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https://www.readbyqxmd.com/read/28813755/genetics-of-alcoholism
#1
Ena C Zhu, Timothy J Soundy, Yueshan Hu
Consuming excessive amounts of alcohol has the potential to modify an individual's brain and lead to alcohol dependence. Alcohol use leads to 88,000 deaths every year in the U.S. alone and can lead to other health issues including cancers, such as colorectal cancer, and mental health problems. While drinking behavior varies due to environmental factors, genetic factors also contribute to the risk of alcoholism. Certain genes affecting alcohol metabolism and neurotransmitters have been found to contribute to or inhibit the risk...
May 2017: South Dakota Medicine: the Journal of the South Dakota State Medical Association
https://www.readbyqxmd.com/read/28812301/changing-treatment-paradigms-for-brain-metastases-from-melanoma-part-1-diagnosis-prognosis-symptom-control-and-local-treatment
#2
REVIEW
Vyshak Alva Venur, Pauline Funchain, Rupesh Kotecha, Samuel T Chao, Manmeet S Ahluwalia
Melanoma is the third most common cause of brain metastases, after lung and breast cancer. The management of melanoma brain metastases can be broadly divided into symptom control and therapeutic strategies. Supportive treatments include corticosteroids to reduce peritumoral edema, antiepileptics for seizure control, and medications to preserve cognitive function. Until recently, therapeutic strategies consisted primarily of local treatments, including surgery, whole-brain radiation therapy (WBRT), and stereotactic radiosurgery (SRS)...
August 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28811384/loss-of-spdef-and-gain-of-tgfbi-activity-after-androgen-deprivation-therapy-promote-emt-and-bone-metastasis-of-prostate-cancer
#3
Wei-Yu Chen, Yuan-Chin Tsai, Hsiu-Lien Yeh, Florent Suau, Kuo-Ching Jiang, Ai-Ning Shao, Jiaoti Huang, Yen-Nien Liu
Androgen deprivation therapy (ADT) targeting the androgen receptor (AR) is a standard therapeutic regimen for treating prostate cancer. However, most tumors progress to metastatic castration-resistant prostate cancer after ADT. We identified the type 1, 2, and 4 collagen-binding protein transforming growth factor-β (TGFβ)-induced protein (TGFBI) as an important factor in the epithelial-to-mesenchymal transition (EMT) and malignant progression of prostate cancer. In prostate cancer cell lines, AR signaling stimulated the activity of the transcription factor SPDEF, which repressed the expression of TGFBI ADT, AR antagonism, or overexpression of TGFBI inhibited the activity of SPDEF and enhanced the proliferation rates of prostate cancer cells...
August 15, 2017: Science Signaling
https://www.readbyqxmd.com/read/28810186/the-efficacy-of-lapatinib-and-capecitabine-in-her-2-positive-breast-cancer-with-brain-metastases-a-systematic-review-and-pooled-analysis
#4
REVIEW
Fausto Petrelli, Michele Ghidini, Veronica Lonati, Gianluca Tomasello, Karen Borgonovo, Mara Ghilardi, Mary Cabiddu, Sandro Barni
INTRODUCTION: Breast cancer (BC) with HER-2/neu overexpression or amplification (HER-2+) is associated with a higher prevalence of brain metastases (BMs) when compared to other subtypes. Among approved drugs for HER-2+ BC, lapatinib (L) is associated with single agent activity toward BMs. We conducted a systematic review to determine the efficacy of L, singly or in combination with capecitabine (C), as a treatment for HER-2+ BMs. MATERIAL AND METHODS: We searched PubMed, EMBASE, The Cochrane Library, SCOPUS, Web of Science, ClinicalTrials...
August 12, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28810147/macrophage-polarization-contributes-to-glioblastoma-eradication-by-combination-immunovirotherapy-and-immune-checkpoint-blockade
#5
Dipongkor Saha, Robert L Martuza, Samuel D Rabkin
Glioblastoma is an immunosuppressive, fatal brain cancer that contains glioblastoma stem-like cells (GSCs). Oncolytic herpes simplex virus (oHSV) selectively replicates in cancer cells while inducing anti-tumor immunity. oHSV G47Δ expressing murine IL-12 (G47Δ-mIL12), antibodies to immune checkpoints (CTLA-4, PD-1, PD-L1), or dual combinations modestly extended survival of a mouse glioma model. However, the triple combination of anti-CTLA-4, anti-PD-1, and G47Δ-mIL12 cured most mice in two glioma models...
August 14, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28809584/risk-of-meningioma-after-ct-of-the-head
#6
Arvid C Nordenskjöld, Robert Bujila, Peter Aspelin, Olof Flodmark, Magnus Kaijser
Purpose To investigate the association between exposure to head computed tomography (CT) and subsequent risk of meningioma. Materials and Methods The study was approved by the local ethics committee. A cohort of 26 370 subjects was retrospectively collected from a radiology archive of CT examinations of the head performed from 1973 through 1992. For comparison, an age- and sex-matched cohort of 96 940 subjects who were not exposed to CT (unexposed cohort) was gathered. The risk of meningioma was assessed by using data from the Swedish Cancer Registry; however, one-third of patients with meningioma had to be excluded because they either had a prevalent meningioma or other brain tumor at the first CT examination or had undergone radiation treatment to the head...
August 14, 2017: Radiology
https://www.readbyqxmd.com/read/28808787/malignant-transformation-of-a-conservatively-managed-incidental-childhood-cerebral-mass-lesion-controversy-regarding-management-paradigm
#7
Jehuda Soleman, Jonathan Roth, Zvi Ram, Michal Yalon, Shlomi Constantini
BACKGROUND: Incidental findings on neuroimaging in the pediatric population are an emerging treatment challenge. Treatment options for these incidental childhood brain mass lesions, which radiologically may be assumed to be low-grade gliomas (LGG), vary, ranging from careful conservative "wait and scan" treatment to surgical biopsy, gross total resection, and upfront radiation and/or chemotherapy. As malignant transformation of LGG in children is extremely rare, some series advocate careful conservative management of these lesions; however, universal treatment protocols are not totally agreed upon...
August 14, 2017: Child's Nervous System: ChNS: Official Journal of the International Society for Pediatric Neurosurgery
https://www.readbyqxmd.com/read/28808404/in-vitro-antioxidant-and-antiproliferative-activities-of-various-solvent-fractions-from-clerodendrum-viscosum-leaves
#8
Anil Khushalrao Shendge, Tapasree Basu, Dipankar Chaudhuri, Sourav Panja, Nripendranath Mandal
BACKGROUND: Free radicals such as reactive oxygen and nitrogen species, generated in the body, play an important role in the fulfillment of various physiological functions but their imbalance in the body lead to cellular injury and various clinical disorders such as cancer, neurodegenaration, and inflammation. OBJECTIVE: The objective of this study is to fight this problem, natural antioxidant from plants can be considered as possible protective agents against various diseases such as cancer which might also modify the redox microenvironment to reduce the genetic instability...
July 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28808055/dynamin-dependent-amino-acid-endocytosis-activates-mechanistic-target-of-rapamycin-complex-1-mtorc1
#9
Shusaku Shibutani, Hana Okazaki, Hiroyuki Iwata
The mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of protein synthesis and potential target for modifying cellular metabolism in various conditions, including cancer and aging. mTORC1 activity is tightly regulated by the availability of extracellular amino acids, and previous studies have revealed that amino acids in the extracellular fluid are transported to the lysosomal lumen. There, amino acids induce recruitment of cytoplasmic mTORC1 to the lysosome by the Rag GTPases, followed by mTORC1 activation by the small GTPase Ras homolog enriched in brain (Rheb)...
August 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28807983/cancer-associated-pathways-and-biomarkers-of-venous-thrombosis
#10
Yohei Hisada, Nigel Mackman
Cancer patients have an increased risk of venous thromboembolism (VTE). In this review, we will summarize common and cancer type-specific pathways of VTE in cancer patients. Increased levels of leukocytes, platelets and tissue factor-positive (TF+) microvesicles are all potential factors that alone or in combination increase cancer-associated thrombosis. Lung and colorectal cancer patients often exhibit leukocytosis. Neutrophils could increase VTE in cancer patients by releasing neutrophil extracellular traps whereas monocytes may express TF...
August 14, 2017: Blood
https://www.readbyqxmd.com/read/28807936/genomic-alterations-in-circulating-tumor-dna-from-diverse-cancer-patients-identified-by-next-generation-sequencing
#11
Maria Schwaederle, Ranajoy Chattopadhyay, Shumei Kato, Paul T Fanta, Kimberly C Banks, In Sil Choi, David E Piccioni, Sadakatsu Ikeda, AmirAli Talasaz, Richard B Lanman, Lyudmila Bazhenova, Razelle Kurzrock
Non-invasive genomic profiling of tumors may be possible with next-generation sequencing (NGS) of blood-derived circulating tumor DNA (ctDNA), but proof of concept in a large cohort <p>of patients with diverse cancers has yet to be reported. Here we report the results of an analysis of plasma-derived ctDNA from 670 patients with diverse cancers.</p> The tumors represented in the patient cohort were mainly gastrointestinal (31.8%), brain (22.7%) or lung (20.7%). ctDNA obtained from most patients (N = 423 (63%)) displayed at least 1 alteration...
August 14, 2017: Cancer Research
https://www.readbyqxmd.com/read/28806249/epidural-metastases-from-follicular-thyroid-cancer-mimicking-meningiomas-in-68ga-dotatate-pet
#12
Marcus Unterrainer, Harun Ilhan, Andrei Todica, Peter Bartenstein, Nathalie Lisa Albert
We report a woman with multifocal lesions suggestive of meningiomas in MRI, which also presented with high Ga-DOTATATE uptake in PET, a finding characteristic for meningioma. A whole-body staging due to a pathological fracture revealed multiple neoplastic lesions throughout the body without detection of a primary site. Subsequent pathological workup of a lung lesion revealed multifocal metastases from follicular thyroid cancer despite thyroidectomy 10 years ago (without pathological finding), and posttreatment scans after radioiodine therapy confirmed the multiple brain lesions to be metastases as well...
August 12, 2017: Clinical Nuclear Medicine
https://www.readbyqxmd.com/read/28805995/germline-pms2-and-somatic-poleexo-mutations-cause-hypermutability-of-the-leading-dna-strand-in-biallelic-mismatch-repair-deficiency-syndrome-brain-tumors
#13
Andrianova Maria, Ghati Kasturirangan Chetan, Madathan Kandi Sibin, Thomas Mckee, Doron Merkler, Rao Kvl Narasinga, Pascale Ribaux, Jean-Louis Blouin, Periklis Makrythanasis, Vladimir B Seplyarskiy, Stylianos E Antonarakis, Sergey I Nikolaev
Biallelic Mismatch Repair Deficiency (bMMRD) in tumors is frequently associated with somatic mutations in the exonuclease domains of DNA polymerases POLE or POLD1 and results to a characteristic mutational profile. In this study we describe the genetic basis of ultramutated high grade brain tumors in the context of bMMRD. We performed exome sequencing of two second-cousin patients from a large consanguineous family of Indian origin with early onset of high grade glioblastoma and astrocytoma. We identified a germline homozygous nonsense variant R802X in the PMS2 gene...
August 14, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28805936/characterizing-hypoxia-in-human-glioma-a-simultaneous-multimodal-mri-and-pet-study
#14
Christine Preibisch, Kuangyu Shi, Anne Kluge, Mathias Lukas, Benedikt Wiestler, Jens Göttler, Jens Gempt, Florian Ringel, Mohamed Al Jaberi, Jürgen Schlegel, Bernhard Meyer, Claus Zimmer, Thomas Pyka, Stefan Förster
Hypoxia plays an important role for the prognosis and therapy response of cancer. Thus, hypoxia imaging would be a valuable tool for pre-therapeutic assessment of tumor malignancy. However, there is no standard validated technique for clinical application available yet. Therefore, we performed a study in 12 patients with high-grade glioma, where we directly compared the two currently most promising techniques, namely the MR-based relative oxygen extraction fraction (MR-rOEF) and the PET hypoxia marker H-1-(3-[(18) F]-fluoro-2-hydroxypropyl)-2-nitroimidazole ([(18) F]-FMISO)...
August 14, 2017: NMR in Biomedicine
https://www.readbyqxmd.com/read/28805815/aav-mediated-direct-in-vivo-crispr-screen-identifies-functional-suppressors-in-glioblastoma
#15
Ryan D Chow, Christopher D Guzman, Guangchuan Wang, Florian Schmidt, Mark W Youngblood, Lupeng Ye, Youssef Errami, Matthew B Dong, Michael A Martinez, Sensen Zhang, Paul Renauer, Kaya Bilguvar, Murat Gunel, Phillip A Sharp, Feng Zhang, Randall J Platt, Sidi Chen
A causative understanding of genetic factors that regulate glioblastoma pathogenesis is of central importance. Here we developed an adeno-associated virus-mediated, autochthonous genetic CRISPR screen in glioblastoma. Stereotaxic delivery of a virus library targeting genes commonly mutated in human cancers into the brains of conditional-Cas9 mice resulted in tumors that recapitulate human glioblastoma. Capture sequencing revealed diverse mutational profiles across tumors. The mutation frequencies in mice correlated with those in two independent patient cohorts...
August 14, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28805788/nrf2-keap1-pathway-promotes-cell-proliferation-and-diminishes-ferroptosis
#16
Z Fan, A-K Wirth, D Chen, C J Wruck, M Rauh, M Buchfelder, N Savaskan
Cancer cells are hallmarked by high proliferation and imbalanced redox consumption and signaling. Various oncogenic pathways such as proliferation and evading cell death converge on redox-dependent signaling processes. Nrf2 is a key regulator in these redox-dependent events and operates in cytoprotection, drug metabolism and malignant progression in cancer cells. Here, we show that patients with primary malignant brain tumors (glioblastomas, WHO °IV gliomas, GBM) have a devastating outcome and overall reduced survival when Nrf2 levels are upregulated...
August 14, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28804724/microrna-regulation-of-glycolytic-metabolism-in-glioblastoma
#17
REVIEW
Huda Alfardus, Alan McIntyre, Stuart Smith
Glioblastoma (GBM) is the most aggressive and common malignant brain tumour in adults. A well-known hallmark of GMB and many other tumours is aerobic glycolysis. MicroRNAs (miRNAs) are a class of short nonprotein coding sequences that exert posttranscriptional controls on gene expression and represent critical regulators of aerobic glycolysis in GBM. In GBM, miRNAs regulate the expression of glycolytic genes directly and via the regulation of metabolism-associated tumour suppressors and oncogenic signalling pathways...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28804551/a-tumor-suppressive-microrna-mirna-485-5p-inhibits-glioma-cell-proliferation-and-invasion-by-down-regulating-tpd52l2
#18
Jin Yu, Shi-Wen Wu, Wei-Ping Wu
Glioblastoma multiforme is the most deadly primary brain tumor and has no effective treatment. Therefore, it is important to identify novel and effective therapies that impede glioma tumorigenesis. MicroRNAs (miRNAs) are helpful analytical biomarkers and may be useful targets for treating multiple human cancers. Previous reports suggest that miRNA-485-5p is dysregulated and contributes to tumorigenesis in some cancer types. Nevertheless, the biological role of miRNA-485-5p in glioma is not well understood. In this study, we demonstrated that miRNA-485-5p expression was reduced in gliomat issues and cell lines...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28804509/lifetime-stress-exposure-and-health-a-review-of-contemporary-assessment-methods-and-biological-mechanisms
#19
Grant S Shields, George M Slavich
Life stress is a central construct in health research because it is associated with increased risk for a variety of serious mental and physical health problems, including anxiety disorders, depression, cardiovascular disease, autoimmune disorders, Alzheimer's disease, certain cancers, and other diseases of aging. In this review, we examine how lifetime stress exposure contributes to elevated disease risk, and explore ongoing measurement and scientific issues related to this topic. To accomplish these goals, we first review existing instruments that have been developed for assessing perceived stress, self-reported life events, interviewer-assessed life stressors, and lifetime stress exposure...
August 2017: Social and Personality Psychology Compass
https://www.readbyqxmd.com/read/28803798/radiosynthesis-and-preclinical-pet-evaluation-of-89-zr-nivolumab-bms-936558-in-healthy-non-human-primates
#20
Erin L Cole, Joonyoung Kim, David J Donnelly, R Adam Smith, Daniel Cohen, Virginie Lafont, Paul E Morin, Richard Y-C Huang, Patrick L Chow, Wendy Hayes, Samuel Bonacorsi
Cancer immunotherapy, unlike traditional cytotoxic chemotherapeutic treatments, engages the immune system to identify cancer cells and stimulate immune responses. The Programmed Death-1 (PD-1) protein is an immunoinhibitory receptor expressed by activated cytotoxic T-lymphocytes (CTL) that seek out and destroy cancer cells. Multiple cancer types express and upregulate the Programmed Death-Ligand 1 (PD-L1) and 2 (PD-L2) which bind to PD-1 as an immune escape mechanism. Nivolumab is a fully human IgG4 anti-PD-1 monoclonal antibody (mAb) approved for treatment of multiple cancer types...
August 4, 2017: Bioorganic & Medicinal Chemistry
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