Serum Apolipoprotein E and Other Inflammatory Markers Can Identify Non-Responding Patients to a Dendritic Cell Vaccine.
Abstract BACKGROUND: Despite the majority of patients do not gain any benefit from dendritic cells (DC) vaccines, this approach has occasionally given rise to dramatic responses in melanoma. Biomarkers are crucial to identify which patients are more likely to respond. We looked for correlations between pre- or post- vaccination biomarkers and clinical outcomes to DC therapy in a cohort of patients with stage IV melanoma receiving a vaccine with autologous ex-vivo expanded DCs pulsed with allogeneic tumor cell lysate. METHODS: Serial serum samples were collected at baseline, week 4 and 12 and they were analyze...
Source: Translational Oncology - December 7, 2018 Category: Cancer & Oncology Authors: Leeman H, Kaminska E, Green D, Bodman-Smith M, Gravett A, Bodman-Smith K, Copier J, Coulton G, Fusi A, Dalgleish AG Tags: Transl Oncol Source Type: research

Discordance between FISH, IHC, and NGS Analysis of ALK Status in Advanced Non-Small Cell Lung Cancer (NSCLC): a Brief Report of 7 Cases.
CONCLUSIONS: In our discordant cases, a coexistent complex pattern (deleted, split, and amplified/polysomic) of ALK gene was observed by FISH analysis. These complex rearranged cases were not detectable by IHC, and it could be speculated that more complex biological mechanisms could modulate protein expression. These data highlight the role of IHC and underscore the complexity of the genetic pattern of ALK. It could be crucial to consider these findings in order to best select patients for anti-ALK treatment in daily clinical practice. PMID: 30529852 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - December 4, 2018 Category: Cancer & Oncology Authors: Scattone A, Catino A, Schirosi L, Caldarola L, Tommasi S, Lacalamita R, Montagna ES, Galetta D, Serio G, Zito FA, Mangia A Tags: Transl Oncol Source Type: research

Associations Between PET Parameters and Expression of Ki-67 in Breast Cancer.
CONCLUSION: SUVmax correlated moderately with expression of Ki-67 and, therefore, cannot be used as a surrogate marker for tumor proliferation. Further studies are needed to evaluate associations between PET parameters and histopathological findings like hormone receptor status in breast cancer. PMID: 30522044 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - December 3, 2018 Category: Cancer & Oncology Authors: Surov A, Meyer HJ, Wienke A Tags: Transl Oncol Source Type: research

Synergistic Activity of Paclitaxel, Sorafenib, and Radiation Therapy in advanced Renal Cell Carcinoma and Breast Cancer.
This study aimed to investigate the involvement of mitochondrial cytochrome c-dependent apoptosis in the mechanism of action of a combination of paclitaxel, sorafenib, and RT in RCC and breast cancer. RCC and breast cancer cell lines were exposed to paclitaxel and sorafenib alone or combined in the presence of radiation, and cell viability was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The synergistic anticancer effects of the combination therapy on cell cycle and intracellular signaling pathways were estimated using flow cytometry and immunoblot analysis. RCC and breast cancer...
Source: Translational Oncology - December 3, 2018 Category: Cancer & Oncology Authors: Choi KH, Jeon JY, Lee YE, Kim SW, Kim SY, Yun YJ, Park KC Tags: Transl Oncol Source Type: research

PTEN Hamartoma Tumor Syndrome and Immune Dysregulation.
Abstract Carriers of a pathogenic germline mutations in the PTEN gene, a well-known tumor suppressor gene, are at increased risk of multiple benign and malignant tumors, e.g. breast, thyroid, endometrial and colon cancer. This is called PTEN Hamartomous Tumor Syndrome (PHTS). PHTS patients may also have an increased risk of immunological dysregulation, such as autoimmunity and immune deficiencies. The effects of PTEN on the immune system have been studied in murine knockout models demonstrating that loss of PTEN function leads to dysregulation of the immune response. This results in susceptibility to autoimmunity,...
Source: Translational Oncology - November 29, 2018 Category: Cancer & Oncology Authors: Eissing M, Ripken L, Schreibelt G, Westdorp H, Ligtenberg M, Netea-Maier R, Netea MG, de Vries IJM, Hoogerbrugge N Tags: Transl Oncol Source Type: research

Serological Assessment of Activated Fibroblasts by alpha-Smooth Muscle Actin ( α-SMA): A Noninvasive Biomarker of Activated Fibroblasts in Lung Disorders.
Serological Assessment of Activated Fibroblasts by alpha-Smooth Muscle Actin (α-SMA): A Noninvasive Biomarker of Activated Fibroblasts in Lung Disorders. Transl Oncol. 2018 Nov 29;12(2):368-374 Authors: Holm Nielsen S, Willumsen N, Leeming DJ, Daniels SJ, Brix S, Karsdal MA, Genovese F, Nielsen MJ Abstract OBJECTIVES: Remodeling of the extracellular matrix (ECM) is a key event in different lung disorders, such as fibrosis and cancer. The most common cell type in the connective tissue is fibroblasts, which transdifferentiate into myofibroblasts upon activation. All myofibroblasts express α-...
Source: Translational Oncology - November 29, 2018 Category: Cancer & Oncology Authors: Holm Nielsen S, Willumsen N, Leeming DJ, Daniels SJ, Brix S, Karsdal MA, Genovese F, Nielsen MJ Tags: Transl Oncol Source Type: research

Microphthalmia-Associated Transcription Factor (MITF) Regulates Immune Cell Migration into Melanoma.
Abstract Microphthalmia-associated transcription factor (MITF) is a key transcription factor in melanoma development and progression. MITF amplification and downregulation have been observed in a significant proportion of melanoma patients and correlate with clinical outcomes. Here, we have investigated the effect of MITF on melanoma chemokine expression and immune cell attraction. In B16F10 melanoma cells, MITF knockdown reduced expression of CXCL10, with concomitantly decreased attraction of immune cells and accelerated tumor outgrowth. Conversely, overexpression of MITF in YUMM1.1 melanoma cells also led to an ...
Source: Translational Oncology - November 28, 2018 Category: Cancer & Oncology Authors: Wiedemann GM, Aithal C, Kraechan A, Heise C, Cadilha BL, Zhang J, Duewell P, Ballotti R, Endres S, Bertolotto C, Kobold S Tags: Transl Oncol Source Type: research

Inhibition of the STAT5/Pim Kinase Axis Enhances Cytotoxic Effects of Proteasome Inhibitors on FLT3-ITD-Positive AML Cells by Cooperatively Inhibiting the mTORC1/4EBP1/S6K/Mcl-1 Pathway.
Abstract FLT3-ITD and FLT3-TKD are the most frequent tyrosine kinase mutations in acute myeloid leukemia (AML), with the former conferring a poor prognosis. We have recently revealed that FLT3-ITD confers resistance to the PI3K/AKT pathway inhibitors by protecting the mTORC1/4EBP1/Mcl-1 pathway through Pim kinases induced by STAT5 activation in AML. The proteasome inhibitor bortezomib has recently been reported as a promising agent for treatment of AML. Here, we show that the proteasome inhibitor bortezomib as well as carfilzomib induces apoptosis through the intrinsic pathway more conspicuously in cells transform...
Source: Translational Oncology - November 22, 2018 Category: Cancer & Oncology Authors: Nogami A, Okada K, Ishida S, Akiyama H, Umezawa Y, Miura O Tags: Transl Oncol Source Type: research

OKN-007 Increases temozolomide (TMZ) Sensitivity and Suppresses TMZ-Resistant Glioblastoma (GBM) Tumor Growth.
In this study, we assessed combining OKN-007 with TMZ in vivo in a human G55 GBM orthotopic xenograft model and in vitro in TMZ-resistant and TMZ-sensitive human GBM cell lines. For the in vivo studies, magnetic resonance imaging was used to assess tumor growth and vascular alterations. Percent animal survival was also determined. For the in vitro studies, cell growth, IC50 values, RNA-seq, RT-PCR, and ELISA were used to assess growth inhibition, possible mechanism-of actions (MOAs) associated with combined OKN-007 + TMZ versus TMZ alone, and gene and protein expression levels, respectively. Microarray analysis of OKN-...
Source: Translational Oncology - November 20, 2018 Category: Cancer & Oncology Authors: Towner RA, Smith N, Saunders D, Brown CA, Cai X, Ziegler J, Mallory S, Dozmorov MG, Coutinho De Souza P, Wiley G, Kim K, Kang S, Kong DS, Kim YT, Fung KM, Wren JD, Battiste J Tags: Transl Oncol Source Type: research

Phosphoproteome Profiling Reveals Multifunctional Protein NPM1 as part of the Irradiation Response of Tumor Cells.
Abstract To fight resistances to radiotherapy, the understanding of escape mechanisms of tumor cells is crucial. The aim of this study was to identify phosphoproteins that are regulated upon irradiation. The comparative analysis of the phosphoproteome before and after irradiation brought nucleophosmin (NPM1) into focus as a versatile phosphoprotein that has already been associated with tumorigenesis. We could show that knockdown of NPM1 significantly reduces tumor cell survival after irradiation. NPM1 is dephosphorylated stepwise within 1 hour after irradiation at two of its major phosphorylation sites: threonine-...
Source: Translational Oncology - November 16, 2018 Category: Cancer & Oncology Authors: Wiesmann N, Gieringer R, Grus F, Brieger J Tags: Transl Oncol Source Type: research

miR-224 Is Significantly Upregulated and Targets Caspase-3 and Caspase-7 During Colorectal Carcinogenesis.
N, Rugge M Abstract miR-224 has recently emerged as a driver oncomiR in sporadic colorectal carcinogenesis, but its pathogenetic role is still controversial. A large phenotypical and molecularly characterized series of preinvasive and invasive colorectal lesions was investigated for miR-224 expression by qRT-PCR and in situ hybridization. The caspase-3 and caspase-7 status was also assessed and correlated to miR-224 dysregulation. miR-224 was significantly upregulated during the adenoma-carcinoma sequence and in the context of inflammatory bowel disease dysplastic lesions, whereas its expression was significantly...
Source: Translational Oncology - November 15, 2018 Category: Cancer & Oncology Authors: Fassan M, Cui R, Gasparini P, Mescoli C, Guzzardo V, Vicentini C, Munari G, Loupakis F, Lonardi S, Braconi C, Scarpa M, D'Angelo E, Pucciarelli S, Angriman I, Agostini M, D'Incá R, Farinati F, Gafà R, Lanza G, Frankel WL, Croce CM, Valeri N, Rugge M Tags: Transl Oncol Source Type: research

A Deep Learning-Based Radiomics Model for Differentiating Benign and Malignant Renal Tumors.
CONCLUSIONS: Deep learning can be used to classify benign and malignant renal tumors from CT images. Our patient-level models could benefit from 3D data to improve the accuracy. PMID: 30448734 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - November 15, 2018 Category: Cancer & Oncology Authors: Zhou L, Zhang Z, Chen YC, Zhao ZY, Yin XD, Jiang HB Tags: Transl Oncol Source Type: research

A Pilot Prospective Study of Refractory Solid Tumor Patients for NGS-Based Targeted Anticancer Therapy.
In conclusion, this study suggests that targeted therapy based on NGS test may be a good choice for improving the care of patients with refractory solid tumors. PMID: 30448735 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - November 15, 2018 Category: Cancer & Oncology Authors: Seol YM, Kwon CH, Lee SJ, Lee SJ, Choi Y, Choi YJ, Kim H, Park DY Tags: Transl Oncol Source Type: research

Establishment of a Novel PDX Mouse Model and Evaluation of the Tumor Suppression Efficacy of Bortezomib Against Liposarcoma.
Abstract The patient-derived xenograft (PDX) model has been adopted as a major tool for studying tumorigenesis and differentiation in various carcinomas. In addition, it has been used in the development of anticancer agents. PDX models have been among the most meaningful tools used to understand the role of stromal cells and vascular cells in the body, which are major factors in cancer development and the application of therapeutic agents. Also, the establishment of PDX models from liposarcoma patients is considered to be important for understanding lipomagenesis and following drugs development. For these reasons,...
Source: Translational Oncology - November 14, 2018 Category: Cancer & Oncology Authors: Jo EB, Hong D, Lee YS, Lee H, Park JB, Kim SJ Tags: Transl Oncol Source Type: research

Co-Expression of VEGF and IL-6 Family Cytokines is Associated with Decreased Survival in HER2 Negative Breast Cancer Patients: Subtype-Specific IL-6 Family Cytokine-Mediated VEGF Secretion.
Abstract Breast cancer cell-response to inflammatory cytokines such as interleukin-6 (IL-6) and oncostatin M (OSM) may affect the course of clinical disease in a cancer subtype-dependent manner. Furthermore, vascular endothelial growth factor A (VEGF) secretion induced by IL-6 and OSM may also be subtype-dependent. Utilizing datasets from Oncomine, we show that poor survival of invasive ductal carcinoma (IDC) breast cancer patients is correlated with both high VEGF expression and high cytokine or cytokine receptor expression in tumors. Importantly, epidermal growth factor receptor-negative (HER2-), but not HER2-po...
Source: Translational Oncology - November 12, 2018 Category: Cancer & Oncology Authors: Tawara K, Scott H, Emathinger J, Ide A, Fox R, Greiner D, LaJoie D, Hedeen D, Nandakumar M, Oler AJ, Holzer R, Jorcyk C Tags: Transl Oncol Source Type: research

High Keratin 8/18 Ratio Predicts Aggressive Hepatocellular Cancer Phenotype.
CONCLUSIONS: We can prove that intermediate filaments and their binding partners are tightly linked to hepatic lipid metabolism and to hepatocarcinogenesis. We suggest KRT8/18 ratio as a novel HCC biomarker for HCC. PMID: 30439626 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - November 12, 2018 Category: Cancer & Oncology Authors: Golob-Schwarzl N, Bettermann K, Mehta AK, Kessler SM, Unterluggauer J, Krassnig S, Kojima K, Chen X, Hoshida Y, Bardeesy NM, Müller H, Svendova V, Schimek MG, Diwoky C, Lipfert A, Mahajan V, Stumptner C, Thüringer A, Fröhlich LF, Stojakovic T, Nilsson Tags: Transl Oncol Source Type: research

Downregulation of IQGAP2 Correlates with Prostate Cancer Recurrence and Metastasis.
Abstract IQGAP2 was recently reported as a tumor suppressor of prostate cancer (PC). Nonetheless, its clinical implications remain unknown. To address this issue, we extracted data related to IQGAP2 mRNA expression and genomic alterations from multiple large datasets within the Oncomine and cBioPortal databases and performed in silico analyses to determine a potential association of IQGAP2 mRNA expression and its genomic alterations with PC progression. In 4 cohorts consisting of 118 normal prostate tissues and 277 PCs, IQGAP2 mRNA expression was significantly elevated particularly in low-grade (primary Gleason sc...
Source: Translational Oncology - November 11, 2018 Category: Cancer & Oncology Authors: Xie Y, Zheng L, Tao L Tags: Transl Oncol Source Type: research

Multi-Spectral Fluorescence Imaging of Colon Dysplasia InVivo Using a Multi-Spectral Endoscopy System.
CONCLUSION: The multi-spectral endoscopy system may allow endoscopists to clearly identify cancerous lesion that has different patterns of various target expression using multiple fluorescent probes. PMID: 30419540 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - November 9, 2018 Category: Cancer & Oncology Authors: Bae SM, Bae DJ, Do EJ, Oh G, Yoo SW, Lee GJ, FChae JS, Yun Y, Kim S, Kim KH, Chung E, Kim JK, Hwang SW, Park SH, Yang DH, Ye BD, Byeon JS, Yang SK, Joo J, Kim SY, Myung SJ Tags: Transl Oncol Source Type: research

Attenuation of CD47-SIRP α Signal in Cholangiocarcinoma Potentiates Tumor-Associated Macrophage-Mediated Phagocytosis and Suppresses Intrahepatic Metastasis.
Attenuation of CD47-SIRPα Signal in Cholangiocarcinoma Potentiates Tumor-Associated Macrophage-Mediated Phagocytosis and Suppresses Intrahepatic Metastasis. Transl Oncol. 2018 Nov 08;12(2):217-225 Authors: Vaeteewoottacharn K, Kariya R, Pothipan P, Fujikawa S, Pairojkul C, Waraasawapati S, Kuwahara K, Wongkham C, Wongkham S, Okada S Abstract The involvement of chronic inflammation in cholangiocarcinoma (CCA) progression is well established. Cluster of differentiation 47 (CD47) is mutually expressed in various cancers and serves as a protective signal for phagocytic elimination. CD47 signaling bl...
Source: Translational Oncology - November 8, 2018 Category: Cancer & Oncology Authors: Vaeteewoottacharn K, Kariya R, Pothipan P, Fujikawa S, Pairojkul C, Waraasawapati S, Kuwahara K, Wongkham C, Wongkham S, Okada S Tags: Transl Oncol Source Type: research

Targeting PIM Kinases Affects Maintenance of CD133 Tumor Cell Population in Hepatoblastoma.
Abstract Hepatoblastoma is the most common primary liver tumor in children, but treatment has not changed significantly in the past 20 years. We have previously demonstrated that Proviral Integration site for Moloney murine leukemia (PIM) kinases promote tumorigenesis in hepatoblastoma. Stem cell-like cancer cells (SCLCCs) are a subset of cells thought to be responsible for chemoresistance, metastasis, relapse, and recurrence. The aim of this study was to identify SCLCCs in hepatoblastoma and determine the role of PIM kinases in SCLCCs. Hepatoblastoma cells were separated into CD133-enriched and CD133-depleted pop...
Source: Translational Oncology - November 6, 2018 Category: Cancer & Oncology Authors: Stafman LL, Williams AP, Garner EF, Aye JM, Stewart JE, Yoon KJ, Whelan K, Beierle EA Tags: Transl Oncol Source Type: research

Enhancing the Radiation Response in KRAS Mutant Colorectal Cancers Using the c-Met Inhibitor Crizotinib.
CONCLUSIONS: Inhibition of c-Met with crizotinib effectively sensitizes cetuximab-resistant KRAS mutant colorectal cancer cell lines to radiation. Crizotinib has the potential to improve outcomes in locally advanced rectal cancer patients undergoing chemoradiation. PMID: 30412912 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - November 6, 2018 Category: Cancer & Oncology Authors: Cuneo KC, Mehta RK, Kurapati H, Thomas DG, Lawrence TS, Nyati MK Tags: Transl Oncol Source Type: research

Therapeutic Targeting Cancer-Initiating Cell Markers by Exosome miRNA: Efficacy and Functional Consequences Exemplified for claudin7 and EpCAM.
CONCLUSIONS: Exo are efficiently loaded with miRNA, miRNA-delivery being supported by Exo tailoring. Partial cld7 and EpC silencing by Exo miRNA affects metastasis-promoting tumor cell activities. The findings suggest miRNA loading of tailored Exo as an easy approachable and efficient adjuvant therapy. PMID: 30393102 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - October 27, 2018 Category: Cancer & Oncology Authors: Kyuno D, Zhao K, Bauer N, Ryschich E, Zöller M Tags: Transl Oncol Source Type: research

MYC-Induced miR-203b-3p and miR-203a-3p Control Bcl-xL Expression and Paclitaxel Sensitivity in Tumor Cells.
io MJ Abstract Taxanes are chemotherapeutic agents used in the treatment of solid tumors, particularly of breast, ovarian, and lung origin. However, patients show divergent therapy responses, and the molecular determinants of taxane sensitivity have remained elusive. Especially the signaling pathways that promote death of the taxane-treated cells are poorly characterized. Here we describe a novel part of a signaling route in which c-Myc enhances paclitaxel sensitivity through upregulation of miR-203b-3p and miR-203a-3p; two clustered antiapoptosis protein Bcl-xL controlling microRNAs. In vitro, the miR-203b-3p dec...
Source: Translational Oncology - October 22, 2018 Category: Cancer & Oncology Authors: Aakko S, Straume AH, Birkeland EE, Chen P, Qiao X, 'Lønning PE, Kallio MJ Tags: Transl Oncol Source Type: research

Advances in Molecular Mechanisms and Treatment of Radiation-Induced Pulmonary Fibrosis.
Abstract Radiation-induced pulmonary fibrosis (RIPF) is a common complication in patients with lung cancer and breast cancer after receiving thoracic radiotherapy. The average incidence of RIPF is 16%-28% after radiotherapy. RIPF includes a heterogeneous group of lung disorders characterized by progressive and irreversible destruction of lung architecture and disruption of gas exchange. The clinical signs of RIPF include increasing dyspnea, deteriorating lung function, and accumulation of interstitial fluid, eventually leading to respiratory failure. No medical therapy for RIPF has been approved for routine clinic...
Source: Translational Oncology - October 17, 2018 Category: Cancer & Oncology Authors: Chen Z, Wu Z, Ning W Tags: Transl Oncol Source Type: research

Genomic Characterization of TP53-Wild-Type Esophageal Carcinoma.
PMID: 30317074 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - October 11, 2018 Category: Cancer & Oncology Authors: Quaas A, Heydt C, Gebauer F, Alakus H, Loeser H, Buettner R, Hillmer A, Bruns C, Merkelbach-Bruse S, Zander T, Frommolt P Tags: Transl Oncol Source Type: research

Preclinical In Vitro and In Vivo Evidence of an Antitumor Effect of CX-4945, a Casein Kinase II Inhibitor, in Cholangiocarcinoma.
CONCLUSION: CX-4945 has an antiproliferative effect on CCA and enhances the effect of gemcitabine and cisplatin through its inhibitory effect on the PI3K/AKT pathway and DNA repair. PMID: 30316146 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - October 10, 2018 Category: Cancer & Oncology Authors: Zakharia K, Miyabe K, Wang Y, Wu D, Moser CD, Borad MJ, Roberts LR Tags: Transl Oncol Source Type: research

The Evolutionarily Conserved Cassette Exon 7b Drives ERG's Oncogenic Properties.
Abstract The oncogene ERG encodes an ETS family transcription factor and is implicated in blood, vascular, and bone development and in prostate, blood, and bone cancer. The ERG gene is alternatively spliced; of particular interest is its cassette exon 7b which adds 24 amino acids, in frame, to the transcriptional activation domain. Higher exon 7b inclusion rates are associated with increased cell proliferation and advanced prostate cancer. The 24 amino acids encoded by exon 7b show evolutionary conservation from humans to echinoderms, highlighting their functional importance. Throughout evolution, these 24 amino a...
Source: Translational Oncology - October 5, 2018 Category: Cancer & Oncology Authors: Jumbe SL, Porazinski SR, Oltean S, Mansell JP, Vahabi B, Wilson ID, Ladomery MR Tags: Transl Oncol Source Type: research

Phenotype of vigilin expressing breast cancer cells binding to the 69 nt 3'UTR element in CSF-1R mRNA.
Abstract Vigilin, a nucleocytoplasmic shuttling protein, post-transcriptionally suppresses proto-oncogene c-fms expression (encoding CSF-1R) in breast cancer by binding to a 69 nt cis-acting 3-UTR element in CSF-1R mRNA. CSF-1R is an important mediator of breast cancer development, metastasis, and survival. We confirm that vigilin decreases in vitro reporter luciferase activity as well as the translation rate of target mRNAs. We further explore the mechanism of suppression of CSF-1R. We show that the 69 nt binding element has profound effects on translation efficiency of CSF-1R mRNA, not seen in the presence of mu...
Source: Translational Oncology - October 3, 2018 Category: Cancer & Oncology Authors: Woo HH, Lee SC, Stoffer JB, Rush D, Chambers SK Tags: Transl Oncol Source Type: research

Phenotypic and Expressional Heterogeneity in the Invasive Glioma Cells.
CONCLUSION: The GBM tumorsphere core promoted invasion, and the invasive front was dominated by a phenotypically defined cell population expressing genes regulating traits found in aggressive cancers. The detected cellular heterogeneity and transcriptional differences between the highly invasive and core cells identifies potential targets for manipulation of GBM invasion. PMID: 30292065 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - October 3, 2018 Category: Cancer & Oncology Authors: Fayzullin A, Sandberg CJ, Spreadbury M, Saberniak BM, Grieg Z, Skaga E, Langmoen IA, Vik-Mo EO Tags: Transl Oncol Source Type: research

Targeting DDX3 in Medulloblastoma Using the Small Molecule Inhibitor RK-33.
In this study, we demonstrate the role of DDX3 in driving medulloblastoma. With the use of a small molecule inhibitor of DDX3, RK-33, we could inhibit growth and promote cell death in two medulloblastoma cell lines, DAOY and UW228, with IC50 values of 2.5 μM and 3.5 μM, respectively. Treatment of DAOY and UW228 cells with RK-33 caused a G1 arrest, resulted in reduced TCF reporter activity, and reduced mRNA expression levels of downstream target genes of the WNT pathway, such as Axin2, CCND1, MYC, and Survivin. In addition, treatment of DAOY and UW228 cells with a combination of RK-33 and radiation exhibited a synergi...
Source: Translational Oncology - October 3, 2018 Category: Cancer & Oncology Authors: Tantravedi S, Vesuna F, Winnard PT, Martin A, Lim M, Eberhart CG, Berlinicke C, Raabe E, van Diest PJ, Raman V Tags: Transl Oncol Source Type: research

MYC Amplification as a Potential Mechanism of Primary Resistance to Crizotinib in ALK-Rearranged Non-Small Cell Lung Cancer: A Brief Report.
CONCLUSIONS: We postulate that the MYC gene may be implicated in the mechanism of primary resistance to ALK inhibitors. We also suggest potential MYC-directed inhibition strategies to overcome primary resistance in advanced ALK-rearranged NSCLC. PMID: 30290287 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - October 2, 2018 Category: Cancer & Oncology Authors: Rihawi K, Alfieri R, Fiorentino M, Fontana F, Capizzi E, Cavazzoni A, Terracciano M, La Monica S, Ferrarini A, Buson G, Petronini PG, Ardizzoni A Tags: Transl Oncol Source Type: research

Investigation of PP2A and Its Endogenous Inhibitors in Neuroblastoma Cell Survival and Tumor Growth.
In conclusion, activation of PP2A may provide a novel therapeutic target for neuroblastoma. PMID: 30286326 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - October 1, 2018 Category: Cancer & Oncology Authors: Williams AP, Garner EF, Waters AM, Stafman LL, Aye JM, Markert H, Stewart JE, Beierle EA Tags: Transl Oncol Source Type: research

Successful Secondary Engraftment of Pancreatic Ductal Adenocarcinoma and Cholangiocarcinoma Patient-Derived Xenografts After Previous Failed Primary Engraftment.
CONCLUSION: Secondary PDX engraftment using cryopreserved primary cancerous is feasible after previous failed engraftment attempts and can result in a 50% increase in overall engraftment efficiency with decreases in LT formation. This technique allows for salvage of critical patient PDX models that would otherwise not exist. SYNOPSIS: Patient-derived xenografts have many important translational applications however can be limited by engraftment failure. We demonstrate optimized methodology utilizing cryopreservation of primary tumor tissue that allows for subsequent successful secondary engraftment and creation of PDX...
Source: Translational Oncology - September 28, 2018 Category: Cancer & Oncology Authors: Hernandez MC, Yang L, Leiting JL, Sugihara T, Bergquist JR, Ivanics T, Graham R, Truty MJ Tags: Transl Oncol Source Type: research

Markers of Mitochondrial Metabolism in Tumor Hypoxia, Systemic Inflammation, and Adverse Outcome of Rectal Cancer.
In conclusion, serum ROS and damaged mtDNA may be markers of the mitochondrial metabolism driven by the state of oxygenation of the primary tumor and possibly implicated in systemic inflammation and adverse outcome of LARC. PMID: 30273860 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - September 28, 2018 Category: Cancer & Oncology Authors: Bousquet PA, Meltzer S, Sønstevold L, Esbensen Y, Dueland S, Flatmark K, Sitter B, Bathen TF, Seierstad T, Redalen KR, Eide L, Ree AH Tags: Transl Oncol Source Type: research

A Syngeneic Mouse Model of Epithelial Ovarian Cancer Port Site Metastases.
Abstract Epithelial ovarian cancer (EOC) is a deadly gynecologic malignancy, but animal models for the study of EOC pathophysiology and drug efficacy are limited. Based on the finding that women with EOC are at risk for metastasis at a trocar site after laparoscopy, we developed a syngeneic murine model of port-site metastasis of EOC. We leveraged the ID8 murine EOC cell line to induce intra-peritoneal tumors in mice. Once durable intraperitoneal tumor was confirmed with bioluminescence imaging, intra-abdominal wall tumors were induced by abdominal wall puncture with a hollow bore needle. This resulted in a robust...
Source: Translational Oncology - September 26, 2018 Category: Cancer & Oncology Authors: Wilkinson-Ryan I, Pham MM, Sergent P, Tafe LJ, Berwin BL Tags: Transl Oncol Source Type: research

Smoking-Induced SLPI Expression Hinders HPV Infections Also in Squamous Cell Carcinomas of the Vulva.
fmann M Abstract In HNSCC, protein- and mRNA-expression of the antileukoproteinase SLPI are significantly inverse correlated with HPV-infection suggesting that elevated expression of SLPI protects against HPV-infections. Moreover, SLPI-expression is up-regulated in HNSCC-patients reporting a smoking habit. Here, we investigate the described correlation in other HPV-driven cancers, namely vulvar squamous cell carcinoma (VSCC). FFPE samples of 99 VSCC were analyzed by PCR for HPV-DNA-expression and by RT-qPCR for SLPI-mRNA-expression. Of 99 VSCC 10 (10.1%) are HPV-positive; 9 were HPV16; 1 HPV18; all were E6/E7 mRNA...
Source: Translational Oncology - September 26, 2018 Category: Cancer & Oncology Authors: Quabius ES, Loehr J, Haaser D, Günther V, Maass N, Röcken C, Mathiak M, Alkatout I, Hoffmann M Tags: Transl Oncol Source Type: research

Vimentin and Non-Muscle Myosin IIA are Members of the Neural Precursor Cell Expressed Developmentally Down-Regulated 9 (NEDD9) Interactome in Head and Neck Squamous Cell Carcinoma Cells.
Abstract Here we demonstrate an interaction between neural precursor cell expressed, developmentally-downregulated 9 (NEDD9) and the cytoskeletal proteins vimentin and non-muscle myosin IIA (NMIIA), based on co-immunoprecipitation and mass spectrometric sequence identification. Vimentin was constitutively phosphorylated at Ser56 but vimentin associated with NEDD9-was not phosphorylated at Ser56. In contrast, NMIIA bound to NEDD9 was phosphorylated on S1943 consistent with its function in invasion and secretion. Treatment of cells with the vimentin-targeting steroidal lactone withaferin A had no effect on vimentin ...
Source: Translational Oncology - September 26, 2018 Category: Cancer & Oncology Authors: Semelakova M, Grauzam S, Betadthunga P, Tiedeken J, Coaxum S, Neskey DM, Rosenzweig SA Tags: Transl Oncol Source Type: research

mTORC1 Prevents Epithelial Damage During Inflammation and Inhibits Colitis-Associated Colorectal Cancer Development.
úlveda N, Nava P Abstract Epithelial cells lining the intestinal mucosa constitute a selective-semipermeable barrier acting as first line of defense in the organism. The number of those cells remains constant during physiological conditions, but disruption of epithelial cell homeostasis has been observed in several pathologies. During colitis, epithelial cell proliferation decreases and cell death augments. The mechanism responsible for these changes remains unknown. Here, we show that the pro-inflammatory cytokine IFNγ contributes to the inhibition of epithelial cell proliferation in intestinal epith...
Source: Translational Oncology - September 25, 2018 Category: Cancer & Oncology Authors: Gutiérrez-Martínez IZ, Rubio JF, Piedra-Quintero ZL, Lopez-Mendez O, Serrano C, Reyes-Maldonado E, Salinas-Lara C, Betanzos A, Shibayama M, Silva-Olivares A, Candelario-Martinez A, Meraz-Ríos MA, Schnoor M, Villegas-Sepúlveda N, Nava P Tags: Transl Oncol Source Type: research

Biomarkers Associated with Tumor Heterogeneity in Prostate Cancer.
CONCLUSIONS: In prostate cancer, ITH, a potential factor affecting tumor progression, is associated with PTEN deletion and cytotoxic T cell inactivation. PMID: 30265975 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - September 25, 2018 Category: Cancer & Oncology Authors: Yun JW, Lee S, Ryu D, Park S, Park WY, Joung JG, Jeong J Tags: Transl Oncol Source Type: research

SERPINB7 Expression Predicts Poor Pancreatic Cancer Survival Upon Gemcitabine Treatment.
In conclusion, SERPINB7 was identified as the first predictive RNA biomarker for PDAC. This study suggests that patients who expressed SERPINB7 might receive another treatment than gem alone. PMID: 30245304 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - September 20, 2018 Category: Cancer & Oncology Authors: Bianconi D, Herac M, Spies D, Kieler M, Brettner R, Unseld M, Fürnkranz K, Famler B, Schmeidl M, Minichsdorfer C, Zielinski C, Heller G, Prager GW Tags: Transl Oncol Source Type: research

Combined Metabolo-Volumetric Parameters of 18F-FDG-PET and MRI Can Predict Tumor Cellularity, Ki67 Level and Expression of HIF 1alpha in Head and Neck Squamous Cell Carcinoma: A Pilot Study.
z S Abstract BACKGROUND: Our purpose was to evaluate associations of combined 18F-FDG-PET and MRI parameters with histopathological features in head and neck squamous cell carcinoma (HNSCC). METHODS: Overall, 22 patients with HNSCC were acquired (10 with G1/2 tumors and 12 with G3 tumors).18F-FDG-PET/CT and MRI was performed and maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG) and metabolic tumor volume (MTV) were estimated. Neck MRI was obtained on a 3 T scanner. Diffusion weighted imaging was performed with estimation of apparent diffusion coefficient (ADC). Perfusion parameters Ktr...
Source: Translational Oncology - September 18, 2018 Category: Cancer & Oncology Authors: Surov A, Meyer HJ, Höhn AK, Sabri O, Purz S Tags: Transl Oncol Source Type: research

Prognostic Impact of Presurgical CA19-9 Level in Pancreatic Adenocarcinoma: A Pooled Analysis.
Valentini V Abstract BACKGROUND: Presurgical carbohydrate antigen 19-9 (CA19-9) level predicts overall survival (OS) in resected pancreatic adenocarcinoma (PaC). The aim of this pooled analysis was to evaluate if presurgical CA19-9 level can also predict local control (LC) and distant metastasis-free survival (DMFS). METHODS: Seven hundred patients with PaC from eight institutions who underwent surgical resection ± adjuvant treatment between 2000 and 2014 were analyzed. Patients were divided based on four presurgical CA19-9 level cutoffs (5, 37, 100, 353 U/ml). Weibull regression model to identify ind...
Source: Translational Oncology - September 17, 2018 Category: Cancer & Oncology Authors: Mattiucci GC, Morganti AG, Cellini F, Buwenge M, Casadei R, Farioli A, Alfieri S, Arcelli A, Bertini F, Calvo FA, Cammelli S, Fuccio L, Giaccherini L, Guido A, Herman JM, Macchia G, Maidment BW, Miller RC, Minni F, Regine WF, Reni M, Partelli S, Falconi M Tags: Transl Oncol Source Type: research

Inhibition of Radiation and Temozolomide-Induced Invadopodia Activity in Glioma Cells Using FDA-Approved Drugs.
In this study, utilizing an array of techniques, including gelatin matrix degradation assays, we show that GBM cell lines can form functional gelatin matrix degrading invadopodia and secrete matrix metalloproteinase 2 (MMP-2), a known invadopodia-associated matrix-degrading enzyme. Furthermore, these cellular activities were augmented in cells that survived radiotherapy and temozolomide treatment, indicating that surviving cells may possess a more invasive phenotype posttherapy. We performed a screen of FDA-approved agents not previously used for treating GBM patients with the aim of investigating their "anti-invadopo...
Source: Translational Oncology - September 13, 2018 Category: Cancer & Oncology Authors: Whitehead CA, Nguyen HPT, Morokoff AP, Luwor RB, Paradiso L, Kaye AH, Mantamadiotis T, Stylli SS Tags: Transl Oncol Source Type: research

Determination of Hepatocellular Carcinoma and Characterization of Hepatic Focal Lesions with Adaptive Multi-Exponential Intravoxel Incoherent Motion Model.
CONCLUSION: The adaptive multi-exponential IVIM model was useful and reliable to distinguish HCC from other hepatic lesions. PMID: 30216762 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - September 11, 2018 Category: Cancer & Oncology Authors: Zhang HX, Zhang XS, Kuai ZX, Zhou Y, Sun YF, Ba ZC, He KB, Sang XQ, Yao YF, Chu CY, Zhu YM Tags: Transl Oncol Source Type: research

Sorcin a Potential Molecular Target for Cancer Therapy.
Abstract Sorcin (Soluble resistance related calcium binding protein) is a small soluble penta EF family (PEF) of calcium (Ca2+) binding protein (22,000 Da). It has been reported to play crucial roles in the regulation of calcium homeostasis, apoptosis, vesicle trafficking, cancer development, and multidrug resistance (MDR). Overexpression of sorcin has been reported to be associated with different cancers such as breast cancer, colorectal cancer, gastric cancer, leukemia, lung cancer, nasopharyngeal cancer, ovarian cancer, etc. Essentially, expression of sorcin has been found to be elevated in cancer cells as comp...
Source: Translational Oncology - September 11, 2018 Category: Cancer & Oncology Authors: Shabnam B, Padmavathi G, Banik K, Girisa S, Monisha J, Sethi G, Fan L, Wang L, Mao X, Kunnumakkara AB Tags: Transl Oncol Source Type: research

Clinical Relevance of Genomic Changes in Recurrent Pediatric Solid Tumors.
Abstract PURPOSE: Relapsed/refractory pediatric cancers show poor prognosis; however, their genomic patterns remain unknown. To investigate the genetic mechanisms of tumor relapse and therapy resistance, we characterized genomic alterations in diagnostic and relapsed lesions in patients with relapsed/refractory pediatric solid tumors using targeted deep sequencing. PATIENTS AND METHODS: A targeted sequencing panel covering the exons of 381 cancer genes was used to characterize 19 paired diagnostic and relapsed samples from patients with relapsed/refractory pediatric solid tumors. RESULTS: The mean covera...
Source: Translational Oncology - September 11, 2018 Category: Cancer & Oncology Authors: Lee B, Lee JW, Shim JH, Joung JG, Yun JW, Bae JS, Shin HT, Sung KW, Park WY Tags: Transl Oncol Source Type: research

Clinical Validation of Automatable Gaussian Normalized CBV in Brain Tumor Analysis: Superior Reproducibility and Slightly Better Association with Survival than Current Standard Manual Normal Appearing White Matter Normalization.
CONCLUSION: GN-nCBV has a slightly better association with clinical gold standard OS than conventional WM-nCBV in our glioblastoma patient cohort. This equivalent or superior validity, combined with the advantages of higher reproducibility, lower interoperator variability, and easier automation, makes GN-nCBV superior to WM-nCBV for clinical and research use in glioma patients. We recommend widespread adoption and incorporation of GN-nCBV into commercial dynamic susceptibility contrast processing software. PMID: 30216765 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - September 11, 2018 Category: Cancer & Oncology Authors: Qin L, Li X, Li A, Cheng S, Qu J, Reinshagen K, Hu J, Himes N, Lu G, Young GS Tags: Transl Oncol Source Type: research

The Mutant p53-Targeting Compound APR-246 Induces ROS-Modulating Genes in Breast Cancer Cells.
Abstract TP53 is the most frequently mutated gene in human cancer and thus an attractive target for novel cancer therapy. Several compounds that can reactive mutant p53 protein have been identified. APR-246 is currently being tested in a phase II clinical trial in high-grade serous ovarian cancer. We have used RNA-seq analysis to study the effects of APR-246 on gene expression in human breast cancer cell lines. Although the effect of APR-246 on gene expression was largely cell line dependent, six genes were upregulated across all three cell lines studied, i.e., TRIM16, SLC7A11, TXNRD1, SRXN1, LOC344887, and SLC7A1...
Source: Translational Oncology - September 6, 2018 Category: Cancer & Oncology Authors: Synnott NC, Madden SF, Bykov VJN, Crown J, Wiman KG, Duffy MJ Tags: Transl Oncol Source Type: research

Autophagy: A New Mechanism of Prosurvival and Drug Resistance in Multiple Myeloma.
to MA Abstract Autophagy is an intracellular self-degradative process that balances cell energy source and regulates tissue homeostasis. In physiological condition, autophagy funnels cytoplasmic constituents to autophagolysosomes for degradation and is an alternative way for cell-death behavior. Here, we inspected autophagy as a prosurvival mechanism essential for drug resistance in multiple myeloma (MM). Accordingly, autophagy inhibitors used in association to conventional anti-MM drugs might enforce the effect against resistant MM plasma cells and render autophagy a new therapeutic target. PMID: 30196237 [P...
Source: Translational Oncology - September 6, 2018 Category: Cancer & Oncology Authors: Desantis V, Saltarella I, Lamanuzzi A, Mariggiò MA, Racanelli V, Vacca A, Frassanito MA Tags: Transl Oncol Source Type: research

Survival Impact of Delaying Postoperative Radiotherapy in Patients with Esophageal Cancer.
Abstract The purpose of the current study was to retrospectively assess the effect of postoperative radiotherapy (RT) delay on survival for patients with esophageal cancer. From 2008 to 2011, patients with esophageal cancer who had undergone postoperative RT in five different hospitals in China were reviewed. Clinical data, including time interval between surgery to RT, were prospectively collected. Kaplan-Meier method was conducted to estimate the effect of each variable on progression-free survival (PFS) and overall survival (OS), with differences assessed by log-rank test. Univariate Cox proportional-hazards mo...
Source: Translational Oncology - September 6, 2018 Category: Cancer & Oncology Authors: Wang Y, Guan S, Bi Y, Lin S, Ma J, Xing Q, Liu C, Zhang R, Qu Z, Jiang P, Chen X, Cheng Y Tags: Transl Oncol Source Type: research