tbuckley/cabot-search huggingface dataset:
Phase 1 study of atrasentan (ABT627), novel endothelin receptor-A antagonist, in Japanese patients with hormone refractory prostate cancer
Authors: Y. Fujisaka, Y. Fujiwara, K. Yamada, T. Shimizu, A. Horiike, N. Yamamoto, Y. Yamada, N. Matsuoka, H. Fujimoto, T. Tamura
Journal: Journal of Clinical Oncology (2006)

14602 Background: Endothelin (ET)-1 and its primary receptor, the ET A receptor, contribute to tumor cell growth, survival, angiogenesis and invasion. Atrasentan is a highly potent, selective ET A receptor antagonist. This study assessed safety and pharmacokinetics (PK) in Japanese patients with hormone refractory prostate cancer. Methods: This open-label, single-center Phase I trial evaluated the safety and PK of escalating oral atrasentan doses (2.5, 10 or 20 mg) given daily on day 1 and day 4 through 27 (except day 2 and 3). Dose-limiting toxicity (DLT) was defined as Grade 3 or greater adverse events related to study drug. Results: Eighteen patients, aged 54–74 (median; 66) were treated in cohorts of 6 patients each. The compliance of all patients was 100%. The most common toxicities were rhinitis, peripheral edema, headache, hypotension and anemia, all of which were well tolerated. These events were consistent with the anticipated vasodilatory effects or with a hemodilution effect of the study drug. DLTs were not observed. Atrasentan was rapidly absorbed following oral administration of 2.5 to 20 mg, maximum plasma concentrations averaged from 0.4 to 0.8 hours. After peaking, plasma concentrations declined bi-exponentially with a terminal half-life of approximately 25 hours. In the 10 mg dosing group, the steady-state maximum plasma concentration (C max ) and the area under the curve (AUC 0–24h ) averaged 135.5 ng/mL and 533 ng h/mL, respectively. The C max and AUC values generally increased linearly with increasing dose after single- and multiple-dose administration. Compared to baseline, PSA decreased 50% or more in 1 patient (20 mg) and increased 25% or more in 10 patients (2.5 mg;2, 10 mg;5, 20 mg;3). The PSA of the remaining 7 patients (2.5 mg;4, 10 mg;1, 20 mg;2) ranged from &lt; 25% increase to &lt; 50% decrease. Fourteen patients continued on study drug in an extension study. Conclusions: Atrasentan is well tolerated, with no dose-limiting adverse events observed up to 20 mg in Japanese patients. The main adverse events are consistent with the vasodilatory effect of the drug. PK are linear and dose-proportional; the half-life is appropriate for once-daily dosing. No significant financial relationships to disclose.
Influenza activity - United States and worldwide, June 13-September 25, 2010.
Authors: M. Jhung, L. Brammer, S. Epperson, L. Blanton, R. Dhara, L. Finelli, L. Gubareva, A. Klimov, T. Wallis, M. Okomo-Adhiambo, J. Bresee, N. Cox, A. Storms
Journal: MMWR Morbidity and Mortality Weekly Report (2010)
Abstract 18036: Heart Rate Response to Adenosine is an Independent Predictor of Long-term Mortality in End Stage Renal Disease
Authors: Himanshu Aggarwal, Shikha Mehta, Roslyn Mannon, Jaekyeong Heo, Ami E Iskandrian, Fadi G Hage
Journal: Circulation (2012)

Introduction:  We have shown that a blunted heart rate response to adenosine (HRR) is an independent predictor of poor outcome in all comers undergoing myocardial perfusion imaging (MPI). Patients with end stage renal disease (ESRD) are at exceptionally high risk. We hypothesized that HRR will be independently associated with mortality in this population.   Methods:  We studied ESRD patients undergoing renal transplant evaluation at our institution between 2003-2007 who had adenosine MPI. All images were reprocessed using an automated program to determine the presence and extent of perfusion defects and measure left ventricular ejection fraction (EF). HRR was calculated as the % heart rate change from baseline during adenosine infusion. Mortality data was prospectively collected and verified against the social security death index database.   Results:  The study population consisted of 792 ESRD patients (age 52.6 ± 0.4 yrs, 60% diabetes mellitus, 95% hypertension). During a mean follow-up of 5.1± 0.1 years, 281 (36%) patients died. The HRR was lower in patients who died than those who survived (19 ± 1 vs. 28 ± 1 %, p   Conclusions:  HRR is a strong independent predictor of mortality in ESRD. A 1% drop in HRR provides similar prognostic data to 1% drop in EF. HRR possibly due to autonomic denervation provides valuable prognostic information in this high-risk population especially in the subset with normal perfusion pattern or normal EF.
Abstract 13147: Outcome of Combined Aortic Stenosis and Mitral Regurgitation
Authors: Robert Zilberszac, Harald Gabriel, Wilfried Wisser, Gerald Maurer, Raphael Rosenhek
Journal: Circulation (2013)

Background: Although aortic stenosis (AS) and mitral regurgitation (MR) frequently coexist, data on this disease are scarce. Methods: 89 consecutive patients (65 female, age 78 ± 9 yrs) with severe...
Replicating Type-C Virus Particles in Monolayer Cell Cultures of Tissues From Cattle With Lymphosarcoma
Authors: M. J. Van Der Maaten, J. M. Miller, A. D. Boothe
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Replicating Type-C Virus Particles in Monolayer Cell Cultures of Tissues From Cattle With Lymphosarcoma Get access M. J. Van Der Maaten, M. J. Van Der Maaten Search for other works by this author on: Oxford Academic PubMed Google Scholar J. M. Miller, J. M. Miller Search for other works by this author on: Oxford Academic PubMed Google Scholar A. D. Boothe A. D. Boothe Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 52, Issue 2, February 1974, Pages 491–497, https://doi.org/10.1093/jnci/52.2.491 Published: 01 February 1974 Article history Received: 17 July 1973 Accepted: 09 October 1973 Published: 01 February 1974
Inflammatory breast cancer and body mass index.
Authors: S Chang, A U Buzdar, S D Hursting
Journal: Journal of Clinical Oncology (1998)

No studies have investigated the etiology of inflammatory breast cancer (IBC), the most lethal form of breast cancer. Because high body mass index (BMI) is associated with decreased risk of premenopausal breast cancer but increased risk of postmenopausal breast cancer, we evaluated whether high BMI was a risk factor for IBC.In a case-comparison study, we matched by ethnicity and registration date 68 IBC patients treated at The University of Texas M.D. Anderson Cancer Center from 1985 to 1996 with 143 patients with non-IBC and 134 patients with cancer at sites other than the breast or reproductive tract (non-breast cancer). The non-breast cancer group was used in lieu of a population-based, healthy control group, which was not available.IBC patients were younger at menarche and the time of their first live birth than non-IBC and non-breast cancer patients. The proportion of premenopausal IBC patients was higher than the proportion of premenopausal women in the comparison groups, although differences were not significant. There were no differences in height, but IBC patients were heavier (77.6 kg) than non-IBC (70.0 kg) and non-breast cancer patients (68.0 kg). After adjusting for other factors, women in the highest BMI tertile (BMI > 26.65 kg/m2) relative to the lowest tertile (BMI < 22.27) had significantly increased IBC risk (IBC v non-IBC, odds ratio [OR] = 2.45, 95% confidence interval [CI] = 1.05 to 5.73; IBC v non-breast cancer, OR = 4.52, 95% CI = 1.85 to 11.04). This association was not significantly modified by menopausal status and was independent of age at menarche, family history of breast cancer, gravidity, smoking status, and alcohol use.Our investigation showed that high BMI was significantly associated with an increased risk of IBC. This association did not vary by menopausal status, although IBC patients were more likely to be premenopausal. Confirming our findings and identifying other IBC risk factors may provide directions for future research on the aggressive nature of IBC.
Antitumor efficacy of OSI-930 and the molecular targeted agent erlotinib in preclinical xenograft models
Authors: M. Rosenfeld-Franklin, S. Silva, C. Pirritt, A. Cooke, M. Bittner, J. Wolf, D. Epstein, R. Wild
Journal: Journal of Clinical Oncology (2008)

14596 Background: OSI-930 is a potent Kit/KDR inhibitor that is currently in Phase I clinical trials. Preclinically OSI-930 has demonstrated significant anti-tumor activity as a monotherapy in a variety of tumor xenograft models. We have previously shown that OSI-930 can be administered safely and effectively with standard-of-care chemotherapeutics in xenograft models of both small cell lung cancer as well as colorectal carcinoma (Srebernak, et al., AACR 2005). In order to further our understanding of the potential clinical utility of OSI-930 we sought to investigate the combination of OSI-930 with erlotinib, a small molecule tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR) in a preclinical setting. Emerging clinical data suggest that continuation of erlotinib treatment in patients with progressive disease may be beneficial even when a new treatment is initiated. Thus, we investigated whether this phenomenon could be reproduced in a preclinical setting and whether combining OSI-930 and erlotinib would show anti-tumor efficacy in a treatment beyond progression setting. Methods: We utilized 2 xenograft models, H292 (NSCLC) and GEO (colon), which show initial sensitivity to erlotinib with a proportion of mice demonstrating tumor progression during treatment. Additionally, PK studies were performed to evaluate potential drug-drug interactions. Results: In these studies we determined a safe and efficacious dose combination regimen for OSI-930 and erlotinib as well as elucidated preclinical drug- drug interactions. We found that in xenograft studies both drugs alone show significant tumor growth inhibition, thus limiting our ability to measure potential additivity or synergy in combination in vivo. However, we also found that after tumor progression on erlotinib monotherapy, the addition of OSI-930 with the continuation of erlotinib treatment resulted in significantly delayed tumor growth. This effect was not observed to the same extent with OSI-930 treatment alone following progression on erlotinib monotherapy. Conclusion: These data support combination strategies employing OSI-930 and erlotinib in patients whose cancers have progressed following erlotinib monotherapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration OSI Oncology
Regression of Hormone-Dependent Mammary Tumors in Rats as a Result of Tamoxifen Pharmacologic Doses of 17 &lt;italic&gt;β&lt;/italic&gt;-Estradiol: Cyclic 3′,5′-Monophosphate-Mediated Events&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn3"&gt;3&lt;/xref&gt;
Authors: J S Bodwin, P H Hirayama, J A Rego, Y S Cho-Chung
Journal: JNCI Journal of the National Cancer Institute (1981)

The estrogen and cyclic adenosine 3′,5′-monophosphate (cAMP)-binding activities changed markedly when 7,12-dimethylbenz[a]anthracene-induced mammary tumors of Sprague-Dawley rats regressed following daily injections of either tamoxifen or pharmacologic doses of 17 β-estradiol. cAMP binding increased eightfold to tenfold. whereas estrogen binding increased twofold to threefold in regressing tumor nuclei at 5 days after either treatment, which resulted in an inversion of the ratio of estrogen binding to cAMP binding found in growing tumor nuclei. Concomitantly, both binding activities were depleted from the cytosol. In the regressing tumors, the cAMP level increased twofold and nuclear cAMP-dependent protein kinase activity increased threefold to fourfold. with a 70–80% decrease in the cytoplasmic protein kinase activity. The rise in the nuclear protein kinase activity was abolished when cycloheximide was given with tamoxifen or with high doses of 17 β-estradiol, which suggests that the increased activity is due to new protein synthesis. In the regressing tumor nuclei, the phosphorylation of the regression-associated proteins increased. whereas the phosphorylation of growth-associated proteins decreased. These data suggest that the mammary tumor regression induced by tamoxifen or high doses of estrogen proceed through a series of cAMP-mediated events.
A multicenter phase 2 trial of neo-adjuvant pemetrexed plus cisplatin (PC) followed by extrapleural pneumonectomy (EPP) and radiation (RT) for malignant pleural mesothelioma (MPM)
Authors: L. M. Krug, H. I. Pass, V. W. Rusch, D. J. Sugarbaker, K. E. Rosenweig, J. S. Friedberg, L. P. Bloss, Z. Ye, C. K. Obasaju, N. J. Vogelzang
Journal: Journal of Clinical Oncology (2005)

7179 Background: The discovery of effective chemotherapy in MPM has sparked interest in studying combined modality therapy for fit patients with early stage disease. Pilot trials have shown treatment with gemcitabine plus cisplatin followed by EPP and hemithoracic RT to be feasible and promising (Weider JCO 2004). This trial builds on that treatment algorithm as the first study utilizing neoaduvant PC followed by EPP & RT to further assess feasibility and survival. Methods: Eligibility criteria: stage T1–3 N0–2, no prior surgical resection, adequate organ function (including predicted post-op FEV1 ≥ 35%) and PS 0 - 1. Patients receive pemetrexed 500 mg/m2 plus cisplatin 75 mg/m2 with vitamin supplementation for 4 cycles. Patients without disease progression undergo EPP followed by hemithoracic RT. The primary endpoint is pathologic complete response rate. The planned sample size is 70 patients. Results: 32 patients have been accrued with data available on 21. Patient characteristics: Median age 65 (range 34–76), M:F=16:5, Stage II:III = 6:13, epithelial:mixed:other = 18:1:2, ECOG PS 0:1 = 4:17. 21 patients are evaluable for toxicity. Patient specific grade 3/4 hematologic toxicities: febrile neutropenia (4.8%), neutropenia (4.8%). Grade 3/4 non-hematologic toxicities: one patient (4.8%) each with dyspnea; respiratory failure; decreased creatinine clearance, and hypersensitivity reaction respectively. Response to neoadjuvant PC for 15 efficacy evaluable pts consisted of CR-0, PR-6 (40%), SD-9 (60%) for an overall response rate of 40% (95% CI= 16 - 68%). Twelve pts have gone to surgery. The EPP completion rate is app. 80%. No pathologic complete response has been seen. In 13 pts with pulmonary function tests, no significant change in pre and post-chemotherapy parameters was demonstrated. Discussion: This preliminary data suggests that neoadjuvant chemotherapy using PC does not compromise resectability. Updated response and toxicity data will be forthcoming. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly Abbott Eli Lilly Abbott, Aventis, OSI, Eli Lilly Abbott, Lilly Oncology, AstraZeneca, Eli Lilly
Which patients experience improved quality of life (QOL) and mood from early palliative care (PC)?
Authors: Ryan David Nipp, Joseph A. Greer, Lara Traeger, Emily R. Gallagher, Elyse R. Park, Vicki A. Jackson, William F. Pirl, Jennifer S. Temel
Journal: Journal of Clinical Oncology (2014)

16 Background: Prior research has demonstrated improved patient outcomes with early PC integrated with standard oncology care (SC), but it is not clear if these associations exist in all patient demographic groups. This study examined whether early integrated PC was associated with improvements in QOL and mood in different demographic groups. Methods: This is a secondary analysis of data from a randomized controlled trial of 151 patients with newly diagnosed metastatic non-small-cell lung cancer presenting to an outpatient cancer center from June 2006 to July 2009. Patients received either early PC integrated with SC or SC alone. QOL (Functional Assessment of Cancer Therapy–Lung [FACT-L] and Trial Outcome Index [TOI]) and mood (Hospital Anxiety and Depression Scale depression subscale [HADS-D] and Patient Health Questionnaire 9 [PHQ-9], scored categorically) were assessed at baseline and 12 weeks. Data were analyzed to assess relationships between outcome variables and patient demographic characteristics (age and gender). Results: At baseline, QOL and mood outcomes did not differ significantly between treatment groups for age or gender. At 12 weeks, the PC group showed better QOL and lower rates of depressive symptoms for males and those &lt; age 65. In comparison, QOL and mood did not differ significantly between study groups for females and those ≥ age 65. Conclusions: Males and patients &lt; age 65 experienced improved QOL and mood with early, integrated PC. However, these outcomes did not differ significantly between treatment groups for patients ≥ age 65 or for females. Further research should confirm these findings and tailor interventions to meet the unique needs of all patients with cancer. [Table: see text]
Codon Usage Selection Can Bias Estimation of the Fraction of Adaptive Amino Acid Fixations
Authors: Tomotaka Matsumoto, Anoop John, Pablo Baeza-Centurion, Boyang Li, Hiroshi Akashi
Journal: Molecular Biology and Evolution (2016)

A growing number of molecular evolutionary studies are estimating the proportion of adaptive amino acid substitutions (α) from comparisons of ratios of polymorphic and fixed DNA mutations. Here, we examine how violations of two of the model assumptions, neutral evolution of synonymous mutations and stationary base composition, affect α estimation. We simulated the evolution of coding sequences assuming weak selection on synonymous codon usage bias and neutral protein evolution, α = 0. We show that weak selection on synonymous mutations can give polymorphism/divergence ratios that yield α-hat (estimated α) considerably larger than its true value. Nonstationary evolution (changes in population size, selection, or mutation) can exacerbate such biases or, in some scenarios, give biases in the opposite direction, α-hat < α. These results demonstrate that two factors that appear to be prevalent among taxa, weak selection on synonymous mutations and non-steady-state nucleotide composition, should be considered when estimating α. Estimates of the proportion of adaptive amino acid fixations from large-scale analyses of Drosophila melanogaster polymorphism and divergence data are positively correlated with codon usage bias. Such patterns are consistent with α-hat inflation from weak selection on synonymous mutations and/or mutational changes within the examined gene trees.
Prostate Cancer Management Under Scrutiny: One Man's Meta-Analysis Is Another Man's Poisson
Authors: Derek Raghavan
Journal: Journal of Clinical Oncology (1999)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1999.17.11.3371 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10550130 Prostate Cancer Management Under Scrutiny: One Man's Meta-Analysis Is Another Man's Poisson Derek RaghavanxDerek RaghavanSearch for articles by this author Show More Division of Medical Oncology, University of Southern California–Norris Comprehensive Cancer Center, Los Angeles, CA https://doi.org/10.1200/JCO.1999.17.11.3371 First Page Full Text PDF Figures and Tables © 1999 by American Society of Clinical Oncology
Prevalence of renal insufficiency in cancer patients: Data from the IRMA-2 study
Authors: N. Janus, S. Oudard, P. Beuzeboc, J. Gligorov, I. Ray-Coquard, J. Morere, J. Spano, X. Pourrat, G. Deray, V. Launay-Vacher
Journal: Journal of Clinical Oncology (2009)

9559 Background: The IRMA-1 study reported the high prevalence of renal insufficiency (RI) in 4,684 cancer patients, with a glomerular filtration rate (GFR) &lt;90 and &lt;60 ml/min/1.73m 2 for 52.9% and 12.0%, respectively. Furthermore, almost 80% of patients were receiving nephrotoxic drugs or drugs necessitating dosage adjustment. The IRMA-2 study was started one year later, in different patients, and consisted of 2 phases: 1) a cross-sectional study, similar to IRMA-1, and 2) a 2-year retrospective follow-up of the patients to describe the evolution of their renal function along with time. Data from the phase 1 were compared to the results of IRMA-1 in terms of RI prevalence. Methods: Data were collected for cancer patients presenting at one of the 19 IRMA-2 centers in March 2005: type of tumour, sex, age, weight, serum creatinine (SCR), and anticancer drugs. Dialysis, myeloma and lymphoma patients were not included. The prevalence of SCR&gt;110 μmol/L was assessed. GFR was estimated with the aMDRD formula, anticancer drugs necessitating dosage adjustment and those potentially nephrotoxic were identified. Results: 4,945 patients (breast 1816, colorectal 747, lung 463, ovarian 294, prostate 251) were included in the IRMA-2 study. Median age 60.0, mean weight 66.2, 62.8% were women. The prevalence of an elevated SCR (SCR&gt;110μmol/l) was 7.2% (vs. 7.2% in IRMA-1), that of a GFR &lt; 90 ml/min/1.73m 2 was 50.2% (vs. 52.9%) and that of a GFR &lt; 60 ml/min/1.73m 2 was 11.9% (vs. 12.0%) ( Table ). 73.2% of treated patients (n=3882) were receiving at least one drug needing dosage adjustment and 75.5% received at least one nephrotoxic drug (vs. 79.9 and 80.1%, respectively). Conclusions: The results of IRMA-2 and IRMA-1 confirm the high prevalence of RI in cancer patients, on 2 different cohorts of nearly 5,000 cancer patients each. This underlines that estimating renal function in cancer patients is mandatory and that this highly frequent co-morbidity should be considered. [Table: see text] No significant financial relationships to disclose.
Abstract 11565: The Unfolded Protein Response Directly Activates the Hexosamine Biosynthetic Pathway to Protect the Heart from Ischemia/Reperfusion Injury
Authors: Zhao V. Wang, Yingfeng Deng, Ningguo Gao, Zully Pedrozo, Dan L. Li, Wei Tan, Nan Jiang, Mark A. Lehrman, Beverly A. Rothermel, Ann-Hwee Lee, Sergio Lavandero, Anwarul Ferdous, Thomas G. Gillette, Philipp E. Scherer, Joseph A. Hill
Journal: Circulation (2013)

Zhao Wang, 2013 Finalist and Presenting Author