tbuckley/cabot-search huggingface dataset:
Comparison of kidney cancer symptoms and quality of life (QoL) in renal cell cancer (RCC) patients (pts) receiving sorafenib vs interferon-α (IFN)
Authors: C. Szczylik, D. Cella, T. Eisen, S. Shah, N. Laferriere, U. Scheuring, B. J. Escudier
Journal: Journal of Clinical Oncology (2008)

9603 Background: Sorafenib, an oral multi-kinase inhibitor with anti-angiogenic and anti-proliferative activity, inhibits VEGFR, PDGFR, c-Kit, Flt-3, RET, and Raf/MEK/ERK. Sorafenib has demonstrated activity in multiple tumor types including BC, HCC, melanoma, NSCLC, and RCC. Methods: The phase II trial randomized 189 pts with advanced RCC who had received no prior systemic therapy to continuous oral sorafenib 400 mg bid or IFN 9 million units tiw. A second trial phase allowed pts to cross over at progression to sorafenib 400 mg bid from the IFN arm or escalate to sorafenib 600 mg bid if they were on the sorafenib arm. Here we report the results of the treatment effect of sorafenib vs IFN on pt reported outcomes (PRO) from the first phase of this trial of pts with advanced RCC receiving first- line therapy. Kidney cancer symptoms were measured using a 15-item functional assessment of Therapy-Kidney Symptom Index (FKSI). QoL was measured using the Functional Assessment of Therapy-Biologic Response Modifier (FACT-BRM). FKSI and FACT-BRM were administered at baseline, at day 1 of each cycle, and at end of treatment visit. Differences between sorafenib and IFN were evaluated using a random coefficient model. Time to health status deterioration was assessed using Kaplan-Meier analysis. Results: At baseline there was no difference in FKSI or FACT-BRM scores. There was a clinically meaningful and statistically significant difference in total FKSI scores between sorafenib and IFN 40.5 vs 34.6 (p=0.015) during the first phase of the study. There was clinically meaningful difference in total FACT-BRM scores between sorafenib (LS mean = 104) vs IFN (LS mean = 93). Pts on sorafenib had a statistically significant longer time to health status deterioration than pts receiving IFN (p=0.0001). The analysis of Treatment Satisfaction Questionnaire for Medication (TSQM) questionnaire showed a statistically significant difference between treatment groups in favor of sorafenib on the global satisfaction domain, (p=0.019). Conclusions: Pts on sorafenib have fewer kidney cancer-related symptoms and concerns, better overall QoL, and greater global treatment satisfaction, compared with pts receiving IFN. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer Bayer Bayer Bayer Bayer
The restrictive–obstructive continuum and the failing heart
Authors: Gunnar Engström
Journal: Thorax (2016)

The close interrelationship between the heart and lungs was early recognised by medical scientists. In a paper from 1895, Alfred Lee Loomis stated that dyspnoea could be divided into four categories on an aetiological basis: laryngeal dyspnoea, bronchial dyspnoea, pulmonic dyspnoea and cardiac dyspnoea. The term cardiac dyspnoea was used if dyspnoea arose ‘from arrest in the passage of blood through the heart to the lungs’.1 Early studies using spirometry observed that patients with heart disease had lower vital capacity than ‘normal individuals’.2 Many years later, prospective analyses of population-based cohorts showed that reduced lung function also could predict the onset of cardiac diseases.3 ,4 Many studies since have shown that reduced vital capacity or FEV1 is associated with increased incidence of cardiovascular diseases among individuals from the general population.5 ,6 The relationships have been quite strong and comparable with the effects of traditional cardiovascular risk factors, such as obesity or hyperlipidaemia. The increased risk is not limited to those with the smallest lung volumes; in many studies there is a dose–response relationship over the whole distribution of FEV1 or FVC.

However, even though much research has been performed over the past decades, the underlying causal reasons for the increased cardiovascular risk remain elusive. …
Abstract P165: Geographic Co-morbidity of Cardiovascular Diseases in South Africa
Authors: Ngianga-Bakwin Kandala, Saverio Stranges, Samuel O Manda, William Tigbe
Journal: Circulation (2012)

Background: The growing burden of non-communicable diseases in Africa is well recognized. However, the interplay between chronic conditions and environmental and lifestyle factors is not well documented in this setting. We used statistical co-morbidity models to jointly estimate risks of four cardiovascular conditions: hypertension, coronary heart disease (CHD), stroke and hypercholesterolaemia that are known to share unhealthy diet and lifestyle as common risk factors. Methods: Data are from 13,827 adults (mean ±SD age 39 ±18, 58.4% women) interviewed in the 1998 South African Health and Demographic Survey aggregated to 52 health districts. We estimated shared-component spatial prevalence models to known individual risk factors, in addition to allowing for disease-specific spatially structured district random effects. Results: There appeared to be an associations between the district prevalence of hypertension and CHD (ρ =0.33), and stroke and hypercholesterolaemia (ρ =0.31). However, on the unadjusted disease-specific prevalence maps, it was not possible to prove geographical trends in prevalence. On covariate-adjusted smoothed maps, the disease-specific log-odds showed clearer spatial patterns. Hypertension and stroke were concentrated highly in south-western parts of the country; whereas CHD and hypercholesterolaemia were highly concentration in central north-eastern and the top north-eastern corridors, respectively. The shared component, which we took to represent nutrition and other lifestyle factors not accounted for in the model, had a larger effect on vascular disease prevalence in south-western areas of the country. The shared component appeared to have greater effect on hypertension and CHD, though the relative weights were not statistically significant. Conclusion: This study provides novel evidence on disease-specific risk and geographic distribution of cardiovascular risk in South Africa. Understanding the underlying risk interactions between diseases might be useful for public health resource allocation in this setting.
&lt;italic&gt;Brief Communication:&lt;/italic&gt; Mouse Mononuclear Cell Chemotaxis: Description of System
Authors: D A Boetcher, M S Meltzer
Journal: JNCI Journal of the National Cancer Institute (1975)

The mononuclear cell chemotaxis assay was adapted for use with normal mouse peritoneal cells. Mouse peritoneal macrophages responded well to endotoxinactivated mouse serum and to chemotactic factors produced by mouse spleen cell cultures stimulated with mitogens or specific antigen. The assay was quantitative, reproducible, and applicable to several mouse strains.
Quality of life as prognostic factor of overall survival in advanced hepatocellular carcinoma: A pooled analysis based on two French clinical trials
Authors: F. Bonnetain, N. Methy, X. Paoletti, S. Collette, M. Doffoel, O. Bouché, J. C. Barbare, L. Bedenne
Journal: Journal of Clinical Oncology (2008)

4596 Background: The aims of our study were to assess prognostic value of QoL and to explore if QoL improves 3 prognostic classifications among French patients with unresectable HCC. Methods: We have pooled 2 RCTs in palliative condition from Federation Francophone de Cancerologie Digestive (FFCD). In each trial QoL have been assessed at baseline using Spitzer QoL index (0 to 10). Three staging systems have been calculated: Okuda, Cancer of the Liver Italian Program (CLIP), Barcelona Clinic Liver Cancer group (BCLC) scores. To explore whether the scores can be improved by QoL, univariate Cox analyses of all potential baseline predictors have been performed. A final Cox model was constructed including multivariate significant predictors eligible to test an improvement of each scoring system. For each score best model were built with forward and backward procedures among baselines variables not redundant with the score. In the aim to retain the best prognostic variable to add from the final model we have compared AIC, LR CHI2 and the Log-likelihood. Harell C Index was calculated. Cox analyses have been stratified on trial. Results: Among 538 included pts, QoL at baseline was available for 489 pts (90%). Median OS were significantly improved with QoL level at Baseline ranging from 2.17 months (Spitzer = 3) to 8.93 months (Spitzer = 10). Variables retained in the multivariate Cox model were: jaundice (HR = 1.36 [1.04–1.79]), Hepatomegalia (1.50 [1.19–1.89]), Hepatalgia (1.43 [1.14–1.80]), portal thrombosis (1.45 [1.19–1.77], Alphafetoprotein (AFP) (1.73 [1.42–2.12 ]), Bilirubin (1.25 [1.01–1.55]), Albumin (0.73 [ 0.59 -0.89], Small HCC (0.56 [0.42–0.77]) and Spitzer QoL Index (0.84 [0.79–0.90]). According to Harrell’s c-index, CLIP plus Spitzer QoL Index had the better discriminant value (c = 0.71) as compared to Okuda plus Spitzer QoL Index (c = 0.69) or BCLC (c= 0.68). Conclusions: Based on this pooled analyzis, our results suggest that CLIP and Okuda could be better by associating Spitzer QOL Index. QoL was an independent prognostic factor instead of WHO PS. External validations of our result are currently performed on another trial in palliative condition. No significant financial relationships to disclose.
211At-Anti-CD45 Radioimmunotherapy Can Replace TBI Prior to Haploidentical Bone Marrow Transplantation and Yield Long-Term Hematopoietic Engraftment
Authors: Johnnie J. Orozco, Aimee L. Kenoyer, Ethan R. Balkin, Donald K. Hamlin, D Scott Wilbur, Sofia H.L. Frost, Mark D. Hylarides, Damian J. Green, Ajay K. Gopal, Brenda M. Sandmaier, Oliver W. Press, Paul V. O'Donnell, John M. Pagel
Journal: Blood (2014)
Molecular risk stratification in pediatric medulloblastoma
Authors: S. M. Pfister, F. Mendrzyk, A. Korshunov, A. Wittmann, G. Toedt, A. Benner, W. Werft, A. Kulozik, W. Scheurlen, B. Radlwimmer, P. Lichter
Journal: Journal of Clinical Oncology (2007)

9506 Background: Medulloblastoma is the most common malignant brain tumor and a significant cause of cancer mortality in children. Despite considerable therapeutic advances, prognosis remains poor, with a five-year-survival rate of about 60% emphasizing the urgent need for markers to allow for a more accurate tailoring of treatment intensity. Methods: We performed genome-wide analysis of DNA-copy number in 112 medulloblastomas using array-CGH. All patients had received craniospinal irradiation after surgery. Standard adjuvant chemotherapy with lomustine, cisplatin and vincristine or a regimen with equal potency had been administered to 73 patients. To identify novel prognostic markers, DNA copy number information was correlated with survival data using log rank and chi-square tests. For selected candidate genes identified by array-CGH, mRNA and protein expression were analyzed by real-time quantitative PCR, and immunohistochemically on tissue microarrays consisting of medulloblastomas from 189 patients. Results: Copy-number gains of chromosomes 6 and 17q, high-level amplifications of MYC and MYCN, and loss of 9p21.3 (CDKN2A locus) were identified as significant adverse prognostic markers; monosomy 6 was associated with good prognosis. Monosomy 6 and gain of 17q were mutually exclusive, whereas trisomy 6 almost always occurred in conjunction with 17q gain. Tumors with trisomy 6 and 17q gains exhibit strong up-regulation of MAP3K7 (chr. 6) and NLK (17q) mRNA, two key-enzymes of the non-canonical calcium-dependent Wnt-signaling pathway. Furthermore, this subgroup exclusively shows high mRNA-expression of several cancer-retina antigens (e.g. GNGT1, GNGT2, PDE6, RCV1, RDS and NRL). Tumors with monosomy 6, in contrast, display highly activated canonical Wnt signaling as indicated by nuclear protein expression of beta-catenin. Conclusions: We propose a model for the molecular risk stratification of medulloblastoma comprising five risk groups with significantly different survival using copy-number status of MYC, MYCN, and chromosomes 6 and 17q. Furthermore, we give evidence for a role of noncanonical calcium-dependent Wnt-signalling in medulloblastoma metastasis in a subset of tumors. Cancer-retina antigens could be used to facilitate the diagnosis and follow-up of this molecular subgroup. No significant financial relationships to disclose.
Antibody targeting of epithelial carcinoma-associated fibroblast activation protein blocks cellular proliferation, migration, and invasion.
Authors: S. Bauer, E. Fischer, T. Wuest, A. M. Scott, R. Schibli, G. Ritter, L. J. Old, C. Renner
Journal: Journal of Clinical Oncology (2010)

e13062 Background: Activated fibroblasts in the stroma of epithelial carcinomas are key mediators of cancer initiation, progression, and metastasis. Their phenotype is characterized by secretion of various growth factors and cytokines, and, amongst others, high expression of the Fibroblast Activation Protein (FAP) on the cell membrane. FAP is a type II serine protease that also has collagenase activity. FAP contributes to the tumor architecture by remodeling of extracellular matrix (ECM) through its proteolytic activity in concert with CD26, b1-integrin, and MMP-1. Thereby, functional impairment of FAP-related bioactivities is recognized to influence malignant growth and invasive cell behavior. Extent of FAP-expression is significantly correlated with a higher risk of tumor recurrence and death in pancreatic carcinoma and has been used as a prognostic marker for colorectal cancer. Since FAP is typically absent from normal adult tissue, it has long been suggested to be a promising therapeutic target. Methods: We selected novel anti-FAP antibodies from a nonimmunized phage library expressing antibody Fab fragments. Binding of most frequently identified clones, ESC11 and ESC14, to FAP was measured by surface Plasmon resonance. Clones were converted into human IgG antibodies and chosen for upscaled production. Reactivity of anti-FAP IgG to activated fibroblasts was assessed by flow cytometry. Interference of novel antibodies with FAP-mediated pro-invasive effects was demonstrated by proliferation assays and invasion of ECM. Results: The novel human antibodies bind to FAP at low nanomolar affinities and specifically target activated fibroblasts. Crosslinking of FAP by ESC11 and ESC14 antibodies significantly reduced its cell surface expression by rapid internalization. Such antibody-mediated conversion of a FAP-positive into a FAP-negative phenotype resulted in significant reduction of proliferation, migration, and invasion of activated fibroblasts. Conclusions: Since malignant and invasive behaviour of epithelial cancers depends on activated fibroblasts, our data strongly provide evidence for clinical development of novel human anti-FAP antibodies. No significant financial relationships to disclose.
Strengthening Surgical Mesh Safety
Authors: Rebecca Voelker
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
Relapsed childhood ALL: Gaining insights and identifying targets by gene expression profiling
Authors: D. Bhojwani, E. Raetz, I.-M. Chen, C. Willman, W. Carroll
Journal: Journal of Clinical Oncology (2005)

8511 Background: In spite of the significant progress made in childhood ALL, the outcome for the 25% of patients who relapse is dismal, necessitating a search for new targets. Methods: Bone marrow samples at relapse from 57 patients enrolled on Children’s Oncology Group (COG) protocol, AALL01P2, for treatment of first marrow relapse were obtained. Paired samples from initial diagnosis for 10 of these patients were retrieved from COG cell banks. Total RNA was extracted, amplified and hybridized to Affymetrix U133-A microarrays. Data was normalized by Robust Multichip Analysis and Genetraffic software was used for unsupervised analysis. Differentially expressed genes were identified by SAM (Significance Analysis of Microarrays). Results: As timing of relapse is the most important predictor of outcome, we identified 156 genes with significant differences in expression between early (< 36 months from diagnosis) and late (>= 36 months from diagnosis) relapse. The median false discovery rate of these genes was less than 2%. Genes from several functional groups were differentially expressed. For example, regulators of apoptosis (survivin, AVEN), cell cycle regulators (cyclins B1, B2, A2, CDC2) and DNA repair genes (TOP2A, APEX1, RAD51) were among those upregulated in the early relapse group. Many of these genes have been shown to be poor prognostic markers in a variety of tumors. In a separate unsupervised analysis of diagnostic and first relapse paired samples, diagnostic samples from patients with early relapse tended to cluster with their respective relapse pair (5/7 pairs), while late relapse pairs did not cluster together (3/3 pairs). Differences in the gene expression profiles between initial diagnostic vs. relapse samples were also observed with upregulation of several emerging and established therapeutic targets (e.g.survivin, cyclin B1, PTTG1, TOP2A) in the relapse cohort. Conclusions: Distinct gene expression profiles characterize newly diagnosed vs. recurrent ALL, and further distinguish relapse that recurs early from that which occurs late. These analyses may provide insight into mechanisms of ALL progression and clonal origins of recurrent disease. No significant financial relationships to disclose.
Abstract A2-60: Phospho-proteomic analysis of MEK inhibition in mutant NRAS melanoma
Authors: Ha Linh Vu, Michael A. Davies, Andrew E. Aplin
Journal: Cancer Research (2015)

Abstract Melanoma is a devastating form of skin cancer with limited therapeutic options. Fifteen to twenty percent of melanoma patients have an activating mutation in NRAS, a small GTPase. NRAS has several downstream effectors, the most well-characterized is RAF leading to activation of MEK/ERK. While there are no FDA-approved targeted therapies for melanoma patients with a primary mutation in NRAS, one form of targeted therapy that has been explored is MEK inhibition. Phase I to III studies of MEK inhibitors in mutant NRAS melanomas have shown disappointing clinical efficacy, the reasons for which are unclear. In 3D systems that mimic the dermal microenvironment, we found a heterogeneous response in our panel of mutant NRAS melanoma cells to the allosteric MEK inhibitor, trametinib. To explore the underlying basis of this heterogeneity, we utilized a high-throughput reverse-phase protein array (RPPA) platform to identify compensatory signaling alterations. The RPPA analysis of phospho-proteomic changes in NRAS mutant melanoma in response to trametinib indicated a compensatory increase in AKT signaling. Interestingly, we detected a decrease in mitogen inducible gene 6 (MIG6), a negative regulator of ERBB receptors. The overexpression of MIG6 led to a negative regulation of EGFR (ERBB1) and ERBB2, and subsequent decrease in AKT activation. Conversely, the depletion of MIG6 increased EGFR and ERBB2 signaling. Either depletion of MIG6 or addition of EGF increased migration of NRAS mutant cells treated with trametinib, an invasive phenotype that may mitigate the negative effects of trametinib on cell growth. Our results indicate a potential role for the combined inhibition of EGF/ERBB receptors and MEK in NRAS mutant melanoma patients. Citation Format: Ha Linh Vu, Michael A. Davies, Andrew E. Aplin. Phospho-proteomic analysis of MEK inhibition in mutant NRAS melanoma. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A2-60.
The effect of chemotherapy for breast cancer on cerebral white matter: A diffusion tensor imaging study
Authors: J. Abraham, M. W. Haut, M. T. Moran, S. Filburn, M. P. Iannetti, S. Lemiuex, H. Kuwabara
Journal: Journal of Clinical Oncology (2005)

606 Background: There is recent evidence of cognitive sequelae from chemotherapy for breast cancer. It has been suggested that chemotherapy affects the white matter of the brain. The purpose of this pilot project was to test the hypothesis that chemotherapy affects the frontal white matter more than the posterior white matter, using Diffusion Tensor Imaging (DTI). Methods: Ten patients with breast cancer (3 patients with stage I, 5 patients with stage II, and 2 patients with stage III) who reported changes in cognitive function after chemotherapy, served as participants. Five patients had received Adriamycin and cytoxan (AC) for 4 cycles and 5 patients had received AC followed by 4 cycles of a taxane. The patients were an average of 22 months post chemotherapy. All participants were screened for other health problems that could potentially affect cognition and brain structure. Seven healthy, age, education, and IQ matched women served as controls. DTI was measured in the axial plane with 30 4mm slices and 25 directions at 3Tesla. All analyses were performed blind to group membership. Fractional Anisotropy (FA) was calculated in the genu and splenium of the corpus callosum. Data were analyzed in a mixed two-way ANOVA. Participants also completed a measure of complex attention and speeded processing (Digit Symbol). Results: There was excellent interrater reliability of the FA measurements (0.96). There was a significant interaction of group x brain regions, F(1, 15)=4.85, p<0.05, with lower FA in the genu, but no difference between groups for FA in the splenium. Digit Symbol performance was significantly lower in patients than controls, F(1, 15)=8.65, p<0.05. FA in the genu was significantly correlated (r=0.46, p<0.05) with Digit Symbol performance. Conclusions: The results of this study suggest that chemotherapy for breast cancer causes changes in the frontal white matter of the brain which may lead to cognitive dysfunction. Prospective studies are warranted. No significant financial relationships to disclose.