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https://www.readbyqxmd.com/read/29783691/old-and-young-actors-playing-novel-roles-in-the-drama-of-multiple-myeloma-bone-marrow-microenvironment-dependent-drug-resistance
#1
REVIEW
Sabrina Manni, Marilena Carrino, Gianpietro Semenzato, Francesco Piazza
Multiple myeloma (MM) is the second most frequent hematologic cancer. In addition to the deleterious effects of neoplastic plasma cell growth and spreading during the disease evolution, this tumor is characterized by the serious pathological consequences due to the massive secretion of monoclonal immunoglobulins and by the derangement of bone physiology with progressive weakening of the skeleton. Despite significant progresses having been made in the last two decades in the therapeutic management of this plasma cell tumor, MM remains invariably lethal, due to its extremely complex genetic architecture and to the constant protection it receives from the tumor niche, which is represented by the bone marrow microenvironment...
May 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29780254/are-ovarian-cancer-stem-cells-the-target-for-innovative-immunotherapy
#2
REVIEW
Liang Wang, Tianmin Xu, Manhua Cui
Cancer stem cells (CSCs), a subpopulation of cancer cells with the ability of self-renewal and differentiation, are believed to be responsible for tumor generation, progression, metastasis, and relapse. Ovarian cancer, the most malignant gynecological cancer, has consistent pathology behavior with CSC model, which suggests that therapies based on ovarian cancer stem cells (OCSCs) can gain a more successful prognosis. Much evidence has proved that epigenetic mechanism played an important role in tumor formation and sustainment...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29779206/old-new-and-emerging-immunohistochemical-markers-in-pheochromocytoma-and-paraganglioma
#3
REVIEW
Veronica K Y Cheung, Anthony J Gill, Angela Chou
The evolution of genetic research over the past two decades has greatly improved the understanding of pheochromocytomas and paragangliomas. It is now accepted that more than one third of pheochromocytoma and paragangliomas arise in the context of syndromic disease, usually hereditary. The genetic profile of these tumors also has important prognostic implications which may help guide treatment. Accompanying the changing molecular landscape is the development of new immunohistochemical markers. Initially used in assisting with diagnosis, immunohistochemical markers have now become an important adjunct to screening programs for inherited conditions and subsequently as prognostic markers...
May 19, 2018: Endocrine Pathology
https://www.readbyqxmd.com/read/29776953/the-landscape-of-actionable-genomic-alterations-in-cell-free-circulating-tumor-dna-from-21-807-advanced-cancer-patients
#4
Oliver A Zill, Kimberly C Banks, Stephen R Fairclough, Stefanie Mortimer, James V Vowles, Reza Mokhtari, David R Gandara, Philip C Mack, Justin I Odegaard, Rebecca J Nagy, Arthur M Baca, Helmy Eltoukhy, Darya I Chudova, Richard B Lanman, AmirAli Talasaz
PURPOSE: Cell-free DNA (cfDNA) sequencing provides a non-invasive method for obtaining actionable genomic information to guide personalized cancer treatment, but the presence of multiple alterations in circulation related to treatment and tumor heterogeneity complicate the interpretation of the observed variants. Experimental Design: We describe the somatic mutation landscape of 70 cancer genes from cfDNA deep-sequencing analysis of 21,807 patients with treated, late-stage cancers across >50 cancer types...
May 18, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29775683/viscoelastic-modeling-of-the-fusion-of-multicellular-tumor-spheroids-in-growth-phase
#5
Guillaume Dechristé, Jérôme Fehrenbach, Elena Griseti, Valérie Lobjois, Clair Poignard
BACKGROUND: Since several decades, the experiments have highlighted the analogy of fusing cell aggregates with liquid droplets. The physical macroscopic models have been derived under incompressible assumptions. The aim of this paper is to provide a 3D model of growing spheroids, which is more relevant regarding embryo cell aggregates or tumor cell spheroids. METHODS: We extend the past approach to a compressible 3D framework in order to account for the tumor spheroid growth...
May 15, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29772764/the-making-of-leukemia
#6
REVIEW
Inés González-Herrero, Guillermo Rodríguez-Hernández, Andrea Luengas-Martínez, Marta Isidro-Hernández, Rafael Jiménez, Maria Begoña García-Cenador, Francisco Javier García-Criado, Isidro Sánchez-García, Carolina Vicente-Dueñas
Due to the clonal nature of human leukemia evolution, all leukemic cells carry the same leukemia-initiating genetic lesions, independently of the intrinsic tumoral cellular heterogeneity. However, the latest findings have shown that the mode of action of oncogenes is not homogeneous throughout the developmental history of leukemia. Studies on different types of hematopoietic tumors have shown that the contribution of oncogenes to leukemia is mainly mediated through the epigenetic reprogramming of the leukemia-initiating target cell...
May 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29771315/palimpsest-an-r-package-for-studying-mutational-and-structural-variant-signatures-along-clonal-evolution-in-cancer
#7
Jayendra Shinde, Quentin Bayard, Sandrine Imbeaud, Théo Z Hirsch, Feng Liu, Victor Renault, Jessica Zucman-Rossi, Eric Letouzé
Summary: Cancer genomes are altered by various mutational processes and, like palimpsests, bear the signatures of these different processes. The Palimpsest R package provides a complete workflow for the characterization and visualization of mutational signatures and their evolution along tumor development. The package covers a wide range of functions for extracting both base substitution and structural variant signatures, inferring the clonality of each alteration and analyzing the evolution of mutational processes between early clonal and late subclonal events...
May 16, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29769258/anti-tumor-efficacy-of-a-novel-clk-inhibitor-via-targeting-rna-splicing-and-myc-dependent-vulnerability
#8
Kenichi Iwai, Masahiro Yaguchi, Kazuho Nishimura, Yukiko Yamamoto, Toshiya Tamura, Daisuke Nakata, Ryo Dairiki, Yoichi Kawakita, Ryo Mizojiri, Yoshiteru Ito, Moriteru Asano, Hironobu Maezaki, Yusuke Nakayama, Misato Kaishima, Kozo Hayashi, Mika Teratani, Shuichi Miyakawa, Misa Iwatani, Maki Miyamoto, Michael G Klein, Wes Lane, Gyorgy Snell, Richard Tjhen, Xingyue He, Sai Pulukuri, Toshiyuki Nomura
The modulation of pre-mRNA splicing is proposed as an attractive anti-neoplastic strategy, especially for the cancers that exhibit aberrant pre-mRNA splicing. Here, we discovered that T-025 functions as an orally available and potent inhibitor of Cdc2-like kinases (CLKs), evolutionally conserved kinases that facilitate exon recognition in the splicing machinery. Treatment with T-025 reduced CLK-dependent phosphorylation, resulting in the induction of skipped exons, cell death, and growth suppression in vitro and in vivo Further, through growth inhibitory characterization, we identified high CLK2 expression or MYC amplification as a sensitive-associated biomarker of T-025...
May 16, 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29769134/advances-on-chimeric-antigen-receptor-modified-t-cell-therapy-for-oncotherapy
#9
REVIEW
Yanyu Pang, Xiaoyang Hou, Chunsheng Yang, Yanqun Liu, Guan Jiang
Tumor treatment is still complicated in the field of medicine. Tumor immunotherapy has been the most interesting research field in cancer therapy. Application of chimeric antigen receptor T (CAR-T) cell therapy has recently achieved excellent clinical outcome in patients, especially those with CD19-positive hematologic malignancies. This phenomenon has induced intense interest to develop CAR-T cell therapy for cancer, especially for solid tumors. However, the performance of CAR-T cell treatment in solid tumor is not as satisfactory as that in hematologic disease...
May 16, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29766388/molecular-evolution-of-metaplasia-to-adenocarcinoma-in-the-esophagus
#10
REVIEW
William M Grady, Ming Yu
Esophageal adenocarcinoma (EAC) develops from Barrett's esophagus (BE), a condition where the normal squamous epithelia is replaced by specialized intestinal metaplasia in response to chronic gastroesophageal acid reflux. In a minority of individuals, BE can progress to low- and high-grade dysplasia and eventually to intra-mucosal and then invasive carcinoma. BE provides researchers with a unique model to characterize the process by which a carcinoma arises from its precursor lesion. Molecular studies of BE have demonstrated that it is not simply a metaplastic tissue, but rather it harbors frequent alterations that are also present in dysplastic BE and in EAC...
May 15, 2018: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29764223/insight-into-carrageenases-major-review-of-sources-category-property-purification-method-structure-and-applications
#11
Benwei Zhu, Fang Ni, Yun Sun, Xianyu Zhu, Heng Yin, Zhong Yao, Yuguang Du
Carrageenan, a kind of linear sulfated polysaccharides consisting of D-galactose with alternating α-1,3 and β-1,4 linkages, has been widely applied in the food and cosmetic industries as thickening and gelling agents due to excellent properties, such as gel-forming ability and chemical stability. It can be degraded by carrageenases to produce a series of even-numbered carrageenan oligosaccharides, which exhibit various fascinating functions, such as anti-inflammation, anti-coagulation, anti-tumor, and anti-thrombosis effects...
May 15, 2018: Critical Reviews in Biotechnology
https://www.readbyqxmd.com/read/29762157/recent-advances-in-the-classification-of-low-grade-papillary-like-thyroid-neoplasms-and-aggressive-papillary-thyroid-carcinomas-evolution-of-diagnostic-criteria
#12
Zhenying Guo, Minghua Ge, Ying-Hsia Chu, Sofia Asioli, Ricardo V Lloyd
Papillary thyroid carcinomas account for ∼80% of well-differentiated thyroid tumors. During the past decade, several new variants of papillary-like thyroid neoplasms and papillary thyroid carcinomas have been recognized. Some of these neoplasms that were previously classified as malignant have been reclassified as low-grade neoplasms, as the diagnostic criteria have evolved. Similarly, some of the papillary thyroid carcinomas that were previously classified as conventional or classic papillary thyroid carcinomas have now been recognized as more aggressive variants of papillary thyroid carcinomas...
May 12, 2018: Advances in Anatomic Pathology
https://www.readbyqxmd.com/read/29761881/expression-of-stem-cell-markers-nanog-and-nestin-in-lip-squamous-cell-carcinoma-and-actinic-cheilitis
#13
Fernanda M Scotti, Verônica C Mitt, Daniella S C Vieira, Michelle T Biz, Renata G Castro, Filipe Modolo
Cancer stem cells ( CSC ) proteins have been observed in several lesions and are associated with tumor beginning, evolution, and resistance to treatment. OBJECTIVES: to investigate the presence of NANOG, NESTIN, and β-tubulin in lip squamous cell carcinoma (LSCC), actinic cheilitis (AC), and normal epithelium (NE). MATERIALS AND METHODS: thirty cases of LSCC, thirty cases of AC (both analyzed according to the WHO classification and AC according to the binary classification), and twenty cases of NE were submitted to an immunohistochemical study...
May 15, 2018: Oral Diseases
https://www.readbyqxmd.com/read/29760052/spatial-mutation-patterns-as-markers-of-early-colorectal-tumor-cell-mobility
#14
Marc D Ryser, Byung-Hoon Min, Kimberly D Siegmund, Darryl Shibata
A growing body of evidence suggests that a subset of human cancers grows as single clonal expansions. In such a nearly neutral evolution scenario, it is possible to infer the early ancestral tree of a full-grown tumor. We hypothesized that early tree reconstruction can provide insights into the mobility phenotypes of tumor cells during their first few cell divisions. We explored this hypothesis by means of a computational multiscale model of tumor expansion incorporating the glandular structure of colorectal tumors...
May 14, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29760044/nk-cells-mediate-synergistic-antitumor-effects-of-combined-inhibition-of-hdac6-and-bet-in-a-sclc-preclinical-model
#15
Yan Liu, Yuyang Li, Shengwu Liu, Dennis O Adeegbe, Camilla L Christensen, Max M Quinn, Ruben Dries, Shiwei Han, Kevin Buczkowski, Xiaoen Wang, Ting Chen, Peng Gao, Hua Zhang, Fei Li, Peter S Hammerman, James E Bradner, Steven N Quayle, Kwok-Kin Wong
Small cell lung cancer (SCLC) has the highest malignancy among all lung cancers, exhibiting aggressive growth and early metastasis to distant sites. For 30 years, treatment options for SCLC have been limited to chemotherapy, warranting the need for more effective treatments. Frequent inactivation of TP53 and RB1 as well as histone dysmodifications in SCLC suggest that transcriptional and epigenetic regulations play a major role in SCLC disease evolution. Here we performed a synthetic lethal screen using the BET inhibitor JQ1 and an shRNA library targeting 550 epigenetic genes in treatment-refractory SCLC xenograft models and identified HDAC6 as a synthetic lethal target in combination with JQ1...
May 14, 2018: Cancer Research
https://www.readbyqxmd.com/read/29755776/gastrointestinal-stromal-tumors-in-the-imatinib-era-15-years-experience-of-a-tertiary-center
#16
Armando Peixoto, Pedro Costa-Moreira, Marco Silva, Ana Luísa Santos, Susana Lopes, Filipe Vilas-Boas, Pedro Moutinho-Ribeiro, Guilherme Macedo
Gastrointestinal stromal tumors (GISTs) were associated with a disease free survival rate of disease of 50% at 5 years, but the actual natural history since the advent of imatinib is poorly described. Our objective was to evaluate the evolution in the treatment and prognosis of patients with GISTs since the start of imatinib. Retrospective analysis of GISTs diagnosed between January 2000 and June 2015 in a Portuguese large volume center. We included 131 patients, 55% female, with a mean age of 64±14 years, followed for a median of 30 months; 64% of cases had gastric involvement; 92% of the tumors were c-Kit positive; 95% of patients were operated...
April 2018: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/29753882/circulating-tumor-microemboli-progress-in-molecular-understanding-and-enrichment-technologies
#17
REVIEW
Muhammad Umer, Ramanathan Vaidyanathan, Nam-Trung Nguyen, Muhammad J A Shiddiky
Circulating tumor cells (CTCs) and their clusters, also known as circulating tumor microemboli (CTM), have emerged as valuable tool that can provide mechanistic insights into the tumor heterogeneity, clonal evolution, and stochastic events within the metastatic cascade. However, recent investigations have hinted that CTM may not be mere aggregates of tumor cells but cells comprising CTM exhibit distinct phenotypic and molecular characteristics in comparison to single CTCs. Moreover, in many cases CTM demonstrated higher metastatic potential and resistance to apoptosis as compared to their single cell counterparts...
May 10, 2018: Biotechnology Advances
https://www.readbyqxmd.com/read/29749920/evolution-of-the-graded-repair-of-csf-leaks-and-skull-base-defects-in-endonasal-endoscopic-tumor-surgery-trends-in-repair-failure-and-meningitis-rates-in-509-patients
#18
Andrew Conger, Fan Zhao, Xiaowen Wang, Amalia Eisenberg, Chester Griffiths, Felice Esposito, Ricardo L Carrau, Garni Barkhoudarian, Daniel F Kelly
OBJECTIVE The authors previously described a graded approach to skull base repair following endonasal microscopic or endoscope-assisted tumor surgery. In this paper they review their experience with skull base reconstruction in the endoscopic era. METHODS A retrospective review of a single-institution endonasal endoscopic patient database (April 2010-April 2017) was undertaken. Intraoperative CSF leaks were graded based on size (grade 0 [no leak], 1, 2, or 3), and repair technique was documented across grades...
May 11, 2018: Journal of Neurosurgery
https://www.readbyqxmd.com/read/29749435/spag6-silencing-induces-apoptosis-in-the-myelodysplastic-syndrome-cell-line-skm%C3%A2-1-via-the-pten-pi3k-akt-signaling-pathway-in-vitro-and-in-vivo
#19
Jiaxiu Yin, Xinxin Li, Zaili Zhang, Xiaohua Luo, Li Wang, Lin Liu
Apoptosis is a multi-step mechanism of cell self‑destruction for maintaining cellular homeostatic balance. Accumulating evidence indicates that abnormal apoptosis promotes the evolution and progression of myelodysplastic syndromes (MDS). As a novel cancer-testis antigen, sperm‑associated antigen 6 (SPAG6) has been reported to regulate apoptosis through the tumor necrosis factor-related apoptosis-inducing ligand signaling pathway in the MDS cell line SKM‑1. However, the mechanism of the intrinsic cell death pathway for apoptosis induction by SPAG6 silencing is unclear...
May 2, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29747434/the-impact-of-human-papilloma-viruses-matrix-metallo-proteinases-and-hiv-protease-inhibitors-on-the-onset-and-progression-of-uterine-cervix-epithelial-tumors-a-review-of-preclinical-and-clinical-studies
#20
REVIEW
Giovanni Barillari, Paolo Monini, Cecilia Sgadari, Barbara Ensoli
Infection of uterine cervix epithelial cells by the Human Papilloma Viruses (HPV) is associated with the development of dysplastic/hyperplastic lesions, termed cervical intraepithelial neoplasia (CIN). CIN lesions may regress, persist or progress to invasive cervical carcinoma (CC), a leading cause of death worldwide. CIN is particularly frequent and aggressive in women infected by both HPV and the Human Immunodeficiency Virus (HIV), as compared to the general female population. In these individuals, however, therapeutic regimens employing HIV protease inhibitors (HIV-PI) have reduced CIN incidence and/or clinical progression, shedding light on the mechanism(s) of its development...
May 9, 2018: International Journal of Molecular Sciences
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