adjust current treatment algorithms.
Authors: Griesinger F, Roeper J, Pöttgen C, Willborn KC, Eberhardt WEE Abstract The progress in molecular biology has revolutionized systemic treatment of advanced non-small-cell lung cancer (NSCLC) from conventional chemotherapy to a treatment stratified by histology and genetic aberrations. Tumors harboring a translocation of the anaplastic-lymphoma-kinase (ALK) gene constitute a distinct genetic and clinico-pathologic NSCLC subtype with patients with ALK-positive disease being at a higher risk for developing brain metastases. Due to the introduction of effective targeted therapy with ALK-inhibitors, today, ...
Source: Oncotarget - November 13, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Correction: The nuclear-cytoplasmic trafficking of a chromatin-modifying and remodelling protein (KMT2C), in osteosarcoma.
Authors: Chiappetta C, Puggioni C, Carletti R, Petrozza V, Rocca CD, Di Cristofano C Abstract [This corrects the article DOI: 10.18632/oncotarget.25755.]. PMID: 30416688 [PubMed - in process] (Source: Oncotarget)
Source: Oncotarget - November 13, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Erratum: Disruption of Myc-Max Heterodimerization with Improved Cell-Penetrating Analogs of the Small Molecule 10074-G5.
Authors: Wang H, Chauhan J, Hu A, Pendleton K, Yap JL, Sabato PE, Jones JW, Perri M, Yu J, Cione E, Kane MA, Fletcher S, Prochownik EV Abstract [This corrects the article DOI: 10.18632/oncotarget.1108.]. PMID: 30416689 [PubMed - in process] (Source: Oncotarget)
Source: Oncotarget - November 13, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Influence of Scribble polarity complex on hematopoiesis and leukemia - a matter of where, when and how.
Authors: Heidel FH, Ellis S PMID: 30410664 [PubMed] (Source: Oncotarget)
Source: Oncotarget - November 11, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Circulating cell-free miR-494 and miR-21 are disease response biomarkers associated with interim-positron emission tomography response in patients with diffuse large B-cell lymphoma.
Authors: Cui Q, Vari F, Cristino AS, Salomon C, Rice GE, Sabdia MB, Guanzon D, Palma C, Mathew M, Talaulikar D, Jain S, Han E, Hertzberg MS, Gould C, Crooks P, Thillaiyampalam G, Keane C, Gandhi MK Abstract MicroRNA (miRNA)s are dysregulated in Diffuse large B-cell lymphoma (DLBCL), where they reflect the malignant B-cells and the immune infiltrate within the tumor microenvironment. There remains a paucity of data in DLBCL regarding cell-free (c-f) miRNA as disease response biomarkers. Immunosuppressive monocyte/macrophages, which are enriched in DLBCL, are disease response markers in DLBCL, with miRNA key regulato...
Source: Oncotarget - November 11, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

The anti-cancer effect of retinoic acid signaling in CRC occurs via decreased growth of ALDH+ colon cancer stem cells and increased differentiation of stem cells.
Conclusions: Retinoid signaling, by regulating ALDH+ colonic CSCs, decreases SC proliferation, sphere formation, and population size, and increases SC differentiation to NECs. Dysregulation of RA signaling in colonic SCs likely contributes to overpopulation of ALDH+ SCs and CRC growth. Implications: That retinoid receptors RXR and RAR are selectively expressed in ALDH+ SCs indicates RA signaling mainly occurs via ALDH+ SCs, which provides a mechanism to selectively target CSCs. PMID: 30410666 [PubMed] (Source: Oncotarget)
Source: Oncotarget - November 11, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

The transgenic expression of the β-subunit of human chorionic gonadotropin influences the growth of implanted tumor cells.
The transgenic expression of the β-subunit of human chorionic gonadotropin influences the growth of implanted tumor cells. Oncotarget. 2018 Oct 05;9(78):34670-34680 Authors: Singh P, Sarkar M, Agrawal U, Huhtaniemi I, Pal R Abstract The beta subunit of human chorionic gonadotropin (βhCG) is secreted by various tumors, and its presence associated with poor prognosis. Though exogenous hCG elicits the synthesis of molecules associated with angiogenesis, invasion, immune suppression and chemoresistance from responsive tumor cells in vitro, the influence of cell-extrinsic βhCG on tumorigenesi...
Source: Oncotarget - November 11, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

ATR suppresses the pro-tumorigenic functions of breast stromal fibroblasts.
Authors: Al-Ansari MM, Aboussekhra A Abstract The ATR protein kinase is a master regulator of the cellular responses to DNA damage and replication stresses. Despite these crucial physiological roles, the implication of ATR in human carcinogenesis remains elusive. We have shown here that the ATR level is reduced in most cancer-associated fibroblasts (CAFs) as compared to their adjacent normal counterparts. Importantly, specific ATR knockdown activated breast fibroblasts, and enhanced their paracrine pro-carcinogenic effects via strong increase in the expression/secretion of SDF-1 and IL-6. Furthermore, ATR-deficient...
Source: Oncotarget - November 11, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Obesity and Alzheimer's disease, does the obesity paradox really exist? A magnetic resonance imaging study.
In conclusion, our data support that weight loss negatively confounds the association between late-life obesity and brain atrophy. The obesity paradox on AD risk might be explained by reverse causation. PMID: 30410669 [PubMed] (Source: Oncotarget)
Source: Oncotarget - November 11, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

β-amyloid wall deposit of temporal artery in subjects with spontaneous intracerebral haemorrhage.
Discussion: Our findings of a higher frequency of amyloid deposition in temporal artery specimens in subjects with spontaneous intracerebral haemorrhage indicate a possible role of temporal artery as a possible diagnostic site of biopsy in subjects at high risk to develop intracranial haemorrhage related to Cerebral Amyloid Angiopathy. PMID: 30410670 [PubMed] (Source: Oncotarget)
Source: Oncotarget - November 11, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

DDB2 regulates Epithelial-to-Mesenchymal Transition (EMT) in Oral/Head and Neck Squamous Cell Carcinoma.
In this study, we show that DDB2 expression is downregulated in advanced HNSCCs and loss of DDB2 expression coincides with reduced survival. Recent meta-analysis of gene expression data characterized the mesenchymal-type (EMT-type) as one most aggressive cancer cluster in HNSCC. Here, we report that DDB2 constitutively represses mRNA expression of the EMT- regulatory transcription factors SNAIL, ZEB1, and angiogenic factor VEGF in HNSCC cells. As a result, re-expression of DDB2 in metastatic cells reversed EMT with transcriptional upregulation of epithelial marker E-cadherin, and downregulation of mesenchymal markers N-cad...
Source: Oncotarget - November 11, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

H19 long non-coding RNA contributes to sphere formation and invasion through regulation of CD24 and integrin expression in pancreatic cancer cells.
In this study, we clarified the mechanisms by which H19 regulates PDAC metastasis, with a focus on cancer stem cells (CSCs), by using H19-overexpressing and knockdown PDAC cells. Whereas the sphere-formation and invasion abilities of PDAC cells depended on H19 expression levels, other CSC characteristics of the cells, including stemness-marker expression and anticancer-drug resistance, were unaffected by H19 levels. Furthermore, metalloproteinase activity, a key mediator of invasion, was also independent of H19 expression. By contrast, H19 promoted cell adhesion through regulation of integrin and CD24 expression. Notably, ...
Source: Oncotarget - November 11, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Modelling ponatinib resistance in tyrosine kinase inhibitor-na ïve and dasatinib resistant BCR-ABL1+ cell lines.
In this study, we investigated the emerging modes of ponatinib resistance in TKI-naïve and dasatinib resistant BCR-ABL1+ cell lines. To investigate potential resistance mechanisms, ponatinib resistance was generated in BCR-ABL1+ cell-lines by long-term exposure to increasing concentrations of ponatinib. Two cell lines with prior dasatinib resistance demonstrated BCR-ABL1 kinase domain (KD) mutation(s) upon exposure to ponatinib. In one of these cell lines the T315I mutation had emerged during dasatinib exposure. When further cultured with ponatinib, the T315I mutation level and BCR-ABL1 mRNA expression level were incr...
Source: Oncotarget - November 11, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Leukemia inhibitory factor via the Toll-like receptor 5 signaling pathway involves aggravation of cachexia induced by human gastric cancer-derived 85As2 cells in rats.
Authors: Terawaki K, Kashiwase Y, Uzu M, Nonaka M, Sawada Y, Miyano K, Higami Y, Yanagihara K, Yamamoto M, Uezono Y Abstract Cancer cachexia is highly prevalent in gastric cancer patients and characterized by decreased food consumption and body weight. We previously created a rat model of cancer cachexia using MKN45cl85 and 85As2 cells derived from human gastric cancer. The 85As2 cells induced cachexia more potently compared to MKN45cl85 cells. To clarify the mechanism underlying the difference in the cachexia-inducing ability of these cells, we conducted DNA microarray analysis, focusing on cell proliferation and ...
Source: Oncotarget - November 11, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Does afatinib plus bevacizumab combination therapy induce positive conversion of T790M in previously-negative patients?
Authors: Hata A, Katakami N, Kaji R, Yokoyama T, Kaneda T, Tamiya M, Inoue T, Kimura H, Yano Y, Tamura D, Morita S, Negoro S, HANSHIN Oncology Group Abstract Third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are markedly effective for T790M-positive patients. To confer their clinical benefit to more patients, a novel therapy to induce positive conversion in T790M-negative patients may be possible. We retrospectively reviewed medical records of patients who had received rebiopsy after completion of ABC-study: a prospective phase II study of Afatinib plus Bevacizumab Combinati...
Source: Oncotarget - November 11, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Deletion of the glucocorticoid receptor chaperone FKBP51 prevents glucocorticoid-induced skin atrophy.
Authors: Baida G, Bhalla P, Yemelyanov A, Stechschulte LA, Shou W, Readhead B, Dudley JT, Sánchez ER, Budunova I Abstract FKBP51 (FK506-binding protein 51) is a known co-chaperone and regulator of the glucocorticoid receptor (GR), which usually attenuates its activity. FKBP51 is one of the major GR target genes in skin, but its role in clinical effects of glucocorticoids is not known. Here, we used FKBP51 knockout (KO) mice to determine FKBP51's role in the major adverse effect of topical glucocorticoids, skin atrophy. Unexpectedly, we found that all skin compartments (epidermis, dermis, dermal adipose and C...
Source: Oncotarget - November 11, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Clinical impact of serum soluble SLAMF7 in multiple myeloma.
The objective of this study was to evaluate the clinical significance of serum soluble SLAMF7 (sSLAMF7) levels in patients with MM (n=103) and furthermore the impact of sSLMF7 on the antitumor activity of anti-SLAMF7 antibody. Thirty-one percent of MM patients, but not patients with monoclonal gammopathy of undetermined significance and healthy controls, had detectable levels of serum sSLAMF7, which were significantly increased in advanced MM patients. Further, MM in sSLAMF7-postive patients exhibited aggressive clinical characteristics with shorter progression-free survival times in comparison with sSLAMF7-negative patien...
Source: Oncotarget - November 11, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Multi-omic based molecular profiling of advanced cancer identifies treatable targets and improves survival in individual patients.
Authors: Samsen A, von der Heyde S, Bokemeyer C, David KA, Flath B, Graap M, Grebenstein B, Heflik L, Hollburg W, Layer P, von Leitner E, Overkamp F, Saeger W, Schneider S, von Seydewitz CU, Stang A, Stein A, Zornig C, Juhl H Abstract A proof-of-concept study was conducted to assess whether patients with advanced stage IV cancer for whom predominantly no standard therapy was available could benefit from comprehensive molecular profiling of their tumor tissue to provide targeted therapy. Tumor samples of 83 patients were collected under highly standardized conditions and analyzed using immunohistochemistry, next-gen...
Source: Oncotarget - November 11, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Peritoneal NK cells are responsive to IL-15 and percentages are correlated with outcome in advanced ovarian cancer patients.
Authors: Hoogstad-van Evert JS, Maas RJ, van der Meer J, Cany J, van der Steen S, Jansen JH, Miller JS, Bekkers R, Hobo W, Massuger L, Dolstra H Abstract The demonstration that ovarian carcinoma (OC) is an immunogenic disease, opens opportunities to explore immunotherapeutic interventions to improve clinical outcome. In this regard, NK cell based immunotherapy could be promising as it has been demonstrated that OC cells are susceptible to killing by cytokine-stimulated NK cells. Here, we evaluated whether percentage, phenotype, function and IL-15 responsiveness of ascites-derived natural killer (NK) cells is relate...
Source: Oncotarget - November 11, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

PARP1 is required for preserving telomeric integrity but is dispensable for A-NHEJ.
Authors: Harvey A, Mielke N, Grimstead JW, Jones RE, Nguyen T, Mueller M, Baird DM, Hendrickson EA Abstract Poly-ADP ribose polymerase 1 (PARP1) is clinically important because of its synthetic lethality with breast cancer allele 1 and 2 mutations, which are causative for inherited breast and ovarian cancers. Biochemically, PARP1 is a single-stranded DNA break repair protein that is needed for preserving genomic integrity. In addition, PARP1 has been implicated in a veritable plethora of additional cellular pathways and thus its precise contribution(s) to human biology has remained obscure. To help address this def...
Source: Oncotarget - November 11, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Extracellular vesicles in oral squamous carcinoma carry oncogenic miRNA profile and reprogram monocytes via NF- κB pathway.
Extracellular vesicles in oral squamous carcinoma carry oncogenic miRNA profile and reprogram monocytes via NF-κB pathway. Oncotarget. 2018 Oct 05;9(78):34838-34854 Authors: Momen-Heravi F, Bala S Abstract Extracellular vesicles (EVs) are carriers of different biomacromolecules that participate in cellular signaling and disease pathogenesis. Although it has been shown that EVs can play an active role in cellular communication and different stages of cancer progression, the role of EVs in oral squamous cell carcinoma (OSCC) cancer pathogenesis, especially in the crosstalk of cancer cells with immu...
Source: Oncotarget - November 11, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Erratum: Targeting Metabolic Remodeling in Glioblastoma Multiforme.
Authors: Wolf A, Agnihotri S, Guha A Abstract [This corrects the article DOI: 10.18632/oncotarget.190.]. PMID: 30410682 [PubMed - in process] (Source: Oncotarget)
Source: Oncotarget - November 11, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Erratum: Drug Discovery Approaches to Target Wnt Signaling in Cancer Stem Cells.
Authors: Curtin JC, Lorenzi MV Abstract [This corrects the article DOI: 10.18632/oncotarget.191.]. PMID: 30410683 [PubMed - in process] (Source: Oncotarget)
Source: Oncotarget - November 11, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Bevacizumab as a chemoprotectant: reducing oxaliplatin induced hepatic sinusoidal injury.
Authors: Mizrahi JD, Overman MJ PMID: 30405879 [PubMed] (Source: Oncotarget)
Source: Oncotarget - November 9, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Genome-wide association analysis identifies SNPs predictive of in vitro leukemic cell sensitivity to cytarabine in pediatric AML.
Authors: Bargal SA, Rafiee R, Crews KR, Wu H, Cao X, Rubnitz JE, Ribeiro RC, Downing JR, Pounds SB, Lamba JK Abstract Cytarabine has been an integral part of acute myeloid leukemia (AML) chemotherapy for over four decades. However, development of resistance and high rates of relapse is a significant impediment in successfully treating AML. We performed a genome-wide association analysis (GWAS) and identified 113 (83 after adjusting for Linkage Disequilibrium) SNPs associated with in vitro cytarabine chemosensitivity of diagnostic leukemic cells from a cohort of 50 pediatric AML patients (p
Source: Oncotarget - November 9, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

High expression level of CD44v8-10 in cancer stem-like cells is associated with poor prognosis in esophageal squamous cell carcinoma patients treated with chemoradiotherapy.
Conclusion: High CD44v8-10 expression was an independent prognostic factor in E-SCC patients treated with dCRT. CD44v8-10-xCT-GSH axis inhibition sensitized CD44v8-10High E-SCC cells to ROS-inducing treatments such as radiotherapy. Targeting CD44v8-10-xCT-GSH axis may improve the prognosis of post-dCRT E-SCC patients. PMID: 30405881 [PubMed] (Source: Oncotarget)
Source: Oncotarget - November 9, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

The anti-psychotic drug pimozide is a novel chemotherapeutic for breast cancer.
In this study we further explore the inhibitory effects of this molecule in cancer cells. We found that Pimozide inhibited cell proliferation in a dose- and time-dependent manner in MDA-MB-231 breast cancer cells and A549 lung cancer cells. Furthermore, we found that Pimozide also promoted apoptosis as demonstrated by cell cycle arrest and induction of double-strand DNA breaks but did not result in any effect in the non-transformed MCF10A breast cell line. In order to shed new lights into the molecular pathways affected by Pimozide, we show that Pimozide downregulated RAN GTPase and AKT at both protein and mRNA levels and ...
Source: Oncotarget - November 9, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Variability in genes regulating vitamin D metabolism is associated with vitamin D levels in type 2 diabetes.
Authors: Bertoccini L, Bailetti D, SUMMER Study in Diabetes Group, Buzzetti R, Cavallo MG, Copetti M, Cossu E, D'Angelo P, De Cosmo S, Di Mauro L, Leonetti F, Morano S, Morviducci L, Napoli N, Prudente S, Pugliese G, Trischitta V, Baroni MG Abstract Mortality rate is increased in type 2 diabetes (T2D). Low vitamin D levels are associated with increased mortality risk in T2D. In the general population, genetic variants affecting vitamin D metabolism (DHCR7 rs12785878, CYP2R1 rs10741657, GC rs4588) have been associated with serum vitamin D. We studied the association of these variants with serum vitamin D in 2163 pat...
Source: Oncotarget - November 9, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Exosomal survivin facilitates vesicle internalization.
Authors: Gonda A, Kabagwira J, Senthil GN, Ferguson Bennit HR, Neidigh JW, Khan S, Wall NR Abstract Survivin, a member of the inhibitor of apoptosis (IAP) protein family plays a significant role in cell fate and function. It is significantly overexpressed in tumor cells and has been identified in most cancer cell types. A novel extracellular population has recently been identified and its function is still unknown. Emerging evidence continues to shed light on the important role the tumor microenvironment (TME) has on tumor survival and progression. This new population of survivin has been seen to enhance the tumor ...
Source: Oncotarget - November 9, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Aldoxorubicin and Temozolomide combination in a xenograft mice model of human glioblastoma.
Authors: Da Ros M, Iorio AL, De Gregorio V, Fantappiè O, Laffi G, de Martino M, Pisano C, Genitori L, Sardi I Abstract Glioblastoma Multiforme (GBM) is still an incurable disease. The front-line Temozolomide (TMZ)-based therapy suffers from poor efficacy, underlining the need of new therapies. Preclinically, Aldoxorubicin (Aldox), a novel prodrug of Doxorubicin (Dox), has been successfully tested against GBM, encouraging the study of its association with other agents. For the first time, we evaluated the effectiveness of Aldox combined to TMZ in preclinical models of GBM. Our in vitro results demonstrated th...
Source: Oncotarget - November 9, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Mechanisms through which lithocholic acid delays yeast chronological aging under caloric restriction conditions.
Authors: Arlia-Ciommo A, Leonov A, Mohammad K, Beach A, Richard VR, Bourque SD, Burstein MT, Goldberg AA, Kyryakov P, Gomez-Perez A, Koupaki O, Titorenko VI Abstract All presently known geroprotective chemical compounds of plant and microbial origin are caloric restriction mimetics because they can mimic the beneficial lifespan- and healthspan-extending effects of caloric restriction diets without the need to limit calorie supply. We have discovered a geroprotective chemical compound of mammalian origin, a bile acid called lithocholic acid, which can delay chronological aging of the budding yeast Saccharomyces cere...
Source: Oncotarget - November 9, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Generation and characterization of novel recombinant anti-hERG1 scFv antibodies for cancer molecular imaging.
In conclusion, the scFv-hERG1-Cys possesses features which make it a suitable tool for application in cancer molecular imaging. PMID: 30405887 [PubMed] (Source: Oncotarget)
Source: Oncotarget - November 9, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

MEK/CDK4,6 co-targeting is effective in a subset of NRAS, BRAF and 'wild type' melanomas.
In this study we investigate response patterns of NRAS, BRAF mutant and 'wild type' melanoma cells in vitro and in vivo when challenged with inhibitors of MEK, CDK4,6 and the combination of both. Data revealed, that in vitro growth response patterns of cells treated with the MEK/CDK4,6 combination correspond to in vivo efficacy of MEK/CDK4,6 co-targeting in melanoma xenograft models. Strikingly, this was consistently observed in NRAS and BRAF mutant, as well as in 'wild type' melanoma cells. Additionally, cells displaying elevated p-Rb levels after single MEK inhibition, showed more effective growth reduction with MEK/CDK4...
Source: Oncotarget - November 9, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Synergistic antitumor effect of a γ-secretase inhibitor PF-03084014 and sorafenib in hepatocellular carcinoma.
Synergistic antitumor effect of a γ-secretase inhibitor PF-03084014 and sorafenib in hepatocellular carcinoma. Oncotarget. 2018 Oct 09;9(79):34996-35007 Authors: Yang X, Xia W, Chen L, Wu CX, Zhang CC, Olson P, Wang XQ Abstract As a multi-kinase inhibitor, sorafenib is beneficial in around 30% of hepatocellular carcinoma (HCC) patients; however, HCC patients develop acquired drug resistance quickly. Clinical benefits of sorafenib, in combination with transarterial chemoembolization (TACE), radiotherapy, and other chemodrugs are limited. We investigated the efficacy and mechanisms of Notch signali...
Source: Oncotarget - November 9, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Effect of therapies-mediated modulation of telomere and/or telomerase on cancer cells radiosensitivity.
Authors: Assani G, Xiong Y, Zhou F, Zhou Y Abstract Cancer is one of the leading causes of death in the world. Many strategies of cancer treatment such as radiotherapy which plays a key role in cancer treatment are developed and used nowadays. However, the side effects post-cancer radiotherapy and cancer radioresistance are two major causes of the limitation of cancer radiotherapy effectiveness in the cancer patients. Moreover, reduction of the limitation of cancer radiotherapy effectiveness by reducing the side effects post-cancer radiotherapy and cancer radioresistance is the aim of several radiotherapy-oncologic...
Source: Oncotarget - November 9, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Correction: Regulation of Aldo-keto-reductase family 1 B10 by 14-3-3 ε and their prognostic impact of hepatocellular carcinoma.
Correction: Regulation of Aldo-keto-reductase family 1 B10 by 14-3-3ε and their prognostic impact of hepatocellular carcinoma. Oncotarget. 2018 Oct 09;9(79):35026 Authors: Liu TA, Jan YJ, Ko BS, Wu YJ, Lu YJ, Liang SM, Liu CC, Chen SC, Wang J, Shyue SK, Liou JY Abstract [This corrects the article DOI: 10.18632/oncotarget.5734.]. PMID: 30405891 [PubMed - in process] (Source: Oncotarget)
Source: Oncotarget - November 9, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Correction: Interaction between physical activity, PITX1 rs647161 genetic polymorphism and colorectal cancer risk in a Korean population: a case-control study.
Authors: Gunathilake MN, Lee J, Cho YA, Oh JH, Chang HJ, Sohn DK, Shin A, Kim J Abstract [This corrects the article DOI: 10.18632/oncotarget.24136.]. PMID: 30405892 [PubMed - in process] (Source: Oncotarget)
Source: Oncotarget - November 9, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

An HTS FP assay able to selectively identify STAT3-DBD inhibitors.
Authors: Meneghetti F, Barlocco D PMID: 30349637 [PubMed] (Source: Oncotarget)
Source: Oncotarget - October 25, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Can drug repurposing stop "chase and run" between aldehydes and reactive sulfur species in anti-cancer therapy?
Can drug repurposing stop "chase and run" between aldehydes and reactive sulfur species in anti-cancer therapy? Oncotarget. 2018 Oct 02;9(77):34453-34454 Authors: Suematsu M PMID: 30349638 [PubMed] (Source: Oncotarget)
Source: Oncotarget - October 25, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Unfolding the roles of resveratrol in p53 regulation.
Authors: Muniz de Queiroz R, Prives C PMID: 30349639 [PubMed] (Source: Oncotarget)
Source: Oncotarget - October 25, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research