tbuckley/cabot-search huggingface dataset:
Preirradiation chemotherapy with cyclophosphamide, doxorubicin, vincristine, and dexamethasone for primary CNS lymphomas: initial report of radiation therapy oncology group protocol 88-06.
Authors: C Schultz, C Scott, W Sherman, B Donahue, J Fields, K Murray, B Fisher, R Abrams, J Meis-Kindblom
Journal: Journal of Clinical Oncology (1996)

PURPOSE This study was a prospective phase I/II trial performed by the Radiation Therapy Oncology Group (RTOG) to test the tolerance and efficacy of preirradiation cyclophosphamide, doxorubicin, vincristine, and dexamethasone (CHOD) chemotherapy followed by large-volume, high-dose brain radiation therapy (RT) for patients with primary CNS lymphoma (PCNSL). PATIENTS AND METHODS Fifty-four (52 assessable) human immunodeficiency virus (HIV)-negative patients with PCNSL were entered on study and received two (n = 20) or three (n = 32) cycles of CHOD (six patients with positive CSF cytology received intrathecal methotrexate in addition to CHOD). Whole-brain RT to 41.4 Gy and tumor boost to 18 Gy (total dose, 59.4 Gy) followed chemotherapy. RESULTS As of July 1994, with a minimum potential follow-up time of 20 months, 12 of 52 assessable patients remain alive without evidence of progression. The median survival time for the entire group is 16.1 months, with a 2-year survival rate of 42%. By univariate analysis, patient age was found to be a significant prognostic factor with respect to survival (P = .005) in favor of age less than 60 years. Karnofsky performance status (KPS) was of borderline significance (P = .057). Survival for patients treated on RTOG 88-06 was compared with that of patients treated on RTOG 83-15, which tested RT alone. No difference in overall survival was found (P = .53). Grade 4 neutropenia developed in 29 of 51 patients during chemotherapy. There were two deaths during chemotherapy: one as a result of sepsis and one of a pulmonary embolus. The worst toxicity during RT was &lt; or = grade 2 in 50 of 52 patients. CONCLUSION Preirradiation CHOD chemotherapy does not significantly improve survival over RT alone for patients with PCNSL. Age remains a powerful prognostic factor independent of therapy and must be considered in testing alternative combined approaches.
Abstract 1272: Vascular Endothelium Growth Factor-165 Gene Therapy Promotes Cardiomyogenesis in Reperfused Myocardial Infarction
Authors: Mayra Guerrero, Krishna Athota, Jason Moy, Laxmi Mehta, Ruben Laguens, Alberto Crottogini, Michael Borrelli, Peter Corry, Ralph Gentry, Judith Boura, Cindy Grines, Gilbert L Raff, Charles Shanley, William O'Neill
Journal: Circulation (2006)

BACKGROUND: Vascular endothelial growth factor (VEGF) 165 has been found to promote cardiomyogenesis in chronic ischemia and non-reperfused myocardial infarction (MI). HYPOTHESIS: VEGF-165 induces ...
Sotagliflozin, a Dual SGLT1 and SGLT2 Inhibitor, as Adjunct Therapy to Insulin in Type 1 Diabetes
Authors: Arthur T. Sands, Brian P. Zambrowicz, Julio Rosenstock, Pablo Lapuerta, Bruce W. Bode, Satish K. Garg, John B. Buse, Phillip Banks, Rubina Heptulla, Marc Rendell, William T. Cefalu, Paul Strumph
Journal: Diabetes Care (2015)

OBJECTIVE To assess the safety and efficacy of dual sodium–glucose cotransporter (SGLT) 1 and SGLT2 inhibition with sotagliflozin as adjunct therapy to insulin in type 1 diabetes. RESEARCH DESIGN AND METHODS We treated 33 patients with sotagliflozin, an oral dual SGLT1 and SGLT2 inhibitor, or placebo in a randomized, double-blind trial assessing safety, insulin dose, glycemic control, and other metabolic parameters over 29 days of treatment. RESULTS In the sotagliflozin-treated group, the percent reduction from baseline in the primary end point of bolus insulin dose was 32.1% (P = 0.007), accompanied by lower mean daily glucose measured by continuous glucose monitoring (CGM) of 148.8 mg/dL (8.3 mmol/L) (P = 0.010) and a reduction of 0.55% (5.9 mmol/mol) (P = 0.002) in HbA1c compared with the placebo group that showed 6.4% reduction in bolus insulin dose, a mean daily glucose of 170.3 mg/dL (9.5 mmol/L), and a decrease of 0.06% (0.65 mmol/mol) in HbA1c. The percentage of time in target glucose range 70–180 mg/dL (3.9–10.0 mmol/L) increased from baseline with sotagliflozin compared with placebo, to 68.2% vs. 54.0% (P = 0.003), while the percentage of time in hyperglycemic range &amp;gt;180 mg/dL (10.0 mmol/L) decreased from baseline, to 25.0% vs. 40.2% (P = 0.002), for sotagliflozin and placebo, respectively. Body weight decreased (1.7 kg) with sotagliflozin compared with a 0.5 kg gain (P = 0.005) in the placebo group. CONCLUSIONS As adjunct to insulin, dual SGLT1 and SGLT2 inhibition with sotagliflozin improved glycemic control and the CGM profile with bolus insulin dose reduction, weight loss, and no increased hypoglycemia in type 1 diabetes.
Measurability of non-small-cell lung cancer on chest radiographs.
Authors: S Herschorn, J Hanley, N Wolkove, C Cohen, H Frank, M Palayew, H Kreisman
Journal: Journal of Clinical Oncology (1986)

Response rates to various drug regimens are determined in multi-center trials by radiographic measurement of tumor dimensions before and after treatment. The way in which lesions are measured may affect the reported results. Lesions due to primary lung cancer may be more difficult to assess than rounded peripheral metastases. No previous study has assessed the variability of tumor measurements in patients with primary lung cancer. Nineteen radiographs from 12 patients with non-small-cell lung cancer (NSCLC) were shown to 25 experienced readers on two separate occasions. Pre- and post-treatment (combined chemotherapy and radiotherapy) radiographs were first shown separately, unidentified and in random order. Three months later, they were shown side by side with the facility for comparison. A decrease in tumor size of greater than or equal to 50% was considered as a "response." Viewing paired films together increased the viewers ability to measure tumors compared with reading each film of the radiographic pair individually. Fifty-one percent of unmeasurable pairs became measurable when read together, whereas 13% of previously measurable pairs now became unmeasurable. The interobserver variation in measurements was 10% to 265%, while the intraobserver variation was 4% to 10%. The correlation between responses calculated on the first and second readings often was no better than chance alone. Subjective impressions of degree of improvement showed no good correlation with response rates measured objectively. Because of the large variation in measurements and consequently in response rate, we recommend that all radiographs be reviewed by a single observer for any particular study, and pre- and post-treatment radiographs be evaluated together.
Brief Report: Spuriously Low Serum IgG4 Concentrations Caused by the Prozone Phenomenon in Patients With IgG4‐Related Disease
Authors: Arezou Khosroshahi, Lynn A. Cheryk, Mollie N. Carruthers, Judith A. Edwards, Donald B. Bloch, John H. Stone
Journal: Arthritis & Rheumatology (2013)

To determine the frequency of the prozone effect in patients with IgG4-related disease (IgG4-RD).After identifying the prozone effect in an index patient with IgG4-RD, we examined additional samples to determine the frequency of this phenomenon. Thirty-eight serum samples obtained from patients with IgG4-RD whose results had been reported previously were retested. The serum IgG4 concentrations determined by this repeat analysis were compared with the originally reported values.In 10 (26%) of 38 patients, the originally reported IgG4 values were falsely low; the prozone effect was identified in each of these 10 samples. Correction of the prozone effect by sample dilution led to revision of the mean serum IgG4 concentration in the 10 samples, from 26 mg/dl to 2,008 mg/dl (normal range 2.4-121 mg/dl). All 10 patients whose samples were affected by the prozone effect had active IgG4-RD. Failure to detect the elevated serum IgG4 concentrations had a direct impact on the decision not to institute treatment in these patients.The prozone effect may lead to major underestimations of IgG4 concentrations in patients with IgG4-RD and offers a potential explanation for the poor correlation observed between disease activity and serum IgG4 levels in some patients. This phenomenon should be considered if the serum IgG4 measurement appears discordant with the clinicopathologic diagnosis and the clinical assessment of disease activity.
Rous Sarcoma Virus-Transformed Hamster Tumor Cells Resistant to 5-Bromodeoxyuridine2
Authors: T. Kuwata, Naoko Morinaga, T. Okazaki, R. Ishitani
Journal: JNCI Journal of the National Cancer Institute (1974)

Rous sarcoma virus (RSV)-transformed hamster sarcoma cells, H-BK strain, were cultured, and induction of RSV by 5-bromodeoxyuridine (BUDR) treatment was attempted. After continuous treatment of the H-BK cells, BUDR-resistant lines were isolated, and biologic characteristics of 3 resistant lines were studied. BUDR-resistant cells, maintained with 50 μg BUDR/ml, did not produce infectious RSV. However, they harbored RSV genomes: When these cells were inoculated into wing webs of chicks, their tumorigenicity was almost the same as that of the BUDR-sensitive parent cells. Moreover, the 3 resistant lines showed the same degree of transplantability to hamsters and agglutinability by concanavalin A as the parent strain.
Prevention and partial reversal of monocrotaline-induced pulmonary arterial hypertension (PAH) by hsp90 inhibitors
Authors: Christiana Dimitropoulou, Connie Snead, Sheldon Litwin, Yunchao Su, John Catravas
Journal: European Respiratory Journal (2012)

We tested the hypothesis that the hsp90 inhibitor, 17-AAG might reverse the hemodynamic alterations associated with PAH. PAH was induced in rats by a single injection of monocrotaline (MCT, 60mg/kg, sc). Four weeks later, a subset of these animals began receiving 17-AAG (1mg/kg 3xweekly, ip) for an additional two weeks. Hemodynamics were monitored weekly by high resolution echocardiography. Right ventricular systolic pressure (RVSP) was also measured invasively at 4 and 6 weeks after MCT. Pulmonary acceleration time (PAT) decreased progressively at 4 and 6 weeks after MCT and reached its nadir at 6 weeks. Similarly, cardiac output (CO) and velocity time integral (VTI) decreased progressively at 4 and 6 weeks post MCT and reached their nadir at 6 weeks. 17-AAG reversed the increase in CO and VTI. At 6 weeks post MCT, both values were statistical similar to those prior to MCT. At 6 weeks post MCT, PAT values in rats treated with 17-AAG between weeks 4 and 6, were higher than those in rats receiving MCT alone for 6 weeks, but similar to those in rats receiving MCT alone for 4 weeks. RVSP and the ratio of the right ventricular weight to either the left ventricular + septum weights (RV/LV+S) or to body weight (RV/BW) increased progressively in MCT-treated rats and reached their maximum at 6 weeks after MCT. At 6 weeks post MCT, RVSP, RV/LV+S and RV/BW values in animals treated with 17-AAG between weeks 4 and 6 were lower than those in rats receiving MCT alone for 6 weeks, but similar to those in rats receiving MCT alone for 4 weeks. These findings suggest that hsp90 inhibitors prevent and partly reverse cardiopulmonary hemodynamic changes associated with MCT-induced PAH.
Ethnic, Racial, and Socioeconomic Disparities in Retinoblastoma
Authors: Bao Truong, Adam L. Green, Paola Friedrich, Karina B. Ribeiro, Carlos Rodriguez-Galindo
Journal: JAMA Pediatrics (2015)

Most children with retinoblastoma in the United States are diagnosed as having a large intraocular tumor burden that requires intensive ocular-salvage treatment or enucleation.To investigate the effect of socioeconomic status, race, and ethnicity on the extent of disease and the outcomes of retinoblastoma.A population-based review of 18 Surveillance, Epidemiology, and End Results (SEER) registries. From January 1, 2000, through December 31, 2010, 830 cases of retinoblastoma were recorded for children aged 0 to 9 years. Data were collected and analyzed from January 1, 2000, through December 31, 2010, with the last follow-up on December 31, 2010.County-based socioeconomic variables analyzed included poverty level, educational attainment, language isolation, crowding, unemployment, and percentage of immigrants.Extent of disease, ocular outcome, and children's survival.Of the 830 individuals included, Hispanic children had a higher percentage of extraocular disease (86 of 261 [33.0%] vs. 102 of 510 non-Hispanic children [20.0%]; odds ratio [OR], 1.97 [95% CI, 1.38-2.79]). The percentage of extraocular cases was also higher in counties with the following low socioeconomic status indicators: higher vs. lower poverty status (115 of 413 [27.8%] vs. 73 of 358 [20.4%]; OR, 1.51; 95% CI, 1.06-2.14); lower vs. higher educational attainment (115 of 400 [28.7%] vs. 73 of 371 [19.7%]; OR, 1.65; 95% CI, 1.16-2.34); higher vs. lower levels of crowding (124 of 398 [31.2%] vs. 64 of 373 [17.2%]; OR, 2.18; 95% CI, 1.53-3.13); higher vs. lower unemployment (119 of 411 [28.9%] vs. 69 of 360 [19.2%]; OR, 1.72; 95% CI, 1.21-2.45); higher vs. lower language isolation (117 of 388 [30.2%] vs. 71 of 383 [18.5%]; OR, 1.89; 95% CI, 1.34-2.70); and higher vs. lower percentage of immigrants (109 of 386 [28.2%] vs. 79 of 385 [20.5%]; OR, 1.52; 95% CI, 1.08-2.16). Higher rates of enucleation were associated with low educational attainment (265 of 401 [66.1%] vs 309 of 421 [73.4%]; OR, 1.42; 95% CI, 1.04-1.93), a higher level of crowding (316 of 416 [76.0%] vs. 258 of 406 [63.5%]; OR, 1.81; 95% CI, 1.32-2.48), and Hispanic origin (202 of 271 [74.5%]; OR, 1.41; 95% CI, 1.01-1.98). Relative survival at 5 years was lower among black compared with non-Hispanic white children (92.7% vs. 99.2%; P < .001).Significant disparities exist in the care and outcomes of children with retinoblastoma. A low socioeconomic status negatively affects disease extent and ocular outcomes, presumably by limiting access to primary and cancer-directed care. Hispanic children in particular have more advanced disease and higher rates of enucleation.
Brief Communication: In Vitro Activation of Armed Macrophages and the Therapeutic Application in Mice
Authors: Henk Van Loveren, Willem Den Otter
Journal: JNCI Journal of the National Cancer Institute (1974)

A specific macrophage arming factor (SMAF) was released when immune spleen lymphocytes were incubated with specific target cells. Cytotoxicity of armed macrophages was enhanced by incubation with immune spleen cells and the specific target cells. The difference in cytotoxicity between allogeneic activated-armed and allogeneic immune macrophages was not significant. In vitro armed and activated syngeneic macrophages significantly prolonged survival time in DBA/2 mice given injections of syngeneic SL2 lymphoma cells.
Mathematical arterialisation for monitoring during exacerbation
Authors: Ulla Møller Weinreich, Beata Rychwicka-Kielek, Bjarne Andersen, Rana Bibi, Lene Birket-Smith, Søren Risom Kristensen, Stephen Edward Rees
Journal: European Respiratory Journal (2011)

Repeated arterial puncture for acid-base and oxygenation status is painful, but quite common in COPD patients admitted for periods of exacerbation. Recently, a method has been presented (Rees, S.E. et. al. Comput. Methods Programs Biomed. 2006;81:18-25) for mathematically transforming values in peripheral venous blood to arterial, potentially eliminating the need for painful arterial puncture. This method has been evaluated at a single time point in COPD patients (Rees, S.E. et. al. Eur J Appl Physiol. 2010;108:483-94).

The aim of this study was to evaluate the method in patients during the whole period of admission to the hospital for exacerbation.

Twenty patients were studied over an admission of on average 5 days, with an average of 3 arterial blood samples taken during this period. For each arterial sample a paired peripheral venous sample was taken and used to calculate arterial values.

Values of pH and arterial PCO2 calculated by the method compared well with those measured with a mean and standard deviation of the difference (measured minus calculated) of 0.000±0.010 pH and -0.03±0.26 kPa PCO2. Figure 1 illustrates the ability of the calculated values (squares, dashed) of arterial pH, PCO2 and PO2 to mirror measured clinical changes (open circles, solid) in a single patient studied on six consecutive days.

![Figure][1] 



Conclusions: The method may be a useful tool to evaluate COPD patients during admission without the need for repeated arterial punctures.

 [1]: pending:yes
Sorafenib in Relapsed AML With FMS-Like Receptor Tyrosine Kinase-3 Internal Tandem Duplication Mutation
Authors: Smith Giri, Shadi Hamdeh, Vijaya Raj Bhatt, James K. Schwarz
Journal: Journal of the National Comprehensive Cancer Network (2015)

Old age (≤65 years), relapsed or refractory disease, and the presence of FMS-like receptor tyrosine kinase-3 (FLT3) internal tandem duplication (ITD) mutation are poor prognostic factors in acute myeloid leukemia (AML). FLT3 inhibitors such as sorafenib have been shown to have a potential role in treating relapsed or refractory AML with FLT3 mutations. In the present report, the use of sorafenib in combination with cytarabine and idarubicin resulted in disease control for 7 months in an older patient with relapsed FLT3-positive AML. This case report and the existing literature indicate that sorafenib has disease activity against relapsed AML with the FLT3-ITD mutation in older patients. Larger multicenter studies should be conducted to confirm these findings, which have the potential to improve outcomes in this high-risk AML subgroup.
Cancer research in Asia: Challenges and opportunities
Authors: John E.L. Wong
Journal: Clinical Cancer Research (2010)

Abstract Cancer is a leading cause of death in Asia, and within the next 20 years, Asia will bear more than half of the world's cancer burden. In Singapore, cancer represents the largest recipient of funding for biomedical research and the leading therapeutic area for clinical trials. Clinical trials should be conducted in Asia for a number of important reasons. First, the phenotypic expression of certain cancers is different between Asia and the West. A commonly cited difference is in non-small cell lung cancer, where the high expression of a mutated epidermal growth factor receptor (EGFR) in nonsmoking Asians, especially women, confers on them a greater sensitivity to EGFR tyrosine kinase inhibitors, e.g. gefitinib and erlotinib. This has led to a change in the management of first line non-small cell lung cancer, with mutation positive patients benefitting from gefitinib more than paclitaxel and carboplatin as first line treatment (NEJM 2009; 361(10): 947-57). The metabolism of certain common cytotoxic drugs, such as doxorubicin, is affected by genotypes that are different in Chinese and Malay populations, compared to Indian and Caucasian populations, leading to differences in toxicities and thus possibly dosages (Pharmacogenetics and Genomics 2008, 18:621—629). Asia has well-trained doctors and scientists who can provide yet another site to accelerate drug development. Singapore was the site of the first-in-world trial of linifanib, a highly active oral inhibitor of vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF). It has moved from phase I to phase III testing in 3 years and has shown promising activity in several common cancers (J Clin Oncol 2009; 27:4718-4726). Asia's economic growth and increasingly educated population has led to a demand for cancer care as well as the means to afford it. Asia is also one of the fastest growing markets for the pharmaceutical industry. For these reasons, universities and research institutes in Asia have formed centers of excellence to complement those in the West.
Abstract 18592: Gender-specific Differences in Phenotypes of Left Ventricular Hypertrophy
Authors: Philipp S Wild, Christoph R Sinning, Christoph Schuh, Sandra Wilde, Andreas Schulz, Francisco M Ojeda, Renate B Schnabel, Tanja Zeller, Till Keller, Edith Lubos, Maria Blettner, Karl J Lackner, Thomas Munzel, Stefan Blankenberg
Journal: Circulation (2010)

Background: Left ventricular hypertrophy (LVH) is independently associated with cardiovascular endpoints, including coronary heart disease and stroke. Gender-specific knowledge about phenotypes of ...
SH2B1: a new player in the regulation of cardiac hypertrophic response in failing hearts: Figure 1
Authors: Yuichi Ikeda, Eiki Takimoto, Issei Komuro
Journal: Cardiovascular Research (2015)

This editorial refers to ‘SH2B1 is critical for the regulation of cardiac remodelling in response to pressure overload’ by G. Wu et al. , pp. 203–215. 

Cardiac hypertrophy is an adaptive process during which cardiomyocytes increase in size in response to various mechanical and hormonal stimuli. Cardiac hypertrophy develops under certain physiological conditions such as pregnancy and exercise, resulting in improved cardiac output to meet the increased oxygen demands. Of note, this physiological cardiac growth is reversible. In contrast, pathological cardiac hypertrophy is an irreversible tissue remodelling that develops in response to prolonged exposure to stress signals. Although both pathological and physiological hypertrophy initially demonstrate enhanced cardiac output, chronic exposure to pathological stimuli eventually leads to impaired cardiac functions. Indeed, pathological hypertrophy serves as an independent risk factor for serious cardiovascular diseases such as heart failure. With a view to developing therapeutics for this condition, molecular mechanisms underlying pathological hypertrophy have been extensively studied.1 Among many signalling pathways identified in cardiomyocytes, the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway is one of the significant signalling pathways involved in this process.2 IL-6 family cytokines play a critical …
Chromosome Studies of Two Transplantable Leukemias of BN Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: U Bregula, I Wlodarska, J Wezyk
Journal: JNCI Journal of the National Cancer Institute (1979)

Karyotypes of two transplantable murine ascites leukemias, LBN/a2 and LBN/b3, were studied with the use of the trypsin-Giemsa technique. The original tumors arose in adult female mice of strains BN/a and BN/b after prolonged antilymphocyte globulin administration. The karyotypes of both leukemias showed similar patterns. Both were hyperdiploid with modal chromosome numbers of 41 and 42 in LBN/a2 and LBN/b3, respectively. The cells consisted of an average of 37 normal chromosomes and 4--5 abnormal chromosomes. The most consistent karyotype deviation was monosomy of the X-chromosome and of several autosomes: no. 9, 14, and 7 in the LBN/a2 line and no. 7, 12, 14, and 9 in the LBN/b3 line. In most LBN/b3 cells and in a lower proportion of LBN/a2 cells, trisomy of chromosome no. 15 was found. With regard to the occurrence of abnormal marker chromosomes, both tumors exhibited great cell-to-cell variation. Two of the markers were common to both leukemia lines.