tbuckley/cabot-search huggingface dataset:
<i>VEGFA</i> amplification/deletion in human breast tumors.
Authors: B. P. Schneider, M. Radovich, B. A. Hancock, N. Kassem, G. H. Vance, G. W. Sledge, K. V. Nielsen, S. Müller, M. A. Thorat, S. S. Badve
Journal: Journal of Clinical Oncology (2010)

e21017 Background: The anti-VEGF antibody, bevacizumab, has been FDA approved for the treatment of breast cancer. While germline variability (i.e. single nucleotide polymorphisms) may serve as a predictive marker for anti-VEGF therapy, to date tumor-specific variability has not. More specifically, amplification or deletion of the VEGFA gene has not been studied or evaluated as a predictive or prognostic biomarker for breast cancer. Methods: A VEGFA/centromere enumerization-6 (CEN-6) probe was created and validated using DNA clones and restriction enzyme fragment measurements. The final product contained a RP11-710-L16 probe covering 183 KB including the VEGFA gene and flanking regions. The CEN-6 probe was developed with fluorescein isothiocyanate labeled peptide nucleic acid oligonucleotides. VEGFA and CEN-6 probes were tested on metaphase spreads to exclude cross-hybridization to other chromosomes. A tissue microarray containing 93 breast cancers was analyzed for the presence of VEGFA gene amplification and/or deletion using a FISH protocol similar to the TOP2A FISH pharmDx Kit. VEGFA/CEN-6 signal ratio in cancer cells was recorded. Normal cells in the tissue sections served as an internal positive control of pretreatment and hybridization efficiency. A ratio of <0.8 was considered deleted, ≥ 1.5-1.99 was considered borderline amplified, whereas a ratio≥ 2.0 was considered amplified. Results: Of the 93 core tissue specimens, FISH analysis was successful in 80 cases (86%) of the cases. Of these, 11% were found to demonstrate VEGFA deletions, 9% were borderline amplified and 5% were amplified. Thus, 25% in total had genetic aberrations of this gene. The aberrations did not correlate with ER or HER2 expression, tumor size, nodal status or grade. Conclusions: VEGFA gene aberrations are relatively common in primary breast cancers. Their role as predictors of response to anti-VEGF therapies remains to be studied. Result n = 80 % Deletion (<0.8) 9 11 Normal (0.8-1.49) 60 75 Borderline (1.5-1.99) 7 9 Amplified (≥2.0) 4 5 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Dako Denmark A/S Molecular Pathology
Analysis of differential methylation pattern between normal prostate cells, prostate cancer cells, and between androgen dependent and independent prostate cancer cells
Authors: Dhruva Mishra, Zujian Chen, Yanyuan Wu, Jaydutt Vadgama
Journal: Cancer Research (2007)

3271   Promoter DNA methylation of CpG island sequences is a somatic alteration and an important epigenetic mechanism in cancer development. We examined the methylation pattern of promoter CpG islands of 82 genes between normal prostate cells, prostate cancer cells and between androgen dependent and androgen independent cells using the promoter methylation array technique (Panomics). Out of 82 gene promoters analyzed, we found 50 candidate genes showing a differential methylation pattern between normal (RWPE-1) and prostate cancer cell lines (LNCaP, PC3, DU145). Among these, we found few novel methylation targets, such as STAT5, LAGE-1, BAGE, RBL1, SYBL1, CIITA THBS1, IGRP, and RIOK3 which were hypermethylated from 4 to 12 fold in cancer cell lines. Along with these we observed additional differences in gene family belonging to: tumor suppressor (Rb, TMS-1, PAX-6, FHIT, SRBC), cell cycle (p21, p27, CDKN2A), drug transporters (MDR1, MLC1), transcription factors (STAT1, POU3F1, MYOD), and glucose metabolizers (IGRP, G6PD, GLUT4). A significant difference (p
Report on the Safety of Velaglucerase Alfa Enzyme Replacement Therapy in Patients with Type 1 Gaucher Disease and the Transition From Clinic to Home Infusions During Treatment Protocol HGT-GCB-058
Authors: Gregory M Pastores, Barry E Rosenbloom, Neal J Weinreb, Ozlem Goker-Alpan, Rebecca Mardach, Mark Lipson, Jennifer Ibrahim, Gabriel M Cohn, David Zahrieh, Pramod K Mistry
Journal: Blood (2011)
The pattern and clinicopathological correlates of programmed death-ligand 1 expression in cutaneous squamous cell carcinoma
Authors: K. Schaper, B. Köther, K. Hesse, I. Satzger, R. Gutzmer
Journal: British Journal of Dermatology (2016)

the incidence of cutaneous squamous cell carcinoma (cSCC) is rising1 and since inoperable cSCC lacks effective therapies, new therapeutic options are needed. Immunooncological agents targeting checkpoints such as programmed death receptor-1 (PD-1) or its ligand PD-L1 are very promising new anti-cancer drugs, while efficacy correlates with PD-L1 expression in various tumor types.

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Germ line mutations in shelterin complex genes are associated with familial chronic lymphocytic leukemia
Authors: Helen E. Speedy, Ben Kinnersley, Daniel Chubb, Peter Broderick, Philip J. Law, Kevin Litchfield, Sandrine Jayne, Martin J. S. Dyer, Claire Dearden, George A. Follows, Daniel Catovsky, Richard S. Houlston
Journal: Blood (2016)
Canadians authorised to use cannabis for medical purposes to be allowed to grow their own again
Authors: Barbara Kermode-Scott
Journal: BMJ (2016)

The Canadian government has announced new rules for medical marijuana use that will let people with a medical need for cannabis to grow it at home—once again.

The Access to Cannabis for Medical Purposes Regulations1 will come into force on 24 August and will allow patients who have been authorised to use cannabis for medical purposes to grow a limited amount for their own use, or to designate someone to produce it for them, rather than buying …
Nifedipine for Hypertensive Emergencies
Authors: David J. Woods
Journal: JAMA (1997)

To the Editor.  —Dr Grossman and colleagues1mention the practical problems associated with the administration of sublingual nifedipine. As an alternative method to cutting the capsule and squeezing its contents into the patient's mouth, nurses and physicians may frequently attempt to withdraw the liquid contents of the capsule using a needle and syringe. We investigated the accuracy and precision of this method of administration.  The preparation of 10-mg doses of nifedipine was simulated by requesting 20 pharmacy staff to withdraw the total contents of a liquid-filled nifedipine capsule (Adalat, 10 mg, Bayer, Auckland, New Zealand) by puncturing the gelatin shell and withdrawing the contents into a preweighed 1-mL needle and syringe. The 10-mg capsules contain 0.34 mL of liquid nifedipine, which has a density of 1.135 gm/L (written communication, data on file, Bayer, Auckland, New Zealand). After removal of the dose, each syringe and needle was reweighed, and the amount of nifedipine
Autologous Stem Cell Transplantation and Addition of Rituximab Independently Prolong Response Duration in Advanced Stage Mantle Cell Lymphoma.
Authors: Eva Hoster, Bernd Metzner, Roswitha Forstpointner, Michael Pfreundschuh, Lorenz Trümper, Michael Hallek, Bernhard Wörmann, Ulrich Dührsen, Christian Gisselbrecht, Hanneke C. Kluin-Nelemans, Achiel Van Hoof, Michael Unterhalt, Wolfgang Hiddemann, Martin H. Dreyling
Journal: Blood (2009)
Screening With Spirometry Is A Useful Predictor Of Later Development Of Non-Infectious Pulmonary Syndromes In Patients Undergoing Allogeneic Stem Cell Transplantation
Authors: Thompson A Philip, Andrew B M Lim, Mark Tacey, Ramzi Hijazi, Ashley P. Ng, Jeffrey Szer, David Ritchie, Ashish R. Bajel
Journal: Blood (2013)
Response to Comment on “Absence of sperm RNA elements correlates with idiopathic male infertility”
Authors: Meritxell Jodar, Edward Sendler, Sergey I. Moskovtsev, Clifford L. Librach, Robert Goodrich, Sonja Swanson, Russ Hauser, Michael P. Diamond, Stephen A. Krawetz
Journal: Science Translational Medicine (2016)

RNAs from other cell types have minimal impact on male fecundity-associated sperm RNA elements.
Adjuvant temozolomide for low grade gliomas: Molecular and radiographic correlates of treatment response in a phase II clinical trial.
Authors: Michael Traut Wahl, Joanna J Phillips, Annette M Molinaro, Yi Lin, Arie Perry, Daphne Haas-Kogan, Joseph F Costello, Manisha Dayal, Nicholas A. Butowski, Jennifer Leigh Clarke, Michael Prados, Mitchel S. Berger, Sarah J. Nelson, Susan Marina Chang
Journal: Journal of Clinical Oncology (2016)

2002 Background: Management of adult low grade gliomas (LGG) remains controversial. Previous results from a phase II clinical trial investigating adjuvant temozolomide (TMZ) as an alternative to radiation demonstrated progression-free survival (PFS) and overall survival (OS) comparable to historical controls receiving radiation alone. Here we present results stratified by newly defined molecular subgroups to determine optimal candidates for adjuvant chemotherapy as a means of delaying or obviating the need for radiation. Methods: 120 patients with newly diagnosed WHO grade II LGGs with gross residual disease after surgical resection were enrolled in a phase II clinical trial. Patients received monthly cycles of TMZ for up to 1 year or until progression, and were monitored with serial MRI at baseline and every 2 months during treatment. 97 patients with available tissue were grouped into molecular subtype based on 1p19q codeletion and IDH1 status (1p19q codel: 1p19q codeleted/IDH1 mutated; IDH1mut: 1p19q intact/IDH1 mutated, IDH1wt: 1p19q intact/IDH1 wild type). For 71 patients with serial imaging, volumetric analysis was performed with tumor volume defined as the hyperintense region on fluid-attenuated inversion-recovery (FLAIR) imaging. Results: Tumor volume significantly decreased after 6 months of treatment in 1p19q codel patients (32% decrease, p<0.001), but not in IDH1mut (22% decrease, p=0.11) or IDH1wt (15% decrease, p=0.13). Molecular subtype was associated with rate of progression during treatment (p<0.001), PFS (p=0.007) and OS (p<0.001). Pretreatment tumor volume was associated with PFS and OS (p<0.001). We identify a low-risk group of patients with 1p19q codeletion and pretreatment tumor volume ≤ 68 cm3with a 0% risk of progression during treatment, median PFS of 4.9 years, and median OS not reached (95% lower CI, 10.8 years). Conclusions: We observe a significant decrease in tumor volume during treatment with TMZ specific to patients with 1p19q codeletion. Molecular subtype and pretreatment tumor volume are predictive factors for PFS and OS; patients with 1p19q codeletion and limited disease after surgery may be optimal candidates for adjuvant TMZ. Clinical trial information: NCT00313729.
Sustained Effect of First Line Sequential Therapy with Intensive Consolidation Chemotherapy and Allogeneic Hematopoietic Stem Cell Transplantation (ASCT) after Reduced Intensity Conditioning (RIC) for Patients with Acute Myeloblastic Leukemia (AML) in First Complete Remission (CR1).
Authors: Didier Blaise, R. Tabrizi, C. Faucher, Mohamad Mohty, J.O. Bay, J.M. Boiron, G. Marit, S. Furst, A.M. Stoppa, A. Charbonnier, T. Prebet, C. Chabannon, N. Vey
Journal: Blood (2006)
Upregulation of multidrug resistance-associated protein 4 in the early stage of vascular invasion of hepatocellular carcinoma.
Authors: K. Higuchi, T. Terada, M. Fukudo, K. Ogasawara, T. Katsura, E. Hatano, I. Ikai, K. Inui
Journal: Journal of Clinical Oncology (2010)

4146 Background: In human liver, many drug transporters play important physiological and pharmacological roles. The expression of hepatic drug transporters is altered in various pathophysiologic conditions such as cholestasis, but limited data are available for hepatocellular carcinoma (HCC). The aims of this study were to identify drug transporters significantly changed in HCC and to clarify their pathophysiologic implications. Methods: The mRNA levels of hepatic solute carrier (SLC) and ATP-binding cassette (ABC) drug transporters were comprehensively analyzed by real-time RT-PCR in 54 patients with HCC. The protein expression of multidrug resistance-associated protein (MRP) 4, which mediates the efflux of cyclic AMP and prostaglandin E2 being involved in HCC progression, was evaluated by Western blot analysis and immunohistochemical staining. The effects of patients' backgrounds and clinicopathological parameters on the mRNA level of MRP4 were examined by Mann-Whitney U test. Results: Among the transporters examined, the mRNA level of MRP4 showed the highest increase in HCC compared with matched nontumorous liver tissues (7.4-fold, p < 0.0001). Furthermore, MRP4 protein at the plasma membranes was also increased in HCC. Portal vein invasion (vp) was significantly related to the elevation of MRP4 mRNA level (p < 0.05). Interestingly, the MRP4 mRNA was profoundly upregulated in the stage of vp1 (invasion in the third or more of the peripheral branches), which was consistent with the strong staining of MRP4. Conclusions: We first revealed that MRP4 was remarkably increased in HCC, especially in the early stage of portal vein invasion. The present results suggest that MRP4 may promote HCC invasion and can be a potential target for the treatment of HCC. No significant financial relationships to disclose.
Predicting Risk of Ischemic or Bleeding Events After Percutaneous Coronary Intervention
Authors: Roxana Mehran, Usman Baber
Journal: JAMA Cardiology (2016)

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<i>Notes from the Field</i>: Cluster of Tuberculosis Cases Among Marshallese Persons Residing in Arkansas — 2014–2015
Authors: Laura Lester Rothfeldt, Naveen Patil, Dirk T. Haselow, Sandy Hainline Williams, J. Gary Wheeler, Leonard N. Mukasa
Journal: MMWR Morbidity and Mortality Weekly Report (2016)

During early September 2014, the Arkansas Department of Health identified an increased number of tuberculosis (TB) cases among a unique population in a well-circumscribed geographical area in northwest Arkansas. The Compact of Free Association Act of 1985 (Public Law 99-239, amended in 2003 by Public Law 108-188) established the Republic of the Marshall Islands (RMI) as an independent nation, and persons from the RMI can travel freely (with valid RMI passport) to and from the United States as nonimmigrants without visas (1). Marshallese started settling in northwest Arkansas during the early 1990s because of employment and educational opportunities (2). According to the 2010 Census, an estimated 4,300 Marshallese resided in Arkansas (2), mostly within one county which ranked 6th in the United States for counties with the highest percentage of Native Hawaiians and Other Pacific Islanders (3). It is estimated that this number has been growing steadily each year since the 2010 Census; however, obtaining an accurate count is difficult. The RMI is a TB high-incidence country, with a case-rate of 212.7 per 100,000 persons for 2014, whereas the case-rate was 3.1 per 100,000 persons in Arkansas and 2.9 per 100,000 persons in the United States (4,5). Screening for either active TB or latent TB infection (LTBI) is not required for Marshallese entry to the United States (1).
Loss of Endothelial Nitric Oxide Synthase Promotes p25 Generation and Tau Phosphorylation in a Murine Model of Alzheimer’s Disease
Authors: Susan A. Austin, Zvonimir S. Katusic
Journal: Circulation Research (2016)

Alzheimer's disease has an unknown pathogenesis; however, cardiovascular risk factors are associated with a higher incidence of Alzheimer's disease. A defining feature of endothelial dysfunction induced by cardiovascular risk factors is reduced bioavailable endothelial nitric oxide (NO). We previously demonstrated that endothelial NO acts as an important signaling molecule in neuronal tissue.We sought to determine the relationship between the loss of endothelial NO synthase (eNOS) and tau phosphorylation in neuronal tissue.We used eNOS knockout (-/-) mice as well as an Alzheimer's disease mouse model, amyloid precursor protein (APP)/PSEN1dE9+/- (PS1) that lacked eNOS (APP/PS1/eNOS-/-) to examine expression of tau kinases and tau phosphorylation. Brain tissue from eNOS-/- mice had statistically higher ratios of p25/p35, indicative of increased cyclin-dependent kinase 5 activity as compared with wild-type (n=8, P<0.05). However, tau phosphorylation was unchanged in eNOS-/- mice (P>0.05). Next, we determined the role of NO in tau pathology in APP/PS1/eNOS-/-. These mice had significantly higher levels of p25, a higher p25/p35 ratio (n=12-14; P<0.05), and significantly higher cyclin-dependent kinase 5 activity (n=4; P<0.001). Importantly, APP/PS1/eNOS-/- mice also had significantly increased tau phosphorylation (n=4-6; P<0.05). No other changes in amyloid pathology, antioxidant pathways, or neuroinflammation were observed in APP/PS1/eNOS-/- mice as compared with APP/PS1 mice.Our data suggests that loss of endothelial NO plays an important role in the generation of p25 and resulting tau phosphorylation in neuronal tissue. These findings provide important new insights into the molecular mechanisms linking endothelial dysfunction with the pathogenesis of Alzheimer's disease.
FOXD1–ALDH1A3 Signaling Is a Determinant for the Self-Renewal and Tumorigenicity of Mesenchymal Glioma Stem Cells
Authors: Peng Cheng, Jia Wang, Indrayani Waghmare, Stefania Sartini, Vito Coviello, Zhuo Zhang, Sung-Hak Kim, Ahmed Mohyeldin, Marat S. Pavlyukov, Mutsuko Minata, Claudia L.L. Valentim, Rishi Raj Chhipa, Krishna P.L. Bhat, Biplab Dasgupta, Concettina La Motta, Madhuri Kango-Singh, Ichiro Nakano
Journal: Cancer Research (2016)

Glioma stem-like cells (GSC) with tumor-initiating activity orchestrate the cellular hierarchy in glioblastoma and engender therapeutic resistance. Recent work has divided GSC into two subtypes with a mesenchymal (MES) GSC population as the more malignant subtype. In this study, we identify the FOXD1-ALDH1A3 signaling axis as a determinant of the MES GSC phenotype. The transcription factor FOXD1 is expressed predominantly in patient-derived cultures enriched with MES, but not with the proneural GSC subtype. shRNA-mediated attenuation of FOXD1 in MES GSC ablates their clonogenicity in vitro and in vivo Mechanistically, FOXD1 regulates the transcriptional activity of ALDH1A3, an established functional marker for MES GSC. Indeed, the functional roles of FOXD1 and ALDH1A3 are likely evolutionally conserved, insofar as RNAi-mediated attenuation of their orthologous genes in Drosophila blocks formation of brain tumors engineered in that species. In clinical specimens of high-grade glioma, the levels of expression of both FOXD1 and ALDH1A3 are inversely correlated with patient prognosis. Finally, a novel small-molecule inhibitor of ALDH we developed, termed GA11, displays potent in vivo efficacy when administered systemically in a murine GSC-derived xenograft model of glioblastoma. Collectively, our findings define a FOXD1-ALDH1A3 pathway in controling the clonogenic and tumorigenic potential of MES GSC in glioblastoma tumors. Cancer Res; 76(24); 7219-30. ©2016 AACR.
Multidisciplinary questions in thoracic oncology: the team experience
Authors: Jean-Paul Sculier
Journal: European Respiratory Journal (2016)

In the context of the European Respiratory Society (ERS) plan for thoracic oncology [1], in 2014 the European Respiratory Journal ( ERJ ) initiated a series of reviews called "Challenges and controversies in thoracic oncology" [2]. The following questions were addressed. The specific contribution of each thoracic staging and treatment modality has not always been unequivocally established: which grey areas remain? Concerning screening programmes for lung cancer, is it time for large-scale screening via chest computed tomography? Is multidisciplinary team management in thoracic oncology more than a concept? Considering tumour tissue sampling for lung cancer management at the era of personalised therapy, what is enough for molecular testing? Which approaches should be used for small sized lung cancer: lobectomy, sublobectomy or stereotactic irradiation? What is the place of multimodality management of malignant pleural mesothelioma? How can non-inferiority trials influence practice in thoracic oncology without valid conclusions? How should advanced nonsmall cell lung cancer (NSCLC) be treated: by targeted therapy, personalised chemotherapy or standard chemotherapy? What is the exact role of palliative care in the patient's management? What should be the approach to the staging of lung cancer, with regard to noninvasive, minimally invasive and invasive techniques? Which examinations (and at what time) should take place during the follow-up of the patient after lung cancer resection? What is the best management option for a patient with NSCLC, with an epidermal growth factor receptor activating mutation or with an Alk translocation? Introducing a new ERJ series examining the multidisciplinary character of thoracic oncology <http://ow.ly/59bY300wrRS>
Array CGH Identifies Copy Number Changes In 10% Of 520 MDS Patients With Normal Karyotype: Deletions Encompass The Genes TET2, DNMT3A, ETV6, NF1, RUNX1, and STAG2 and Are Associated With Shorter Survival
Authors: Claudia Haferlach, Melanie Zenger, Marita Staller, Andreas Roller, Kathrin Raitner, Jinda Holzwarth, Wolfgang Kern, Susanne Schnittger, Yasunobu Nagata, Seishi Ogawa, Alexander Kohlmann, Torsten Haferlach
Journal: Blood (2013)
Nanoparticle Arsenic Compound Realgar Effectively Targets Myeloma Stem-Like Side Population
Authors: Jana Jakubikova, Teru Hideshima, Richard W.J. Groen, Danka Cholujova, Zdenka Bujnakova, Jacob P. Laubach, Nikhil C. Munshi, Paul G. Richardson, Constantine S. Mitsiades, Peter Balaz, Jan Sedlak, Kenneth C. Anderson
Journal: Blood (2013)