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molecular oncology

M Herreros-Villanueva, Chih-Chieh Chen, Eing-Mei Tsai, Tze-Kiong Er
Endometriosis is defined as the presence of ectopic endometrial tissue outside of the uterine cavity, most commonly in the ovaries and peritoneum. It is a complex disease that is influenced by multiple factors. It is also a common gynecological disorder and affects approximately 10-15% of all women of reproductive age. Recent molecular and pathological studies indicate that endometriosis may serve as a precursor of ovarian cancer (endometriosis-associated ovarian cancer, EAOC), particularly endometrioid and clear cell ovarian cancers...
February 15, 2019: Clinica Chimica Acta; International Journal of Clinical Chemistry
Xiangqi Meng, Chunbin Duan, Hengyuan Pang, Qun Chen, Bo Han, Caijun Zha, Magafurov Dinislam, Pengfei Wu, Ziwei Li, Shihong Zhao, Ruijia Wang, Lin Lin, Chuanlu Jiang, Jinquan Cai
BACKGROUND: DNA damage repair (DDR) alterations are important events in cancer initiation, progression, and therapeutic resistance. However, the involvement of DDR alterations in glioma malignancy needs further investigation. This study aims to characterize the clinical and molecular features of gliomas with DDR alterations and elucidate the biological process of DDR alterations that regulate the cross talk between gliomas and the tumor microenvironment. METHODS: Integrated transcriptomic and genomic analyses were undertaken to conduct a comprehensive investigation of the role of DDR alterations in glioma...
February 14, 2019: EBioMedicine
Andrew D J Pearson, Nicole Scobie, Koenraad Norga, Franca Ligas, Davy Chiodin, Amos Burke, Veronique Minard-Colin, Peter Adamson, Lynley V Marshall, Arun Balakumaran, Bouchra Benettaib, Pankaj Bhargava, Catherine M Bollard, Ellen Bolotin, Simon Bomken, Jochen Buechner, Birgit Burkhardt, Hubert Caron, Christopher Copland, Pierre Demolis, Anton Egorov, Mahdi Farhan, Gerhard Zugmaier, Thomas Gross, Danielle Horton-Taylor, Wolfram Klapper, Giovanni Lesa, Robert Marcus, Rodney R Miles, Kerri Nottage, Lida Pacaud, Rosanna Ricafort, Martin Schrappe, Jaroslav Sterba, Remus Vezan, Susan Weiner, Su Young Kim, Gregory Reaman, Gilles Vassal
Paediatric Strategy Forums have been created by the multistakeholder organisation, ACCELERATE, and the European Medicines Agency to facilitate dialogue between all relevant stakeholders and suggest strategies in critical areas of paediatric oncology drug development. As there are many medicines being developed for B-cell malignancies in adults but comparatively few in children with these malignancies, a Paediatric Strategy Forum was held to discuss the best approach to develop these products for children. It was concluded that as current frontline therapy is highly successful, despite associated acute toxicity, de-escalation of this or substitution of presently used drugs with new medicines can only be undertaken when there is an effective salvage regimen, which is currently not available...
February 14, 2019: European Journal of Cancer
Erik Nutma, Hugh Willison, Martino Gianvito, Sandra Amor
Neuroimmunology as a separate discipline has its roots in the fields of neurology, neuroscience and immunology. Early studies of the brain by Golgi and Cajal, the detailed clinical and neuropathology studies of Charcot, and Thompson's seminal paper on graft acceptance in the central nervous system kindled a now rapidly expanding research area with the aim of understanding pathological mechanisms of inflammatory components of neurological disorders. Whilst neuroimmunologists originally focussed on classical neuroinflammatory disorders such as multiple sclerosis and infections, there is strong evidence to suggest that the immune response contributes to genetic white matter disorders, epilepsy, neurodegenerative diseases, neuropsychiatric disorders, peripheral nervous system and neuro-oncological conditions, as well as ageing...
February 15, 2019: Clinical and Experimental Immunology
Eric J Chow, Kasey J Leger, Neel S Bhatt, Daniel A Mulrooney, Colin J Ross, Sanjeev Aggarwal, Neha Bansal, Matthew J Ehrhardt, Saro H Armenian, Jessica M Scott, Borah Hong
With five-year survival of children with cancer exceeding 80% in developed countries, premature cardiovascular disease is now a major cause of early morbidity and mortality. In addition to the acute and chronic cardiotoxic effects of anthracyclines, related chemotherapeutics, and radiation, a growing number of new molecular targeted agents may also have detrimental effects on the cardiovascular system. Survivors of childhood cancer also may have earlier development of conventional cardiovascular risk factors such as hypertension, dyslipidemia, and diabetes, which further increase their risk of serious cardiovascular disease...
February 15, 2019: Cardiovascular Research
Fenglin Cao, Xingang Li, Yiju Yang, Honghong Fang, Haixia Qu, Naibai Chang, Qingwei Ma, Weifan Cao, Jin Zhou, Wei Wang
The introduction of arsenic trioxide (ATO) in treatment of acute promyelocytic leukemia (APL) has resulted in high clinical complete remission (CR) rates over 90%. On the contrary, the risk for early death (ED) in APL patients treated with ATO continues to have a negative impact for optimization of APL therapeutics. There is an urgent need for precision medicine and biomarkers in clinical monitoring of ATO toxicity in APL, and ED in particular. This retrospective case series cohort proteomics study was conducted as a hypothesis generation effort and provides here several potential molecular leads on serum peptides expressed at different times after treatment with ATO in patients with APL...
February 2019: Omics: a Journal of Integrative Biology
Hisataka Kobayashi
Near infrared photoimmunotherapy(NIR-PIT)is a new molecularly-targeted cancer photo-therapy based on conjugating a near infrared silica-phthalocyanine dye, IRDye700DX(IR700), to a monoclonal antibody(mAb)targeting cell-surface molecules. NIR-PIT targetingEGFR usingthe cetuximab-IR700 conjugate is now in transition to fast-track global Phase Ⅲ clinical trial in late-stage head and neck squamous cell cancer patients. When exposed to NIR light, the conjugate induces a highlyselective necrotic/immunogenic cell death(ICD)only in target-positive, mAb-IR700-bound cancer cells...
January 2019: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Alex Avendano, Marcos Cortes-Medina, Jonathan W Song
The physical remodeling associated with cancer progression results in barriers to mass transport in the tumor interstitial space. This hindrance ultimately affects the distribution of macromolecules that govern cell fate and potency of cancer therapies. Therefore, knowing how specific extracellular matrix (ECM) and cellular components regulate transport in the tumor interstitium could lead to matrix normalizing strategies that improve patient outcome. Studies over the past decades have provided quantitative insights into interstitial transport in tumors by characterizing two governing parameters: (1) molecular diffusivity and (2) hydraulic conductivity...
2019: Frontiers in Bioengineering and Biotechnology
Michael W Ruff, Joon H Uhm, Eduardo E Benarroch
The field of neuro-oncology has recently experienced a renaissance in the understanding of the molecular underpinnings and pathophysiology of glioma. Genetic markers have significant implications regarding treatment responsiveness and prognosis and are now the primary basis for classification. This article gives an updated understanding of the pathogenesis and mechanisms of resistance of glioma via discussion of 4 molecular and genetic markers: MGMT, IDH , 1p/19q, and TERT .
February 13, 2019: Neurology
Timothy J Robinson, Jennifer A Freedman, Muthana Al Abo, April E Deveaux, Bonnie LaCroix, Brendon M Patierno, Daniel J George, Steven R Patierno
Studies of Alternative RNA Splicing (ARS) have the potential to provide an abundance of novel targets for development of new biomarkers and therapeutics in oncology, which will be necessary to improve outcomes for cancer patients and mitigate cancer disparities. ARS, a key step in gene expression enabling individual genes to encode multiple proteins, is emerging as a major driver of abnormal phenotypic heterogeneity. Recent studies have begun to identify RNA splicing-related genetic and genomic variation in tumors, oncogenes dysregulated by ARS, RNA splice variants driving race-related cancer aggressiveness and drug response, spliceosome-dependent transformation, and RNA splicing-related immunogenic epitopes in cancer...
February 12, 2019: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
David Schiff, Martin van den Bent, Michael A Vogelbaum, Wolfgang Wick, C Ryan Miller, Martin Taphoorn, Whitney Pope, Paul D Brown, Michael Platten, Rakesh Jalali, Terri Armstrong, Patrick Y Wen
The finding that most grade II and III gliomas harbor isocitrate dehydrogenase (IDH) mutations conveying a relatively favorable and fairly similar prognosis in both tumor grades highlights that these tumors represent a fundamentally different entity from IDH wild-type gliomas exemplified in most glioblastoma. Herein we review the most recent developments in molecular neuropathology leading to reclassification of these tumors based upon IDH and 1p/19q status, as well as the potential roles of methylation profiling and CDKN2A/B deletional analysis...
February 8, 2019: Neuro-oncology
Francesco Bussu, Camille Ragin, Paolo Boscolo-Rizzo, Davide Rizzo, Roberto Gallus, Giovanni Delogu, Patrizia Morbini, Massimo Tommasino
BACKGROUND: A consensus about the most appropriate diagnostic method(s) for head and neck human papillomavirus (HPV)-induced carcinogenesis is still lacking because most of the commercially available assays have been designed for the cervix. METHODS: This article summarizes current data and trends concerning HPV diagnostic strategies in oropharyngeal squamous cell carcinoma (OPSCC). Six main approaches are described. RESULTS: The diagnostic gold standard for HPV-related OPSCC, focusing on E6/E7 mRNA detection, requires fresh samples...
February 12, 2019: Head & Neck
Sergey S Shishkin, Leonid I Kovalev, Natalya V Pashintseva, Marina A Kovaleva, Ksenia Lisitskaya
Heterogeneous nuclear ribonucleoproteins (hnRNPs) are structurally and functionally distinct proteins containing specific domains and motifs that enable the proteins to bind certain nucleotide sequences, particularly those found in human telomeres. In human malignant cells (HMCs), hnRNP-A1-the most studied hnRNP-is an abundant multifunctional protein that interacts with telomeric DNA and affects telomerase function. In addition, it is believed that other hnRNPs in HMCs may also be involved in the maintenance of telomere length...
February 10, 2019: International Journal of Molecular Sciences
Yu-Long Lan, Yu-Jie Zou, Jia-Cheng Lou, Jin-Shan Xing, Xun Wang, Shuang Zou, Bin-Bin Ma, Yan Ding, Bo Zhang
Bufalin is the primary component of the traditional Chinese medicine "Chan Su," which has been widely used for cancer treatment at oncology clinics in certain countries. Evidence suggests that this compound possesses potent antitumor activities, although the exact molecular mechanism(s) require further elucidation. Therefore, this study aimed to further clarify the in vitro and in vivo antiglioma effects of bufalin and the molecular mechanism underlying the regulation of drug sensitivity. The anticancer effects of bufalin were determined by colony formation assays, apoptosis assays, and cellular redox state tests of glioma cells...
February 9, 2019: Cell Biology and Toxicology
Abdullah Ladha, Jianzhi Zhao, Elliot M Epner, Jeffrey J Pu
Mantle cell lymphoma is a relatively new recognized hematological malignant disease, comprising of 2.5-6% non-Hodgkin's lymphomas. The complexity of its clinical presentations (nodular pattern, diffuse pattern, and blastoid variant), variety in disease progression, and treatment response, make this disease a research focus to both experimental oncology and clinical oncology. Overexpression of cyclin D1 and chromosome t(11,14) translocation are the known molecular biomarkers of this disease. Mantle cell international prognostic index (MIPI), ki-67 proliferation index, and TP53 mutation are emerging as the prognostic biomarkers...
2019: Experimental Hematology & Oncology
Giuseppe Vassalli
Aldehyde dehydrogenase (ALDH) is a superfamily of enzymes that detoxify a variety of endogenous and exogenous aldehydes and are required for the biosynthesis of retinoic acid (RA) and other molecular regulators of cellular function. Over the past decade, high ALDH activity has been increasingly used as a selectable marker for normal cell populations enriched in stem and progenitor cells, as well as for cell populations from cancer tissues enriched in tumor-initiating stem-like cells. Mounting evidence suggests that ALDH not only may be used as a marker for stem cells but also may well regulate cellular functions related to self-renewal, expansion, differentiation, and resistance to drugs and radiation...
2019: Stem Cells International
Servando Hernandez Vargas, Sukhen C Ghosh, Ali Azhdarinia
Intraoperative detection of tumors has had a profound impact on how cancer surgery is performed and addresses critical unmet needs in surgical oncology. Through the use of fluorescent contrast agents, tumor deposits, margins, and residual cancer can be imaged during surgical procedures to complement visual and tactile guidance. The combination of fluorescent and nuclear contrast into a multimodality agent builds upon these capabilities by adding quantitative, non-invasive nuclear imaging capabilities to intraoperative imaging...
February 7, 2019: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Qing Luo, Xuan Shi, Jiarong Ding, Zhenzhen Ma, Xumei Chen, Yuanxiu Leng, Xuhui Zhang, Yang Liu
Background: As the malignant tumor with the highest incidence in teenagers, osteosarcoma has become a major problem in oncology research. In addition to surgical management, the pharmacotherapeutic strategy for osteosarcoma treatment is an attractive way to explore. It has been demonstrated that biochanin A has an antitumor capacity on multiple kinds of solid tumor, including osteosarcoma. But the precise mechanism of biochanin A against osteosarcoma is still needed to be discovered. Objective: To identify the potential therapeutic targets of biochanin A in treating osteosarcoma...
2019: Evidence-based Complementary and Alternative Medicine: ECAM
Philipp Karschnia, Michael W Parsons, Jorg Dietrich
Cognitive dysfunction is a challenging adverse effect of chemotherapy and radiotherapy that has limited treatment options. Clinical trials for proposed pharmacotherapeutic interventions to help manage these cognitive symptoms have had conflicting results and no standard of care has yet been established. Pharmacotherapeutic approaches for cancer therapy-induced cognitive symptoms include CNS stimulants (eg, methylphenidate and modafinil), medications used in patients with memory impairment (eg, donepezil, memantine, and ginkgo biloba), and bone marrow supporting agents (eg, erythropoietin)...
February 2019: Lancet Oncology
Mihaela Ghita, Kathryn H Brown, Olivia J Kelada, Edward E Graves, Karl T Butterworth
Translational research aims to provide direct support for advancing novel treatment approaches in oncology towards improving patient outcomes. Preclinical studies have a central role in this process and the ability to accurately model biological and physical aspects of the clinical scenario in radiation oncology is critical to translational success. The use of small animal irradiators with disease relevant mouse models and advanced in vivo imaging approaches offers unique possibilities to interrogate the radiotherapy response of tumors and normal tissues with high potential to translate to improvements in clinical outcomes...
February 1, 2019: Cancers
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