Decentralization of Next-Generation RNA Sequencing-Based MammaPrint ® and BluePrint® Kit at University Hospitals Leuven and Curie Institute Paris.
Decentralization of Next-Generation RNA Sequencing-Based MammaPrint® and BluePrint® Kit at University Hospitals Leuven and Curie Institute Paris. Transl Oncol. 2019 Sep 09;12(12):1557-1565 Authors: Slembrouck L, Darrigues L, Laurent C, Mittempergher L, Delahaye LJ, Vanden Bempt I, Vander Borght S, Vliegen L, Sintubin P, Raynal V, Bohec M, Reyes C, Rapinat A, Helsmoortel C, Jongen L, Hoste G, Neven P, Wildiers H, Smeets A, Nevelsteen I, Punie K, Van Nieuwenhuysen E, Han S, Vincent Salomon A, Laas Faron E, Cynober T, Gentien D, Baulande S, Snel MH, Witteveen AT, Neijenhuis S, Glas AM, Reyal F, Floris G ...
Source: Translational Oncology - September 9, 2019 Category: Cancer & Oncology Authors: Slembrouck L, Darrigues L, Laurent C, Mittempergher L, Delahaye LJ, Vanden Bempt I, Vander Borght S, Vliegen L, Sintubin P, Raynal V, Bohec M, Reyes C, Rapinat A, Helsmoortel C, Jongen L, Hoste G, Neven P, Wildiers H, Smeets A, Nevelsteen I, Punie K, Van Tags: Transl Oncol Source Type: research

Mast Cells Are Directly Activated by Cancer Cell-Derived Extracellular Vesicles by a CD73- and Adenosine-Dependent Mechanism.
Abstract We have recently shown that mast cells (MCs), which constitute an important part of the tumor microenvironment (TME), can be directly activated by cancer cells under conditions that recapitulate cell to cell contact. However, MCs are often detected in the tumor periphery rather than intratumorally. Therefore, we investigated the possibility of MC activation by cancer cell-derived extracellular vesicles (EVs). Here we show that exposure of MCs to EVs derived from pancreatic cancer cells or non-small cell lung carcinoma results in MC activation, evident by the increased phosphorylation of the ERK1/2 MAP kin...
Source: Translational Oncology - September 4, 2019 Category: Cancer & Oncology Authors: Gorzalczany Y, Merimsky O, Sagi-Eisenberg R Tags: Transl Oncol Source Type: research

Next-Generation Sequencing May Discriminate Extreme Long-term versus Short-term Survival in Patients with Metastatic Small Cell Lung Cancer (SCLC).
CONCLUSIONS: Consolidation radiation therapy and higher predicted drug sensitivity for off compendium were associated with LT compared to ST patients in SCLC. NGS profiling of extreme survivals may improve classification of SCLC and possibly identify clinically relevant new targets. PMID: 31476386 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - August 30, 2019 Category: Cancer & Oncology Authors: Lohinai Z, Megyesfalvi Z, Dome B, Weiss GJ Tags: Transl Oncol Source Type: research

Towards the Optical Detection of Field Cancerization in the Buccal Mucosa of Patients with Lung Cancer.
CONCLUSIONS: We have demonstrated that μs' at 800 nm is increased in the buccal mucosa of patients with lung cancer compared to controls with COPD. This might be an indication of field cancerization in the oral cavity of patients with lung cancer. PMID: 31473370 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - August 29, 2019 Category: Cancer & Oncology Authors: Bugter O, van Brummelen SE, van der Leest KH, Aerts JGJV, Maat APWM, Baatenburg de Jong RJ, Amelink A, Robinson DJ Tags: Transl Oncol Source Type: research

Results from a Phase 1 Study of Sodium Selenite in Combination with Palliative Radiation Therapy in Patients with Metastatic Cancer.
Abstract In preclinical studies, selenite had single agent activity and radiosensitized tumors in vivo. Here we report results from a Phase 1 trial in 15 patients with metastatic cancer treated with selenite (5.5 to 49.5 mg) orally as a single dose 2 hours before each radiation therapy (RT) treatment. Patients received RT regimens that were standard of care. The primary objective of the study was to assess the safety of this combination therapy. Secondary objectives included measurement of pharmacokinetics (PK) and evaluation of efficacy. Endpoints included assessment of PK, toxicity, tumor response, and pain befo...
Source: Translational Oncology - August 24, 2019 Category: Cancer & Oncology Authors: Knox SJ, Jayachandran P, Keeling CA, Stevens KJ, Sandhu N, Stamps-DeAnda SL, Savic R, Shura L, Buyyounouski MK, Grimes K Tags: Transl Oncol Source Type: research

DZIP1 Promotes Proliferation, Migration, and Invasion of Oral Squamous Carcinoma Through the GLI1/3 Pathway.
CONCLUSIONS: DZIP1 promotes the proliferation, migration, and invasion of oral squamous carcinoma through the GLI1/3 pathway. PMID: 31450126 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - August 23, 2019 Category: Cancer & Oncology Authors: Yan W, Deng Y, Zhang Y, Luo J, Lu D, Wan Q, Mao L, Chen Y Tags: Transl Oncol Source Type: research

Novel Therapeutic Anti-ADAM17 Antibody A9(B8) Enhances EGFR-TKI-Mediated Anticancer Activity in NSCLC.
Abstract Epidermal growth factor receptor (EGFR) mutations were found in 30%-40% of non-small cell lung cancer (NSCLC) patients, who often responded well to EGFR tyrosine kinase inhibitors (EGFR-TKIs) as exemplified by erlotinib and gefitinib in the past decades. However, EGFR mutation-led drug resistance usually occurred upon prolonged treatment with EGFR-TKI. Herein, we study the anticancer effects of EGFR-TKI in combination with a newly developed antibody, A9(B8), to target a disintegrin and metalloprotease (ADAM) 17 that was overexpressed in NSCLC patients. NSCLC cell lines with different EGFR mutations were u...
Source: Translational Oncology - August 23, 2019 Category: Cancer & Oncology Authors: Yang Z, Chan KI, Kwok HF, Tam KY Tags: Transl Oncol Source Type: research

Impacts on Histological Features and 11C-Methyl-L-methionine Uptake After "One-Shot" Administration with Bevacizumab Before Surgery in Newly Diagnosed Glioblastoma.
CONCLUSIONS: The present study showed that even one course of BEV administration induced reductions in microvessels, vascular pericytes, and LAT1 expression in glioblastomas. One course of BEV therapy also reduced 11C-met uptake, which might have been largely attributed to reductions in microvessels rather than reductions in LAT1 expression. PMID: 31446307 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - August 22, 2019 Category: Cancer & Oncology Authors: Beppu T, Sato Y, Yamada N, Terasaki K, Sasaki T, Sugai T, Ogasawara K Tags: Transl Oncol Source Type: research

Prognostic Factors and Treatment Strategies for Intrahepatic Cholangiocarcinoma from 2004 to 2013: Population-Based SEER Analysis.
Abstract BACKGROUND: Seventy percent of intrahepatic cholangiocarcinoma (ICC) patients are inoperable. Treatment for unresectable patients is essential to improve poor survival. AIMS: We aimed to evaluate the prognostic factors for ICC patients, and investigate the potential treatment strategies for unresectable patients. METHODS: ICC patients were identified in SEER registry in 2004-2013. Univariate and multivariate Cox proportional hazard regression analysis were performed to evaluate the effect of treatment strategies. RESULTS: Of 2248 cases diagnosed in 2010-2013 and staged according to the Amer...
Source: Translational Oncology - August 22, 2019 Category: Cancer & Oncology Authors: Liu J, Zhong M, Feng Y, Zeng S, Wang Y, Xu H, Zhou H Tags: Transl Oncol Source Type: research

Cancer Panel Assay for Precision Oncology Clinic: Results from a 1-Year Study.
Abstract Next-generation sequencing (NGS)-based cancer panel tests are actively being applied in the clinic for precision oncology. Given the importance of NGS panel tests in the palliative clinical setting, it is critical to understand success rates, factors responsible for test failures, and the incidence of clinically meaningful genetic alterations. We performed NGS cancer panel test with tumors from the stomach (n = 234), colorectum (n = 196), and rare tumors (n = 105) from 535 recurrent or metastatic cancer patients for 1 year. Sequencing was successful in 483 (95.3%) archival tumor samples to fin...
Source: Translational Oncology - August 20, 2019 Category: Cancer & Oncology Authors: Kwon D, Kim B, Shin HC, Kim EJ, Ha SY, Jang KT, Kim ST, Lee J, Kang WK, Park JO, Kim KM Tags: Transl Oncol Source Type: research

Functional and Phenotypic Characterization of Tumor-Infiltrating Leukocyte Subsets and Their Contribution to the Pathogenesis of Hepatocellular Carcinoma and Cholangiocarcinoma.
MR, Paiva A Abstract Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) represent the most common primary liver malignancies whose outcome is influenced by the immune response. In the present study, we evaluated the tumor-infiltrating leukocyte (TIL) populations in 21 HCC patients and 8 CCA patients by flow cytometry immediately after the surgical procedure. Moreover, CD4+T cells, CD8+T cells, monocytes, and macrophages were purified by cell sorting for further analysis of gene expression by quantitative reverse-transcription polymerase chain reaction. Regarding tumor-infiltrating macrophages, we observed...
Source: Translational Oncology - August 16, 2019 Category: Cancer & Oncology Authors: Martín-Sierra C, Martins R, Laranjeira P, Coucelo M, Abrantes AM, Oliveira RC, Tralhão JG, Botelho MF, Furtado E, Domingues MR, Paiva A Tags: Transl Oncol Source Type: research

Targeted Radionuclide Therapy Decreases Melanoma Lung Invasion by Modifying Epithelial-Mesenchymal Transition-Like Mechanisms.
We report herein that [131I]ICF01012 decreases the epithelial-mesenshymal transition-like (EMT-like) markers in both in vivo and in vitro three-dimensional (3D) melanoma spheroid models. [131I]ICF01012 spheroids irradiation resulted in reduced clonogenic capacity of all pigmented spheroids accompanied by increased protein expression levels of phosphorylated H2A.X, p53 and its downstream target p21. In addition, [131I]ICF01012 treatment leads to a significant increase of cell pigmentation as demonstrated in SK-MEL3 human xenograft model. We also showed that [131I]ICF01012 decreases the size and the number of melanoma lung c...
Source: Translational Oncology - August 14, 2019 Category: Cancer & Oncology Authors: Akil H, Rouanet J, Viallard C, Besse S, Auzeloux P, Chezal JM, Miot-Noirault E, Quintana M, Degoul F Tags: Transl Oncol Source Type: research

MTHFD1L, A Folate Cycle Enzyme, Is Involved in Progression of Colorectal Cancer.
Abstract Identification of new molecular targets is needed for the treatment of colorectal cancer (CRC). Methylenetetrahydrofolate dehydrogenase 1 like (MTHFD1L), an enzyme in the folate cycle, is involved in formate generation and therefore in one-carbon metabolism. Here, we examined the expression and the role of MTHFD1L in CRC progression. Bioinformatics analysis of several public databases showed overexpression of MTHFD1L in CRC tissues as compared to normal tissues. Quantitative real-time PCR and Western blotting revealed that expressions of MTHFD1L RNA and protein were higher in CRC tissues compared to their...
Source: Translational Oncology - August 14, 2019 Category: Cancer & Oncology Authors: Agarwal S, Behring M, Hale K, Al Diffalha S, Wang K, Manne U, Varambally S Tags: Transl Oncol Source Type: research

Influence of BRCA1 Germline Mutations in the Somatic Mutational Burden of Triple-Negative Breast Cancer.
Abstract The majority of the hereditary triple-negative breast cancers (TNBCs) are associated with BRCA1 germline mutations. Nevertheless, the understanding of the role of BRCA1 deficiency in the TNBC tumorigenesis is poor. In this sense, we performed whole-exome sequencing of triplet samples (leucocyte, tumor, and normal-adjacent breast tissue) for 10 cases of early-onset TNBC, including 5 hereditary (with BRCA1 germline pathogenic mutation) and 5 sporadic (with no BRCA1 or BRCA2 germline pathogenic mutations), for assessing the somatic mutation repertoire. Protein-affecting somatic mutations were identified for ...
Source: Translational Oncology - August 13, 2019 Category: Cancer & Oncology Authors: Ferreira EN, Brianese RC, de Almeida RVB, Drummond RD, de Souza JE, da Silva IT, de Souza SJ, Carraro DM Tags: Transl Oncol Source Type: research

Concomitant Genetic Alterations are Associated with Worse Clinical Outcome in EGFR Mutant NSCLC Patients Treated with Tyrosine Kinase Inhibitors.
Abstract Epidermal growth factor receptor- tyrosine kinase inhibitors (EGFR-TKI) are recommended first-line therapy for advanced non-small cell lung cancer (NSCLC) with sensitizing EGFR mutations. It is of clinical interest to identify concurrent genetic mutations in NSCLC patients with EGFR mutations in the hopes of discovering predictive biomarkers towards EGFR-TKI treatment. We retrospectively analyzed a cohort of patients with advanced EGFR mutant NSCLC who underwent treatment with first generation TKIs at our hospital by a multi-gene panel via next generation sequencing. A total of 33 patients with mutant EGF...
Source: Translational Oncology - August 8, 2019 Category: Cancer & Oncology Authors: Chang SC, Lai YC, Chang CY, Huang LK, Chen SJ, Tan KT, Yu PN, Lai JI Tags: Transl Oncol Source Type: research

Kr üppel-like Factor 5 Promotes Sonic Hedgehog Signaling and Neoplasia in Barrett's Esophagus and Esophageal Adenocarcinoma.
Krüppel-like Factor 5 Promotes Sonic Hedgehog Signaling and Neoplasia in Barrett's Esophagus and Esophageal Adenocarcinoma. Transl Oncol. 2019 Aug 08;12(11):1432-1441 Authors: Ng CK, Ma K, Cheng Y, Miyashita T, Harmon JW, Meltzer SJ Abstract Krüppel-like Factor 5 (KLF5) is a zinc-finger transcription factor associated with cell cycle progression and cell survival. KLF5 plays a key role in mammalian intestinal epithelium development and maintenance, expressed at high levels in basal proliferating cells and low levels in terminally differentiated cells. Considering Barrett's esophagus (BE) and...
Source: Translational Oncology - August 8, 2019 Category: Cancer & Oncology Authors: Ng CK, Ma K, Cheng Y, Miyashita T, Harmon JW, Meltzer SJ Tags: Transl Oncol Source Type: research

Expression and Role of Methylenetetrahydrofolate Dehydrogenase 1 Like (MTHFD1L) in Bladder Cancer.
In this study we examined MTHFD1L expression in bladder cancer. By using publicly available cancer transcriptome data analysis web-portal UALCAN, we found overexpression of MTHFD1L in bladder cancer and expression was associated with overall survival. RT-PCR and immunoblot analysis confirmed the overexpression of MTHFD1L in muscle invasive bladder cancer tissues compared to normal urothelium. Furthermore, our investigations suggested a critical role for MTHFD1L in bladder cancer cell proliferation, colony formation and invasion. Thus, in this study, we show the significance of the folate metabolic enzyme MTHFD1L in aggress...
Source: Translational Oncology - August 7, 2019 Category: Cancer & Oncology Authors: Eich ML, Rodriguez Pena MDC, Chandrashekar DS, Chaux A, Agarwal S, Gordetsky JB, Ferguson JE, Sonpavde GP, Netto GJ, Varambally S Tags: Transl Oncol Source Type: research

CD63-GPC1-Positive Exosomes Coupled with CA19-9 Offer Good Diagnostic Potential for Resectable Pancreatic Ductal Adenocarcinoma.
Abstract Tumor-released extracellular vesicles (EVs) contain tumor-specific cargo distinguishing them from healthy EVs, and making them eligible as circulating biomarkers. Glypican 1 (GPC1)-positive exosome relevance as liquid biopsy elements is still debated. We carried out a prospective study to quantify GPC1-positive exosomes in sera from pancreatic ductal adenocarcinoma (PDAC) patients undergoing up-front surgery, as compared to controls including patients without cancer history and patients displaying pancreatic preneoplasic lesions. Sera were enriched in EVs, and exosomes were pulled down with anti-CD63 coup...
Source: Translational Oncology - August 7, 2019 Category: Cancer & Oncology Authors: Buscail E, Chauvet A, Quincy P, Degrandi O, Buscail C, Lamrissi I, Moranvillier I, Caumont C, Verdon S, Brisson A, Marty M, Chiche L, Laurent C, Vendrely V, Moreau-Gaudry F, Bedel A, Dabernat S Tags: Transl Oncol Source Type: research

Adipocytes Isolated from Visceral and Subcutaneous Depots of Donors Differing in BMI Crosstalk with Colon Cancer Cells and Modulate their Invasive Phenotype.
CONCLUSIONS: We conclude that interaction between adipocytes and colon cancer cells, especially the highly malignant cells, results in metabolic alterations in colon cancer cells and in highly hypertrophy phenotype which characterized by increasing adipokines secretion from the adipocytes. PMID: 31400580 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - August 7, 2019 Category: Cancer & Oncology Authors: Nimri L, Peri I, Yehuda-Shnaidman E, Schwartz B Tags: Transl Oncol Source Type: research

Gene Alterations in Triple-Negative Breast Cancer Patients in a Phase I/II Study of Eribulin and Olaparib Combination Therapy.
CONCLUSION: These findings suggested somatic BRCA mutation and EGFR-negativity as a potential biomarker for predicting the efficacy of eribulin/olaparib combination therapy. (UMIN000018721). PMID: 31382135 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - August 2, 2019 Category: Cancer & Oncology Authors: Shimomura A, Yonemori K, Yoshida M, Yoshida T, Yasojima H, Masuda N, Aogi K, Takahashi M, Naito Y, Shimizu S, Nakamura R, Hamada A, Michimae H, Hashimoto J, Yamamoto H, Kawachi A, Shimizu C, Fujiwara Y, Tamura K Tags: Transl Oncol Source Type: research

DIVERSet JAG Compounds Inhibit Topoisomerase II and Are Effective Against Adult and Pediatric High-Grade Gliomas.
Abstract High-grade gliomas (HGGs) are aggressive primary brain tumors with local invasive growth and poor clinical prognosis in both adult and pediatric patients. Clinical response is compounded by resistance to standard frontline antineoplastic agents, an absence of novel therapeutics, and poor in vitro models to evaluate these. We screened a range of recently identified anticancer compounds in conventional adult, pediatric, and new biopsy-derived HGG models. These in vitro lines showed a range of sensitivity to standard chemotherapeutics, with varying expression levels of the prognostic markers hypoxia-induced ...
Source: Translational Oncology - July 30, 2019 Category: Cancer & Oncology Authors: Howarth A, Simms C, Kerai N, Allen O, Mihajluk K, Madureira PA, Sokratous G, Cragg S, Lee SY, Morley AD, Keyoumars A, Cox PA, Pilkington GJ, Hill R Tags: Transl Oncol Source Type: research

UAB30, A Novel Rexinoid Agonist, Decreases Stemness In Group 3 Medulloblastoma Human Cell Line Xenografts.
CONCLUSIONS: CD133 is a marker for medulloblastoma SCLCCs. Both CD133-enriched and CD133-depleted medulloblastoma cell populations demonstrated sensitivity to UAB30, indicating its potential as a therapeutic option for group 3 medulloblastoma. PMID: 31362265 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - July 26, 2019 Category: Cancer & Oncology Authors: Williams AP, Garner EF, Stafman LL, Aye JM, Quinn CH, Marayati R, Stewart JE, Atigadda VR, Mroczek-Musulman E, Moore BP, Beierle EA, Friedman GK Tags: Transl Oncol Source Type: research

Hedgehog Signaling: An Achilles' Heel in Cancer.
Abstract Hedgehog signaling pathway originally identified in the fruit fly Drosophila is an evolutionarily conserved signaling mechanism with crucial roles in embryogenesis, growth and patterning. It exerts its biological effect through a signaling mechanism that terminates at glioma-associated oncogene (GLI) transcription factors which alternate between activator and repressor forms and mediate various responses. The important components of the pathway include the hedgehog ligands (SHH), the Patched (PTCH) receptor, Smoothened (SMO), Suppressor of Fused (SuFu) and GLI transcription factors. Activating or inactiva...
Source: Translational Oncology - July 25, 2019 Category: Cancer & Oncology Authors: Niyaz M, Khan MS, Mudassar S Tags: Transl Oncol Source Type: research

A Novel Drug, CC-122, Inhibits Tumor Growth in Hepatocellular Carcinoma through Downregulation of an Oncogenic TCF-4 Isoform.
Abstract Immunomodulatory drugs such as lenalidomide (LEN) have shown significant anti-tumor activity against hematologic malignancies and they may have similar actions on solid tumors as well. We studied the effect of a new analog of the immunomodulatory drugs (CC-122) on the growth of hepatocellular carcinoma (HCC) and explored mechanisms of anti-tumor activity by analyzing expression of a novel oncogenic T-cell factor (TCF)-4 J and its downstream gene activation. LEN and CC-122 significantly reduced the expression levels of TCF-4 J and its target genes (SPP1, AXIN2, MMP7, ASPH, CD24, ANXA1, and CAMK2N1); howeve...
Source: Translational Oncology - July 25, 2019 Category: Cancer & Oncology Authors: Tomimaru Y, Aihara A, Wands JR, Aloman C, Kim M Tags: Transl Oncol Source Type: research

Emerging Pathogenic and Prognostic Significance of Paired Box 3 (PAX3) Protein in Adult Gliomas.
Abstract Gliomas present the most common type of brain tumors in adults, characterized by high morbidity and mortality. In search of potential molecular targets, members of paired box (PAX) family have been found expressed in neural crest cells, regulating their proliferation, apoptosis, migration and differentiation. Recently, PAX3 overexpression has been implicated in glioma tumorigenesis by enhancing proliferation, increasing invasiveness and inducing resistance to apoptosis of glioma cells, while maintaining brain glioma stem cells (BGSCs) stemness. Although the oncogenic potential of PAX3 in gliomas is still ...
Source: Translational Oncology - July 25, 2019 Category: Cancer & Oncology Authors: Angelopoulou E, Paudel YN, Piperi C Tags: Transl Oncol Source Type: research

m1A Regulated Genes Modulate PI3K/AKT/mTOR and ErbB Pathways in Gastrointestinal Cancer.
CONCLUSION: This study demonstrated for the first time the dysregulation of m1A regulators in GI cancer and its signaling pathways and will contribute to the understanding of RNA modification in cancer. PMID: 31352195 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - July 24, 2019 Category: Cancer & Oncology Authors: Zhao Y, Zhao Q, Kaboli PJ, Shen J, Li M, Wu X, Yin J, Zhang H, Wu Y, Lin L, Zhang L, Wan L, Wen Q, Li X, Cho CH, Yi T, Li J, Xiao Z Tags: Transl Oncol Source Type: research

Orally bioavailable glutamine antagonist prodrug JHU-083 penetrates mouse brain and suppresses the growth of MYC-driven medulloblastoma.
Abstract A subset of poor-prognosis medulloblastoma has genomic amplification of MYC. MYC regulates glutamine metabolism in multiple cellular contexts. We modified the glutamine analog 6-diazo-5-oxo-l-norleucine (DON) to mask its carboxylate and amine functionalities, creating a prodrug termed JHU-083 with increased oral bioavailability. We hypothesized that this prodrug would kill MYC-expressing medulloblastoma. JHU-083 treatment caused decreased growth and increased apoptosis in human MYC-expressing medulloblastoma cell lines. We generated a mouse MYC-driven medulloblastoma model by transforming C57BL/6 mouse ce...
Source: Translational Oncology - July 21, 2019 Category: Cancer & Oncology Authors: Hanaford AR, Alt J, Rais R, Wang SZ, Kaur H, Thorek DLJ, Eberhart CG, Slusher BS, Martin AM, Raabe EH Tags: Transl Oncol Source Type: research

Upregulated Circular RNA circ-UBE2D2 Predicts Poor Prognosis and Promotes Breast Cancer Progression by Sponging miR-1236 and miR-1287.
Abstract Emerging evidence suggests that circular RNAs (circRNAs) are linked to the development and progression of human cancers. Nevertheless, their contribution to breast cancer (BC) is still largely unknown. In the current study, we screened and identified a novel circRNA, circ-UBE2D2, which was highly expressed in BC cell lines and tissues and was closely related to aggressive clinical features and dismal prognosis. Small interfering RNA (siRNA)-mediated circ-UBE2D2 silencing notably inhibited the proliferation, migration and invasion of BC cells, whereas circ-UBE2D2 overexpression displayed opposite effects. ...
Source: Translational Oncology - July 20, 2019 Category: Cancer & Oncology Authors: Wang Y, Li J, Du C, Zhang L, Zhang Y, Zhang J, Wang L Tags: Transl Oncol Source Type: research

Clinical Implications and Translation of an Off-Target Pharmacology Profiling Hit: Adenosine Uptake Inhibition In Vitro.
We report clinical consequences of an off-target activity observed during profiling of AMG 337, a selective inhibitor of the mesenchymal-epithelial transition factor being evaluated for treatment of solid tumors. In our screen of 151 potential off-targets, AMG 337 inhibited only adenosine transporter (AT). During clinical trials, headache emerged as the dose-limiting AE in the first-in-human trial. It was thought that headache was caused by extracellular accumulation of adenosine from inhibition of AT by AMG 337 and subsequent adenosine-mediated vasodilation through adenosine receptors (ARs). Further nonclinical studies we...
Source: Translational Oncology - July 19, 2019 Category: Cancer & Oncology Authors: Amouzadeh HR, Dimery I, Werner J, Ngarmchamnanrith G, Engwall MJ, Vargas HM, Arrindell D Tags: Transl Oncol Source Type: research

Breast Cancer Treatment Response Monitoring Using Quantitative Ultrasound and Texture Analysis: Comparative Analysis of Analytical Models.
CONCLUSION: An early stage treatment response prediction model developed by quantitative ultrasound and texture analysis combined with modern computational methods permits offering effective alternatives to standard treatment for refractory patients. PMID: 31325763 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - July 17, 2019 Category: Cancer & Oncology Authors: Sannachi L, Gangeh M, Tadayyon H, Gandhi S, Wright FC, Slodkowska E, Curpen B, Sadeghi-Naini A, Tran W, Czarnota GJ Tags: Transl Oncol Source Type: research

Association of miR-34b/c rs4938723 and TP53 Arg72Pro Polymorphisms with Neuroblastoma Susceptibility: Evidence from Seven Centers.
This study was performed to validate the association of these two polymorphisms and neuroblastoma risk with 819 cases and 1780 controls. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to assess the strength of the associations. False positive report possibility analysis was adopted to dissect out real significant associations from chance findings. We found that both TP53 Arg72Pro (CG/GG vs. CC: adjusted OR = 0.82, 95% CI = 0.69-0.98) and miR-34b/c rs4938723 (TC/CC vs. TT: adjusted OR = 0.64, 95% CI = 0.54-0.75) were associated with decreased neuroblastoma susceptibility. Strati...
Source: Translational Oncology - July 17, 2019 Category: Cancer & Oncology Authors: Li L, Zhu J, Lu T, Liu W, Tang J, Zhang J, Wang Y, Li Y, Li S, Zhou H, Xia H, He J, Cheng J Tags: Transl Oncol Source Type: research

Monoclonal Antibodies Against Human Papillomavirus E6 and E7 Oncoproteins Inhibit Tumor Growth in Experimental Cervical Cancer.
In this report, we describe the utilization of anti-HPV E6 and HPV E7 mAbs in an experimental murine model of human cervical cancer tumors. We used differential dosing strategies of mAbs C1P5 (anti-HPV 16 E6) and TVG701Y (anti-HPV E7) administered via intraperitoneal or intratumoral injections. We compared mAbs to the action of chemotherapeutic agent Cisplatin and demonstrated the capacity of mAbs to significantly inhibit tumor growth. Furthermore, we investigated the contribution of the immune system and found increased complement deposition in both C1P5 and TVG701Y treated tumors compared to irrelevant mAb therapy. Taken...
Source: Translational Oncology - July 17, 2019 Category: Cancer & Oncology Authors: Jiang Z, Albanese J, Kesterson J, Warrick J, Karabakhtsian R, Dadachova E, Phaëton R Tags: Transl Oncol Source Type: research

Magnetic Resonance Colonography Enables the Efficacy Assessment of Immune Checkpoint Inhibitors in an Orthotopic Colorectal Cancer Mouse Model.
Abstract Immune checkpoint inhibitors (ICIs) have become an effective therapeutic option for colorectal cancer and studies on these drugs have therefore increased greatly. Efficacy assessments of ICIs in preclinical orthotopic colorectal cancer using MRI have not been reported however due to the difficulties in conducting colorectal imaging. The purpose of this present study was to investigate the feasibility of using magnetic resonance colonography (MRC) to evaluate the efficacy of an ICI, an anti-PD-L1 antibody, in an orthotopic colorectal cancer mouse model. The mouse model was generated by the engraftment of c...
Source: Translational Oncology - July 11, 2019 Category: Cancer & Oncology Authors: Chae YJ, Kim J, Heo H, Woo CW, Kim ST, Kim MJ, Choi JR, Kim DH, Woo DC, Kim KW, Choi Y Tags: Transl Oncol Source Type: research

The Combination of Olaratumab with Doxorubicin and Cisplatinum Regresses a Chemotherapy-Resistant Osteosarcoma in a Patient-Derived Orthotopic Xenograft Mouse Model.
Abstract Chemotherapy-resistant osteosarcoma is a recalcitrant disease. It is a frequent cause of death to the patients who are usually adolescent or young adults. The goal of the present study was to determine the efficacy of the combination of olaratumab (OLA), doxorubicin (DOX), and cisplatinum (CDDP) on osteosarcoma, which is resistant to first-line therapy, in a patient-derived orthotopic xenograft (PDOX) model. The osteosarcoma PDOX model was randomized into six treatment groups of six mice: control; CDDP alone; DOX and CDDP; OLA + DOX; OLA + CDDP; and OLA + DOX and CDDP. Tumor size and body weig...
Source: Translational Oncology - July 9, 2019 Category: Cancer & Oncology Authors: Higuchi T, Sugisawa N, Miyake K, Oshiro H, Yamamoto N, Hayashi K, Kimura H, Miwa S, Igarashi K, Bouvet M, Singh SR, Tsuchiya H, Hoffman RM Tags: Transl Oncol Source Type: research

Interferon β and Anti-PD-1/PD-L1 Checkpoint Blockade Cooperate in NK Cell-Mediated Killing of Nasopharyngeal Carcinoma Cells.
In conclusion, combination of IFNβ and anti-PD-1, augmenting cytotoxicity of NK cells against NPC cells, could be a strategy to improve NPC-directed therapy and warrants further evaluation in vivo. PMID: 31295651 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - July 8, 2019 Category: Cancer & Oncology Authors: Makowska A, Braunschweig T, Denecke B, Shen L, Baloche V, Busson P, Kontny U Tags: Transl Oncol Source Type: research

Building CT Radiomics-Based Models for Preoperatively Predicting Malignant Potential and Mitotic Count of Gastrointestinal Stromal Tumors.
CONCLUSION: The radiomic models using CE-CT showed a good predictive performance for preoperative risk stratification of GISTs and hold great potential for personalized clinical decision making. PMID: 31280094 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - July 4, 2019 Category: Cancer & Oncology Authors: Wang C, Li H, Jiaerken Y, Huang P, Sun L, Dong F, Huang Y, Dong D, Tian J, Zhang M Tags: Transl Oncol Source Type: research

Lysosome Inhibition by Mefloquine Preferentially Enhances the Cytotoxic Effects of Tyrosine Kinase Inhibitors in Blast Phase Chronic Myeloid Leukemia.
Abstract Despite the efficacy of BCR-ABL tyrosine kinase inhibitors (TKIs) in chronic phase-chronic myeloid leukemia, the management of blast phase-chronic myeloid leukemia (BP-CML) remains a challenge. Therefore, there is an urgent need to identify alternative agents that act synergistically with BCR-ABL TKIs in BP-CML. Our results show that the anti-malarial agent, mefloquine augments the efficacy of TKIs in CML cell lines and primary CML cells in vitro, including those with the T315I mutation. This effect is selective as mefloquine is more effective in inducing apoptosis, inhibiting colony formation and self-re...
Source: Translational Oncology - July 2, 2019 Category: Cancer & Oncology Authors: Lam Yi H, Than H, Sng C, Cheong MA, Chuah C, Xiang W Tags: Transl Oncol Source Type: research

Circulating Mitochondrial DNA is Linked to Progression and Prognosis of Epithelial Ovarian Cancer.
g Z Abstract As peripheral blood contains fluctuated levels of circulating cell-free mitochondrial DNA (ccf mtDNA), we aimed to evaluate ccf mtDNA as a biomarker for diagnosis and prognosis of epithelial ovarian cancer (EOC). In the present study, we recruited 165 EOC patients and 60 healthy women. Quantitative RT-PCR was applied to amplify 79-bp and 230-bp fragments of the mitochondrial 16 s RNA gene in sera of these participants. MtDNA integrity was defined as the ratio of long to short mtDNA fragments. We observed that the levels of mtDNA79 and mtDNA230 were significantly increased (P = .0001), whereas the ...
Source: Translational Oncology - July 1, 2019 Category: Cancer & Oncology Authors: Meng X, Schwarzenbach H, Yang Y, Müller V, Li N, Tian D, Shen Y, Gong Z Tags: Transl Oncol Source Type: research

Preclinical Pharmacokinetic and Safety Studies of Copper-Diacetyl-Bis(N4-Methylthiosemicarbazone) (Cu-ATSM): Translational Studies for Internal Radiotherapy.
In this study, the concentrations of Cu-ATSM and ATSM in mouse plasma after intravenous administration were determined by liquid chromatography-tandem mass spectrometry, and the half-lives were estimated to be 21.5 and 22.4 minutes for Cu-ATSM and ATSM, respectively. Based on this result, approach 2 of the current ICH M3 [R2] guideline was adopted, and a 7-day intravenous toxicity study was conducted in mice. Cu-ATSM and ATSM in a ratio of 2:25 mimicking our current investigational drug was used, and no adverse effects were observed when Cu-ATSM and ATSM were administered at 81 μg/kg. These results and those of prev...
Source: Translational Oncology - June 25, 2019 Category: Cancer & Oncology Authors: Matsumoto H, Yoshii Y, Baden A, Kaneko E, Hashimoto H, Suzuki H, Kawamura K, Zhang MR, Higashi T, Kurihara H Tags: Transl Oncol Source Type: research

Identification of a Novel Fusion Gene, FAM174A-WWC1, in Early-Onset Colorectal Cancer: Establishment and Characterization of Four Human Cancer Cell Lines from Early-Onset Colorectal Cancers.
Abstract Colorectal cancer (CRC) is the third most common cancer diagnosed worldwide and represents the second most common cause of all cancer-related deaths in Korea. Although epidemiological data indicate a sharp increase in the incidence of CRC among individuals older than 50 years, more than 10% of CRCs occur before reaching 50. These are known as early-onset CRCs (EOCRCs) and are likely to be suggestive of hereditary predisposition. However, known familial CRC syndromes account for only 20% of genetic aberrations of EOCRC, and the remaining 80% are still in question. Therefore, we aimed to establish reprodu...
Source: Translational Oncology - June 19, 2019 Category: Cancer & Oncology Authors: Kim SC, Shin R, Seo HY, Kim M, Park JW, Jeong SY, Ku JL Tags: Transl Oncol Source Type: research

Tumor Site-Dependent Transport Properties Determine Nanotherapeutics Delivery and Its Efficacy.
Abstract Insufficient delivery of systemically administered anticancer drugs to tumors can compromise therapeutic efficacy and develop drug delivery-based therapeutic resistance. Nanotherapeutics such as PEGylated liposomal doxorubicin (PLD) are designed to preferentially accumulate in tumors utilizing enhanced permeation and retention effect. However, their antitumor effects and resulting clinical outcomes are modest and heterogeneous among tumors. Here, we aimed to investigate whether the amount and efficacy of PLD delivered to tumors are tumor site dependent. We established orthotopic primary tumor or liver met...
Source: Translational Oncology - June 19, 2019 Category: Cancer & Oncology Authors: Kai M, Ziemys A, Liu YT, Kojic M, Ferrari M, Yokoi K Tags: Transl Oncol Source Type: research

Monitoring Breast Cancer Response to Neoadjuvant Chemotherapy Using Ultrasound Strain Elastography.
Abstract Strain elastography was used to monitor response to neoadjuvant chemotherapy (NAC) in 92 patients with biopsy-proven, locally advanced breast cancer. Strain elastography data were collected before, during, and after NAC. Relative changes in tumor strain ratio (SR) were calculated over time, and responder status was classified according to tumor size changes. Statistical analyses determined the significance of changes in SR over time and between response groups. Machine learning techniques, such as a naïve Bayes classifier, were used to evaluate the performance of the SR as a marker for Miller-Payne p...
Source: Translational Oncology - June 18, 2019 Category: Cancer & Oncology Authors: Fernandes J, Sannachi L, Tran WT, Koven A, Watkins E, Hadizad F, Gandhi S, Wright F, Curpen B, El Kaffas A, Faltyn J, Sadeghi-Naini A, Czarnota G Tags: Transl Oncol Source Type: research

High Glucose Promotes Human Glioblastoma Cell Growth by Increasing the Expression and Function of Chemoattractant and Growth Factor Receptors.
Abstract Diabetes mellitus, characterized by hyperglycemia, is considered as a risk factor of cancers including malignant gliomas. However, the direct effect of high glucose on cancer cell behavior is not clear. We therefore investigated the effect of hyperglycemia on the growth of human glioblastoma (GBM) cells. Our results revealed that high glucose (HG) promoted the proliferation and inhibited the apoptosis of a human GBM cell line U87. Mechanistically, HG upregulated the expression and function of a G-protein coupled chemoattractant receptor (GPCR) formyl peptide receptor 1 (FPR1) and epidermal growth factor r...
Source: Translational Oncology - June 14, 2019 Category: Cancer & Oncology Authors: Bao Z, Chen K, Krepel S, Tang P, Gong W, Zhang M, Liang W, Trivett A, Zhou M, Wang JM Tags: Transl Oncol Source Type: research

Telomere Maintenance-Associated PML Is a Potential Specific Therapeutic Target of Human Colorectal Cancer.
Abstract Telomere length maintenance is essential for cell proliferation, which is particularly prominent in cancer. We validate that the primary colorectal tumors exhibit heterogeneous telomere lengths but mostly (90%) short telomeres relative to normal tissues. Intriguingly, relatively short telomeres are associated with tumor malignancy as indicated by poorly differentiated state, and these tumors contain more cancer stem-like cells (CSLCs) identified by several commonly used markers CD44, EPHB2 or LGR5. Moreover, promyelocytic leukemia (PML) and ALT-associated PML nuclear bodies (APBs) are frequently found in ...
Source: Translational Oncology - June 14, 2019 Category: Cancer & Oncology Authors: Gong P, Wang H, Zhang J, Fu Y, Zhu Z, Wang J, Yin Y, Wang H, Zhou Z, Yang J, Liu L, Gou M, Zeng M, Yuan J, Wang F, Pan X, Xiang R, Weissman SM, Qi F, Liu L Tags: Transl Oncol Source Type: research

Immune-related somatic mutation genes are enriched in PDACs with diabetes.
Abstract The bidirectional interaction between pancreatic cancer (PanCa) and diabetes has been confirmed by epidemiological studies, but until now, the underlying molecular mechanisms for this connection is not fully understood yet. Here, we analyzed the clinical and genomic data of 26 pancreatic ductal adenocarcinoma (PDAC) patients without diabetes, and six diabetic PDAC patients, whose tumors underwent targeted next-generation sequencing (551 cancer-related genes included). Ingenuity Pathway Analysis (IPA) was performed to investigate genetic alterations and biological consequences associated with PDACs with or...
Source: Translational Oncology - June 13, 2019 Category: Cancer & Oncology Authors: Wang K, Zhou W, Meng P, Wang P, Zhou C, Yao Y, Wu S, Wang Y, Zhao J, Zou D, Jin G Tags: Transl Oncol Source Type: research

Pathological Pattern of Intrahepatic HBV in HCC is Phenocopied by PDX-Derived Mice: a Novel Model for Antiviral Treatment.
CONCLUSION: We delineated pathological HBV profiles of HCC specimens and perilesional areas, which provided evidence for virus-based therapy in the future. PDX mice may phenocopy virological and cellular features of patient tissues, which is novel in the virus-related hepatocarcinogenesis field. PMID: 31202090 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - June 12, 2019 Category: Cancer & Oncology Authors: Liu J, Chen S, Zou Z, Tan D, Liu X, Wang X Tags: Transl Oncol Source Type: research

Allele Loss and Reduced Expression of CYCLOPS Genes is a Characteristic Feature of Chromophobe Renal Cell Carcinoma.
Abstract Copy-number alterations Yielding Cancer Liabilities Owing to Partial losS (CYCLOPS) genes have been recently identified as the most enriched class of copy-number associated gene dependencies in human cancer. These genes are cell essential and render tumor cells highly sensitive to the expression of the remaining copy. Chromophobe renal cell carcinoma (chRCC) is characterized by frequent chromosomal deletions, but the relevance of CYCLOPS genes in this tumor subtype is unclear. We found 39 (31%) of 124 recently published candidate CYCLOPS genes (B. Paolella et al., eLife 2017;6:e23268) located on 7 autosom...
Source: Translational Oncology - June 11, 2019 Category: Cancer & Oncology Authors: Ohashi R, Schraml P, Batavia A, Angori S, Simmler P, Rupp N, Ajioka Y, Oliva E, Moch H Tags: Transl Oncol Source Type: research

Knockdown of Lumican Inhibits Proliferation and Migration of Bladder Cancer.
Abstract Lumican (LUM) is differentially expressed between normal and cancer tissues. The purpose of this study was to investigate the role of LUM in the proliferation and migration of bladder cancer (BCa) cells. Our study included 97 cases of BCa diagnosis from our hospital between June 2013 and June 2016. The expression of LUM was analyzed by immunohistochemistry and Western blot. To characterize the function of LUM, BCa cells were stably infected with a lentivirus against LUM, and cell proliferation, migration and cell cycle were investigated. In addition, xenograft experiments were performed in nude mice to ev...
Source: Translational Oncology - June 6, 2019 Category: Cancer & Oncology Authors: Mao W, Luo M, Huang X, Wang Q, Fan J, Gao L, Zhang Y, Geng J Tags: Transl Oncol Source Type: research

The role of natural killer cells in hepatocellular carcinoma development and treatment: A narrative review.
Abstract A major obstacle for treatment of HCC is the inadequate efficacy and limitation of the available therapeutic options. Despite the recent advances in developing novel treatment options, HCC still remains one of the major causes of cancer morbidity and mortality around the world. Achieving effective treatment and eradication of HCC is a challenging task, however recent studies have shown that targeting Natural Killer cells, as major regulators of immune system, can help with the complete treatment of HCC, restoration of normal liver function and subsequently higher survival rate of HCC patients. Studies hav...
Source: Translational Oncology - June 6, 2019 Category: Cancer & Oncology Authors: Juengpanich S, Shi L, Iranmanesh Y, Chen J, Cheng Z, Khoo AK, Pan L, Wang Y, Cai X Tags: Transl Oncol Source Type: research

Two-Week Aflibercept or Erlotinib Administration Does Not Induce Changes in Intestinal Morphology in Male Sprague-Dawley Rats But Aflibercept Affects Serum and Urine Metabolic Profiles.
In this study, we aimed to characterize the gastrointestinal and metabolic changes after a 2-week treatment period with aflibercept, an antiangiogenic VEGFR decoy, and with erlotinib, a tyrosine-kinase inhibitor. Male rats were treated either with aflibercept or erlotinib for 2 weeks. During the 2-week treatment period, the animals in the aflibercept group received two subcutaneous doses of 25 mg/kg aflibercept. The erlotinib group got 10 mg/kg of erlotinib by oral gavage every other day. The control groups were treated similarly but received either saline injections or oral gavage of water. Intestinal toxicity was ass...
Source: Translational Oncology - June 6, 2019 Category: Cancer & Oncology Authors: Forsgård RA, Marrachelli VG, Lindén J, Frias R, Collado MC, Korpela R, Monleon D, Spillmann T, Österlund P Tags: Transl Oncol Source Type: research