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Molecular Cancer Research: MCR

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https://www.readbyqxmd.com/read/29133595/targeted-next-gen-sequencing-for-detecting-mll-gene-fusions-in-leukemia
#1
Sadia Afrin, Christine Rc Zhang, Claus Meyer, Caedyn L Stinson, Thy Pham, Timothy Jc Bruxner, Nicola C Venn, Toby N Trahair, Rosemary Sutton, Rolf Marschalek, J Lynn Fink, Andrew S Moore
Mixed Lineage Leukemia (MLL) gene rearrangements characterize approximately 70% of infant and 10% of adult and therapy-related leukemia. Conventional clinical diagnostics, including cytogenetics and fluorescence in situ hybridization (FISH) fail to detect MLL translocation partner genes (TPGs) in many patients. Long-Distance Inverse (LDI)-PCR, the 'gold standard' technique that is used to characterize MLL breakpoints is laborious and requires a large input of genomic DNA (gDNA). To overcome the limitations of current techniques, a targeted Next-Generation Sequencing (NGS) approach that requires low RNA input was tested...
November 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29133594/competitive-kinase-enrichment-proteomics-reveals-that-abemaciclib-inhibits-gsk3%C3%AE-and-activates-wnt-signaling
#2
Emily M Cousins, Dennis Goldfarb, Feng Yan, Jose Roques, David B Darr, Gary L Johnson, Michael B Major
The cellular and organismal phenotypic response to a small-molecule kinase inhibitor is defined collectively by the inhibitor's targets and their functions. The selectivity of small-molecule kinase inhibitors is commonly determined in vitro, using purified kinases and substrates. Recently, competitive chemical proteomics has emerged as a complementary, unbiased, cell-based methodology to define the target landscape of kinase inhibitors. Here, we evaluated and optimized a competitive multiplexed inhibitor bead mass spectrometry (MIB/MS) platform using cell lysates, live cells, and treated mice...
November 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29133593/adipose-derived-vegf-mtor-signaling-promotes-endometrial-hyperplasia-and-cancer-implications-for-obese-women
#3
Subhransu S Sahoo, Janine Lombard, Yvette Ius, Rachel O'Sullivan, Lisa G Wood, Pravin Nahar, Kenneth Simon Jaaback, Pradeep Tanwar
Obesity is responsible for increased morbidity and mortality in endometrial cancer (EC). Despite the positive correlation of body mass index (BMI) or obesity in endometrial carcinogenesis, the contribution of adipose tissue to the pathogenesis of endometrial hyperplasia and cancer is unclear. This study clarifies the role of adipocytes in the pathogenesis of EC by demonstrating that adipocyte-conditioned medium (ACM) increases proliferation, migration, and survival of EC cells compared to pre-adipocyte-conditioned medium (PACM)...
November 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29133592/parp1-trapping-and-dna-replication-stress-enhance-radiosensitization-with-combined-wee1-and-parp-inhibitors
#4
Leslie A Parsels, David Karnak, Joshua Parsels, Qiang Zhang, Jonathan Vélez-Padilla, Zachery Reichert, Daniel R Wahl, Jonathan Maybaum, Mark J O'Connor, Theodore S Lawrence, Meredith A Morgan
KRAS mutations in non-small cell lung cancer (NSCLC) cause increased levels of DNA damage and replication stress, suggesting that inhibition of the DNA damage response (DDR) is a promising strategy for radiosensitization of NSCLC. This study investigates the ability of a WEE1 inhibitor (AZD1775) and a PARP inhibitor (olaparib) to radiosensitize KRAS mutant NSCLC cells and tumors. In addition to inhibiting the DDR, these small-molecule inhibitors of WEE1 and PARP induce DNA replication stress via nucleotide exhaustion and PARP trapping, respectively...
November 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29133591/chemokine-signaling-facilitates-early-stage-breast-cancer-survival-and-invasion-through-fibroblast-dependent-mechanisms
#5
Gage Brummer, Diana S Acevedo, Qingting Hu, Mike Portsche, Wei Fang, Min Yao, Brandon Zinda, Megan Myers, Nehemiah S Alvarez, Patrick Fields, Yan Hong, Fariba Behbod, Nikki Cheng
Ductal carcinoma in situ (DCIS) is the most common form of breast cancer, with 50,000 cases diagnosed every year in the United States. Over-treatment and under-treatment remain significant clinical challenges in patient care. Identifying key mechanisms associated with DCIS progression could uncover new biomarkers to better predict patient prognosis and improve guided treatment. Chemokines are small soluble molecules that regulate cellular homing through molecular gradients. CCL2-mediated recruitment of CCR2+ macrophages are a well-established mechanism for metastatic progression...
November 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29133590/genotoxic-damage-activates-the-ampk-%C3%AE-1-isoform-in-the-nucleus-via-ca2-camkk2-signaling-to-enhance-tumor-cell-survival
#6
Diana Vara Ciruelos, Madhumita Dandapani, Alexander Gray, Ejaife O Egbani, A Mark Evans, D Grahame Hardie
Many genotoxic cancer treatments activate AMP-activated protein kinase (AMPK), but the mechanisms of AMPK activation in response to DNA damage, and its downstream consequences, have been unclear. In this study, etoposide activates the α1 but not the α2 isoform of AMPK, primarily within the nucleus. AMPK activation is independent of ataxia-telangiectasia mutated (ATM), a DNA damage-activated kinase, and the principal upstream kinase for AMPK, LKB1, but correlates with increased nuclear Ca2+ and requires the Ca2+/calmodulin-dependent kinase, CaMKK2...
November 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29133589/precision-oncology-beyond-targeted-therapy-combining-omics-data-with-machine-learning-matches-the-majority-of-cancer-cells-to-effective-therapeutics
#7
Michael Q Ding, Lujia Chen, Gregory F Cooper, Jonathan D Young, Xinghua Lu
Precision oncology involves identifying drugs that will effectively treat a tumor and then prescribing an optimal clinical treatment regimen. However, most first-line chemotherapy drugs do not have biomarkers to guide their application. For molecularly targeted drugs, using the genomic status of a drug target as a therapeutic indicator has limitations. In this study, machine learning methods (e.g., deep learning) were used to identify informative features from genome scale omics data and to train classifiers for predicting the effectiveness of drugs in cancer cell lines...
November 13, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29117945/adipocytes-sequester-and-metabolize-the-chemotherapeutic-daunorubicin
#8
Xia Sheng, Jean-Hugues Parmentier, Jonathan Tucci, Hua Pei, Omar Cortez-Toledo, Christina M Dieli-Conwright, Matthew J Oberley, Michael Neely, Etan Orgel, Stan G Louie, Steven D Mittelman
Obesity is associated with poorer outcome for many cancers. Previously, we observed that adipocytes protect acute lymphoblastic leukemia (ALL) cells from the anthracycline, daunorubicin. In this study, it is determined whether adipocytes clear daunorubicin from the tumor microenvironment (TME). Intracellular daunorubicin concentrations were evaluated using fluorescence. Daunorubicin and its largely inactive metabolite, daunorubicinol, were analytically measured in media, cells, and tissues using liquid chromatography/mass spectrometry (LC/MS)...
November 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29117944/small-molecule-sigma1-modulator-induces-autophagic-degradation-of-pd-l1
#9
Christina M Maher, Jeffrey D Thomas, Derick A Haas, Charles G Longen, Halley M Oyer, Jane Y Tong, Felix J Kim
Emerging evidence suggests that Sigma1 (SIGMAR1, also known as sigma-1 receptor) is a unique ligand-regulated integral membrane scaffolding protein that contributes to cellular protein and lipid homeostasis. Previously, we demonstrated that some small molecule modulators of Sigma1 alter endoplasmic reticulum (ER) associated protein homeostasis pathways in cancer cells, including the unfolded protein response and autophagy. Programmed death-ligand 1 (PD-L1) is a type 1 integral membrane glycoprotein that is co-translationally inserted into the ER and is processed and transported through the secretory pathway...
November 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29117943/fbxo31-suppresses-gastric-cancer-emt-by-targeting-snail1-for-proteasomal-degradation
#10
Shuiyan Zou, Cunying Ma, Fenghua Yang, Xia Xu, Jihui Jia, Zhifang Liu
The F-box protein FBXO31, a component of the Skp1/Cul1/F-box (SCF) E3 ubiquitin ligase complex, plays an important regulatory role in neuronal development, stress response and tumorigenesis. Our recent report indicates that FBXO31 functions as a tumor suppressor in gastric cancer and the loss of FBXO31 protein is associated with a higher malignant phenotype and poorer prognosis. However, little is known about the underlying mechanism. In this study, FBXO31 inhibits gastric cancer progression by suppressing the epithelial-mesenchymal transition (EMT)...
November 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29117942/er%C3%AE-sensitizes-nsclc-to-chemotherapy-by-regulating-dna-damage-response
#11
Fotis Nikolos, Christoforos Thomas, Igor Bado, Jan-Ake Gustafsson
The expression of wild-type estrogen receptor β (ESR2/ERβ1) correlates with clinical outcome in patients with Non-Small Cell Lung Cancer (NSCLC). However, the molecular mechanism that accounts for this association is currently poorly understood. ERβ1 was previously linked to chemotherapy response in patients with breast cancer and in breast cancer cells. The effect of the receptor in NSCLC cells after chemotherapy treatment, a common remedy for advanced NSCLC, has not been studied. Here, upregulation of ERβ1 increases the sensitivity of NSCLC cells to treatment with doxorubicin and etoposide...
November 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29117941/loss-of-uracil-dna-glycosylase-selectively-re-sensitizes-p53-mutant-and-deficient-cells-to-5-fdu
#12
Yan Yan, Yulan Qing, John J Pink, Stanton L Gerson
Thymidylate synthase (TS) inhibitors including fluoropyrimidines [e.g., 5-Fluorouracil (5-FU) and 5-Fluorodeoxyuridine (5-FdU, floxuridine)] and antifolates (e.g., pemetrexed) are widely used against solid tumors. Previously, we reported that shRNA-mediated knockdown (KD) of uracil DNA glycosylase (UDG) sensitized cancer cells to 5-FdU. Since p53 has also been shown as a critical determinant of the sensitivity to TS inhibitors, we further interrogated 5-FdU cytotoxicity after UDG depletion with regard to p53 status...
November 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29117940/etv4-facilitates-cell-cycle-progression-in-pancreatic-cells-through-transcriptional-regulation-of-cyclin-d1
#13
Nikhil Tyagi, Sachin K Deshmukh, Sanjeev K Srivastava, Shafquat Azim, Aamir Ahmad, Ahmed Al-Ghadhban, Ajay P Singh, James E Carter, Bin Wang, Seema Singh
The ETS family transcription factor ETV4 is aberrantly expressed in a variety of human tumors and plays an important role in carcinogenesis through upregulation of relevant target gene expression. Here, it is demonstrated that ETV4 is overexpressed in pancreatic cancer (PC) tissues as compared to the normal pancreas, and is associated with enhanced growth and rapid cell cycle progression of PC cells. ETV4 expression was silenced through stable expression of a specific short-interfering hairpin RNA (shRNA) in two PC cell lines (ASPC1 and Colo357), while it was ectopically expressed in BXPC3 cells...
November 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29117939/novel-signaling-complex-between-troy-and-egfr-mediates-glioblastoma-cell-invasion
#14
Zonghui Ding, Alison Roos, Jean Kloss, Harshil Dhruv, Sen Peng, Patrick Pirrotte, Jennifer M Eschbacher, Nhan L Tran, Joseph C Loftus
Glioblastoma is the most frequent primary brain tumor in adults and a highly lethal malignancy with a median survival of about 15 months. The aggressive invasion of the surrounding normal brain makes complete surgical resection impossible, increases the resistance to radiation and chemotherapy, and assures tumor recurrence. Thus, there is an urgent need to develop innovative therapeutics to target the invasive tumor cells for improved treatment outcomes of this disease. Expression of TROY (TNFRSF19), a member of the tumor necrosis factor (TNF) receptor family, increases with increasing glial tumor grade and inversely correlates with patient survival...
November 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29066471/correction-a-transcriptional-program-for-detecting-tgf%C3%AE-induced-emt-in-cancer
#15
(no author information available yet)
No abstract text is available yet for this article.
October 24, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29061667/novel-yap1-activator-identified-by-transcription-based-functional-screen-limits-multiple-myeloma-growth
#16
Junichi Maruyama, Kazutoshi Inami, Fumiyoshi Michishita, Xinliang Jiang, Hiroaki Iwasa, Kentaro Nakagawa, Mari Ishigami-Yuasa, Hiroyuki Kagechika, Norio Miyamura, Jun Hirayama, Hiroshi Nishina, Daichi Nogawa, Kouhei Yamamoto, Yutaka Hata
Yes-associated protein 1 (YAP1) interacts with numerous transcription factors including TEA-domain family proteins (TEAD) and p73. YAP1 is negatively regulated by the tumor suppressor Hippo pathway. In human cancers, the deregulation of the Hippo pathway and YAP1 gene amplification lead to the activation of YAP1, which induces epithelial-mesenchymal transition (EMT) and drug resistance. YAP1 inhibitors are expected to be useful in cancer therapy. On the other hand, in certain cancers, YAP1 up-regulates p73-dependent gene transcription and behaves as a tumor suppressor...
October 23, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29042487/differential-response-of-glioma-stem-cells-to-arsenic-trioxide-therapy-is-regulated-by-mnk1-and-mrna-translation
#17
Jonathan B Bell, Frank Eckerdt, Harshil Dhruv, Darren Finlay, Sen Peng, Seungchan Kim, Barbara Kroczynska, Elspeth Beauchamp, Kristen Alley, Jessica Clymer, Stewart Goldman, Shi-Yuan Cheng, C David James, Ichiro Nakano, Craig Horbinski, Andrew P Mazar, Kristiina Vuori, Priya Kumthekar, Jeffery Raizer, Michael E Berens, Leonidas C Platanias
Mesenchymal (MES) and proneural (PN) are two distinct glioma stem cells (GSCs) populations that drive therapeutic resistance in glioblastoma (GBM). We screened a panel of 650 small molecules against patient-derived GBM cells to discover compounds targeting specific GBM subtypes. Arsenic trioxide (ATO), a FDA-approved drug that crosses the blood-brain barrier, was identified as a potent PN-specific compound in the initial screen and follow-up validation studies. Furthermore, MES and PN GSCs exhibited differential sensitivity to ATO...
October 17, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29025958/mir-34a-regulates-expression-of-the-stathmin-1-oncoprotein-and-prostate-cancer-progression
#18
Balabhadrapatruni V S K Chakravarthi, Darshan S Chandrashekar, Sumit Agarwal, Sai Akshaya Hodigere Balasubramanya, Satya S Pathi, Moloy T Goswami, Xiaojun Jing, Rui Wang, Rohit Mehra, Irfan A Asangani, Arul M Chinnaiyan, Upender Manne, Guru Sonpavde, George J Netto, Jennifer Gordetsky, Sooryanarayana Varambally
In aggressive prostate cancers, the oncoprotein STMN1 (also known as stathmin 1 and oncoprotein 18) is often overexpressed. STMN1 is involved in various cellular processes, including cell proliferation, motility, and tumor metastasis. Here, it was found that the expression of STMN1 RNA and protein is elevated in metastatic prostate cancers. Knockdown of STMN1 resulted in reduced proliferation and invasion of cells and tumor growth and metastasis in vivo Furthermore, miR-34a downregulated STMN1 by directly binding to its 3'-UTR...
October 12, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29021233/divergent-activity-of-pseudogene-ptenp1-in-er-positive-and-negative-breast-cancer
#19
Synnøve Yndestad, Eilin Austreid, Kai Ove Skaftnesmo, Per Eystein Lønning, Hans P Eikesdal
Transcripts derived from the PTEN pseudogene (PTENP1) function as decoys to adsorb microRNAs (miRs) targeting the PTEN tumor suppressor for degradation, and PTENP1 upregulation is known to inhibit growth in preclinical cancer models. Here, PTENP1 3'UTR transduction influences PTEN, AKT/mTOR signaling, and tumor progression in estrogen receptor (ER)-positive and negative breast cancer cells. PTENP1 upregulation decreases PTEN gene expression in the ER-positive MCF7 and T47D human breast carcinoma cells and accelerates MCF7 tumor growth in vivo...
October 11, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29021232/pkc%C3%AE%C2%B5-controls-mitotic-progression-by-regulating-centrosome-migration-and-mitotic-spindle-assembly
#20
Silvia Martini, Tanya Soliman, Giuliana Gobbi, Prisco Mirandola, Cecilia Carubbi, Elena Masselli, Giulia Pozzi, Peter J Parker, Marco Vitale
To form a proper mitotic spindle, centrosomes must be duplicated and driven poleward in a timely and controlled fashion. Improper timing of centrosome separation and errors in mitotic spindle assembly may lead to chromosome instability, a hallmark of cancer. Protein Kinase C epsilon (PKCε) has recently emerged as a regulator of several cell cycle processes associated with the resolution of mitotic catenation during the metaphase-anaphase transition and in regulating the abscission checkpoint. However, an engagement of PKCε in earlier (pre)mitotic events has not been addressed...
October 11, 2017: Molecular Cancer Research: MCR
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