tbuckley/cabot-search huggingface dataset:
Association between genetic polymorphisms in <i>SLCO1B3</i> gene and response to ketoconazole (K) in men with castration-resistant prostate cancer (CRPC).
Authors: M. Taplin, M. Nakabayashi, L. Werner, M. Yang, W. Xie, T. Sun, M. Pomerantz, M. Freedman, G. M. Lee, P. Kantoff
Journal: Journal of Clinical Oncology (2010)

4557 Background: In a castrate state, synthesis of adrenal and intratumoral androgens is crucial for the survival of prostate cancer cells. K, a CYP17 lyase inhibitor, has been shown to have activity in CRPC. The organic anion transport polypeptide, SLCO1B3, is involved in steroid hormone uptake. Genetic variants have been shown to determine the amount of testosterone uptake into cells (slow versus rapid transporters) and in turn affect response to primary androgen deprivation therapy. We hypothesized that genetic variations in SLCO1B3 influence response to K in patients with CRPC. Methods: Using our CRIS database, we identified patients with CRPC treated with K. Two previously described single nucleotide polymorphisms (SNPs) in SLCO1B3, rs4149117 (334T>G; Ser112Ala) and rs7311358 (669G>A; Met233Ile) were analyzed with respect to their impact on % PSA decline, time to progression (TTP) and overall survival (OS) with K. To define TTP, we used both modified PSA working group criteria 2 (PSAWG2) (N=179) and another criteria defined as stopping K due to rising PSA at their physicians’ request but while not meeting the PSAWG2 progression criteria (N=259). Results: A cohort of 329 CRPC patients of European ancestry was genotyped for the 2 selected SNPs. Median PSA at start of K was 21.96 ng/ml (q1-q3: 6.01-66.58). 103 men (31%) experienced a PSA decline ≥ 50%. A total of 217 men (66%) had died at the time of analysis. The numbers of subjects carrying GG and TT/GT genotypes for SNP rs419117 were 213 and 111, respectively, and the ones carrying AA and AG/GG genotypes for rs731358 were 213 and 116, respectively. The only significant association made was between the G allele of rs4149117 in SLCO1B3 (believed to be slow testosterone transporter) and longer TTP (HR=1.31, 95% CI: 1.02- 1.70, p=0.034). Conclusions: The findings suggest that the rapid T uptake induced by germline genetic variation of the androgen transporter gene shortens duration of response to K and perhaps other CYP 17 lyase inhibitors in men with CRPC. Further analysis and validation of data are needed. No significant financial relationships to disclose.
Microvessel density, endothelial cell proliferation and tumour cell proliferation in human colorectal adenocarcinomas
Authors: P.B. Vermeulen, D. Verhoeven, G. Hubens, E. Van Marck, G. Goovaerts, M. Huyghe, E.A. De Bruijn, A.T. Van Oosterom, L.Y. Dirix
Journal: Annals of Oncology (1995)
Augmented vascular regeneration byrransplanted human stem cell-derived vascular progenitor cells with adrenomedullin
Authors: Ting-Hsing Chao, H Itoh, K Yamahara, M Sone, K Miyashita, K Park, N Oyamada, N Sawada, D Taura, H Tsujimoto, A Nonoguchi, K Nakao
Journal: Journal of the American College of Cardiology (2006)
Therapeutics of the Gastro-Intestinal Tract.
Journal: JAMA (1913)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Investigation of the relationship between serum hepcidin and prohepcidin in anemia of cancer (AoC) patients with the anemia of inflammation (AI)
Authors: B. J. Sasu, H. Li, M. J. Rose, T. C. Arvedson, L. Goyal
Journal: Journal of Clinical Oncology (2008)

20644 Background: The anemia observed in cancer patients is complex and may result from a combination of causes; iron deficiency, inflammation (AI), toxicity related to therapy, marrow infiltration, dyserythropoiesis and others. Determining effective anemia treatment can therefore be complex, requiring a combination of diagnostic tests. Algorithms exist to quantify the contribution of iron deficiency versus AI but are complex and as yet unvalidated. Hepcidin, a peptide reducing iron availability for erythropoiesis is induced by inflammation, and elevated hepcidin levels may underlie functional iron deficiency in cancer patients. Hepcidin levels have been suggested as an appropriate marker of AI but in the absence of a readily available serum hepcidin assay, a commercial assay to detect prohepcidin (DRG ELISA) has been used. Several studies have attempted to establish a relationship between prohepcidin and inflammation. Here we have contrasted the quantification of prohepcidin with mature hepcidin to define the role of either in the etiology of AoC. Methods: Sera from healthy controls (n=33) and AoC (n=41, Hb ≤10g/dL) were analyzed. Soluble transferrin receptor (sTfR), iron parameters and C-reactive protein (CRP) were used to stratify patients as AI (n=15), iron deficiency anemia (IDA, n=15), mixed anemia (markers of AI and IDA, n=9) or anemia of another origin (n=2). Hepcidin concentration was assessed by a sensitive, quantitative HPLC-MS/MS method. Prohepcidin was measured by a commercial ELISA (DRG). Results: Hepcidin was elevated in AoC patients compared to normal donors (28±47 versus 6±9ng/ml). Hepcidin levels in subgroups of AoC were as follows: AI = 64±63ng/ml; mixed anemia = 10±15ng/ml; IDA = 2±4ng/ml; anemia of another origin = 5±7ng/ml. Prohepcidin levels were largely unrelated to anemia category (332±186; 311±156; 295±129 and 535±414ng/ml for above categories, respectively). Conclusions: These studies suggest that serum hepcidin but not prohepcidin can be used in a new diagnostic algorithm to identify patients where hepcidin may be a marker of inflammatory AoC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Amgen Amgen
Annals On Being a Doctor Story Slam - Christmas on Call
Authors: Michael Knight
Journal: Annals of Internal Medicine (2016)

Web Exclusives19 January 2016Annals On Being a Doctor Story Slam - Christmas on CallFREEMichael Knight, MDMichael Knight, MDFrom the Robert Wood Johnson Foundation Clinical Scholars Program, University of Pennsylvania, and Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/V15-0023 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals On Being a Doctor Story Slam - Christmas on Call This story, "Christmas on Call," by Dr. Michael Knight, is from the Annals On Being a Doctor Story Slam held on 18 November 2015 in Philadelphia, with support from the Josiah Macy Jr. Foundation. (Duration 4:53)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals On Being a Doctor Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: From the Robert Wood Johnson Foundation Clinical Scholars Program, University of Pennsylvania, and Crescenz Veterans Affairs Medical Center, Philadelphia, Pennsylvania.Note: This story is from the Annals On Being a Doctor Story Slam held on 18 November 2015 in Philadelphia, with support from the Josiah Macy Jr. Foundation.Corresponding Author: Michael Knight, MD, Robert Wood Johnson Foundation Clinical Scholars Program, University of Pennsylvania, and Crescenz Veterans Affairs Medical Center, Philadelphia, PA 19104; e-mail, [email protected]med.upenn.edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 January 2016Volume 164, Issue 2Page: SS12 ePublished: 19 January 2016 Issue Published: 19 January 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.Loading ...
Cytidine Deaminase (CD) and Dihydropyrimidine Dehydrogenase (DPD) single nucleotide polymorphisms (SNPs) in capecitabine-treated colorectal cancer (CRC)
Authors: R. Ibeas, M. Monzo, I. Moreno, R. Hernandez, M. Campayo, J. Pie, D. Fuster, G. Torres, A. Alcaide, J. Jove
Journal: Journal of Clinical Oncology (2004)

3662 Background: CD is an enzyme that metabolizes 5'DeoxyFluorocytidine (5'dFCR) to 5' DeoxyFluorouridine (5'dFUR), which converts to 5-FU in the presence of Thymidine Phosphorilase (TP). The rate-limiting enzyme in 5-FU catabolims is DPD, which converts 5-FU to dihydrofluorouracil (DHFU). We analyzed CD and DPD SNPs and correlate the results with toxicity and response in capecitabine-treated CRC patients (pts) Methods: 33 CRC pts recruited between August 2002 and September 2003 were treated with capecetabine. DNA was obtained from peripheral blood cells at baseline, and allelic discrimination assay with ABI Prism 7700 was used to analyze SNPs at CD Lys27Gln, DPD1 Arg16Cys and DPD2 Ile530Val. Results: Pts characteristics: age 61 (44–77); all pts, PS 0–1; 26 stage IV pts received capecitabine-based combination chemotherapy, 7 stage II/III pts received capecitabine plus radiotherapy. 33 pts evaluable for toxicity. Pts with CD genotypes A/C and C/C showed greater hematological toxicity (61%) than those with A/A (29%) (p=0.08). DPD1 genotypes C/C showed greater skin toxicity (40%) than those with C/T and T/T (0%) (p=0.01). 24 stage IV pts evaluable for response. Pts with CD genotype A/A had longer median survival (11.5 mos) than those with A/C and C/C (5 m) (Gehan-Wilcoxon p=0.0009). Conclusions: CD A/C+C/C and DPD1 C/C may be related to greater toxicity, and CD A/A may be a predictive marker of survival in capecitabine-treated CRC pts. Studies with a larger number of patients should be carried out to confirm these results. No significant financial relationships to disclose.
Risk of congestive heart failure with VEGF-targeted therapy: A systematic review and meta-analysis of clinical trials.
Authors: F. A. Schutz, Y. Je, G. R. Azzi, T. K. Choueiri
Journal: Journal of Clinical Oncology (2010)

4602 Background: Vascular endothelial growth factor (VEGF)-targeted therapies have shown to be active in several malignancies. Pre-clinical evidence suggests that VEGF plays a role in the homeostasis and regeneration of the myocardium. Some trials with VEGF inhibitors have reported congestive heart failure (CHF), although the overall incidence and relative risk (RR) remains unclear. We did a meta-analysis to determine the risk associated with the use of Food and Drug Administration (FDA)-approved VEGF targeted agents. Methods: The databases of Medline were searched for articles from 1966 to Dec. 2009. Abstracts presented at the American Society of Clinical Oncology (ASCO) meetings were searched for relevant clinical trials. Randomized phase II or III trials with bevacizumab (BEV), sunitinib (SUN), sorafenib (SOR) or pazopanib (PAZ), reporting grade 3/4 CHF, were included in the analysis. Statistical analyses were conducted to calculate the summary incidence, RR and 95% confidence intervals (CI), using random-effects or fixed-effects models based on the heterogeneity of included studies. Results: A total of 6,586 patients from 11 randomized trials were included. We found no PAZ or SOR randomized trials reporting CHF. Overall incidence for high grade CHF with BEV and SUN- was 1.8% (RR 1.98; 95% CI, 1.18-3.35, p=.01). Stratified analyses by drug type or underlying malignancy demonstrated a higher RR with SUN, RR 3.04 (1.07-8.64, p=.036) vs. BEV, RR 1.72 (0.94-3.15, p=.080), and a higher RR with breast cancer, RR 3.33 (1.41-7.82, p=.006) vs. non- breast cancer patients, RR 1.46 (0.75-2.82, p=.27). No significant differences by drug type or underlying malignancy were found (p=.60 and p=.23, respectively). No evidence of publication bias or heterogeneity among studies was detected. Conclusions: This is the first meta- analysis to show that BEV and SUN treatment is associated with an increased risk of CHF. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories, Agennix, Bayer/Onyx Pharmaceuticals, Genentech, GlaxoSmithKline, Novartis, Pfizer
Abstract 11889: Impact of Beta-blockers on Long-term Survival in the Reperfusion Era
Authors: Viviane Nguyen, Simon Kouz, Jean-Claude Tardif, Marc Afilalo, Erick Schampaert, Michel Nguyen, Martine Montigny, Stephane Rinfret, Mark J Eisenberg, Claudia Blais, Jean-Pierre Dery, Claude Lauzon, Thao Huynh
Journal: Circulation (2012)

Background: Although benefits of beta-blockers (BB) have been shown prior to the reperfusion era, it remains unclear whether BB improve survival in patients with ST-segment elevation myocardial inf...
Predictors of the Development of Post-Thrombotic Syndrome after Acute Symptomatic Deep Vein Thrombosis: Two-Year Results from a Canadian Multicenter Prospective Cohort Study (The VETO Study).
Authors: Susan R. Kahn, Thierry Ducruet, Louise Arsenault, Marie Jose Miron, Andre Roussin, Sylvie Desmarais, France Joyal, Jeannine Kassis, Susan Solymoss, Jeffrey S. Ginsberg, Louis Desjardins, Mira Johri, Donna L. Lamping, Ian Shrier
Journal: Blood (2005)
Monoclonal antibodies targeting cell surface deposited complement fragment C3d potentiate cancer immunotherapy and eliminate antigen loss variants
Authors: Martin Skarzynski, Margeret Lindorfer, Vicent Butera, Berengere Vire, Mohammed Farooqui, Christoph Rader, Ronald Taylor, Adrian Wiestner
Journal: Journal for ImmunoTherapy of Cancer (2015)

Meeting abstracts Treatment-induced loss of targeted cell surface antigens through trogocytosis or internalization reduces efficacy of monoclonal antibody (mAb) therapy of cancer. However, cells that escape therapy mediated by complement-fixing mAbs carry covalently deposited complement activation
The biologic therapy of prostate cancer using plasminogen activator inhibitor-1 (PAI-1)
Authors: S. Chen, D. O. Henry, M. K. Wong
Journal: Journal of Clinical Oncology (2006)

14596 Background: Treating prostate cancer through the expression of intrinsic biologic modifiers is a relatively unexplored aspect of prostate cancer therapy. Plasminogen Activator Inhibitor-1 (PAI-1) is expressed at low levels in prostate cancer cells. PAI-1 is both an anti-angiogenesis agent, and also potently inhibits tumor proteases responsible for tumor invasion and metastases such as uPA and tPA. Thus we hypothesized that stimulation of tumor endogenous PAI-1 would result in a particularly powerful and profound prostate cancer regression. We present proof-of-concept from our experimental models that demonstrate significant tumor regression in experimental prostate tumors and supports this hypothesis. Methods and Results: Human prostate adenocarcinoma (PC3 cell line) xenograft tumors engineered to conditionally express either PAI-1 or Green Fluorescent Protein (GFP, control) were used to test our hypothesis. Stable cell lines were created that conditionally express either GFP or PAI-1 under the regulation of a doxycycline-responsive promoter (Tet-On). Thus gene expression is switched on in the presence of doxycycline. PC3 tumors were inoculated and allowed to reach at least 200 mm 3 in size whereby the tumor-bearing mice were given doxycycline-doped drinking water. Genes were significantly turned on within 48 hours as monitored by the appearance of a GFP signal in control mice. The induction of PAI-1 results in significant inhibition of tumor growth as compared to GFP control. Importantly, in vitro induction of PAI-1 expression in PC-3 has no direct effects on cell growth as compared to any PC-3 control. Histological analysis of these tumors revealed a rich nexus of fine angiogenic vessels at the interface between control tumors and surrounding stroma. PAI-1 secreting tumors were significantly smaller and were pale, bland, and lacked peritumoral vessels. Protease activity measured by in-situ zymography directly on these tumors revealed that this was significantly reduced in PAI-1 expressing tumors as compared to GFP controls. Conclusion: PAI-1 expression results in tumor inhibition through direct anti-angiogenic effects and inhibition of tumor protease activity. No significant financial relationships to disclose.
Impaired insulin action in the liver, but not in adipose tissue or muscle, is a distinct metabolic feature of impaired fasting glucose in obese humans
Authors: Kasper W. ter Horst, Pim W. Gilijamse, Mariette T. Ackermans, Maarten R. Soeters, Max Nieuwdorp, Johannes A. Romijn, Mireille J. Serlie
Journal: Metabolism (2016)
Amantadine in Uncomplicated Influenza A
Authors: R G Stevens, J A Lee, S H Moolgavkar
Journal: New England Journal of Medicine (1980)

Recently Beral et al. reported an association between oral contraceptives and malignant melanoma in a population of California women belonging to a health-maintenance organization.  The findings were based on an interim analysis of an ongoing prospective study that relied on small numbers and suggested a small relative risk.  We have investigated this question from a different perspective.  Since OCs have been widely used for almost 20 years we reasoned that if they greatly increased the risk of malignant melanoma the incidence of and mortality from the disease in women 15-44 years old should have increased relative to background changes in rates during the past 2 decades.  Rates have been increasing rapidly in the U.S. and interpretation of specific changes is therefore difficult.  OCs were introduced in the early 1960s and 1 way in which background changes in rates of disease in women might be gauged is to compare the temporal trends in disease rates among females with those among males.  We learned the age-specific incidence of melanoma in 15-44 year olds of both sexes in Connecticut (1935-1974) Denmark (1943-1972) and Finland (1953-1974) and the mortality from melanoma in the U.S. (1951-1975) Canada (1951-1975) and England and Wales (1951-1975).  Data on each population covered at least 10 years before and after the introduction of OCs.  Using methodology similar to that used to analyze the incidence of breast cancer we examined melanoma rates and tested the hypothesis that rates in males were a constant multiple of rates in females over the period of study.  Our findings were consistent with this hypothesis.  Thus there was no perturbation in rates in females relative to those in males at or after the period of OC introduction.  We conclude that either the relative risk associated with these drugs is very close to 1 or the latent period of malignant melanoma is very long.  (full text)
Somatic Mutations in Splicing Factor 3b, Subunit 1 (SF3B1) Are a Useful Biomarker to Differentiate Between Clonal and Non-Clonal Causes of Sideroblastic Anemia
Authors: Valeria Visconte, Ali Tabarroki, Christopher Gerace, Karam Al-Issa, Eric D. Hsi, Heesun J. Rogers, Mikkael A. Sekeres, Bernard J. Silver, Alan E. Lichtin, Sudipto Mukherjee, Ramon V. Tiu
Journal: Blood (2014)
Randomized phase II study of cisplatin plus gemcitabine administered either as short infusion or at a fixed dose rate in non-small cell lung cancer (NSCLC)
Authors: J. R. Pereira, L. Fein, P. Carvajal, A. Giglio, C. Blajman, E. Richardet, G. Schwartsmann, M. Orlando, B. J. Hall, M. Van Kooten
Journal: Journal of Clinical Oncology (2006)

17037 Background: Previous studies have indicated that, in combination with cisplatin (cis), fixed dose rate gemcitabine (gem) may be more efficacious than standard infusion gem. This open-label, randomized, multicenter Phase II study (B9E-LA-S350) was aimed to compare the efficacy and safety of these regimens as treatment for advanced NSCLC in Latin American patients (pts). Methods: Major eligibility criteria included histologic/cytologic diagnosis of stage IIIB/IV NSCLC not amenable to curative surgery; and at least one measurable lesion. Pts were randomized to receive up to 6 cycles of treatment with cis 75 mg/m 2 on Day 1 plus either gem 1000 mg/m 2 over 30 min on Days 1 and 8 of a 21-day cycle (standard arm) or gem 1000 mg/m 2 at a fixed dose rate of 10 mg/ m 2 /min on Days 1 and 8 of a 21-day cycle (FDR arm). The primary endpoint was the objective response rate (ORR; assessed by RECIST criteria) and secondary endpoints included overall survival (OS), progression-free survival (PFS), duration of tumor response (TR), and toxicity. Results: The results from this interim analysis assessed all objectives. Sixty-four pts were randomized to treatment (N = 33 standard arm; N = 31 FDR arm): 22 females; mean age 60 ± 9 yrs; 20% stage IIIB, 80% stage IV. In the standard arm, 9 (27%) pts responded (CR or PR) compared to 6 (20%) pts in the FDR arm (Odds ratio: 0.67, 95% CI 0.21–2.2, p = .56). As shown in the table below, there were no statistically significant differences in median ORR, OS, PFS, TR times, and Grade (G) 3/4 toxicities. Conclusions: The standard and FDR gem and cis treatment regimens produced similar results for both efficacy and toxicity in this patient population. This trial does not support the use of a FDR administration of gem in Latin American pts with NSCLC. [Table: see text] [Table: see text]