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Molecular Oncology

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https://www.readbyqxmd.com/read/27838215/corrigendum-to-infiltrating-t-cells-promote-prostate-cancer-metastasis-via-modulation-of-fgf11%C3%A2-mirna-541%C3%A2-androgen-receptor-ar-%C3%A2-mmp9-signaling-mol-oncol-9-1-2015-44-57
#1
Shuai Hu, Lei Li, Shuyuan Yeh, Yun Cui, Xin Li, Hong-Chiang Chang, Jie Jin, Chawnshang Chang
No abstract text is available yet for this article.
November 4, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/27839676/prospective-validation-of-a-blood-based-9-mirna-profile-for-early-detection-of-breast-cancer-in-a-cohort-of-women-examined-by-clinical-mammography
#2
Maria B Lyng, Annette R Kodahl, Harald Binder, Henrik J Ditzel
Mammography is the predominant screening method for early detection of breast cancer, but has limitations and could be rendered more accurate by combination with a blood-based biomarker profile. Circulating microRNAs (miRNAs) are increasingly recognized as strong biomarkers, and we previously developed a 9-miRNA profile using serum and LNA-based qPCR that effectively stratified patients with early stage breast cancer vs. healthy women. To further develop the test into routine clinical practice, we collected serum of women examined by clinical mammography (N = 197) according to standard operational procedures (SOPs) of the Danish Cancer Biobank...
November 1, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/27856179/exosomal-proteins-as-prognostic-biomarkers-in-non-small-cell-lung-cancer
#3
B Sandfeld-Paulsen, N Aggerholm-Pedersen, R Bæk, K R Jakobsen, P Meldgaard, B H Folkersen, T R Rasmussen, K Varming, M M Jørgensen, B S Sorensen
BACKGROUND: Use of exosomes as biomarkers in non-small cell lung cancer (NSCLC) is an intriguing approach in the liquid-biopsy era. Exosomes are nano-sized vesicles with membrane-bound proteins that reflect their originating cell. Prognostic biomarkers are needed to improve patient selection for optimal treatment. We here evaluate exosomes by protein phenotyping as a prognostic biomarker in NSCLC. METHODS: Exosomes from plasma of 276 NSCLC patients were phenotyped using the Extracellular Vesicle Array; 49 antibodies captured the proteins on the exosomes, and a cocktail of biotin-conjugated antibodies binding the general exosome markers CD9, CD81 and CD63 was used to visualise the captured exosomes...
October 21, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/27825696/a-pilot-study-exploring-the-molecular-architecture-of-the-tumor-microenvironment-in-human-prostate-cancer-using-laser-capture-microdissection-and-reverse-phase-protein-microarray
#4
Elisa Pin, Steven Stratton, Claudio Belluco, Lance Liotta, Ray Nagle, K Alex Hodge, Jianghong Deng, Ting Dong, Elisa Baldelli, Emanuel Petricoin, Mariaelena Pierobon
The cross-talk between tumor epithelium and surrounding stromal/immune microenvironment is essential to sustain tumor growth and progression and provides new opportunities for the development of targeted treatments focused on disrupting the tumor ecology. Identification of novel approaches to study these interactions is of primary importance. Using laser capture microdissection (LCM) coupled with reverse phase protein microarray (RPPA) based protein signaling activation mapping we explored the molecular interconnection between tumor epithelium and surrounding stromal microenvironment in 18 prostate cancer (PCa) specimens...
October 14, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/27756687/epigenetic-determinants-of-metastasis
#5
Saroor A Patel, Sakari Vanharanta
Genetic analyses of cancer progression in patient samples and model systems have thus far failed to identify specific mutational drivers of metastasis. Yet, at least in experimental systems, metastatic cancer clones display stable traits that can facilitate progression through the many steps of metastasis. How cancer cells establish and maintain the transcriptional programmes required for metastasis remains mostly unknown. Emerging evidence suggests that metastatic traits may arise from epigenetically altered transcriptional output of the oncogenic signals that drive tumour initiation and early progression...
October 8, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/27727085/corrigendum-to-molecular-imaging-for-personalized-cancer-care-mol-oncol-6-2-2012-182-195
#6
Moritz F Kircher, Hedvig Hricak, Steven M Larson
No abstract text is available yet for this article.
October 2, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/27729194/vcp-inhibitors-induce-endoplasmic-reticulum-stress-cause%C3%A2-cell-cycle-arrest-trigger-caspase-mediated-cell-death%C3%A2-and-synergistically-kill-ovarian-cancer-cells-in-combination-with-salubrinal
#7
Prabhakar Bastola, Lisa Neums, Frank J Schoenen, Jeremy Chien
Valosin-containing protein (VCP) or p97, a member of AAA-ATPase protein family, has been associated with various cellular functions including endoplasmic reticulum-associated degradation (ERAD), Golgi membrane reassembly, autophagy, DNA repair, and cell division. Recent studies identified VCP and ubiquitin proteasome system (UPS) as synthetic lethal targets in ovarian cancer. Here, we describe the preclinical activity of VCP inhibitors in ovarian cancer. Results from our studies suggest that quinazoline-based VCP inhibitors initiate G1 cell cycle arrest, attenuate cap-dependent translation and induce programmed cell death via the intrinsic and the extrinsic modes of apoptosis...
September 28, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/27720576/concordance-of-immune-checkpoints-within-tumor-immune-contexture-and-their-prognostic-significance-in-gastric-cancer
#8
Congqi Dai, Ruixuan Geng, Chenchen Wang, Angela Wong, Min Qing, Jianjun Hu, Yu Sun, A W I Lo, Jin Li
Checkpoint blockade therapy has emerged as a novel approach for cancer immunotherapy in several malignancies. However, patient prognosis and disease progression relevant to immune checkpoints in gastric tumor microenvironment are not defined. This study aims to investigate the expression and prognostic significance of immune checkpoints within gastric cancer. In the study, a cohort of 398 cancer tissues from stage I to IV gastric cancer patients were assessed for programmed cell death 1 ligand 1 (PD-L1) expression and tumor-infiltrating lymphocyte (TIL) infiltration using immunohistochemistry to ascertain their survival correlation...
September 24, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/27717710/dysregulation-of-histone-methyltransferases-in-breast-cancer-opportunities-for-new-targeted-therapies
#9
Ewa M Michalak, Jane E Visvader
Histone methyltransferases (HMTs) catalyze the methylation of lysine and arginine residues on histone tails and non-histone targets. These important post-translational modifications are exquisitely regulated and affect chromatin compaction and transcriptional programs leading to diverse biological outcomes. There is accumulating evidence that genetic alterations of several HMTs impinge on oncogenic or tumor-suppressor functions and influence both cancer initiation and progression. HMTs therefore represent an opportunity for therapeutic targeting in those patients with tumors in which HMTs are dysregulated, to reverse the histone marks and transcriptional programs associated with aggressive tumor behavior...
September 23, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/27693040/mir-634-exhibits-anti-tumor-activities-toward-hepatocellular-carcinoma-via-rab1a-and-dhx33
#10
Chris Zhiyi Zhang, Yun Cao, Jia Fu, Jing-Ping Yun, Mei-Fang Zhang
Deregulation of microRNAs contributes to the aberrant growth of hepatocellular carcinoma (HCC). Here, we showed that miR-634 expression was frequently decreased in HCC. Low miR-634 expression was significantly associated with larger tumor size, poorer tumor differentiation, advanced TNM stage, vascular invasion, absence of tumor capsule and unfavorable overall survival. Overexpression of miR-634 markedly attenuated cell viability, colony formation, tumor growth and metastasis, whereas miR-634 inhibition resulted in the opposite phenotypes...
September 20, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/27692894/mrna-expression-profiles-of-colorectal-liver-metastases-as-a-novel-biomarker-for-early-recurrence-after-partial-hepatectomy
#11
E P van der Stok, M Smid, A M Sieuwerts, P B Vermeulen, S Sleijfer, N Ayez, D J Grünhagen, J W M Martens, C Verhoef
BACKGROUND: Identification of specific risk groups for recurrence after surgery for isolated colorectal liver metastases (CRLM) remains challenging due to the heterogeneity of the disease. Classical clinicopathologic parameters have limited prognostic value. The aim of this study was to identify a gene expression signature measured in CRLM discriminating early from late recurrence after partial hepatectomy. METHODS: CRLM from two patient groups were collected: I) with recurrent disease ≤12 months after surgery (N = 33), and II) without recurrences and disease free for ≥36 months (N = 30)...
September 20, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/27692344/autophagy-inhibition-upregulates-cd4-tumor-infiltrating-lymphocyte-expression-via-mir-155-regulation-and-trail-activation
#12
Paul Zarogoulidis, Savvas Petanidis, Kalliopi Domvri, Efrosini Kioseoglou, Doxakis Anestakis, Lutz Freitag, Konstantinos Zarogoulidis, Wolfgang Hohenforst-Schmidt, Wilfried Eberhardt
Chemoresistance is a major challenge in lung cancer treatment. Recent findings have revealed that autophagic mechanism contributes significantly to immunosuppressive related chemoresistance. For that reason, targeting autophagy-related immunosuppression is an important approach to reverse tumor drug resistance. In this study, we report for the first time that autophagy inhibition triggers upregulation of CD4(+), Foxp3(+) tumor infiltrating lymphocytes in late metastatic lung cancer tissues. Furthermore, autophagy blockage induces chemosensitization to carboplatin, immune activation and cell cycle arrest...
September 16, 2016: Molecular Oncology
https://www.readbyqxmd.com/read/27599694/transcript-signatures-that-predict-outcome-and-identify-targetable-pathways-in-mycn-amplified-neuroblastoma
#13
Robin M Hallett, Alex B K Seong, David R Kaplan, Meredith S Irwin
BACKGROUND: In the pediatric cancer neuroblastoma (NB), patients are stratified into low, intermediate or high-risk subsets based in part on MYCN amplification status. While MYCN amplification in general predicts unfavorable outcome, no clinical or genomic factors have been identified that predict outcome within these cohorts of high-risk patients. In particular, it is currently not possible at diagnosis to determine which high-risk neuroblastoma patients will ultimately fail upfront therapy...
November 2016: Molecular Oncology
https://www.readbyqxmd.com/read/27592281/citral-reduces-breast-tumor-growth-by-inhibiting-the-cancer-stem-cell-marker-aldh1a3
#14
Margaret Lois Thomas, Roberto de Antueno, Krysta Mila Coyle, Mohammad Sultan, Brianne Marie Cruickshank, Michael Anthony Giacomantonio, Carman Anthony Giacomantonio, Roy Duncan, Paola Marcato
Breast cancer stem cells (CSCs) can be identified by increased Aldefluor fluorescence caused by increased expression of aldehyde dehydrogenase 1A3 (ALDH1A3), as well as ALDH1A1 and ALDH2. In addition to being a CSC marker, ALDH1A3 regulates gene expression via retinoic acid (RA) signaling and plays a key role in the progression and chemotherapy resistance of cancer. Therefore, ALDH1A3 represents a druggable anti-cancer target of interest. Since to date, there are no characterized ALDH1A3 isoform inhibitors, drugs that were previously described as inhibiting the activity of other ALDH isoforms were tested for anti-ALDH1A3 activity...
November 2016: Molecular Oncology
https://www.readbyqxmd.com/read/27590684/biglycan-stimulates-vegf-expression-in-endothelial-cells-by-activating-the-tlr-signaling-pathway
#15
Lei Hu, Ming-de Zang, He-Xiao Wang, Jian-Fang Li, Li-Ping Su, Min Yan, Chen Li, Qiu-Meng Yang, Bing-Ya Liu, Zheng-Gang Zhu
Biglycan (BGN) is an important component of the extracellular matrix (ECM) that is implicated in a variety of human cancers. In our previous study, we reported that BGN was overexpressed in gastric cancer (GC) tissues and promoted cancer metastasis. Moreover, the tubular formation capacity in HUVECs was promoted by stimulation with culture media from BGN-overexpressing GC cells, but the exact underlying mechanism is still unknown. The purpose of this study was to determine the role and molecular mechanism of BGN in VEGF expression in endothelial cells...
November 2016: Molecular Oncology
https://www.readbyqxmd.com/read/27582092/spatial-and-temporal-clonal-evolution-during-development-of-metastatic-urothelial-carcinoma
#16
Mathilde B H Thomsen, Iver Nordentoft, Philippe Lamy, Søren Høyer, Søren Vang, Jakob Hedegaard, Michael Borre, Jørgen B Jensen, Torben F Ørntoft, Lars Dyrskjøt
Patients with metastatic bladder cancer have a median survival of only 13-14 months. Precision medicine using targeted therapy may improve survival. Here we investigated spatial and temporal tumour evolution and tumour heterogeneity in order to evaluate the potential use of targeted treatment of metastatic bladder cancer. We performed a proof-of-concept study by whole exome sequencing of multiple tumour regions (n = 22) from three patients with metastatic bladder cancer. DNA from primary and metastatic tumour biopsies was analysed for mutations using Mutect and potential therapeutic targets were identified...
November 2016: Molecular Oncology
https://www.readbyqxmd.com/read/27555543/concordance-between-her-2-status-determined-by-qpcr-in-fine-needle-aspiration-cytology-fnac-samples-compared-with-ihc-and-fish-in-core-needle-biopsy-cnb-or-surgical-specimens-in-breast-cancer-patients
#17
Claudia Rodriguez, Voichita Suciu, Audrey Poterie, Ludovic Lacroix, Isabelle Miran, Amélie Boichard, Suzette Delaloge, Jacqueline Deneuve, Sandy Azoulay, Marie-Christine Mathieu, Alexander Valent, Stefan Michiels, Monica Arnedos, Philippe Vielh
Determining the status of HER2-neu amplification and overexpression in breast cancer is crucial for prognosis but mostly for treatment purposes. Standard techniques include the determination of IHC in combination with in situ hybridization techniques to confirm a HER2-neu amplification in case of IHC2+ using either a core-needle biopsy or a surgical specimen. qPCR has been also demonstrated to be able to determine HER2 status, mostly in core biopsies or in surgical specimens. Fine-needle aspiration is a reliable, quicker and less invasive technique that is widely used for diagnosis of invasive breast cancer...
November 2016: Molecular Oncology
https://www.readbyqxmd.com/read/27555542/a-large-scale-analysis-of-alternative-splicing-reveals-a-key-role-of-qki-in-lung-cancer
#18
Fernando J de Miguel, María J Pajares, Elena Martínez-Terroba, Daniel Ajona, Xabier Morales, Ravi D Sharma, Francisco J Pardo, Ana Rouzaut, Angel Rubio, Luis M Montuenga, Ruben Pio
Increasing interest has been devoted in recent years to the understanding of alternative splicing in cancer. In this study, we performed a genome-wide analysis to identify cancer-associated splice variants in non-small cell lung cancer. We discovered and validated novel differences in the splicing of genes known to be relevant to lung cancer biology, such as NFIB, ENAH or SPAG9. Gene enrichment analyses revealed an important contribution of alternative splicing to cancer-related molecular functions, especially those involved in cytoskeletal dynamics...
November 2016: Molecular Oncology
https://www.readbyqxmd.com/read/27522468/non-canonical-wnt5a-signaling-up-regulates-the-expression-of-the-tumor-suppressor-15-pgdh-and-induces-differentiation-of-colon-cancer-cells
#19
Lubna M Mehdawi, Chandra Prakash Prasad, Roy Ehrnström, Tommy Andersson, Anita Sjölander
The tumor suppressor 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is the key enzyme in prostaglandin E2 catabolism and is down-regulated in colorectal cancer (CRC) tissue. Canonical Wnt signaling is frequently elevated in colon cancers and has been shown to down-regulate 15-PGDH expression. Therefore, we have in the current study investigated if the non-canonical ligand WNT5A relates to increased expression of 15-PGDH in colon cancer cells. In the same cohort of patients, we demonstrated a parallel and significant loss of 15-PGDH and WNT5A protein expression in CRC tissues compared with matched normal colon tissues...
November 2016: Molecular Oncology
https://www.readbyqxmd.com/read/27511871/a-ribonucleotide-reductase-inhibitor-with-deoxyribonucleoside-reversible-cytotoxicity
#20
Mikael Crona, Paula Codó, Venkateswara Rao Jonna, Anders Hofer, Aristi P Fernandes, Fredrik Tholander
Ribonucleotide Reductase (RNR) is the sole enzyme that catalyzes the reduction of ribonucleotides into deoxyribonucleotides. Even though RNR is a recognized target for antiproliferative molecules, and the main target of the approved drug hydroxyurea, few new leads targeted to this enzyme have been developed. We have evaluated a recently identified set of RNR inhibitors with respect to inhibition of the human enzyme and cellular toxicity. One compound, NSC73735, is particularly interesting; it is specific for leukemia cells and is the first identified compound that hinders oligomerization of the mammalian large RNR subunit...
November 2016: Molecular Oncology
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