51,340 results match your criteria Cancer research[Journal]


A Novel Form of 4-1BBL Prevents Cancer Development via Nonspecific Activation of CD4 T and Natural Killer Cells.

Cancer Res 2019 Feb;79(4):783-794

Institute for Cellular Therapeutics, University of Louisville, Louisville, Kentucky.

: Costimulation through 4-1BB (CD137) receptor generates robust CD8 T-effector and memory responses. The only known ligand, 4-1BBL, is a trimeric transmembrane protein that has no costimulatory activity as a soluble molecule. Thus, agonistic antibodies to the receptor have been used for cancer immunotherapy in preclinical models and are currently being evaluated in the clinic. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-2401DOI Listing
February 2019

ATM Inhibition Sensitizes Tumors to High-Dose Irradiation.

Authors:
Dennis Hallahan

Cancer Res 2019 Feb;79(4):704-705

Washington University School of Medicine, St. Louis, Missouri.

Mechanistic studies of high-dose irradiation are important to improve our understanding on how the efficacy of stereotactically delivered high-dose irradiation can be enhanced by therapeutics such as ataxia-telangiesctasia-mutated (ATM) inhibitors. In this issue of , Torok and colleagues found that a single 15 Gy radiation dose eliminated lung tumor growth in mice when ATM was deleted in cancer cells versus when deleted in endothelial cells. These data support the establishment of clinical trials testing ATM inhibitors in combination with highly conformal radiotherapy or high-dose rate brachytherapy. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-4072DOI Listing
February 2019

A PET Glutamate Analogue to Measure Cancer Cell Redox State and Oxidative Stress: Promise and Paradox.

Cancer Res 2019 Feb;79(4):701-703

Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania.

[F]FSPG was shown to provide an indirect measure of the cellular redox state and may be used as an early indicator of therapy response to cancer therapies that cause oxidative stress. A somewhat paradoxical finding was that reduced [F]FSPG cellular uptake was associated with either lower cellular concentrations of cystine or glutamate, despite opposing the transport of these substances in the Xc antiporter, for which [F]FSPG is also a substrate. Further studies of the kinetics of [F]FSPG will help elucidate the factors mediating a decline in [F]FSPG with oxidative stress. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-4034DOI Listing
February 2019

Multimodal Action of Mas Activation for Systemic Cancer Cachexia Therapy.

Cancer Res 2019 Feb;79(4):699-700

Department of Biochemistry and Molecular Biology, Indianapolis, Indiana.

Cancer cachexia remains a largely intractable, deadly condition for patients with no approved, effective therapies. However, research progress over the past few decades demonstrates that cachexia is a disease with specific, targetable mechanisms. New work by Murphy and colleagues in this issue of suggests that activation of the alternative renin-angiotensin system with the nonpeptide Mas receptor agonist AVE 0991 holds promise for reducing muscle wasting in cancer. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-3910DOI Listing
February 2019

Disruption of endolysosomal RAB5/7 efficiently eliminates colorectal cancer stem cells.

Cancer Res 2019 Feb 14. Epub 2019 Feb 14.

Gastroenterological Surgery, Graduate School of Medicine, Osaka University

Given that cancer stem cells (CSC) play a key role in drug resistance and relapse, targeting CSC remains a promising in cancer therapy. Here we show that RAB5/7, which are involved in the endolysosomal pathway, play key roles in the maintenance of CSC survival via regulation of the mitophagic pathway. Inhibition of RAB5/7 efficiently eliminated colorectal CSC and disrupted cancer foci. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-2192DOI Listing
February 2019

MDH1 and MPP7 regulate autophagy in pancreatic ductal adenocarcinoma.

Cancer Res 2019 Feb 14. Epub 2019 Feb 14.

Molecular Cell Biology of Autophagy, Francis Crick Institute.

Pancreatic ductal adenocarcinoma (PDAC) is driven by metabolic changes in pancreatic cells caused by oncogenic mutations and dysregulation of p53. PDAC cell lines and PDAC-derived xenografts grow as a result of altered metabolic pathways, changes in stroma, and autophagy. Selective targeting and inhibition of one of these may open avenues for the development of new therapeutic strategies. Read More

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http://cancerres.aacrjournals.org/lookup/doi/10.1158/0008-54
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http://dx.doi.org/10.1158/0008-5472.CAN-18-2553DOI Listing
February 2019
1 Read

Cytochrome c-deficiency Confers Apoptosome and Mitochondrial Dysfunction in African-American Men with Prostate Cancer.

Cancer Res 2019 Feb 14. Epub 2019 Feb 14.

Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo

Although African-American (AA) prostate cancer (PCa) patients tend to develop greater therapeutic resistance and faster PCa recurrence compared to Caucasian-American men, the molecular mechanisms of this racial PCa disparity remain undefined. In this study, we provide the first comprehensive evidence that cytochrome c (CC) deficiency in AA primary tumors and cancer cells abrogates apoptosome-mediated caspase activation and contributes to mitochondrial dysfunction, thereby promoting therapeutic resistance and PCa aggressiveness in AA men. In AA PCa cells, decreased nuclear accumulation of Nrf1 and its subsequent loss of binding to the CC promoter mediated CC deficiency. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-2383DOI Listing
February 2019

NRF2 Activation in Cancer: From DNA to Protein.

Cancer Res 2019 Feb 13. Epub 2019 Feb 13.

Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, North Carolina.

The Cancer Genome Atlas catalogued alterations in the Kelch-like ECH-associated protein 1 and nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway in 6.3% of patient samples across 226 studies, with significant enrichment in lung and upper airway cancers. These alterations constitutively activate NRF2-dependent gene transcription to promote many of the cancer hallmarks, including cellular resistance to oxidative stress, xenobiotic efflux, proliferation, and metabolic reprogramming. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-2723DOI Listing
February 2019

Deoxyribozymes as Catalytic Nanotherapeutic Agents.

Cancer Res 2019 Feb 13. Epub 2019 Feb 13.

Vascular Biology and Translational Research, School of Medical Sciences, Faculty of Medicine, University of New South Wales, Sydney, Australia.

RNA-cleaving deoxyribozymes (DNAzymes) are synthetic single-stranded DNA-based catalytic molecules that can be engineered to bind to and cleave target mRNA at predetermined sites. These have been used as therapeutic agents in a range of preclinical cancer models and have entered clinical trials in Europe, China, and Australia. This review surveys regulatory insights into mechanisms of disease brought about by use of catalytic DNA and , including recent uses as nanosensors, nanoflowers, and nanosponges, and the emerging role of adaptive immunity underlying DNAzyme inhibition of cancer growth. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-2474DOI Listing
February 2019

Cancer Res 2019 Feb 13. Epub 2019 Feb 13.

Cancer Center, University of Hawaii at Manoa.

Studies involving transcriptomics have revealed multiple molecular subtypes of hepatocellular carcinoma (HCC). PET/CT has also identified distinct molecular imaging subtypes, including those with increased and decreased choline metabolism as measured by tissue uptake of the radiopharmaceutical 18F-flurocholine. Gene signatures reflecting the molecular heterogeneity of HCC may identify the biological and clinical significance of these imaging subtypes. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-3837DOI Listing
February 2019
9.329 Impact Factor

ACE: A Workbench using Evolutionary Genetic Algorithms for analyzing association in TCGA Data.

Cancer Res 2019 Feb 13. Epub 2019 Feb 13.

Centre for Cancer Research and Cell Biology, Queen's University Belfast

Modern methods of acquiring molecular data have improved rapidly in recent years, making it easier for researchers to collect large volumes of information. However, this has increased the challenge of recognizing interesting patterns within the data. Atlas Correlation Explorer (ACE) is a user-friendly workbench for seeking associations between attributes in the cancer genome atlas (TCGA) database. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-1976DOI Listing
February 2019

YY1 complex promotes Quaking expression via super-enhancer binding during EMT of hepatocellular carcinoma.

Cancer Res 2019 Feb 13. Epub 2019 Feb 13.

State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University.

Quaking (QKI) is an alternative splicing factor that can regulate circRNA formation in the progression of epithelial-mesenchymal transition, but the mechanism remains unclear. High expression of QKI is correlated with short survival time, metastasis, and high clinical stage and pathology grade in hepatocellular carcinoma (HCC). Here we report that transcription of the QKI gene was activated by the Yin-Yang 1 (YY1)/p65/p300 complex, in which YY1 bound to the super-enhancer and promoter of QKI, p65 combined with the promoter, and p300 served as a mediator to maintain the stability of the complex. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-2238DOI Listing
February 2019

A MicroRNA Expression Signature in Breast Tumor Tissue is Associated with Risk of Distant Metastasis.

Cancer Res 2019 Feb 13. Epub 2019 Feb 13.

Hackensack University Medical Center.

Dysregulation of microRNA (miRNA) expression may influence breast cancer progression, and experimental evidence suggests that miRNA silencing might suppress breast cancer metastasis. However, the relationship between miRNA and metastasis must be confirmed before this approach can be applied in the clinic. To this end, we conducted a 2-stage study in a cohort of 3760 breast cancer patients to first identify and then validate the association between miRNA expression and risk of distant metastasis. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-2779DOI Listing
February 2019

Acidification of tumor at stromal boundaries drives transcriptome alterations associated with aggressive phenotypes.

Cancer Res 2019 Feb 12. Epub 2019 Feb 12.

David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology

Acidosis is a fundamental feature of the tumor microenvironment that directly regulates tumor cell invasion by affecting immune cell function, clonal cell evolution, and drug resistance. Despite the important association of tumor microenvironment acidosis with tumor cell invasion, relatively little is known regarding which areas within a tumor are acidic and how acidosis influences gene expression to promote invasion. Here we injected a labeled pH-responsive peptide to mark acidic regions within tumors. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-1604DOI Listing
February 2019

T-type Cav3.1 channels mediate progression and chemotherapeutic resistance in glioblastoma.

Cancer Res 2019 Feb 12. Epub 2019 Feb 12.

Experimental Medicine, IRBLleida-University of Lleida

T-type Ca2+ channels (TTCC) have been identified as key regulators of cancer cell cycle and survival. In vivo studies in glioblastoma (GBM) murine xenografts have shown that drugs able to block TTCC in vitro (such as tetralol derivatives mibefradil/NNC-55-096, or different 3,4-dihydroquinazolines) slow tumor progression. However, currently available TTCC pharmacological blockers have limited selectivity for TTCC, and are unable to distinguish between TTCC isoforms. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-1924DOI Listing
February 2019

MDM2 and MDM4 are Therapeutic Vulnerabilities in Malignant Rhabdoid Tumors.

Cancer Res 2019 Feb 12. Epub 2019 Feb 12.

Comprehensive Cancer Center, St. Jude Children's Research Hospital

Malignant rhabdoid tumors (MRT) are highly aggressive pediatric cancers that respond poorly to current therapies. In this study, we screened several MRT cell lines with large-scale RNAi, CRISPR-Cas9, and small-molecule libraries to identify potential drug targets specific for these cancers. We discovered MDM2 and MDM4, the canonical negative regulators of p53, as significant vulnerabilities. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-3066DOI Listing
February 2019

Upregulation of PD-L1 via HMGB1-activated IRF3 and NF-kB contributes to UV radiation-induced immune suppression.

Cancer Res 2019 Feb 8. Epub 2019 Feb 8.

Pathology, University of Tennessee Health Science Center

Solar ultraviolet radiation (UVR) suppresses skin immunity, which facilitates initiation of skin lesions and establishment of tumors by promoting immune evasion. It is unclear whether immune checkpoints are involved in the modulation of skin immunity by UVR. Here we report that UVR exposure significantly increased expression of immune checkpoint molecule PD-L1 in melanoma cells. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-3134DOI Listing
February 2019
9.329 Impact Factor

Tumor suppressor microRNA-204-5p regulates growth, metastasis, and immune microenvironment remodeling in breast cancer.

Cancer Res 2019 Feb 8. Epub 2019 Feb 8.

Department of Surgery and Cancer Research Institute, Seoul National University College of Medicine

Various microRNAs (miRNAs) play critical roles in the development and progression of solid tumors. In this study, we describe the role of miR-204-5p in limiting growth and progression of breast cancer. In breast cancer tissues, miR-204-5p was significantly downregulated compared to normal breast tissues, and its expression levels were associated with increased survival outcome in breast cancer patients. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-0891DOI Listing
February 2019
9.329 Impact Factor

EZH2 inhibitor GSK126 suppresses anti-tumor immunity by driving production of myeloid-derived suppressor cells.

Cancer Res 2019 Feb 8. Epub 2019 Feb 8.

Institute of Cancer, Xinqiao Hospital, Third Military Medical University

Enhancer of Zeste homolog (EZH2) is a key epigenetic regulator of gene expression and is frequently overexpressed in various cancer types, suggesting a role in oncogenesis. The therapeutic potential of EZH2 inhibitors is currently being explored, but their effect on anti-tumor immunity is largely unknown. Here we report that suppressing EZH2 activity using EZH2 inhibitor GSK126 resulted in increased numbers of myeloid-derived suppressor cells (MDSC) and fewer CD4+ and IFN-γ+CD8+ T cells, which are involved in anti-tumor immunity. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-2395DOI Listing
February 2019

Epithelial-to-mesenchymal transition is a mechanism of ALK inhibitor resistance in lung cancer independent of ALK mutation status.

Cancer Res 2019 Feb 8. Epub 2019 Feb 8.

Division of Medical Oncology, Cancer Research Institute, Kanazawa University

Mutations in the ALK gene are detectable in ~40% of ALK-rearranged lung cancers resistant to ALK inhibitors. While epithelial-to-mesenchymal transition (EMT) is a mechanism of resistance to various targeted drugs, its involvement in ALK-inhibitor resistance is largely unknown. In this study, we report that both ALK mutant L1196M and EMT were concomitantly detected in a single crizotinib-resistant lesion in an ALK-rearranged lung cancer patient. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-2052DOI Listing
February 2019

Spleen tyrosine kinase-mediated autophagy is required for epithelial-mesenchymal plasticity and metastasis in breast cancer.

Cancer Res 2019 Feb 7. Epub 2019 Feb 7.

Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University

The ability of breast cancer cells to transiently transition between epithelial and mesenchymal states contributes to their metastatic potential. Therefore, driving tumor cells into a stable mesenchymal state, as opposed to complete tumor cell eradication, presents an opportunity to pharmacologically limit disease progression by promoting an asymptomatic state of dormancy. Here we compare a reversible model of epithelial-mesenchymal transition (EMT) induced by TGF-β to a stable mesenchymal phenotype induced by chronic exposure to the ErbB kinase inhibitor lapatinib. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-2636DOI Listing
February 2019
1 Read
9.329 Impact Factor

Loss of Foxp3 and Tsc1 Accelerate Prostate Cancer Progression through a Synergistic Transcriptional and Post-translational Regulation of c-MYC.

Cancer Res 2019 Feb 7. Epub 2019 Feb 7.

Genetics, University of Alabama at Birmingham

Although c-MYC and mTOR are frequently activated proteins in prostate cancer, any interaction between the two is largely untested. Here we characterize the functional crosstalk between FOXP3-c-MYC and TSC1-mTOR signaling during tumor progression. Deletion of Tsc1 in mouse embryonic fibroblasts (MEF) decreased phosphorylation of c-MYC at threonine 58 (pT58) and increased phosphorylation at serine 62 (pS62), an observation validated in prostate cancer cells. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-2049DOI Listing
February 2019
2 Reads

Phosphatase 1 nuclear targeting subunit mediates recruitment and function of poly (ADP-ribose) polymerase 1 in DNA repair.

Cancer Res 2019 Feb 7. Epub 2019 Feb 7.

Oral Biology, University of Nebraska Medical Center

Poly (ADP-ribose) polymerases (PARP), particularly PARP1, play an essential role in the detection and repair of DNA single strand breaks (SSB) and double strand breaks (DSB). PARP1 accumulates at DNA damage sites within seconds after DNA damage to catalyze the massive induction of substrate protein poly ADP-ribosylation (PARylation). However, the molecular mechanisms underlying the recruitment and activation of PARP1 in DNA repair are not fully understood. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-1673DOI Listing
February 2019
9.329 Impact Factor

Immuno-Oncological Efficacy of RXDX-106, a Novel Small Molecule Inhibitor of the TAM (TYRO3, AXL, MER) Family of Kinases.

Cancer Res 2019 Feb 5. Epub 2019 Feb 5.

Department of Pathology, University of California, San Diego

Expression of the TAM (TYRO3, AXL, MER) family of receptor tyrosine kinases (RTK) has been associated with cancer progression, metastasis, and drug resistance. In immune cells, TAM RTKs can dampen inflammation in favor of homeostatic wound healing responses, thus potentially contributing to the evasion of cancer cells from immune surveillance. Here we characterize the small molecule RXDX-106 as a selective and potent pan-TAM RTK inhibitor with slow dissociation kinetics and significant anti-tumor activity in multiple syngeneic tumor models. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-2022DOI Listing
February 2019
1 Read

Whole genome-derived tiled peptide arrays detect pre-diagnostic autoantibody signatures in non-small cell lung cancer.

Cancer Res 2019 Feb 5. Epub 2019 Feb 5.

Clinical Cancer Prevention, University of Texas MD Anderson Cancer Center

The majority of non-small cell lung cancer (NSCLC) cases are diagnosed at advanced stages, primarily because earlier stages of the disease are either asymptomatic or may be attributed to other causes such as infection or long-term effects from smoking. Therefore, early detection of NSCLC would likely increase response and survival rates due to timely intervention. Here we utilize a novel approach based on whole genome-derived tiled peptide arrays to identify epitopes associated with autoantibody reactivity in NSCLC as a potential means for early detection. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-1536DOI Listing
February 2019
2 Reads

Genome-wide screening and functional analysis identifies tumor suppressor long non-coding RNAs epigenetically silenced in hepatocellular carcinoma.

Cancer Res 2019 Feb 4. Epub 2019 Feb 4.

School of Biomedical Sciences, Chinese University of Hong Kong

Long non-coding RNAs (lncRNA) play critical roles in the development of cancer including hepatocellular carcinoma (HCC). However, the mechanisms underlying their deregulation remain largely unexplored. In this study, we report that two lncRNA frequently downregulated in HCC function as tumor suppressors and are epigenetically silenced by histone methyltransferase EZH2. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-1659DOI Listing
February 2019

Targeting APLN/APLNR improves anti-angiogenic efficiency and blunts pro-invasive side effects of VEGFA/VEGFR2-blockade in glioblastoma.

Cancer Res 2019 Feb 4. Epub 2019 Feb 4.

Neurosurgical Research, Department of Neurosurgery, University Hospital, LMU Munich

Anti-angiogenic therapy of glioblastoma with bevacizumab, a vascular endothelial growth factor-A (VEGFA)-blocking antibody, may accelerate tumor cell invasion and induce alternative angiogenic pathways. Here we investigate the roles of the pro-angiogenic receptor APLNR and its cognate ligand apelin in VEGFA/VEGFR2 anti-angiogenic therapy against distinct subtypes of glioblastoma. In proneural glioblastoma, apelin levels were downregulated by VEGFA or VEGFR2 blockade. Read More

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http://cancerres.aacrjournals.org/lookup/doi/10.1158/0008-54
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http://dx.doi.org/10.1158/0008-5472.CAN-18-0881DOI Listing
February 2019
7 Reads

Novel Third-Generation EGFR Tyrosine Kinase Inhibitors and Strategies to Overcome Therapeutic Resistance in Lung Cancer.

Cancer Res 2019 Feb 4;79(4):689-698. Epub 2019 Feb 4.

University of California San Diego, Moores Cancer Center, La Jolla, California.

EGFR-activating mutations are observed in approximately 15% to 20% of patients with non-small cell lung cancer. Tyrosine kinase inhibitors have provided an illustrative example of the successes in targeting oncogene addiction in cancer and the role of tumor-specific adaptations conferring therapeutic resistance. The compound osimertinib is a third-generation tyrosine kinase inhibitor, which was granted full FDA approval in March 2017 based on targeting EGFR T790M resistance. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-1281DOI Listing
February 2019
1 Read
9.329 Impact Factor

Landscape of germline and somatic mitochondrial DNA mutations in pediatric malignancies.

Cancer Res 2019 Feb 1. Epub 2019 Feb 1.

Pathology and Laboratory Medicine, Children's Hospital of Los Angeles

Little is known about the spectrum of mitochondrial DNA (mtDNA) mutations across pediatric malignancies. In this study, we analyzed matched tumor and normal whole genome sequencing data from 616 pediatric patients with hematopoietic malignancies, solid tumors, and brain tumors. We identified 391 mtDNA mutations in 284 tumors including 45 loss-of-function mutations, which clustered at 4 statistically significant hotspots in MT-COX3, MT-ND4, and MT-ND5, and at a mutation hotspot in MT-tRNA-MET. Read More

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http://cancerres.aacrjournals.org/lookup/doi/10.1158/0008-54
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http://dx.doi.org/10.1158/0008-5472.CAN-18-2220DOI Listing
February 2019
5 Reads

CCL27/CCL28-CCR10 CHEMOKINE SIGNALING MEDIATES MIGRATION OF LYMPHATIC ENDOTHELIAL CELLS.

Cancer Res 2019 Feb 1. Epub 2019 Feb 1.

Tumour Angiogenesis Program, Peter MacCallum Cancer Centre

The formation of new lymphatic vessels (lymphangiogenesis) and remodeling of existing lymphatics are thought to facilitate the entry and transport of tumor cells into lymphatic vessels and on to distant organs. The migration of lymphatic endothelial cells (LEC) toward guidance cues is critical for lymphangiogenesis. While chemokines are known to provide directional navigation for migrating immune cells, their role in mediating LEC migration during tumor-associated lymphangiogenesis is not well defined. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-1858DOI Listing
February 2019
2 Reads

Transcriptome-wide association study identifies new candidate susceptibility genes for glioma.

Cancer Res 2019 Feb 1. Epub 2019 Feb 1.

Division of Genetics and Epidemiology, Institute of Cancer Research.

Genome-wide association studies (GWAS) have so far identified 25 loci associated with glioma risk, with most showing specificity for either glioblastoma (GBM) or non-GBM tumors. The majority of these GWAS susceptibility variants reside in non-coding regions and the causal genes underlying the associations are largely unknown. Here we performed a transcriptome-wide association study to search for novel risk loci and candidate causal genes at known GWAS loci using Genotype-Tissue Expression Project (GTEx) data to predict cis-predicted gene expression in relation to GBM and non-GBM risk in conjunction with GWAS summary statistics on 12,488 glioma cases (6,183 GBM, 5,820 non-GBM) and 18,169 controls. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-2888DOI Listing
February 2019

The deubiquitylase OTUB1 mediates ferroptosis via stabilization of SLC7A11.

Cancer Res 2019 Feb 1. Epub 2019 Feb 1.

Institute for Cancer Genetics, Columbia University

Although cell cycle arrest, senescence, and apoptosis are established mechanisms of tumor suppression, accumulating evidence reveals that ferroptosis, an iron-dependent, non-apoptotic form of cell death, represents a new regulatory pathway in suppressing tumor development. Ferroptosis is triggered by lipid peroxidation and is tightly regulated by SLC7A11, a key component of the cystine-glutamate antiporter. Although many studies demonstrate the importance of transcriptional regulation of SLC7A11 in ferroptotic responses, it remains largely unknown how the stability of SLC7A11 is controlled in human cancers. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-3037DOI Listing
February 2019

Eomes+T-betlow CD8+ T cells are functionally impaired and are associated with poor clinical outcome in patients with acute myeloid leukemia (AML).

Cancer Res 2019 Feb 1. Epub 2019 Feb 1.

Hematology and Oncology, Penn State Hershey Cancer Institute

Acute myeloid leukemia (AML) is a devastating blood cancer with poor prognosis. Immunotherapy targeting inhibitory pathways to unleash the anti-leukemia T cell response is a promising strategy for the treatment of leukemia, but we must first understand the underlying molecular mechanisms. Eomesodermin (Eomes) and T-bet are both T-box transcription factors that regulate CD8+ T cell responses in a context-specific manner. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-3107DOI Listing
February 2019
2 Reads

A Dynamic -Regulation Pattern Underlying Epithelial Ovarian Cancer Susceptibility.

Cancer Res 2019 Feb;79(3):439-440

Laboratory of Translational Genomics, Division of Cancer Epidemiology & Genetics, NCI, Bethesda, Maryland.

Efforts from the past decade in genomic analyses improved our understanding of genetic susceptibility to epithelial ovarian cancer (EOC). While genome-wide association studies (GWAS) have successfully identified approximately 40 genomic loci contributing to risk, a functional understanding of the molecular mechanisms underlying all but a few of these loci is lacking. The work by Buckley and colleagues has comprehensively characterized an EOC locus on chromosome band 9p22. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-3938DOI Listing
February 2019
1 Read

Epigenetic Drift in Colorectal Cancer-It's Probably Later Than You Think.

Authors:
Carmen Sapienza

Cancer Res 2019 Feb;79(3):437-438

Fels Institute for Cancer Research and Molecular Biology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania.

The analysis of age-related methylation changes in patients with colorectal cancer indicates that tumors have their origins earlier in life than previously suspected. The implication is that healthy lifestyle modifications designed to prevent colorectal cancer should be adopted early in life.. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-3806DOI Listing
February 2019

p300 mediates muscle wasting in Lewis lung carcinoma.

Cancer Res 2019 Jan 31. Epub 2019 Jan 31.

Department of Integrative Biology & Pharmacology, University of Texas Health Science Center at Houston.

C/EBPβ is a key mediator of cancer-induced skeletal muscle wasting. However, the signaling mechanisms that activate C/EBPβ in the cancer milieu are poorly defined. Here we report cancer-induced muscle wasting requires the transcriptional co-factor p300 which is critical for the activation of C/EBPβ. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-1653DOI Listing
January 2019
1 Read

Nod1 imprints inflammatory and carcinogenic responses toward the gastric pathogen Helicobacter pylori.

Cancer Res 2019 Jan 29. Epub 2019 Jan 29.

Medicine/Gastroenterology, Vanderbilt University

Helicobacter pylori is the strongest known risk for gastric cancer. The H. pylori cag type IV secretion system is an oncogenic locus which translocates peptidoglycan into host cells where it is recognized by NOD1, an innate immune receptor. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-2651DOI Listing
January 2019
9.329 Impact Factor

Pomalidomide alters pancreatic macrophage populations to generate an immune-responsive environment at precancerous and cancerous lesions.

Cancer Res 2019 Jan 29. Epub 2019 Jan 29.

Department of Cancer Biology, Mayo Clinic

During development of pancreatic cancer, alternatively-activated macrophages contribute to fibrogenesis, pancreatic intraepithelial neoplasia (PanIN) lesion growth, and generation of an immunosuppressive environment. Here we show that the immunomodulatory agent pomalidomide depletes pancreatic lesion areas of alternatively-activated macrophage populations. Pomalidomide treatment resulted in downregulation of interferon regulatory factor 4 (IRF4), a transcription factor for M2 macrophage polarization. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-1153DOI Listing
January 2019

Cervical cancer-instructed stromal fibroblasts enhance IL-23 expression in dendritic cells to support expansion of Th17 cells.

Cancer Res 2019 Jan 29. Epub 2019 Jan 29.

Institute of Virology, Saarland University Medical Center.

Persistent infection with high-risk human papillomavirus (HPV) is a prerequisite for the development of cervical cancer. HPV-transformed cells actively instruct their microenvironment, promoting chronic inflammation and cancer progression. We previously demonstrated that cervical cancer cells contribute to T-helper-17 (Th17) cell recruitment, a cell type with pro-tumorigenic properties. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-1913DOI Listing
January 2019

The transcriptional regulator Sin3A contributes to the oncogenic potential of STAT3.

Cancer Res 2019 Jan 28. Epub 2019 Jan 28.

Immunology, Transplantation and Infectious Disease, IRCCS San Raffaele Scientific Institute

Epigenetic silencing of promoter and enhancer regions is a common phenomenon in malignant cells. The transcription factor Signal transducer and activator of transcription (STAT) 3 is aberrantly activated in several tumors, where its constitutive acetylation accounts for the transcriptional repression of a number of tumor suppressor genes (TSG) via molecular mechanisms that remain to be understood. Using NPM-ALK+ ALCL as model system, we found in cells and patient-derived tumor xenografts that STAT3 is constitutively acetylated as a result of ALK activity. Read More

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http://cancerres.aacrjournals.org/lookup/doi/10.1158/0008-54
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http://dx.doi.org/10.1158/0008-5472.CAN-18-0359DOI Listing
January 2019
4 Reads

Cognate Non-Lytic Interactions between CD8+ T cells and Breast Cancer Cells Induce Cancer Stem Cell-like Properties.

Cancer Res 2019 Jan 28. Epub 2019 Jan 28.

Department of Obstetrics and Gynecology, Universitätsklinikum Würzburg

Targeting of tumor immune escape mechanisms holds enormous therapeutic potential. Still, most patients progress under immune checkpoint blockade and some even become hyper-progressors. To investigate how cancer cells respond to activated but ineffective T cells, we challenged peptide-loaded MCF-7 breast cancer cells with antigen-specific CD8+ T cells in which lytic granules had been destroyed by pre-treatment with Concanamycin A. Read More

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http://cancerres.aacrjournals.org/lookup/doi/10.1158/0008-54
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http://dx.doi.org/10.1158/0008-5472.CAN-18-0387DOI Listing
January 2019
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Local delivery of OX40L, CD80, and CD86 mRNA kindles global anti-cancer immunity.

Cancer Res 2019 Jan 28. Epub 2019 Jan 28.

Division of Oncology, Stanford University Hospital and Clinics

Localized expression of effector molecules can initiate anti-tumor responses through engagement of specific receptors on target cells in the tumor microenvironment. These locally induced responses may also have a systemic effect, clearing additional tumors throughout the body. In this study, to evoke systemic anti-tumor responses, we utilized charge-altering releasable transporters (CART) for local intratumoral delivery of mRNA coding for co-stimulatory and immune-modulating factors. Read More

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http://cancerres.aacrjournals.org/lookup/doi/10.1158/0008-54
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http://dx.doi.org/10.1158/0008-5472.CAN-18-2867DOI Listing
January 2019
8 Reads

PAK4 phosphorylates fumarase and blocks TGF-β-induced cell growth arrest in lung cancer cells.

Cancer Res 2019 Jan 25. Epub 2019 Jan 25.

State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease.

The metabolic activity of fumarase (FH) participates in gene transcription linking to tumor cell growth. However, whether this effect is implicated in lung cancer remains unclear. Here, we show TGF-β induces p38-mediated FH phosphorylation at Thr 90, which leads to a FH/CSL (also known as RBP-Jκ) /p53 complex formation and FH accumulation at p21 promoter under concomitant activation of Notch signaling; in turn, FH inhibits histone H3 Lys 36 demethylation and thereby promotes p21 transcription and cell growth arrest. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-2575DOI Listing
January 2019
5 Reads
9.329 Impact Factor

Interplay between TRAP1 and sirtuin-3 modulates mitochondrial respiration and oxidative stress to maintain stemness of glioma stem cells.

Cancer Res 2019 Jan 25. Epub 2019 Jan 25.

Biological Sciences, UNIST

Glioblastoma (GBM) cancer stem cells (CSC) are primarily responsible for metastatic dissemination, resistance to therapy, and relapse of GBM, the most common and aggressive brain tumor. Development and maintenance of CSC require orchestrated metabolic rewiring and metabolic adaptation to a changing microenvironment. Here we show that cooperative interplay between the mitochondrial chaperone TRAP1 and the major mitochondria deacetylase sirtuin-3 (SIRT3) in glioma stem cells (GSC) increases mitochondrial respiratory capacity and reduces production of reactive oxygen species. Read More

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http://cancerres.aacrjournals.org/lookup/doi/10.1158/0008-54
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http://dx.doi.org/10.1158/0008-5472.CAN-18-2558DOI Listing
January 2019
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Anti-PD-L1 treatment results in functional remodeling of the macrophage compartment.

Cancer Res 2019 Jan 24. Epub 2019 Jan 24.

Translational Oncology, Genentech

Checkpoint inhibitors like anti-PD1/PD-L1 have demonstrated significant therapeutic efficacy in a subset of patients partly through reinvigoration of CD8 T cells. However, their impact on myeloid cells remains largely unknown. Here we report that anti-PD-L1 treatment favorably impacts the phenotype and function of tumor macrophages by polarizing the macrophage compartment towards a more pro-inflammatory phenotype. Read More

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http://dx.doi.org/10.1158/0008-5472.CAN-18-3208DOI Listing
January 2019
1 Read