Immunohistochemical analysis of RHAMM expression in normal and neoplastic human tissues: a cell cycle protein with distinctive expression in mitotic cells and testicular germ cells.
Authors: Chen YT, Chen Z, Du YN Abstract Expression of Receptor for Hyaluronic Acid Mediated Motility (RHAMM) increases cellular motility and RHAMM overexpression promotes invasive phenotype and metastasis of cancer cells. RHAMM has been suggested as a biomarker for poor prognosis in several tumor types, including lung, breast, colorectal, gastric, pancreatic ductal, and ovarian cancers. RNA studies showed restricted RHAMM expression in normal tissues, but its protein expression data in tissues were limited. In light of its potential as a prognostic marker and a therapeutic target, we performed immunohistochemical ...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

DHX9 regulates production of hepatitis B virus-derived circular RNA and viral protein levels.
Authors: Sekiba K, Otsuka M, Ohno M, Kishikawa T, Yamagami M, Suzuki T, Ishibashi R, Seimiya T, Tanaka E, Koike K Abstract Hepatitis B virus (HBV) infection, which is a major health concern worldwide, can lead to liver cirrhosis and hepatocellular carcinoma. Although current nucleos(t)ide analogs efficiently inhibit viral reverse transcription and viral DNA load clinically, episomal viral covalently closed circular DNA (cccDNA) minichromosomes and transcripts from cccDNA continue to be expressed over the long term. We hypothesized that, under these conditions, viral transcripts may have biological functions involve...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

20(S)-protopanaxadiol regio-selectively targets androgen receptor: anticancer effects in castration-resistant prostate tumors.
Authors: Ben-Eltriki M, Deb S, Hassona M, Meckling G, Fazli L, Chin MY, Lallous N, Yamazaki T, Jia W, Rennie PS, Cherkasov A, Tomlinson Guns ES Abstract We have explored the effects of 20(S)-protopanaxadiol (aPPD), a naturally derived ginsenoside, against androgen receptor (AR) positive castration resistant prostate cancer (CRPC) xenograft tumors and have examined its interactions with AR. In silico docking studies for aPPD binding to AR, alongside transactivation bioassays and in vivo efficacy studies were carried out in the castration-resistant C4-2 xenograft model. Immunohistochemical (IHC) and Western blot anal...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Wnt5a-induced cell migration is associated with the aggressiveness of estrogen receptor-positive breast cancer.
Authors: Kobayashi Y, Kadoya T, Amioka A, Hanaki H, Sasada S, Masumoto N, Yamamoto H, Arihiro K, Kikuchi A, Okada M Abstract Elevated expression of Wnt5a is associated with malignancy, cell invasion, and metastasis. The role of Wnt5a expression in breast cancer remains elusive. We investigated the significance of Wnt5a expression in breast cancer. The relationship between Wnt5a expression and clinicopathologic factors was assessed in invasive breast cancer (n = 178) resected at Hiroshima University Hospital between January 2011 and February 2014. Wnt5a was expressed in 69 of 178 cases (39%) of invasive breast cance...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Cancer cell-selective, clathrin-mediated endocytosis of aptamer decorated nanoparticles.
Authors: Engelberg S, Modrejewski J, Walter JG, Livney YD, Assaraf YG Abstract Lung cancer is the leading cause of cancer mortality worldwide, resulting in 88% deaths of all diagnosed patients. Hence, novel therapeutic modalities are urgently needed. Single-stranded oligonucleotide-based aptamers (APTs) are excellent ligands for tumor cell targeting. However, the molecular mechanisms underlying their internalization into living cells have been poorly studied. Towards the application of APTs for active drug targeting to cancer cells, we herein studied the mechanism underlying S15-APT internalization into human non-s...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Selective dissociation between LSD1 and GFI1B by a LSD1 inhibitor NCD38 induces the activation of ERG super-enhancer in erythroleukemia cells.
Authors: Yamamoto R, Kawahara M, Ito S, Satoh J, Tatsumi G, Hishizawa M, Suzuki T, Andoh A Abstract Lysine-specific demethylase 1 (LSD1) is a histone modifier for transcriptional repression involved in the regulation of hematopoiesis. We previously reported that a LSD1 inhibitor NCD38 induces transdifferentiation from erythroid lineage to granulomonocytic lineage and exerts anti-leukemia effect through de-repression of the specific super-enhancers of hematopoietic regulators including ERG in a human erythroleukemia cell line, HEL. However, the mechanistic basis for this specificity of NCD38 has remained unclear. He...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Targeting the mevalonate pathway is a novel therapeutic approach to inhibit oncogenic FoxM1 transcription factor in human hepatocellular carcinoma.
Authors: Ogura S, Yoshida Y, Kurahashi T, Egawa M, Furuta K, Kiso S, Kamada Y, Hikita H, Eguchi H, Ogita H, Doki Y, Mori M, Tatsumi T, Takehara T Abstract Dysregulation of cell metabolism is a hallmark of cancer. The mevalonate pathway in lipid metabolism has been implicated as a potential target of cancer therapy for hepatocellular carcinoma (HCC). The role of the Forkhead Box M1 (FoxM1) transcription factor in HCC development has been well documented, however, its involvement in cancer metabolism of HCC has not been fully determined. Here, we hypothesized that FoxM1 is involved in the mevalonate pathway of choles...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Increasing aggressiveness of patient-derived xenograft models of cervix carcinoma during serial transplantation.
This study showed that serially transplanted PDXs may not necessarily mirror the donor patients' diseases, and consequently, proper use of serially transplanted PDX models in translational cancer research requires careful molecular monitoring of the models. PMID: 29765518 [PubMed] (Source: Oncotarget)
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Long noncoding RNAs are associated with metabolic and cellular processes in the jejunum mucosa of pre-weaning calves in response to different diets.
Authors: Weikard R, Hadlich F, Hammon HM, Frieten D, Gerbert C, Koch C, Dusel G, Kuehn C Abstract Long noncoding RNAs (lncRNAs) emerged as important regulatory component of mechanisms involved in gene expression, chromatin modification and epigenetic processes, but they are rarely annotated in the bovine genome. Our study monitored the jejunum transcriptome of German Holstein calves fed two different milk diets using transcriptome sequencing (RNA-seq). To identify potential lncRNAs within the pool of unknown transcripts, four bioinformatic lncRNA prediction tools were applied. The intersection of the alignment-free...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Histogram analysis parameters of dynamic contrast-enhanced magnetic resonance imaging can predict histopathological findings including proliferation potential, cellularity, and nucleic areas in head and neck squamous cell carcinoma.
Authors: Surov A, Meyer HJ, Leifels L, Höhn AK, Richter C, Winter K Abstract Our purpose was to analyze possible associations between histogram analysis parameters of dynamic contrast-enhanced magnetic resonance imaging DCE MRI and histopathological findings like proliferation index, cell count and nucleic areas in head and neck squamous cell carcinoma (HNSCC). 30 patients (mean age 57.0 years) with primary HNSCC were included in the study. In every case, histogram analysis parameters of Ktrans, Ve, and Kep were estimated using a mathlab based software. Tumor proliferation index, cell count, and nucleic areas ...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Long term deficiency of vitamin D in germ cell testicular cancer survivors.
Authors: Nappi L, Ottaviano M, Rescigno P, Fazli L, Gleave ME, Damiano V, De Placido S, Palmieri G Abstract Background: Cisplatin-based chemotherapy significantly improved the survival of patients with germ cell testicular cancer. However, long term side effects of chemotherapy have non-negligible impact on the quality of life of these young patients, who have a long life expectancy after being successfully treated. Materials and Methods: 25-OH vitamin D, testosterone, FSH and LH of patients with testicular cancer were retrospectively evaluated and for each patient clinical information were collected. The tissu...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Establishment of preclinical chemotherapy models for gastroenteropancreatic neuroendocrine carcinoma.
Authors: Ohmoto A, Suzuki M, Takai E, Rokutan H, Fujiwara Y, Morizane C, Yanagihara K, Shibata T, Yachida S Abstract Gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) is a rare and devastating malignancy, and preclinical studies are needed to evaluate potential therapeutic regimens. Here, we examined the antitumor effects of cisplatin (CDDP), etoposide (ETP) and irinotecan (CPT-11) and their combinations on GEP-NEC using three small-cell GEP-NEC cell lines (pancreatic NEC, A99; esophageal NEC, TYUC-1; duodenum NEC, TCC-NECT-2). In vitro studies were conducted using cell viability assays. In vivo experiments...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Overexpressing TPTE2 (TPIP), a homolog of the human tumor suppressor gene PTEN, rescues the abnormal phenotype of the PTEN-/- mutant.
Authors: Lusche DF, Buchele EC, Russell KB, Soll BA, Vitolo MI, Klemme MR, Wessels DJ, Soll DR Abstract One possible approach to normalize mutant cells that are metastatic and tumorigenic, is to upregulate a functionally similar homolog of the mutated gene. Here we have explored this hypothesis by generating an overexpressor of TPTE2 (TPIP), a homolog of PTEN, in PTEN-/- mutants, the latter generated by targeted mutagenesis of a human epithelial cell line. Overexpression of TPTE2 normalized phenotypic changes associated with the PTEN mutation. The PTEN-/- -associated changes rescued by overexpressing TPTE2 included...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Cross-platform comparison for the detection of RAS mutations in cfDNA (ddPCR Biorad detection assay, BEAMing assay, and NGS strategy).
Authors: Garcia J, Forestier J, Dusserre E, Wozny AS, Geiguer F, Merle P, Tissot C, Ferraro-Peyret C, Jones FS, Edelstein DL, Cheynet V, Bardel C, Vilchez G, Xu Z, Bringuier PP, Barritault M, Brengle-Pesce K, Guillet M, Chauvenet M, Manship B, Brevet M, Rodriguez-Lafrasse C, Hervieu V, Couraud S, Walter T, Payen L Abstract CfDNA samples from colon (mCRC) and non-small cell lung cancers (NSCLC) (CIRCAN cohort) were compared using three platforms: droplet digital PCR (ddPCR, Biorad); BEAMing/OncoBEAM™-RAS-CRC (Sysmex Inostics); next-generation sequencing (NGS, Illumina), utilizing the 56G oncology panel (Swift ...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Clinical characteristics of non-small cell lung cancer harboring mutations in exon 20 of EGFR or HER2.
Authors: Takeda M, Sakai K, Hayashi H, Tanaka K, Tanizaki J, Takahama T, Haratani K, Nishio K, Nakagawa K Abstract Unlike common epidermal growth factor receptor gene (EGFR) mutations that confer sensitivity to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC), mutations in exon 20 of either EGFR or the human EGFR2 gene (HER2) are associated with insensitivity to EGFR-TKIs, with treatment options for patients with such mutations being limited. Clinical characteristics, outcome of EGFR-TKI or nivolumab treatment, and the presence of coexisting mutations were reviewed for NSCLC patients with exo...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Esophageal cancer cells resistant to T-DM1 display alterations in cell adhesion and the prostaglandin pathway.
Authors: Sauveur J, Matera EL, Chettab K, Valet P, Guitton J, Savina A, Dumontet C Abstract Trastuzumab-emtansine (T-DM1) is an antibody-drug conjugate that specifically targets HER2 thanks to its antibody component trastuzumab. In spite of responses to this novel agent, acquired resistance to treatment remains a major obstacle. Prolonged in vitro exposure of the gastroesophageal junction cancer cell line OE-19 to T-DM1, in the absence or presence of ciclosporin A resulted in the selection of two resistant cell lines to T-DM1. T-DM1-resistant cells presented an increased expression of adhesion genes, altered spread...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

LpMab-23-recognizing cancer-type podoplanin is a novel predictor for a poor prognosis of early stage tongue cancer.
Conclusions: LpMab-23 positive cases may be considered to present a useful predictor of poor prognosis for early stage tongue cancer. PMID: 29765527 [PubMed] (Source: Oncotarget)
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Metabolic changes associated with metformin potentiates Bcl-2 inhibitor, Venetoclax, and CDK9 inhibitor, BAY1143572 and reduces viability of lymphoma cells.
Authors: Chukkapalli V, Gordon LI, Venugopal P, Borgia JA, Karmali R Abstract Metformin exerts direct anti-tumor effects by activating AMP-activated protein kinase (AMPK), a major sensor of cellular metabolism in cancer cells. This, in turn, inhibits pro-survival mTOR signaling. Metformin has also been shown to disrupt complex 1 of the mitochondrial electron transport chain. Here, we explored the lymphoma specific anti-tumor effects of metformin using Daudi (Burkitt), SUDHL-4 (germinal center diffuse large B-cell lymphoma; GC DLBCL), Jeko-1 (Mantle-cell lymphoma; MCL) and KPUM-UH1 (double hit DLBCL) cell lines. We ...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

MYC gene amplification is a rare event in atypical fibroxanthoma and pleomorphic dermal sarcoma.
Authors: Gaiser T, Hirsch D, Orouji A, Bach M, Kind P, Helbig D, Quaas A, Utikal J, Marx A, Gaiser MR Abstract Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are rare malignancies typically occurring in elderly patients and predominantly located in skin regions exposed to UV-light. Thus, a role of UV-radiation-induced damage for AFX and PDS tumorigenesis has been postulated. MYC gene amplification has been demonstrated as a distinctive feature of radiation-induced angiosarcoma. In order to investigate whether chronic exposure to UV-light might also lead to MYC copy number changes, 51 AFX and 24 P...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Mean platelet volume as a predictive marker for venous thromboembolism in patients treated for Hodgkin lymphoma.
Authors: Rupa-Matysek J, Gil L, Barańska M, Dytfeld D, Komarnicki M Abstract Mean platelet volume (MPV) is reported to be associated with the risk of venous thromboembolism (VTE) and mortality in patients with cancer. We sought to determine the association of MPV with symptomatic VTE occurrence in patients treated for newly diagnosed Hodgkin lymphoma (HL) and their outcomes. We retrospectively studied 167 consecutive adult patients treated with HL. During first-line treatment 12 (7.2%) patients developed VTE and 14 (8%) died within the observation period. The pre-chemotherapy values of MPV were significantly lower...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Comparison of coronary artery bypass grafting and percutaneous coronary intervention in patients with heart failure with reduced ejection fraction and multivessel coronary artery disease.
Conclusions: In patients with HFrEF and multivessel CAD revascularization both with CABG and PCI resulted in similar survival rates. PCI is associated with increased risk of recurrent MI and urgent repeat revascularization, whereas the risk of stroke is similar in both methods. PMID: 29765531 [PubMed] (Source: Oncotarget)
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Chemopreventive activity of celastrol in drug-resistant human colon carcinoma cell cultures.
Authors: Moreira H, Szyjka A, Gąsiorowski K Abstract Celastrol (tripterine) a pentacyclic triterpenoid extracted from the roots of Tripterygium wilfordii Hook f., exhibits potent antioxidant and anti-inflammatory activity and also exerts important anti-cancer effects, as induction of apoptosis and lowering the level of drug resistance of several cancers. Increased level of cellular resistance to cytostatic drugs is typical for colorectal cancers, and largely determines the failure of chemotherapy for this tumor. The purpose of our research was to evaluate the chemopreventive effect of celastrol on cultures of colo...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

GSTM1, GSTT1, and GSTP1 polymorphisms and colorectal cancer risk in Polish nonsmokers.
This study assessed potential relationships between GSTM1, GSTT1, and GSTP1 polymorphisms and colorectal cancer (CRC) risk in Polish nonsmokers. We also analyzed the influence of GST gene polymorphisms on CRC clinical and histopathological features. Our study included 197 CRC patients and 104 healthy controls. GSTM1, GSTT1, and GSTP1 polymorphisms were evaluated using qPCR. Polymorphism frequencies observed in our control group corresponded to those in other European populations. The GSTM1 null and GSTT1 null genotypes were observed with similar frequencies in both CRC patients and controls (GSTM1 null: 46.7% vs. 45.2%; GS...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

BI2536 induces mitotic catastrophe and radiosensitization in human oral cancer cells.
Authors: Cheng CY, Liu CJ, Huang YC, Wu SH, Fang HW, Chen YJ Abstract BI2536 has been developed as a potential therapeutic agent for various cancers but not in oral cancer cells. Since BI2536 exhibits mitosis-regulating activity which are the most radiosensitive, we hypothesized that BI2536 might modulate the radiosensitivity of oral cancer cells. Human normal fibroblasts, oral cancer SAS, and OECM1 cells were treated with BI2536 (0-50 nM) and/or radiation (0-4 Gy). MTT assay, Liu's staining, flow cytometry, clonogenic assay, Annexin V/propidium iodide (PI) staining, western blot analysis, and small interfering RNA...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Effects of CB2 and TRPV1 receptors' stimulation in pediatric acute T-lymphoblastic leukemia.
Authors: Punzo F, Manzo I, Tortora C, Pota E, Angelo V, Bellini G, Di Paola A, Verace F, Casale F, Rossi F Abstract T-Acute Lymphoblastic Leukemia (T-ALL) is less frequent than B-ALL, but it has poorer outcome. For this reason new therapeutic approaches are needed to treat this malignancy. The Endocannabinoid/Endovanilloid (EC/EV) system has been proposed as possible target to treat several malignancies, including lymphoblastic diseases. The EC/EV system is composed of two G-Protein Coupled Receptors (CB1 and CB2), the Transient Potential Vanilloid 1 (TRPV1) channel, their endogenous and exogenous ligands and enzym...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Predicting hepatocellular carcinoma through cross-talk genes identified by risk pathways.
Authors: Liu L, Pang L, Wang Y, Hu M, Shao Z, Huo D, Zhang D, Xie H, Yang J, Liu Q, Chen X Abstract Hepatocellular carcinoma (HCC) is the most frequent type of liver cancer with poor survival rate and high mortality. Despite efforts on the mechanism of HCC, new molecular markers are needed for exact diagnosis, evaluation and treatment. Here, we combined transcriptome of HCC with networks and pathways to identify reliable molecular markers. Through integrating 249 differentially expressed genes with syncretic protein interaction networks, we constructed a HCC-specific network, from which we further extracted 480 piv...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

STAT3-activated CD36 facilitates fatty acid uptake in chronic lymphocytic leukemia cells.
Authors: Rozovski U, Harris DM, Li P, Liu Z, Jain P, Ferrajoli A, Burger J, Thompson P, Jain N, Wierda W, Keating MJ, Estrov Z Abstract Although several studies established that unlike normal B cells chronic lymphocytic leukemia (CLL) cells metabolize fatty acids (FA), how CLL cells internalize FA is poorly understood. Because in various cell types CD36 facilitates FA uptake, we wondered whether a similar mechanism is operative CLL. We found that CD36 levels are higher in CLL cells than in normal B cells, and that small interfering RNA, CD36 neutralizing antibodies or sulfosuccinimidyl oleate (SSO) that inhibits CD...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Prognostic value of the DNA integrity index in patients with malignant lung tumors.
Conclusion: The results of this study show a potential use of Alu repeats ratios for prognostic purposes in the advanced setting for lung cancer patients. PMID: 29765538 [PubMed] (Source: Oncotarget)
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

CRM1/XPO1 expression in pancreatic adenocarcinoma correlates with survivin expression and the proliferative activity.
Authors: Saulino DM, Younes PS, Bailey JM, Younes M Abstract CRM1/XPO1 (CRM1) is a nuclear export chaperone that mediates the export of proteins essential to growth regulation and tumor suppression. Its overexpression in tumors was found to be associated with poor prognosis. Selective inhibitors of nuclear export are in phase I and II clinical trials for several tumor types. Our aim was to investigate CRM1 expression in pancreatic adenocarcinoma (PAC) and its relationship to survivin expression and the proliferative activity. Sections of tissue microarray containing 76 formalin fixed and paraffin embedded PAC were ...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Could a plant derived protein potentiate the anticancer effects of a stem cell in brain cancer?
In conclusion, these results indicate that in cocultured MSC/U87 cells EcTI impairs the metabolic activity, proliferation, and reduced invasion, possibly associated with observed cytokines secretion. In this context, we confirmed that the plant derived protein potentiated the anticancer effects, induced by MSC, as represented by GBM U87 cell line. PMID: 29765540 [PubMed] (Source: Oncotarget)
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

The effect of antiviral therapy on serum lipid profiles in chronic hepatitis C.
Conclusion: The clearance of the HCV RNA is the main determinant of the increase of lipids after PegIFN/RBV treatment. However advanced fibrosis also has an effect in increase of lipids after the treatment. PMID: 29765541 [PubMed] (Source: Oncotarget)
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

SMAR1 inhibits Wnt/ β-catenin signaling and prevents colorectal cancer progression.
SMAR1 inhibits Wnt/β-catenin signaling and prevents colorectal cancer progression. Oncotarget. 2018 Apr 20;9(30):21322-21336 Authors: Taye N, Alam A, Ghorai S, Chatterji DG, Parulekar A, Mogare D, Singh S, Sengupta P, Chatterjee S, Bhat MK, Santra MK, Salunkhe PB, Finston SK, Chattopadhyay S Abstract Reduced expression of Scaffold/Matrix Attachment Region Binding Protein 1 (SMAR1) is associated with various cancers resulting in poor prognosis of the diseases. However, the precise underlying mechanism elucidating the loss of SMAR1 requires ongoing study. Here, we show that SMAR1 is highly downregul...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

IgG4-related kidney disease: the effects of a Rituximab-based immunosuppressive therapy.
Authors: Quattrocchio G, Barreca A, Demarchi A, Solfietti L, Beltrame G, Fenoglio R, Ferro M, Mesiano P, Murgia S, Del Vecchio G, Massara C, Rollino C, Roccatello D Abstract IgG4-related disease (IgG4-RD) is a recently recognized disorder, characterized by elevated serum IgG4 concentrations, dense tissue infiltration of IgG4-positive plasma cells and storiform fibrosis. Treatment is usually based on steroids, however, relapses and long-term adverse effects are frequent. We prospectively studied 5 consecutive patients with histologically-proven IgG4-RD and renal involvement, treated with an extended Rituximab protoc...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Comparison of infectivity and spread between HSV-1 and HSV-2 based oncolytic viruses on tumor cells with different receptor expression profiles.
Authors: Fu X, Tao L, Wang PY, Cripe TP, Zhang X Abstract Herpes simplex virus (HSV) is one of the many viruses that have been modified or adapted for oncolytic purposes. There are two serotypes of HSV, HSV-1 and HSV-2. The majority of oncolytic HSVs, including T-VEC which has recently been approved by the US Food and Drug Administration (FDA) for clinical use in treating late stage melanoma patients, are derived from HSV-1. Recently, we and others have developed several HSV-2 based oncolytic viruses. During our in vitro characterization of oncolytic viruses developed from both serotypes (Baco-1 from HSV-1 and FusO...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Multi-institution analysis of racial disparity among African-American men eligible for prostate cancer active surveillance.
Authors: Dinizo M, Shih W, Kwon YS, Eun D, Reese A, Giusto L, Trabulsi EJ, Yuh B, Ruel N, Marchalik D, Hwang J, Kundu SD, Eggener S, Kim IY Abstract There is a significant controversy on whether race should be a factor in considering active surveillance for low-risk prostate cancer. To address this question, we analyzed a multi-institution database to assess racial disparity between African-American and White-American men with low risk prostate cancer who were eligible for active surveillance but underwent radical prostatectomy. A retrospective analysis of prospectively collected clinical, pathologic and oncologic ...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Proteomic screening identifies the zonula occludens protein ZO-1 as a new partner for ADAM12 in invadopodia-like structures.
Authors: Dekky B, Ruff M, Bonnier D, Legagneux V, Théret N Abstract The epithelial mesenchymal transition (EMT) is a key process for cancer cell invasion and migration. This complex program whereby epithelial tumor cells loose polarity and acquire mesenchymal phenotype is driven by the regulation of cell-cell adhesion and cell-substrate interactions. We recently described the association of ADAM12 with EMT and we now use immunoprecipitation and proteomic approaches to identify interacting partners for ADAM12 during EMT. We identify twenty proteins that are involved in molecular mechanisms associated with adh...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Signature program: a platform of basket trials.
Authors: Slosberg ED, Kang BP, Peguero J, Taylor M, Bauer TM, Berry DA, Braiteh F, Spira A, Meric-Bernstam F, Stein S, Piha-Paul SA, Salvado A Abstract Investigating targeted therapies can be challenging due to diverse tumor mutations and slow patient accrual for clinical studies. The Signature Program is a series of 8 phase 2, agent-specific basket protocols using a rapid study start-up approach involving no predetermined study sites. Each protocol evaluated 1 agent (buparlisib, dovitinib, binimetinib, encorafenib, sonidegib, BGJ398, ceritinib, or ribociclib) in patients with solid or hematologic malignancies and ...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Transformation of mouse T cells requires MYC and AKT activity in conjunction with inhibition of intrinsic apoptosis.
Authors: Högstrand K, Darmanin S, Forshell TP, Grandien A Abstract Peripheral T-cell lymphoma is an aggressive non-Hodgkin's lymphoma characterized by excessive proliferation of transformed mature T cells. The number and nature of genetic aberrations required and sufficient for transformation of normal T cells into lymphomas is unknown. Here, using a combinatorial in vitro-approach, we demonstrate that overexpression of MYC together with activated AKT in conditions of inhibition of intrinsic apoptosis rapidly resulted in transformation of mature mouse T cells with a frequency approaching 100%. Injection of tra...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Deregulation of methylation of transcribed-ultra conserved regions in colorectal cancer and their value for detection of adenomas and adenocarcinomas.
Authors: Kottorou AE, Antonacopoulou AG, Dimitrakopoulos FD, Diamantopoulou G, Sirinian C, Kalofonou M, Theodorakopoulos T, Oikonomou C, Katsakoulis EC, Koutras A, Makatsoris T, Demopoulos N, Stephanou G, Stavropoulos M, Thomopoulos KC, Kalofonos HP Abstract Expression of Transcribed Ultraconserved Regions (T-UCRs) is often deregulated in cancer. The present study assesses the expression and methylation of three T-UCRs (Uc160, Uc283 and Uc346) in colorectal cancer (CRC) and explores the potential of T-UCR methylation in circulating DNA for the detection of adenomas and adenocarcinomas. Expression levels of Uc160, U...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

MTBP inhibits the Erk1/2-Elk-1 signaling in hepatocellular carcinoma.
Authors: Ranjan A, Iyer SV, Ward C, Link T, Diaz FJ, Dhar A, Tawfik OW, Weinman SA, Azuma Y, Izumi T, Iwakuma T Abstract Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and the prognosis of HCC patients, especially those with metastasis, remains extremely poor. This is partly due to unclear molecular mechanisms underlying HCC metastasis. Our previous study indicates that MDM2 Binding Protein (MTBP) suppresses migration and metastasis of HCC cells. However, signaling pathways regulated by MTBP remain unknown. To identify metastasis-associated signaling pathways governed by MTBP, we have p...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Functional significance of co-occurring mutations in PIK3CA and MAP3K1 in breast cancer.
Authors: Avivar-Valderas A, McEwen R, Taheri-Ghahfarokhi A, Carnevalli LS, Hardaker EL, Maresca M, Hudson K, Harrington EA, Cruzalegui F Abstract The PI3Kα signaling pathway is frequently hyper-activated in breast cancer (BrCa), as a result of mutations/amplifications in oncogenes (e.g. HER2), decreased function in tumor suppressors (e.g. PTEN) or activating mutations in key components of the pathway. In particular, activating mutations of PIK3CA (~45%) are frequently found in luminal A BrCa samples. Genomic studies have uncovered inactivating mutations in MAP3K1 (13-20%) and MAP2K4 (~8%), two upstream kinase...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Higher enterococcus counts indicate a lower risk of colorectal adenomas: a prospective cohort study.
Authors: Kawano A, Ishikawa H, Mutoh M, Kubota H, Matsuda K, Tsuji H, Matsumoto K, Nomoto K, Tanaka R, Nakamura T, Wakabayashi K, Sakai T Abstract Intestinal bacteria play an important role in human health. This prospective cohort study aimed to investigate the relationship between the abundance of different intestinal bacteria and the risk of developing colorectal cancer (CRC). Fecal samples from CRC patients (n = 157) were collected at the start of the study wherein patients subsequently underwent endoscopy to remove polyps. Gut bacteria were isolated by using specific culture methods and the fecal counts of vari...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Acquired resistance to everolimus in aromatase inhibitor-resistant breast cancer.
Authors: Kimura M, Hanamura T, Tsuboi K, Kaneko Y, Yamaguchi Y, Niwa T, Narui K, Endo I, Hayashi SI Abstract We previously reported the establishment of several types of long-term estrogen-depleted-resistant (EDR) cell lines from MCF-7 breast cancer cells. Type 1 EDR cells exhibited the best-studied mechanism of aromatase inhibitor (AI) resistance, in which estrogen receptor (ER) expression remained positive and PI3K signaling was upregulated. Type 2 EDR cells showed reduced ER activity and upregulated JNK-related signaling. The mTOR inhibitor everolimus reduced growth in cells similar to Type 1 EDR cells. The pres...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Targeted nanoparticle delivery of therapeutic antisense microRNAs presensitizes glioblastoma cells to lower effective doses of temozolomide in vitro and in a mouse model.
Authors: Malhotra M, Sekar TV, Ananta JS, Devulapally R, Afjei R, Babikir HA, Paulmurugan R, Massoud TF Abstract Temozolomide (TMZ) chemotherapy for glioblastoma (GBM) is generally well tolerated at standard doses but it can cause side effects. GBMs overexpress microRNA-21 and microRNA-10b, two known oncomiRs that promote cancer development, progression and resistance to drug treatment. We hypothesized that systemic injection of antisense microRNAs (antagomiR-21 and antagomiR-10b) encapsulated in cRGD-tagged PEG-PLGA nanoparticles would result in high cellular delivery of intact functional antagomiRs, with conseque...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

A protein folding molecular imaging biosensor monitors the effects of drugs that restore mutant p53 structure and its downstream function in glioblastoma cells.
Authors: Paulmurugan R, Afjei R, Sekar TV, Babikir HA, Massoud TF Abstract Misfolding mutations in the DNA-binding domain of p53 alter its conformation, affecting the efficiency with which it binds to chromatin to regulate target gene expression and cell cycle checkpoint functions in many cancers, including glioblastoma. Small molecule drugs that recover misfolded p53 structure and function may improve chemotherapy by activating p53-mediated senescence. We constructed and optimized a split Renilla luciferase (RLUC) complementation molecular biosensor (NRLUC-p53-CRLUC) to determine small molecule-meditated folding c...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Antibody-assisted target identification reveals afatinib, an EGFR covalent inhibitor, down-regulating ribonucleotide reductase.
Authors: Yu CH, Chou CC, Tu HF, Huang WC, Ho YY, Khoo KH, Lee MS, Chang GD Abstract Afatinib, used for the first-line treatment of non-small-cell lung carcinoma (NSCLC) patients with distinct epidermal growth factor receptor (EGFR) mutations, inactivates EGFR by mimicking ATP structure and forming a covalent adduct with EGFR. We developed a method to unravel potential targets of afatinib in NSCLC cells through immunoprecipitation of afatinib-labeling proteins with anti-afatinib antiserum and mass spectrometry analysis. Ribonucleotide reductase (RNR) is one of target proteins of afatinib revealed by this method. Tre...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Coffee consumption and risk of myocardial infarction: a dose-response meta-analysis of observational studies.
Authors: Mo L, Xie W, Pu X, Ouyang D Abstract Background: Previous epidemiological studies have provided inconsistent conclusions on the effect of coffee consumption in the development of myocardial infarction (MI). The aim of the study was to evaluate the influence of coffee consumption and its potential dose-response patterns on the risk of developing MI. Materials and Methods: Three databases were searched for evidence of eligible studies. A random-effects model was used to pool the fully adjusted odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). Dose-response analysis was performed to ...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

The fallopian tube microbiome: implications for reproductive health.
Authors: Pelzer ES, Willner D, Buttini M, Hafner LM, Theodoropoulos C, Huygens F Abstract Objective: There is a paucity of data characterizing the microbiota of the female upper genital tract, which controversially is described as a sterile site. We examine whether the fallopian tube harbours an endogenous microbial community. Design: This prospective study collected from women undergoing total hysterectomy or salpingectomy-oophorectomy. Setting: Private hospital gynaecology department. Patients: Fallopian tubes were collected from women diagnosed with benign disease or for prophylaxis. Intervention...
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Patients with high serum substance P levels previously to liver transplantation for hepatocellular carcinoma have higher risk of one-year liver transplantation mortality.
Conclusions: We believe that our study is the first study reporting data on circulating levels of substance P previously to LT for HCC, and an association between elevated levels of serum substance P before LT and mortality during the first year of LT. PMID: 29765559 [PubMed] (Source: Oncotarget)
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Transarterial chemoembolization as a substitute to radiofrequency ablation for treating Barcelona Clinic Liver Cancer stage 0/A hepatocellular carcinoma.
This study aimed to elucidate the prognosis for BCLC stage 0/A HCC patients treated with TACE or with radiofrequency ablation (RFA). Materials and Methods: The prognosis of 242 BCLC stage 0/A HCC patients within Milan criteria who underwent initially TACE or RFA were retrospectively analyzed using propensity score matching analysis. Results: The analyses of baseline patient characteristics revealed that the maximum tumor size and the proportion of BCLC stage A patients were significantly higher in patients treated with TACE than in those treated with RFA (P
Source: Oncotarget - May 18, 2018 Category: Cancer & Oncology Tags: Oncotarget Source Type: research