tbuckley/cabot-search huggingface dataset:
Economic Implications of 21-Gene Recurrence Score Assay: US Multicenter Experience
Authors: John Hornberger, Gary H. Lyman, Rebecca Chien
Journal: Journal of Clinical Oncology (2010)

Lo et al 1 reported the first prospective treatment impact study of the 21-gene recurrence score (RS) assay (Oncotype DX, Genomic Health, Redwood City, CA) in the United States, administered to 89 women.They cited our economic analyses of the RS, where we found that the RS should be associated with similar efficacy and lower costs. 2,3As these estimates were based on projected treatment changes reported during early adoption of the RS, Lo et al 1 suggested that "it would be interesting to recalculate cost-effectiveness based on a 20% to 30% treatment change resulting from the use of the RS assay, with most resulting in less chemotherapy use."We have performed the economic analyses suggested, applying their estimates, and also estimating effectiveness as quality-adjusted years of life gained (QALYs) associated with lower rate of chemotherapyrelated adverse events and reduced 10-year distant recurrence rate.The average QALY gained exceeded 0.2 years, and was associated with a direct medical savings of $2,099 for chemotherapy drugs, $902 for supportive care, $1,049 for management of adverse events, and $230 resulting from fewer recurrences.Including the cost of the RS, the average total direct medical savings exceeded $300 dollars per patient tested.As reported in the original economic analyses, results may vary for other centers based on their unit costs, use of medical resources (eg, type of chemotherapy used and level of supportive care), selection of patients to be tested, and how physicians and patient elect to interpret the test results.The estimates herein are likely to be conservative from a societal perspective as they exclude indirect costs associated with work productivity and the rare but meaningful consequences of chemotherapy on fertility and risk of secondary chemotherapy-related cancers.Our economic models also have been applied to the largest managed care organization in Israel. 4The managed care organization found the RS resulted in a 16% treatment change, associated with an average 0.17-year gain in QALYs.Unit costs are lower for cancer management in Israel, such that RS resulted in higher average cost per patient tested.The cost per QALY gained was $10,770, which was well within acceptable economic boundaries for adopting technologies in Israel.Altogether, these studies demonstrate that our early projections of the economic impact of the RS were credible.
Hath1, Down-Regulated in Colon Adenocarcinomas, Inhibits Proliferation and Tumorigenesis of Colon Cancer Cells
Authors: Ching Ching Leow, Maria S. Romero, Sarajane Ross, Paul Polakis, Wei-Qiang Gao
Journal: Cancer Research (2004)

A striking feature of colon tumors is the significant reduction of goblet cells. Although targeted deletion of Math1 in mice leads to a loss of intestinal secretory cells, including goblet cells, the role of Hath1 in colon tumorigenesis remains unknown. Here we report that Hath1, the human ortholog of Math1, was dramatically down-regulated in colon tumor samples and colon cancer cell lines. Overexpression of Hath1 in HT29, an aggressive colon cancer cell line, resulted in a significant inhibition on cell proliferation, anchorage-independent growth in soft agar and, more importantly, growth of human colon cancer cell xenografts in athymic nude mice. Such inhibition was accompanied by altered expression of a goblet cell differentiation marker, MUC2, and cell cycle regulators cyclin D1 and p27kip1. Hath1 expression also was up-regulated on inhibition of the Wnt pathway, which has been well implicated in colon tumorigenesis. Hence, this study suggests that Hath1 may be a novel factor downstream of the Wnt pathway capable of suppressing anchorage-independent growth of colon cancer cell lines. More importantly, this study is the first to establish a link between down-regulation of Hath1 expression and colon tumorigenesis.
Glucocorticoid receptor mRNA levels are selectively decreased in neutrophils of children with sepsis
Authors: Erica L. T. van den Akker, Jan W. Koper, Koen Joosten, Frank H. de Jong, Jan A. Hazelzet, Steven W. J. Lamberts, Anita C. S. Hokken-Koelega
Journal: Intensive Care Medicine (2009)

Corticosteroids are used in sepsis treatment to benefit outcome. However, discussion remains on which patients will benefit from treatment. Inter-individual variations in cortisol sensitivity, mediated through the glucocorticoid receptor, might play a role in the observed differences. Our aim was to study changes in mRNA levels of three glucocorticoid receptor splice variants in neutrophils of children with sepsis.Twenty-three children admitted to the pediatric intensive care unit with sepsis or septic shock were included. Neutrophils were isolated at days 0, 3 and 7, and after recovery (>3 months). mRNA levels of the glucocorticoid receptor splice variants GR-alpha (determining most of the cortisol effect), GR-P (increasing GR-alpha effect) and GR-beta (inhibitor of GR-alpha) were measured quantitatively.Neutrophils from sepsis patients showed decreased levels of glucocorticoid receptor mRNA of the GR-alpha and GR-P splice variants on day 0 compared to after recovery. GR-alpha and GR-P mRNA levels showed a gradual recovery on days 3 and 7 and normalized after recovery. GR-beta mRNA levels did not change significantly during sepsis. GR expression was negatively correlated to interleukin-6 (a measure of disease severity, r = -0.60, P = 0.009).Children with sepsis or septic shock showed a transient depression of glucocorticoid receptor mRNA in their neutrophils. This feature may represent a tissue-specific adaptation during sepsis leading to increased cortisol resistance of neutrophils. Our study adds to understanding the mechanism of cortisol sensitivity in immune cells. Future treatment strategies, aiming at timing and tissue specific regulation of glucocorticoids, might benefit patients with sepsis or septic shock.
Promoter Hypermethylation as an Independent Prognostic Factor for Relapse in Patients with Prostate Cancer Following Radical Prostatectomy
Authors: Eli Rosenbaum, Mohammad Obaidul Hoque, Yoram Cohen, Marianna Zahurak, Mario A. Eisenberger, Jonathan I. Epstein, Alan W. Partin, David Sidransky
Journal: Clinical Cancer Research (2005)

To analyze the prognostic significance of six epigenetic biomarkers (APC, Cyclin D2, GSTP1, TIG1, Rassf1A, and RARbeta2 promoter hypermethylation) in a homogeneous group of prostate cancer patients, following radical prostatectomy alone.Biomarker analyses were done retrospectively on tumors from 74 prostate cancer patients all with a Gleason score of 3 + 4 = 7 and minimum follow-up period of 7 years. Using quantitative methylation-specific PCR, we analyzed six gene promoters in primary prostate tumor tissues. Time to any progression was the primary end point, and development of metastatic disease and/or death from prostate cancer was a secondary point. The association of clinicopathologic and biomolecular risk factors to recurrence was done using the log-rank test and Cox proportional hazards model for multivariate analysis. To identify independent prognostic factors, a stepwise selection method was used.At a median follow-up time of 9 years, 37 patients (50%) had evidence of recurrence: biochemical/prostate-specific antigen relapse, metastases, or death from prostate cancer. In the final multivariate analysis for time to progression (TTP), the significant factors were age > 60 [hazard ratio (HR), 0.4; 95% confidence interval (95% CI), 0.2-0.8; P = 0.01], hypermethylation of GSTP1 (HR, 0.23; 95% CI; 0.09-0.64; P = 0.004), and hypermethylation of APC (HR, 3.0; 95% CI, 1.42-6.32; P = 0.004). In another multivariate analysis, a profile of hypermethylation of APC and cyclin D2 hypermethylation was significant as well: if either any one was hypermethylated (HR, 1.84; 95% CI, 0.92-3.72; P = 0.09) or if both were hypermethylated (HR, 4.3; 95% CI, 1.52-12.33; P = 0.01).Methylation status of selected genes in the prostate cancer specimen may predict for time to recurrence in Gleason 3 + 4 = 7 patients undergoing prostatectomy. These results should be validated in a larger and unselected cohort.
Evaluation of a Pharmacist-Led Medication Assessment Used to Identify Prevalence of and Associations With Polypharmacy and Potentially Inappropriate Medication Use Among Ambulatory Senior Adults With Cancer
Authors: Ginah Nightingale, Emily Hajjar, Kristine Swartz, Jocelyn Andrel-Sendecki, Andrew Chapman
Journal: Journal of Clinical Oncology (2015)

Purpose The use of multiple and/or inappropriate medications in seniors is a significant public health problem, and cancer treatment escalates its prevalence and complexity. Existing studies are limited by patient self-report and medical record extraction compared with a pharmacist-led comprehensive medication assessment. Patients and Methods We retrospectively examined medication use in ambulatory senior adults with cancer to determine the prevalence of polypharmacy (PP) and potentially inappropriate medication (PIM) use and associated factors. PP was defined as concurrent use of five or more and less than 10 medications, and excessive polypharmacy (EPP) was defined as 10 or more medications. PIMs were categorized by 2012 Beers Criteria, Screening Tool of Older Person's Prescriptions (STOPP), and the Healthcare Effectiveness Data and Information Set (HEDIS). Results A total of 248 patients received a geriatric oncology assessment between January 2011 and June 2013 (mean age was 79.9 years, 64% were women, 74% were white, and 87% had solid tumors). Only 234 patients (evaluated by pharmacists) were included in the final analysis. Mean number of medications used was 9.23. The prevalence of PP, EPP, and PIM use was 41% (n = 96), 43% (n = 101), and 51% (n = 119), respectively. 2012 Beers, STOPP, and HEDIS criteria classified 173 occurrences of PIMs, which were present in 40%, 38%, and 21% of patients, respectively. Associations with PIM use were PP (P &lt; .001) and increased comorbidities (P = .005). Conclusion A pharmacist-led comprehensive medication assessment demonstrated a high prevalence of PP, EPP, and PIM use. Medication assessments that integrate both 2012 Beers and STOPP criteria and consider cancer diagnosis, prognosis, and cancer-related therapy are needed to optimize medication use in this population.
Telomerase activation in adenocarcinoma-bronchioloalveolar carcinoma
Authors: E. Brambilla, S. Lantuejoul
Journal: European Respiratory Journal (2006)

At present, human bronchioloalveolar carcinoma (BAC) is a disease with an evolving definition.The clinical concept of BAC needs to be re-evaluated with careful attention to the 2004 World Health Organization (WHO) criteria [1] due to major clinical implications.Series published in the literature before 2000, i.e. before the WHO definition of BAC, had not discerned a specific survival advantage and clinical behaviour for BAC as compared with other nonsmall cell lung cancers (NSCLC).Instead, existing data indicate that patients with solitary small peripheral BAC, characterised by pure lepidic growth pattern with no evidence of stromal vascular or pleural invasion, represent only 2-6% of NSCLC diseases and have 100% 5-yr survival.This survival advantage may be extended to the micro-invasive BAC according to Japanese observations [2].
Dendritic Cells Fused with Allogeneic Colorectal Cancer Cell Line Present Multiple Colorectal Cancer–Specific Antigens and Induce Antitumor Immunity against Autologous Tumor Cells
Authors: Shigeo Koido, Eiichi Hara, Sadamu Homma, Akira Torii, Yoichi Toyama, Hidejiro Kawahara, Michiaki Watanabe, Katsuhiko Yanaga, Kiyotaka Fujise, Hisao Tajiri, Jianlin Gong, Gotaro Toda
Journal: Clinical Cancer Research (2005)

Abstract The aim of antitumor immunotherapy is to induce CTL responses against autologous tumors. Previous work has shown that fusion of human dendritic cells and autologous tumor cells induce CTL responses against autologous tumor cells in vitro. However, in the clinical setting of patients with colorectal carcinoma, a major difficulty is the preparation of sufficient amounts of autologous tumor cells. In the present study, autologous dendritic cells from patients with colorectal carcinoma were fused to allogeneic colorectal tumor cell line, COLM-6 (HLA-A2−/HLA-24−), carcinoembryonic antigen (CEA)+, and MUC1+ as an alternative strategy to deliver shared colorectal carcinoma antigens to dendritic cells. Stimulation of autologous T cells by the fusion cells generated with autologous dendritic cells (HLA-A2+ and/or HLA-A24+) and allogeneic COLM-6 resulted in MHC class I– and MHC class II–restricted proliferation of CD4+ and CD8+ T cells, high levels of IFN-γ production in both CD4+ and CD8+ T cells, and the simultaneous induction of CEA- and MUC1-specific CTL responses restricted by HLA-A2 and/or HLA-A24. Finally, CTL induced by dendritic cell/allogeneic COLM-6 fusion cells were able to kill autologous colorectal carcinoma by HLA-A2- and/or HLA-A24-restricted mechanisms. The demonstration of CTL activity against shared tumor-associated antigens using an allogeneic tumor cell line, COLM-6, provides that the presence of alloantigens does not prevent the development of CTL with activity against autologous colorectal carcinoma cells. The fusion of allogeneic colorectal carcinoma cell line and autologous dendritic cells could have potential applicability to the field of antitumor immunotherapy through the cross-priming against shared tumor antigens and provides a platform for adoptive immunotherapy.
Cancer Incidence in the Mexican-American 2
Authors: H. R. Menck, B. E. Henderson, M. C. Pike, T. Mack, S. P. Martin, J. SooHoo
Journal: JNCI Journal of the National Cancer Institute (1975)

Lower incidence rates of cancer for all anatomic sites combined were found in male and female Spanish-surnamed residents of Los Angeles County when compared to other whites. These Mexican-Americans were at lower risk for cancer of the buccal cavity, colon, rectum, larynx, lung, breast, bladder, prostate, and testis, and were at higher risk for cancer of the stomach, gallbladder, liver, and cervix. Immigrant Mexican-Americans had incidence rates most divergent from other whites, whereas indigenous Mexican-Americans had rates between the other two groups. The cancer pattern in Mexican-Americans was generally similar to that in American Indians. These data were most consistent with environmental variations in cause.
Cumulative Lead Exposure and Tooth Loss in Men: The Normative Aging Study
Authors: Manish Arora, Jennifer Weuve, Marc G. Weisskopf, David Sparrow, Huiling Nie, Raul I. Garcia, Howard Hu
Journal: Environmental Health Perspectives (2009)

BackgroundIndividuals previously exposed to lead remain at risk because of endogenous release of lead stored in their skeletal compartments. However, it is not known if long-term cumulative lead exposure is a risk factor for tooth loss.ObjectivesWe examined the association of bone lead concentrations with loss of natural teeth.MethodsWe examined 333 men enrolled in the Veterans Affairs Normative Aging Study. We used a validated K-shell X-ray fluorescence (KXRF) method to measure lead concentrations in the tibial midshaft and patella. A dentist recorded the number of teeth remaining, and tooth loss was categorized as 0, 1–8 or ≥ 9 missing teeth. We used proportional odds models to estimate the association of bone lead biomarkers with tooth loss, adjusting for age, smoking, diabetes, and other putative confounders.ResultsParticipants with ≥ 9 missing teeth had significantly higher bone lead concentrations than those who had not experienced tooth loss. In multivariable-adjusted analyses, men in the highest tertile of tibia lead (> 23 μg/g) and patella lead (> 36 μg/g) had approximately three times the odds of having experienced an elevated degree of tooth loss (≥ 9 vs. 0–8 missing teeth or ≥ 1 vs. 0 missing teeth) as those in the lowest tertile [prevalence odds ratio (OR) = 3.03; 95% confidence interval (CI), 1.60–5.76 and OR = 2.41; 95% CI, 1.30–4.49, respectively]. Associations between bone lead biomarkers and tooth loss were similar in magnitude to the increased odds observed in participants who were current smokers.ConclusionLong-term cumulative lead exposure is associated with increased odds of tooth loss.
Effect of Ruxolitinib Therapy on Myelofibrosis-Related Symptoms and Other Patient-Reported Outcomes in COMFORT-I: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Ruben A. Mesa, Jason Gotlib, Vikas Gupta, John V. Catalano, Michael W. Deininger, Alan L. Shields, Carole B. Miller, Richard T. Silver, Moshe Talpaz, Elliott F. Winton, Jimmie H. Harvey, Thomas Hare, Susan Erickson-Viitanen, William Sun, Victor Sandor, Richard S. Levy, Hagop M. Kantarjian, Srdan Verstovsek
Journal: Journal of Clinical Oncology (2013)

Purpose To assess the effects of ruxolitinib on symptom burden and quality of life (QoL) and to evaluate the ability of the modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 to measure meaningful changes in myelofibrosis-related symptoms in patients with myelofibrosis. Patients and Methods COMFORT-I (Controlled Myelofibrosis Study With Oral JAK Inhibitor Treatment–I) is a double-blind, placebo-controlled phase III study evaluating ruxolitinib in patients with intermediate-2 or high-risk myelofibrosis. Exploratory analyses were conducted on the following patient-reported outcomes (PROs) assessments: modified MFSAF v2.0 (individual symptoms and Total Symptom Score [TSS]), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue Scale, and Patient Global Impression of Change (PGIC). Results Patients receiving ruxolitinib experienced improvements in individual myelofibrosis-related symptoms, although patients receiving placebo experienced worsening (P &lt; .001). The majority (91%) of ruxolitinib-treated patients designated as ≥ 50% TSS responders (≥ 50% TSS improvement) self-reported their condition as either “Much improved” or “Very much improved” on the PGIC. These patients achieved significant improvements in the EORTC QLQ-C30 functional domains and Global Health Status/QoL versus patients receiving placebo, who experienced worsening on these measures (P ≤ .0135). Ruxolitinib-treated patients with a lesser degree of symptom improvement (&lt; 50% TSS responders) also achieved improvements over placebo on these measures. The degree of spleen volume reduction with ruxolitinib correlated with improvements in TSS, PGIC, PROMIS Fatigue Scale, and EORTC Global Health Status/QoL. Ruxolitinib-treated patients who achieved a ≥ 35% reduction in spleen volume experienced the greatest improvements in these PROs. Conclusion Ruxolitinib-treated patients achieved clinically meaningful improvements in myelofibrosis-related symptoms and QoL, but patients receiving placebo reported worsening of symptoms and other PROs.
The Four-Year Course of Major Depressive Disorder: The Role of Staging and Risk Factor Determination
Authors: Lynn Boschloo, Robert A. Schoevers, Aartjan T.F. Beekman, Johannes H. Smit, Albert M. van Hemert, Brenda W.J.H. Penninx
Journal: Psychotherapy and Psychosomatics (2014)

Much is still unclear about the mechanisms underlying the course of major depressive disorder (MDD). This study aimed to identify risk factors that predict a poor prognosis of MDD while taking into consideration its chronicity at baseline.In patients with MDD (n = 767), we examined whether baseline clinical factors, sociodemographics, childhood trauma, personality and life events predicted the 4-year course (i.e., sustained recovery, temporary recovery and chronic course) of MDD. Baseline chronicity of MDD was taken into account by testing whether associations were different for patients with nonchronic versus chronic MDD at baseline.In patients with nonchronic MDD at baseline, 27.8% developed a chronic disorder during follow-up, whereas 53.0% of patients with chronic MDD at baseline had a persistent chronic disorder during follow-up. Severity of MDD, childhood trauma and greater age were important general risk factors for a poor prognosis, independent of MDD chronicity at baseline. In contrast, low extraversion was only important for the course of nonchronic MDD at baseline, while higher education and negative life events (in patients with high neuroticism) were only relevant for the course of chronic MDD at baseline.One out of 4 patients with nonchronic MDD progressed to a chronic disorder, while half of the patients with chronic MDD remained chronic during follow-up. Since several risk factors for a poor prognosis differed for patients with nonchronic and chronic MDD at baseline, treatment targets should be adjusted for current chronicity of MDD.
Intraportal glucose delivery enhances the effects of hepatic glucose load on net hepatic glucose uptake in vivo.
Authors: S R Myers, D W Biggers, D W Neal, A D Cherrington
Journal: Journal of Clinical Investigation (1991)

Although the importance of the hepatic glucose load in the regulation of liver glucose uptake has been clearly demonstrated in in vitro systems, the relationship between the hepatic glucose load and hepatic glucose uptake has yet to be defined in vivo. Likewise, the effects of the route of glucose delivery (peripheral or portal) on this relationship have not been explored. The aims of the present study were to determine the relationship between net hepatic glucose uptake (NHGU) and the hepatic glucose load in vivo and to examine the effects of the route of glucose delivery on this relationship. NHGU was evaluated at three different hepatic glucose loads in 42-h fasted, conscious dogs in both the absence (n = 7) and the presence (n = 6) of intraportal glucose delivery. In the absence of intraportal glucose delivery and in the presence of hepatic glucose loads of 50.5 +/- 5.9, 76.5 +/- 10.0, and 93.6 +/- 10.0 mg/kg/min and arterial insulin levels of approximately 33 microU/ml, NHGU was 1.16 +/- 0.37, 2.78 +/- 0.82, and 5.07 +/- 1.20 mg/kg/min, respectively. When a portion of the glucose load was infused into the portal vein and similar arterial insulin levels (approximately 36 microU/ml) and hepatic glucose loads (52.5 +/- 4.5, 70.4 +/- 5.6, and 103.6 +/- 18.4 mg/kg/min) were maintained, NHGU was twice that seen in the absence of portal loading (3.77 +/- 0.40, 4.80 +/- 0.59, and 9.62 +/- 1.43 mg/kg/min, respectively). Thus, net hepatic glucose uptake demonstrated a direct dependence on the hepatic glucose load that did not reach saturation even at elevations in the hepatic glucose load of greater than three times basal. In addition, the presence of intraportal glucose delivery increased net hepatic glucose uptake apparently by lowering the threshold at which the liver switched from net glucose output to net glucose uptake.
Pathogenesis and Treatment of Graft-Versus-Host Disease After Bone Marrow Transplant
Authors: Georgia B. Vogelsang, Linda Lee, Debra M. Bensen-Kennedy
Journal: Annual Review of Medicine (2003)

Stem cell transplantation is being used to treat a number of hematologic malignancies as well as hematologic and immune deficiency states. The ages of patients being offered this therapy and the donor marrow sources have been expanded. One persistent problem has been graft-versus-host disease (GVHD). This article reviews the basic biology of GVHD, clinical manifestations of acute and chronic GVHD, prophylaxis and treatment of acute GVHD, and treatment of chronic GVHD.
Syncopal episodes in a young amateur body builder
Authors: G Manoharan, N P S Campbell, C J O'Brien
Journal: British Journal of Sports Medicine (2002)

A 36 year old male weight training enthusiast suffered several syncopal episodes. An electrocardiogram confirmed atrial fibrillation with normal ventricular response. The patient admitted to taking anabolic steroids and bromocriptine. The atrial fibrillation was considered to be due to bromocriptine misuse.