tbuckley/cabot-search huggingface dataset:
Feasibility of dc vaccine combined with low dose endoxan and high dose il-2 treatment associated with taurolidine for advanced, multi-resistant melanoma patients.
Authors: Gustavo A Moviglia, Ralf Kleef
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts 2014 Dillman and coworkers reported 40% 5-year survival of advanced malignant melanoma (MM) patients treated with a combination of Tumor Vaccine in combination with High dose IL-2 versus 13% of similar patients treated only with High Dose of IL-2 (HD IL-2). In order to improve the
Comparison of high sensitive IHC, FISH, and RT-PCR direct sequencing for detection of ALK translocation in lung cancer.
Authors: T. Mitsudomi, K. Tomizawa, Y. Horio, T. Hida, Y. Yatabe
Journal: Journal of Clinical Oncology (2011)

7534 Background: A subset of lung cancer with ALK translocation shows remarkable sensitivity to ALK tyrosine kinase inhibitors such as crizotinib. Although its diagnosis is of crucial importance, the method has not been standardized. Methods: 345 resected lung cancer specimens and 44 biopsy specimens were used. RNA was extracted from frozen tumors or touch imprint cytologic prepareations and RT-PCR direct sequencing for EML4-ALK fusion or KRAS, EGFR gene mutations was performed. High-sensitivity immunohistochemistry (IHC) was performed using a mouse monoclonal antibody against ALK (clone 5A4, Santa Cruz) and the Envision Flex+ system (DAKO) in which the linker and the labeled polymer amplifies the signal of the primary antibody. Tissue microarray was created for 345 resected specimens. An ALK break-apart probe (Vysis LSI ALK Dual Color, Break Apart Rearrangement Probe, Abbott Molecular) was used for Fluorescent in situ hybridization (FISH). Results: In tissue microarray experiments, 12 tumors unequivocally overexpressed ALK protein (3.5%). All these 12 tumors were also positive by FISH. 8 of 12 were confirmed to have rearranged EML4-ALK by sequencing, while 4 were not. We also confirmed that these 4 did not have KIF5B-ALK or TFG-ALK by RT-PCR, indicating that overexpressed ALK with gene rearrangement in these cases might be due to ALK fusion with a novel gene (not yet confirmed). In biopsy specimens, 6 were positive by IHC and all harbored rearranged ALK by FISH. Direct sequencing revealed that all 6 harbored EML4-ALK fusion. Conversely, none of IHC negative tumors were positive for FISH or direct sequencing. In both experiments, strict mutually exclusionary relationship among ALK, EGFR and KRAS was confirmed. Conclusions: IHC using commercially available ALK antibody and high sensitive visualization kit was feasible for archival samples and small biopsy specimens. It was easy and yet reliable, and thus considered as the best suitable method for screening ALK-positive tumors. IHC FISH RT-PCR direct sequence +/- EML4-ALK/EGFR/KRAS/WT Tissue microarray (n=345) +12 12/0 8/0/0/4 -333 Not determined 0/132/33/168 Biopsy specimens (n= 44) +6 6/0 6/0/0/0 -38 0/38 0/15/1/22
Blocking HSP90 Addiction Inhibits Tumor Cell Proliferation, Metastasis Development, and Synergistically Acts with Zoledronic Acid to Delay Osteosarcoma Progression
Authors: Benjamin Ory, Marc Baud'huin, Franck Verrecchia, Bénédicte Brounais-Le Royer, Thibaut Quillard, Jérôme Amiaud, Séverine Battaglia, Dominique Heymann, Francoise Redini, Francois Lamoureux
Journal: Clinical Cancer Research (2015)

Despite recent improvements in therapeutic management of osteosarcoma, ongoing challenges in improving the response to chemotherapy warrants the development of new strategies to improve overall patient survival. Among them, HSP90 is a molecular chaperone involved in the maturation and stability of various oncogenic proteins leading to tumor cells survival and disease progression. We assessed the antitumor properties of a synthetic HSP90 inhibitor, PF4942847, alone or in combination with zoledronic acid in osteosarcoma.The effects of PF4942847 were evaluated on human osteosarcoma cells growth and apoptosis. Signaling pathways were analyzed by Western blotting. The consequence of HSP90 therapy combined or not with zoledronic acid was evaluated in mice bearing HOS-MNNG xenografts on tumor growth, associated bone lesions, and pulmonary metastasis. The effect of PF4942847 on osteoclastogenesis was assessed on human CD14(+) monocytes.In osteosarcoma cell lines, PF4942847 inhibited cell growth in a dose-dependent manner (IC50 ±50 nmol/L) and induced apoptosis with an increase of sub-G1 fraction and cleaved PARP. These biologic events were accompanied by decreased expression of Akt, p-ERK, c-Met, and c-RAF1. When administered orally to mice bearing osteosarcoma tumors, PF4942847 significantly inhibited tumor growth by 80%, prolonged survival compared with controls, and inhibited pulmonary metastases by blocking c-Met, FAK, and MMP9 signaling. In contrast to 17-allylamino-17-demethoxygeldanamycin (17-AAG), PF4942847 did not induce osteoclast differentiation, and synergistically acted with zoledronic acid to delay osteosarcoma progression and prevent bone lesions.All these data provide a strong rationale for clinical evaluation of PF4942847 alone or in combination with zoledronic acid in osteosarcoma. Clin Cancer Res; 22(10); 2520-33. ©2015 AACR.
A Novel Three–Dimensional Human Peritubular Microvascular System
Authors: Giovanni Ligresti, Ryan J. Nagao, Jun Xue, Yoon Jung Choi, Jin Xu, Shuyu Ren, Takahide Aburatani, Susan K. Anderson, James W. MacDonald, Theo K. Bammler, Stephen M. Schwartz, Kimberly A. Muczynski, Jeremy S. Duffield, Jonathan Himmelfarb, Ying Zheng
Journal: Journal of the American Society of Nephrology (2015)

Human kidney peritubular capillaries are particularly susceptible to injury, resulting in dysregulated angiogenesis, capillary rarefaction and regression, and progressive loss of kidney function. However, little is known about the structure and function of human kidney microvasculature. Here, we isolated, purified, and characterized human kidney peritubular microvascular endothelial cells (HKMECs) and reconstituted a three-dimensional human kidney microvasculature in a flow-directed microphysiologic system. By combining epithelial cell depletion and cell culture in media with high concentrations of vascular endothelial growth factor, we obtained HKMECs of high purity in large quantity. Unlike other endothelial cells, isolated HKMECs depended on high vascular endothelial growth factor concentration for survival and growth and exhibited high tubulogenic but low angiogenic potential. Furthermore, HKMECs had a different transcriptional profile. Under flow, HKMECs formed a thin fenestrated endothelium with a functional permeability barrier. In conclusion, this three-dimensional HKMEC-specific microphysiologic system recapitulates human kidney microvascular structure and function and shows phenotypic characteristics different from those of other microvascular endothelial cells.
Genetic engineering of T cells with receptors from NY-ESO-1-specific tumor-recognizing CD4+ T cell as a novel approach for adoptive T cell therapy
Authors: Junko Matsuzaki, Takemasa Tsuji, Immanuel Luescher, Hiroshi Shiku, Junichi Mineno, Sachiko Okamoto, Lloyd Old, Protul Shrikant, Sacha Gnjatic, Kunle Odunsi
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Tumor antigen-specific CD4+ T cells generally orchestrate and regulate innate and adaptive immune cells to provide immune surveillance against malignancy. However, activation of antigen-specific CD4+ T cells is restricted at local tumor sites where antigen-presenting cells are
Are Longitudinal, Natural History Studies the Next Step in Genotype-Phenotype Translational Genomics in Hypertrophic Cardiomyopathy?**Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Michael J. Ackerman, Sara L. Van Driest, Martijn Bos
Journal: Journal of the American College of Cardiology (2005)
Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer
Authors: Erica J Childs, Evelina Mocci, Daniele Campa, Paige M Bracci, Steven Gallinger, Michael Goggins, Donghui Li, Rachel E Neale, Sara H Olson, Ghislaine Scelo, Laufey T Amundadottir, William R Bamlet, Maarten F Bijlsma, Amanda Blackford, Michael Borges, Paul Brennan, Hermann Brenner, H Bas Bueno-de-Mesquita, Federico Canzian, Gabriele Capurso, Giulia M Cavestro, Kari G Chaffee, Stephen J Chanock, Sean P Cleary, Michelle Cotterchio, Lenka Foretova, Charles Fuchs, Niccola Funel, Maria Gazouli, Manal Hassan, Joseph M Herman, Ivana Holcatova, Elizabeth A Holly, Robert N Hoover, Rayjean J Hung, Vladimir Janout, Timothy J Key, Juozas Kupcinskas, Robert C Kurtz, Stefano Landi, Lingeng Lu, Ewa Malecka-Panas, Andrea Mambrini, Beatrice Mohelnikova-Duchonova, John P Neoptolemos, Ann L Oberg, Irene Orlow, Claudio Pasquali, Raffaele Pezzilli, Cosmeri Rizzato, Amethyst Saldia, Aldo Scarpa, Rachael Z Stolzenberg-Solomon, Oliver Strobel, Francesca Tavano, Yogesh K Vashist, Pavel Vodicka, Brian M Wolpin, Herbert Yu, Gloria M Petersen, Harvey A Risch, Alison P Klein
Journal: Nature Genetics (2015)
The target cell of transformation is distinct from the leukemia stem cell in murine CALM/AF10 leukemia models
Authors: S Dutta, A Krause, S Vosberg, T Herold, B Ksienzyk, L Quintanilla-Martinez, B Tizazu, M Chopra, A Graf, S Krebs, H Blum, P A Greif, A Vetter, K Metzeler, M Rothenberg-Thurley, M R Schneider, M Dahlhoff, K Spiekermann, U Zimber-Strobl, E Wolf, S K Bohlander
Journal: Leukemia (2015)
Fine-Mapping and Genome Editing Reveal An Essential Erythroid Enhancer At The HbF-Associated BCL11A Locus
Authors: Daniel E. Bauer, Sophia C. Kamran, Samuel Lessard, Jian Xu, Yuko Fujiwara, Carrie Lin, Zhen Shao, Matthew C. Canver, Elenoe C. Smith, Luca Pinello, Peter J. Sabo, Jeff Vierstra, Richard A. Voit, Guo-Cheng Yuan, Matthew H. Porteus, John Stamatoyannopoulos, Guillaume Lettre, Stuart H. Orkin
Journal: Blood (2013)
Of Microbes and Men: Figure 1
Authors: Ele Ferrannini
Journal: Diabetes Care (2015)

In this issue of Diabetes Care , Simon et al. (1) report the results of a study testing the hypothesis that the administration of Lactobacillus reuteri in subjects without diabetes improves insulin sensitivity. A quick review of the background may help us put this work in context.

Our digestive tract hosts some 2 kg of microbes, made up of ∼100 trillion microorganisms. Present in sparse colonies in the upper intestine, this indigenous microbial community (microbiota) jams into the cecum, colon, and rectum; the appendix is the ultimate shelter when antibiotics wage a mass killing. The taxonomy lists hundreds of species of bacteria (and minority groups of yeasts and viruses), whose collective genome is called microbiome (ninefold larger than our genome). Having coevolved with Homo sapiens , these microbes are so adapted to the human gut environment that they do not grow in culture as easily as do other germs and are therefore identified by their genetic material that is usually retrieved from feces.

Microbiota have long been known to train our immune system, process indigestible foodstuffs, manufacture vitamins, and break down toxins and medications. In the past decade, variants of gut microbiome have been associated with diverse human diseases ranging from enterocolitis to psychiatric disorders. Of special interest to us is the association with obesity (2 …
Role of Magnetic Resonance Imaging in Prostate Cancer Screening: A Pilot Study Within the Göteborg Randomised Screening Trial
Authors: Anna Grenabo Bergdahl, Ulrica Wilderäng, Gunnar Aus, Sigrid Carlsson, Jan-Erik Damber, Maria Frånlund, Kjell Geterud, Ali Khatami, Andreas Socratous, Johan Stranne, Mikael Hellström, Jonas Hugosson
Journal: European Urology (2015)
Update: Influenza Activity — United States,
Authors: Sophie Smith, Lenee Blanton, Krista Kniss, Desiree Mustaquim, Craig Steffens, Carrie Reed, Anna Bramley, Brendan Flannery, Alicia M. Fry, Lisa A. Grohskopf, Joseph Bresee, Teresa Wallis, Rebecca Garten, Xiyan Xu, Anwar Isa Abd Elal, Larisa Gubareva, John Barnes, David E. Wentworth, Erin Burns, Jacqueline Katz, Daniel Jernigan, Lynnette Brammer
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

CDC collects, compiles, and analyzes data on influenza activity year-round in the United States. The influenza season generally begins in the fall and continues through the winter and spring months; however, the timing and severity of circulating influenza viruses can vary by geographic location and season. Influenza activity in the United States remained low through October and November in 2015. Influenza A viruses have been most frequently identified, with influenza A (H3) viruses predominating. This report summarizes U.S. influenza activity for the period October 4-November 28, 2015.
Comparative Study of Liver Gene Transfer With AAV Vectors Based on Natural and Engineered AAV Capsids
Authors: Lili Wang, Peter Bell, Suryanarayan Somanathan, Qiang Wang, Zhenning He, Hongwei Yu, Deirdre McMenamin, Tamara Goode, Roberto Calcedo, James M Wilson
Journal: Molecular Therapy (2015)

Vectors based on the clade E family member adeno-associated virus (AAV) serotype 8 have shown promise in patients with hemophilia B and have emerged as best in class for human liver gene therapies. We conducted a thorough evaluation of liver-directed gene therapy using vectors based on several natural and engineered capsids including the clade E AAVrh10 and the largely uncharacterized and phylogenically distinct AAV3B. Included in this study was a putatively superior hepatotropic capsid, AAVLK03, which is very similar to AAV3B. Vectors based on these capsids were benchmarked against AAV8 and AAV2 in a number of in vitro and in vivo model systems including C57BL/6 mice, immune-deficient mice that are partially repopulated with human hepatocytes, and nonhuman primates. Our studies in nonhuman primates and human hepatocytes demonstrated high level transduction of the clade E-derived vectors and equally high transduction with vectors based on AAV3B. In contrast to previous reports, AAVLK03 vectors are not superior to either AAV3B or AAV8. Vectors based on AAV3B should be considered for liver-directed gene therapy when administered following, or before, treatment with the serologically distinct clade E vectors. Vectors based on the clade E family member adeno-associated virus (AAV) serotype 8 have shown promise in patients with hemophilia B and have emerged as best in class for human liver gene therapies. We conducted a thorough evaluation of liver-directed gene therapy using vectors based on several natural and engineered capsids including the clade E AAVrh10 and the largely uncharacterized and phylogenically distinct AAV3B. Included in this study was a putatively superior hepatotropic capsid, AAVLK03, which is very similar to AAV3B. Vectors based on these capsids were benchmarked against AAV8 and AAV2 in a number of in vitro and in vivo model systems including C57BL/6 mice, immune-deficient mice that are partially repopulated with human hepatocytes, and nonhuman primates. Our studies in nonhuman primates and human hepatocytes demonstrated high level transduction of the clade E-derived vectors and equally high transduction with vectors based on AAV3B. In contrast to previous reports, AAVLK03 vectors are not superior to either AAV3B or AAV8. Vectors based on AAV3B should be considered for liver-directed gene therapy when administered following, or before, treatment with the serologically distinct clade E vectors.
Effect of Intensive Versus Moderate Lipid-Lowering Therapy on Epicardial Adipose Tissue in Hyperlipidemic Post-Menopausal Women
Authors: Nikolaos Alexopoulos, Bekir H. Melek, Chesnal D. Arepalli, Gregory-Randell Hartlage, Zhengjia Chen, Sungjin Kim, Arthur E. Stillman, Paolo Raggi
Journal: Journal of the American College of Cardiology (2013)

This study sought to evaluate the effect of intensive and moderate statin therapy on epicardial adipose tissue (EAT). EAT has been associated with coronary artery disease severity and outcome. It is currently unknown whether EAT volume changes over time when patients are exposed to statin therapy. Subanalysis of a randomized study of atorvastatin 80 mg/day versus pravastatin 40 mg/day for 1 year in a clinical trial designed to assess the progression of coronary artery calcium (CAC) in hyperlipidemic post-menopausal women. Patients underwent cardiac computed tomography scans at the start and end of the trial period. Of 420 patients, 194 received atorvastatin and 226 pravastatin; the median low-density lipoprotein change was −53.3% and −28.3% with atorvastatin and pravastatin, respectively (p < 0.001). Baseline EAT correlated with age, body mass index, hypertension, diabetes mellitus, high-density lipoprotein, triglyceride levels, and CAC (p < 0.001). At the end of follow-up, EAT regressed more in the atorvastatin than in the pravastatin group (median, −3.38% vs. −0.83%, p = 0.025). The EAT percent change from baseline was significant in the atorvastatin, but not the pravastatin group (p < 0.001 and p = 0.2, respectively). There was no correlation between lipid lowering and EAT regression. CAC progressed significantly in both groups from baseline. In hyperlipidemic post-menopausal women, statin therapy induced EAT regression, although intensive therapy was more effective than moderate-intensity therapy. This effect does not seem linked to low-density lipoprotein lowering and may be secondary to other actions of statins such as anti-inflammatory effects.
Persistence of seropositivity among persons vaccinated for hepatitis A during infancy by maternal antibody status: 15‐year follow‐up
Authors: Philip R. Spradling, Lisa R. Bulkow, Susan E. Negus, Chriss Homan, Michael G. Bruce, Brian J. McMahon
Journal: Hepatology (2015)

The effect of passively transferred maternal antibody to hepatitis A virus (anti‐HAV) on the duration of seropositivity after hepatitis A vaccination during infancy and early childhood is unclear. We obtained levels of anti‐HAV at intervals through age 15‐16 years among three groups of Alaskan Native children who initiated a two‐dose inactivated hepatitis A vaccination series at ages 6 months (group 1), 12 months (group 2), and 15 months (group 3), each group randomized according to maternal anti‐HAV status. Seropositivity (anti‐HAV ≥20 mIU/mL) 30 years after the second vaccine dose among the three groups was predicted using a random effects model. One hundred eighty‐three children participated in the study; follow‐up did not differ significantly by vaccine group or maternal anti‐HAV status. Although the frequency of seropositivity among all participants through age 10 years was high (100% among groups 2 and 3 and &gt;90% among group 1), there was a decrease thereafter through age 15‐16 years among group 1 children, who initiated vaccination at age 6 months (50%‐75%), and among maternal anti‐HAV‐positive children in groups 2 and 3 (67%‐87%), who initiated vaccination at ages 12 months and 15 months, respectively. Nonetheless, the model indicated that anti‐HAV seropositivity should persist for ≥30 years after vaccination in 64% of all participants; among those seropositive at age 15‐16 years, 84% were predicted to remain so for ≥30 years. Conclusion : Most children vaccinated during early childhood available for sampling maintained seropositivity through age 15‐16 years; however, seropositivity was less frequent among those starting vaccination at age 6 months and among maternal antibody‐positive participants who started vaccination at age 12 months or 15 months; overall, our findings support current vaccine recommendations and continued follow‐up of this cohort. (H epatology 2016;63:703–711)
Re: Yvonne Vergouwe, Ewout W. Steyerberg, Richard S. Foster, et al. Predicting Retroperitoneal Histology in Postchemotherapy Testicular Germ Cell Cancer: A Model Update and Multicentre Validation with More Than 1000 Patients. Eur Urol 2007;51:424–32
Authors: Nahid Punjani, Nicholas Power, Eric Winquist
Journal: European Urology (2015)
Prevalence of HTLV-III Infection among New Haven, Connecticut, Parenteral Drug Abusers in 1982–1983
Authors: R D'Aquila, A B Williams, H D Kleber, A E Williams
Journal: New England Journal of Medicine (1986)

The acquired immunodeficiency syndrome (AIDS) is etiologically linked to human T-cell lymphotropic virus type III (HTLV-III).  Intravenous drug use is the primary known risk factor in 17% of US cases of AIDS.  The authors report the presence of HTLV-III antibody confirmed by Western blot assay in at least 10% of a group New Haven Connecticut parenteral drug abusers in 1982-1983.  The adequacy of using only enzyme linked immunosorbent assy (ELISA) testing in this risk group is questioned.  Serum specimens were collected from 283 persons who were a part of a study of on-A non-B hepatitis from March 1982 until July 1983.  All subjects had recently used drugs parenterally most were asymptomatic and many had moderate transaminase elevations and seropositivity for hepatitis B virus.  Serum samples were stored under coade at -20 degrees Centigrade and were tested annonymously by ELISA (Abbott Laboratoties) according to the manufacturers specifications.  Western blots were done with use of purified HTLV-III virion lysates prepared form infected H9 lymphocytes.  84 of the 283 samples (30%) were reactive on ELISA testing.  28 of the 84 ELISA-positive serum samples (33%) reacted with HTLV-III proteins on Western blots.  4 of these 28 samples were reactive only with p24.  The other 24 serum samples were reactive with the full spectrum of HTLV-III related peptides.  In all 148 cases of AIDS have been reported to the State of Connecticut Department of Health.  45 patients admitted intravenous drug use and in 31 cases it was the only known risk factor.  Previous reports have noted a high prevalence of ELISA seropositivity for HTLV-III to parenteral drug abusers in areas of both high and low apparent AIDS risk in such abusers.  Given the relatively high false positive rate of HTLV-III ELISA in low-risk groups and the known factors other than HTLV-III infection that account for some positive ELISAs it seems best for epidemiologic purposes to corroborate the high degree of HTLV-III ELISA seropositivity in parenteral drug abusers with a more specific test.  Only 2 earlier studies used Western blots in addition to ELISAs.  This study confirms that HTLV-III infection is not unusual in asymptomatic parenteral drug abusers in areas of the urban northeastern US despite the few reported AIDS cases in admitted parenteral drug abusers.  The high false-positive ELISA rate (67%) in this study and the high false-negative ELISA rate (57%) observed in another study suggest that ELISA alone is not a useful screening test for HTLV-III infection in parenteral drug abusers.