tbuckley/cabot-search huggingface dataset:
Prognostic implication of p53 mutations in HNSCC: Results of Intragroup margin study (E4393)
Authors: L. M. Poeta, M. A. Goldwasser, A. Forastiere, N. Benoit, J. Califano, J. A. Ridge, J. Goodwin, D. Kenady, D. Sidransky, W. M. Koch
Journal: Journal of Clinical Oncology (2006)

5504 Background: The role of p53 as a prognostic marker in head and neck squamous cell carcinoma (HNSCC) is controversial. The intent of this study was to evaluate rigorously the prognostic value of p53 genetic status. Methods: Tumor samples from 480 HNSCC patients treated surgically with curative intent were collected in a prospective multicenter study over 5 years. 57 cases were not analyzed due to technical or administrative factors. Mutation status was determined in the 423 remaining cases, using p53 chip (GP53 GeneChip from Affymetrix, Inc., Santa Clara, CA) which identifies mutations in exons 2 through 11. Indeterminate calls were investigated using Surveyor and/or DHPLC analysis and all mutations were confirmed with an automated fluorescent system or manual sequencing. Clinical follow-up was accomplished following Eastern Cooperative Oncology Group protocol. Results: Median follow-up of the 423 evaluable subjects was 5.4 years with all patients followed at least 3 years. Mutation of p53 gene was present in 224 (53%) cases. There we significantly fewer mutations in tumors arising in the oropharynx (chi-square p = 0.02). The presence of p53 mutation was significantly associated with decreased overall survival. Median survival for patients with tumors with p53 mutation was 3.1 years compared to 5.4 years fro WT tumors (HR = 1.4, 95% CI =1.1 to 1.8, p = 0.01 log-rank test). This proved to be independent of tumor site in multivariate analysis. When mutations were segregated according to their effect on biological function through alteration of key DNA binding domains a Cox regression analysis revealed a statistically significant linear effect of the more disruptive mutations on overall survival with a HR of 1.3 for comparison of each group to the one of lower risk (more vs. less disruptive mutation v. WT (p = 0.001 Wald test). Conclusions: This large prospective series shows a strong relationship between TP53 mutation and prognosis in HNSCC patients. Furthermore, the biological impact of specific mutations has a predictable graded relation to clinical outcome. The results set the stage for use of p53 genetic status in the design of future clinical trials and support the development of targeted therapy to restore wild-type p53 function. No significant financial relationships to disclose.
Antibody-Mediated In Vivo Suppression of EL4 Leukemia in a Syngeneic Hos2
Authors: Jacob Zighelboim, Benjamin Bonavida, John L. Fahey
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Antibody-Mediated In Vivo Suppression of EL4 Leukemia in a Syngeneic Hos Get access Jacob Zighelboim, Jacob Zighelboim Search for other works by this author on: Oxford Academic PubMed Google Scholar Benjamin Bonavida, Benjamin Bonavida Search for other works by this author on: Oxford Academic PubMed Google Scholar John L. Fahey John L. Fahey 3Department of Microbiology and Immunology, School of Medicine, University of California at Los Angeles, Los Angeles, Calif. 90024. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 52, Issue 3, March 1974, Pages 879–881, https://doi.org/10.1093/jnci/52.3.879 Published: 01 March 1974 Article history Received: 28 August 1973 Accepted: 26 November 1973 Published: 01 March 1974
Acute Myocardial Infarction in Women
Authors: Laxmi S. Mehta, Theresa M. Beckie, Holli A. DeVon, Cindy L. Grines, Harlan M. Krumholz, Michelle N. Johnson, Kathryn J. Lindley, Viola Vaccarino, Tracy Y. Wang, Karol E. Watson, Nanette K. Wenger
Journal: Circulation (2016)

Cardiovascular disease is the leading cause of mortality in American women. Since 1984, the annual cardiovascular disease mortality rate has remained greater for women than men; however, over the last decade, there have been marked reductions in cardiovascular disease mortality in women. The dramatic decline in mortality rates for women is attributed partly to an increase in awareness, a greater focus on women and cardiovascular disease risk, and the increased application of evidence-based treatments for established coronary heart disease. This is the first scientific statement from the American Heart Association on acute myocardial infarction in women. Sex-specific differences exist in the presentation, pathophysiological mechanisms, and outcomes in patients with acute myocardial infarction. This statement provides a comprehensive review of the current evidence of the clinical presentation, pathophysiology, treatment, and outcomes of women with acute myocardial infarction.
The prognostic significance of epidermal growth factor receptor (EGFR) expression in ovarian cancer (OC) metastasis
Authors: J. Rahaman, N. Nagarsheth, F. Nezhat, C. Cohen, T. Kalir
Journal: Journal of Clinical Oncology (2005)

5067 Background: Prompted by the recent interest in therapies targeting EGFR, we sought to evaluate whether expression of EGFR in metastatic implants was of prognostic significance in a cohort of stage III OC patients treated uniformly at a single institution. Methods: Metastatic implants were analyzed from 80 patients with stage III OC who were treated from January 1985 to December 1994. All patients underwent primary cytoreduction and platinum-based combination chemotherapy and all subsequent care by the same team of gynecologic oncologists. Paraffin-embedded tissue slide sections from metastatic tumor were examined immunohistochemically for expression of EGFR using a Dako Cytomation Inc kit (Carpinteria, CA). The stain for EGFR was considered positive when at least 10% of the tumor cells showed distinct staining of the cytoplasmic membrane. Survival analysis were performed using the Kaplan-Meier method and the log-rank test, and Cox proportional hazard model used for multivariate analysis of prognostic variables. Results: The median age of the patients was 59.2 (range 32.5 - 86.8). The median follow up was 38.1 months (range 0.7 - 182 months). 17 of the 80 metastatic tumor specimens (21.25%) were positive for EGFR. The EGFR status did not correlate with any of the known prognostic variables including residual disease after primary cytoreduction, age, presence of ascites, performance status, tumor grade or histologic subtype. The median progression free interval was 9.0 months in the EGFR positive group versus 9.7 months in the negative group (p= .6326) Similarly, there was no survival difference (p= .5858) with a median overall survival of 38.7 months in the EGFR positive group versus 37.0 months in the EGFR negative group. In this study only the ability to achieve optimal cytoreduction (with residual disease < 1cm, p< .0003) was a significant independent adverse prognostic indicators on multivariate analysis. Conclusions: EGFR expression in metastatic ovarian cancer was not an independent prognostic factor in this uniformly treated cohort of stage III OC patients. No significant financial relationships to disclose.
Population pharmacokinetics of bevacizumab
Authors: J. Gaudreault, G. Greig, V. Cosson, M. Gupta, N. Jumbe, A. C. Hooker
Journal: Journal of Clinical Oncology (2008)

14570 Background: Bevacizumab (BEV) is an antibody targeting vascular endothelial growth factor (VEGF), and is approved in the EU and other countries for the treatment of breast, renal cell, colorectal, and non small cell lung carcinoma. Simultaneous characterization of BEV pharmacokinetics (PK) in ∼770 patients with different underlying disease was performed using a population (popPK) approach in order to improve the factors which may impact on BEV disposition. Methods: Patients with several carcinoma type received multiple intravenous (IV) infusions of BEV (either single agent or with chemotherapies) ranging from 1 to 20 mg/kg with administration ranging from weekly to every 3 weeks. Multiple samples were collected from each patient, and BEV serum concentrations were determined by ELISA. BEV PK was characterized by a 2- compartment model with first order elimination. The data were analyzed using non linear mixed effects modeling (NONMEM). Results: 6108 BEV samples from 773 patients (52% male, median body weight [BW] =73 kg) were included in the analyses. For a typical subject, clearance (CL) was 9.2 mL/hr, central volume of distribution (Vc) was 3280 mL, intercompartmental clearance (Q) was 15 mL/hr and the peripheral volume (Vp) was 3850 mL. The parameters were well estimated with relative standard error from 1.4 to 33% and the between subject variability ranged from 15 to 43%. The significant covariates, in order of decreasing influence on the variability of the parameters were 1) CL: baseline body weight (BW), albumin, tumor burden (TB) and sex 2) Vc: BW, sex, TB and protein 3) Vp: sex and chemotherapies. Conclusions: The final popPK model adequately described BEV PK profiles across all disease types. BEV has moderately variable PK and demographic/disease factors were identified to be correlated with PK parameters. BW was the covariate with impact on variability of both CL and Vc and supports the current dosing scheme based on body weight, while the clinical impact of other covariates do not warrant dose adjustments. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Roche Genentech™ BioOncology Genentech™ BioOncology, Hoffman-La Roche Roche
Long-term survival of patients receiving multimodality neoadjuvant therapy for resectable or borderline resectable pancreatic ductal adenocarcinoma.
Authors: Kinsey McCormick, Samuel H. Whiting, Grace Gyurkey, Wui-Jin Koh, Mika Sinanan, Andrew L. Coveler
Journal: Journal of Clinical Oncology (2014)

309 Background: While surgery offers the only chance for cure in localized PDA, outcomes remain poor for those who have undergone surgical resection (SR). Neoadjuvant therapy (NATx) has several advantages, including early treatment of micrometastatic disease, the potential for tumor downstaging, and improved selection of patients (pts) for surgery by excluding those with chemotherapy-refractory disease. Methods: We report long-term follow-up on consecutive pts with resectable or borderline resectable (R/BR) PDA treated at our institution with an off-protocol, but defined regimen of multi-modality NATx. Demographic, clinical and outcomes data were extracted from medical records. Overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan-Meier analysis. Results: 16 pts with R/BR PDA were treated with NATx; median follow-up is now 41 months (mo) (7.9-91.5). The median age was 57, 50% were female, and all had an ECOG PS &lt;2. Fourteen (88%) had BR disease, and 9 (56%) had radiographic evidence of nodal involvement. All pts received NA gemcitabine, docetaxel and capecitabine and 13 (81%) also received NA chemoradiotherapy with capecitabine +/- oxaliplatin. 14 pts (88%) underwent SR; of those, 11 (79%) received adjuvant chemotherapy. The median decline in CA19-9 over the course of NATx was 80%. An R0 resection was achieved in 11 pts (79%), and there were 2 pCR. To date, 12 pts have died, 4 are alive (including 2 with CA19-9 &gt;1000 at dx), and 3 are without recurrence. The mPFS and mOS were 27.4 and 41 mo, respectively. 1- and 3-year survival rates were 94% and 56%, respectively. When analyses were restricted to pts who underwent SR, the mPFS and mOS were 29 mo and 47.8 mo, respectively. There were no surgery-related deaths. 3 pts had postoperative wound complications. Conclusions: In this series of mostly BR pancreatic cancer pts, treatment with multi-modality NATx resulted in an almost doubling of mOS when compared to historical controls. NATx was also safe, and did not increase surgical morbidity or mortality. Based on these encouraging results, a phase II protocol of multi-modality NATx for R/BR PDA was initiated and has now completed accrual.
Hemochromatosis gene (HFE) mutations and chemotherapy-related cardiovascular risk profile in testicular cancer survivors (TCS)
Authors: E. C. De Haas, C. Meijer, N. Zwart, G. Van der Steege, H. M. Boezen, S. Sleijfer, F. E. Van Leeuwen, A. J. Smit, D. T. Sleijfer, J. A. Gietema
Journal: Journal of Clinical Oncology (2006)

14589 Background: TCS show an increased incidence of treatment-related cardiovascular disease. Standard chemotherapy (CT) may cause tissue damage by inducing free oxygen radicals through release of redox-active iron from body iron stores. HFE mutations associated with altered body iron load may therefore contribute to an increase in CT-induced free oxygen radicals and tissue damage. We investigated whether two HFE mutations (C282Y and H63D) are associated with cardiovascular risk profile in TCS. Methods: From a group of 90 TCS with a known cardiovascular status (JCO 2005; 23: 3718–25), genomic DNA for genotyping was available for 63 TCS (median (range) age at follow-up 35 y (24–54) and median follow-up duration 7 y (3–13)). Two HFE genotype groups were composed: HFE mutation (mut) (n = 19; any mutation C282Y and/or H63D) and HFE wild type (wt) (n = 44). Both groups were compared for cardiovascular risk profile, using Mann-Whitney U Test or Fisher’s Exact Test. Results: Groups had received comparable CT regimens. Body iron stores as reflected by plasma ferritin and transferrin saturation were not different for the HFE mut vs HFE wt group, respectively 104 μg/l (21–413) vs. 90 μg/l (22–569); p = 0.53 and 31% (20–49) vs. 30% (11–59); p = 0.15. Signs of vascular damage estimated by urinary albumin excretion and Von Willebrand factor levels were not significantly different: respectively 8.3 mg/24 h (4–165) vs. 7.7 mg/24 h (3–647); p = 0.90 and 90% (52–296) vs. 102% (28–235); p = 0.25. The prevalence of cardiovascular risk factors obesity (BMI &gt; 27.8 kg/m 2 ), metabolic syndrome (NCEP ATP III-criteria) and hypertension (mean 24-h blood pressure &gt;135/85 mmHg) are shown in the table. Conclusion: TCS with a mutation in the HFE gene do not show more signs of cardiovascular damage after CT compared to TCS with wt HFE. However, the data suggest that TCS with a HFE mutation may have more frequently cardiovascular risk factors. Further study in a larger group of TCS is needed to explore this observation. [Table: see text] No significant financial relationships to disclose.
Gene expression profile (GEP) for the prediction of pathologic complete response (pCR): Preliminary data from a neoadjuvant study of capecitabine (C), oxaliplatin (OXP), and radiation (RT) for esophageal cancer (EC).
Authors: N. I. Khushalani, G. Yang, W. Tan, J. Miecznikowski, D. Wang, R. V. Iyer, S. S. Yendamuri, C. E. Nwogu, H. R. Nava, M. M. Javle
Journal: Journal of Clinical Oncology (2010)

4100 Background: A pCR following chemoradiation (CRT) is associated with improved survival in EC patients (pts). Our prior study noted the safety of combination C, OXP and RT. The present phase II neoadjuvant (NA) EC trial was designed to examine the pCR rate using C, OXP and RT, correlate GEP with pCR, and assess toxicity. Methods: EC pts with stages II-IVa, adequate organ function and performance status were eligible. Treatment (Rx) consisted of OXP, 85 mg/m2 iv on days 1, 15 and 29, C (oral or enteral tube) 625 mg/m2 bid with RT, and 50.4 Gy RT (3D conformal), followed by surgery (S) 4-6 wks later. 2 cycles of OXP + C were given post-operatively. GEP using Agilent microarrays was conducted on primary tumor tissue pre-Rx, day (D) 17 of CRT and at S.More than 50% viable tumor cells were required. Results: 32 pts enrolled (27 M); median age 58.5 yrs; 25 adenocarcinomas and 7 squamous. Stage: II (9), III (19) and IVa (4). 30 pts completed NA Rx; 4 pts did not undergo S (2 disease progression, 2 declined). 21 pts have undergone S with 7 pCR (33%). 10/13 pts starting adjuvant therapy completed 2 cycles. No G4 nonhematologic toxicity during NA Rx; G3 toxicity: anorexia (1), esophagitis (1), fatigue (1), hyperbilirubinemia (2), elevated AST (6), OXP hypersensitivity (2), neutropenia (1). Post-op complications: pneumonia (2), infection (4), leak (2), esophageal fistula (1) and bowel obstruction (2). 1 pt developed acute leukemia, likely OXP-related 17 months post-Rx. Analysis on pre-Rx GEP on 22 pts via gene set analysis revealed several enriched genetic pathways comparing pCR with non-pCR pts. Specifically, the KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways glutathione metabolism and base excision repair, 2 pathways that may be important for chemotherapy resistance, were found to be enriched. Conclusions: C, OXP and RT is effective and well tolerated in resectable EC. Ongoing work will further validate the noted pathways in determining chemotherapy resistance. Acknowledgement: The study was approved and funded by the National Comprehensive Cancer Network (NCCN) from general research support provided by Roche Laboratories, Inc. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche
Social Disease vs Disease of Society
Authors: G L Fite
Journal: JAMA (1972)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Risk of testicular cancer in boys with cryptorchidism
Authors: M. Davenport, A J Swerdlow, C D Higgins, M C Pike
Journal: BMJ (1997)

Progress in reducing inpatient mortality from acute myocardial infarction is slowEditor-Brown et al report a substantial increase in the use of beneficial interventions for patients admitted to hospital with acute myocardial infarction in Nottingham from 1982 to 1992. 1 However, they found no change in inpatient mortality adjusted for age and sex.This contrasts with findings in Ontario, Canada, where hospital discharge abstracts show that inpatient mortality fell from 1981 to 1991 2 and has since fallen further (data on request).Brown et al suggest that the disparate results may reflect coding errors in the Ontario administrative data.Our group has assessed the classification of deaths from acute myocardial infarction in inpatients in the Ontario discharge abstracts.Matching Ontario administrative data to data from the GUSTO-I and LATE trials, we found the specificity of the administrative data to be 100% (1403/1403 alive), with overall sensitivity of 94% (104/111 deaths detected). 3he classification of acute myocardial infarction itself is more problematic.The sensitivity of the primary diagnosis of acute myocardial infarction is high, but specificity varies. 4 5There are two common reasons for false positive coding.Firstly, patients may be admitted to a coronary care unit with possible acute myocardial infarction but this diagnosis is ruled out and they are sent home quickly.Alternatively, patients recently admitted to hospital with acute myocardial infarction are readmitted for coronary angiography or with complications other than overt reinfarction, and the code for acute myocardial infarction is wrongly used again.Thus the analysis of outcomes in Ontario excluded both patients with a primary diagnosis of acute myocardial infarction who were discharged in under four days and patients who had been admitted to hospital for acute myocardial infarction in the preceding three months. 2t is therefore doubtful that imprecise coding explains the improving outcomes of acute myocardial infarction in Ontario.Indeed, only systematic coding errors could explain the observed trends in inpatient mortality, and we have found neither evidence nor a rationale for this.Ontario's administrative data do mirror the findings of Brown et al in two respects 2 : admissions for acute myocardial infarction, particularly among elderly patients, increased over the period studied, and inpatient mortality ranged from 16% to 21%, which is much higher than in the large randomised trials of thrombolytic treatment.Thus while the trends in Ontario are more positive than those in Nottingham, we agree with Brown et al that the cardiovascular megatrials have been enrolling skewed patient populations 3 and that progress in the battle to reduce inpatient mortality from acute myocardial infarction remains slow.
Congress Seeks FDA Documents About Generic Drug Approvals
Authors: Rita Rubin
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal