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Cancer evolution

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https://www.readbyqxmd.com/read/28434147/increasing-the-safety-and-efficacy-of-chimeric-antigen-receptor-t-cell-therapy
#1
REVIEW
Hua Li, Yangbing Zhao
Chimeric antigen receptor (CAR) T cell therapy is a promising cancer treatment that has recently been undergoing rapid development. However, there are still some major challenges, including precise tumor targeting to avoid off-target or "on-target/off-tumor" toxicity, adequate T cell infiltration and migration to solid tumors and T cell proliferation and persistence across the physical and biochemical barriers of solid tumors. In this review, we focus on the primary challenges and strategies to design safe and effective CAR T cells, including using novel cutting-edge technologies for CAR and vector designs to increase both the safety and efficacy, further T cell modification to overcome the tumor-associated immune suppression, and using gene editing technologies to generate universal CAR T cells...
April 22, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28432789/probing-protein-flexibility-reveals-a-mechanism-for-selective-promiscuity
#2
Nicolas A Pabon, Carlos J Camacho
Many eukaryotic regulatory proteins adopt distinct bound and unbound conformations, and use this structural flexibility to bind specifically to multiple partners. However, we lack an understanding of how an interface can select some ligands, but not others. Here, we present a molecular dynamics approach to identify and quantitatively evaluate the interactions responsible for this selective promiscuity. We apply this approach to the anti-cancer target PD-1 and its ligands PD-L1 and PD-L2. We discover that while unbound PD-1 exhibits a hard-to-drug hydrophilic interface, conserved specific triggers encoded in the cognate ligands activate a promiscuous binding pathway that reveals a flexible hydrophobic binding cavity...
April 22, 2017: ELife
https://www.readbyqxmd.com/read/28432125/sequential-adaptive-changes-in-a-c-myc-driven-model-of-hepatocellular-carcinoma
#3
James M Dolezal, Huabo Wang, Sucheta Kulkarni, Laura Jackson, Jie Lu, Sarangarajan Ranganathan, Eric S Goetzman, Sivakama Bharathi, Kevin Beezhold, Craig A Byersdorfer, Edward V Prochownik
Hepatocellular carcinoma (HCC) is a common cancer that frequently over-expresses the c-Myc (Myc) oncoprotein. Using a mouse model of Myc-induced HCC, we studied the metabolic, biochemical and molecular changes accompanying HCC progression, regression and recurrence. These involved altered rates of pyruvate and fatty acid β-oxidation and the likely re-directing of glutamine into biosynthetic rather than energy-generating pathways. Initial tumors also showed reduced mitochondrial mass and differential contributions of electron transport chain Complexes I and II to respiration...
April 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28431643/advances-in-circulating-tumor-dna-analysis
#4
Samantha Perakis, Martina Auer, Jelena Belic, Ellen Heitzer
The analysis of cell-free circulating tumor DNA (ctDNA) is a very promising tool and might revolutionize cancer care with respect to early detection, identification of minimal residual disease, assessment of treatment response, and monitoring tumor evolution. ctDNA analysis, often referred to as "liquid biopsy" offers what tissue biopsies cannot-a continuous monitoring of tumor-specific changes during the entire course of the disease. Owing to technological improvements, efforts for the establishment of preanalytical and analytical benchmark, and the inclusion of ctDNA analyses in clinical trial, an actual clinical implementation has come within easy reach...
2017: Advances in Clinical Chemistry
https://www.readbyqxmd.com/read/28431544/strategies-for-monitoring-and-combating-resistance-to-combination-kinase-inhibitors-for-cancer-therapy
#5
REVIEW
Leanne G Ahronian, Ryan B Corcoran
Targeted therapies such as kinase inhibitors and monoclonal antibodies have dramatically altered cancer care in recent decades. Although these targeted therapies have improved patient outcomes in several cancer types, resistance ultimately develops to these agents. One potential strategy proposed to overcome acquired resistance involves taking repeat tumor biopsies at the time of disease progression, to identify the specific molecular mechanism driving resistance in an individual patient and to select a new agent or combination of agents capable of surmounting that specific resistance mechanism...
April 21, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28430874/developmental-sall2-transcription-factor-a-new-player-in-cancer
#6
Viviana E Hermosilla, Matias I Hepp, David Escobar, Carlos Farlas, Elizabeth N Riffo, Ariel F Castro, Roxana Pincheira
SALL2, also known as Spalt-like transcription factor 2, is a member of the SALL family of transcription factors involved in development and conserved through evolution. Since its identification in 1996, findings indicate that SALL2 plays a role in neurogenesis, neuronal differentiation and eye development. Consistently, SALL2 deficiency associates with neural tube defects and coloboma, a congenital eye disease. Relevant to cancer, clinical studies indicate that SALL2 is deregulated in various cancers, and is a specific biomarker for Synovial Sarcoma...
April 18, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28430160/subverting-host-cell-p21-activated-kinase-a-case-of-convergent-evolution-across-pathogens
#7
REVIEW
Simona John Von Freyend, Terry Kwok-Schuelein, Hans Netter, Gholamreza Haqshenas, Jean-Philippe Semblat, Christian Doerig
Intracellular pathogens have evolved a wide range of strategies to not only escape from the immune systems of their hosts, but also to directly exploit a variety of host factors to facilitate the infection process. One such strategy is to subvert host cell signalling pathways to the advantage of the pathogen. Recent research has highlighted that the human serine/threonine kinase PAK, or p21-activated kinase, is a central component of host-pathogen interactions in many infection systems involving viruses, bacteria, and eukaryotic pathogens...
April 21, 2017: Pathogens
https://www.readbyqxmd.com/read/28429898/subclassification-of-the-molecular-types-of-breast-cancer-based-on-the-expression-of-immunohistochemical-markers-and-evolution
#8
Aldo Reigosa, David Hardisson, Francisco Sanzi, Eduardo Caleiras, Felipe Saldivia, Angel Fernández
Breast carcinomas have been classified from the molecular point of view into four major groups (Luminal A, Luminal B, HER2 and triple negative). However, these groups are not homogeneous and there is a need to establish subcategories that can be identified by immunohistochemistry (IHC), to better predict prognosis and carry out treatments that are more effective. This study was conducted in 354 patients diagnosed with invasive ductal breast carci- noma. The expression of 22 molecules was analyzed by tissue matrices and the results obtained were compared with molecular classes defined by IHC, according to the expression of estrogen receptor (ER), progesterone receptor (PR) and HER2, and the overall survival...
June 2016: Investigación Clínica
https://www.readbyqxmd.com/read/28429724/clonal-evolution-in-myelodysplastic-syndromes
#9
Pedro da Silva-Coelho, Leonie I Kroeze, Kenichi Yoshida, Theresia N Koorenhof-Scheele, Ruth Knops, Louis T van de Locht, Aniek O de Graaf, Marion Massop, Sarah Sandmann, Martin Dugas, Marian J Stevens-Kroef, Jaroslav Cermak, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Theo de Witte, Nicole M A Blijlevens, Petra Muus, Gerwin Huls, Bert A van der Reijden, Seishi Ogawa, Joop H Jansen
Cancer development is a dynamic process during which the successive accumulation of mutations results in cells with increasingly malignant characteristics. Here, we show the clonal evolution pattern in myelodysplastic syndrome (MDS) patients receiving supportive care, with or without lenalidomide (follow-up 2.5-11 years). Whole-exome and targeted deep sequencing at multiple time points during the disease course reveals that both linear and branched evolutionary patterns occur with and without disease-modifying treatment...
April 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28429102/improved-systemic-treatment-for-early-breast-cancer-improves-cure-rates-modifies-metastatic-pattern-and-shortens-post-metastatic-survival-35-year-results-from-the-munich-cancer-registry
#10
Dieter Hölzel, Renate Eckel, Ingo Bauerfeind, Bernd Baier, Thomas Beck, Michael Braun, Johannes Ettl, Ulrich Hamann, Marion Kiechle, Sven Mahner, Christian Schindlbeck, Johann de Waal, Nadia Harbeck, Jutta Engel
PURPOSE: Systemic therapies (ATHs) in early breast cancer have improved the survival of breast cancer (BC) patients in recent decades. The magnitude of the changes in overall, metastasis-free (MFS) and post-metastatic (PMS) survival and in the metastasis (MET) pattern will be described. PATIENT AND METHODS: We analysed 60,227 patients with a diagnosis of T-N-M0 BC between 1978 and 2013 and 11,983 patients with metastases (MET) in the Munich Cancer Registry. Patients will be divided into four time periods to identify relationships between BC and METs...
April 20, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28426839/medical-history-in-the-hellenic-journal-of-nuclear-medicine
#11
EDITORIAL
Andreas Otte, Byeong Cheol Ahn
The Hellenic Journal of Nuclear Medicine is about to celebrate its 20th anniversary end of 2017. On board of the editorial team since 2003, this journal has influenced me like a good friend over the many past years. From time to time, the journal has published interesting and valuable historical notes. They show that nuclear medicine has a history and that medicine is its basis. They also teach us today, and some of the ancient perspectives and approaches are still valid. The reader of HJNM may be interested in these historical contributions, as they are timeless...
January 2017: Hellenic Journal of Nuclear Medicine
https://www.readbyqxmd.com/read/28424337/physical-and-chemical-gradients-in-the-tumor-microenvironment-regulate-tumor-cell-invasion-migration-and-metastasis
#12
Madeleine J Oudin, Valerie M Weaver
Cancer metastasis requires the invasion of tumor cells into the stroma and the directed migration of tumor cells through the stroma toward the vasculature and lymphatics where they can disseminate and colonize secondary organs. Physical and biochemical gradients that form within the primary tumor tissue promote tumor cell invasion and drive persistent migration toward blood vessels and the lymphatics to facilitate tumor cell dissemination. These microenvironment cues include hypoxia and pH gradients, gradients of soluble cues that induce chemotaxis, and ions that facilitate galvanotaxis, as well as modifications to the concentration, organization, and stiffness of the extracellular matrix that produce haptotactic, alignotactic, and durotactic gradients...
April 19, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28423542/dna-methylation-intratumor-heterogeneity-in-localized-lung-adenocarcinomas
#13
Kelly Quek, Jun Li, Marcos Estecio, Jiexin Zhang, Junya Fujimoto, Emily Roarty, Latasha Little, Chi-Wan Chow, Xingzhi Song, Carmen Behrens, Taiping Chen, William N William, Stephen Swisher, John Heymach, Ignacio Wistuba, Jianhua Zhang, Andrew Futreal, Jianjun Zhang
Cancers are composed of cells with distinct molecular and phenotypic features within a given tumor, a phenomenon termed intratumor heterogeneity (ITH). Previously, we have demonstrated genomic ITH in localized lung adenocarcinomas; however, the nature of methylation ITH in lung cancers has not been well investigated. In this study, we generated methylation profiles of 48 spatially separated tumor regions from 11 localized lung adenocarcinomas and their matched normal lung tissues using Illumina Infinium Human Methylation 450K BeadChip array...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28423296/eltrombopag-added-to-standard-immunosuppression-for-aplastic-anemia
#14
Danielle M Townsley, Phillip Scheinberg, Thomas Winkler, Ronan Desmond, Bogdan Dumitriu, Olga Rios, Barbara Weinstein, Janet Valdez, Jennifer Lotter, Xingmin Feng, Marie Desierto, Harshraj Leuva, Margaret Bevans, Colin Wu, Andre Larochelle, Katherine R Calvo, Cynthia E Dunbar, Neal S Young
Background Acquired aplastic anemia results from immune-mediated destruction of bone marrow. Immunosuppressive therapies are effective, but reduced numbers of residual stem cells may limit their efficacy. In patients with aplastic anemia that was refractory to immunosuppression, eltrombopag, a synthetic thrombopoietin-receptor agonist, led to clinically significant increases in blood counts in almost half the patients. We combined standard immunosuppressive therapy with eltrombopag in previously untreated patients with severe aplastic anemia...
April 20, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28423240/biochemical-cellular-physiological-and-pathological-consequences-of-human-loss-of-n-glycolylneuraminic-acid
#15
Jonathan Okerblom, Ajit Varki
About 2-3 million years ago, Alu-mediated deletion of a critical exon in the CMAH gene became fixed in the hominin lineage ancestral to humans, possibly through a stepwise process of selection by pathogen targeting of the CMAH product (the sialic acid Neu5Gc), followed by reproductive isolation via female anti-Neu5Gc antibodies. Loss of CMAH has occurred independently in some other lineages, but is functionally intact in Old World primates, including our closest relatives, the chimpanzees. While the biophysical and biochemical ramifications of losing tens of millions of Neu5Gc hydroxyl groups at most cell surfaces remains poorly understood, there are multi-scale effects functionally relevant to both sides of the host-pathogen interface...
April 19, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28422868/meta-analysis-of-possible-role-of-cadherin-gene-methylation-in-evolution-and-prognosis-of-hepatocellular-carcinoma-with-a-prisma-guideline
#16
Chunxiao Zhu, Xuefeng Feng, Guoliang Ye, Tao Huang
BACKGROUND: Cadherins (CDHs) have been reported to be associated with cancer. However, the clinical significance of CDH gene methylation in hepatocellular carcinoma (HCC) remains unclear. METHODS: Based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement criteria, available studies were identified from online electronic database. The overall odds ratio (OR) and the corresponding 95% confidence interval (95% CI) were calculated and analyzed...
April 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28422318/computational-analysis-of-breast-cancer-gwas-loci-identifies-the-putative-deleterious-effect-of-stxbp4-and-znf404-gene-variants
#17
Tariq Ahmad Masoodi, Babajan Banaganapalli, Venkatesh Vaidyanathan, Venkateswar Rao Talluri, Noor Ahmad Shaik
The genome-wide association studies (GWAS) have enabled us in identifying different breast cancer susceptibility loci. However, majority of these are non-coding variants with no annotated biological function. We investigated such 78 noncoding genome wide associated SNPs of breast cancer and further expanded the list to 2162 variants with strong linkage-disequilibrium (LD, r2 ≥0.8). Using multiple publically available algorithms such as CADD, GWAVA and FATHAMM, we classified all these variants in to deleterious, damaging or benign categories...
April 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28420128/ar-signaling-and-the-pi3k-pathway-in-prostate-cancer
#18
REVIEW
Megan Crumbaker, Leila Khoja, Anthony M Joshua
Prostate cancer is a leading cause of cancer-related death in men worldwide. Aberrant signaling in the androgen pathway is critical in the development and progression of prostate cancer. Despite ongoing reliance on androgen receptor (AR) signaling in castrate resistant disease, in addition to the development of potent androgen targeting drugs, patients invariably develop treatment resistance. Interactions between the AR and PI3K pathways may be a mechanism of treatment resistance and inhibitors of this pathway have been developed with variable success...
April 15, 2017: Cancers
https://www.readbyqxmd.com/read/28417598/genetic-analysis-of-a-morphologically-heterogeneous-ovarian-endometrioid-carcinoma
#19
Felipe C Geyer, Fresia Pareja, Kathleen A Burke, Anne M Schultheis, Yaser R Hussein, Jiqing Ye, Maria R De Filippo, Caterina Marchio, Gabriel S Macedo, Salvatore Piscuoglio, Raymond S Lim, Eugene Toy, Rajmohan Murali, Achim A Jungbluth, Jorge S Reis-Filho, Robert A Soslow, Britta Weigelt
AIMS: Low-grade ovarian endometrioid carcinomas may be associated with high-grade components. Whether the latter are clonally-related to and originate from the low-grade endometrioid carcinoma remains unclear. Here we employed massively parallel sequencing to characterize the genomic landscape and clonal relatedness of an ovarian endometrioid carcinoma containing low- and high-grade components. METHODS AND RESULTS: DNA samples extracted from each tumor component (low-grade endometrioid, high-grade anaplastic, high-grade squamous) and matched normal tissue were subjected to targeted massively parallel sequencing using the 410 gene Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) sequencing assay...
April 18, 2017: Histopathology
https://www.readbyqxmd.com/read/28416802/rna-editing-dependent-epitranscriptome-diversity-in-cancer-stem-cells
#20
REVIEW
Qingfei Jiang, Leslie A Crews, Frida Holm, Catriona H M Jamieson
Cancer stem cells (CSCs) can regenerate all facets of a tumour as a result of their stem cell-like capacity to self-renew, survive and become dormant in protective microenvironments. CSCs evolve during tumour progression in a manner that conforms to Charles Darwin's principle of natural selection. Although somatic DNA mutations and epigenetic alterations promote evolution, post-transcriptional RNA modifications together with RNA binding protein activity (the 'epitranscriptome') might also contribute to clonal evolution through dynamic determination of RNA function and gene expression diversity in response to environmental stimuli...
April 18, 2017: Nature Reviews. Cancer
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