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Cancer Discovery

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https://www.readbyqxmd.com/read/28428334/four-groups-win-cruk-grand-challenge
#1
(no author information available yet)
Four research teams were each awarded Cancer Research UK's "Grand Challenge" prize of up to £20 million, or about $25 million, over 5 years. The winning teams bring together scientists and technologists from around the world to tackle some of the most pressing unsolved problems in cancer research.
April 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28424193/study-suggests-treatment-approaches-for-cholangiocarcinomas
#2
(no author information available yet)
A comprehensive genome profile of cholangiocarcinoma reveals that the tumors fall into four molecular classes. The study suggests that patients with IDH1/2 mutations could benefit from drugs that inhibit oxidative phosphorylation or that target mutations in chromatin remodeling genes. The work also shows that some liver cancers are closely related to cholangiocarcinomas.
April 19, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28416471/chemotherapy-resistant-human-acute-myeloid-leukemia-cells-are-not-enriched-for-leukemic-stem-cells-but-require-oxidative-metabolism
#3
Thomas Farge, Estelle Saland, Fabienne de Toni, Nesrine Aroua, Moshen Hosseini, Robin Perry, Claudie Bosc, Mayumi Sugita, Lucille Stuani, Marine Fraisse, Sarah Scotland, Clément Larrue, Héléna Boutzen, Virginie Féliu, Marie-Laure Nicolau-Travers, Stephanie Cassant-Sourdy, Nicolas Broin, Marion David, Nizar Serhan, Audrey Sarry, Suzanne Tavitian, Tony Kaoma, Laurent Vallar, Jason Iacovoni, Laetitia K Linares, Camille Montersino, Remy Castellano, Emmanuel Griessinger, Yves Collette, Olivier Duchamp, Yara Barreira, Pierre Hirsch, Tony Palama, Lara Gales, Francois Delhommeau, Barbara H Garmy-Susini, Jean-Charles Portais, Francois Vergez, Mary Selak, Gwenn Danet-Desnoyers, Martin Carroll, Christian Récher, Jean Emmanuel Sarry
Chemotherapy-resistant human acute myeloid leukemia (AML) cells are thought to be enriched in quiescent immature leukemic stem cells (LSCs). To validate this hypothesis in vivo, we developed a clinically relevant chemotherapeutic approach treating patient-derived xenograft (PDX) with cytarabine. Cytarabine residual AML cells are enriched neither in immature, quiescent cells nor LSCs. Strikingly, cytarabine-resistant pre-existing and persisting cells displayed high levels of reactive oxygen species, showed increased mitochondrial mass, and retained active polarized mitochondria, consistent with a high oxidative phosphorylation (OXPHOS) status...
April 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28411208/lgr5-cancer-stem-cells-drive-primary-and-metastatic-colorectal-cancer
#4
(no author information available yet)
LGR5(+) colorectal cancer CSCs are dispensable for primary tumor growth due to plasticity.
April 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28411207/transdifferentiation-as-a-mechanism-of-treatment-resistance-in-a-mouse-model-of-castration-resistant-prostate-cancer
#5
Min Zou, Roxanne Toivanen, Antonina Mitrofanova, Nicolas Floc'h, Sheida Hayati, Yanping Sun, Clementine Le Magnen, Daniel Chester, Elahe A Mostaghel, Andrea Califano, Mark A Rubin, Michael M Shen, Cory Abate-Shen
Current treatments for castration-resistant prostate cancer (CPRC) that target androgen receptor (AR) signaling improve patient survival, yet ultimately fail. Here we provide novel insights into treatment response for the anti-androgen abiraterone by analyses of a genetically-engineered mouse model (GEMM) with combined inactivation of Trp53 and Pten, which are frequently co-mutated in human CRPC. These NPp53 mice fail to respond to abiraterone, and display accelerated progression to tumors resembling treatment-related CRPC with neuroendocrine differentiation (CRPC-NE) in humans...
April 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28411206/type-1-t-helper-cells-promote-tumor-vessel-normalization
#6
(no author information available yet)
TH1 cells promote tumor vessel pericyte coverage and vessel normalization to suppress metastasis.
April 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28411205/vista-upregulation-may-promote-resistance-to-ctla-4-blockade
#7
(no author information available yet)
CTLA-4 blockade with ipilimumab activates the immune inhibitory VISTA checkpoint in prostate cancer.
April 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28411204/rock-inhibition-primes-tumor-tissue-to-sensitize-cells-to-chemotherapy
#8
(no author information available yet)
Short-term ROCK targeting improves cytotoxic drug efficacy in primary and metastatic pancreatic cancers.
April 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28411203/ascorbate-alters-iron-metabolism-to-drive-anticancer-toxicity
#9
(no author information available yet)
Ascorbate disrupts iron metabolism to cause H2O2-mediated oxidative damage to NSCLC and GBM.
April 14, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28408401/synergistic-immunostimulatory-effects-and-therapeutic-benefit-of-combined-histone-deacetylase-and-bromodomain-inhibition-in-non-small-cell-lung-cancer
#10
Dennis Adeegbe, Yan Liu, Patrick H Lizotte, Yusuke Kamihara, Amir R Aref, Christina Almonte, Ruben Dries, Yuyang Li, Shengwu Liu, Xiaoen Wang, Tiquella Warner-Hatten, Jessica Castrillon, Guo-Cheng Yuan, Neermala Poudel-Neupane, Haikuo Zhang, Jennifer L Guerriero, Shiwei Han, Mark M Awad, David A Barbie, Jerome Ritz, Simon S Jones, Peter S Hammerman, James E Bradner, Steven N Quayle, Kwok-Kin Wong
Effective therapies for non-small cell lung cancer (NSCLC) remain challenging despite an increasingly comprehensive understanding of somatically altered oncogenic pathways. It is now clear that therapeutic agents with potential to impact the tumor immune microenvironment potentiate immune-orchestrated therapeutic benefit. Herein we evaluated the immunoregulatory properties of histone deacetylase (HDAC) and bromodomain inhibitors, two classes of drugs that modulate the epigenome, with a focus on key cell subsets that are engaged in an immune response...
April 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28408400/epigenetic-identity-in-aml-depends-on-disruption-of-non-promoter-regulatory-elements-and-is-affected-by-antagonistic-effects-of-mutations-in-epigenetic-modifiers
#11
Jacob Glass, Duane C Hassane, Bas Wouters, Hiroyoshi Kunimoto, Roberto Avellino, Francine E Garrett-Bakelman, Olga A Guryanova, Robert Bowman, Shira Redlich, Andrew Intlekofer, Cem Meydan, Tingting Qin, Mame P Fall, Alicia Alonso, Monica L Guzman, Peter Jm Valk, Craig B Thompson, Ross L Levine, Olivier Elemento, Ruud Delwel, Ari Melnick, Maria E Figueroa
Aberrant DNA methylation of gene promoters is a hallmark of AML. To define more precisely how cytosine methylation is redistributed in AML, we performed base-pair resolution methylome sequencing in 119 patients. We find that leukemic DNA methylation patterning is tightly linked to somatic mutations and primarily driven by regulatory elements outside of promoters and by CpG shores as opposed to CpG islands. Active enhancers displayed much stronger focal differential methylation than promoters and were generally aberrantly hypomethylated except in IDH2 mutant and CEBPA silenced AMLs...
April 13, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28404569/analysis-suggests-wider-use-for-parp-inhibitors
#12
(no author information available yet)
Researchers have developed a new tool, HRDetect, to pinpoint tumors that display BRCA deficiency but don't harbor BRCA1/2 mutations. Evaluating their method in breast, ovarian, and pancreatic cancers, they identified patients whose tumors were potentially vulnerable to PARP inhibition but who didn't carry these mutations.
April 12, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28400417/car-t-cell-therapy-defining-response-characteristics
#13
(no author information available yet)
Findings from a phase I study suggest that the durability of patients' response to CAR T-cell therapy, and their long-term survival, are influenced by whether they have minimal residual or morphologic disease prior to treatment. The former fared better overall, and also experienced less-severe side effects from this form of immunotherapy.
April 11, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28400416/top-medical-centers-sign-on-to-single-irb-model
#14
(no author information available yet)
All 64 member institutions of the NIH's Clinical and Translational Science Awards program have agreed to a common framework for running multisite trials under the umbrella of just one Institutional Review Board. The NCI has long offered a centralized review board option. Come September, single Institutional Review Boards will be mandatory for all NIH-backed studies.
April 11, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28389576/integrated-profiling-uncovers-lymphoma-immunoglobulin-neoantigens
#15
(no author information available yet)
CD4(+) T cells specific for immunoglobulin-derived neoantigens target autologous lymphoma cells.
April 7, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28389575/blinatumomab-has-activity-in-patients-with-tki-refractory-ph-all
#16
(no author information available yet)
Blinatumomab achieved complete remission with full or partial hematologic recovery in 36% of patients.
April 7, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28389574/lactb-may-be-a-tumor-suppressor-gene-in-breast-cancer
#17
(no author information available yet)
LACTB promotes breast cancer cell differentiation and suppresses breast tumorigenesis in vivo.
April 7, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28389573/a-foxo4-inhibitory-peptide-limits-chemotoxicity-in-mice
#18
(no author information available yet)
The FOXO4 inhibitory peptide FOXO4-DRI promotes targeted apoptosis of senescent cells.
April 7, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28381406/exploiting-defective-dna-repair-in-idh-mutant-cancers
#19
(no author information available yet)
Data from a preclinical study suggest rethinking the "oncometabolite hypothesis," which calls for blocking the product of neomorphic IDH1/2 mutations to halt tumor progression. Instead, exploiting the vulnerability of IDH1/2-mutant tumor cells to PARP inhibition, as a result of defective DNA repair, appears to be a more effective strategy that will soon be tested in the clinic.
April 5, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28381405/coxsackievirus-a21-synergizes-with-checkpoint-inhibitors
#20
(no author information available yet)
Treatment with a combination of a proprietary formulation of coxsackievirus and either an anti-CTLA-4 or anti-PD-1 checkpoint inhibitor yielded a higher response rate in phase I testing for melanoma than any of these drugs given on their own. Because the viral therapy adds little toxicity, it might prove an effective part of a dual regimen, according to interim trial data presented at the American Association for Cancer Research Annual Meeting 2017.
April 5, 2017: Cancer Discovery
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