tbuckley/cabot-search huggingface dataset:
Association of critical losses in X chromosome with melanoma progression: An EORTC Melanoma group study
Authors: A. Spatz, C. Richon, B. Job, S. Michiels, A. Dumay, M. Barrois, D. Schadendorf, A. M. Eggermont, P. Dessen, J. J. Van den Oord
Journal: Journal of Clinical Oncology (2008)

9000 Background: Integrative studies correlating DNA changes and expression data are powerful to identify new genetic defects involved in tumor progression. In order to identify new pathways involved in melanoma progression and to better understand the gender effect on melanoma prognosis, we correlated micro-array comparative genomic hybridization (aCGH) with expression levels of several genes in frozen melanoma samples. Methods: 48 primary melanomas from 32 females and 16 males with a median follow-up of 4 years (range: 0.6–15 years), and for which DNA and RNA were co-extracted from the same frozen slices, were analysed using long oligo 244K aCGH slides (Agilent Technologies; Pao Alto). Each sample was hybridized in single versus a standard pool of DNA with matched sex. Expression data and copy number modifications were correlated and adjusted for the False Discovery Rate. The active or inactive X chromosome (chr) status was characterized by RNA FISH with a DNA probe detecting Xist RNA. The relative abundance of PPP2R3B gene was measured on 47pts by TaqMan Q-PCR normalized for 18S and RPLPO transcripts. The clinical endpoint was distant metastasis-free survival (DMFS) and logrank tests were applied to test prognostic effects. Results: A significant correlation between DNA copy number and mRNA level was detected for 1455 genes (FDR-adjusted p<0.05). Among the 32 females, losses in X chr were significantly associated with DMFS (logrank p=0.009). The affected X chr was always the inactive X (9/9). Among the 16 males, losses in the Y chr were associated with DMFS (p=0.015). Because of these findings in the X and Y chr, we screened all genes located on the X chr in females, escaping inactivation of the inactive X chr, as well as those located on the Y chr in males. The PPP2R3B gene, located on Xp22 in females and Yp11 in males, was the only known gene to fulfil all these criteria. Its normalized expression was significantly associated with DMFS (p=0.0008) even when gender, age, ulceration, and thickness were entered into the Cox multivariate model (p=0.0007). Conclusions: The aCGH study revealed a specific pattern of X and Y chromosome losses associated with tumor progression. The PPP2R3B gene appears as an important tumor suppression gene whose loss is associated with melanoma progression. No significant financial relationships to disclose.
Changing Epidemiology and Improved Survival In Patients With Waldenstrom Macroglobulinemia: Review Of Surveillance, Epidemiology, and End Results (SEER) Data
Authors: Sydney Nelson, Lawrence H. Boise, Jonathan L. Kaufman, Leonard T Heffner, Nishi N Shah, Mary Jo Lechowicz, Sagar Lonial, Ajay K. Nooka
Journal: Blood (2013)
PSA trend before and during salvage radiation therapy: Prognostic factor for biochemical control.
Authors: R. Hannan, J. Rossinow, Y. Chen, R. Kabarri, W. Skinner, E. M. Landau, M. Spierer, C. Guha, S. Kalnicki, M. Garg
Journal: Journal of Clinical Oncology (2010)

e15048 Background: Post-prostatectomy patients undergoing salvage radiation therapy (S-RT) has a high rate of biochemical recurrence (BR). Early initiation of androgen deprivation therapy has been shown to improve outcome in this cohort. We hypothesize that measuring the PSA trends during S-RT has predicitive value in defining a cohort of patients at higher risk of BR. Methods: Sixty-five patients with BR (ASTRO definition) were enrolled in this IRB-approved study. Patients receiving ADT prior to S-RT or adjuvant S-RT were excluded. Patients were treated by a single radiation oncologist using IMRT to a dose of 66 Gy. PSA was measured prior to the initiation of S-RT and during S-RT at two week intervals. BR after S-RT was defined as PSA value > or = 0.1 ng/ml above the post-S-RT PSA nadir confirmed by a second measurement that, or no response in PSA, or the initiation of ADT. Univariate Kaplan-Meier (KM) analysis with log rank test and Cox regression multivariate hazard ratio (HR) was used to analyze the probability of BR for the variables listed in the table below. Results: The BRFS, overall survival, and PCa specific survival in this group at a median follow-up of 40 months (m) is 71.2%, 95.5% and 97% respectively with a median time to BR of 16.4m. 90% of the patients with a decreasing PSA trend during S-RT were free of BR compared to only 15% of patients with an increasing PSA trend during S-RT (p<0.001; cox HR 0.08 [0.029<95CI<0.216 ]). In KM analysis pre-S-RT PSA velocity of <0.075/m also predicted BR (p=0.01; cox HR 0.252 [0.81<95%CI<0.782]). In multivariate Cox regression modeling, S-RT PSA trend remained significant with p<0.001 and HR of 0.044 (0.008<95%CI<0.214). Conclusions: Increasing PSA during S-RT or pre-S-RT PSA velocity>0.075/m are predictive of biochemical failure. Identifying these patients at an earlier stage of their management may be beneficial for the addition of systemic therapy leading to an improved outcome. N %BR KM log rank p Total patient # 65 28.8 Pre-treatment PSA >10 46 26.1 0.4 Pathology on Ppr G>6 47 36 0.031 VI 16 25 0.32 ECE 19 36.8 0.8 PNI 29 41.3 0.083 Margin + 38 23.7 0.23 S-RT decreasing PSA trend 14 85.7 <0.001 Pre-S-RT PSA nadir >0.2 24 37.5 0.48 Pre-S-RT PSA velocity>0.075/m 13 46 0.01 Pre-S-RT PSA >1 9 33 0.45 No significant financial relationships to disclose.
Differences in Breast Cancer Between Japan and the United States 2
Authors: T. Nemoto, T. Tominaga, A. Chamberlain, Z. Iwasa, H. Koyama, M. Hama, I. Bross, T. Dao
Journal: JNCI Journal of the National Cancer Institute (1977)

Two surgically treated series of 375 Japanese and 352 American women with breast cancer were compared with respect to overall survival and recurrence-free survival rates. Recurrence-free survival rates in Japanese women were superior to those in American women. Overall survival rates were also better in Japanese women, although the difference was not nearly as great as for recurrence-free survival. This seemed due to an improved survival after metastasis in the American women. In analyzing recurrence-free survival rates by age, we found that Japanese women 40 to 54 years old had better recurrence-free survival rates than other age subgroups. This age advantage was not observed in American women. For other age groups, there was relatively little advantage in survivorship in the Japanese series.
P0136 : Alfapump for the treatment of refractory ascites in cirrhotic patients
Authors: G. Stirnimann, T. Berg, L. Spahr, S. Zeuzem, S. McPherson, F. Lammert, J. Babatz, V. Vargas, V. Banz, F. Storni, A. De Gottardi
Journal: Journal of Hepatology (2015)
Should bevacizumab (B) be included in the first-line treatment of elderly patients with advanced colorectal cancer (CRC)? Results from a community-based Italian observational study.
Authors: Stefania Eufemia Lutrino, Marta Schirripa, Lorenzo Calvetti, Gerardo Rosati, Riccardo Giampieri, Antonio Avallone, Stefano Sergio Cordio, Massimiliano Berretta, Fabiola Lorena Rojas Llimpe, Luisa Foltran, Fotios Loupakis, Mario Scartozzi, Sara Lonardi, Carmine Pinto, Alfredo Falcone, Stefano Cascinu, Roberto Bordonaro, Vittorina Zagonel, Gianpiero Fasola, Giuseppe Aprile
Journal: Journal of Clinical Oncology (2012)

e14040 Background: Data on B for elderly patients with advanced CRC are scarce, although recent analyses demonstrated safety for its use. To investigate the efficacy and safety of treating older pts with B and chemotherapy in the clinical practice a national cohort was analyzed. Methods: In this observational cohort study 213 elderly patients from 9 Italian centers who received first-line B combined with chemotherapy were enrolled. Demographics and comorbidities were captured, along with efficacy and toxicity results. Predefined endpoints were response rate, progression-free, overall survival, and safety. Survival curves were generated with Kaplan-Maier methodology. Results: Median age was 72 (66-84), PS was 0-1 in 96%. Comorbidities at study entry were reported in 153 pts (72%): cardiovascular (including hypertension) 107, diabetes 32, respiratory 15, endocrine 10, neurological 10, renal 7, other diseases 51. Comprehensive geriatric evaluation with ADL, IADL and CIRS scores was available for only 64 pts (29%) reporting median values of 6, 8 and 20 respectively. Companion chemotherapy was 5-FU alone for 27 (12.6%), oxaliplatin-based doublet for 75 (35.2%) and irinotecan-based combination for 111 (52.1%). 81 pts had chemotherapy dose reduction, and 23 interrupted B before progression. Disease control was achieved in 86%, with median PFS/OS of 8.8/18.9 months. 76 pts were maintained on B alone or B plus 5-FU. Main toxicities were neutropenia (44%), anemia (37.5%), diarrhea (40.8%), mucositis (25.8%) and hand-foot syndrome (14.1%). Sensorial neurotoxicity was frequent among pts receiving oxaliplatin. Specific B-induced toxicities were induced or worsened hypertension in 48 pts (22.5%), proteinuria in 24 (11%), and venous or artherial thromboembolism in 16 (7.5%). Conclusions: To treat elderly CRC pts with B and chemotherapy is safe and major efficacy endpoints did not differ from expected. Geriatric evaluation is underused in the common practice and better tools are required to select elderly to be treated with antiangiogenics.
Participation in Physical Activity and Risk for Amyotrophic Lateral Sclerosis Mortality Among Postmenopausal Women
Authors: Yvonne L. Eaglehouse, Evelyn O. Talbott, Yuefang Chang, Lewis H. Kuller
Journal: JAMA Neurology (2016)

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal disease with no known cause. Case studies primarily of athletes and several case-control studies have suggested that high levels of strenuous physical activity (PA) may increase the risk for ALS. This relationship has yet to be evaluated among women in population-based cohort studies.To evaluate the relationship between PA and risk for ALS mortality in a large cohort of postmenopausal women.The Women's Health Initiative (WHI) enrolled 161 809 postmenopausal women, aged 50 to 79 years (mean [SD] age, 63.6 [7.24] years), between 1993 and 1998 into either a clinical trial or an observational study at 40 clinical research centers across the United States. We conducted a cohort study from November 2014 to September 2015 using baseline and mortality data during an average of 9.6 years of follow-up from the entire WHI cohort, through September 1, 2013 (with 1.1% lost to follow-up), to address whether there is a relationship between PA and ALS mortality.The WHI assessed frequency and duration of mild, moderate, and strenuous PA at baseline via self-administered questionnaire.Underlying cause of death from ALS collected from death certificates.The WHI enrolled 161 809 women, of whom 165 died of ALS; women who died of ALS were older (median age, 66 years; interquartile range, 61-69 years) compared with the total WHI study population (median age, 63 years; interquartile range, 57-69 years). Age-adjusted ALS mortality rates varied from 7.4 (95% CI, 5.5-9.9)/100 000 person-years for no strenuous PA to 10.6 (95% CI, 5.6-20.0)/100 000 person-years for strenuous PA 3 or more days per week (P = .07). Adjusted for age and body mass index (calculated as weight in kilograms divided by height in meters squared), the odds ratio for death from ALS for participants with strenuous PA 3 or more days per week compared with no reported strenuous PA was 1.56 (95% CI, 1.02-2.37; P = .04).To our knowledge, this is the first cohort study to report an increased risk for ALS mortality associated with strenuous PA in postmenopausal women. The association between strenuous PA and ALS risk observed does not compromise the overall benefit of strenuous PA for total mortality, coronary heart disease, and breast cancer reported in other WHI investigations, but it may provide an important clue to the etiology of ALS, if replicated by other studies.
Pharmacogenomic and pharmacokinetic assessment of liposome encapsulated SN-38 (LE-SN38) in advanced cancer patients
Authors: E. H. Kraut, M. N. Fishman, P. M. Lorusso, J. L. Steinberg, J. A. Nieves, G. J. Fetterly, I. M. Darling, S. P. Wanaski, J. L. Dul, J. W. Sherman
Journal: Journal of Clinical Oncology (2004)

2501 Background: The prodrug irinotecan is converted into its active moiety, SN-38, with wide interpatient variability, due in part to differential expression of cellular carboxylesterases responsible for prodrug hydrolysis. The enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1) detoxifies SN-38 by metabolizing it to SN-38 glucuronide. Polymorphisms in the UGT1A1 promoter lead to decreased expression of the enzyme and are associated with increased risk of irinotecan toxicity. This Phase I study in patients with advanced cancer is designed to assess the pharmacogenomics, pharmacokinetics, and safety of liposome encapsulated SN-38 (LE-SN38). Methods: Patients are stratified prospectively according to their UGT1A1 genotype, as defined by the number of TA repeats in the A(TA)nTAA promoter sequence. Strata consist of homozygous wild-type, homozygous variant, and heterozygous patients, who are expected to have normal, low, and intermediate levels of glucuronidation activity, respectively. LE-SN38 is infused intravenously over 90 minutes every 21 days until disease progression or unacceptable toxicity occurs. Dose escalation is planned with separate patient cohorts receiving 2.5 to 90 mg/m2 of LE-SN38. Tumor progression is monitored radiographically after every 2 cycles. Results: As of 16 December 2003, genotype frequencies of 90 screened patients were 43% homozygous wild-type, 43% heterozygous, and 13% homozygous variant. Dose escalation for the 3 strata has reached 40 mg/m2, 30 mg/m2, and 20 mg/m2, respectively. Diarrhea and neutropenia have not been dose limiting. Drug pharmacokinetic parameters appeared to be linear over the doses assessed. At the 10 mg/m2 LE-SN38 dose level, greatest SN-38 systemic exposure occurred in homozygous variant patients: AUCs were 2- to 3-fold higher than for heterozygous or homozygous wild-type patients, respectively. Conclusions: Dose escalation and patient accrual in all strata are continuing. These data show that drug exposure varies across genotypes. Thus, pharmacogenomic assessments should be used prospectively as a component of individualized patient dosing decisions. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration NeoPharm, Inc.
Evaluation of statistical designs of phase I/II clinical trials for cancer patients published in 2005
Authors: N. Houede, A. Kramar, X. Paoletti
Journal: Journal of Clinical Oncology (2007)

14077 Background: Phase I trials determine the maximal safe dose that could be used in phase II trials. Designs are based on the assumption that efficacy and toxicity increase with dose. Phase I/II trials determine the safety, dosage levels, and response rate. This review addresses statistical issues of phase I/II studies designs. Methods: We reviewed phase I/II clinical trials for cancer patients published in 2005. The main criteria were: type of treatment, statistical design, endpoints, expected efficacy and toxicity, one- or two-steps designs, dose levels, definition of Dose Limiting Toxicity and recommended dose, objective response, survival, patient selection and follow-up. Results: 41 phase I/II trials were found. All but one, targeted a specific type of tumor. 14 studies included combined cytotoxic therapies. 21 studies included a cytotoxic agent combined with a targeted therapy (12) or with radiations (9). Others used monochemotherapy, immunotherapy, vaccine or gene therapy. 23 studies were a two steps design, i.e. a phase I followed by a phase II trial, and used a classical Fibonacci escalation dose model. All others used a one-step design evaluating efficacy and toxicity concomitantly. Among them, 3 had a Fibonacci-like design with a desescalation model and 4 had a randomization to different dose levels. In 1 trial, dose escalation was performed in the same patient. In the 10 remaining studies, 1 evaluated only one dose level and was improperly presented as a phase I/II study, and 9 did not describe any statistical design. DLT was described in only 27 trials. Also, recommended doses for further trials were only provided in 30 studies. Efficacy was evaluated with clinical or radiological response for 34 studies, biological marker was evaluated in 5 cases and time to progression in 2 cases. Conclusion: Most of the phase I/II trials published in 2005 used a classical two steps design with an adapted Fibonacci dose escalation. None of them used new designs such as continual reassessment method (CRM), which have the advantage to incorporate data during the course of the trial, leading to optimization of the study in terms of cost and speed. Methodological progresses are necessary to address issues related to multiple endpoints and to help clinicians to feel comfortable with the CRM. No significant financial relationships to disclose.
Pharmacokinetic evaluation of two HFA pMDI formulations of salmeterol xinafoate administered through a spacer in healthy subjects
Authors: Saumya Chandran, Nazma Morde, Juliet Rebello, Siddarth Chachad, Shrinivas Purandare, Geena Malhotra, Ratnakar Jadhav, Krishnan Iyer, Raghu Naidu
Journal: European Respiratory Journal (2011)

Background: No pharmacokinetic studies of salmeterol HFA pMDI with a spacer device have been published. In this study comparative bioavailability of two salmeterol HFA pMDI formulations administered through a spacer device was evaluated using pharmacokinetic endpoints.

Aim: To compare the rate and extent of absorption of the test product Salmeterol xinafoate HFA pMDI (Cipla Ltd.) with that of the reference product Serevent Evohaler (supplied by Allen & Hanburys, UK), both administered using a spacer.

Methods: This was a balanced, open label, randomised, two-period, single dose, crossover comparative bioavailability study in 24 healthy subjects. Eligible subjects were randomly assigned to receive a single dose of 100μg of both test and reference product administered with a spacer in a crossover manner on two treatment days. The two treatment days were separated with a washout period of 1 week. The blood samples were collected upto 24 hrs. Safety assessments including ECG, tremor assessment, serum potassium and blood glucose were also done at predefined time points. The primary endpoints were Cmax and AUC0-t.

Results: The plasma concentration–time profile of the test product (T) was similar in shape to that of the reference product (R). The T/R ratio of the geometric mean for Cmax and AUC0-t was 94.54 (90% CI 87.11-102.61) and 90.68 (90% CI 83.87–98.03) respectively. The CI limits for Cmax and AUC0-t was well within the bioequivalence range of 80 – 125%.

Conclusion: The bioavailability of the two HFA formulations of salmeterol when administered with a spacer was comparable and both the treatments were safe and well tolerated.
Chemical and Biochemical Aspects of Photosensitization in Livestock and Poultry&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;
Authors: G. Wayne Ivie
Journal: JNCI Journal of the National Cancer Institute (1982)

Certain synthetic and naturally occurring chemicals, particularly those found in some range plants, may interact with livestock and poultry in the presence of activating light to produce photosensitization. Such photosensitization may have serious implications for livestock producers as a result of causing reduced performance of and even death of affected animals. The mechanisms producing photosensitization in livestock and poultry are discussed in context with the chemical nature of major livestock photosensitizers. The possibility that photosensitizing agents for livestock may have toxicologic significance in humans consuming photoactive residues in meat or animal byproducts is considered.
慢性阻塞性肺疾病中肺活量计的使用 可行，但在全科医疗中应用率低
Authors: Patrick, Poels, Tjard, Schemer, Chris, van, Weel, Peter, Calverley, 潘杨（译）, 黄克武（校）
Journal: BMJ (2007)

慢性阻塞性肺疾病（COPD）患者大约占英国总人口的1％，该病也是全世界范围内主要的致残和致死疾病。及时诊断和对疾病的严重程度进行分期都需要用到肺活量计，从理论上说，接受过培训的全科医生（GPs）及其执业人员均能完成这项测定。然而，在初级保健中，测定肺活量遇到了很多困难。
A computerized decision support system (TREAT) to reduce inappropriate antibiotic therapy of bacterial infection
Authors: E. Tacconelli, M. Paul, M.A. Cataldo, N. Almanasreh, Alina Zalounina, Anders Møller Nielsen, Steen Andreassen, U. Frank, R. Cauda, L. Leibovici
Journal: Clinical Microbiology and Infection (2004)
Abnormal Monocyte Chemotaxis in Patients With Breast Cancer: Evidence for a Tumor-Mediated Effect2
Authors: R. Snyderman, L. Meadows, W. Holder, S. Wells
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article Abnormal Monocyte Chemotaxis in Patients With Breast Cancer: Evidence for a Tumor-Mediated Effect Get access R. Snyderman, R. Snyderman 3Division of Rheumatic and Genetic Diseases, Department of Medicine, Duke University Medical Center, Durham, N.C. 277105Department of Microbiology and Immunology, Duke University Medical Center Search for other works by this author on: Oxford Academic PubMed Google Scholar L. Meadows, L. Meadows 3Division of Rheumatic and Genetic Diseases, Department of Medicine, Duke University Medical Center, Durham, N.C. 277105Department of Microbiology and Immunology, Duke University Medical Center Search for other works by this author on: Oxford Academic PubMed Google Scholar W. Holder, W. Holder 6Department of Surgery, Duke University Medical Center Search for other works by this author on: Oxford Academic PubMed Google Scholar S. Wells, Jr. S. Wells, Jr. 6Department of Surgery, Duke University Medical Center Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 60, Issue 4, April 1978, Pages 737–740, https://doi.org/10.1093/jnci/60.4.737 Published: 01 April 1978 Article history Received: 11 May 1977 Accepted: 02 November 1977 Published: 01 April 1978
Abstract 16138: Identification of Rare Variants for Low Levels of Serum High-Density Lipoprotein Cholesterol
Authors: MV Prasad Linga Reddy, Iulia Iulia Iatan, Daphna Weissglas-Volkov, Elina Nikkola, Blake Haas, Ray W Chui, Isabelle Ruel, Janet S Sinsheimer, Jacques Genest, Paivi Pajukanta
Journal: Circulation (2012)

Low level of serum high density lipoprotein cholesterol (HDL-C) is a well-established risk factor for coronary artery disease (CAD). CAD is the major cause of mortality world-wide. We used exome se...