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https://www.readbyqxmd.com/read/27904983/vdbp-cyp27b1-and-25-hydroxyvitamin-d-gene-polymorphism-analyses-in-a-group-of-sicilian-multiple-sclerosis-patients
#1
L Agnello, C Scazzone, B Lo Sasso, C Bellia, G Bivona, S Realmuto, F Brighina, R Schillaci, P Ragonese, G Salemi, Marcello Ciaccio
Multiple sclerosis (MS) is a chronic demyelinating disease of central nervous system regarded as one of the most common causes of neurological disability in young adults. The exact etiology of MS is not yet known, although epidemiological data indicate that both genetic susceptibility and environmental exposure are involved. A poor vitamin D status has been proposed as the most attractive environmental factor. Several evidence have highlighted the importance of mutations in vitamin D-regulating genes for vitamin D status...
November 30, 2016: Biochemical Genetics
https://www.readbyqxmd.com/read/27869830/inactivation-of-capicua-drives-cancer-metastasis
#2
Ross A Okimoto, Frank Breitenbuecher, Victor R Olivas, Wei Wu, Beatrice Gini, Matan Hofree, Saurabh Asthana, Gorjan Hrustanovic, Jennifer Flanagan, Asmin Tulpule, Collin M Blakely, Henry J Haringsma, Andrew D Simmons, Kyle Gowen, James Suh, Vincent A Miller, Siraj Ali, Martin Schuler, Trever G Bivona
Metastasis is the leading cause of death in people with lung cancer, yet the molecular effectors underlying tumor dissemination remain poorly defined. Through the development of an in vivo spontaneous lung cancer metastasis model, we show that the developmentally regulated transcriptional repressor Capicua (CIC) suppresses invasion and metastasis. Inactivation of CIC relieves repression of its effector ETV4, driving ETV4-mediated upregulation of MMP24, which is necessary and sufficient for metastasis. Loss of CIC, or an increase in levels of its effectors ETV4 and MMP24, is a biomarker of tumor progression and worse outcomes in people with lung and/or gastric cancer...
November 21, 2016: Nature Genetics
https://www.readbyqxmd.com/read/27852038/transcriptomic-metabolomic-reprogramming-in-egfr-mutant-nsclc-early-adaptive-drug-escape-linking-tgf%C3%AE-2-bioenergetics-mitochondrial-priming
#3
Praveena S Thiagarajan, Xiaoliang Wu, Wei Zhang, Ivy Shi, Rakesh Bagai, Patrick Leahy, Yan Feng, Martina Veigl, Daniel Lindner, David Danielpour, Lihong Yin, Rafael Rosell, Trever G Bivona, Zhenfeng Zhang, Patrick C Ma
The impact of EGFR-mutant NSCLC precision therapy is limited by acquired resistance despite initial excellent response. Classic studies of EGFR-mutant clinical resistance to precision therapy were based on tumor rebiopsies late during clinical tumor progression on therapy. Here, we characterized a novel non-mutational early adaptive drug-escape in EGFR-mutant lung tumor cells only days after therapy initiation, that is MET-independent. The drug-escape cell states were analyzed by integrated transcriptomic and metabolomics profiling uncovering a central role for autocrine TGFβ2 in mediating cellular plasticity through profound cellular adaptive Omics reprogramming, with common mechanistic link to prosurvival mitochondrial priming...
November 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27834212/preclinical-efficacy-of-a-raf-inhibitor-that-evades-paradoxical-mapk-pathway-activation-in-protein-kinase-braf-mutant-lung-cancer
#4
Ross A Okimoto, Luping Lin, Victor Olivas, Elton Chan, Evan Markegard, Andrey Rymar, Dana Neel, Xiao Chen, Golzar Hemmati, Gideon Bollag, Trever G Bivona
Oncogenic activation of protein kinase BRAF drives tumor growth by promoting mitogen-activated protein kinase (MAPK) pathway signaling. Because oncogenic mutations in BRAF occur in ∼2-7% of lung adenocarcinoma (LA), BRAF-mutant LA is the most frequent cause of BRAF-mutant cancer mortality worldwide. Whereas most tumor types harbor predominantly the BRAF(V600E)-mutant allele, the spectrum of BRAF mutations in LA includes BRAF(V600E) (∼60% of cases) and non-V600E mutant alleles (∼40% of cases) such as BRAF(G469A) and BRAF(G466V) The presence of BRAF(V600E) in LA has prompted clinical trials testing selective BRAF inhibitors such as vemurafenib in BRAF(V600E)-mutant patients...
November 22, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27736114/-just-be-a-light-experiences-of-peers-working-on-acute-inpatient-psychiatric-units
#5
Thomas E Smith, Maria Abraham, Michael Bivona, Myles J Brakman, Isaac S Brown, Gita Enders, Sara Goodman, Liam McNabb, Joseph W Swinford
Objective: The study aimed to clarify the potential role and impact of behavioral health peer support providers on community hospital acute inpatient psychiatric units. Method: Qualitative interviews were conducted to examine perspectives of peer support providers (peers) and individuals who initially received peer services (recipients) during an inpatient stay on a community hospital psychiatric unit. Interviews elicited perspectives on interactions between peers and recipients, the role of peers vis-à-vis the clinical treatment team, and involvement of peers in discharge planning and transitions to community-based care...
October 13, 2016: Psychiatric Rehabilitation Journal
https://www.readbyqxmd.com/read/27728891/comparison-of-postoperative-venous-thromboembolism-incidence-in-gastrointestinal-and-gynecologic-solid-tumors
#6
Tina Melancon, Cory Bivona, Susan Klenke, Michelle Rockey, Jane Huh, Dave Henry, Dennis Grauer, Mazin Al-Kasspooles, Gary Johnson, Evelyn Reynolds, Julia Chapman
INTRODUCTION: Studies have shown the benefit of 28days of extended postoperative venous thromboembolism (VTE) prophylaxis for patients undergoing major cancer surgery in the abdomen or pelvis. We retrospectively evaluated the VTE incidence at the University of Kansas Hospital between gynecologic (GYN) cancer patients, who receive extended prophylaxis, and gastrointestinal (GI) cancer patients, who do not. METHODS: Patients were evaluated between January of 2010 and December of 2013, and VTE data for eligible patients were collected for 30 and 90days postoperatively...
October 6, 2016: Thrombosis Research
https://www.readbyqxmd.com/read/27686974/hsp70-dependence-in-rhabdomyosarcoma-seed-or-soil
#7
Amit J Sabnis, Trever G Bivona
No abstract text is available yet for this article.
September 29, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27686362/quality-of-life-after-brain-injury-qolibri-italian-validation-of-the-proxy-version
#8
Rita Formisano, Daniela Silvestro, Eva Azicnuda, Eloïse Longo, Carmen Barba, Jessica Rigon, Mariagrazia D'Ippolito, Marco Giustini, Umberto Bivona
To validate the proxy version of the Quality of Life after Brain Injury (QOLIBRI) questionnaire to utilize caregivers for comparison and to evaluate the correspondence between patients' self-perceived and caregivers' perception of patients' Health-Related Quality of Life (HRQoL). Ninety-two patients with severe TBI and their main caregivers were enrolled. Patients' and caregivers' HRQoL was assessed by the Patient-QOLIBRI (Pt-QOLIBRI) and the Proxy-QOLIBRI (Pro-QOLIBRI), respectively. The Pro-QOLIBRI is a modified version of the QOLIBRI to investigate caregivers' perception of patients' HRQoL (Pro-QOLIBRIpatient-centered), and their degree of satisfaction and botheredness (Pro-QOLIBRIcaregiver centered)...
September 29, 2016: Internal and Emergency Medicine
https://www.readbyqxmd.com/read/27478041/salt-inducible-kinase-2-couples-ovarian-cancer-cell-metabolism-with-survival-at-the-adipocyte-rich-metastatic-niche
#9
Fabrizio Miranda, David Mannion, Shujuan Liu, Yiyan Zheng, Lingegowda S Mangala, Clara Redondo, Sandra Herrero-Gonzalez, Ruoyan Xu, Charlotte Taylor, Donatien Fotso Chedom, Mohammad Karaminejadranjbar, Ashwag Albukhari, Dahai Jiang, Sunila Pradeep, Cristian Rodriguez-Aguayo, Gabriel Lopez-Berestein, Eidarus Salah, Kamal R Abdul Azeez, Jonathan M Elkins, Leticia Campo, Kevin A Myers, Daniel Klotz, Serena Bivona, Sunanda Dhar, Robert C Bast, Hideyuki Saya, Hwan Geun Choi, Nathanael S Gray, Roman Fischer, Benedikt M Kessler, Christopher Yau, Anil K Sood, Takeshi Motohara, Stefan Knapp, Ahmed Ashour Ahmed
The adipocyte-rich microenvironment forms a niche for ovarian cancer metastasis, but the mechanisms driving this process are incompletely understood. Here we show that salt-inducible kinase 2 (SIK2) is overexpressed in adipocyte-rich metastatic deposits compared with ovarian primary lesions. Overexpression of SIK2 in ovarian cancer cells promotes abdominal metastasis while SIK2 depletion prevents metastasis in vivo. Importantly, adipocytes induce calcium-dependent activation and autophosphorylation of SIK2...
August 8, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27450084/combined-chemical-genetic-approach-identifies-cytosolic-hsp70-dependence-in-rhabdomyosarcoma
#10
Amit J Sabnis, Christopher J Guerriero, Victor Olivas, Anin Sayana, Jonathan Shue, Jennifer Flanagan, Saurabh Asthana, Adrienne W Paton, James C Paton, Jason E Gestwicki, Peter Walter, Jonathan S Weissman, Peter Wipf, Jeffrey L Brodsky, Trever G Bivona
Cytosolic and organelle-based heat-shock protein (HSP) chaperones ensure proper folding and function of nascent and injured polypeptides to support cell growth. Under conditions of cellular stress, including oncogenic transformation, proteostasis components maintain homeostasis and prevent apoptosis. Although this cancer-relevant function has provided a rationale for therapeutically targeting proteostasis regulators (e.g., HSP90), cancer-subtype dependencies upon particular proteostasis components are relatively undefined...
August 9, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27401613/transforming-big-data-into-cancer-relevant-insight-an-initial-multi-tier-approach-to-assess-reproducibility-and-relevance
#11
(no author information available yet)
The Cancer Target Discovery and Development (CTD(2)) Network was established to accelerate the transformation of "Big Data" into novel pharmacologic targets, lead compounds, and biomarkers for rapid translation into improved patient outcomes. It rapidly became clear in this collaborative network that a key central issue was to define what constitutes sufficient computational or experimental evidence to support a biologically or clinically relevant finding. This article represents a first attempt to delineate the challenges of supporting and confirming discoveries arising from the systematic analysis of large-scale data resources in a collaborative work environment and to provide a framework that would begin a community discussion to resolve these challenges...
August 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27378174/neoadjuvant-oncogene-targeted-therapy-in-early-stage-non-small-cell-lung-cancer-as-a-strategy-to-improve-clinical-outcome-and-identify-early-mechanisms-of-resistance
#12
Caroline E McCoach, Trever G Bivona, Collin M Blakely, Robert C Doebele
Evaluations of resistance mechanisms to targeted treatments in non-small-cell lung cancer (NSCLC) are necessary for development of improved treatment after disease progression and to help delay progression of disease. Populations of cells that survive after initial treatment form the basis of resistance via outgrowth of resistant clones or activation of alternative signaling pathways. In this report we describe a clinical trial approach in which patients with epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), C-ros-1 proto-oncogene (ROS1), and hepatocyte growth factor receptor (MET) exon 14 alterations and early stage (IA-IIIA) NSCLC will be treated with induction EGFR tyrosine kinase inhibitor (TKI) or crizotinib, a TKI that inhibits ALK, ROS1, and MET...
June 8, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/27343980/an-improved-ctc-isolation-scheme-for-pairing-with-downstream-genomics-demonstrating-clinical-utility-in-metastatic-prostate-lung-and-pancreatic-cancer
#13
Gayatri Premasekharan, Elizabeth Gilbert, Ross A Okimoto, Ashiya Hamirani, Karla J Lindquist, Vy T Ngo, Ritu Roy, Jeffrey Hough, Matthew Edwards, Rosa Paz, Adam Foye, Riddhi Sood, Kirsten A Copren, Matthew Gubens, Eric J Small, Trever G Bivona, Eric A Collisson, Terence W Friedlander, Pamela L Paris
Improvements in technologies to yield purer circulating tumor cells (CTCs) will enable a broader range of clinical applications. We have previously demonstrated the use of a commercially available cell-adhesion matrix (CAM) assay to capture invasive CTCs (iCTCs). To improve the purity of the isolated iCTCs, here we used fluorescence-activated cell sorting (FACS) in combination with the CAM assay (CAM + FACS). Our results showed an increase of median purity from the CAM assay to CAM + FACS for the spiked-in cell lines and patient samples analyzed from three different metastatic cancer types: castration resistant prostate cancer (mCRPC), non-small cell lung cancer (mNSCLC) and pancreatic ductal adenocarcinoma cancer (mPDAC)...
September 28, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27308613/ras-mapk-signaling-influences-the-efficacy-of-alk-targeting-agents-in-lung-cancer
#14
Gorjan Hrustanovic, Trever G Bivona
ALK (anaplastic lymphoma kinase) inhibitors are approved in for ALK gene rearrangement positive (ALK+) lung cancer, but resistance remains a challenge. We discovered that RAS-RAF-MEK-ERK signaling controls the ALK inhibitor response in ALK+ lung cancer and is critical for ALK inhibitor resistance. Upfront ALK-MEK inhibitor polytherapy may enhance response and forestall resistance.
March 2016: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/27308535/the-hippo-effector-yap-regulates-the-response-of-cancer-cells-to-mapk-pathway-inhibitors
#15
Luping Lin, Trever G Bivona
RAF- and MEK-targeted therapies are approved for patients with BRAF(V600E) melanoma and under investigation in a several other tumor types, but resistance remains a major challenge. We uncovered yes-associated protein 1 (YAP1) as a mechanism of resistance to RAF-MEK inhibition in BRAF- and RAS-mutant cancers, providing a rationale for co-targeting YAP and RAF-MEK to enhance patient outcomes.
January 2016: Molecular & Cellular Oncology
https://www.readbyqxmd.com/read/27260951/a-biopsychosocial-analysis-of-sexuality-in-adult-males-and-their-partners-after-severe-traumatic-brain-injury
#16
Umberto Bivona, Gabriella Antonucci, Marianna Contrada, Federica Rizza, Federica Leoni, Nathan D Zasler, Rita Formisano
PURPOSE: The primary aim of this study was to investigate changes in sexual function in males and their partners following severe TBI. Secondary aims of the study were to explore the relationship between selected sociodemographic, emotional/behavioural and sexual function variables. METHODS: Twenty males with a history of severe TBI and 20 healthy controls (HC) and their respective partners were recruited. Sexual life was assessed with the Sexuality Evaluation Schedule Assessment Monitoring (SESAMO)...
2016: Brain Injury: [BI]
https://www.readbyqxmd.com/read/27154801/association-between-hypovitaminosis-d-and-systemic-sclerosis-true-or-fake
#17
REVIEW
Giulia Bivona, Luisa Agnello, Alessia Pivetti, Salvatore Milano, Concetta Scazzone, Bruna Lo Sasso, Marcello Ciaccio
BACKGROUND: Vitamin D insufficiency/deficiency is considered a major factor triggering and enhancing several autoimmune disorders; hypovitaminosis D has been reported to be common in Systemic Sclerosis (SSc). Previous studies assessing vitamin D insufficiency/deficiency in SSc have been reviewed, and the relation with pathogenesis and clinical features has been examined. CONTENT: Eligibility criteria were: reporting measurement of Vitamin D serum levels in all participants and evaluating adult onset-SSc individuals as patients group...
July 1, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/27149220/a-framework-for-understanding-and-targeting-residual-disease-in-oncogene-driven-solid-cancers
#18
Trever G Bivona, Robert C Doebele
Molecular targeted therapy has the potential to dramatically improve survival in patients with cancer. However, complete and durable responses to targeted therapy are rare in individuals with advanced-stage solid cancers. Even the most effective targeted therapies generally do not induce a complete tumor response, resulting in residual disease and tumor progression that limits patient survival. We discuss the emerging need to more fully understand the molecular basis of residual disease as a prelude to designing therapeutic strategies to minimize or eliminate residual disease so that we can move from temporary to chronic control of disease, or a cure, for patients with advanced-stage solid cancers...
May 5, 2016: Nature Medicine
https://www.readbyqxmd.com/read/27135790/vitamin-a-or-e-and-a-catechin-synergize-as-vaccine-adjuvant-to-enhance-immune-responses-in-mice-by-induction-of-early-interleukin-15-but-not-interleukin-1%C3%AE-responses
#19
Sapna Patel, Archana Akalkotkar, Joseph J Bivona, Ji-Young Lee, Young-Ki Park, Mingke Yu, Sara L Colpitts, Michael Vajdy
Vitamins A and E and select flavonoids in the family of catechins are well-defined small molecules that, if proven to possess immunomodulatory properties, hold promise as vaccine adjuvants and various therapies. In an effort to determine the in vivo immunomodulatory properties of these molecules, we found that although mucosal and systemic vaccinations with a recombinant HIV-1BaL gp120 with either a catechin, epigallo catechin gallate (EGCG) or pro-vitamin A (retinyl palmitate) alone in a vegetable-oil-in-water emulsion (OWE) suppressed antigen-specific responses, the combination of EGCG and vitamin A or E in OWE (Nutritive Immune-enhancing Delivery System, NIDS) synergistically enhanced adaptive B-cell, and CD4(+) and CD8(+) T-cell responses, following induction of relatively low local and systemic innate tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-17, but relatively high levels of early systemic IL-15 responses...
August 2016: Immunology
https://www.readbyqxmd.com/read/27107498/corrigendum-to-procalcitonin-and-community-acquired-pneumonia-cap-in-children-clin-chim-acta-451-pt-b-2015-dec-7-215-8
#20
Giulia Bivona, Luisa Agnello, Concetta Scazzone, Bruna Lo Sasso, Chiara Bellia, Marcello Ciaccio
No abstract text is available yet for this article.
April 20, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
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