Candidate biomarker assessment for pharmacological response.
Abstract Using the information from our CellMiner (https://discover.nci.nih.gov/cellminer/) and CellMinerCDB (https://discover.nci.nih.gov/cellminercdb/) web-based applications, we identified 3978 molecular events with significant links to pharmacological response for genes that are either targets, biomarkers, or have established causal linkage to drugs. Molecular events included DNA copy number, methylation and mutation; and transcript; and whole or phospho-protein expression for the NCI-60 human cancer cell lines. While all forms of molecular data were informative in some (gene-drug) pairings, the type of signif...
Source: Translational Oncology - July 8, 2020 Category: Cancer & Oncology Authors: Reinhold WC, Elloumi F, Varma S, Robert J, Mills GB, Pommier Y Tags: Transl Oncol Source Type: research

Quantifying DNA damage induced by ionizing radiation and hyperthermia using single DNA molecule imaging.
d F Abstract Ionizing radiation (IR) is a common mode of cancer therapy, where DNA damage is the major reason of cell death. Here, we use an assay based on fluorescence imaging of single damaged DNA molecules isolated from radiated lymphocytes, to quantify IR induced DNA damage. The assay uses a cocktail of DNA-repair enzymes that recognizes and excises DNA lesions and then a polymerase and a ligase incorporate fluorescent nucleotides at the damage sites, resulting in a fluorescent "spot" at each site. The individual fluorescent spots can then be counted along single stretched DNA molecules and the globa...
Source: Translational Oncology - July 8, 2020 Category: Cancer & Oncology Authors: Singh V, Johansson P, Torchinsky D, Lin YL, Öz R, Ebenstein Y, Hammarsten O, Westerlund F Tags: Transl Oncol Source Type: research

CpG-coated Prussian blue nanoparticles-based photothermal therapy combined with anti-CTLA-4 immune checkpoint blockade triggers a robust abscopal effect against neuroblastoma.
Abstract High-risk neuroblastoma, which is associated with regional and systemic metastasis, is a leading cause of cancer-related mortality in children. Responding to this need for novel therapies for high-risk patients, we have developed a "nanoimmunotherapy," which combines photothermal therapy (PTT) using CpG oligodeoxynucleotide-coated Prussian blue nanoparticles (CpG-PBNPs) combined with anti-CTLA-4 (aCTLA-4) immunotherapy. Our in vitro studies demonstrate that in addition to causing ablative tumor cell death, our nanoimmunotherapy alters the surface levels of co-stimulatory, antigen-presenting, and...
Source: Translational Oncology - July 8, 2020 Category: Cancer & Oncology Authors: Cano-Mejia J, Shukla A, Ledezma DK, Palmer E, Villagra A, Fernandes R Tags: Transl Oncol Source Type: research

Combined blockade of EGFR and glutamine metabolism in preclinical models of colorectal cancer.
In conclusion, this therapeutic combination represents a promising new precision medicine approach for patients with refractory metastatic WT RAS CRC. PMID: 32652471 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - July 8, 2020 Category: Cancer & Oncology Authors: Cohen AS, Geng L, Zhao P, Fu A, Schulte ML, Graves-Deal R, Washington MK, Berlin J, Coffey RJ, Manning HC Tags: Transl Oncol Source Type: research

Anillin facilitates cell proliferation and induces tumor growth of hepatocellular carcinoma via miR-138/SOX4 axis regulation.
In this study, we examined and verified the anomalous high expression of Anillin in both HCC patients' specimens and HCC cell lines. High expression of Anillin is associated with dismal clinicopathologic features of HCC patients and poor prognosis. We conducted loss-of and gain-of function studies in HCC Hep3B cells. Anillin presented a significantly facilitating effect on cell proliferation in vitro and induced remarkable tumor growth in vivo. We found that the over-expression of Anillin was driven by a potential axis of miR-138/SOX4. Transcription factor SOX4 presented a high expression profile positive correlated with A...
Source: Translational Oncology - July 6, 2020 Category: Cancer & Oncology Authors: Xiao JX, Xu W, Fei X, Hao F, Wang N, Chen Y, Wang J Tags: Transl Oncol Source Type: research

Skp2 Depletion Reduces Tumor-Initiating Properties and Promotes Apoptosis in Synovial Sarcoma.
In this study, we investigated whether S phase kinase-associated protein (Skp2) plays an oncogenic role in tumor initiation, progression, and metastasis of SS. Our study revealed that Skp2 is frequently overexpressed in SS specimens and SS18-SSX transgenic mouse tumors, as well as correlated with clinical stages. Next, we identified that genetic depletion of Skp2 reduced mesenchymal and stemness markers, and inhibited the invasive and proliferative capacities of SS cell lines. Furthermore, Skp2 depletion markedly suppressed the growth of SS xenografts tumors. Treatment of SS cell lines with the skp2 inhibitor flavokawain A...
Source: Translational Oncology - July 2, 2020 Category: Cancer & Oncology Authors: Wang J, Sato K, O'Donnell E, Singla A, Yaguare S, Aldahamsheh O, Batko B, Borjihan H, Tingling J, Zhang J, Weiser DA, Loeb DM, Gorlick R, Schwartz EL, Yang R, Zi X, Zhao H, Geller DS, Hoang BH Tags: Transl Oncol Source Type: research

Programmed Cell Death-Ligand 2: A Neglected But Important Target in the Immune Response to Cancer?
Abstract Programmed cell death-ligand 2 (PD-L2) is one of the two ligands of the programmed cell death-1 (PD-1) receptor, an inhibitory protein mainly expressed on activated immune cells that is targeted in the clinic, with successful and remarkable results. The PD-1/PD-Ls axis was shown to be one of the most relevant immunosuppressive pathways in the immune microenvironment, and blocking this interaction gave rise to an impressive clinical benefit in a broad variety of solid and hematological malignancies. Although PD-L2 has been historically considered a minor ligand, it binds to PD-1 with a two- to six-fold hig...
Source: Translational Oncology - July 1, 2020 Category: Cancer & Oncology Authors: Solinas C, Aiello M, Rozali E, Lambertini M, Willard-Gallo K, Migliori E Tags: Transl Oncol Source Type: research

The neural stem-cell marker CD24 is specifically upregulated in IDH-mutant glioma.
Abstract BACKGROUND: Malignant gliomas have disproportionally high morbidity and mortality. Heterozygous mutations in the isocitrate dehydrogenase 1 (IDH1) gene are most common in glioma, resulting in predominantly arginine to histidine substitution at codon 132. Because IDH1R132H requires a wild-type allele to produce (D)-2-hydroxyglutarate for epigenetic reprogramming, loss of IDH1R132H heterozygosity is associated with glioma progression in an IDH1-wildtype-like phenotype. Although previous studies have reported that transgenic IDH1R132H induces the expression of nestin-a neural stem-cell marker, the underlying...
Source: Translational Oncology - July 1, 2020 Category: Cancer & Oncology Authors: Tiburcio PDB, Locke MC, Bhaskara S, Chandrasekharan MB, Huang LE Tags: Transl Oncol Source Type: research

Radiomics nomograms of tumors and peritumoral regions for the preoperative prediction of spread through air spaces in lung adenocarcinoma.
Abstract To evaluate the clinical features and radiomics nomograms of tumors and peritumoral regions for the preoperative prediction of the presence of spread through air spaces (STAS) in patients with lung adenocarcinoma. A total of 107 STAS-positive lung adenocarcinomas were selected and matched to 105 STAS-negative lung adenocarcinomas. Thin-slice CT imaging annotation and region of interest (ROI) segmentation were performed with semi-automatic in-house software. Radiomics features were extracted from all nodules and incremental distances of 5, 10, and 15 mm outside the lesion segmentation. A radiomics nomogr...
Source: Translational Oncology - July 1, 2020 Category: Cancer & Oncology Authors: Zhuo Y, Feng M, Yang S, Zhou L, Ge D, Lu S, Liu L, Shan F, Zhang Z Tags: Transl Oncol Source Type: research

A possible asymmetry at the checkpoint.
Abstract A recently published systematic review and meta-analysis indicated that anti-PD-1 treatment may confer superior survival outcomes as compared to anti-PD-L1. We propose mechanistic explanations supporting this finding. PMID: 32619818 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - June 30, 2020 Category: Cancer & Oncology Authors: Milano G Tags: Transl Oncol Source Type: research

S2 Subunit of SARS-nCoV-2 Interacts with Tumor Suppressor Protein p53 and BRCA: an In Silico Study.
Abstract Novel coronavirus disease 2019 (COVID-19) is the biggest threat to human being globally. The first case was identified in a patient with flu symptoms along with severe acute respiratory syndrome in Wuhan, China in December 2019 and now it has spread in more than 200 countries. COVID-19 is more lethal in the elderly and people with an underlying condition such as asthma, cancer, diabetes. Here we performed bioinformatic analysis to investigate the interaction of S2 subunit protein of SARS-nCoV-2 of novel coronavirus with tumor suppressor proteins p53 and BRCA-1/2. In this short communication we report the ...
Source: Translational Oncology - June 29, 2020 Category: Cancer & Oncology Authors: Singh N, Bharara Singh A Tags: Transl Oncol Source Type: research

Prognostic indicators for gastrointestinal stromal tumors: a review.
Abstract Gastrointestinal stromal tumors (GISTs) are potentially malignancies that can occur anywhere in the digestive tract. Tyrosine kinase inhibitors (TKIs) such as imatinib have proven effective since the discovery of KIT and PDGFRA. The current version of NCNN, ESMO and EURACAN guidelines recognized that the three main prognostic factors are the mitotic rate, tumor size and tumor site. In addition, tumor rupture is also recognized as an independent risk factor. However, recent evidence shows that various types of gene mutations are associated with prognosis, and influencing factors such as gastrointestinal bl...
Source: Translational Oncology - June 26, 2020 Category: Cancer & Oncology Authors: Zhang H, Liu Q Tags: Transl Oncol Source Type: research

Analysis of the efficacy, safety and survival factors of stereotactic body radiation therapy in patients with recurrence of pancreatic cancer.
This study aims to evaluate the efficacy and safety of stereotactic body radiation therapy (SBRT) using Cyber Knife (CK) in the treatment of patients with recurrent pancreatic cancer after surgery, and analyze its survival-related factors. METHODS: The primary endpoint was freedom from local progression (FFLP) and local control (LC) rate after CK. The secondary endpoints were overall survival (OS), progression-free survival (PFS), symptom relief and toxicities. Receiver operating characteristic (ROC) curves were used to determine the optimal cut-off values of inflammatory composite indicators NLR, PLR, SII and PNI. Th...
Source: Translational Oncology - June 24, 2020 Category: Cancer & Oncology Authors: Li J, Wang Z, Li AM, Zhou H, Zhu XX Tags: Transl Oncol Source Type: research

Characteristics of Head and Neck Squamous Cell Carcinoma Cell Lines Reflect Human Tumor Biology Independent of Primary Etiologies and HPV Status.
Abstract Explanations for the differences in clinical outcomes in head and neck squamous cell carcinomas (HNSCCs) when compared by similar tumor location, stage, nodal status, human papillomavirus (HPV) status, and patient history remain elusive. Cell lines are an excellent tool of study for understanding the in vitro properties of cancers. However, HNSCC cell lines from progression-free and/or HPV-positive tumors are very rare. Here we studied HPV-positive and HPV-negative University of Michigan squamous cell carcinoma cell lines (2 HPV-, 2 HPV16+, 1 HPV18+) coming from donors with nonoropharyngeal sites and vari...
Source: Translational Oncology - June 20, 2020 Category: Cancer & Oncology Authors: Nair TS, Thomas TB, Yang L, Kakaraparthi BN, Morris AC, Clark AM, Campredon LP, Brouwer AF, Eisenberg MC, Meza R, Carey TE Tags: Transl Oncol Source Type: research

Ibrutinib is not an effective drug in primografts of TCF3-PBX1.
CONCLUSIONS: We conclude that ibrutinib is not the precision medicine of choice for TCF3-PBX1 positive BCP-ALL. PMID: 32563910 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - June 18, 2020 Category: Cancer & Oncology Authors: van de Ven C, Boeree A, Stalpers F, Zwaan CM, Den Boer ML Tags: Transl Oncol Source Type: research

MicroRNA200a Enhances Antitumor Effects in Combination with Doxorubicin in Hepatocellular Carcinoma.
This study identifies a novel role of miR-200a in potentiating doxorubicin-mediated therapeutic effects in HCC. PMID: 32563177 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - June 17, 2020 Category: Cancer & Oncology Authors: Cui X, Zhou D, Du Q, Wan P, Dong K, Hou H, Geller DA Tags: Transl Oncol Source Type: research

Mass Spectrometry-Based Lipidomics of Oral Squamous Cell Carcinoma Tissue Reveals Aberrant Cholesterol and Glycerophospholipid Metabolism - A Pilot Study.
In conclusion, we have demonstrated a shift in the lipid metabolism in these OSCC samples by characterizing the detailed landscape. Predominantly, cholesterol and GPL metabolism were altered, suggesting that interactions with sterol regulatory binding proteins may be involved. The FA composition changes of the GPLs suggest increased de novo lipogenesis. PMID: 32559714 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - June 16, 2020 Category: Cancer & Oncology Authors: Dickinson A, Saraswat M, Joenväärä S, Agarwal R, Jyllikoski D, Wilkman T, Mäkitie A, Silén S Tags: Transl Oncol Source Type: research

MicroRNA Signatures in Blood or Bone Marrow Distinguish Subtypes of Pediatric Acute Lymphoblastic Leukemia.
Abstract OncomiRs are microRNAs that are associated with early onset of specific cancers. To identify microRNAs involved in pediatric acute lymphoblastic leukemia (ALL) subtypes T-ALL and B-ALL, peripheral blood and bone marrow samples were independently subjected to microarray analysis using two different high-fidelity array platforms. The unique and common gene signatures from both arrays were validated by TaqMan individual assays in 100 pediatric ALL samples. Survival studies were carried out in the test set and validation set with 50 randomly selected samples in each set. MicroRNA expression profile revealed c...
Source: Translational Oncology - June 9, 2020 Category: Cancer & Oncology Authors: Nair RA, Verma VK, Beevi SS, Rawoof A, Alexander LE, Prasad ER, Kumari PK, Kumar P, Dinesh Kumar L Tags: Transl Oncol Source Type: research

Low Expression of Smurf1 Enhances the Chemosensitivity of Human Colorectal Cancer to Gemcitabine and Cisplatin in Patient-Derived Xenograft Models.
In conclusion, the results indicated that Smurf1 inhibits the chemosensitivity of CRC to gemcitabine, cisplatin, and gemcitabine plus cisplatin. Therefore, downregulati1ng the Smurf1 expression is a potential strategy to increase the efficacy of gemcitabine and cisplatin in CRC patients. PMID: 32512228 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - June 5, 2020 Category: Cancer & Oncology Authors: Guo J, Xu G, Mao C, Wei R Tags: Transl Oncol Source Type: research

Corrigendum to 'Up-Regulation of RFC3 Promotes Triple Negative Breast Cancer Metastasis and is Associated With Poor Prognosis Via EMT' [Translational Oncology 10 (2017); 1-9].
PMID: 32460969 [PubMed - in process] (Source: Translational Oncology)
Source: Translational Oncology - May 30, 2020 Category: Cancer & Oncology Authors: He ZY, Wu SG, Peng F, Zhang Q, Luo Y, Chen M, Bao Y Tags: Transl Oncol Source Type: research

Evaluation of Somatostatin and CXCR4 Receptor Expression in a Large Set of Prostate Cancer Samples Using Tissue Microarrays and Well-Characterized Monoclonal Antibodies.
CONCLUSION: Overall, SST and CXCR4 expression levels are clearly of no therapeutic relevance in PCa. SST- or CXCR4-based therapy might be feasible, however, in rare cases of small-cell-type neuroendocrine carcinoma of the prostate. PMID: 32460182 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - May 24, 2020 Category: Cancer & Oncology Authors: Werner C, Dirsch O, Dahmen U, Grimm MO, Schulz S, Lupp A Tags: Transl Oncol Source Type: research

A Dodecapeptide Selected by Phage Display as a Potential Theranostic Probe for Colon Cancers.
CONCLUSION: The noble dodecapeptide probe can be a promising candidate for both colon tumor diagnosis and targeted drug delivery. PMID: 32454443 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - May 23, 2020 Category: Cancer & Oncology Authors: Kwak MH, Yi G, Yang SM, Choe Y, Choi S, Lee HS, Kim E, Lim YB, Na K, Choi MG, Koo H, Park JM Tags: Transl Oncol Source Type: research

Prostate Cancer Cell Phenotypes Remain Stable Following PDE5 Inhibition in the Clinically Relevant Range.
Abstract Widespread cGMP-specific phosphodiesterase 5 (PDE5) inhibitor use in male reproductive health and particularly in prostate cancer patients following surgery has generated interest in how these drugs affect the ability of residual tumor cells to proliferate, migrate, and form recurrent colonies. Prostate cancer cell lines were treated with PDE5 inhibitors at clinically relevant concentrations. Proliferation, colony formation, and migration phenotypes remained stable even when cells were co-treated with a stimulator of cGMP synthesis that facilitated cGMP accumulation upon PDE5 inhibition. Surprisingly, sup...
Source: Translational Oncology - May 23, 2020 Category: Cancer & Oncology Authors: Hankey W, Sunkel B, Yuan F, He H, Thomas-Ahner JM, Chen Z, Clinton SK, Huang J, Wang Q Tags: Transl Oncol Source Type: research

Cancer Susceptibility Candidate 9 (CASC9): A Novel Targetable Long Noncoding RNA in Cancer Treatment.
Abstract Based on epidemiological data provided by the World Health Organization (2018), cancer is the second most prevalent cause of death worldwide. Several factors are thought to contribute to the high mortality rate in cancer patients, including less-than-optimal diagnostic and therapeutic strategies. Thus, there is an urgent need to identify accurate biomarkers with diagnostic, prognostic, and potential therapeutic applications. In this regard, long noncoding RNAs (lncRNAs) hold immense potential due to their regulatory roles in cancer development and associated cancer hallmarks. Recently, CASC9 transcripts h...
Source: Translational Oncology - May 22, 2020 Category: Cancer & Oncology Authors: Sharma U, Barwal TS, Acharya V, Tamang S, Vasquez KM, Jain A Tags: Transl Oncol Source Type: research

Advanced Cancer Patient Knowledge of and Attitudes towards Tumor Molecular Profiling.
Abstract Limited research has indicated that despite their overwhelming interest in tumor molecular profiling (MP),1 cancer patients have poor knowledge about MP. The current study aimed to investigate demographic and psychological predictors of knowledge and perceived importance of MP in an advanced cancer patient cohort. Eligible participants had advanced solid cancers of any histological type with sufficient accessible tissue for MP and were enrolled in the Molecular Screening and Therapeutics (MoST) Program. A questionnaire was completed by 1074 participants (91% response rate) after consent, prior to undergoi...
Source: Translational Oncology - May 22, 2020 Category: Cancer & Oncology Authors: Davies G, Butow P, Napier CE, Bartley N, Juraskova I, Meiser B, Ballinger ML, Thomas DM, Schlub TE, Best MC, members of the PiGeOn Project Tags: Transl Oncol Source Type: research

Preemptive Homology-Directed DNA Repair Fosters Complex Genomic Rearrangements in Hepatocellular Carcinoma.
This study assessed the relationship between DNA damage response (DDR) and chromosome instability in hepatocellular carcinoma (HCC). We investigated DDR signaling in HCC cells by analyzing DNA damage-dependent redistribution of major DDR proteins to damaged chromatin using immunofluorescence microscopy and Western blotting experimentations. We also performed gene conversion and metaphase analyses to address whether dysregulated DDR may bear any biological significance during hepatocarcinogenesis. Accordingly, we found that HCC cell lines suffered from elevated spontaneous DNA double-strand breaks (DSBs). In addition, analy...
Source: Translational Oncology - May 22, 2020 Category: Cancer & Oncology Authors: Sy SM, Guo Y, Lan Y, Ng H, Huen MS Tags: Transl Oncol Source Type: research

Experimental Treatment of Mucinous Peritoneal Metastases Using Patient-Derived Xenograft Models.
ark K Abstract Mucinous peritoneal metastases (PM) generally respond poorly to systemic treatment, and there is a clear unmet need for new treatment strategies to improve survival and quality of life for patients with PM. In this work, the growth inhibitory effect of five drugs (oxaliplatin (OXA; 5 mg/kg), irinotecan (IRI; 60 mg/kg), cabazitaxel (CBZ; 15 or 30 mg/kg), regorafenib (REG; 10, 30 or 60 mg/kg), and capecitabine (CAP; 359 or 755 mg/kg) was investigated in three orthotopic patient-derived xenograft models that mimic mucinous PM. Drugs were administered intraperitoneally (i.p.) as monotherapy weekly for 4...
Source: Translational Oncology - May 21, 2020 Category: Cancer & Oncology Authors: Fleten KG, Lund-Andersen C, Waagene S, Abrahamsen TW, Mørch Y, Boye K, Torgunrud A, Flatmark K Tags: Transl Oncol Source Type: research

The Novel Phospholipid Mimetic KPC34 Is Highly Active Against Acute Myeloid Leukemia with Activated Protein Kinase C.
Abstract Acute myeloid leukemia (AML) is an aggressive malignancy with poor outcomes. Nucleoside analogs are subject to resistance mechanisms including downregulation of equilibrative nucleoside transporter (ENT1) and deoxycytidine kinase (dCK). KPC34 is a novel phospholipid mimetic that when cleaved by phospholipase C (PLC) liberates gemcitabine monophosphate and a diacylglycerol mimetic that inhibits the classical isoforms of protein kinase C (PKC). KPC34 acts independently of ENT1 and dCK. KPC34 was active against all AML cell lines tested with IC50s in the nanomolar range. Enforced expression of PLC increased ...
Source: Translational Oncology - May 16, 2020 Category: Cancer & Oncology Authors: Alexander PM, Kucera GL, Pladna KM, Pardee TS Tags: Transl Oncol Source Type: research

Tumor Location Is Associated With the Prevalence of Braf And Pik3ca Mutations in Patients with Wild-Type Ras Colorectal Cancer: A Prospective Multi-Center Cohort Study in Japan.
CONCLUSIONS: More than half of the patients with right-sided CRC and wild-type RAS harbored BRAF/PIK3CA mutations, including BRAFnon-V600E, which may contribute to the difference in the anti-EGFR efficacy between the right- and left-sided CRC. PMID: 32428838 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - May 16, 2020 Category: Cancer & Oncology Authors: Taniguchi H, Uehara K, Nakayama G, Nakayama H, Aiba T, Hattori N, Kataoka M, Nakano Y, Kawase Y, Okochi O, Matsuoka H, Utsunomiya S, Sakamoto E, Mori Y, Umeda S, Shikano T, Komori K, Tajika M, Kadowaki S, Muro K, Yatabe Y Tags: Transl Oncol Source Type: research

Gene Alterations in Paired Supernatants and Precipitates from Malignant Pleural Effusions of Non-Squamous Non-Small Cell Lung Cancer.
CONCLUSIONS: These results demonstrated that MPE supernatants were comparable to precipitate samples for detection of genetic alterations. However, gene mutation heterogeneity was found between these two media types. PMID: 32428850 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - May 16, 2020 Category: Cancer & Oncology Authors: Li J, Li X, Wang W, Shao Y, Zhang Y, Song Z Tags: Transl Oncol Source Type: research

IGF1R Axis Inhibition Restores Dendritic Cell Antitumor Response in Ovarian Cancer.
Abstract Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy. The insulin-like growth factor (IGF) system plays a key role in regulating growth and invasiveness in several malignancies, including ovarian cancer. IGF1R targeting showed antiproliferative activity of EOC cells. However, clinical studies failed to show significant benefit. EOC cells suppress antitumor immune responses by inducing dendritic cell (DC) dysfunction. The IGF1 axis can regulate DC maturation. The current study evaluated involvement of the IGF1 axis in DC differentiation in EOC. Studies were conducted on EOC and on a ...
Source: Translational Oncology - May 16, 2020 Category: Cancer & Oncology Authors: Somri-Gannam L, Meisel-Sharon S, Hantisteanu S, Groisman G, Limonad O, Hallak M, Bruchim I Tags: Transl Oncol Source Type: research

N-Acetyltransferase 10 Promotes Micronuclei Formation to Activate the Senescence-Associated Secretory Phenotype Machinery in Colorectal Cancer Cells.
Abstract The formation of micronuclei (MN) is prevalent in human cancer cells and its role in activating the senescence-associated secretory phenotype (SASP) machinery has been identified recently. However, the role of MN in regulation of SASP signaling still needs to define in practical cancers. Here, we reported that in colorectal cancer cells the expression of NAT10 (N-acetyltransferase 10) could mediate MN formation through DNA replication and NAT10-positive MN could activate SASP by binding to cGAS. The chemical inhibition of NAT10 by Remodelin or genomic depletion could markedly reduce MN formation, SASP act...
Source: Translational Oncology - May 16, 2020 Category: Cancer & Oncology Authors: Cao Y, Yao M, Wu Y, Ma N, Liu H, Zhang B Tags: Transl Oncol Source Type: research

Frequency and Clinicopathological Profile Associated with Braf Mutations in Patients with Advanced Melanoma in Spain.
This study aimed to assess the frequency of BRAF V600 mutations in Spanish patients with advanced or metastatic melanoma and to identify clinical and histopathological features associated with BRAF-mutated tumors. A multicenter, cross-sectional epidemiological study was conducted in 33 Spanish hospitals in adult patients with stage IIIc/IV melanoma. A total of 264 patients were included. The median age was 68 years and 57% were male. Melanoma mainly involved skin with intermittent (40.4%) and low or no sun exposure (43.5%). Most patients (85.6%) had stage IV disease (M1a: 19.3%; M1b: 13.3%; M1c: 22.7%). Serum lactate deh...
Source: Translational Oncology - May 15, 2020 Category: Cancer & Oncology Authors: Lopez-Martin JA, Arance Fernández A, Ríos-Martín JJ, Hernández-Losa J, Alós Hernández L, Cerezuela Fuentes P, Ortiz Reina S, Ortega Izquierdo E, Martí RM, Soberino García J, Ferrer Fábrega B, Rodríguez Peralto JL, ABSOLUT-BRAF Study Group Tags: Transl Oncol Source Type: research

MK2206 Enhances Cisplatin-Induced Cytotoxicity and Apoptosis in Testicular Cancer Through Akt Signaling Pathway Inhibition.
CONCLUSION: These results suggested that the concomitant use of MK2206 could enhance the CDDP-induced cytotoxicity and apoptosis in testicular cancer with the suppressed expression of Akt pathway. PMID: 32422572 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - May 15, 2020 Category: Cancer & Oncology Authors: Sun D, Wang J, Zhang H, Liu S, Wei P, Wang H, Xu Z, Fu Q, Zhang K Tags: Transl Oncol Source Type: research

Comprehensive Characterization of the Mutational Landscape in Localized Anal Squamous Cell Carcinoma.
In conclusion, sequencing of ASCC clinical samples appears an encouraging tool for the molecular portrait of this disease. PMID: 32422573 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - May 15, 2020 Category: Cancer & Oncology Authors: Trilla-Fuertes L, Ghanem I, Maurel J, G-Pastrián L, Mendiola M, Peña C, López-Vacas R, Prado-Vázquez G, López-Camacho E, Zapater-Moros A, Heredia V, Cuatrecasas M, García-Alfonso P, Capdevila J, Conill C, García-Carbonero R, Heath KE, Ramos-Ruiz R, Tags: Transl Oncol Source Type: research

Blood Outgrowth Endothelial Cells as a Cellular Carrier for Oncolytic Vesicular Stomatitis Virus Expressing Interferon- β in Preclinical Models of Non-Small Cell Lung Cancer.
Blood Outgrowth Endothelial Cells as a Cellular Carrier for Oncolytic Vesicular Stomatitis Virus Expressing Interferon-β in Preclinical Models of Non-Small Cell Lung Cancer. Transl Oncol. 2020 May 15;13(7):100782 Authors: Patel MR, Jacobson BA, Ji Y, Hebbel RP, Kratzke RA Abstract Oncolytic viruses have demonstrated efficacy in numerous tumor models including non-small cell lung cancer (NSCLC). One limitation of viral therapy for metastatic lung cancer is that systemic administration can be hindered by complement and antiviral immunity. Thus, we investigated whether ex vivo-infected blood outgrow...
Source: Translational Oncology - May 15, 2020 Category: Cancer & Oncology Authors: Patel MR, Jacobson BA, Ji Y, Hebbel RP, Kratzke RA Tags: Transl Oncol Source Type: research

PAICS, a De Novo Purine Biosynthetic Enzyme, Is Overexpressed in Pancreatic Cancer and Is Involved in Its Progression.
Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with an extremely poor prognosis. There is an urgent need to identify new therapeutic targets and also understand the mechanism of PDAC progression that leads to aggressiveness of the disease. To find therapeutic targets, we analyzed data related to PDAC transcriptome sequencing and found overexpression of the de novo purine metabolic enzyme phosphoribosylaminoimidazole succinocarboxamide synthetase (PAICS). Immunohistochemical analysis of PDAC tissues showed high expression of the PAICS protein. To assess the biological roles of PAICS, we us...
Source: Translational Oncology - May 14, 2020 Category: Cancer & Oncology Authors: Agarwal S, Chakravarthi BVSK, Kim HG, Gupta N, Hale K, Balasubramanya SAH, Oliver PG, Thomas DG, Eltoum IA, Buchsbaum DJ, Manne U, Varambally S Tags: Transl Oncol Source Type: research

Redox Modulation and Induction of Ferroptosis as a New Therapeutic Strategy in Hepatocellular Carcinoma.
Abstract Ferroptosis, a newly discovered form of cell death mediated by reactive oxygen species (ROS) and lipid peroxidation, has recently been shown to have an impact on various cancer types; however, so far there are only few studies about its role in hepatocellular carcinoma (HCC). The delicate equilibrium of ROS in cancer cells has found to be crucial for cell survival, thus increased levels may trigger ferroptosis in HCC. In our study, we investigated the effect of different ROS modulators and ferroptosis inducers on a human HCC cell line and a human hepatoblastoma cell line. We identified a novel synergistic...
Source: Translational Oncology - May 13, 2020 Category: Cancer & Oncology Authors: Lippmann J, Petri K, Fulda S, Liese J Tags: Transl Oncol Source Type: research

Integrative Analysis of Periostin in Primary and Advanced Prostate Cancer.
Abstract Periostin (POSTN) is an extracellular matrix protein associated with tumor progression and shorter survival in prostate cancer (PCa). Here, we performed an integrative analysis of POSTN's role in patients with PCa. Clinical and POSTN data from large-scale datasets were analyzed. POSTN cutoffs were identified with X-Tile, and STRING was used for protein-protein interaction analysis. In a cohort of 48 patients with metastatic castration-resistant prostate cancer (mCRPC), we used the AdnaTest platform to isolate circulating tumor cells and extract POSTN mRNA. Plasma samples were also tested for POSTN protein...
Source: Translational Oncology - May 13, 2020 Category: Cancer & Oncology Authors: Cattrini C, Barboro P, Rubagotti A, Zinoli L, Zanardi E, Capaia M, Boccardo F Tags: Transl Oncol Source Type: research

Safety and Long-Term Outcome of Intratumoral Injection of OK432-Stimulated Dendritic Cells for Hepatocellular Carcinomas After Radiofrequency Ablation.
Abstract Dendritic cell (DC)-based immunotherapies are believed to help eradicate residual tumor cells, including hepatocellular carcinoma (HCC). Here, we assessed the safety and clinical response to OK432-stimulated monocyte-derived DCs (MoDCs) in treating HCC after radiofrequency ablation (RFA). MoDCs were derived from 30 HCC patients in the presence of interleukin-4 and granulocyte-macrophage colony stimulating factor for 5 days and then cultured for 2 more days in the medium (basic protocol) or stimulated with OK432. On day 7, DCs were harvested and percutaneously injected into HCC tumors after RFA. We obser...
Source: Translational Oncology - May 12, 2020 Category: Cancer & Oncology Authors: Kitahara M, Mizukoshi E, Terashima T, Nakagawa H, Horii R, Iida N, Arai K, Yamashita T, Sakai Y, Yamashita T, Honda M, Nakamoto Y, Kaneko S Tags: Transl Oncol Source Type: research

Peripheral Blood Stem Cell Harvest HPC Count Is an Effective Surrogate Marker for CD34+ Cell Count in Allogeneic Stem Cell Transplant Setting.
CONCLUSION: XN-HPC has a highly promising potential to serve as a cost-effective and time-saving surrogate for CD34+ cell count. PMID: 32408157 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - May 11, 2020 Category: Cancer & Oncology Authors: Jamal A, Khan MT, Parveen S, Rizvi Q, Farzana T, Zaidi U, Borhany M, Siddiqui S, Ansari SH, Shamsi TS Tags: Transl Oncol Source Type: research

Hypomethylating Agent Azacitidine Is Effective in Treating Brain Metastasis Triple-Negative Breast Cancer Through Regulation of DNA Methylation of Keratin 18 Gene.
In this study, we evaluated the hypomethylating agent azacitidine (AZA) for its potential as a novel therapeutic in preclinical models of brain metastasis of breast cancer. We used the parental triple-negative breast cancer MDA-MB-231 (231) cells and their brain colonizing counterpart (231Br) to ascertain phenotypic differences in response to AZA. We observed that 231Br cells have higher metastatic potential compared to 231 cells. With regard to therapeutic value, the AZA IC50 value in 231Br cells is significantly lower than that in parental cells (P 
Source: Translational Oncology - May 11, 2020 Category: Cancer & Oncology Authors: Butler C, Sprowls S, Szalai G, Arsiwala T, Saralkar P, Straight B, Hatcher S, Tyree E, Yost M, Kohler WJ, Wolff B, Putnam E, Lockman P, Liu T Tags: Transl Oncol Source Type: research

Heterogeneous Drug Efficacy of an Antibody-Drug Conjugate Visualized Using Simultaneous Imaging of Its Delivery and Intracellular Damage in Living Tumor Tissues.
This study is the first to simultaneously evaluate the delivery and intracellular efficacy of ADCs in living tumor tissue. Accurate evaluation of the efficacy of ADCs is important for the development of effective anticancer drugs. PMID: 32403030 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - May 10, 2020 Category: Cancer & Oncology Authors: Gonda K, Negishi H, Takano-Kasuya M, Kitamura N, Furusawa N, Nakano Y, Hamada Y, Tokunaga M, Higuchi H, Tada H, Ishida T Tags: Transl Oncol Source Type: research

Analyses of Nivolumab Exposure and Clinical Safety Between 3-mg/kg Dosing and 240-mg Flat Dosing in Asian Patients with Advanced Renal Cell Carcinoma in the Real-World Clinical Setting.
In conclusion, serum Alb was a potential clinically relevant covariate for nivolumab pharmacokinetics in Japanese RCC patients. Further studies should verify whether serum Alb affects nivolumab efficacy and toxicity. PMID: 32375081 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - May 3, 2020 Category: Cancer & Oncology Authors: Kato R, Ikarashi D, Matsuura T, Maekawa S, Kato Y, Kanehira M, Takata R, Tokuyama R, Tamai K, Harigai N, Nakazaki Y, Obara W Tags: Transl Oncol Source Type: research

Risk of Dyslipidemia Associated with VEGF/VEGFR Inhibitors: A Meta-Analysis.
Abstract OBJECTIVE: This meta-analysis was performed to investigate hyperlipidemia in patients with carcinoma treated with vascular endothelial growth factor (VEGF)/vascular endothelial growth factor receptor (VEGFR) inhibitors. METHODS: We searched for eligible phase II and III studies using PubMed and Embase databases. We then summarized reported occurrences of hyperlipidemia in patients with different cancers. Relative risk ratios (RRs) and 95% confidence intervals (CIs) were calculated by Revman 5 software in meta-analysis. RESULTS: Eleven trials (4760 subjects) were included in this meta-analysis. O...
Source: Translational Oncology - May 3, 2020 Category: Cancer & Oncology Authors: Dai H, Liu C, Li P, Mai Z, Tan X, Chen S, Zhou Z, Tang Z, Miao J, Liu L, Fang Y Tags: Transl Oncol Source Type: research

Comparing Long-Term Survival and Late Toxicities of Different Sequential Chemotherapy Regimens with Intensity-Modulated Radiotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma.
CONCLUSIONS: Sequential chemotherapy combined with IMRT achieved satisfactory survival outcomes in locoregionally advanced NPC with acceptable late toxicities. The GP regimen significantly improved local control compared with PF regimen. Further phase III randomized clinical studies were warranted. PMID: 32361309 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - April 29, 2020 Category: Cancer & Oncology Authors: Wu M, Ou D, Hu C, He X Tags: Transl Oncol Source Type: research

Adrenergic Blockade Promotes Maintenance of Dormancy in Prostate Cancer Through Upregulation of GAS6.
Abstract Men diagnosed with localized prostate cancer can develop metastases many years after initial treatment, resulting in a poor prognosis. The purpose of this study was to investigate the mechanisms by which signaling through norepinephrine (NE) may incite relapse of quiescent prostate cancer. We used an unbiased bioinformatics pipeline to examine mechanisms for recurrence related to sympathetic signaling in the bone marrow. A transcription factor cell array identified ATF1, RAR, and E2F as key nodes in prostate cancer cells exiting quiescence through adrenergic signaling. Subsequent secretome analysis identi...
Source: Translational Oncology - April 28, 2020 Category: Cancer & Oncology Authors: Decker AM, Decker JT, Jung Y, Cackowski FC, Daignault-Newton S, Morgan TM, Shea LD, Taichman RS Tags: Transl Oncol Source Type: research

Immune Suppression in Pregnancy and Cancer: Parallels and Insights.
Abstract Immune system has evolved to maintain homeostatic balance between effector and regulatory immunity, which is critical to both elicit an adequate protective response to fight pathogens and disease, such as cancer, and to prevent damage to healthy tissues. Transient immune suppression can occur under normal physiological conditions, such as during wound healing to enable repair of normal tissue, or for more extended periods of time during fetal development, where the balance is shifted towards regulatory immunity to prevent fetal rejection. Interestingly, tumors can exhibit patterns of immune suppression ve...
Source: Translational Oncology - April 27, 2020 Category: Cancer & Oncology Authors: Kareva I Tags: Transl Oncol Source Type: research

Epithelial-Mesenchymal Transition in Cancer: A Historical Overview.
Abstract Epithelial-mesenchymal transitions (EMTs), the acquisition of mesenchymal features from epithelial cells, occur during some biological processes and are classified into three types: the first type occurs during embryonic development, the second type is associated with adult tissue regeneration, and the third type occurs in cancer progression. EMT occurring during embryonic development in gastrulation, renal development, and the origin and fate of the neural crest is a highly regulated process, while EMT occurring during tumor progression is highly deregulated. EMT allows the solid tumors to become more ma...
Source: Translational Oncology - April 22, 2020 Category: Cancer & Oncology Authors: Ribatti D, Tamma R, Annese T Tags: Transl Oncol Source Type: research

Acquired Uniparental Disomy Regions Are Associated with Disease Outcome in Patients with Oral Cavity and Oropharynx But Not Larynx Cancers.
Abstract Acquired uniparental disomy (aUPD) regions pinpoint homozygousity and monoallelic expressed genes. We analyzed The Cancer Genome Atlas single-nucleotide polymorphism arrays and expression data from oral cavity, oropharynx, and larynx cancers to identify frequency of aUPD in each tumor type and association of aUPD regions and differentially expressed genes in the regions with survival. Cox proportional hazard models were used for survival function; and Student's t test, for differentially expressed genes between groups. The frequency of aUPD was highest in larynx cancers (88.35%) followed by oral cavity (8...
Source: Translational Oncology - April 15, 2020 Category: Cancer & Oncology Authors: Tuna M, I Amos C, B Mills G Tags: Transl Oncol Source Type: research