tbuckley/cabot-search huggingface dataset:
Abstract 2619: Synergistic anticancer effect of Noscapine and Camptothecin is mediated through apoptosis and cell cycle arrest in A549 lung cancer
Authors: Ravi Doddapaneni, Ketan Patel, Mandip Singh
Journal: Cancer Research (2015)

Abstract Background: The aim of this study was to evaluate the anticancer activity of a natural product Noscapine (Nos) and Camptothecin (CMP) combination (Nos+CMP) against non-small cell lung cancer (NSCLC) and to elucidate the underlying mechanism of action. Methods: A549 cells were treated with Nos, CMP or their combination and combination index (CI) values were calculated using isobolographic method. The apoptotic proportion of the cells and cell cycle effects were analyzed using flow cytometry. The expression of apoptotic proteins was detected by western blot analysis such as anti-apoptotic protein Bcl2, cell survival marker survivin, extracellular matrix proteins like MMP-2, MMP-9 and cell cycle regulatory proteins like p21 and cyclin dependent kinase 2 (CDK2). Results: The CI values (&amp;lt;0.61) were suggestive of synergistic behavior between Nos and CMP. To investigate the underlying mechanism of the Nos antiproliferative effect, cell cycle-analysis was conducted with A549 cells. Nos+CMP treatment group induced G2/M phase arrest (using the the fluorescence-activated cell sorting analysis) and the number of apoptotic cells were also increased significantly in a dose-dependent manner compared to Nos and CMP alone and control treatments. Furthermore, western blot analysis revealed that Nos+CMP treatment significantly upregulated 0.9 fold (p&amp;lt;0.05) the expression of tumor suppressor protein p21 Waf1/Cip1 (suggesting inhibition of cell cycle progression) compared to single agent treated and control groups. Expression of CDK2 (an important component of cell machinery) and cyclin D1 (another important regulator of cell cycle progression) was significantly downregulated 1.03 fold (p&amp;lt;0.05) and 0.7 fold (p&amp;lt;0.05) respectively in Nos+CMP compared to other groups. Also, expression of Bcl2, survivin, MMP-2 and MMP-9 was significantly downregulated in Nos+CMP treated cells (p&amp;lt;0.05). Further, investigations are currently being conducted to evaluate the synergistic anticancer effect of Nos and CMP in lung tumor xenografts in nude mice. Conclusion: Nos potentiated the anticancer activity of CMP in an additive to synergistic manner against lung cancer via cell cycle and apoptotic pathways. These findings suggest potential benefit for use of Nos+CMP in treatment of lung cancer. Citation Format: Ravi Doddapaneni, Ketan Patel, Mandip Singh. Synergistic anticancer effect of Noscapine and Camptothecin is mediated through apoptosis and cell cycle arrest in A549 lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2619. doi:10.1158/1538-7445.AM2015-2619
Incidence and Outcome In Adults With Acute Lymphoblastic Leukemia With Primary Central Nervous System Involvement
Authors: Muhamed Baljevic, Hagop M Kantarjian, Deborah Thomas, Michael Rytting, Jyothsna Dasarathula, Gautam Borthakur, Jan A. Burger, Farhad Ravandi, Elias Jabbour, Marina Konopleva, Sherry Pierce, Mark Brandt, Susan O'Brien, Jorge E. Cortes
Journal: Blood (2013)
An Epidemiologic Study of Breast Cancer2
Authors: B. E. Henderson, D. Powell, I. Rosario, C. Keys, R. Hanisch, M. Young, J. Casagrande, V. Gerkins, M. C. Pike
Journal: JNCI Journal of the National Cancer Institute (1974)

Epidemiologic data were studied and found incompatible with the horizontal transmission of a human breast cancer virus through milk. Regardless of the patient's age at diagnosis of breast cancer, no evidence of an increased risk associated with breast feeding was found. In addition, increased familial risk of breast cancer occurred in both paternal and maternal lines. The familial aggregation of the disease seemed related to an altered state of estrogen excretion or metabolism; the mothers of breast cancer patients had the delayed age at first delivery and at menopause characteristics of the patients. A decreased risk of breast cancer was associated with hormone administration at natural menopause.
Stage of breast cancer at presentation in non-U.S. citizens as compared to U.S. citizens.
Authors: T. Aiti, K. Grauslyte, T. Mackevicius, E. A. Marcus, G. Lazzaro, J. Greager, T. E. Lad
Journal: Journal of Clinical Oncology (2010)

e12030 Background: Non-U.S. Citizenship status as a risk factor in cancer is understudied in literature. The purpose of this study was to investigate the relationship between U.S. citizenship status and the stage of breast cancer at clinical presentation in underserved population. Methods: A retrospective cohort study on female patients who were diagnosed and/or treated for breast cancer at our institution between 2000 and 2009 was conducted. Age, Race, U.S. citizenship status and AJCC Staging information were collected. Stages 0,1, and 2 were considered early, and stages 3 and 4 were considered late. Univariate and multivariate logistic analysis were done. Retrospective power calculation for cohort study was done. P value of ≤ 0.05 was considered significant. Results: 1,163 patients met the search criteria. U.S. citizens group composed of 892 and non-U.S. citizens group composed of 271, with mean age of 44 and 47.5 respectively. Number of patients with early stage and late stage was 638 and 254 amongst U.S. citizens while in the group of non- U.S. citizens it was 166 and 105 respectively. Risk of late stage in US citizen group is 28% and in non U.S. citizen group was 38%. Univariate analysis of non- U.S. Citizenship factor showed odd ratio: OR = 1.59 > 1, 95% CI = 1.20-2.11, p = 0.001. Multivariate analysis with adjusting for race and age showed: OR = 1.63 > 1, 95%CI = 1.19-2.23, p = 0.002, very high significant. Study power based on normal approximation was 88.13%. Conclusions: Patients of non-U.S. group are more likely to present with late stage disease with its associated poorer prognosis. Even amongst the underserved population seen in our institution, non-U.S. citizens still have worse stage at presentation. Further studies examining the health care provided to the non-U.S. citizen population needed to help understand this ethical and economic dilemma and identify targets for intervention. No significant financial relationships to disclose.
Phase II Study of Sequential Administration of Docetaxel Followed by Doxorubicin and Cyclophosphamide as First-Line Chemotherapy in Metastatic Breast Cancer
Authors: D. Khayat, P. Chollet, E. C. Antoine, S. Monfardini, G. Ambrosini, A. Benhammouda, M.-F. Mazen, R. Sorio, O. Borg-Olivier, A. Riva, C. Ramazeilles, N. Azli
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To evaluate the feasibility and efficacy of a sequential administration of four cycles of docetaxel (100 mg/m 2 every 3 weeks) followed by four cycles of doxorubicin and cyclophosphamide (AC; 60/600 mg/m 2 every 3 weeks), with subsequent consolidation with docetaxel or AC, as first-line chemotherapy in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Forty-eight patients received 443 cycles of chemotherapy (median, 11 cycles/patient; range, 1 to 13 cycles). A total of 267 cycles of docetaxel (60.3%) and 176 of AC (39.7%) were given. Consolidation therapy was given to 33 patients (29 with docetaxel). RESULTS: Grade 4 neutropenia was the most frequent toxicity (83% of patients). This was not cumulative and was rarely complicated by febrile neutropenia or severe infection. The nonhematologic safety profile was favorable: there were no grade 4 adverse events, and grade 3 episodes were infrequent. Docetaxel-specific toxicities were generally not severe. With a median cumulative doxorubicin dose of 397 mg/m 2 (range, 150 to 543 mg/m 2 ), two incidences of unrelated congestive heart failure after further treatment with anthracyclines and two of asymptomatic left ventricular ejection fraction decrease were observed. Among the 42 assessable patients, five (12%) had complete and 25 (60%) had partial responses, for an overall response rate of 71% (95% confidence interval, 55% to 84%). Median duration of response was 53 weeks (range, 12 to 72 weeks), and median time to progression was 46 weeks (range, 3 of 72 weeks). With a median follow-up of 40.4 months, median survival was 32 months (range, 2 to 55 months). CONCLUSION: This docetaxel-based sequential schedule is safe and effective in first-line therapy for MBC, without incurring cumulative toxicity, and provides a feasible chemotherapeutic option in this clinical setting.
Abstract 13863: Angiotensin Converting Enzyme Inhibitor/Angiotensin Receptor Blocker Administration following Cardiac Catheterization Reduces Contrast-Induced Nephropathy
Authors: Craig D Robison, Heidi T May, Benjamin D Horne, Donald L Lappe, Joseph B Muhlestein, Jeffrey L Anderson
Journal: Circulation (2013)

Background: Contrast-induced nephropathy (CIN) is a complication of cardiac catheterization. Angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are often prescr...
Phase I study of AEE788, a novel multitargeted inhibitor of ErbB and VEGF receptor family tyrosine kinases: A pharmacokinetic (PK)-pharmacodynamic (PD) study to identify the optimal therapeutic dose regimen
Authors: J. Baselga, F. Rojo, H. Dumez, A. Mita, C. H. Takimoto, J. Tabernero, C. Dilea, K. Parker, M. Dugan, A. T. van Oosterom
Journal: Journal of Clinical Oncology (2005)

3028 Background: AEE788 is an orally active, small-molecule, multitargeted kinase inhibitor with potent inhibitory activity against multiple tyrosine kinases, including EGFR, HER2, and VEGFR2. This phase I study is being conducted to assess its safety, PK, PD, maximum tolerated dose, and optimal biologic dose in pts with advanced solid tumors. Methods: AEE788 was given PO at 25, 50, 100, 150, 225, 300, 400, 450, 500, and 550 mg/day in 28-day cycles to 3–6 pt cohorts. 24-hr PK profiles were performed on days 1, 15, 28. PK parameters of AEE788 and AQM674 (active metabolite) were computed by model-independent methods. PD markers were analyzed in skin (SK), wound and tumor (TU) biopsies pre- and post-treatment. Emax models were used to characterize concentration-effect relationships. % change in PD markers (%dE=100*1-Et/Eo) were computed, Eo and Et are pre- and post-treatment. Emax and IC50 were estimated by non-linear least squares regression, and doses corresponding to 80% Emax were computed. Results: 69 pts were treated with a median of 2 cycles (range <1–10). AEE788 and AQM674 concentrations varied widely and increased with dose and duration. IC50 values were estimated for pEGFR (42nM), pMAPK (38nM), Ki67 (7nM) in SK and pEGFR (28nM), pMAPK (22nM) in TU; 80% Emax was achieved with 100–300 mg/day. Conclusions: A dose-dependent inhibition of EGFR signaling in SK and TU was observed; profound receptor inhibition is achieved with ≥ 300 mg/day. As expected, inhibition of endothelial pMAPK and Ki67 occurs at higher doses than EGFR inhibition (≥ 300 mg). Exposure dependent effects were observed and estimated IC50 values agree with preclinical data. Integration of PK, PD, and clinical response will suggest a potentially therapeutic regimen for further clinical evaluation. Model development will continue as more data become available. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Aventis, Bristol-Myers Squibb, Lilly Oncology, Merck KgaA (A), Novartis, Pfizer, Pharma Mar, Roche, Roche (A) Novartis Aventis, Novartis, Pfizer, Roche ILEX Oncology, Novartis
A Population-Based Cohort Study of Undervaccination in 8 Managed Care Organizations Across the United States
Authors: Denise M. Goodman
Journal: JAMA (2013)

An abstract of a study by Glanz et al examining the patterns and trends of undervaccination in children aged 2 to 24 months and comparing health care utilization rates between undervaccinated and age-appropriately vaccinated children is presented. Of 323,247 children born between 2004 and 2008, 48.7% were undervaccinated for at least 1 day before age 24 months. The prevalence of undervaccination and specific patterns of undervaccination increased over time (P<.00 1). In a matched cohort analysis, undervaccinated children had lower outpatient visit rates compared with children who were age-appropriately vaccinated (incidence rate ratio [IRR], 0.89; 95% CI, 0.89-0.90). In contrast, undervaccinated children had increased inpatient admission rates compared with age-appropriately vaccinated children (IRR, 1.21; 95% CI, 1.18-1.23). In a second matched cohort analysis, children who were undervaccinated because of parental choice had lower rates of outpatient visits (IRR,0.94; 95% CI, 0.93-0.95) and emergency department encounters (IRR, 0.91; 95% CI, 0.88-0.94) than age-appropriately vaccinated children.
Risks of severe adverse events of docetaxel, cisplatin, and 5-fluorouracil (DCF) combination chemotherapy of esophageal cancer.
Authors: Sayako Yuda, Ken Kato, Yusuke Sasaki, Naoki Takahashi, Hirokazu Shoji, Atsuo Takashima, Natsuko T. Okita, Yoshitaka Honma, Satoru Iwasa, Tetsuya Hamaguchi, Yasuhide Yamada, Kengo Nagashina, Narikazu Boku
Journal: Journal of Clinical Oncology (2015)

43 Background: Although adding docetaxel to cisplatin plus 5-fluorouracil (i.e. the DCF regimen) for esophageal cancer treatment may improve outcomes, this regimen has increased toxicity. However, the risk factors for severe non-hematological toxicities remain unknown. Methods: We analyzed data on esophageal cancer patients given at least one cycle of DCF between July 2009 and April 2014 at the National Cancer Center Hospital, Japan. DCF consisted of docetaxel 70 mg/m 2 /day (day 1), cisplatin 70 mg/m 2 /day (day 1), and continuous infusion of 5-fluorouracil 750 mg/m 2 /day (days 1–5), repeated every 3 weeks. Data on adverse events developing within three cycles were collected from medical records. Risk factors for severe adverse events were analyzed. Results: One hundred patients were enrolled, with a median age of 63 (range, 37 to 76); 81 male and 19 female; 96 squamous cell carcinomas and 4 adenocarcinomas; clinical situation neoadjuvant/induction/palliative: 69/23/8/1; clinical stage I/II/III/IV: 1/12/64/23; and performance status (PS) 0/1/2: 44/55/1. Forty patients (40%) developed grade 3 or more non-hematological adverse events, including anorexia (12%), mucositis (6%), and esophagitis (2%); 45 developed grade 4 hematological adverse events. Seventeen experienced febrile neutropenia (FN). There was one case of treatment-related death from serious infection. In multivariate analysis, age≥63 was at significantly increased risk of FN (P=0.013). Conclusions: DCF chemotherapy was safe in most patients and its toxicity was controllable. However, elderly patients may suffer from intense toxicity during DCF therapy.
Abstract P231: Gene-by-smoking Interaction Analyses of Kidney Traits in the NHLBI Candidate-gene Association Resources Care Cohorts
Authors: Nora Franceschini, Ching-Ti Liu, W Linda Kao, Leslie Lange, Kari E North, Taylor Young, Michael Nalls, L Adrienne Cupples, Albert Dreisbach, Caroline Fox
Journal: Circulation (2012)

Smoking is a known risk factor for progression of chronic kidney disease (CKD) but little is known of the role of smoking exposure on genetic effects of variants influencing kidney traits in the general population. We examined the evidence for effect modification of current smoking on the association of single nucleotide polymorphisms (SNP) with estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR), two well established markers of kidney disease, in 23,767 white and 8,110 African American individuals from five studies genotyped using the custom SNP array ITMAT-Broad-CARe (IBC array) in the CARe consortium. We obtained study- and race-specific residuals from linear regression models of natural log-transformed eGFR or UACR regressed on age, sex and study site. We then stratified residuals by current smoking exposure and performed genome wide association analyses using additive genetic models adjusted for 10 principal components, and accounting for family structure using mixed models, if needed. Meta-analyses across smoking-specific strata within each self-reported race were performed using the inverse variance weighted fixed effect models. We assessed smoking interaction using a heterogeneity test (P&lt;0.10) and I 2 metric. Among SNPs reaching the array wide specific significance threshold (2.0x10 -6 ) for association with eGFR or UACR, there was significant between smoking-strata heterogeneity for rs7422339 ( CPS1 , P=0.03, I 2 =77.7%) and rs13333226 ( UMOD , P=0.06, I 2 =71.1%) for eGFR in whites, with larger decreases in eGFR among current smokers compared to past/never smokers. For UACR, rs1801239 (missense variant of CUBN , between smoking-strata heterogeneity P=0.09, I 2 =64.8%) T allele showed less protective effect among current smokers than non-smokers in whites only. These loci have been previously identified in genome wide association studies. Our findings, if replicated, suggest possible important interactions of smoking exposure on the genetic effects of known loci associated with kidney traits. Funding(This research has received full or partial funding support from the American Heart Association, National Center)
Association Between Cage Shelf Level and Spontaneous and Induced Neoplasms in Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: David L. Greenman, Ralph L. Kodell, Winslow G. Sheldon
Journal: JNCI Journal of the National Cancer Institute (1984)

Data from a chronic feeding study with 2-acetylaminofluorene [(2-AAF) CAS: 53-96-3; N-fluoren-2-yl-acetamide] done on 20,880 female BALB/c mice were analyzed for associations between cage shelf level and occurrence of induced and spontaneous neoplasms. Each cage was maintained on a rack at a given shelf level throughout the experiment, allowing analysis of data by shelf level. Differences in the crude incidence of 2-AAF-induced liver and bladder neoplasms appeared to be shelf related, but these differences were small and disappeared when shelf-level analyses of time-to-tumor onset distributions were performed. There was evidence for a shelf-level influence on 5 of the 6 major spontaneous neoplasms noted. Time to onset of uterine polyps and reticulum cell sarcomas was significantly delayed on the top shelf of five of six animal rooms. Also, there was a significant delay in onset of lymphomas, adrenocortical adenomas, and lung alveolar cell tumors on the top shelf when data were combined from all six animal rooms, but these delays on the top shelf were significant in no more than two of six animal rooms when rooms were analyzed separately. There was no indication of any shelf-level influence on the development of harderian gland adenomas. In conclusion, shelf level is an environmental factor that should be considered in the design and analysis of carcinogenesis studies.
Abstract 17828: Genome-wide Association Study Identifies Two Loci Associated with Platelet Distribution Width in Healthy Adults
Authors: Rehan Qayyum, Diane M Becker, Lisa R Yanek, Rasika Mathias, Dhananjay Vaidya, Brian G Kral, Taryn F Moy, Lewis C Becker
Journal: Circulation (2012)

Platelet distribution width (PDW) is a measure of heterogeneity in circulating platelet volume and reflects platelet turnover or activation. We have previously found that higher PDW is associated w...
RhoA/Rho-Kinase in the Cardiovascular System
Authors: Hiroaki Shimokawa, Shinichiro Sunamura, Kimio Satoh
Journal: Circulation Research (2016)

Twenty years ago, Rho-kinase was identified as an important downstream effector of the small GTP-binding protein, RhoA. Thereafter, a series of studies demonstrated the important roles of Rho-kinase in the cardiovascular system. The RhoA/Rho-kinase pathway is now widely known to play important roles in many cellular functions, including contraction, motility, proliferation, and apoptosis, and its excessive activity induces oxidative stress and promotes the development of cardiovascular diseases. Furthermore, the important role of Rho-kinase has been demonstrated in the pathogenesis of vasospasm, arteriosclerosis, ischemia/reperfusion injury, hypertension, pulmonary hypertension, and heart failure. Cyclophilin A is secreted by vascular smooth muscle cells and inflammatory cells and activated platelets in a Rho-kinase–dependent manner, playing important roles in a wide range of cardiovascular diseases. Thus, the RhoA/Rho-kinase pathway plays crucial roles under both physiological and pathological conditions and is an important therapeutic target in cardiovascular medicine. Recently, functional differences between ROCK1 and ROCK2 have been reported in vitro. ROCK1 is specifically cleaved by caspase-3, whereas granzyme B cleaves ROCK2. However, limited information is available on the functional differences and interactions between ROCK1 and ROCK2 in the cardiovascular system in vivo. Herein, we will review the recent advances about the importance of RhoA/Rho-kinase in the cardiovascular system.
Re: Eduard Baco, Erik Rud, Lars Magne Eri, et al. A Randomized Controlled Trial to Assess and Compare the Outcomes of Two-core Prostate Biopsy Guided by Fused Magnetic Resonance and Transrectal Ultrasound Images and Traditional 12-core Systematic Biopsy. Eur Urol 2016;69:149–56.
Authors: Yi Zhou, Weigang Yan, Hanzhong Li
Journal: European Urology (2016)
Polymorphisms in the lectin pathway of complement activation influence the incidence of acute rejection and graft outcome after kidney transplantation
Authors: Déla Golshayan, Agnieszka Wójtowicz, Stéphanie Bibert, Nitisha Pyndiah, Oriol Manuel, Isabelle Binet, Leo H. Buhler, Uyen Huynh-Do, Thomas Mueller, Jürg Steiger, Manuel Pascual, Pascal Meylan, Pierre-Yves Bochud, Rita Achermann, John-David Aubert, Philippe Baumann, Guido Beldi, Christian Benden, Christoph Berger, Isabelle Binet, Pierre-Yves Bochud, Elsa Boely, Heiner Bucher, Leo Bühler, Thierry Carell, Emmanuelle Catana, Yves Chalandon, Sabina de Geest, Olivier de Rougemont, Michael Dickenmann, Michel Duchosal, Thomas Fehr, Sylvie Ferrari-Lacraz, Christian Garzoni, Yvan Gasche, Paola Gasche Soccal, Emiliano Giostra, Déla Golshayan, Daniel Good, Karine Hadaya, Christoph Hess, Sven Hillinger, Hans H. Hirsch, Günther Hofbauer, Uyen Huynh-Do, Franz Immer, Richard Klaghofer, Michael Koller, Thomas Kuntzen, Bettina Laesser, Roger Lehmann, Christian Lovis, Oriol Manuel, Hans-Peter Marti, Pierre Yves Martin, Pascal Meylan, Paul Mohacsi, Isabelle Morard, Philippe Morel, Ulrike Mueller, Nicolas J. Mueller, Helen Mueller-McKenna, Thomas Müller, Beat Müllhaupt, David Nadal, Gayathri Nair, Manuel Pascual, Jakob Passweg, Chantal Piot Ziegler, Juliane Rick, Eddy Roosnek, Anne Rosselet, Silvia Rothlin, Frank Ruschitzka, Urs Schanz, Stefan Schaub, Christian Seiler, Nasser Semmo, Susanne Stampf, Jürg Steiger, Christian Toso, Dimitri Tsinalis, Christian Van Delden, Jean-Pierre Venetz, Jean Villard, Madeleine Wick, Markus Wilhelm, Patrick Yerly
Journal: Kidney International (2016)