tbuckley/cabot-search huggingface dataset:
Personalized Genetic Risk Counseling to Motivate Diabetes Prevention
Authors: Richard W. Grant, Kelsey E. O’Brien, Jessica L. Waxler, Jason L. Vassy, Linda M. Delahanty, Laurie G. Bissett, Robert C. Green, Katherine G. Stember, Candace Guiducci, Elyse R. Park, Jose C. Florez, James B. Meigs
Journal: Diabetes Care (2012)

OBJECTIVE To examine whether diabetes genetic risk testing and counseling can improve diabetes prevention behaviors. RESEARCH DESIGN AND METHODS We conducted a randomized trial of diabetes genetic risk counseling among overweight patients at increased phenotypic risk for type 2 diabetes. Participants were randomly allocated to genetic testing versus no testing. Genetic risk was calculated by summing 36 single nucleotide polymorphisms associated with type 2 diabetes. Participants in the top and bottom score quartiles received individual genetic counseling before being enrolled with untested control participants in a 12-week, validated, diabetes prevention program. Middle-risk quartile participants were not studied further. We examined the effect of this genetic counseling intervention on patient self-reported attitudes, program attendance, and weight loss, separately comparing higher-risk and lower-risk result recipients with control participants. RESULTS The 108 participants enrolled in the diabetes prevention program included 42 participants at higher diabetes genetic risk, 32 at lower diabetes genetic risk, and 34 untested control subjects. Mean age was 57.9 ± 10.6 years, 61% were men, and average BMI was 34.8 kg/m2, with no differences among randomization groups. Participants attended 6.8 ± 4.3 group sessions and lost 8.5 ± 10.1 pounds, with 33 of 108 (30.6%) losing ≥5% body weight. There were few statistically significant differences in self-reported motivation, program attendance, or mean weight loss when higher-risk recipients and lower-risk recipients were compared with control subjects (P &amp;gt; 0.05 for all but one comparison). CONCLUSIONS Diabetes genetic risk counseling with currently available variants does not significantly alter self-reported motivation or prevention program adherence for overweight individuals at risk for diabetes.
Characterization of novel and complex genomic aberrations in glioblastoma using a 32K BAC array
Authors: Helena Nord, Christian Hartmann, Robin Andersson, Uwe Menzel, Susan Pfeifer, Arkadiusz Piotrowski, Adam Bogdan, Wojciech Kloc, Johanna Sandgren, Tommie Olofsson, Göran Hesselager, Erik Blomquist, Jan Komorowski, Andreas von Deimling, Carl E.G. Bruder, Jan P. Dumanski, Teresita Díaz de Ståhl
Journal: Neuro-Oncology (2009)

Glioblastomas (GBs) are malignant CNS tumors often associated with devastating symptoms. Patients with GB have a very poor prognosis, and despite treatment, most of them die within 12 months from diagnosis. Several pathways, such as the RAS, tumor protein 53 (TP53), and phosphoinositide kinase 3 (PIK3) pathways, as well as the cell cycle control pathway, have been identified to be disrupted in this tumor. However, emerging data suggest that these aberrations represent only a fraction of the genetic changes involved in gliomagenesis. In this study, we have applied a 32K clone-based genomic array, covering 99% of the current assembly of the human genome, to the detailed genetic profiling of a set of 78 GBs. Complex patterns of aberrations, including high and narrow copy number amplicons, as well as a number of homozygously deleted loci, were identified. Amplicons that varied both in number (three on average) and in size (1.4 Mb on average) were frequently detected (81% of the samples). The loci encompassed not only previously reported oncogenes (EGFR, PDGFRA, MDM2, and CDK4) but also numerous novel oncogenes as GRB10, MKLN1, PPARGC1A, HGF, NAV3, CNTN1, SYT1, and ADAMTSL3. BNC2, PTPLAD2, and PTPRE, on the other hand, represent novel candidate tumor suppressor genes encompassed within homozygously deleted loci. Many of these genes are already linked to several forms of cancer; others represent new candidate genes that may serve as prognostic markers or even as therapeutic targets in the future. The large individual variation observed between the samples demonstrates the underlying complexity of the disease and strengthens the demand for an individualized therapy based on the genetic profile of the patient.
Docetaxel plus Prednisone or Mitoxantrone plus Prednisone for Advanced Prostate Cancer
Authors: Ian F. Tannock, Ronald de Wit, William R. Berry, Jozsef Horti, Anna Pluzanska, Kim N. Chi, Stephane Oudard, Christine Théodore, Nicholas D. James, Ingela Turesson, Mark A. Rosenthal, Mario A. Eisenberger
Journal: New England Journal of Medicine (2004)

Mitoxantrone plus prednisone reduces pain and improves the quality of life in men with advanced, hormone-refractory prostate cancer, but it does not improve survival. We compared such treatment with docetaxel plus prednisone in men with this disease.From March 2000 through June 2002, 1006 men with metastatic hormone-refractory prostate cancer received 5 mg of prednisone twice daily and were randomly assigned to receive 12 mg of mitoxantrone per square meter of body-surface area every three weeks, 75 mg of docetaxel per square meter every three weeks, or 30 mg of docetaxel per square meter weekly for five of every six weeks. The primary end point was overall survival. Secondary end points were pain, prostate-specific antigen (PSA) levels, and the quality of life. All statistical comparisons were against mitoxantrone.As compared with the men in the mitoxantrone group, men in the group given docetaxel every three weeks had a hazard ratio for death of 0.76 (95 percent confidence interval, 0.62 to 0.94; P=0.009 by the stratified log-rank test) and those given weekly docetaxel had a hazard ratio for death of 0.91 (95 percent confidence interval, 0.75 to 1.11; P=0.36). The median survival was 16.5 months in the mitoxantrone group, 18.9 months in the group given docetaxel every 3 weeks, and 17.4 months in the group given weekly docetaxel. Among these three groups, 32 percent, 45 percent, and 48 percent of men, respectively, had at least a 50 percent decrease in the serum PSA level (P<0.001 for both comparisons with mitoxantrone); 22 percent, 35 percent (P=0.01), and 31 percent (P=0.08) had predefined reductions in pain; and 13 percent, 22 percent (P=0.009), and 23 percent (P=0.005) had improvements in the quality of life. Adverse events were also more common in the groups that received docetaxel.When given with prednisone, treatment with docetaxel every three weeks led to superior survival and improved rates of response in terms of pain, serum PSA level, and quality of life, as compared with mitoxantrone plus prednisone.
Dapsone for autoimmune thrombocytopenic purpura
Authors: Bertrand Godeau, Eric Oksenhendler, Philippe Bierling
Journal: American Journal of Hematology (1993)

Abstract Twenty‐one human immunodeficiency virus (HIV)‐free and six HIV‐infected adults with autoimmune thrombocytopenic purpura (AITP) were treated with dapsone (100 mg/day). A response was observed in 13 patients (median platelet count before 25 × 10 9 /L, range 3–49; after 109 × 10 9 /L, range 69–241). Thrombocytopenia recurred in four of the responders in whom dapsone was discontinued. No response was observed in 12 patients. Dapsone had to be withdrawn after two weeks of treatment in the remaining two patients and after six to eight weeks in three other patients due to intolerance. No serious hematological complications were observed. These results confirm that dapsone is a safe, inexpensive, and effective treatment of AITP. © 1993 Wiley‐Liss, Inc.
Neonatal pemphigus vulgaris: role of passively transferred pemphigus antibodies
Authors: B. MONCADA, S. KETTELSEN, J.L. HERNANDEZ-MOCTEZUMA, F. RAMIREZ
Journal: British Journal of Dermatology (1982)

Journal Article Neonatal pemphigus vulgaris: role of passively transferred pemphigus antibodies Get access B. MONCADA, B. MONCADA Central Hospital, University of San Luis Potosi, School of Medicine, San Luis Potosi, Mexico B.Moncada, M.D., University of San Luis Potosi, School of Medicine, V. Carranza 2405, San Luis Potosi, S.L.P., Mexico. Search for other works by this author on: Oxford Academic Google Scholar S. KETTELSEN, S. KETTELSEN Central Hospital, University of San Luis Potosi, School of Medicine, San Luis Potosi, Mexico Search for other works by this author on: Oxford Academic Google Scholar J.L. HERNÁNDEZ‐MOCTEZUMA, J.L. HERNÁNDEZ‐MOCTEZUMA Central Hospital, University of San Luis Potosi, School of Medicine, San Luis Potosi, Mexico Search for other works by this author on: Oxford Academic Google Scholar F. RAMIREZ F. RAMIREZ Central Hospital, University of San Luis Potosi, School of Medicine, San Luis Potosi, Mexico Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 106, Issue 4, 1 April 1982, Pages 465–468, https://doi.org/10.1111/j.1365-2133.1982.tb04542.x Published: 01 April 1982 Article history Accepted: 20 June 1981 Published: 01 April 1982
A genome-wide map of aberrantly expressed chromosomal islands in colorectal cancer.
Authors: Eike Staub, Jörn Gröne, Detlev Mennerich, Stefan Röpcke, Irina Klamann, Bernd Hinzmann, Esmeralda Castanos-Velez, Benno Mann, Christian Pilarsky, Thomas Brümmendorf, Birgit Weber, Heinz-Johannes Buhr, André Rosenthal
Journal: Molecular Cancer (2006)

Cancer development is accompanied by genetic phenomena like deletion and amplification of chromosome parts or alterations of chromatin structure. It is expected that these mechanisms have a strong effect on regional gene expression.We investigated genome-wide gene expression in colorectal carcinoma (CRC) and normal epithelial tissues from 25 patients using oligonucleotide arrays. This allowed us to identify 81 distinct chromosomal islands with aberrant gene expression. Of these, 38 islands show a gain in expression and 43 a loss of expression. In total, 7.892 genes (25.3% of all human genes) are located in aberrantly expressed islands. Many chromosomal regions that are linked to hereditary colorectal cancer show deregulated expression. Also, many known tumor genes localize to chromosomal islands of misregulated expression in CRC.An extensive comparison with published CGH data suggests that chromosomal regions known for frequent deletions in colon cancer tend to show reduced expression. In contrast, regions that are often amplified in colorectal tumors exhibit heterogeneous expression patterns: even show a decrease of mRNA expression. Because for several islands of deregulated expression chromosomal aberrations have never been observed, we speculate that additional mechanisms (like abnormal states of regional chromatin) also have a substantial impact on the formation of co-expression islands in colorectal carcinoma.
Vestibulocochlear dysfunction in a patient with rheumatoid disease and vasculitis.
Authors: P K Merrin, D G Macfarlane
Journal: Annals of the Rheumatic Diseases (1991)

The case is described of a patient with rheumatoid disease and evidence of vasculitis who developed acute vestibuloauditory dysfunction resulting in total deafness, which was assumed to be secondary to a vasculitic process affecting the vestibulocochlear nerve. Treatment of the underlying vasculitic process, despite effecting a general improvement of the patient9s rheumatoid disease, did not significantly improve the auditory dysfunction.
Coronary Microvascular Dysfunction and Prognosis in Hypertrophic Cardiomyopathy
Authors: Franco Cecchi, Iacopo Olivotto, Roberto Gistri, Roberto Lorenzoni, Giampaolo Chiriatti, Paolo G. Camici
Journal: New England Journal of Medicine (2003)

Microvascular dysfunction, reflected by an inadequate increase in myocardial blood flow in response to dipyridamole infusion, is a recognized feature of hypertrophic cardiomyopathy. Its long-term effect on the prognosis is unknown. We prospectively evaluated a cohort of patients with hypertrophic cardiomyopathy after they had undergone quantitative assessment of myocardial blood flow by positron-emission tomography (PET).Fifty-one patients (New York Heart Association class I or II) were followed for a mean (+/-SD) of 8.1+/-2.1 years after PET. Twelve subjects with atypical chest pain served as controls. Measurement of flow was performed at base line and after the infusion of the coronary vasodilator dipyridamole, with the use of nitrogen-13-labeled ammonia. Patients were then divided into three equal groups with increasing values of myocardial blood flow.The response of myocardial blood flow to dipyridamole was severely blunted in the patients, as compared with the controls (1.50+/-0.69 vs. 2.71+/-0.94 ml per minute per gram of tissue, P<0.001). Sixteen patients (31 percent) had an unfavorable outcome (death from cardiovascular causes, progression to New York Heart Association class III or IV, or sustained ventricular arrhythmias requiring the implantation of a cardioverter-defibrillator) 2.2 to 9.1 years after PET. Reduced blood flow in response to dipyridamole was strongly associated with an unfavorable outcome. Multivariate analysis showed that among patients in the lowest of the three flow groups the age-adjusted relative hazard of death from cardiovascular causes was 9.6 (P=0.02) and the relative hazard of an unfavorable outcome (a combined end point) was 20.1 (P=0.003), as compared with patients in the two other flow groups. Specifically, all four patients who died from heart failure and three of five who died suddenly were in this subgroup.In patients with hypertrophic cardiomyopathy, the degree of microvascular dysfunction is a strong, independent predictor of clinical deterioration and death. Severe microvascular dysfunction is often present in patients with mild or no symptoms and may precede clinical deterioration by years.
AntiMüllerian Hormone: New Perspectives for a Sexist Molecule
Authors: NATHALIE JOSSO
Journal: Endocrine Reviews (1986)

ANTIMÜLLERIA hormone (AMH) started out as a concept and a string of terms. Jost (1) was the first to suggest that regression of Müllerian ducts in male fetuses is mediated by a discrete testicular factor, different from testosterone. He named this factor hormone inhibitrice or antifeminine factor because it inhibits the development of female characteristics of fetal genital ducts in contrast to testosterone, which promotes the differentiation of male-specific organs. Other names given this molecule are Müllerian inhibitor, Jost's factor X, Müllerian-inhibitory factor (MIF), or Müllerian-inhibiting substance (MIS). Our group prefers AMH, and, for the sake of simplicity, we use this term in this review. Research in this area, triggered initially by the development of an in vitro bioassay for the hormone (2), has generated more data than can be incorporated in a review of reasonable length. This article will focus on issues not covered by previous reviews of the subject (3, 4), and aspects which have come to light after the purification of AMH to homogeneity (5) and the cloning of its complementary DNA (cDNA) (6) and gene (7).
MicroRNA Signature Predicts Survival and Relapse in Lung Cancer
Authors: Sung-Liang Yu, Hsuan-Yu Chen, Gee-Chen Chang, Chih-Yi Chen, Huei-Wen Chen, Sher Singh, Chiou-Ling Cheng, Chong-Jen Yu, Yung-Chie Lee, Han-Shiang Chen, Te-Jen Su, Ching-Cheng Chiang, Han-Ni Li, Qi-Sheng Hong, Hsin-Yuan Su, Chun-Chieh Chen, Wan-Jiun Chen, Chun-Chi Liu, Wing-Kai Chan, Wei J. Chen, Ker-Chau Li, Jeremy J.W. Chen, Pan-Chyr Yang
Journal: Cancer Cell (2008)
Claudin-1 overexpression in intestinal epithelial cells enhances susceptibility to adenamatous polyposis coli-mediated colon tumorigenesis
Authors: Jillian L Pope, Rizwan Ahmad, Ajaz A Bhat, Mary K Washington, Amar B Singh, Punita Dhawan
Journal: Molecular Cancer (2014)

The tight junction protein Claudin-1, a claudin family member, has been implicated in several gastro-intestinal pathologies including inflammatory bowel disease (IBD) and colorectal cancer (CRC). In this regard, we have demonstrated that claudin-1 expression in colon cancer cells potentiates their tumorigenic ability while in vivo expression of claudin-1 in the intestinal epithelial cells (IECs) promotes Notch-activation, inhibits goblet cell differentiation and renders susceptibility to mucosal inflammation. Notably, a key role of inflammation in colon cancer progression is being appreciated. Therefore, we examined whether inflammation plays an important role in claudin-1-dependent upregulation of colon carcinogenesis. APCmin mice were crossed with Villin-claudin-1 transgenic mice to generate APC-Cldn1 mice. H&E stained colon tissues were assessed for tumor number, size and histological grade. Additionally, microarray and qPCR analyses of colonic tumors were performed to assess molecular changes due to claudin-1 expression. APC-Cldn1 and APCmin controls were assessed for colonic permeability via rectal administration of FITC-dextran, and bacterial translocation via qPCR analysis of 16S rDNA. Claudin-1 overexpression in APCmin mice significantly increased (~4-fold) colonic tumor growth and size, and decreased survival. Furthermore, transcriptome analysis supported upregulated proliferation, and increased Wnt and Notch-signaling in APC-Cldn1 mice. APC-Cldn1 mice also demonstrated inhibition of mucosal defense genes while expression of pro-inflammatory genes was sharply upregulated, especially the IL-23/IL-17 signaling. We predict that increased Notch/Wnt-signaling underlie the early onset of adenoma formation in APC-Cldn1 mice. An increase in mucosal permeability due to the adenomas and the inherent barrier defect in these mice further facilitate bacterial translocation into the mucosa to induce inflammation, which in turn promote the tumorigenesis. Taken together, these results confirm the role of claudin-1 as a promoter of colon tumorigenesis and further identify the role of the dysregulated antigen-tumor interaction and inflammation in claudin-1-dependent upregulation of colon tumorigenesis.
Effect of candesartan on prevention (DIRECT-Prevent 1) and progression (DIRECT-Protect 1) of retinopathy in type 1 diabetes: randomised, placebo-controlled trials
Authors: Nish Chaturvedi, Massimo Porta, Ronald Klein, Trevor Orchard, John Fuller, Hans Henrik Parving, Rudy Bilous, Anne Katrin Sjølie
Journal: The Lancet (2008)
Concerns About Cancer Risk and Experiences With Genetic Testing in a Diverse Population of Patients With Breast Cancer
Authors: Reshma Jagsi, Kent A. Griffith, Allison W. Kurian, Monica Morrow, Ann S. Hamilton, John J. Graff, Steven J. Katz, Sarah T. Hawley
Journal: Journal of Clinical Oncology (2015)

To evaluate preferences for and experiences with genetic testing in a diverse cohort of patients with breast cancer identified through population-based registries, with attention to differences by race/ethnicity.We surveyed women diagnosed with nonmetastatic breast cancer from 2005 to 2007, as reported to the SEER registries of metropolitan Los Angeles and Detroit, about experiences with hereditary risk evaluation. Multivariable models evaluated correlates of a strong desire for genetic testing, unmet need for discussion with a health care professional, and receipt of testing.Among 1,536 patients who completed the survey, 35% expressed strong desire for genetic testing, 28% reported discussing testing with a health care professional, and 19% reported test receipt. Strong desire for testing was more common in younger women, Latinas, and those with family history. Minority patients were significantly more likely to have unmet need for discussion (failure to discuss genetic testing with a health professional when they had a strong desire for testing): odds ratios of 1.68, 2.44, and 7.39 for blacks, English-speaking Latinas, and Spanish-speaking Latinas compared with whites, respectively. Worry in the long-term survivorship period was higher among those with unmet need for discussion (48.7% v 24.9%; P <.001). Patients who received genetic testing were younger, less likely to be black, and more likely to have a family cancer history.Many patients, especially minorities, express a strong desire for genetic testing and may benefit from discussion to clarify risks. Clinicians should discuss genetic risk even with patients they perceive to be at low risk, as this may reduce worry.
Pathway-specific differences between tumor cell lines and normal and tumor tissue cells
Authors: Adam Ertel, Arun Verghese, Stephen W Byers, Michael Ochs, Aydin Tozeren
Journal: Molecular Cancer (2006)

Cell lines are used in experimental investigation of cancer but their capacity to represent tumor cells has yet to be quantified. The aim of the study was to identify significant alterations in pathway usage in cell lines in comparison with normal and tumor tissue.This study utilized a pathway-specific enrichment analysis of publicly accessible microarray data and quantified the gene expression differences between cell lines, tumor, and normal tissue cells for six different tissue types. KEGG pathways that are significantly different between cell lines and tumors, cell lines and normal tissues and tumor and normal tissue were identified through enrichment tests on gene lists obtained using Significance Analysis of Microarrays (SAM).Cellular pathways that were significantly upregulated in cell lines compared to tumor cells and normal cells of the same tissue type included ATP synthesis, cell communication, cell cycle, oxidative phosphorylation, purine, pyrimidine and pyruvate metabolism, and proteasome. Results on metabolic pathways suggested an increase in the velocity nucleotide metabolism and RNA production. Pathways that were downregulated in cell lines compared to tumor and normal tissue included cell communication, cell adhesion molecules (CAMs), and ECM-receptor interaction. Only a fraction of the significantly altered genes in tumor-to-normal comparison had similar expressions in cancer cell lines and tumor cells. These genes were tissue-specific and were distributed sparsely among multiple pathways.Significantly altered genes in tumors compared to normal tissue were largely tissue specific. Among these genes downregulation was a major trend. In contrast, cell lines contained large sets of significantly upregulated genes that were common to multiple tissue types. Pathway upregulation in cell lines was most pronounced over metabolic pathways including cell nucleotide metabolism and oxidative phosphorylation. Signaling pathways involved in adhesion and communication of cultured cancer cells were downregulated. The three way pathways comparison presented in this study brings light into the differences in the use of cellular pathways by tumor cells and cancer cell lines.
Processing and cross-presentation of individual HLA-A, -B, or -C epitopes from NY-ESO-1 or an HLA-A epitope for Melan-A differ according to the mode of antigen delivery
Authors: Neil C. Robson, Tristan McAlpine, Ashley J. Knights, Max Schnurr, Amanda Shin, Weisan Chen, Eugene Maraskovsky, Jonathan Cebon
Journal: Blood (2010)
Association Between Use of Unconventional Therapies and Conventional Medical Services
Authors: Benjamin G. Druss
Journal: JAMA (1999)

ContextThe terms alternative and complementary medicine suggest 2 contradictory possibilities.Whether individuals use unconventional therapies as a substitute for or as an "add on" to conventional medical treatments is uncertain.Objective To determine the association between use of unconventional therapies and conventional medical care in a national sample. Design, Setting, and ParticipantsThe 1996 Medical Expenditure Panel Survey was distributed to a probability sample of the noninstitutionalized civilian US population.Of 24 676 individuals responding (77.7% response rate), 16 068 adults 18 years or older were included in the analysis.