tbuckley/cabot-search huggingface dataset:
The effect of low serum sodium on treatment outcome to vascular endothelial growth factor (VEGF)-targeted therapy in metastatic renal cell carcinoma: Results from a large international collaboration.
Authors: F. A. Schutz, W. Xie, D. Y. Heng, F. Donskov, L. Wood, U. N. Vaishampayan, M. Tan, M. J. MacKenzie, C. K. Kollmannsberger, T. K. Choueiri
Journal: Journal of Clinical Oncology (2011)

322 Background: Hyponatremia has been associated with poor survival in many solid tumors and more recently found to be of prognostic and predictive value in metastatic renal cell cancer (mRCC) patients (pts) treated with immunotherapy (Jeppesen et al, Br J Cancer. 2010). We sought to investigate the influence of baseline hyponatremia in mRCC pts treated with contemporary vascular endothelial growth factor (VEGF)- targeted therapy in a larger international and multi-institutional database. Methods: Baseline characteristics and outcomes on 855 pts treated with first-line anti-VEGF therapy for mRCC were available from 8 Cancer Centers to study the impact of hyponatremia (defined as serum Na&lt;135 mmol/L) on clinical outcome as measured by overall survival (OS), time to treatment failure (TTF), best response (CR, PR, SD and PD). Results: Median OS after treatment initiation was 16.8 months (mos) (95% CI: 14.9, 18.5 mos), with 334 (39%) of patients remaining alive. Median follow-up in pts alive was 18.8 mos. Median baseline serum sodium was 138 mmol/L (range: 122–159), and hyponatremia was found in 16.7% of pts. On univariate analysis, hyponatremia was associated with shorter OS (6.5 vs. 18.8 mos; HR 2.32 [95% CI: 1.86–2.89], p&lt;0.0001), shorter TTF (2.8 vs. 6.9 mos.; HR 2.20 [95% CI: 1.81–2.68], p&lt;0.0001), and lower disease control rate (DCR) as defined by CR+PR+SD (51.2% vs. 74.6%, OR 0.36 [95% CI: 0.2–0.57], p&lt;0.0001). In multivariate analysis adjusted for MSKCC or Heng's risk criteria (JCO 2009), these effects remain significant with p&lt;0.001 for OS and TTF and p=0.01 for DCR. The results were similar (p&lt;0.001) if sodium was analyzed as a continuous variable. Conclusions: This is the first large multi-institutional report to show that low serum sodium is independently associated with a worse outcome in mRCC pts treated with VEGF-targeted agents. No significant financial relationships to disclose.
Molecular Phenotype of Malignant CD34+ Hematopoietic Stem and Progenitor Cells in Chronic Myelogenous Leukemia.
Authors: Ralf Kronenwett, Elena Diaz-Blanco, Thorsten Graef, Ulrich Steidl, Slawomir Kliszewski, Ingmar Bruns, Frank Neumann, Simone Bork, Ulf Butterweck, Nicole Roes, Benedikt Brors, Roland Eils, Guido Kobbe, Norbert Gattermann, Rainer Haas
Journal: Blood (2005)
Sentinel lymph node biopsy following neoadjuvant chemotherapy in clinically node-negative breast cancer patients.
Authors: K. Enokido, S. Nakamura, K. Tsugawa, Y. Kojima, H. Iwata, S. Ohno, F. Akiyama, K. Motomura
Journal: Journal of Clinical Oncology (2011)

15 Background: Sentinel lymph node biopsy (SLNB) is a widely accepted staging method for patients with early breast cancer. But SLNB following neoadjuvant chemotherapy (NAC) is also controversial because of insufficient evidence to recommend as a standard procedure. The aim of our study was to demonstrate the feasibility of SNLB following NAC. Methods: The clinical study of SLNB for clinically node-negative breast cancer patient was conducted as a large cohort study to confirm the identification rate and safety of this procedure. It was investigated by The Japanese Breast Cancer Society and was accomplished between the years March 2008 and October 2009. In this study 11,228 cases are registered before SLNB from 64 institutions. Of the 11,228 eligible cases, analysis was conducted among 489 cases that were introduced neoadjuvant chemotherapy. Results: SLNB was performed in 110 cases before NAC, 379 cases after NAC. The sentinel node identification rate before NAC was 106/110 cases (96.4%), after NAC was 373/379 cases (98.4%). Intraoperative frozen section analysis was performed in 280 cases, 71 cases were positive. The remaining 219 patients displayed no metastasis in the intraoperative examination, and 6 of these 219 (2.7%) were positive in the final pathological analysis. Conclusions: The identification rate of SLNB following NAC is not inferior to the result of major clinical studies previously reported in the world. There is insufficient evidence to recommend this as a standard procedure. Further research with subgroup analysis is necessary to identify whether SLNB following NAC is feasible or not (planned study). The primary end point for Group A is local relapse rate, Group B is not only the accuracy and false negative rate also the utility of One-step Nucleic Acid Amplification (OSNA).
The influence of race and treatment choice in 16,508 men treated either conservatively, with radiotherapy, or surgically for clinically localized prostate cancer.
Authors: P. Sooriakumaran, T. Field, M. John, R. Leung, A. Tewari
Journal: Journal of Clinical Oncology (2011)

210 Background: There are known variations in cancer survival based on race and treatment choices. We report the long-term survival probability, based on race, in 16,508 men with localized prostate cancer treated either conservatively or by radiotherapy or radical prostatectomy. Methods: We extracted survival data from tumor registries of six Cancer Research Network sites in the United States. Patients were stratified into four racial groups: Caucasians, African Americans, Hispanics, and Asians. The Cox proportional-hazards regression model was used to compare long-term survival in the three treatment groups. Kaplan-Meier survival curves and competing risk analysis was also performed. Results: Survival was improved for patients who underwent radical prostatectomy compared to radiotherapy or watchful waiting. This was true for all patients combined (Table) as well as for all races individually. Radiotherapy had at least equivalent survival outcomes as watchful waiting in all groups. The differences between treatments were greater for overall survival than for prostate cancer specific survival in all groups, though the extent of the differences varied by race. Conclusions: Radical prostatectomy increases survival in men with localized prostate cancer compared to both radiotherapy and watchful waiting, especially for Caucasian men. Radiotherapy was at least equivalent to watchful waiting for all races. Racial disparities in outcome may influence treatment choices for men with clinically localized prostate cancer. [Table: see text] [Table: see text]
Aggressive phenotype for prostate cancer cells that survive high-dose ionizing radiation.
Authors: Tao Wang, Robert Carraway, Joshua Briggs, Thomas J Fitzgerald
Journal: Journal of Clinical Oncology (2012)

236 Background: Radiation therapy (RT) is an important primary treatment for localized prostate cancer (PCa). However, certain patients can relapse and become resistant to RT. To identify the molecular mechanisms underlying RT resistance, we studied human PCa cells that survive fractionated high dose IR in vitro. Methods: DU145 (DU), a human cell line from PCa metastasized to brain, was exposed to fractionated ionizing radiation (IR) up to 40 Gy. The cancer biology of the surviving cells (DUIR) after 4 month in culture was studied. Cell growth and survival were assessed using cell counting, SRB and clonogenic assay. Invasiveness was measured using Boyden chambers. Caspase activity was determined for apoptosis. Activation of signaling molecules and expression of biomarkers was assessed using Immunoblot. Hormone binding to receptors was assayed using iodinated ligands. Results: Whereas DU was squamous in shape, DUIR displayed fibroblast-like morphology with long protrusions resembling cells undergoing epithelial-mesenchymal transition (EMT) confirmed by reduced E-cadherin and enhanced vimentin expression. DUIR cells showed higher level of neurotensin receptor 1 (NTR1) and chromogranin B resembling a neuroendocrine (NE) phenotype. DUIR has significantly higher survival than DU when exposed to IR (6–10 Gy) or zinc-directed toxins and grows significantly faster in response to serum or NT at a dose dependent manner. Addition of NTR1 antagonist SR486923 abolished the NT enhanced cell growth. DUIR had increased invasiveness through the matrigel-coated membrane. ERK and PKC, but not AKT, were constitutively active in DUIR. BCL2 level was upregulated in DUIR. NT stimulation reduced apoptosis while SR486923 enhanced apoptosis in DUIR cells upon IR. Conclusions: PCa cells that survive high dose IR display an aggressive phenotype characterized by NE and EMT features including invasion and resistance to IR/drug induced cell death. These changes could be due to constitutive activation of growth signaling pathways and upregulation of anti-apoptosis/necrosis molecules. Further study may provide insight into the mechanism of cellular resistance to therapy and establish strategies for novel therapeutic applications.
Predicting Response to Therapy for Graft-vs-Host Disease (GvHD) with a Rapid Immune Function Assay.
Authors: Elias J. Anaissie, Jose A. Diaz, Monica L. Grazziutti, Marisa H. Miceli, Michele Fox-Cottler, Bart Barlogie, Frits van Rhee
Journal: Blood (2007)
Prostate cancer hypoxia as a predictor of early biochemical and local failure after radiotherapy.
Authors: M. Milosevic, R. G. Bristow, C. Menard, P. W. Chung, A. Bayley, M. McLean, A. Toi, M. K. Gospodarowicz, C. Catton, P. R. Warde
Journal: Journal of Clinical Oncology (2011)

20 Background: Tumor hypoxia is an important determinant of patient outcome in many human malignancies, and has been associated with radioresistance and the development of metastases. The aim of this study was to determine the predictive effect of hypoxia in prostate cancer patients treated with RT. Methods: A total of 256 patients with clinically localized prostate cancer underwent pre-treatment, transrectal, ultrasound-guided measurement of tumor oxygen using a needle electrode. The median pO 2 (mpO 2 ) was 6.7 mm Hg and the median hypoxic proportion &lt;10 mm Hg (HP 10 ) was 0.63. Most patients were treated with IMRT to the prostate alone using doses in the range of 75.6-79.8 Gy. Sixty-one received neoadjuvant and concurrent hormonal therapy. The Phoenix definition of biochemical relapse was used, and the median follow-up was 5.4 years. Results: The 5-year bRFR was 78%. High PSA and Gleason score were independently associated with biochemical relapse, and formed the baseline clinical multivariate model. The effect of hypoxia was found to vary with the duration of patient follow- up. HP 10 , when added to the clinical multivariate model as a time-dependent variable, was a significant, independent predictor of early bRFR (p=0.015). The predictive effect of hypoxia diminished with increasing follow-up and was lost by 36 to 48 months. The relationship between hypoxia and early biochemical recurrence was more pronounced when the analysis was restricted to 144 patients with bulk tumor at the site of the oxygen measurements (p=0.008). Prostate biopsy was performed in 73 patients a median of 36 months after completing RT. Hypoxia was the only factor predictive of local recurrence in this sub-group, with the effect being greatest early in follow-up (p=0.038). Conclusions: This is the largest clinical study of prostate cancer hypoxia with direct measurement of tumor oxygen levels. It suggests that hypoxia in the index tumor increases the risk of recurrence early after completing RT but not at longer times. The results imply a complex interaction between hypoxia and local vs. distant failure, which may be better elucidated with longer follow-up. No significant financial relationships to disclose.
Household energy and health: where next for research and practice?
Authors: Majid Ezzati, Jill C Baumgartner
Journal: The Lancet (2016)

Cooking and home heating with coal and biomass fuels (wood, crop residues, animal dung, and charcoal) are ideal subjects for well intentioned epidemiology. Cooking and heating with such fuels generate large amounts of pollutants that can harm people's health throughout the lifecourse, a risk that largely affects poor communities. In a simple world, epidemiology would investigate the hazardous effects and test the benefits of any interventions, and rational individuals and policy bodies would use this information to initiate positive change.
Diffusion-weighted magnetic resonance imaging in patients with known or suspected breast malignancy: Correlation between apparent diffusion coefficient and histopathologic diagnoses.
Authors: A. C. Kim, D. Ying, P. Sheth, J. M. Park
Journal: Journal of Clinical Oncology (2011)

65 Background: Magnetic resonance imaging (MRI) is an important imaging modality for evaluating patients at high risk for breast malignancy. However, the role and utility of diffusion-weighted imaging (DWI) in breast MRI has not been fully elucidated. This study was designed to investigate the relationship between apparent diffusion coefficient (ADC) values and histopathologic diagnoses in benign and malignant breast pathologies as well as to assess the relative diagnostic value of this parameter. Methods: We searched our database for patients who received breast MRI studies from February 2010 through March 2011. We then identified those patients who had either known or suspected breast malignancy and who had also undergone DWI. Breast abnormalities were identified through a review of the short tau inversion recovery (STIR) and T1-weighted pre- and post-contrast images. DWI images were evaluated and the corresponding ADC values were calculated. These lesions were correlated with histopathologic results when available. Results: A total of 174 patient MRI studies were evaluated. Single dominant lesions were assessed and included biopsy-proven infiltrating ductal carcinoma (IDC), biopsy-proven ductal carcinoma in situ (DCIS), and benign lesions including cysts. The median ADC value for IDC was 118 x 10 -5 mm 2 s -1 . The median ADC value for DCIS was 123 x 10 -5 mm 2 s -1 . Finally, the median ADC value for breast cysts was 217 x 10 -5 mm 2 s -1 . Conclusions: As the role of MRI continues to evolve in the evaluation of breast pathology, the addition of DWI may increase diagnostic confidence for breast cancer, allowing for further differentiation from benign lesions. DWI is feasible to implement in many clinical practices and correlates with imaging features of breast cancer. The DWI images are acquired rapidly and without intravenous contrast. This method of imaging could be used in short intervals to assess treatment response to therapies such as biologic inhibitors or radiation therapy.
Passive frame theory: A new synthesis
Authors: Ezequiel Morsella, Christine A. Godwin, Tiffany K. Jantz, Stephen C. Krieger, Adam Gazzaley
Journal: Behavioral and Brain Sciences (2016)

Passive frame theory attempts to illuminate what consciousness is, in mechanistic and functional terms; it does not address the "implementation" level of analysis (how neurons instantiate conscious states), an enigma for various disciplines. However, in response to the commentaries, we discuss how our framework provides clues regarding this enigma. In the framework, consciousness is passive albeit essential. Without consciousness, there would not be adaptive skeletomotor action.
Conformation-Specific Detection of α-Synuclein
Authors: Tim Bartels
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
Chromosome 1q21 Gains Confer Inferior Outcomes In Multiple Myeloma Treated With Bortezomib But Copy Number Variation and Percentage Of Plasma Cells Involved Have No Additional Prognostic Value
Authors: Gang An, Yan Xu, Shuhui Deng, Dehui Zou, Weiwei Sui, Lihui Shi, Fenghuang Zhan, Lugui Qiu
Journal: Blood (2013)
A novel immunoassay to quantify paclitaxel in plasma using monoclonal antibody–coated nanoparticles.
Authors: D. J. Cline, G. D. Lundell, R. L. Harney, H. Zhang, H. Raiz, Y. Li, J. B. Courtney, J. R. Bertino, S. J. Salamone
Journal: Journal of Clinical Oncology (2011)

e11544 Background: Paclitaxel (PTX) is used in first line treatment of patients having a variety of solid tumors including breast, ovarian, and NSCL carcinomas. Paclitaxel has substantial variability in PK parameters, with up to 10-fold inter-patient differences in Cmax and/or AUC. This variability has critical clinical consequences for severe toxicities at high concentrations and decreased efficacy at low concentrations. The time above a critical paclitaxel plasma concentration of 0.05 µmol/L (Tc>0.05, 42 ng/mL) is correlated to toxicity and efficacy in many clinical studies. The current chromatographic methods for measuring paclitaxel blood levels are time-consuming and expensive. A new nanoparticle-based automated assay provides a rapid, simple and cost-effective measurement of PTX levels in patients undergoing treatment to allow timely personalized dose adjustment. Methods: A prototype automated homogenous immunoassay to quantify PTX, requiring less than 10μL plasma, was developed for use on the Beckman Coulter AU400 clinical analyzer. Total imprecision and linearity of the assay were evaluated using normal human plasma (NHP) pools spiked with PTX. Background of assay was determined by measuring >200 NHP samples. Selectivity was characterized by testing metabolites and degradation products of PTX for cross-reactivity at relevant concentrations. Results: With a quantitation range from 20 to 320 ng/mL, and instrument auto-dilution, plasma PTX levels can be measured up to 12,000 ng/mL. Time-to-first result was < 9 minutes and 400 samples per hour could be measured using a stored calibration curve. The total imprecision of spiked NHP was < 5% CV and the assay was linear from 15 to 300 ng/mL. The background of the assay was < 8 ng/mL. Cross-reactivities to 6α- and 3’-p-hydroxypaclitaxel, the major metabolites of PTX, were 16% and 7%, respectively, and <1% for the major degradation product, baccatin III. Conclusions: This immunoassay is suitable for routine measurement of plasma PTX concentrations with the advantages of speed, small sample size, no sample pretreatment, and application on automated instrumentation, and may provide a tool for optimization of PTX blood levels with PK-guided dosing.
Prognostic significance of LINE-1 methylation level in esophageal squamous cell carcinoma.
Authors: Yoshifumi Baba, Shiro Iwagami, Masayuki Watanabe, Hironobu Shigaki, Satoshi Ida, Yohei Nagai, Takatsugu Ishimoto, Masaaki Iwatsuki, Yasuo Sakamoto, Yuji Miyamoto, Hideo Baba
Journal: Journal of Clinical Oncology (2012)

26 Background: Genome-wide DNA hypomethylation plays a role in genomic instability and carcinogenesis. DNA methylation in the long interspersed nucleotide element-1, L1 (LINE-1) repetitive element is a good indicator of global DNA methylation level. LINE-1 methylation is a useful marker for predicting cancer prognosis and monitoring efficacy of adjuvant therapy. Esophageal squamous cell carcinoma, the major histological type of esophageal cancer in East Asian countries, is one of the most aggressive malignant tumors. Nonetheless, prognostic significance of LINE-1 hypomethylaiton in esophageal cancer remains uncertain. Methods: Using 217 curatively resected esophageal squamous cell carcinomas, we quantified LINE-1 methylation using bisulfite-PCR-pyrosequencing assay. Cox proportional hazards model was used to calculate mortality hazard ratio (HR), adjusted for clinical, epidemiologic, and pathological variables. Results: Esophageal cancers showed significantly lower LINE-1 methylation level compared to matched normal esophageal mucosa (p&lt;0.0001; N=50). Tumoral LINE-1 methylation ranged from 24.8 to 91.8 of 0-100 scale (N=217; mean 64.5; median 65.0; standard deviation 12.8). LINE-1 hypomethylation was significantly associated with disease-free survival [log-rank p=0.0008; univariate HR= 2.31, 95% confidence interval (CI) 1.38-3.84, p=0.0017; multivariate HR=1.81, 95% CI 1.06-3.05, p=0.031] and overall survival (log-rank p=0.0013; univariate HR=2.21, 95% CI 1.33-3.60, p=0.0026; multivariate HR=1.87, 95% CI 1.12-3.08, p=0.018]. Conclusions: LINE-1 hypomethylation in esophageal cancer is associated with shorter survival, suggesting its role as a prognostic biomarker. Given that epigenetic changes, including DNA methylation alterations, are reversible and can thus be targets for therapy or chemoprevention, our findings may have considerable clinical implications.
CAL-101, a Potent Selective Inhibitor of the p110δ Isoform of Phosphatidylinositol 3-kinase, Attenuates Pathway Signaling, Induces Apoptosis, and Overcomes Signals From the Microenvironment In Cellular Models of Hodgkin Lymphoma
Authors: Sarah A Meadows, Adam Kashishian, Dave Johnson, Volker Diehl, Brian Lannutti
Journal: Blood (2010)
DMT1 Mutation in a Patient with Hypochromic Microcytic Anemia: Functional Consequences and Response to Erythropoietin.
Authors: Monika Priwitzerova, Dagmar Pospisilova, Guangjun Nie, Alex D. Sheftel, Martha P. Mims, Josef T. Prchal, Vladimir Divoky, Prem Ponka
Journal: Blood (2005)