tbuckley/cabot-search huggingface dataset:
Population Parameters Underlying an Ongoing Soft Sweep in Southeast Asian Malaria Parasites
Authors: Timothy J.C. Anderson, Shalini Nair, Marina McDew-White, Ian H. Cheeseman, Standwell Nkhoma, Fatma Bilgic, Rose McGready, Elizabeth Ashley, Aung Pyae Phyo, Nicholas J. White, François Nosten
Journal: Molecular Biology and Evolution (2016)

Multiple kelch13 alleles conferring artemisinin resistance (ART-R) are currently spreading through Southeast Asian malaria parasite populations, providing a unique opportunity to observe an ongoing soft selective sweep, investigate why resistance alleles have evolved multiple times and determine fundamental population genetic parameters for Plasmodium We sequenced kelch13 (n = 1,876), genotyped 75 flanking SNPs, and measured clearance rate (n = 3,552) in parasite infections from Western Thailand (2001-2014). We describe 32 independent coding mutations including common mutations outside the kelch13 propeller associated with significant reductions in clearance rate. Mutations were first observed in 2003 and rose to 90% by 2014, consistent with a selection coefficient of ∼0.079. ART-R allele diversity rose until 2012 and then dropped as one allele (C580Y) spread to high frequency. The frequency with which adaptive alleles arise is determined by the rate of mutation and the population size. Two factors drive this soft sweep: (1) multiple kelch13 amino-acid mutations confer resistance providing a large mutational target-we estimate the target is 87-163 bp. (2) The population mutation parameter (Θ = 2Neμ) can be estimated from the frequency distribution of ART-R alleles and is ∼5.69, suggesting that short term effective population size is 88 thousand to 1.2 million. This is 52-705 times greater than Ne estimated from fluctuation in allele frequencies, suggesting that we have previously underestimated the capacity for adaptive evolution in Plasmodium Our central conclusions are that retrospective studies may underestimate the complexity of selective events and the Ne relevant for adaptation for malaria is considerably higher than previously estimated.
Venous thromboembolism in 9,489 patients with glioma
Authors: T. J. Semrad, R. O’Donnell, H. Zhou, T. Wun, R. White
Journal: Journal of Clinical Oncology (2006)

1538 Background: Venous thromboembolic events (VTE) are a commonly reported complication of brain tumors. The objective of this study was to define the incidence, risk factors, and outcomes associated with VTE in a population-based cohort. Methods: This was a retrospective analysis of all glioma cases diagnosed in California between 1993–1995 and 1997–1999. Glioma cases in the California Cancer Registry were linked to the California Patient Discharge Database to identify incident VTE. Cox models were generated to analyze the association of pre-specified risk factors with VTE or death within one year of the cancer diagnosis. Results: There were 9489 cases: 76% were Caucasians and 56% were men. The 1-year cumulative incidence of VTE was 663 (7%) with an incidence rate during the first year of 11.1 events per 100 person-years. Sixty-six percent of all VTE diagnosed in the first year occurred within 3 months of the cancer diagnosis with a corresponding incidence rate of 21.6 events per 100 person-years. Of 663 first year VTE, 405 (61%) occurred &lt;2 months after an invasive neurosurgical procedure. Glioblastoma multiforme (GBM) was associated with an increased risk of VTE (HR=1.6, CI: 1.3–2.0) compared to other gliomas. The risk of VTE was strongly associated with the number of chronic co-morbidities (HR=4.0, CI: 3.1–5.0 for ≥3 chronic co-morbidities). Asian race was associated with significantly lower risk of VTE (HR=0.3, CI: 0.2–0.6) and female gender conferred a modestly lower risk (HR=0.8, CI: 0.7–0.9). A VTE in the first year was associated with slightly lower risk of death (HR = 0.8; CI: 0.8–0.9), whereas increasing age (HR=6.3, CI: 5.6–7.0 for age≥75), number of co-morbidities (HR=1.9, CI: 1.7–2.0 for ≥3 chronic co-morbidities), and GBM (HR=2.2, CI: 2.0–2.4) or anaplastic astrocytoma (HR=1.5, CI: 1.3–1.7) histology were associated with a higher risk of death within 1 year. Conclusions: In this large glioma cohort, the incidence of symptomatic VTE was very high. Two-thirds of all VTE occurred early after the diagnosis of glioma, and most of these occurred within 2 months of an invasive neurosurgical procedure. The presence of chronic medical co-morbidities and GBM histology were strong predictors of VTE. A diagnosis of VTE was not associated with an increased risk of death within 1 year. No significant financial relationships to disclose.
Allograft Cell Content and GVHD Differ in Murine Recipients of AMD3100 Versus G-CSF Mobilized Peripheral Blood Stem Cells.
Authors: A. Lundqvist, N. Hamoui, J. Andersson, M. Elshal, Y. Takahashi, R. Srinivasan, D. Suffredini, P. J. McCoy, R. Childs
Journal: Blood (2005)
Hematopoietic Cell Transplantation from an HLA-Mismatched Familial Donor After Reduced-Intensity Conditioning Containing Busulfan, Fludarabine, and Antithymocyte Globulin for Patients with Acute Leukemia and Myelodysplastic Syndrome
Authors: Kyoo Hyung Lee, Je-Hwan Lee, Jung-Hee Lee, Dae-Young Kim, Young-Shin Lee, Miee Seol, Young-Ah Kang, Mijin Jeon
Journal: Blood (2010)
Differential Expression of BIRC Family Genes In The Course Of Chronic Myeloid Leukemia – BIRC3 and BIRC8 As Potential New Candidates To Identify Disease Progression
Authors: Eliza Glodkowska-Mrowka, Iwona Solarska, Piotr Mrowka, Katarzyna Bajorek, Joanna Niesiobedzka-Krezel, Ilona Seferynska, Katarzyna Borg, Tomasz Stoklosa
Journal: Blood (2013)
Desmopressin and Epsilon Amino-Caproic Acid (EACA) in Adenotonsillectomy (T &amp; A): Are We Under-Treating Patients with Mild Type 1 von Willebrand Disease (VWD) and Mild Platelet Function Defects (PFD)?.
Authors: Joan Cox Gill, Ronyanika Rowe, Stephen Conley, Cheryl Hillery, Julie Panepinto, J. Paul Scott, Robert R. Montgomery
Journal: Blood (2004)
P0205 : Management of gastric varices: A french national survey
Authors: D. Weil, J.P. Cervoni, N. Fares, M. Rudler, C. Bureau, A. Plessier, T. Dao, A. Pauwels, D. Thabut, P. Castellani, F. Oberti, N. Carbonell, V. Di Martino, T. Thévenot
Journal: Journal of Hepatology (2015)
Associations Between Baseline Mutation Status and Response to Treatment with Omacetaxine Mepesuccinate in Heavily Pretreated Patients with Chronic Myeloid Leukemia
Authors: Jeffrey H. Lipton, Franck E. Nicolini, Meir Wetzler, Luke Akard, Michele Baccarani, Hagop M. Kantarjian, Adam Craig, Jorge E Cortes
Journal: Blood (2012)
Residual tumor status in clinical trials of advanced ovarian cancer: A systematic review
Authors: M. Beltrán, X. Hernández, C. Abal, M. Velasco, J. Rubio, R. Colomer
Journal: Journal of Clinical Oncology (2006)

15024 Background: To determine whether the proportion of optimal disease status after surgery has changed along a defined period (the platinum era) on the setting of randomized clinical trials (RCT) in advanced ovarian cancer ( AOC). Methods: All RCT of chemotherapy for AOC in the platinum era (accrual period from 1980 to 2002) were searched. Studies were identified in an intensive review in MEDLINE, EMBASE and Cochrane Database, plus bibliographic references in the articles. We included those studies reporting stage, residual disease status and accruing both optimal and suboptimal disease. Simple linear regression models (slrm) were generated to evaluate the proportion of optimal disease status and of FIGO stages over time. Results are reported as two-side p values and 95% confidence intervals. Results: Seventy-five randomized studies, including 20,981 patients, fulfilled the inclusion criteria. Forty-two % of cases had optimal disease after surgery. Stage distribution was as follows: stage I-II, 7.5%, stage III, 72%, stage IV, 20%. Optimal disease status after surgery increased steadily over time, with larger proportions in more recent studies (r=.55; p &lt; .005). Although there was a significant increase in stage I-II cases (r=.41; p &lt; .005), inclusion of patients with stage III and stage IV did not change over time. Conclusions: Reported randomized clinical trials of chemotherapy for advanced ovarian cancer from 1980 to 2002 show a significant trend towards better postsurgical status of residual disease, with a larger proportion of patients with optimal disease in the more recent trials. This is marginally influenced by FIGO stage and therefore, occurs more likely from more extensive surgical debulking procedures. These changes in surgical approach result in an improvement of outcome, that may be independent of the postsurgical treatment used. No significant financial relationships to disclose.
Effect of curcumin on lapatinib sensitivity and lapatinib resistance associated EMT and stem-like phenotype in HER2 positive breast cancer.
Authors: Junjun Liu, Xiaosong Chen, Yan Mao, Kunwei Shen
Journal: Journal of Clinical Oncology (2015)

e11594 Background: Lapatinib acquired resistance remains an important reason influencing lapatinib clinical efficacy in HER2+ breast cancer. The epithelial-mesenchymal transition (EMT) and stem-like phenotype are key development programs often associated with cancer progression and drug resistance. Curcumin has potential therapeutic activities against breast cancer through multiple signaling pathways. We wished to determine the effect of curcumin on EMT and stem-like cells elicited by lapatinib resistance and investigate curcumin as a potential therapeutic agent for HER2+ breast cancer. Methods: Two HER2+ breast cancer cell lines, SKBR3 and BT474 were continuously exposed to increasing concentrations of lapatinib (0.25-2.6μmol/L) to establish two stable lapatinib-resistant cell lines, SK-LR and BT-LR. Protein expression was determined by western-blot. Invasion ability was analyzed by transwell. Results: Both two lapatinib-resistant cell lines, SK-LR and BT-LR had EMT and stem-like phenotype with higher invasion ability compared to naive sensitive cells. Western-blot showed curcumin could reverse the EMT of SK-LR and BT-LR with E-cadherin up-regulated and snail, vimentin, N-cadherin down-regulated at the concentration of 10μM. A significant reduction of CD44, ALDH1, ABCG2 and SOX2 expression was also confirmed. After curcumin treatment, the inhibition of mammosphere forming efficiency and capability of invasion was observed in SK-LR and BT-LR, as well as the reduction of CD44high/CD24low fraction to lapatinib-sensitive cell level by FCM. Alama Blue assay and colony formation assay showed combination of curcumin with lapatinib could reverse lapatinib resistance. Conclusions: Our results suggested that the EMT induced by lapatinib resistance could be reversed by curcumin, as well as reduction of CD44high/CD24low fraction and mammosphere formation in lapatinib-resistant cell lines. Curcumin's ability to reduce invasion and stem-like phenotype makes curcumin a potential alternative that could not only reverse lapatinib resistance but also reduce the potential for metastases in HER2+ breast cancer.
A Prognostic Score System for Survival in Secondary AML: Review of 1073 Patients Observed At MDACC
Authors: Francesco Paolo Tambaro, Guillermo Garcia-Manero, Wei Qiao, Sherry A. Pierce, Mimmo Ripaldi, Stefan Faderl, Hagop M Kantarjian, William G. Wierda, Jorge E Cortes
Journal: Blood (2012)
Final results of a phase I study using oral temozolomide (TMZ) daily for 14 days with weekly paclitaxel in patients (pts) with advanced malignancies
Authors: J. A. Figueroa, I. Tafur, D. Close, P. Cardona, J. Cruz, D. Quick, I. Shalaby, L. Dinunno, P. Ortiz
Journal: Journal of Clinical Oncology (2006)

12020 Background: TMZ is an alkylating agent with activity in a variety of neoplasms. The optimal schedule of administration for TMZ has not been established and only a few studies have studied it in combination with other agents. Repair of TMZ-induced DNA damage is associated with the activity of O-6 alkylguanine-DNA-alkyl transferase (AGT). Preclinical and clinical data indicate that prolonged exposure to TMZ results, not only in enhanced DNA alkylation, but also in depletion of AGT. This serves as the rationale to study TMZ using protracted schedules. Methods: The aim of this study was to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of oral TMZ given daily for 14 days with weekly paclitaxel in pts with advanced cancers. Forty-five pts received 136 cycles of TMZ at escalating doses (50, 75, 100, 125 and 150 mg/m 2 /day × 14 days) plus paclitaxel at 80 mg/m 2 on days 1, 8, and 15. Pts were stratified as lightly (LP) or heavily (HP) pretreated and MTD defined as the dose level (DL) at which 1/6 patients developed DLT. Results: Twenty-four LP patients were treated at 5 DLs with all but one evaluable for toxicity. Febrile neutropenia and grade 3 thrombocytopenia were the DLTs. MTD in this group was the 125 mg/m 2 /day level. Twenty-six HP were treated at 5 DLs and 21 were evaluable for toxicity. Febrile neutropenia and grade 3 thrombocytopenia were the DLTs. MTD for this group was also 125 mg/m 2 /day. Thirty-eight (84%) pts were evaluable for response after 2 cycles of therapy. Three (8%) pts had a partial response (lung, lymphoma, ependymoma), 20 (53%) remained stable and 15 (39%) developed disease progression. Six (16%) pts remained stable for 6 cycles or more (2 sarcomas, 2 lung, 1 pancreas, 1 glioblastoma). Conclusions: We concluded that combining oral TMZ at a dose of 125 mg/m 2 /day for 14 days with standard-dose weekly paclitaxel is safe in both HP and LP pts. [Table: see text]
Prognostic Value of Monosomal Karyotype in Patients with Primary Acute Myeloid Leukemia On Behalf of Spanish CETLAM Group.
Authors: Isabel Granada, Salut Brunet, Montserrat Hoyos, Dolors Costa, Anna Aventín, Isabel Marugán, Teresa Vallespí, Marta Barnues, JJ Duarte, Francesc Solé, Montserrat Teixidó, M. Mascaró, Andreu Llorente, Ramon Guardia, Mar Tormo, Rafael F. Duarte, Fuensanta Millá, Jordi Esteve, Josep-Maria Ribera, Jordi Sierra
Journal: Blood (2009)
Occult Primary
Authors: David S. Ettinger, Mark Agulnik, Justin M. M. Cates, Mihaela Cristea, Crystal S. Denlinger, Keith D. Eaton, Panagiotis M. Fidias, David Gierada, Jon P. Gockerman, Charles R. Handorf, Renuka Iyer, Renato Lenzi, John Phay, Asif Rashid, Leonard Saltz, Lawrence N. Shulman, Jeffrey B. Smerage, Gauri R. Varadhachary, Jonathan S. Zager, Weining (Ken) Zhen
Journal: Journal of the National Comprehensive Cancer Network (2011)

OverviewOccult primary tumors, or cancers of unknown primary (CUPs), are defined as histologically proven metastatic malignant tumors whose primary site cannot be identified during pretreatment evaluation. 1,2 They have a wide variety of clinical presentations and a poor prognosis in most patients.Patients with occult primary tumors often present with general complaints, such as anorexia and weight loss.Clinical absence of primary tumor, early dissemination, aggressiveness, and unpredictability of metastatic pattern are characteristic of these tumors. 3Life expectancy is very short, with a median survival of 6 to 9 months. 4 In most patients, occult primary tumors are refractory to systemic treatments, and chemotherapy
Outcomes of Salvage Chemotherapy and Autologous Stem Cell Transplantation for Relapsed or Refractory Primary Mediastinal Large B Cell Lymphoma (PMLCL) Are Inferior to Diffuse Large B Cell Lymphoma (DLBCL).
Authors: John Kuruvilla, Tracy Nagy, Melania Pintilie, Armand Keating, Michael Crump
Journal: Blood (2005)
Phase I study of vorinostat, a histone deacetylase (HDAC) inhibitor, in combination with carboplatin (Cb) and paclitaxel (P) for patients with advanced solid malignancies (NCI #6922)
Authors: S. Ramalingam, R. A. Parise, M. J. Egorin, A. Argiris, R. Stoller, L. Beattie, A. Aparicio, E. M. Newman, J. Zwiebel, C. P. Belani
Journal: Journal of Clinical Oncology (2006)

2077 Background: Vorinostat (SAHA) induces differentiation &amp; growth arrest in a variety of human carcinoma cell lines by inhibiting HDAC. It also enhances the efficacy of chemotherapy. We are conducting a phase I study to evaluate the combination of vorinostat, Cb &amp; P for patients with advanced solid malignancies. Methods: Patients with advanced solid malignancies who were candidates for combination therapy with Cb &amp; P were eligible. Vorinostat was given orally on d 1–14 of each 21-d-cycle, except in cycle 1 when begun on d -4 to facilitate PK studies. Cb &amp; P were given on d 1 of each cycle. Plasma concentrations of vorinostat, &amp; its 2 major metabolites were quantitated with a novel LC-MS/MS assay. Results: Dose level 4 has been determined as the recommended phase II dose (RP2D) for the combination, since the RP2D of single agent vorinostat is 400 mg on this schedule. Observed toxicities included nausea, vomiting, neutropenia &amp; thrombocytopenia, none of which were dose-limiting. Of 9 patients evaluable for response, 4 had PR (1 head &amp; neck cancer, 3 non-small cell lung cancer), &amp; 2 had stable disease. Vorinostat was rapidly absorbed &amp; AUC increased with dose. Vorinostat PK parameters included Tmax 0.5–2 h, t1/2 1.6 ± 0.5 h, &amp; CL/F 5.8 ± 1.7 l/min. Cb &amp; P did not alter vorinostat PK. 4-Anilino-4-oxobutanoic acid was the major, &amp; long-lived, vorinostat metabolite, with Cmax 1.5–7 fold &gt; vorinostat Cmax &amp; t ½ ∼6h. Vorinostat glucuronide Cmax was 1–5 fold &gt; vorinostat Cmax &amp; glucuronide t ½ ∼2h. The RP2D cohort is being expanded to 12 patients to obtain additional clinical &amp; PK data. Conclusions: Vorinostat can be safely administered in combination with Cb &amp; P at their recommended doses. Vorinostat PK are not altered by Cb &amp; P. Promising anti-cancer activity has been noted in patients with advanced NSCLC. Support: U01CA099168–01, U01CA62505, NIH/NCCR/GCRC grant 5M01RR 00056. [Table: see text] No significant financial relationships to disclose.
Novel Tyrosine Kinase Inhibitors Trigger Drug Sensitivity of Primary CLL Cells by Controlling Glucosylation of Ceramides
Authors: Janine Schwamb, Valeska Feldhaus, Michael Baumann, Michaela Patz, Susanne Brodesser, Reinhild Brinker, Julia Claasen, Christian P. Pallasch, Michael Hallek, Clemens-Martin Wendtner, Lukas P. Frenzel
Journal: Blood (2012)
Brazilian Experience Using High Dose Sequential (HDS) Followed by Autologous Hematopoietic Stem Cell Transplantation (AHSCT) for Relapse/Refractory Aggressive Non-Hodgkin Lymphoma (NHL).
Authors: Bruno K.L. Duarte, I.S. Valente, Afonso C. Vigorito, Francisco J.P. Aranha, Gislaine B. Oliveria, Eliana C.M. Miranda, Irene Lorand-Metze, Katia B.B. Pagnano, Carmino A. De Souza
Journal: Blood (2007)
Lower Erythropoietin Doses and Medicare Payment Reform
Authors: Robert Steinbrook
Journal: JAMA Internal Medicine (2016)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Internal Medicine journal
Reproductive history and risk of colorectal cancer in postmenopausal women.
Authors: A. Zervoudakis, A. Schatzkin, H. D. Strickler, Y. Park, A. Hollenbeck, M. J. Gunter
Journal: Journal of Clinical Oncology (2010)

3618 Background: Estrogen/progestin hormone therapy (HT) use has been associated with a low risk of colorectal cancer. Endogenous estrogen levels, in contrast, have been reported to have a positive relationship with incidence of colorectal cancer in recent studies. An important surrogate measure of estrogen exposure, which has been associated with estrogen-related cancers such as breast cancer, is reproductive history. Therefore, we were interested in studying the relationship of reproductive history with incident colorectal cancer. Methods: We prospectively analyzed the association between reproductive factors and development of colorectal cancer. Subjects were postmenopausal women enrolled in the NIH-AARP Diet and Health Study, a cohort of 566,402 individuals (age 50-71) who completed a baseline questionnaire on demographics and lifestyle factors. Hazard ratios (HR) and 95% confidence intervals (95% CI) for the association of age at menarche, age at first child's birth, and age at menopause, as well as total parity and oral contraceptive use, were assessed using multivariate Cox models. Covariates included current age, body mass index (BMI), alcohol consumption, smoking, race, family history of colorectal cancer, physical activity, education, HT use, and diabetes. Results: During a median of 8.2 years of follow-up, 2,305 postmenopausal women were diagnosed with colorectal cancer. Compared with women who underwent menopause at < 40 years of age, menopause after 55 years of age was associated with an increased risk of colorectal cancer (HR = 1.45, 95%CI: 1.21-1.74; p-trend = 0.003). Among leaner women (BMI ≤ 25 Kg/M2), increasing parity was inversely related with colorectal cancer incidence; p-trend = 0.04), while later age at first child's birth (≥ 30 compared with ≤ 19 years) was associated with an increased risk of colorectal cancer (HR = 1.56, 95%CI: 1.13-2.14; p-trend, 0.02). Conclusions: These data support a role for sex hormones in colorectal tumorigenesis and suggest that higher endogenous estrogen exposure may increase risk of colorectal cancer. No significant financial relationships to disclose.
Corrected vs Uncorrected Obesity in Childbearing Women—What Really Drives Fetal Risks?
Authors: Aaron J. Dawes, Danielle M. Dawes, Melinda Maggard-Gibbons
Journal: JAMA Surgery (2016)

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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Surgery journal