tbuckley/cabot-search huggingface dataset:
A genomic approach to identify therapeutic targets in histologic subtypes of soft tissue sarcoma
Authors: R. F. Riedel, D. Friedman, P. G. Febbo
Journal: Journal of Clinical Oncology (2008)

10577 Background: Sarcomas are a rare, heterogeneous group of tumors with varying degrees of aggressiveness and responsiveness to therapy. In the advanced setting, chemotherapy results in unsatisfactory long-term outcomes. Novel therapeutic strategies that rationally target specific sarcoma subtypes are desired to improve outcomes and limit chemotherapy resistance. Our research uses a genomic approach to identify unique biological mechanisms and signaling pathways associated with specific sarcoma subtypes so as to guide future rational combinations of standard cytotoxic agents with novel “targeted” therapies. Methods: Publicly-available gene expression datasets (GSE6481, GSE2719) were obtained from Gene Expression Omnibus (GEO) representing 141 human sarcoma samples across 12 histologic subtypes. Datasets were combined, adjusted and standardized using ComBat to limit batch effect and assessed using hierarchical clustering (Gene Pattern) with filtering. Gene set enrichment analysis (GSEA) was performed using a two-class discriminator (i.e., synovial sarcoma vs. other sarcomas) to identify biologic pathways unique to specific histologic subtypes. Gene sets with a false discovery rate (FDR) <0.25 were deemed statistically significant as originally described. Results: Hierarchical clustering identified well-defined clusters for synovial sarcoma, GIST, and myxoid/round cell liposarcoma with less organized clustering for the remaining subtypes. GSEA identified 11 enriched gene sets, representing biological pathways of activity, at FDR <0.25 for synovial sarcoma with 3 of 11 gene sets related to Wnt signaling (WNTPATHWAY, PITX2PATHWAY, PS1PATHWAY). Twenty-nine gene sets were significant at FDR <0.25 for myxoid/round cell liposarcoma with 2 gene sets related to mTOR signaling (MTORPATHWAY, IGF1MTORPATHWAY). Additional pathways and subtypes are being analyzed and will be reported. Conclusions: These preliminary data support the use of a genomic approach to identify pathways associated with specific histologic sarcoma subtypes. This strategy may be used to identify novel agents that can be used alone or in combination with conventional cytotoxic chemotherapy. No significant financial relationships to disclose.
Advancing Medical Professionalism in US Military Detainee Treatment
Authors: Leonard S. Rubenstein, Scott A. Allen, Phyllis A. Guze
Journal: PLoS Medicine (2016)

The United States Department of Defense and Central Intelligence Agency (CIA) promulgated policies and requirements that required health professionals to participate in the mistreatment of counter-terrorism detainees through participation in such practices as abusive interrogation and force-feeding of detainees, in violation of ethical standards established by associations representing the health professions.• A report of the Defense Health Board to the Secretary of Defense on military medical ethics released in 2015 found that the Department of Defense "does not have an enterprise-wide, formal, integrated infrastructure to systematically build, support, sustain, and promote an evolving ethical culture within the military health care environment."• The Board also found that ethical codes promulgated by the health professions, including the duty to avoid harm, provide a sound
Second malignancies after treatment of Hodgkin's disease: the influence of treatment, follow-up time, and age.
Authors: J F Abrahamsen, A Andersen, E Hannisdal, O Nome, A F Abrahamsen, S Kvaløy, H Høst
Journal: Journal of Clinical Oncology (1993)

PURPOSE In the period 1968 through 1988, The Norwegian Radium Hospital (NRH) treated an unselected population of 1,152 patients with Hodgkin's disease (HD) that comprised more older patients (mean age, 43 years) than most other institutions. We considered it important to evaluate these patients for development of second cancers (SCs). PATIENTS AND METHODS The Norwegian Cancer Registry identified previously untreated patients with HD treated at NRH who had developed a SC more than 1 year after diagnosis of HD. The relative risk ratio (RR) (observed/expected cases) and the cumulative risk were calculated. RESULTS Sixty-eight patients had developed a SC, including nine acute nonlymphocytic leukemias (ANLLs), eight non-Hodgkin's lymphomas (NHLs), and 51 solid tumors, including 11 lung cancers. The RR of SC and leukemia was 1.86 (95% confidence interval [CI], 1.4 to 2.4) and 24.3 (95% CI, 11.1 to 46.2), respectively. The RR of SC was highest in younger patients (&lt; 41 years, RR = 3.8). No significant association between splenectomy and development of ANLL was found. The influence of treatment and follow-up time on the development of SC agrees with data from other large cancer institutions. CONCLUSION (1) The low RR of developing a SC in this study is probably due to the number of older patients included, who have a lower RR of developing a SC due to less aggressive treatment, shorter follow-up time, and higher incidence of cancer in the expected background population. (2) The low RR and cumulative risk of developing ANLL may be due to the limited use of extensive chemotherapy (CT) in our hospital in the earlier years.
Long-term results of the APO protocol (vincristine, doxorubicin [adriamycin], and prednisone) for treatment of mediastinal lymphoblastic lymphoma.
Authors: H J Weinstein, J R Cassady, R Levey
Journal: Journal of Clinical Oncology (1983)

Twenty-one patients with biopsy-proven mediastinal lymphoblastic lymphoma were treated with the APO protocol (vincristine, doxorubicin, and prednisone). Treatment consisted of two years of therapy with a modified doxorubicin-containing acute lymphoblastic leukemia regimen with preventive cranial irradiation and intrathecal methotrexate. The median age in the group was 13 years (range, 2.5-22 years). Complete remission was obtained in 20 of 21 patients. Three patients required mediastinal irradiation for successful remission induction. Six patients have subsequently relapsed: two in the central nervous system, one in the central nervous system and testicle, one in the testicle, one in the pleura, and one in the abdomen. The median follow-up is six years (range, 16 months to 9.5 years) and a Kaplan-Meier estimate of disease-free survival at three years is 58% +/- 23% (2 SE).
P0773 : The prevalence and the effect of HCV NS5A resistance associated variants in subjects with compensated cirrhosis treated with ledipasvir/sofosbuvir +/- RBV
Authors: C. Sarrazin, H. Dvory-Sobol, E.S. Svarovskaia, B. Doehle, R. Martin, S. Zeuzem, E. Lawitz, R. Hyland, P.S. Pang, S. Knox, E. Gane, R. Reddy, N. Afdhal, M. Mizokami, M. Omata, M.D. Miller, H. Mo, M. Bourlière
Journal: Journal of Hepatology (2015)
A Novel Leukemia T-Cell Line (PF-382) With Phenotypic and Functional Features of Suppressor Lymphocytes&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: L Pegoraro, M T Fierro, P Lusso, B Giovinazzo, E Lanino, M Giovarelli, L Matera, R Foa
Journal: JNCI Journal of the National Cancer Institute (1985)

A human leukemia T-cell line (PF-382) spontaneously derived from the pleural effusion of a child with T-cell acute lymphoblastic leukemia is described. The cell line, which has been maintained in culture for over 10 months, has a modal number of 46 chromosomes and is characterized by a chromosomal abnormality, present in most of the cells, consisting of a translocation between chromosome X and chromosome 15 (46X,Xq-,15p+). The cells are not recognized by the OKT3 and OKT11 monoclonal antibodies (MoAb), nor do they form rosettes with sheep erythrocytes. By contrast, they react with the OKT6, Leu-1, and Leu-9 MoAb, which detect early T-lymphocytes, and express the more mature OKT8 antigen. The presence of the OKT8 marker is associated with suppressor activity on the pokeweed mitogen-induced proliferation and differentiation of normal B-cells, both by the PF-382 cells and by their supernatant. However, no cytotoxic activity against natural killer (NK)-sensitive target cells (K562) was found, indicating that the proliferating cells do not correspond to the subset of NK cells expressing the OKT8 antigen. Furthermore, the cells are incapable of both spontaneous and mitogen-induced interleukin-2 and interferon production. The ability of the PF-382 cell line to release a soluble factor(s) capable of modulating the differentiation of the B-cell compartment suggests that this new cell line represents a valuable model for the investigation of the interrelationships between T-cell subsets and other hematopoietic cell lineages.
ME-12 * THE TUMOR SUPPRESSOR LRIG1 IS DOWNREGULATED BY HYPOXIA AND REGULATES GLIOBLASTOMA CELL INVASION
Authors: F. Mao, C. Holmlund, M. Faraz, T. Bergenheim, M. Johansson, R. Henriksson, H. Hedman
Journal: Neuro-Oncology (2014)

Hypoxia, i.e., inadequate oxygen supply, is a common condition in glioblastomas and other tumors that appears to promote malignant progression. Many of the cellular effects of hypoxia are mediated by transcription factors belonging to the hypoxia-inducible factor (HIF) family. However, the downstream targets of HIFs and their role in malignant progression are not fully understood. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a proposed tumor suppressor that inhibits glioma growth and that is downregulated in glioblastomas compared with lower grade gliomas. Here, we show that LRIG1 was universally downregulated by hypoxia in cancer cells. Hypoxia-induced downregulation of LRIG1 was, at least partly, dependent on HIF1-alpha (HIF1A) and involved an apparently reduced LRIG1 protein synthesis rate. A primary glioblastoma cell line, TB107, was established, and the role of LRIG1 expression was evaluated by transducing the cells with LRIG1 expression or control vectors. In vivo, LRIG1 strongly suppressed the intracranial spread of orthotopically transplanted TB107 cells, and, in vitro, cell migration was suppressed. In summary, our results suggest that LRIG1 downregulation might be an important factor contributing to the hypoxia-driven malignant progression of various tumors, including malignant glioma.
Silent Monosodium Urate Crystal Deposits Are Associated With Severe Coronary Calcification in Asymptomatic Hyperuricemia: An Exploratory Study
Authors: Mariano Andrés, María‐Amparo Quintanilla, Francisca Sivera, José Sánchez‐Payá, Eliseo Pascual, Paloma Vela, Juan‐Miguel Ruiz‐Nodar
Journal: Arthritis & Rheumatology (2016)

Objective To evaluate the association between monosodium urate (MSU) crystal deposits in patients with asymptomatic hyperuricemia and the severity and extension of coronary artery disease (CAD). Methods In this cross‐sectional study, consecutive inpatients with a non–ST elevation acute coronary event and asymptomatic hyperuricemia (serum uric acid concentration of ≥7.0 mg/dl) or normouricemia (serum uric acid concentration of &lt;7.0 mg/dl) were enrolled. In patients with asymptomatic hyperuricemia, the presence of MSU crystals was determined by ultrasound evaluation of both knees and first metatarsophalangeal joints and by compensated polarized light microscopy. CAD was assessed by coronary angiography, and the following variables were considered: 1) the presence of moderate‐to‐severe coronary artery calcification, 2) the number of significant coronary stenoses, and 3) the presence of multivessel disease. The association between variables indicating the severity of CAD and the presence of MSU crystals was analyzed by multivariate regression. Results One hundred forty patients were enrolled. After ultrasonography and microscopic analyses were performed, the patients were classified as having normouricemia (n = 66), asymptomatic hyperuricemia alone (n = 61), and asymptomatic hyperuricemia with MSU crystals (n = 13). The prevalence of moderate‐to‐severe coronary calcification was significantly higher in the patients with asymptomatic hyperuricemia with MSU crystals compared with patients with asymptomatic hyperuricemia alone and patients with normouricemia ( P = 0.003). An independent association was observed between the presence of moderate‐to‐severe calcification and asymptomatic hyperuricemia with crystals (odds ratio 16.8, P = 0.002). No significant association was observed for the other variables. Conclusion Silent deposition of MSU crystals in patients with asymptomatic hyperuricemia was associated with more severe coronary calcification, which suggests more severe CAD in relation to crystal deposition.
Randomized or historical control groups in cancer clinical trials: are historical controls valid?
Authors: E A Gehan
Journal: Journal of Clinical Oncology (1986)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1986.4.7.1024 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3723163 Randomized or historical control groups in cancer clinical trials: are historical controls valid? E A GehanxE A GehanSearch for articles by this author https://doi.org/10.1200/JCO.1986.4.7.1024 PDF "Randomized or historical control groups in cancer clinical trials: are historical controls valid?." Journal of Clinical Oncology, 4(7), pp. 1024–1025© 1986 by American Society of Clinical Oncology
Follow-up MRI screening of BRCA1/2 mutation carriers
Authors: P. Shah, M. A. Rosen, J. Stopfer, J. D. Siegfried, B. A. Mason, K. L. Nathanson, M. Schnall, S. M. Domchek
Journal: Journal of Clinical Oncology (2008)

11000 Background: Annual MRI screening is recommended as an adjunct to mammography for BRCA1 and BRCA2 mutation carriers (B1/2). Prophylactic oophorectomy (PO) has been shown to decrease breast cancer (BC) risk in B1/2; however, most studies of MRI surveillance of B1/2 either do not report or have low rates of PO. Methods: 91 B1/2 carriers underwent baseline mammogram within 3 months of first study MRI, and then underwent yearly mammograms and yearly MRI scans. Study endpoints were defined as date of BC diagnosis, date of prophylactic mastectomy, or date of most recent contact. Results: Of 91 patients, 79 (87%) had PO (72% prior to study entry, 15% in follow-up). Mean age was 47. 50 (55%) had B1 mutations; 41 (45%) had B2 mutations. 9 BC were detected in 91 women (9.9%) with a median follow-up of 3.18 years per person. 279 MRI scans were performed. 26 of 91 (29%) patients had at least one BIRADS 3 MRI. 15 of 91 (16%) patients had at least one BIRADS 4 or 5 MRI. A total of 18 MRI scans were scored as BIRADS 4 or 5 with 6 BC detected (33%). Of these 6 cancers, 2 were found on MRI only. Two additional cancers were diagnosed on study entry mammogram: both were seen on MRI (BIRADS 6). The final cancer was detected on breast self-exam 8 months after negative mammogram and MRI screening. At the time of clinical detection, the cancer was seen on both mammogram and MRI (BIRADS 4). All BC occurred in B1 carriers. 8/9 were invasive ductal carcinomas (one, DCIS); 7/9 were node negative. Both node positive BC occurred in women whose last MRI was 20 or more months prior to diagnosis. At year one, 18/91 (20%) MRI were BIRADS 3, while at year 3, 2/38 MRI were BIRADS 3 (5%) (p= 0.02). Conclusions: In this population of B1/2 carriers, the majority of whom had PO, all BC occurred in B1 carriers. In addition, the two node positive BC were found in patients who had not had annual MRI screening, underscoring the importance of the current recommendation for annual MRI. BIRADS 3 category MRI (and need for short interval follow up scans) decrease with annual screening. No significant financial relationships to disclose.
Trauma History as a Predictor of Psychologic Symptoms in Women With Breast Cancer
Authors: Bonnie L. Green, Janice L. Krupnick, Julia H. Rowland, Steven A. Epstein, Patricia Stockton, Ilyse Spertus, Nicole Stern
Journal: Journal of Clinical Oncology (2000)

PURPOSE: To identify predictors of psychiatric problems in women with early-stage breast cancer. PATIENTS AND METHODS: One hundred sixty women with early-stage breast cancer were recruited from three treatment centers. They filled out self-report questionnaires, including a medical history and demographic survey, the Trauma History Questionnaire, Life Event Questionnaire, Brief Symptom Inventory, Beck Depression Inventory, and Duke-UNC Functional Social Support Questionnaire, and were evaluated using the Structured Clinical Interview for DSM-III-R. RESULTS: Hierarchical regression analyses indicated that four of five variable sets made a significant incremental contribution to outcome prediction, with 35% to 37% of the variance explained. Outcomes were predicted by demographic variables, trauma history variables, precancer psychiatric diagnosis, recent life events, and perceived social support. Cancer treatment variables did not predict outcome. CONCLUSION: The findings highlight the important roles of trauma history and recent life events in adjustment to cancer and have implications for screening and treatment.
Use of carbonic anhydrase IX (CAIX) expression and Von Hippel Lindau (VHL) gene mutation status to predict survival in renal cell carcinoma
Authors: A. J. Pantuck, Q. Trinh, P. I. Karakiewicz, P. Fergelot, N. Rioux-Leclercq, R. Figlin, J. Said, A. Belldegrun, J. Patard
Journal: Journal of Clinical Oncology (2007)

5042 Background: VHL gene mutations induce the expression of CAIX, and previous studies have shown that low CAIX results in worse prognosis for RCC. We attempt to further describe the relationship between CAIX expression, VHL gene mutations and tumor characteristics. Methods: Radical nephrectomy was performed in 100 patients at 2 centers. Genomic DNA was extracted from frozen tumor samples using the QIAmp DNA mini kit. Four amplimers covering the whole coding sequence of the VHL gene were synthesized by PCR and sequenced by Big Dye. Mutation bearing sequences were confirmed by a second round of sequencing. The monoclonal antibody M75 was used to score the expression of the CAIX protein. Life table, Kaplan-Meier and Cox regression analyses addressed RCC-specific mortality (RCC-SM). Results: VHL mutations were identified in 58 patients (58%) and CAIX tumor expression ranged from 0% to 100%. Low CAIX expression (&lt;85%) was associated with absence of VHL mutation (p=0.02), larger tumors (p=0.002), higher T stage (p=0.007), nodal metastases (p=0.001) and higher Fuhrman grade (p=0.006). Absence of VHL mutation was associated with worse ECOG (p=0.005), higher T stage (p=0.01) and presence of nodal (p=0.03) and distant metastases (p=0.02). Categorically-coded, CAIX was a statistically significant predictor of RCC-SM (p=0.002), while VHL mutation approached statistical significance (p=0.08) and a trend was observed for worse survival when VHL was not mutated. Patients with both high CAIX and VHL mutation had better survival (95.9% 1 year and 6 year median survival) than their counterparts with low CAIX expression and absence of VHL mutation (62.9% 1 year and 1.5 year median survival) (p&lt;0.001). In Cox regression analyses, neither CAIX (p=0.06) nor VHL (p=0.4) achieved independent predictor status, when adjusted for age, gender, TNM stage, tumor size, Fuhrman and ECOG. Conclusions: Low CAIX expression is associated with the absence of VHL mutation and aggressive tumor characteristics, and is a statistically significant predictor of poor prognosis in patients with clear cell RCC. No significant financial relationships to disclose.
Abstract 13935: Effect of Dietary Salt Restriction on Blood Pressure in Chinese Adults: A Meta-Analysis
Authors: Miao Wang, Andrew E. Moran, Jing Liu, Yue Qi, Wuxiang Xie, Keane Tzong, Dong Zhao
Journal: Circulation (2014)

Introduction:  Controlling elevated blood pressure by reducing dietary salt intake might reduce cardiovascular disease. The effects of salt restriction on blood pressure and a culturally-tailored salt reduction strategy (potassium-for-sodium salt substitution) have not been summarized in Chinese adults.   Methods:  PubMed and China National Knowledge Infrastructure databases were searched for studies satisfying search criteria. Outcomes extracted from each study were 24-hour urinary sodium excretion, NaCl intake, and SBP before and after dietary salt lowering. A random-effects meta-analysis was performed using Stata software and results were evaluated for publication bias and excess heterogeneity. Most studies aggregated results for hypertensive and normotensive participants. We therefore stratified pooled meta-analysis results into two groups: hypertensive participants only and a mixture of hypertensive and normotensive participants. Salt substitution studies did not report SBP change separately for hypertensive and normotensive participants.   Results:  Data were pooled for five studies, representing 2,458 Chinese participants. In hypertensive participants, the pooled estimate of change in 24-hour urinary Na excretion was -163.0 (95% CI: -233.5 to -92.5) mmol/day, which was associated with a reduction of -8.9 (95%CI: -14.1 to -3.7) mmHg in SBP and -5.9 (95%CI: -9.7 to -2.1) mmHg DBP. Each 1g dietary NaCl reduction was associated with reductions of 0.94 mmHg SBP (95%CI: 0.69 to 1.03). These SBP effects in the hypertensive group were 1.96 times more compared with the mixed hypertensive and normotensive group. Salt substitution was associated with a -2.3 (95%CI: -5.6 to 0.9) mmHg change in SBP level.   Conclusions:  The Chinese population might gain improved blood pressure control from salt restriction and hypertensives would benefit the most. The effect of salt substitution intervention on blood pressure in hypertensive patients should be examined.
Epitope Spreading of Autoantibody Response to PLA2R Associates with Poor Prognosis in Membranous Nephropathy
Authors: Barbara Seitz-Polski, Guillaume Dolla, Christine Payré, Christophe A. Girard, Joel Polidori, Kevin Zorzi, Eléonore Birgy-Barelli, Perrine Jullien, Cécile Courivaud, Thierry Krummel, Sylvia Benzaken, Ghislaine Bernard, Stéphane Burtey, Christophe Mariat, Vincent L.M. Esnault, Gérard Lambeau
Journal: Journal of the American Society of Nephrology (2015)

The phospholipase A2 receptor (PLA2R1) is the major autoantigen in idiopathic membranous nephropathy. However, the value of anti-PLA2R1 antibody titers in predicting patient outcomes is unknown. Here, we screened serum samples from 50 patients positive for PLA2R1 for immunoreactivity against a series of PLA2R1 deletion mutants covering the extracellular domains. We identified reactive epitopes in the cysteine-rich (CysR), C-type lectin domain 1 (CTLD1), and C-type lectin domain 7 (CTLD7) domains and confirmed the reactivity with soluble forms of each domain. We then used ELISAs to stratify 69 patients positive for PLA2R1 by serum reactivity to one or more of these domains: CysR ( n =23), CysRC1 ( n =14), and CysRC1C7 ( n =32). Median ELISA titers measured using the full-length PLA2R1 antigens were not statistically different between subgroups. Patients with anti-CysR–restricted activity were younger ( P =0.008), had less nephrotic range proteinuria ( P =0.02), and exhibited a higher rate of spontaneous remission ( P =0.03) and lower rates of renal failure progression ( P =0.002) and ESRD ( P =0.01) during follow-up. Overall, 31 of 69 patients had poor renal prognosis (urinary protein/creatinine ratio &gt;4 g/g or eGFR&lt;45 ml/min per 1.73 m 2 at end of follow-up). High anti-PLA2R1 activity and epitope spreading beyond the CysR epitope were independent risk factors of poor renal prognosis in multivariable Cox regression analysis. Epitope spreading during follow-up associated with disease worsening ( n =3), whereas reverse spreading from a CysRC1C7 profile back to a CysR profile associated with favorable outcome ( n =1). We conclude that analysis of the PLA2R1 epitope profile and spreading is a powerful tool for monitoring disease severity and stratifying patients by renal prognosis.