Pathogenic mutations and overall survival in 3,084 patients with cancer: the Hellenic Cooperative Oncology Group Precision Medicine Initiative.
Authors: Fountzilas E, Kotoula V, Koliou GA, Giannoulatou E, Gogas H, Papadimitriou C, Tikas I, Zhang J, Papadopoulou K, Zagouri F, Christodoulou C, Koutras A, Makatsoris T, Chrisafi S, Linardou H, Varthalitis I, Papatsibas G, Razis E, Papakostas P, Samantas E, Aravantinos G, Bafaloukos D, Kosmidis P, Koumarianou A, Psyrri A, Pentheroudakis G, Pectasides D, Futreal A, Fountzilas G, Tsimberidou AM Abstract Background: We evaluated the association between pathogenic mutations and overall survival (OS) in patients with cancer referred to Hellenic Cooperative Oncology Group-affiliated Departments. Patients and methods:...
Source: Oncotarget - February 1, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Evaluation of the genomic alterations in the androgen receptor gene during treatment with high-dose testosterone for metastatic castrate-resistant prostate cancer.
CONCLUSIONS: HDT led to a decrease in AR copy number and mutations which was independent from responses to therapy. Further understanding of the genomic alterations as potential predictor of response to HDT is needed. PMID: 32002120 [PubMed] (Source: Oncotarget)
Source: Oncotarget - February 1, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

PDLIM4/RIL-mediated regulation of Src and malignant properties of breast cancer cells.
Authors: Kravchenko DS, Ivanova AE, Podshivalova ES, Chumakov SP Abstract RIL/PDLIM4 gene was identified as a tumor suppressor, its expression is frequently altered in various types of malignancies. The product of RIL/PDLIM4 gene is an adapter protein involved in the actin cytoskeleton remolding and assembly of stress fibers crucial for cell motility and epithelial-mesenchymal transition. Although the exact mechanism tethering RIL to cancer development remains unknown some pieces of evidence suggest that RIL may act by suppressing activation of the proto-oncogene tyrosine-protein kinase Src. To further explore this...
Source: Oncotarget - February 1, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Novel functional anti-HER3 monoclonal antibodies with potent anti-cancer effects on various human epithelial cancers.
Authors: Okita K, Okazaki S, Uejima S, Yamada E, Kaminaka H, Kondo M, Ueda S, Tokiwa R, Iwata N, Yamasaki A, Hayashi N, Ogura D, Hirotani K, Yoshioka T, Inoue M, Masuko K, Masuko T Abstract Resistance of progressive cancers against chemotherapy is a serious clinical problem. In this context, human epidermal growth factor receptor 3 (HER3) can play important roles in drug resistance to HER1- and HER2- targeted therapies. Since clinical testing of anti-HER3 monoclonal antibodies (mAbs) such as patritumab could not show remarkable effect compared with existing drugs, we generated novel mAbs against anti-HER3. Novel ra...
Source: Oncotarget - February 1, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

The synergistic inhibitory effect of combining therapies targeting EGFR and mitochondria in sarcomas.
Authors: Wang X, Yeo RX, Hogg PJ, Goldstein D, Crowe P, Dilda PJ, Yang JL Abstract Our group previously demonstrated that sarcoma cell lines were insensitive to epidermal growth factor receptor (EGFR) inhibitor gefitinib monotherapy. PENAO, an anti-tumour metabolic compound created in our laboratory, is currently in clinical trials. Considering the positive regulation of tumour energy production by both the EGFR signalling and tumour metabolism pathways, this study aimed to investigate the effect and mechanisms of combination therapy using gefitinib and PENAO in sarcoma cell lines in vitro and in vivo. PENAO monoth...
Source: Oncotarget - February 1, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Toxoplasma gondii GRA8-derived peptide immunotherapy improves tumor targeting of colorectal cancer.
Authors: Kim JS, Lee D, Kim D, Mun SJ, Cho E, Son W, Yang CS Abstract Targeted tumor and efficient, specific biological drug delivery in vivo has been one of the main challenges in protein-based cancer-targeted therapies. Mitochondria are potential therapeutic targets for various anti-cancer drugs. We have previously reported that protein kinase Cα-mediated phosphorylation of Toxoplasma gondii GRA8 is required for mitochondrial trafficking and regulating the interaction of the C-terminal of GRA8 with ATP5A1/SIRT3 in mitochondria. Furthermore, SIRT3 facilitates ATP5A1 deacetylation, mitochondrial activation, a...
Source: Oncotarget - February 1, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

A novel function of AAA-ATPase p97/VCP in the regulation of cell motility.
Authors: Khong ZJ, Lai SK, Koh CG, Geifman-Shochat S, Li HY Abstract High level of the multifunctional AAA-ATPase p97/VCP is often correlated to the development of cancer; however, the underlying mechanism is not understood completely. Here, we report a novel function of p97/VCP in actin regulation and cell motility. We found that loss of p97/VCP promotes stabilization of F-actin, which cannot be reversed by actin-destabilizing agent, Cytochalasin D. Live-cell imaging demonstrated reduced actin dynamics in p97/VCP-knockdown cells, leading to compromised cell motility. We further examined the underlying mechanism an...
Source: Oncotarget - February 1, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Baseline neutrophil-to-lymphocyte ratio and c-reactive protein predict efficacy of treatment with bevacizumab plus paclitaxel for locally advanced or metastatic breast cancer.
Authors: Miyagawa Y, Yanai A, Yanagawa T, Inatome J, Egawa C, Nishimukai A, Takamoto K, Morimoto T, Kikawa Y, Suwa H, Taji T, Yamaguchi A, Okada Y, Sata A, Fukui R, Bun A, Ozawa H, Higuchi T, Fujimoto Y, Imamura M, Miyoshi Y Abstract The effect of bevacizumab plus paclitaxel therapy on progression-free survival (PFS) is prominent; however, no overall survival (OS) benefit has been demonstrated. Our aim was to study the predictive efficacy of peripheral immune-related parameters, neutrophil-to-lymphocyte ratio (NLR), absolute lymphocyte count (ALC), and c-reactive protein (CRP) in locally advanced and metastatic bre...
Source: Oncotarget - February 1, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Identification of signature genes associated with therapeutic resistance to anti-VEGF therapy.
Authors: Jaiprasart P, Dogra S, Neelakantan D, Devapatla B, Woo S Abstract VEGF-mediated tumor angiogenesis is a validated clinical target in many cancers, but modest efficacy and rapid development of resistance are major challenges of VEGF-targeted therapies. To establish a molecular signature of this resistance in ovarian cancer, we developed preclinical tumor models of adaptive resistance to chronic anti-VEGF treatment. We performed RNA-seq analysis and reverse-phase protein array to compare changes in gene and protein expressions in stroma and cancer cells from resistant and responsive tumors. We identified a u...
Source: Oncotarget - February 1, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Correction: Upregulation of microRNA-125b by G-CSF promotes metastasis in colorectal cancer.
Authors: Zhang X, Ma X, An H, Xu C, Cao W, Yuan W, Ma J Abstract [This corrects the article DOI: 10.18632/oncotarget.16892.]. PMID: 32002128 [PubMed - in process] (Source: Oncotarget)
Source: Oncotarget - February 1, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Mesothelioma: Hippo pathway as a target, lessons from COMMAND.
Authors: Fennell DA, Baitei EY PMID: 31976036 [PubMed] (Source: Oncotarget)
Source: Oncotarget - January 26, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Targeting the non-canonical roles of PCNA modifies and increases the response to targeted anti-cancer therapy.
In this study, we show how targeting PCNA increased the anti-cancer activity of EGFR/HER2/VEGFR inhibition in vitro as well as in vivo. The combination treatment resulted in reduced tumor load and increased the survival compared to either single agent treatments. The combination treatment affected multiple cellular signaling responses not seen by EGFR/HER2/VEGFR inhibition alone, and changes were seen in pathways determining protein degradation, ER-stress, apoptosis and autophagy. Our results suggest that targeting the non-canonical roles of PCNA in cellular signaling have the potential to improve targeted therapies. P...
Source: Oncotarget - January 12, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Probiotic Propionibacterium freudenreichii requires SlpB protein to mitigate mucositis induced by chemotherapy.
Authors: do Carmo FLR, Rabah H, Cordeiro BF, da Silva SH, Pessoa RM, Fernandes SOA, Cardoso VN, Gagnaire V, Deplanche M, Savassi B, Figueiroa A, Oliveira ER, Fonseca CC, Queiroz MIA, Rodrigues NM, Sandes SHC, Nunes ÁC, Lemos L, Alves JL, Faria AMC, Ferreira Ê, Le Loir Y, Jan G, Azevedo V Abstract Propionibacterium freudenreichii CIRM-BIA 129 (P. freudenreichii wild type, WT) is a probiotic bacterium, which exerts immunomodulatory effects. This strain possesses extractable surface proteins, including SlpB, which are involved in anti-inflammatory effect and in adhesion to epithelial cells. We decide...
Source: Oncotarget - January 12, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Low-dose metronomic cyclophosphamide complements the actions of an intratumoral C-class CpG TLR9 agonist to potentiate innate immunity and drive potent T cell-mediated anti-tumor responses.
Authors: Leong WI, Ames RY, Haverkamp JM, Torres L, Kline J, Bans A, Rocha L, Gallotta M, Guiducci C, Coffman RL, Janatpour MJ Abstract The synthetic oligonucleotide SD-101 is a potent and specific agonist for toll-like receptor 9. Intratumoral injection of SD-101 induces significant anti-tumor immunity in preclinical and clinical studies, especially when combined with PD-1 blockade. To build upon this strategy, we studied the enhancement of SD-101 activities by combination with low-dose cyclophosphamide, a well-characterized agent with potentially complementary activities. In multiple mouse tumor models, we demons...
Source: Oncotarget - January 12, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Dysregulation of adenosine kinase isoforms in breast cancer.
In this study, we examined the expression profiles of ADK isoforms in breast cancer tissues from 46 patient and followed up with an in vitro investigation by knocking down the expression of ADK-L or ADK-S using CRISPR gene editing to evaluate the role of ADK isoform in cancer progression and metastasis of cultured triple-negative breast cancer cell line MDA-MB-231. We demonstrated that (i) ADK-L expression level was significantly increased in breast cancer tissues versus paired normal tissues adjacent to tumor, whereas the ADK-S expression levels were not significantly different between cancerous and normal tissues; (ii) C...
Source: Oncotarget - January 12, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Head and neck squamous cancer progression is marked by CLIC4 attenuation in tumor epithelium and reciprocal stromal upregulation of miR-142-3p, a novel post-transcriptional regulator of CLIC4.
Authors: Carofino BL, Dinshaw KM, Ho PY, Cataisson C, Michalowski AM, Ryscavage A, Alkhas A, Wong NW, Koparde V, Yuspa SH Abstract Chloride intracellular channel 4 (CLIC4) is a tumor suppressor implicated in processes including growth arrest, differentiation, and apoptosis. CLIC4 protein expression is diminished in the tumor parenchyma during progression in squamous cell carcinoma (SCC) and other neoplasms, but the underlying mechanisms have not been identified. Data from The Cancer Genome Atlas suggest this is not driven by genomic alterations. However, screening and functional assays identified miR-142-3p as a re...
Source: Oncotarget - January 12, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Effects of neoadjuvant FOLFIRONOX and gemcitabine-based chemotherapy on cancer cell survival and death in patients with pancreatic ductal adenocarcinoma.
Authors: Xie L, Xia L, Klaiber U, Sachsenmaier M, Hinz U, Bergmann F, Strobel O, Büchler MW, Neoptolemos JP, Fortunato F, Hackert T Abstract Background: The progression and response to systemic treatment of cancer is substantially dependent on the balance between cancer cell death (apoptosis and necroptosis) and cancer cell survival (autophagy). Although well characterized in experimental systems, the status of cancer cell survival and cell death in human pancreatic ductal adenocarcinoma (PDAC), especially in response to chemotherapy and different types of chemotherapy is poorly described. Results: The median ...
Source: Oncotarget - January 12, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Schwann cell reprogramming and lung cancer progression: a meta-analysis of transcriptome data.
In this study, we report valuable data for further experimental and clinical analysis, because the proposed biomolecules have significant potential as systems biomarkers for screening or for therapeutic purposes in perineural invasion of lung cancer. PMID: 31921388 [PubMed] (Source: Oncotarget)
Source: Oncotarget - January 12, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Single cell correlation analysis of liquid and solid biopsies in metastatic colorectal cancer.
Authors: Gerdtsson AS, Thiele JA, Shishido SN, Zheng S, Schaffer R, Bethel K, Curley S, Lenz HJ, Hanna DL, Nieva J, Kolatkar A, Ruiz C, Rodriguez-Lee M, Oakley Iii GJ, Lee JSH, Hicks J, Kuhn P Abstract As cancer care is transitioning to personalized therapies with necessary complementary or companion biomarkers there is significant interest in determining to what extent non-invasive liquid biopsies reflect the gold standard solid biopsy. We have established an approach for measuring patient-specific circulating and solid cell concordance by introducing tumor touch preparations to the High-Definition Single Cell Ana...
Source: Oncotarget - January 8, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Gas6/MerTK signaling is negatively regulated by NF- κB and supports lung carcinogenesis.
Gas6/MerTK signaling is negatively regulated by NF-κB and supports lung carcinogenesis. Oncotarget. 2019 Dec 17;10(66):7031-7042 Authors: Novitskiy SV, Zaynagetdinov R, Vasiukov G, Gutor S, Han W, Serezani A, Matafonov A, Gleaves LA, Sherrill TP, Polosukhin VV, Blackwell TS Abstract Growth arrest-specific 6 (Gas6) has been implicated in carcinogenesis through activation of its receptors, particularly MerTK. To investigate whether Gas6 plays a role in resistance to NF-κB inhibitors, which have not proven to be effective agents for lung cancer therapy, we studied lung cancer models induced by...
Source: Oncotarget - January 8, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

IGFBP-2 acts as a tumour suppressor and plays a role in determining chemosensitivity in bladder cancer cells.
In this study we determined the role that IGFBP-2 played on the phenotype and chemosensitivity of a selection of bladder cancer cell lines and investigated how the abundance of IGFBP-2 was regulated. We found that IGFBP-2 was more abundant in the epithelial bladder cancer cells, RT4 and UMUC3 and absent in the more mesenchymal T24 and TCCSUP cells. Silencing IGFBP-2 using siRNA in epithelial RT4 cells promoted cell proliferation, invasion, colony formation, resulted in a reduction in epithelial (E-cadherin) and an increase in mesenchymal (N-cadherin) markers and increased sensitivity to cisplatin-induced cell death. Conver...
Source: Oncotarget - January 8, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

CRISPR/Cas9 genome-wide screening identifies KEAP1 as a sorafenib, lenvatinib, and regorafenib sensitivity gene in hepatocellular carcinoma.
Authors: Zheng A, Chevalier N, Calderoni M, Dubuis G, Dormond O, Ziros PG, Sykiotis GP, Widmann C Abstract Sorafenib is the first-line drug used for patients with advanced hepatocellular carcinoma (HCC). However, acquired sorafenib resistance in cancer patients limits its efficacy. Here, we performed the first genome-wide CRISPR/Cas9-based screening on sorafenib-treated HCC cells to identify essential genes for non-mutational mechanisms related to acquired sorafenib resistance and/or sensitivity in HCC cells. KEAP1 was identified as the top candidate gene by Model-based Analysis of Genome-wide CRISPR/Cas9 Knockout ...
Source: Oncotarget - January 8, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

A close relationship between HIF-1 α expression and bone metastases in advanced NSCLC, a retrospective analysis.
A close relationship between HIF-1α expression and bone metastases in advanced NSCLC, a retrospective analysis. Oncotarget. 2019 Dec 17;10(66):7071-7079 Authors: Pezzuto A, Perrone G, Orlando N, Citarella F, Ciccozzi M, Scarlata S, Tonini G Abstract Background: Hypoxia-inducible factor (HIF-1) is a transcription factor produced in hypoxia condition, it is closely associated with tumor angiogenesis and metastasis. Aim: To investigate the expression of HIF-1α in relation with the presence or absence of bone metastasis. Methods A retrospective analysis was carried out on samples deriving from ...
Source: Oncotarget - January 8, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

EGFR806-CAR T cells selectively target a tumor-restricted EGFR epitope in glioblastoma.
Authors: Ravanpay AC, Gust J, Johnson AJ, Rolczynski LS, Cecchini M, Chang CA, Hoglund VJ, Mukherjee R, Vitanza NA, Orentas RJ, Jensen MC Abstract Targeting solid tumor antigens with chimeric antigen receptor (CAR) T cell therapy requires tumor specificity and tolerance toward variability in antigen expression levels. Given the relative paucity of unique cell surface proteins on tumor cells for CAR targeting, we have focused on identifying tumor-specific epitopes that arise as a consequence of target protein posttranslational modification. We designed a CAR using a mAb806-based binder, which recognizes tumor-specif...
Source: Oncotarget - January 8, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Nuclear up regulation of the BRCA1-associated ubiquitinase BAP1 is associated with tumor aggressiveness in prostate cancers lacking the TMPRSS2:ERG fusion.
Authors: Steurer S, Schwemmer L, Hube-Magg C, Büscheck F, Höflmayer D, Tsourlakis MC, Clauditz TS, Luebke AM, Simon R, Sauter G, Izbicki J, Schroeder C, Schlomm T, Huland H, Heinzer H, Haese A, Graefen M, Göbel C, Weidemann S, Lebok P, Dum D, Fraune C, Minner S, Meiners J Abstract Loss of the putative tumor suppressor BAP1 is a candidate biomarker for adverse prognosis in many cancer types, but conversely for improved survival in others. Studies on the expression and prognostic role of BAP1 in prostate cancer are currently lacking. We used a tissue microarray of 17,747 individual prostate cancer samp...
Source: Oncotarget - January 8, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Inhibitory effects of SEL201 in acute myeloid leukemia.
We examined the antileukemic properties of a novel MNK inhibitor, SEL201. Our studies provide evidence that SEL201 suppresses eIF4E phosphorylation on Ser209 in AML cell lines and in primary patient-derived AML cells. Such effects lead to growth inhibitory effects and leukemic cell apoptosis, as well as suppression of leukemic progenitor colony formation. Combination of SEL201 with 5'-azacytidine or rapamycin results in synergistic inhibition of AML cell growth. Collectively, these results suggest that SEL201 has significant antileukemic activity and further underscore the relevance of the MNK pathway in leukemogenesis. ...
Source: Oncotarget - January 8, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

ISG15 induction is required during L1-mediated colon cancer progression and metastasis.
Authors: Cheriyamundath S, Basu S, Haase G, Doernberg H, Gavert N, Brabletz T, Ben-Ze'ev A Abstract Hyperactivation of Wnt/β-catenin target gene expression is a hallmark of colorectal cancer (CRC) development. We identified L1-CAM (L1) and Nr-CAM, members of the immunoglobulin family of nerve cell adhesion receptors, as target genes of the Wnt/β-catenin pathway in CRC cells. L1 overexpression in CRC cells enhances their motile and tumorigenic capacity and promotes liver metastasis. L1 is often localized at the invasive edge of CRC tissue. Using gene arrays and proteomic analyses we identified downstream s...
Source: Oncotarget - January 8, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Efficacy of a third-generation oncolytic herpes simplex virus in neuroendocrine tumor xenograft models.
CONCLUSIONS: T-01 effectively inhibits tumor cell proliferation in a poorly differentiated NEC mouse model. These results suggest that the third-generation oncolytic HSV-1 may serve as a novel treatment for patients with neuroendocrine tumors. PMID: 31903171 [PubMed] (Source: Oncotarget)
Source: Oncotarget - January 8, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Prognostic value of immune cells in the tumor microenvironment of early-stage lung cancer: a meta-analysis.
CONCLUSIONS: Immune cell components of the TME have prognostic value in early-stage, surgically resected NSCLC, and may reveal which patients are more likely to need additional systemic treatment, including immunotherapy. Clinical covariates need to be considered when evaluating the prognostic value of immune cells in the TME. PMID: 31903172 [PubMed] (Source: Oncotarget)
Source: Oncotarget - January 8, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Prognostic role of microRNAs in breast cancer: A systematic review.
In conclusion, the collective data presented in this review indicate that miRNAs could serve as novel prognostic tools in breast cancer, while the clinical application of these findings has yet to be verified. PMID: 31903173 [PubMed] (Source: Oncotarget)
Source: Oncotarget - January 8, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Correction: Loss of ZNF32 augments the regeneration of nervous lateral line system through negative regulation of SOX2 transcription.
Authors: Wei Y, Li K, Yao S, Gao J, Li J, Shang Y, Zhang J, Zhang L, Li Y, Mo X, Meng W, Xiang R, Hu J, Lin P, Wei Y Abstract [This corrects the article DOI: 10.18632/oncotarget.11895.]. PMID: 31903174 [PubMed] (Source: Oncotarget)
Source: Oncotarget - January 8, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Correction: Regulation of tumor suppressor EAF2 polyubiquitination by ELL1 and SIAH2 in prostate cancer cells.
Authors: Yu X, Ai J, Cai L, Jing Y, Wang D, Dong J, Pascal LE, Zhang J, Luo R, Wang Z Abstract [This corrects the article DOI: 10.18632/oncotarget.8588.]. PMID: 31903175 [PubMed] (Source: Oncotarget)
Source: Oncotarget - January 8, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Correction: MiR-1 downregulation correlates with poor survival in clear cell renal cell carcinoma where it interferes with cell cycle regulation and metastasis.
Authors: Xiao H, Zeng J, Li H, Chen K, Yu G, Hu J, Tang K, Zhou H, Huang Q, Li A, Li Y, Ye Z, Wang J, Xu H Abstract [This corrects the article DOI: 10.18632/oncotarget.3915.]. PMID: 31903176 [PubMed] (Source: Oncotarget)
Source: Oncotarget - January 8, 2020 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Modulation of proliferation factors in lung adenocarcinoma with an analysis of the transcriptional consequences of genomic EGFR activation.
This study examines complex components in lung adenocarcinoma (LUAD) closely, correlating changes in the genome and transcriptome with proliferation and overall survival. Molecular subtypes (The Cancer Genome Atlas (TCGA), 2014) based on copy number, DNA methylation, and mRNA expression had variable proliferation levels, the highest correlating with decreased survival. A pattern of increased expression typified by POLE2 and POLQ was found for multiple replication factors over thirty-seven tumor types. EGFR altered cases unanticipatedly inversely correlated with proliferation factor expression in LUAD, Colon adenocarcinoma,...
Source: Oncotarget - December 22, 2019 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Analog-sensitive cell line identifies cellular substrates of CDK9.
Authors: Decker TM, Forné I, Straub T, Elsaman H, Ma G, Shah N, Imhof A, Eick D Abstract Transcriptional cyclin-dependent kinases regulate all phases of transcription. Cyclin-dependent kinase 9 (CDK9) has been implicated in the regulation of promoter-proximal pausing of RNA polymerase II and more recently in transcription termination. Study of the substrates of CDK9 has mostly been limited to in vitro approaches that lack a quantitative assessment of CDK9 activity. Here we analyzed the cellular phosphoproteome upon inhibition of CDK9 by combining analog-sensitive kinase technology with quantitative phosphopr...
Source: Oncotarget - December 22, 2019 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

The phytohormone forchlorfenuron decreases viability and proliferation of malignant mesothelioma cells in vitro and in vivo.
Authors: Blum W, Henzi T, Pecze L, Diep KL, Bochet CG, Schwaller B Abstract Malignant mesothelioma (MM) is one of the most aggressive cancer types with a patient's life expectancy of typically less than one year upon diagnosis. The urgency of finding novel therapeutic approaches to treat mesothelioma is evident. Here we tested the effect of the plant-growth regulator forchlorfenuron (FCF), an inhibitor of septin function(s) in mammalian cells, on the viability and proliferation of MM cell lines, as well as other tumor cell lines derived from lung, prostate, colon, ovary, cervix and breast. Exposure to FCF strongly ...
Source: Oncotarget - December 22, 2019 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

An innovative diagnostic strategy for the detection of rare molecular targets to select cancer patients for tumor-agnostic treatments.
We report an innovative diagnostic strategy for a rapid and economically affordable detection of this uncommon targets. Malignant tumor samples are selected at the time of histopathological diagnosis and further processed for simultaneous analysis of multiple samples on Tissue Micro Arrays (TMAs) and Tissue Slice Arrays (TSAs). The TSA approach was specifically designed for large scale screening of small biopsies. TMA sections and TSA were first screened by immunohistochemistry (IHC) for the expression of mismatch repair and TRK proteins. Positive cases were subjected to confirmation tests (fragment analysis/FISH/NGS). In ...
Source: Oncotarget - December 22, 2019 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Flow cytometric significance of cellular alkaline phosphatase activity in acute myeloid leukemia.
Authors: Rico LG, Juncà J, Ward MD, Bradford JA, Petriz J Abstract In this prospective hospital-based cohort study that included 43 newly diagnosed patients with acute myeloid leukemia, flow cytometric cellular alkaline phosphatase (ALP) activity within primitive leukemic cells allowed us to identify two groups of patients at diagnosis according to the numbers of leukemic blasts expressing ≥ 12% of ALP+ cells (27 patients, Group A) and less than 12% of ALP+ cells (16 patients, Group B). Differences in outcome for complete response, relapse or treatment resistance, and exitus were statistically analyzed an...
Source: Oncotarget - December 22, 2019 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Crizotinib and PARP inhibitors act synergistically by triggering apoptosis in high-grade serous ovarian cancer.
In this study, new combinatorial treatment strategies targeting key signaling pathways were explored to enhance the activity of PARP inhibitors in HGSOC. Carboplatin, olaparib, niraparib, the PI3K inhibitor LY294002 and the c-Met inhibitor crizotinib were used for this investigation. PARP inhibitors and carboplatin alone and in combination caused accumulation of DNA double-strand breaks and G2/M cell cycle arrest. In contrast, crizotinib alone or in combination with PARP inhibitors induced accumulation of cells in sub-G1. Crizotinib together with either of the PARP inhibitors was more strongly synergistic than combinations...
Source: Oncotarget - December 22, 2019 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

p53-inducible SESTRINs might play opposite roles in the regulation of early and late stages of lung carcinogenesis.
Authors: Ding B, Haidurov A, Chawla A, Parmigiani A, van de Kamp G, Dalina A, Yuan F, Lee JH, Chumakov PM, Grossman SR, Budanov AV Abstract SESTRINs (SESN1-3) are proteins encoded by an evolutionarily conserved gene family that plays an important role in the regulation of cell viability and metabolism in response to stress. Many of the effects of SESTRINs are mediated by negative and positive regulation of mechanistic target of rapamycin kinase complexes 1 and 2 (mTORC1 and mTORC2), respectively, that are often deregulated in human cancers where they support cell growth, proliferation, and cell viability. Besides t...
Source: Oncotarget - December 22, 2019 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Correction: A novel PI3K inhibitor PIK-C98 displays potent preclinical activity against multiple myeloma.
Authors: Zhu J, Wang M, Yu Y, Qi H, Han K, Tang J, Zhang Z, Zeng Y, Cao B, Qiao C, Zhang H, Hou T, Mao X Abstract [This corrects the article DOI: 10.18632/oncotarget.2688.]. PMID: 31857854 [PubMed - in process] (Source: Oncotarget)
Source: Oncotarget - December 22, 2019 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Correction: Inhibition of ATM kinase upregulates levels of cell death induced by cannabidiol and γ-irradiation in human glioblastoma cells.
Correction: Inhibition of ATM kinase upregulates levels of cell death induced by cannabidiol and γ-irradiation in human glioblastoma cells. Oncotarget. 2019 Dec 10;10(65):7012-7013 Authors: Ivanov VN, Wu J, Wang TJC, Hei TK Abstract [This corrects the article DOI: 10.18632/oncotarget.26582.]. PMID: 31857855 [PubMed - in process] (Source: Oncotarget)
Source: Oncotarget - December 22, 2019 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Correction: FGFR1 β is a driver isoform of FGFR1 alternative splicing in breast cancer cells.
Correction: FGFR1β is a driver isoform of FGFR1 alternative splicing in breast cancer cells. Oncotarget. 2019 Dec 10;10(65):7014-7015 Authors: Zhao M, Zhuo ML, Zheng X, Su X, Meric-Bernstam F Abstract [This corrects the article DOI: 10.18632/oncotarget.26530.]. PMID: 31857856 [PubMed - in process] (Source: Oncotarget)
Source: Oncotarget - December 22, 2019 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

A mouse model of prostate cancer bone metastasis in a syngeneic immunocompetent host.
We report the establishment of B6CaP, an allograft tumor line from a Hi-Myc transgenic mouse that had been backcrossed onto C57BL/6J background. This tumor line grows subcutaneously in wildtype C57BL/6J immunocompetent mice, expresses AR, and has a luminal cytokeratin profile. When digested into single cells and injected via intracardiac injection, B6CaP produces metastatic widespread metastases including frequent bone lesions. Metastatic lesions occur most often in the femur, spine, and skull, and have a mixed osteolytic/osteoblastic phenotype. B6CaP allografts are androgen dependent, and regress after castration. However...
Source: Oncotarget - December 17, 2019 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Chromatin protein PC4 is downregulated in breast cancer to promote disease progression: Implications of miR-29a.
In this study, PC4 downregulation was observed in a significant proportion of mammary tissues obtained from Breast cancer patient samples as well as in a subset of highly invasive and metastatic Breast cancer patient-derived cell lines. We have identified a miRNA, miR-29a which potentially reduce the expression of PC4 both in RNA and protein level. This miR-29a was found to be indeed overexpressed in a substantial number of Breast cancer patient samples and cell lines as well, suggesting one of the key mechanisms of PC4 downregulation. Stable Knockdown of PC4 in MCF7 cells induced its migratory as well as invasive properti...
Source: Oncotarget - December 17, 2019 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

BRAFV600E -mutated ovarian serous borderline tumors are at relatively low risk for progression to serous carcinoma.
Authors: Chui MH, Kjaer SK, Frederiksen K, Hannibal CG, Wang TL, Vang R, Shih IM Abstract Ovarian serous borderline tumor (SBT) is a known precursor of low-grade serous carcinoma. While most SBTs are cured surgically, some progress to carcinoma and a risk predictor for malignant relapse is needed to ensure vigilant follow-up and additional treatment. Activating mutations in KRAS or BRAF are present in around 60% of SBTs, but their relative impact on progression is unclear. We performed mutational analysis of KRAS and BRAF on 201 SBTs identified from a longitudinal cohort of SBTs after centralized pathology review. ...
Source: Oncotarget - December 17, 2019 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Expression of matrix metalloproteinase 2 and 9 in breast cancer and breast fibroadenoma: a randomized, double-blind study.
Authors: Martins LM, de Melo Escorcio Dourado CS, Campos-Verdes LM, Sampaio FA, Revoredo CMS, Costa-Silva DR, da Conceição Barros-Oliveira M, de Jesus Nery Junior E, do Rego-Medeiros LM, Gebrim LH, Alves-Ribeiro FA, Rodrigues GP, Chagas DC, do Nascimento Marreiro D, da Silva BB Abstract Background: Matrix metalloproteinases (MMPs) 2 and 9 may play an important role in cell proliferation and dissemination of cancer. However, few studies have compared the expression of these proteins between breast cancer and fibroadenoma. Material and methods: A randomized, double-blind study was carried out in 66 ...
Source: Oncotarget - December 17, 2019 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Survival correlation of immune response in human cancers.
CONCLUSIONS: Immune responses have different impacts on patient outcome in different human cancers. Prospective verification is needed before the findings can be applied for clinical trial development. PMID: 31839882 [PubMed] (Source: Oncotarget)
Source: Oncotarget - December 17, 2019 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

A way forward for cancer prevention therapy: personalized risk assessment.
This article will review the rationale for evaluating multiple risk factors so as to identify individuals at highest risk. It will use breast and lung cancer as examples, will describe currently available risk assessment tools, and will discuss ongoing efforts to expand the impact of this approach. The high potential of this strategy to provide a way forward for developing cancer prevention therapy will be highlighted. PMID: 31839883 [PubMed] (Source: Oncotarget)
Source: Oncotarget - December 17, 2019 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Ezrin, more than a metastatic detERMinant?
Authors: Hoskin V, Ghaffari A, Elliott BE PMID: 31827718 [PubMed] (Source: Oncotarget)
Source: Oncotarget - December 13, 2019 Category: Cancer & Oncology Tags: Oncotarget Source Type: research