tbuckley/cabot-search huggingface dataset:
Correlation of standard histological features and biomarkers with overall survival in breast carcinoma
Authors: G. F. Beadle, G. D. Francis, S. R. Stein, N. Pandeya, D. Purdie
Journal: Journal of Clinical Oncology (2004)

9683 Background: More than 100 variables have been described to predict prognosis in breast cancer but only maximum tumour size (T), histological grade, nodal status, ER and HER-2 are routinely incorporated into clinical practice. In this study both classic histological features and novel biomarkers using immunohistochemistry (IHC) were evaluated to assess overall survival. Methods: Formalin fixed paraffin embedded tissue was collected from 414 breast cancer patients with invasive ductal carcinoma. 247 patients were node negative. Median follow-up was 110 months (Range 1–148 months). Routine histological parameters were assessed and a number of antigens including ER, PR, HER-2, p53, Ki67 and microvessel density were evaluated using IHC. ER, PR, HER-2 and p53 were assessed semiquantitatively using the Quickscore method. Microvessel density was counted over a 200x field and adjusted to mm2, and 500 tumour cells were counted for assessment of Ki67. Tumour size was estimated using T while volume was modeled as an ellipsoid. Results: With univariate analysis, grade (p <0.001), nodal status (p <0.001), tumour volume (p <0.01), HER-2 (p = 0.006), Ki67 (p <0.001), mitotic rate (p <0.001) and T (p <0.001) were statistically significant. For node negative patients grade (p = 0.02), tumour volume (p = 0.03) and mitotic rate (p = 0.009) were significant. Using multivariate analysis, mitotic rate (p = 0.0005) and tumour volume (p <0.001) predicted nodal involvement, and grade (p = 0.002), nodal status (p = 0.001) and T (p <0.001) predicted overall survival. Conclusions: This analysis validates the current staging system. Additional IHC markers failed to predict overall survival when standard histological features were utilised. Mitotic rate and tumour volume were independent predictors of nodal metastases. Tumour volume estimation may be superior to T in predicting nodal metastases and requires further evaluation to determine its potential role in staging. No significant financial relationships to disclose.
CALGB 9840: Phase III study of weekly (W) paclitaxel (P) via 1-hour(h) infusion versus standard (S) 3h infusion every third week in the treatment of metastatic breast cancer (MBC), with trastuzumab (T) for HER2 positive MBC and randomized for T in HER2 normal MBC
Authors: A. D. Seidman, D. Berry, C. Cirrincione, L. Harris, L. Dressler, H. Muss, L. Norton, E. Winer, C. Hudis
Journal: Journal of Clinical Oncology (2004)

512 Background: W P is active, well tolerated and feasible with high efficacy alone or with T (Seidman et al. JCO 1998 and 2001). The primary aims of this trial were to determine whether: 1) W P improves response rate (RR) vs. S P, regardless of HER2 status and assignment to T, and 2) T added to P improves RR vs. P alone for HER2 normal tumors. Secondary objectives were to evaluate time to progression (TTP) and overall survival (OS) with respect to the above comparisons. Methods: Patients (pts) with measurable MBC, 0–1 prior chemotherapy regimens for locally advanced or MBC, ≥ 1 year from adjuvant taxane (if any) were stratified by line of therapy and randomized unequally (40:60) to S P 175 mg/m2 or W P 80 mg/m2. After accrual of the first 171 pts, when T became accepted as standard therapy for pts with HER2 positive MBC (Slamon et al NEJM 2001), HER2 status was assessed locally, pts with HER2 positive MBC received T and pts with HER2 normal MBC were randomized for T (standard weekly dosing). 158 pts treated with S P in the prior CALGB 9342 trial (Winer et al. JCO 2004) contributed data to the S P group in C9840 by pre-designed analyses. Results: 585 pts entered (488 first-line/97 second-line), and 577 were treated (n=735 with C9342 pts). Efficacy was analyzed as prescribed in adjusted multivariate models, controlling for relevant covariates including line of therapy and trastuzumab use. W P was superior to S P with respect to RR: 40% vs. 28%, (OR=1.61, p=0.017), and TTP: 9 vs. 5 mos, (HR=1.45, p = 0.0008). In this model, OS was 24 mos for W P vs. 16 mos for S P, (HR=1.19, p = 0.17). For pts with HER2 normal MBC, T did not improve RR: 35% vs. 29%, p=0.34, TTP: 7 vs. 6 mos, p=0.09, or OS: 22 vs. 20 mos, p=0.67. W P caused more grade 3 sensory/motor neuropathy (23/8% vs. 12/4%, p=0.001/0.04), and less grade ≥ 3 granulocytopenia (8 vs. 15%, p=0.013). 5 pts (0.8%) experienced significant cardiac dysfunction, 4 on T arms. There were 2 treatment related deaths, both due to pneumonia, on W P. Conclusions: W P is superior to S P in the management of MBC. T does not improve efficacy of P in HER2 normal MBC. Characterization of tumor tissue for HER2 (immunohistochemistry and fluorescent in situ hybridization) and other potential correlates of T sensitivity is ongoing centrally, as are analyses of serial changes in serum HER2 extracellular domain and quality of life. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb
Improvements in technique for whole-brain irradiation
Authors: M. T. Carpenter, J. C. Flickinger, M. A. Quader, C. E. Miles
Journal: Journal of Clinical Oncology (2004)

1539 Background: Brain metastases are commonly addressed with whole-brain irradiation, using unblocked opposed lateral fields, delivering 30 Gy in 10 fractions via 6 MV photons prescribed to midplane, with the isocenter set in the center of the cranial contents. A frequent result in long term survivors is permanent partial epilation in a strip of skin along the skull apex, a so-called “reverse Mohawk”. The object of our study was to determine if simple measures would be able to decrease radiation dose in this region at risk. We also investigated the dose delivered to the lens. Methods: A 6-cm wide, 4-mm thick strip of scalp on the top of the head, and bilateral lenses were contoured using the ADAC treatment planning system. Data from five patients undergoing CT simulation for brain irradiation were used for dose measurements. We investigated the dosimetry with an open-field whole-brain set up (WB), with a 1-cm inferior margin below all brain tissue, whole-brain set up with a scalp block drawn 1-cm external to the inner table of the skull (WBB), whole-brain set up with half beam (HB), with the isocenter at the inferior border and whole-brain set up with half beam with the same scalp block (HBB). To verify relative doses to regions of the scalp, dose was measured at representative points in a phantom, using thermoluminescent detectors (TLD) placed under a 3-mm slab of bolus to match the depth of hair follicles. Results: The percent of the scalp strip receiving > 90% of the prescribed dose for each set up was WB 16.4%, WBB 9.5%, HB 12.8% and HBB 4.8%. Dose to the whole brain was not affected. TLD measurements with the phantom confirmed that the top of the scalp received 22% more dose than the sides of the head. The percentage of the total dose delivered to the lenses with each technique was WB 78.6%, WBB 20.5%, HB 80% and HBB 15.1%. Conclusions: Dose to the strip of scalp at risk for permanent epilation from whole-brain irradiation is reduced by using a half-beam technique, and conformal blocking 1-cm external to the inner table of the skull. Both of these changes in technique also reduce lens dose while ensuring that the whole brain is adequately irradiated. This approach prevents development of the “reverse Mohawk” and can improve quality of life. No significant financial relationships to disclose.
Escalating teniposide systemic exposure to increase dose intensity for pediatric cancer patients.
Authors: J H Rodman, W L Furman, M Sunderland, G Rivera, W E Evans
Journal: Journal of Clinical Oncology (1993)

PURPOSE The primary objective for this study was to determine whether controlling pharmacokinetic variability, by designing patient-specific dosage regimens for teniposide using a Bayesian estimation control strategy, would permit an increase in dose intensity without increased toxicity. PATIENTS AND METHODS Twenty patients with relapsed acute lymphocytic leukemia were given teniposide as part of their induction and maintenance therapy. Before beginning reinduction therapy, an intensive pharmacokinetic study was performed based on 12 measured teniposide plasma concentrations. Doses were determined to achieve a targeted systemic exposure defined by an area under the plasma concentration time curve (AUC) beginning at an AUC consistent with that predicted for a patient with average pharmacokinetic parameters receiving the currently accepted maximal-tolerated dose. The targeted systemic exposure was then escalated in increments of 25% in cohorts of at least three patients until unacceptable toxicity occurred. In 36 follow-up studies, when teniposide was administered during maintenance therapy, a Bayesian strategy based on only three or five measured drug concentrations was evaluated for precision and bias for achieving the targeted systemic exposure against the full pharmacokinetic study. RESULTS Teniposide clearance varied over a fivefold range (3.7 to 21.6 mL/min/m2). With the use of the patient-specific dosage regimens, the intensity of systemic exposure was increased 50% (1,656 mumol.h v 1,060 mumol/L.h) over that previously possible with standard fixed doses, with no increase in acute, nonhematologic toxicity. Teniposide concentrations (n = 265) were well predicted (R2 = .82) with as few as three measured values from the initial study. CONCLUSION Targeting systemic exposure is clinically feasible, precise, and allows increased dose intensity for teniposide without increased risk of acute, nonhematologic toxicity, when compared with fixed-dose regimens.
Abstract 193: Transthoracic Impedance Patterns During Systole Reveal Changes in Cardiac Hemodynamics Using External Defibrillators
Authors: Jean-philippe Didon, Irena Jekova, Sarah Ménétré, Elina Trendafilova, Vessela Krasteva
Journal: Circulation (2012)

BACKGROUND: This study aims to test the Automated external defibrillators (AED) transthoracic impedance cardiogram (EICG) as a potential sensor for detection of compromised hemodynamics in different arrythmias (atrial fibrillation (AFIB), atrial flutter (AFL), ventricular tachycardia (VT)) vs. sinus rhythm (SR). METHOD: ECG and ICG recordings via pads in antero-apical position from 106 patients with AFIB, AFL, VT, who received external cardioversion (ECV) with external cardioverter/defibrillator are retrospectively processed. EICG patterns are accumulated to compute EICG measures (maximal EICG velocity (dZ/dt-PEAK), ventricular ejection time (VET), ventricular ejection ratio (VER=VET/ RR interval)), static impedance (Z). Hemodynamical indices are collected: heart rate (HR), HR variability (HRV), systolic and diastolic blood pressure (SYS, DIA). RESULTS: ANOVA test indicates that EICG measures significantly differ in AFIB, AFL, VT vs. SR (Table 1). Multiple linear regression shows that EICG measures are significantly dependent on hemodynamical indices (HR, HRV, SYS, DIA) with multiple correlation coefficient R=0.49 (VET), 0.54 (dZ/dt-PEAK), p&lt;0.001, whereas Z is not correlated. Linear discriminant analysis (LDA) shows that a combination of dZ/dt-PEAK, VET, VER is able to discriminate either AFIB, or AFL, or VT from SR with respective accuracy of 92.8%, 93.9%, 99.1%. CONCLUSION: EICG measures are significantly correlated to hemodynamical indices and are altered in AFIB, AFL, VT compared to SR. EICG is a potential sensor for compromised cardiac hemodynamics in AFIB, AFL, VT with a discrimination ability for VT vs. SR of 99.1%, but lower for AFIB and AFL vs. SR (around 93%).
Laboratory Manual in General Microbiology.
Journal: JAMA (1926)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Abstract 15313: Novel Single-Nucleotide Polymorphisms Predict Inverse Association With Non-Pulmonary Vein Triggers in Patients With Paroxysmal Atrial Fibrillation: Results From a Prospective Study (DECAF)
Authors: Sanghamitra Mohanty, Amelia W Hall, Prasant Mohanty, Chintan Trivedi, Luigi Di Biase, Rong Bai, Amin Al-Ahmad, Rodney Horton, John D Burkhardt, Javier Sanchez, Jason Zagrodzky, Shane Bailey, Joseph G Gallinghouse, Patrick Hranitzky, Vishwanath R Iyer, Andrea Natale
Journal: Circulation (2014)

Introduction: Although pulmonary veins (PV) are major sites of ectopic triggers initiating paroxysmal AF (PAF), triggers arising from non-PV sites also play a critical role in origination of PAF. As the exact mechanism of origin of the non-PV triggers is not known yet, we hypothesized that some common genetic variants are associated with the occurrence of these triggers. To examine our hypothesis we evaluated the association of several AF-specific genetic variants with prevalence of non-PV triggers in PAF patients undergoing catheter ablation. Methods: Four hundred AF patients (67% male, 62±12 year, left atrial size 45.3±7 mm, 64% non-paroxysmal) undergoing catheter ablation were prospectively enrolled. DNA extraction and genotyping for 16 AF-associated SNPS were performed from collected blood samples using Qiagen QiaAMP 96 well blood kit and TaqMan assay respectively. Three hundred seventy-two DNA samples were available for genotyping. Multivariate logistic regression analysis (adjusted covariates: age, ...
Cancer gene therapy: connecting basic research with clinical inquiry.
Authors: G Dranoff
Journal: Journal of Clinical Oncology (1998)

Molecular genetics has spawned an impressive outpouring of insights into the biology of neoplastic transformation and the host-tumor relationship. This deeper understanding of cancer pathogenesis presents a rich opportunity to develop novel therapeutic agents with improved selectivity for cancer cells. One promising approach involves gene therapy, which is the introduction of genetic material into a patient's tissues with the intent to achieve therapeutic benefit. A number of gene transfer systems have been designed that enable the genetic modification of relevant target cells, albeit with varying strengths and limitations. Several strategies to exploit gene transfer as a tool to target specific molecular defects intrinsic to cancer cells, enhance tumor chemosensitivity, and augment tumor immunogenicity are under intensive investigation. A number of these approaches have entered initial clinical testing and already provide intriguing new information about the biology of cancer in patients. In this review, I will highlight the critical issues and controversies that underscore preclinical experiments in cancer gene therapy, discuss some of the preliminary findings from the first wave of clinical trials, and speculate about the prospects that cancer gene therapy will change the way that cancer medicine is practiced.
My Weight Loss Journey
Authors: Fiona Clement
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
Defining the competing risk of local-regional and distant recurrence in 1,256 patients treated with mastectomy and doxorubicin-based adjuvant chemotherapy
Authors: T. A. Buchholz, W. A. Woodward, S. L. Tucker, E. A. Strom, K. K. Hunt, A. U. Buzdar, G. H. Perkins, N. R. Schechter, G. N. Hortobagyi
Journal: Journal of Clinical Oncology (2004)

555 Background: It has been suggested that patients with 1–3 positive lymph nodes (+LN) (Stage II) are more likely to achieve a survival benefit from postmastectomy radiation (PMRT) than those with 4–9 +LN (Stage IIIA), because patients with Stage II disease have a lowerer competing risk of distant metastases (DM). To evaluate this, we compared the proportional risks of local-regional recurrence (LRR) and DM according to stage of disease and whether treatment included PMRT. Methods: We retrospectively studied the records of 1256 patients who met the following criteria: treatment with mastectomy and doxorubicin-based adjuvant chemotherapy; treatment on an institutional prospective clinical trial; sufficient information available to retrospectively restage the extent of disease according to 2003 AJCC pathological staging guidelines; and pathological stage IIA-IIIC disease. Within this cohort, 370 (29%) were treated with PMRT. Results: After a median follow-up of 10.4 years, the crude rates of developing a LRR or DM according to stage were: IIA-19%, IIB-39%, IIIA-48%, IIIB/C-64%. The table shows the percentage of total events that were isolated LRR within each stage according to the use of radiation. Radiation reduced the competing risk of LRR in all stages. The greatest percentage of of total events that were isolated LRR occurred in patients with stage IIIA disease and accordingly, PMRT had the greatest reduction in the percentage of total events that were isolated LRR in these patients. Conclusions: Postmastectomy radiation reduces the percentage of events that are LRR across all subcategories of stage II and III breast cancer. When considered in light of the competing risk of DM, radiation would be predicted to have the biggest survival benefit for patients with 4–9 +LN (stage IIIA disease). No significant financial relationships to disclose.
Suppression of NFκB and its regulated pathways by oral administration of green tea polyphenols in an autochthonous mouse model of prostate cancer
Authors: Yogeshwer Shukla, Vaqar M. Adhami, Imtiaz A. Siddiqui, Najia Zaman, Sami Sarfaraz, Hasan Mukhtar
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4893 

Green tea polyphenols (GTP) possess strong chemopreventive properties against a variety of animal tumor models and in some human epidemiological studies. We have earlier shown that oral infusion of GTP inhibits the growth and progression of prostate cancer (PCa) in transgenic adenocarcinoma of mouse prostate (TRAMP) model and that inhibition of insulin like growth factor-I (IGF-I) signaling plays a major role in this process. IGF-I is known to stimulate sustained activation of NFκB and constitutive activation of NFκB occurs during PCa progression in humans and TRAMP. In this study we examined the role of proteins involved in NFκB signaling and other associated molecules during GTP mediated chemoprevention of PCa in TRAMP mice. Four weeks old male TRAMP mice were fed orally with 0.1% GTP as the sole source of drinking fluid throughout and water-fed animals served as controls. The animals were sacrificed at 4, 8, 20 and 28 weeks following GTP feeding and dorsolateral prostate tissues were collected. GTP feeding to TRAMP resulted in significant inhibition of constitutive NFκB activation. This corresponded with suppression of receptor activator of NFκB (RANK), known to up-regulate anti-apoptotic proteins. Inhibition of NFκB accompanied inhibition of NFκB inducing kinase (NIK), IKKα, IκBα and phospho-NFκB. This inhibition of NFκB signaling was observed in GTP-fed animals at all time points examined. Osteopontin, an extracellular matrix protein secreted by infiltrating macrophages and tumor cells, plays a role in the transition to metastatic PCa and is expressed at high levels in poorly differentiated carcinomas in TRAMP. Since osteopontin is known to stimulate tumor growth through activation of NFκB, we next determined the expression of osteopontin during GTP-mediated inhibition of PCa. An inhibition in the expression of osteopontin by oral infusion of GTP, particularly at 24 and 32 weeks of age was observed. Increased resistance to apoptosis also occurs due to constitutive activation of signal transducer and activator of transcription (STAT)-3. We observed an increased expression of STAT-3 in TRAMP as a function of age that was inhibited by oral infusion of GTP. Inhibition of NFκB signaling is known to activate apoptotic and inhibit anti-apoptotic proteins. Therefore, we next analyzed Bax and Bcl2 levels in the dorsolateral prostate of TRAMP mice fed GTP. We observed increasing levels of Bax and decreasing levels of Bcl2 in each treatment group of GTP-fed, tilting the balance between Bax and Bcl2 in favor of apoptosis. Taken together, our data strongly suggests that oral consumption of GTP inhibits NFκB signaling which may contribute to induction of apoptosis observed in GTP-fed TRAMP mice.