Cytological Immunostaining of HMGA2, LRP1B, and TP63 as Potential Biomarkers for Triaging Human Papillomavirus-Positive Women.
In this study, we investigated the performance of three HPV integration hot-spots, HMGA2, LRP1B, and TP63, as potential triage markers in HPV screening tests. MATERIALS AND METHODS: This cross-sectional study was conducted from November 2016 to December 2017 in the First Affiliated Hospital of Sun Yat-sen University. Immunocytochemistry was carried out using residual cervical cell samples from 121 HPV-positive cases (23 normal, 24 cervical intraepithelial neoplasia (CIN) 1, and 74 CIN2+). RESULTS: Of the 121 cases, 77 showed completely paired for the three biomarkers. In these 77 cases, receiver operating charact...
Source: Translational Oncology - May 15, 2019 Category: Cancer & Oncology Authors: Jiang Y, Zhu C, He D, Gao Q, Tian X, Ma X, Wu J, Das BC, Severinov K, Hitzeroth II, Debata PR, Liu R, Zou L, Shi L, Xu H, Wang K, Bao Y, Ka-Kit LR, You Z, Cui Z, Hu Z Tags: Transl Oncol Source Type: research

DPS-2: A Novel Dual MEK/ERK and PI3K/AKT Pathway Inhibitor with Powerful Ex Vivo and In Vivo Anticancer Properties.
Abstract Development of novel bioactive compounds against KRAS and/or BRAF mutant colorectal cancer (CRC) is currently an urgent need in oncology. In addition, single or multitarget kinase inhibitors against MEK/ERK and PI3K/AKT pathways are of potential therapeutic advantage. A new compound based on the benzothiophene nucleus was synthesized, based on previous important outcomes on other pharmaceutical preparations, to be tested as potential anticancer agent. Treatments by 2-5 μM DPS-2 of several CRC and melanoma cell lines bearing either BRAF or KRAS mutations have shown a remarkable effect on cell viability ...
Source: Translational Oncology - May 13, 2019 Category: Cancer & Oncology Authors: Goulielmaki M, Assimomytis N, Rozanc J, Taki E, Christodoulou I, Alexopoulos LG, Zoumpourlis V, Pintzas A, Papahatjis D Tags: Transl Oncol Source Type: research

A Three-dimensional Ex Vivo Viability Assay Reveals a Strong Correlation Between Response to Targeted Inhibitors and Mutation Status in Melanoma Lymph Node Metastases.
P, Mælandsmo GM Abstract Although clinical management of melanoma has changed considerably in recent years, intrinsic treatment resistance remains a severe problem and strategies to design personal treatment regimens are highly warranted. We have applied a three-dimensional (3D) ex vivo drug efficacy assay, exposing disaggregated cells from 38 freshly harvested melanoma lymph node metastases and 21 patient derived xenografts (PDXs) to clinical relevant drugs for 7 days, and examined its potential to evaluate therapy response. A strong association between Vemurafenib response and BRAF mutation status was achieved (P 
Source: Translational Oncology - May 13, 2019 Category: Cancer & Oncology Authors: Flørenes VA, Flem-Karlsen K, McFadden E, Bergheim IR, Nygaard V, Nygård V, Farstad IN, Øy GF, Emilsen E, Giller-Fleten K, Ree AH, Flatmark K, Gullestad HP, Hermann R, Ryder T, Wernhoff P, Mælandsmo GM Tags: Transl Oncol Source Type: research

Activation of Pyroptotic Cell Death Pathways in Cancer: An Alternative Therapeutic Approach.
Abstract Cancer can be considered the result of a series of genetic variations that lead to a normal cell being transformed into a malignant one while avoiding cell death-atypical characteristics of tumor development. Although a large number of genomics and epigenetic alterations have been identified in cells undergoing apoptotic, autophagic or necrotic cell death, the treatment of cancer remains thought-provoking. Pyroptosis is differentiated from other types of programmed cell death and is mainly activated by Caspase-1. To initiate pyroptosis, cells receive specific "death" messages, produce cytokines,...
Source: Translational Oncology - May 11, 2019 Category: Cancer & Oncology Authors: Nagarajan K, Soundarapandian K, Thorne RF, Li D, Li D Tags: Transl Oncol Source Type: research

Novel Small Molecule MEK Inhibitor URML-3881 Enhances Cisplatin Sensitivity in Clear Cell Ovarian Cancer.
Abstract Advanced clear cell ovarian cancer (CCOC) is a highly fatal malignancy with a scarcity of effective treatment options. CCOC is inherently chemotherapy resistance, but the exact mechanism of this resistance has yet to be established. Prosurvival signaling, such as through the MAPK cascade, is one way in which cancer cells can evade chemotherapy. We have determined that CCOC exhibits baseline elevated levels of MAPK activity, which increase further upon cisplatin exposure. We have developed a novel MEK inhibitor, URML-3881, to test the effect of MAPK inhibition in CCOC. URML-3881 was found to reduce in vitr...
Source: Translational Oncology - May 10, 2019 Category: Cancer & Oncology Authors: Rowswell-Turner RB, Rutishauser JA, Kim KK, Khazan N, Sivagnanalingam U, Jones AM, Singh RK, Moore RG Tags: Transl Oncol Source Type: research

Host Genome Variation is Associated with Neurocognitive Outcome in Survivors of Pediatric Medulloblastoma.
Abstract Host genome analysis is a promising source of predictive information for long-term morbidity in cancer survivors. However, studies on genetic predictors of long-term outcome, particularly neurocognitive function following chemoradiation in pediatric oncology, are limited. Here, we evaluated variation in host genome of long-term survivors of medulloblastoma and its association with neurocognitive outcome. Whole-genome sequencing was conducted on peripheral blood of long-term survivors of pediatric medulloblastoma who also completed neuropsychological testing. Cognitively impaired and less impaired survivor...
Source: Translational Oncology - May 9, 2019 Category: Cancer & Oncology Authors: Siegel BI, King TZ, Rupji M, Dwivedi B, Carter AB, Kowalski J, MacDonald TJ Tags: Transl Oncol Source Type: research

Chemically Modified Variants of Fenofibrate with Antiglioblastoma Potential.
Abstract Anticancer effects of a common lipid-lowering drug, fenofibrate, have been described in the literature for a quite some time; however, fenofibrate has not been used as a direct anticancer therapy. We have previously reported that fenofibrate in its unprocessed form (ester) accumulates in the mitochondria, inhibits mitochondrial respiration, and triggers a severe energy deficit and extensive glioblastoma cell death. However, fenofibrate does not cross the blood brain barrier and is quickly processed by blood and tissue esterases to form the PPARα agonist fenofibric acid, which is practically ineffect...
Source: Translational Oncology - May 8, 2019 Category: Cancer & Oncology Authors: Stalinska J, Zimolag E, Pianovich NA, Zapata A, Lassak A, Rak M, Dean M, Ucar-Bilyeu D, Wyczechowska D, Culicchia F, Marrero L, Del Valle L, Sarkaria J, Peruzzi F, Jursic BS, Reiss K Tags: Transl Oncol Source Type: research

Preclinical Evaluation of the Acute Radiotoxicity of the α-Emitting Molecular-Targeted Therapeutic Agent 211At-MABG for the Treatment of Malignant Pheochromocytoma in Normal Mice.
Preclinical Evaluation of the Acute Radiotoxicity of the α-Emitting Molecular-Targeted Therapeutic Agent 211At-MABG for the Treatment of Malignant Pheochromocytoma in Normal Mice. Transl Oncol. 2019 May 08;12(7):879-888 Authors: Sudo H, Tsuji AB, Sugyo A, Nagatsu K, Minegishi K, Ishioka NS, Ito H, Yoshinaga K, Higashi T Abstract The α-emitter 211At-labeled meta-astatobenzylguanidine (211At-MABG) has a strong antitumor effect on pheochromocytoma xenograft tumors and holds great promise as a new therapeutic option for malignant pheochromocytoma. To evaluate the acute radiation-related toxici...
Source: Translational Oncology - May 8, 2019 Category: Cancer & Oncology Authors: Sudo H, Tsuji AB, Sugyo A, Nagatsu K, Minegishi K, Ishioka NS, Ito H, Yoshinaga K, Higashi T Tags: Transl Oncol Source Type: research

Serum Levels of Hepatocyte Growth Factor and CD40 Ligand Predict Radiation-Induced Liver Injury.
CONCLUSIONS: Our study identifies high HGF and low CD40L as potential markers of liver toxicity following radiation therapy. PMID: 31078059 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - May 8, 2019 Category: Cancer & Oncology Authors: Cuneo KC, Devasia T, Sun Y, Schipper MJ, Karnak D, Davis MA, Owen D, Feng M, El Naqa I, Bazzi L, Ten Haken R, Lawrence TS Tags: Transl Oncol Source Type: research

Overexpressed ABCB1 Induces Olaparib-Taxane Cross-Resistance in Advanced Prostate Cancer.
Abstract Castration-resistant prostate cancer remains as an incurable disease. Exploiting DNA damage repair defects via inhibition of poly (ADP-ribose) polymerase (PARP) is becoming an attractive therapeutic option. The TOPARP-A clinical trial demonstrated that the PARP inhibitor olaparib may be an effective strategy for treating prostate cancer. However, several unanswered questions regarding the use of olaparib remain: 1) How do we best stratify patients for olaparib treatment? 2) Where do we place olaparib in the treatment sequence paradigm? 3) Is there cross-resistance between olaparib and currently used thera...
Source: Translational Oncology - May 7, 2019 Category: Cancer & Oncology Authors: Lombard AP, Liu C, Armstrong CM, D'Abronzo LS, Lou W, Chen H, Dall'Era M, Ghosh PM, Evans CP, Gao AC Tags: Transl Oncol Source Type: research

Metadherin Is a Prognostic Apoptosis Modulator in Mesothelioma Induced via NF- κB-Mediated Signaling.
Metadherin Is a Prognostic Apoptosis Modulator in Mesothelioma Induced via NF-κB-Mediated Signaling. Transl Oncol. 2019 May 01;12(6):859-870 Authors: Zhang L, Singh A, Plaisier C, Pruett N, Ripley RT, Schrump DS, Hoang CD Abstract Therapies against malignant pleural mesothelioma (MPM) have yielded disappointing results, in part, because pathologic mechanisms remain obscure. In searching for rational molecular targets, we identified metadherin (MTDH), a multifunctional gene associated with several tumor types but previously unrecognized in MPM. Cox proportional hazards regression analysis delinea...
Source: Translational Oncology - May 1, 2019 Category: Cancer & Oncology Authors: Zhang L, Singh A, Plaisier C, Pruett N, Ripley RT, Schrump DS, Hoang CD Tags: Transl Oncol Source Type: research

Comparison of T790M Acquisition Between Patients Treated with Afatinib and Gefitinib as First-Line Therapy: Retrospective Propensity Score Matching Analysis.
Abstract Afatinib, a second-generation, irreversible pan-HER inhibitor, shows better suppression of T790M-positive lung cancer cells than gefitinib in preclinical studies. However, whether the effect of afatinib on T790M acquisition differs from that of gefitinib when used clinically as first-line therapy remains unclear. To reaffirm the preclinical efficacy of afatinib on T790M-positive lung cancer cells, H1975 cells and established PC-9 cells resistant to gefitinib and erlotinib by T790M were used. In total, 398 patients with second biopsy at progression with stage IIIB/IV non-small cell lung cancer with EGFR mu...
Source: Translational Oncology - April 25, 2019 Category: Cancer & Oncology Authors: Yoon BW, Kim JH, Lee SH, Choi CM, Rho JK, Yoon S, Lee DH, Kim SW, Jang TW, Lee JC Tags: Transl Oncol Source Type: research

Fusobacterium nucleatum Contributes to the Carcinogenesis of Colorectal Cancer by Inducing Inflammation and Suppressing Host Immunity.
Abstract The presence of Fusobacterium nucleatum (F. nucleatum) in the gut is associated with the development of colorectal cancer (CRC). F. nucleatum promotes tumor development by inducing inflammation and host immune response in the CRC microenvironment. Adhesion to the intestinal epithelium by the cell surface proteins FadA, Fap2 and RadD expressed by F. nucleatum can cause the host to produce inflammatory factors and recruit inflammatory cells, creating an environment which favors tumor growth. Furthermore, F. nucleatum can induce immune suppression of gut mucosa by suppressing the function of immune cells suc...
Source: Translational Oncology - April 12, 2019 Category: Cancer & Oncology Authors: Wu J, Li Q, Fu X Tags: Transl Oncol Source Type: research

An Integrated Next-Generation Sequencing System for Analyzing DNA Mutations, Gene Fusions, and RNA Expression in Lung Cancer.
Abstract We developed and characterized a next-generation sequencing (NGS) technology for streamlined analysis of DNA and RNA using low-input, low-quality cancer specimens. A single-workflow, targeted NGS panel for non-small cell lung cancer (NSCLC) was designed covering 135 RNA and 55 DNA disease-relevant targets. This multiomic panel was used to assess 219 formalin-fixed paraffin-embedded NSCLC surgical resections and core needle biopsies. Mutations and expression phenotypes were identified consistent with previous large-scale genomic studies, including mutually exclusive DNA and RNA oncogenic driver events. Eva...
Source: Translational Oncology - April 11, 2019 Category: Cancer & Oncology Authors: Haynes BC, Blidner RA, Cardwell RD, Zeigler R, Gokul S, Thibert JR, Chen L, Fujimoto J, Papadimitrakopoulou VA, Wistuba II, Latham GJ Tags: Transl Oncol Source Type: research

A Phase Ib Study of Pembrolizumab as Second-Line Therapy for Chinese Patients With Advanced or Metastatic Melanoma (KEYNOTE-151).
CONCLUSIONS: Pembrolizumab was well tolerated and provided clinically meaningful antitumor activity as second-line therapy in Chinese patients with advanced melanoma. PMID: 30981094 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - April 9, 2019 Category: Cancer & Oncology Authors: Si L, Zhang X, Shu Y, Pan H, Wu D, Liu J, Lou F, Mao L, Wang X, Wen X, Gu Y, Zhu L, Lan S, Cai X, Diede SJ, Zhou Y, Ge J, Li J, Wu H, Guo J Tags: Transl Oncol Source Type: research

Tobacco Smoking Modifies the Association between Hormonal Factors and Lung Cancer Occurrence among Post-Menopausal Chinese Women.
Abstract Inconsistent evidence has been reported on the role of female hormonal factors in the development of lung cancer. This population-based case-control study evaluated the main effect of menstrual/reproductive factors on the risk of lung cancer, and the effect modification by smoking status. Multivariable unconditional logistic regression models were applied adjusted for age, income, education, county of residence, body mass index, smoking status, pack-years of smoking, and family history of lung cancer. Among 680 lung cancer cases and 1,808 controls, later menopause (at>54 vs.
Source: Translational Oncology - April 5, 2019 Category: Cancer & Oncology Authors: Jin K, Wu M, Zhou JY, Yang J, Han RQ, Jin ZY, Liu AM, Gu X, Zhang XF, Wang XS, Su M, Hu X, Sun Z, Li G, Kim CH, Mu LN, He N, Zhao JK, Zhang ZF Tags: Transl Oncol Source Type: research

Inactivation of SAG or ROC1 E3 Ligase Inhibits Growth and Survival of Renal Cell Carcinoma Cells: Effect of BIM.
Abstract SAG (Sensitive to Apoptosis Gene) and ROC1 (Regulator of Cullin-1) are two family members of the RING component of CRL (Cullin RING ligase). Both members are essential for growth and survival of several types of human cancer cells; their role in renal cell carcinoma (RCC), however, remains elusive. Here we reported that compared to adjacent normal tissues, both SAG and ROC1 are overexpressed in RCC, which is positively correlated with poor patient survival, particularly for SAG. Depletion of SAG or ROC1 inhibited growth and survival of RCC cells by inducing G2/M arrest, senescence, and apoptosis likely du...
Source: Translational Oncology - April 4, 2019 Category: Cancer & Oncology Authors: Wang Y, Tan M, Li H, Li H, Sun Y Tags: Transl Oncol Source Type: research

Homoharringtonine Combined with the Heat Shock Protein 90 Inhibitor IPI504 in the Treatment of FLT3-ITD Acute Myeloid Leukemia.
In conclusion, our findings indicate that the combination of HHT and HSP90 inhibitor provides an alternative way for the treatment of FLT3-ITD positive acute myeloid leukemia, especially for relapsed/refractory AML. PMID: 30953928 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - April 3, 2019 Category: Cancer & Oncology Authors: Wu Z, Zhuang H, Yu Q, Zhang X, Jiang X, Lu X, Xu Y, Yang L, Wu B, Ma A, Zhang L, Xiao X, Liang Y, Gao R, Shen J, Xu R Tags: Transl Oncol Source Type: research

A Novel Synthetic Compound, Bismuth Zinc Citrate, Could Potentially Reduce Cisplatin-Induced Toxicity Without Compromising the Anticancer Effect Through Enhanced Expression of Antioxidant Protein.
In conclusion, pretreatment of BiZn decreased cisplatin-induced renal toxicity without affecting its antitumor activity. BiZn-induced antioxidant proteins MT and GSH may contribute to the renal protection effect. PMID: 30921749 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - March 25, 2019 Category: Cancer & Oncology Authors: Chan S, Wang R, Man K, Nicholls J, Li H, Sun H, Chan GC Tags: Transl Oncol Source Type: research

LMP1 and 2A Induce the Expression of Nrf2 Through Akt Signaling Pathway in Epstein-Barr Virus-Transformed B Cells.
In conclusion, our study demonstrates that Nrf2 promotes proliferation of EBV-transformed B cells through the EBV-related proteins LMP1 and 2A and Akt signaling, implicating Nrf2 as a potential molecular target for EBV-associated disease. PMID: 30909091 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - March 22, 2019 Category: Cancer & Oncology Authors: Yun SM, Kim YS, Hur DY Tags: Transl Oncol Source Type: research

Isolated 5' Signals Are an Atypical Pattern To Be Considered as Positive for ALK Rearrangement: A Brief Report of Three Cases and Review of the Literature.
We report three young nonsmoking patients with stage IV lung adenocarcinoma. Strong ALK expression in tumor cells detected by immunohistochemistry was observed in all cases, but FISH revealed an isolated 5' signal pattern. Massive parallel "next-generation" sequencing was performed in two patients and confirmed ALK rearrangement. The three patients were treated and responded to crizotinib after 14, 10, and 31 months. PMID: 30909092 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - March 22, 2019 Category: Cancer & Oncology Authors: Guyard A, Charpy C, Théou-Anton N, Cremades A, Grassin F, Bourgogne A, Leroy K, Pujals A, Copie-Bergman C, Chouaid C, Mansuet-Lupo A Tags: Transl Oncol Source Type: research

Chemotherapy Modulates Endocrine Therapy-Related Resistance Mutations in Metastatic Breast Cancer.
CONCLUSION: Together, these results suggest that mTOR inhibition may be a useful chemotherapy adjuvant to suppress chemotherapy-induced gene mutations that render tumors resistant to endocrine therapy in metastatic breast cancer patients with PD. PMID: 30893632 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - March 17, 2019 Category: Cancer & Oncology Authors: Zhou D, Ouyang Q, Liu L, Liu J, Tang Y, Xiao M, Wang Y, He Q, Hu ZY Tags: Transl Oncol Source Type: research

Arterial Spin Labeling for Glioma Grade Discrimination: Correlations with IDH1 Genotype and 1p/19q Status.
Abstract Since accurate grading of gliomas has important clinical value, the aim of this study is to evaluate the diagnostic efficacy of perfusion values derived from arterial spin labeling (ASL) to grade gliomas. In addition, the correlation between perfusion and isocitrate dehydrogenase 1 (IDH1) genotypes and chromosome arms 1p and 19q (1p/19q) status of gliomas was assessed. A total of 52 cases of supratentorial gliomas in adults who received ASL imaging were enrolled in this retrospective study. The cerebral blood flow (CBF) images derived from ASL and anatomical maps were normalized to the Montreal Neurologic...
Source: Translational Oncology - March 14, 2019 Category: Cancer & Oncology Authors: Wang N, Xie SY, Liu HM, Chen GQ, Zhang WD Tags: Transl Oncol Source Type: research

Treatment of Locally Advanced Nasopharyngeal Carcinoma by Helical Tomotherapy: An Observational, Prospective Analysis.
We present the preliminary (2-year) clinical outcomes of HT in 85 patients with locally advanced NPC (LA-NPC). Of these patients, 3 patients (3.5%) experienced treatment interruption due to severe pulmonary infection, and 82 (96.5%) completed radiation treatments. The 2-year estimate of progression-free survival, local relapse-free survival, nodal relapse-free survival, distant metastases-free survival, and overall survival rate were 90%, 96.3%, 98.8%, 96.3%, and 96.3%, respectively. Among the three patients that died, one had stage III disease and died from fatal nasopharyngeal bleeding after radiotherapy, while the other...
Source: Translational Oncology - March 14, 2019 Category: Cancer & Oncology Authors: Liu Z, Xu C, Jiang R, Liu G, Liu Q, Zhou J, Liu F, Yao J, Wang S, Jiang W Tags: Transl Oncol Source Type: research

IKZF1 Deletions with COBL Breakpoints Are Not Driven by RAG-Mediated Recombination Events in Acute Lymphoblastic Leukemia.
Abstract IKZF1 deletion (ΔIKZF1) is an important predictor of relapse in both childhood and adult B-cell precursor acute lymphoblastic leukemia (B-ALL). Previously, we revealed that COBL is a hotspot for breakpoints in leukemia and could promote IKZF1 deletions. Through an international collaboration, we provide a detailed genetic and clinical picture of B-ALL with COBL rearrangements (COBL-r). Patients with B-ALL and IKZF1 deletion (n = 133) were included. IKZF1 ∆1-8 were associated with large alterations within chromosome 7: monosomy 7 (18%), isochromosome 7q (10%), 7p loss (19%), and interstitial de...
Source: Translational Oncology - March 13, 2019 Category: Cancer & Oncology Authors: Lopes BA, Meyer C, Barbosa TC, Poubel CP, Mansur MB, Duployez N, Bashton M, Harrison CJ, Zur Stadt U, Horstmann M, Pombo-de-Oliveira MS, Palmi C, Cazzaniga G, Venn NC, Sutton R, Alonso CN, Tsaur G, Gupta SK, Bakhshi S, Marschalek R, Emerenciano M Tags: Transl Oncol Source Type: research

Cancer-Testis Antigen Peptide Vaccine for Cancer Immunotherapy: Progress and Prospects.
Abstract Cancer vaccines, including peptide-based vaccines, have been considered a key tool of effective and protective cancer immunotherapy because of their capacity to provide long-term clinical benefit for tumors. Among a large number of explorations of peptide antigen-based vaccines, cancer-testis antigens (CTAs), which are activated in cancers but silenced in normal tissues (except testis tissue), are considered as ideal targets. Currently, personalized treatment for cancer has become a trend due to its superior clinical efficacy. Thus, we envisage rational selection of CTA peptides to design "personaliz...
Source: Translational Oncology - March 13, 2019 Category: Cancer & Oncology Authors: Wei X, Chen F, Xin K, Wang Q, Yu L, Liu B, Liu Q Tags: Transl Oncol Source Type: research

Prognostic Impact of Src, CDKN1B, and JAK2 Expression in Metastatic Breast Cancer Patients Treated with Trastuzumab.
CONCLUSIONS: Low CDKN1B and JAK2 mRNA expressions were unfavorable prognosticators in a cohort of T-treated MBC patients. Our results suggest that CDKN1B and JAK2, if validated, may serve as prognostic factors potentially implicated in T resistance, which seems to be associated with distinct pathways in de novo and R-MBC. PMID: 30877976 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - March 13, 2019 Category: Cancer & Oncology Authors: Economopoulou P, Kotoula V, Koliou GA, Papadopoulou K, Christodoulou C, Pentheroudakis G, Lazaridis G, Arapantoni-Dadioti P, Koutras A, Bafaloukos D, Papakostas P, Patsea H, Pavlakis K, Pectasides D, Kotsakis A, Razis E, Aravantinos G, Samantas E, Kaloger Tags: Transl Oncol Source Type: research

Matrix Metalloprotease Generated Fragments of Type VI Collagen Have Serum Biomarker Potential in Cancer - A Proof of Concept Study.
This study evaluates four COL6 fragments measured in serum as potential biomarkers for cancer. METHODS: C6Ma1 (MMP-generated neo-epitope on the a1 chain), C6Ma3 (MMP-generated neo-epitope on the a3 chain), PRO-C6 (C-terminal of the a3 chain) and IC-6 (internal epitope on the a1 chain) were measured by ELISA in serum from patients with various stage 1-4 cancer indications (n = 4-11 per indication, total n = 65) and healthy controls (n = 13). RESULTS: C6Ma1 and C6Ma3 were significantly elevated in most cancer types compared to controls; PRO-C6 and IC6 were not. No significant differences were seen accor...
Source: Translational Oncology - March 8, 2019 Category: Cancer & Oncology Authors: Willumsen N, Bager C, Karsdal MA Tags: Transl Oncol Source Type: research

Diffusion-weighted magnetic resonance imaging is useful for the response evaluation of chemotherapy and/or radiotherapy to recurrent lesions of lung cancer.
Abstract Diffusion-weighted magnetic resonance imaging (DWI) has been reported to be useful for the assessment of lung cancer staging. It is uncertain whether DWI is more accurate for the response evaluation of chemotherapy and/or radiotherapy compared to computed tomography (CT). The purpose of this study is to compare the response evaluation of DWI for chemotherapy and/or radiotherapy to recurrent tumors of lung cancer with that of CT which is a standard tool in RECIST (Response Evaluation Criteria in Solid Tumours). Forty-one patients who agreed to this project and had CT scan and DWI examinations within a mont...
Source: Translational Oncology - March 8, 2019 Category: Cancer & Oncology Authors: Usuda K, Iwai S, Funasaki A, Sekimura A, Motono N, Matoba M, Doai M, Yamada S, Ueda Y, Uramoto H Tags: Transl Oncol Source Type: research

The Third-Generation EGFR Inhibitor, Osimertinib, Promotes c-FLIP Degradation, Enhancing Apoptosis Including TRAIL-Induced Apoptosis in NSCLC Cells with Activating EGFR Mutations.
Abstract The third-generation EGFR inhibitor, osimertinib (AZD9291), selectively and irreversibly inhibits EGFR activating and T790 M mutants while sparing wild-type EGFR. Osimertinib is now an approved drug for non-small cell lung cancer (NSCLC) patients with activating EGFR mutations (first-line) or those who have become resistant to 1st generation EGFR inhibitors through the T790 M mutation (second-line). Unfortunately, all patients eventually relapse and develop resistance to osimertinib. Hence, it is essential to fully understand the biology underlying the development of resistance to osimertinib in order to ...
Source: Translational Oncology - March 8, 2019 Category: Cancer & Oncology Authors: Shi P, Zhang S, Zhu L, Qian G, Ren H, Ramalingam SS, Chen M, Sun SY Tags: Transl Oncol Source Type: research

Circulating miRNA Profiling of Women at High Risk for Ovarian Cancer.
This study, which requires validation, suggests that, via miRNA dysregulation, involvement of both hypoxia and its related androgen pathways may contribute to the HR state. This pilot study is the first report to our knowledge that studies circulating miRNA profiling of HR and LR women. PMID: 30856556 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - March 8, 2019 Category: Cancer & Oncology Authors: Pandey R, Woo HH, Varghese F, Zhou M, Chambers SK Tags: Transl Oncol Source Type: research

Metformin Augments Panobinostat's Anti-Bladder Cancer Activity by Activating AMP-Activated Protein Kinase.
Abstract Panobinostat, a histone deacetylase inhibitor, induces histone acetylation and acts against cancer but attenuates its anticancer activity by activating the mammalian target of rapamycin (mTOR) pathway. AMP-activated protein kinase (AMPK) is a cellular energy sensor that reportedly inhibits the mTOR pathway. The antidiabetic drug metformin is also a potent AMPK activator and we investigated whether it augmented panobinostat's antineoplastic activity in bladder cancer cells (UMUC3, J82, T24 and MBT-2). Metformin enhanced panobinostat-induced apoptosis and the combination inhibited the growth of bladder canc...
Source: Translational Oncology - March 5, 2019 Category: Cancer & Oncology Authors: Okubo K, Isono M, Asano T, Sato A Tags: Transl Oncol Source Type: research

Novel Synergistic Combination of Mitotic Arrest and Promotion of Apoptosis for Treatment of Pancreatic Adenocarcinoma.
Abstract The BCL-2 family of proteins, including anti-apoptotic members BCL-2, BCL-XL and MCL-1, are part of a complex network that controls apoptosis. BH3-mimetics such as ABT-263 inhibit anti-apoptotic BCL-2 proteins and have been developed as potential cancer therapeutics. Aurora Kinase A (AKA) is over-expressed in pancreatic cancer (PC) and controls G2-M transition during mitosis and AKA inhibitors have been developed that induce mitotic arrest. We hypothesized that mitotic arrest induced by AKA inhibition may sensitize PC to accelerated apoptosis by a BH3-mimetic. Our results demonstrated that ABT-263 plus ML...
Source: Translational Oncology - March 4, 2019 Category: Cancer & Oncology Authors: Duan Z, Chinn D, Tu MJ, Zhang QY, Huynh J, Chen J, Mack P, Yu AM, Kim EJ Tags: Transl Oncol Source Type: research

Androgen Receptor mRNA Expression in Urothelial Carcinoma of the Bladder: A Retrospective Analysis of Two Independent Cohorts.
eck B Abstract INTRODUCTION: Gender-specific differences have led to the androgen receptor (AR) being considered a possible factor in the pathophysiology of urothelial carcinoma of the bladder (UCB), but the exact role remains unclear. MATERIALS AND METHODS: The association of AR mRNA expression with clinicopathological features was retrospectively analyzed in two previously described cohorts. The first cohort consisted of 41 patients with all stages of UCB treated at Aarhus University Hospital, Denmark. The second cohort consisted of 323 patients with muscle-invasive bladder cancer (MIBC) accumulated by the ...
Source: Translational Oncology - March 1, 2019 Category: Cancer & Oncology Authors: Sikic D, Wirtz RM, Wach S, Dyrskjøt L, Erben P, Bolenz C, Breyer J, Otto W, Hoadley KA, Lerner SP, Eckstein M, Hartmann A, Keck B Tags: Transl Oncol Source Type: research

Phase II Study of a Bi-Weekly Chemotherapy Regimen of Combined Liposomal Paclitaxel and Nedaplatin for the Treatment of Advanced Squamous Cell Lung Cancer.
Abstract The platinum-based, two-drug, 3-week regimen is currently the main first-line chemotherapy program for the treatment of advanced squamous cell lung cancer. The aim of this phase II clinical study was to evaluate the efficacy and adverse events of the bi-weekly program of liposomal paclitaxel combined with nedaplatin as a first-line treatment for advanced squamous cell lung cancer. A total of 52 cases of advanced squamous cell lung cancer were included in this phase II clinical trial. Patients received intravenous infusion of liposomal paclitaxel (100 mg/m2) and nedaplatin (50 mg/m2) on days 1 and 15 of a ...
Source: Translational Oncology - February 26, 2019 Category: Cancer & Oncology Authors: Lv WZ, Lin Z, Wang SY, Lv BJ, Wang ZH, Xiao M, Xu XL, Peng PJ Tags: Transl Oncol Source Type: research

Large Cell Neuroendocrine Carcinoma Shares Similarity with Small Cell Carcinoma on the Basis of Clinical and Pathological Features.
CONCLUSION: In clinical features, survival and immunoprofile, LCNEC showed more similarity with SCLC rather than carcinoid, which might guide novel therapy for pulmonary NETs. PMID: 30818166 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - February 25, 2019 Category: Cancer & Oncology Authors: Xu F, Chen K, Lu C, Gu J, Zeng H, Xu Y, Ji Y, Ge D Tags: Transl Oncol Source Type: research

Osimertinib Regresses an EGFR-Mutant Cisplatinum- Resistant Lung Adenocarcinoma Growing in the Brain in Nude Mice.
Abstract The goal of the present study was to determine the efficacy of osimertinib (AZD9291), a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor for the treatment of aggressive EGFR-mutant non-small cell lung cancer (NSCLC), compared to cisplatinum (CDDP) + pemetrexed (PEM). The NSCLC cell line PC-9 expressing green fluorescence protein (PC-9-GFP) was implanted in the brain of nude mice and was treated with CDDP + PEM or AZD9291. Tumors were observed by non-invasive fluorescence imaging. AZD9291 treatment caused tumor regression in contrast to CDDP + PEM which had only a slig...
Source: Translational Oncology - February 22, 2019 Category: Cancer & Oncology Authors: Higuchi T, Oshiro H, Zhang Z, Miyake K, Sugisawa N, Katsuya Y, Yamamoto N, Hayashi K, Kimura H, Miwa S, Igarashi K, Zhao M, Bouvet M, Singh SR, Tsuchiya H, Hoffman RM Tags: Transl Oncol Source Type: research

Cisplatin and Fluorouracil Induction Chemotherapy With or Without Docetaxel in Locoregionally Advanced Nasopharyngeal Carcinoma.
In this study, we aim to compare the progression-free survival (PFS) rates and side effects of induction chemotherapy based on docetaxel, cisplatin and fluorouracil (TPF) versus cisplatin and fluorouracil (PF) in patients with locoregionally-advanced nasopharyngeal carcinoma who received subsequent chemoradiotherapy. We randomly assigned 278 patients with stage III or IV NPC (without distant metastases) to receive either TPF or PF induction chemotherapy, followed by cisplatin-based chemoradiotherapy every 3 weeks and intensity-modulated radiation therapy for 5 days per week. After a minimum of 2 years follow-up, a PFS bene...
Source: Translational Oncology - February 20, 2019 Category: Cancer & Oncology Authors: Jin T, Qin WF, Jiang F, Jin QF, Wei QC, Jia YS, Sun XN, Li WF, Chen XZ Tags: Transl Oncol Source Type: research

RRx-001 Acts as a Dual Small Molecule Checkpoint Inhibitor by Downregulating CD47 on Cancer Cells and SIRP- α on Monocytes/Macrophages.
RRx-001 Acts as a Dual Small Molecule Checkpoint Inhibitor by Downregulating CD47 on Cancer Cells and SIRP-α on Monocytes/Macrophages. Transl Oncol. 2019 Feb 06;12(4):626-632 Authors: Cabrales P Abstract RRx-001 is a pleiotropic anticancer agent in phase III clinical trials, which polarizes tumor-associated macrophages from a low phagocytic M2 phenotype to a high phagocytic M1 phenotype. One of the ways in which tumors promote M2 polarization and evade macrophage-mediated destruction is through upregulation of CD47 expression. As a myeloid-specific immune checkpoint, CD47 interacts with signal-r...
Source: Translational Oncology - February 6, 2019 Category: Cancer & Oncology Authors: Cabrales P Tags: Transl Oncol Source Type: research

Canonical WNT Signaling Pathway is Altered in Mesenchymal Stromal Cells From Acute Myeloid Leukemia Patients And Is Implicated in BMP4 Down-Regulation.
to R Abstract Mesenchymal stromal cells (hMSCs) are key components of the bone marrow microenvironment (BMM). A molecular signature in hMSCs from Acute myeloid leukemia patients (hMSC-AML) has been proposed where BMP4 is decreased and could be regulated by WNT signaling pathway. Therefore, the aim of this work was to verify whether the WNT signaling pathway can regulate the BMP4 gene in hMSCs. The results showed differentially expressed genes in the WNT canonical pathway between hMSC-AML and hMSCs from healthy donors and a real-time quantitative assay corroborated with these findings. Moreover, the main WNT canoni...
Source: Translational Oncology - January 28, 2019 Category: Cancer & Oncology Authors: Azevedo PL, Oliveira NCA, Corrêa S, Castelo-Branco MTL, Abdelhay E, Binato R Tags: Transl Oncol Source Type: research

Effects of Neddylation and mTOR Inhibition in Acute Myelogenous Leukemia.
Abstract Acute myelogenous leukemia (AML) is a heterogeneous disease and often relapses after standard chemotherapy. Recently, the neddylation (NEDD8) and the mammalian target of rapamycin (mTOR) signaling pathways have emerged as promising pharmaceutical targets for AML therapy. However, the interaction of these two pathways remains unclear. Here we evaluated the effects of pevonedistat, an inhibitor of the NEDD8 activating enzyme (NAE), and sapanisertib (TAK-228), an inhibitor of mTORC1 and mTORC2 as single agents or in combination on AML cell lines. We found that inhibition of neddylation with pevonedistat part...
Source: Translational Oncology - January 27, 2019 Category: Cancer & Oncology Authors: Guo N, Azadniv M, Coppage M, Nemer M, Mendler J, Becker M, Liesveld J Tags: Transl Oncol Source Type: research

Combination of Docetaxel Plus Savolitinib in Refractory Cancer Patients: A Report on Phase I Trial.
Abstract MET amplification is a frequently observed genomic aberration in solid tumors. We conducted a phase I trial to evaluate dose-limiting toxicity (DLT) and recommended phase II dose (RP2D) for the combination therapy. The following dose levels were tested in this single-arm phase I study: docetaxel as an intravenous infusion over 1 hour at 60 mg/m2 once every 3 weeks of a 21-day schedule plus savolitinib (level 1, 200 mg qd; level 2, 400 mg qd; level 3, 600 mg qd; level 4800 mg qd). In total, there were 17 patients enrolled on to this study [7 gastric cancer (GC) patients, 5 melanoma patients, ...
Source: Translational Oncology - January 26, 2019 Category: Cancer & Oncology Authors: Kim ST, Lee S, Park M, Park SH, Park JO, Lim HY, Park YS, Kang WK, Gangolli EA, Shin H, Kim KM, Hollingsworth SJ, Mortimer PGS, Lee J Tags: Transl Oncol Source Type: research

Intratumoral, rather than stromal, CD8+ T cells could be a potential negative prognostic marker in invasive breast cancer patients.
Abstract BACKGROUND: Tumor infiltrating lymphocytes (TILs) are widely considered a key sign of the immune interaction between host and tumor, and potentially prognostic biomarkers of good or bad outcome in many cancers, included invasive breast cancer (BC). However, results about the association between TIL typology, location and BC prognosis, are controversial. The aim of the study was to evaluated the prognostic significance of TIL subtypes (CD4+, CD8+, FOXP3+ T cells) and their location (stromal "s" and intratumoral "i" CD4+ and CD8+) in BC patients, focusing on the association between these...
Source: Translational Oncology - January 22, 2019 Category: Cancer & Oncology Authors: Catacchio I, Silvestris N, Scarpi E, Schirosi L, Scattone A, Mangia A Tags: Transl Oncol Source Type: research

Reference MicroRNAs for RT-qPCR Assays in Cervical Cancer Patients and Their Application to Studies of HPV16 and Hypoxia Biomarkers.
In conclusion, miR-151-5p, miR-152-3p, and miR-423-3p are suitable reference miRNAs in cervical cancer. MiR-9-5p and miR-210-3p are promising HPV16 and hypoxia biomarkers, respectively. PMID: 30660934 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - January 17, 2019 Category: Cancer & Oncology Authors: Nilsen A, Jonsson M, Aarnes EK, Kristensen GB, Lyng H Tags: Transl Oncol Source Type: research

Claudin 1 Is Highly Upregulated by PKC in MCF7 Human Breast Cancer Cells and Correlates Positively with PKC ε in Patient Biopsies.
Claudin 1 Is Highly Upregulated by PKC in MCF7 Human Breast Cancer Cells and Correlates Positively with PKCε in Patient Biopsies. Transl Oncol. 2019 Jan 15;12(3):561-575 Authors: Blanchard AA, Ma X, Wang N, Hombach S, Penner C, Ozturk A, Klonisch T, Pitz M, Murphy L, Leygue E, Myal Y Abstract Recent studies provide compelling evidence to suggest that the tight junction protein claudin 1, aberrantly expressed in several cancer types, plays an important role in cancer progression. Dysregulation of claudin 1 has been shown to induce epithelial mesenchymal transition (EMT). Furthermore, activation...
Source: Translational Oncology - January 15, 2019 Category: Cancer & Oncology Authors: Blanchard AA, Ma X, Wang N, Hombach S, Penner C, Ozturk A, Klonisch T, Pitz M, Murphy L, Leygue E, Myal Y Tags: Transl Oncol Source Type: research

Mitogen Inducible Gene-6 Is a Prognostic Marker for Patients with Colorectal Liver Metastases.
CONCLUSIONS: MIG-6 expression is inversely associated with survival after hepatectomy and may be used to improve traditional prognostic schemes that rely on clinicopathologic data such as the Clinical Risk Score. PMID: 30639964 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - January 9, 2019 Category: Cancer & Oncology Authors: Donner DB, Ruan DT, Toriguchi K, Bergsland EK, Nakakura EK, Lin MH, Antonia RJ, Warren RS Tags: Transl Oncol Source Type: research

STAT-3 RNAscope Determination in Human Diffuse Large B-Cell Lymphoma.
CONCLUSIONS: These data confirm other reports showing that STAT3 is highly expressed and activated in ABC-DLBCL and our previously published data demonstrating that, in primary central nervous system lymphoma, tumor vessels appeared lined by endothelial cells expressing both FVIII and STAT3. PMID: 30639963 [PubMed - as supplied by publisher] (Source: Translational Oncology)
Source: Translational Oncology - January 6, 2019 Category: Cancer & Oncology Authors: Tamma R, Ingravallo G, Albano F, Gaudio F, Annese T, Ruggieri S, Lorusso L, Errede M, Maiorano E, Specchia G, Ribatti D Tags: Transl Oncol Source Type: research

Primary Central Nervous System Lymphoma: Molecular Pathogenesis and Advances in Treatment.
Abstract Primary central nervous system lymphoma (PCNSL) is a group of extranodal non-Hodgkin lymphoma that exhibits specific biological characteristics and clinical behavior, with an aggressive disease course and unsatisfactory patient outcomes. It is of great importance to identify aberrant genetic loci and important molecular pathways that might suggest potential targets for new therapeutics and provide prognostic information. In this review, we listed various genetic and epigenetic alterations that are involved in PCNSL pathogenesis. In the aspect of treatment, we summarized the related literatures and evaluat...
Source: Translational Oncology - January 4, 2019 Category: Cancer & Oncology Authors: Cai Q, Fang Y, Young KH Tags: Transl Oncol Source Type: research

Urinary Cysteine-Rich Protein 61 and Trefoil Factor 3 as Diagnostic Biomarkers for Colorectal Cancer.
Abstract Since a fecal occult blood test for colorectal cancer (CRC) does not offer sufficient diagnostic power for CRC, novel non-invasive biomarkers are hopeful for CRC screening. We conducted the current study to discover non-invasive urinary biomarkers for diagnosing CRC. Among urine samples from 258 patients (CRC, n = 148; healthy controls, n = 110), a cohort of 176 patients composed of 88 patients with GC and 88 healthy controls was selected after age- and sex-matching using propensity score. This cohort was then randomly divided into 2 groups: 53 pairs (106 patients) in the training cohort, and 35 p...
Source: Translational Oncology - January 3, 2019 Category: Cancer & Oncology Authors: Shimura T, Iwasaki H, Kitagawa M, Ebi M, Yamada T, Yamada T, Katano T, Nisie H, Okamoto Y, Ozeki K, Mizoshita T, Kataoka H Tags: Transl Oncol Source Type: research

Subcutaneous Inoculation of 3D Pancreatic Cancer Spheroids Results in Development of Reproducible Stroma-Rich Tumors.
Abstract Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease characterized by high expression of extracellular matrix in tumor tissue, which contributes to chemoresistance and poor prognosis. Here, we developed 3D pancreatic cancer spheroids, based on pancreatic cancer cells and fibroblast co-culture, which demonstrate innate desmoplastic properties and stay poorly permeable for model nanoparticles. Our study revealed that establishment of tumors by transplantation of spheroids significantly improved subcutaneous xenograft model of PDAC, which stays the most widely used animal model for testing of new drug...
Source: Translational Oncology - December 19, 2018 Category: Cancer & Oncology Authors: Durymanov M, Kroll C, Permyakova A, O'Neill E, Sulaiman R, Person M, Reineke J Tags: Transl Oncol Source Type: research