tbuckley/cabot-search huggingface dataset:
Evaluation of the tumor marker Ca27.29 for risk stratification and treatment monitoring in primary breast cancer
Authors: E. M. Genss, B. Rack, H. L. Sommer, I. Schrader, R. Lorenz, H. Tesch, U. Söling, S. Noeding, M. W. Beckmann, W. Lichtenegger
Journal: Journal of Clinical Oncology (2007)

11005 Background: Several trials have shown an earlier detection of metast. disease in breast cancer pts by the use of TU- markers. Whether this lead time advantage can be translated into improved outcome is discussed controversially. We prospectively evaluated the role of Ca27.29 in breast cancer pts at primary diagnosis and during adjuvant systemic treatment within the German SUCCESS-Trial (n=3658 pts planned). Methods: The SUCCESS-Trial compares sequential chemotherapy with FEC-Docetaxel(Doc) vs. FEC- DocGemcitabine, followed by zoledronate 2 vs. 5 years in primary high risk N0 and N+ breast cancer pts. Ca27.29 levels were assessed using the specific ST AIA-PACK Ca27.29 reagents directed against MUC-1 for AIA-600II (Tosoh Bioscience, Tessenderlo, Belgium). Cut-off levels for the assay was 24 U/ml. Results: We analyzed 1098 breast cancer pts prospectively before start and after completion of chemotherapy. 21% of pts (n=226; median 17U/ml; range 4–410) had tumor marker elevation = 24 U/ml before and 48% (n=524; median 23U/ml; range 4–198) after completion of chemotherapy. Ca27.29 levels before and after chemo correl. significantly (p&lt;.001). Of those pts who presented with elevated values initially, 14% remained positive, while 84% had normal Ca27.29 after chemo. Those pts with initially negative blood sampling, returned with high Ca27.29 in 38% and normal values in 62% of cases. While Ca27.29 was well balanced between the two treatment arms at primary diagnosis with a rate of 10% with elevated Ca27.29 in each arm, significantly more pts showed high Ca27.29 with FEC-DocGemcitabine compared to FEC-Doc (27% vs. 21%, p&lt;.001). Ca27.29 elevation did not correl. with most conventional prognostic factors such as tumor size (p=.23), histopath. grading (p=.98) or HR-status (p=.46). However, we found a significant correlation of Ca 27.29 with the presence of lymph node metastases (p=.01) and Her2/neu-over-expression of the primary tumor (p=.04). Conclusions: Measurement Ca27.29 in peripheral blood of primary breast cancer is feasible and reproducible. Whether it can be used for risk stratification leading to more tailored treatment approaches and for the monitoring of treatment efficacy in individual pts will show further follow-up of the SUCCESS-Study. No significant financial relationships to disclose.
Vegetarian Dietary Patterns and the Risk of Colorectal Cancers
Authors: Michael J. Orlich, Pramil N. Singh, Joan Sabaté, Jing Fan, Lars Sveen, Hannelore Bennett, Synnove F. Knutsen, W. Lawrence Beeson, Karen Jaceldo-Siegl, Terry L. Butler, R. Patti Herring, Gary E. Fraser
Journal: JAMA Internal Medicine (2015)

IMPORTANCEColorectal cancers are a leading cause of cancer mortality, and their primary prevention by diet is highly desirable.The relationship of vegetarian dietary patterns to colorectal cancer risk is not well established.OBJECTIVE To evaluate the association between vegetarian dietary patterns and incident colorectal cancers. DESIGN, SETTING, AND PARTICIPANTSThe Adventist Health Study 2 (AHS-2) is a large, prospective, North American cohort trial including 96 354 Seventh-Day Adventist men and women recruited between January 1, 2002, and December 31, 2007.Follow-up varied by state and was indicated by the cancer registry linkage dates.Of these participants, an analytic sample of 77 659 remained after exclusions.Analysis was conducted using Cox proportional hazards regression, controlling for important demographic and lifestyle confounders.The analysis was conducted between June 1, 2014, and October 20, 2014.EXPOSURES Diet was assessed at baseline by a validated quantitative food frequency questionnaire and categorized into 4 vegetarian dietary patterns (vegan, lacto-ovo vegetarian, pescovegetarian, and semivegetarian) and a nonvegetarian dietary pattern. MAIN OUTCOMES AND MEASURESThe relationship between dietary patterns and incident cancers of the colon and rectum; colorectal cancer cases were identified primarily by state cancer registry linkages.RESULTS During a mean follow-up of 7.3 years, 380 cases of colon cancer and 110 cases of rectal cancer were documented.The adjusted hazard ratios (HRs) in all vegetarians combined vs nonvegetarians were 0.78 (95% CI, 0.64-0.95)for all colorectal cancers, 0.81 (95% CI, 0.65-1.00)for colon cancer, and 0.71 (95% CI, 0.47-1.06)for rectal cancer.The adjusted HR for colorectal cancer in vegans was 0.84 (95% CI, 0.59-1.19); in lacto-ovo vegetarians, 0.82 (95% CI, 0.65-1.02); in pescovegetarians, 0.57 (95% CI, 0.40-0.82);and in semivegetarians, 0.92 (95% CI, 0.62-1.37)compared with nonvegetarians.Effect estimates were similar for men and women and for black and nonblack individuals.CONCLUSIONS AND RELEVANCE Vegetarian diets are associated with an overall lower incidence of colorectal cancers.Pescovegetarians in particular have a much lower risk compared with nonvegetarians.If such associations are causal, they may be important for primary prevention of colorectal cancers.
Attenuated Expression of DFFB is a Hallmark of Oligodendrogliomas with 1p-Allelic Loss
Authors: J Matthew McDonald, Valerie Dunmire, Ellen Taylor, Raymond Sawaya, Janet Bruner, Gregory N Fuller, Kenneth Aldape, Wei Zhang
Journal: Molecular Cancer (2005)

Abstract Allelic loss of chromosome 1p is frequently observed in oligodendroglioma. We screened 177 oligodendroglial tumors for 1p deletions and found 6 tumors with localized 1p36 deletions. Several apoptosis regulation genes have been mapped to this region, including Tumor Protein 73 (p73) , DNA Fragmentation Factor subunits alpha ( DFFA ) and beta ( DFFB ), and Tumor Necrosis Factor Receptor Superfamily Members 9 and 25 ( TNFRSF9, TNFRSF25 ). We compared expression levels of these 5 genes in pairs of 1p-loss and 1p-intact tumors using quantitative reverse-transcriptase PCR (QRTPCR) to test if 1p deletions had an effect on expression. Only the DFFB gene demonstrated decreased expression in all tumor pairs tested. Mutational analysis did not reveal DFFB mutations in 12 tested samples. However, it is possible that DFFB haploinsufficiency from 1p allelic loss is a contributing factor in oligodendroglioma development.
Questionable Universal Validity of <i>PAX3/FOXO1</i> Fusion Gene Status As Molecular Marker for Improvement of Risk Stratification in Rhabdomyosarcoma Therapy
Authors: Sabine Stegmaier, Stefan S. Bielack, Ivo Leuschner, Thomas Klingebiel, Ewa Koscielniak
Journal: Journal of Clinical Oncology (2012)

0][11] The current C10403 trial conducted by the US adult cooperative groups is a critical study, which we support fully.However, the adult cooperative groups have not yet demonstrated that equivalent results to those obtained in pediatric trials can be obtained for older adolescents.Hence, we stand by our recommendation that the optimal treatment for an older adolescent with ALL is referral to a pediatric center and enrollment onto a pediatric group cooperative trial.
Phenylthiocarbamide Perception in Patients With Schizophrenia and First-Degree Family Members
Authors: Paul J. Moberg, David R. Roalf, Catherine C. Balderston, Stephen J. Kanes, Raquel E. Gur, Bruce I. Turetsky
Journal: American Journal of Psychiatry (2005)

The inability to taste phenylthiocarbamide (PTC) has been associated with medical and neurological illnesses not typically related to taste. The authors examined PTC sensitivity in schizophrenia patients and their non-ill relatives to determine whether this represented a vulnerability marker.PTC sensitivity was assessed in 42 schizophrenia patients, 23 healthy comparison subjects, and 12 first-degree relatives of the patients.More nontasters were found among patients and family members than healthy comparison subjects. Among patients, nontasters had more positive symptoms. Differences were not explained by sex, age, medication, smoking, or cognitive impairment.The prevalence of PTC nontasters was greater among schizophrenia patients and non-ill first-degree family members. Phenotypic variation in PTC sensitivity is genetic in origin. This suggests a higher risk for illness among subjects with recessive alleles.
Quartz exposure and lung function
Authors: Karl Hochgatterer, Hanns Moshammer, Daniela Haluza
Journal: European Respiratory Journal (2012)

Occupational exposure to quartz not only leads to silicosis but also to chronic bronchitis and obstructive lung disease. In Austria more stringent occupational limit values for dusts have been introduced in 2007. We assumed that (a) workers exposed to mineral dusts (quartz) have a poorer lung function (LF) than other workers that undergo repeated LF testing because of other occupational exposures (dusts and fumes), (b) LF decline is fastest in the quartz-group, and (c) the decline slowed down after the introduction of stricter limit values.

We examined repeated LF data (FVC, FEV1, MEF50) from the routine examination (usually every two years) performed by one occupational health centre from the years 2002 through 2010. Three main linear regression models were analysed on each LF parameter. (a) The effect of quartz exposure on the raw parameter after controlling for age, height, weight (quadratic term), gender, and smoking. (b) The effect of quartz exposure on the difference between actual value and the age-sex-height-dependent Austrian norm value. This approach allowed us to additionally control for the impact of duration of exposure. (c) The impact of quartz exposure on the intra-individual decline in LF parameters per year. In this analysis we could also check for differences in the slope before and after the introduction of new limit values.

We analysed 7315 data-sets (on average 5 per person, mostly males). Nearly 40% of these were from workers exposed to quartz dusts. The remaining workers were welders or were exposed aluminium or other dusts. Both smoking and quartz exposure lead to lower LF values. Duration of quartz exposure also was a significant predictor of LF decline. The decline slowed after the introduction of stricter limit values.
Phase II Study of Fenretinide (NSC 374551) in Adults With Recurrent Malignant Gliomas: A North American Brain Tumor Consortium Study
Authors: Vinay K. Puduvalli, W.K. Alfred Yung, Kenneth R. Hess, John G. Kuhn, Morris D. Groves, Victor A. Levin, James Zwiebel, Susan M. Chang, Timothy F. Cloughesy, Larry Junck, Patrick Wen, Frank Lieberman, Charles A. Conrad, Mark R. Gilbert, Christina A. Meyers, Vivien Liu, Minesh P. Mehta, M. Kelly Nicholas, Michael Prados
Journal: Journal of Clinical Oncology (2004)

Fenretinide induces apoptosis in malignant gliomas in vitro. This two-stage phase II trial was conducted to determine the efficacy of fenretinide in adults with recurrent malignant gliomas.Twenty-two patients with anaplastic gliomas (AG) and 23 patients with glioblastoma (GBM) whose tumors had recurred after radiotherapy and no more than two chemotherapy regimens were enrolled. Fenretinide was given orally on days 1 to 7 and 22 to 28 in 6-week cycles in doses of 600 or 900 mg/m(2) bid.Six of 21 (29%) patients in the AG arm and two of 23 (9%) patients in the GBM arm had stable disease at 6 months. One patient with AG treated at 900 mg/m(2) bid dosage had a partial radiologic response. Median progression-free survival (PFS) was 6 weeks for the AG arm and 6 weeks for the GBM arm. PFS at 6 months was 10% for the AG arm and 0% for the GBM arm. Grade 1 or 2 fatigue, dryness of skin, anemia, and hypoalbuminemia were the most frequent toxicities reported. The trial was closed after the first stage because of the inadequate activity at the fenretinide doses used. The first-administration mean plasma C(max) for fenretinide was 832 +/- 360 ng/mL at the 600 mg/m(2) bid dosage and 1,213 +/- 261 ng/mL at the 900 mg/m(2) bid dosage.Fenretinide was inactive against recurrent malignant gliomas at the dosage used in this trial. However, additional studies using higher doses of the agent are warranted based on the tolerability of the agent and the potential for activity of a higher fenretinide dosage, as suggested in this trial.
<i>HER2</i> Testing by Local, Central, and Reference Laboratories in Specimens From the North Central Cancer Treatment Group N9831 Intergroup Adjuvant Trial
Authors: Edith A. Perez, Vera J. Suman, Nancy E. Davidson, Silvana Martino, Peter A. Kaufman, Wilma L. Lingle, Patrick J. Flynn, James N. Ingle, Daniel Visscher, Robert B. Jenkins
Journal: Journal of Clinical Oncology (2006)

Purpose To evaluate concordance between local and central laboratory HER2 testing results in patients from the North Central Cancer Treatment Group (NCCTG) N9831 adjuvant trial of trastuzumab. Patients and Methods NCCTG N9831 is a randomized, phase III clinical trial comparing three drug regimens: doxorubicin/cyclophosphamide followed by paclitaxel with trastuzumab added concurrently, sequentially, or not at all as adjuvant therapy for women with HER2-positive resected breast cancer. Originally, patients were eligible if their tumors were HER2 positive by either local laboratory immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH). A protocol modification in 2002 made central laboratory testing mandatory, with additional testing of discordant cases conducted by a reference laboratory. Concordance between local and central laboratory, and level of agreement between central and reference laboratory HER2 findings in discordant cases were examined. Results HER2 positivity was confirmed in 85.8% of 2,535 patients registered since March 2002. When local and central evaluation used the same methodology, concordance was 88.1% for FISH and 81.6% for a diagnostic test for presence of the HER2 protein. Among discordant cases examined at the reference laboratory, there was 94.3% agreement for IHC (0, 1+, 2+) and 95.2% agreement for FISH (not gene amplified). Conclusion There was a high degree of discordance between local and central testing for IHC and FISH, but a high degree of agreement between central and reference laboratories. These findings support the importance of using high-volume, experienced laboratories for HER2 testing to improve the process of selecting patients likely to benefit from trastuzumab therapy.
Reduced Purkinje Cell Size in the Cerebellar Vermis of Elderly Patients With Schizophrenia
Authors: Khoa D. Tran, Gregory S. Smutzer, Richard L. Doty, Steven E. Arnold
Journal: American Journal of Psychiatry (1998)

Objective: The authors’ goal was to compare the size and linear density of Purkinje cells in the cerebellar vermis of subjects with and without schizophrenia. Method: Blocks of alcohol-fixed cerebellar vermis were dissected at autopsy from the brains of 14 elderly patients with schizophrenia and 13 elderly subjects with no history of neuropsychiatric illness. The blocks of vermis were sectioned and stained with 1% cresyl violet. The linear density and cross-sectional area of Purkinje cells were measured by using computer-assisted image analysis. The subjects with schizophrenia had been assessed with clinical rating scales within 1 year prior to death.Results: The average cross-sectional areas of Purkinje cells of the patients with schizophrenia were significantly smaller (by 8.3%) than those of the subjects without neuropsychiatric illness. No difference in Purkinje cell linear density was observed between the two groups. Significant correlations were seen between Purkinje cell size and scores on the Mini-Mental State, the Brief Psychiatric Rating Scale, and the antipsychotic drug dose.Conclusions: These data indicate cerebellar involvement in schizophrenia; they are also consistent with reports of reduced neuronal size in other brain regions of patients with schizophrenia. These findings support a model of widespread central nervous system abnormality in schizophrenia. Am J Psychiatry 1998; 155: 1288-1290
Male reproductive development: gene expression profiling of maize anther and pollen ontogeny
Authors: Jiong Ma, David S Skibbe, John Fernandes, Virginia Walbot
Journal: Genome biology (2008)

During flowering, central anther cells switch from mitosis to meiosis, ultimately forming pollen containing haploid sperm. Four rings of surrounding somatic cells differentiate to support first meiosis and later pollen dispersal. Synchronous development of many anthers per tassel and within each anther facilitates dissection of carefully staged maize anthers for transcriptome profiling. Global gene expression profiles of 7 stages representing 29 days of anther development are analyzed using a 44 K oligonucleotide array querying approximately 80% of maize protein-coding genes. Mature haploid pollen containing just two cell types expresses 10,000 transcripts. Anthers contain 5 major cell types and express >24,000 transcript types: each anther stage expresses approximately 10,000 constitutive and approximately 10,000 or more transcripts restricted to one or a few stages. The lowest complexity is present during meiosis. Large suites of stage-specific and co-expressed genes are identified through Gene Ontology and clustering analyses as functional classes for pre-meiotic, meiotic, and post-meiotic anther development. MADS box and zinc finger transcription factors with constitutive and stage-limited expression are identified. We propose that the extensive gene expression of anther cells and pollen represents the key test of maize genome fitness, permitting strong selection against deleterious alleles in diploid anthers and haploid pollen. Because flowering plants show a substantial bias for male-sterile compared to female-sterile mutations, we propose that this fitness test is general. Because both somatic and germinal cells are transcriptionally quiescent during meiosis, we hypothesize that successful completion of meiosis is required to trigger maturation of anther somatic cells.
Platelet alpha-granule release in cocaine users.
Authors: H M Rinder, K A Ault, P I Jatlow, T R Kosten, B R Smith
Journal: Circulation (1994)

BACKGROUND Cocaine use has been associated with arterial occlusion resulting from platelet-rich thrombi and with an accelerated, often atypical atherosclerotic lesion that could be ascribed to platelet activation and platelet alpha-granule release. METHODS AND RESULTS Using a flow cytometric method to quantitate the percent of circulating activated platelets in whole blood (those that express the alpha-granule membrane protein P-selectin), we found that 5 of 25 samples from 12 long-term cocaine users had a baseline level of circulating activated platelets &gt; 3 SD (range, 19% to 60%) above the mean (4.4 +/- 3.7%, mean +/- 1 SD) for 85 nonusers (sample n = 130). This subset resulted in a significantly higher mean baseline level of circulating activated platelets (11.8 +/- 14.4%) for all cocaine users (P = .01). By contrast, cocaine and its metabolites, at concentrations documented as obtainable during in vivo cocaine use (10(-7) to 10(-5) mol/L), had no effect on in vitro platelet activation or aggregation, either directly or in concert with platelet agonists. However, in experiments in which cocaine users received blinded infusions of placebo or cocaine, the mean percent of circulating activated platelets rose significantly (P &lt; .05) after infusion of either placebo (peak 77 +/- 31%) or cocaine (peak 65 +/- 28%), the latter at doses resulting in peak plasma cocaine levels averaging &lt; 10(-6) mol/L. CONCLUSIONS Long-term cocaine use in some subjects is intermittently associated with high basal levels of circulating platelets that have undergone alpha-granule release. The inability of cocaine and its metabolites at concentrations of 10(-7) to 10(-5) mol/L to cause platelet P-selectin expression in vitro in this study, coupled with the acute increase in circulating activated platelets observed in vivo after either cocaine or placebo infusion, suggests that in vivo platelet alpha-granule release associated with cocaine use may occur through indirect rather than direct effects of the drug.
Cardiac assessment of veteran endurance athletes: a 12 year follow up study.
Authors: S Hood, R J Northcote
Journal: British Journal of Sports Medicine (1999)

OBJECTIVES: Sustained aerobic dynamic exercise is beneficial in preventing cardiovascular disease. The effect of lifelong endurance exercise on cardiac structure and function is less well documented, however. A 12 year follow up of 20 veteran athletes was performed, as longitudinal studies in such cohorts are rare. METHODS: Routine echocardiography was repeated as was resting, exercise, and 24 hour electrocardiography. RESULTS: Nineteen returned for screening. Mean (SD) age was 67 (6.2) years (range 56-83). Two individuals had had permanent pacemakers implanted (one for symptomatic atrial fibrillation with complete heart block, the other for asystole lasting up to 15 seconds). Only two athletes had asystolic pauses in excess of two seconds compared with seven athletes in 1985. Of these seven, five had no asystole on follow up. Two of these five had reduced their average running distance by about 15-20 miles a week. One athlete sustained an acute myocardial infarction during a competitive race in 1988. Three athletes had undergone coronary arteriography during the 12 years of follow up but none had obstructive coronary artery disease. Ten of 19 (53%) had echo evidence of left ventricular hypertrophy in 1997 but only two (11%) had left ventricular dilatation. Ten athletes had ventricular couplets on follow up compared with only two in 1985. CONCLUSIONS: Although the benefits of moderate regular exercise are undisputed, high intensity lifelong endurance exercise may be associated with altered cardiac structure and function. These adaptations to more extreme forms of exercise merit caution in the interpretation of standard cardiac investigations in the older athletic population. On rare occasions, these changes may be deleterious.
Bβ15–42 Attenuates the Effect of Ischemia-Reperfusion Injury in Renal Transplantation
Authors: Inga Sörensen, Song Rong, Nathan Susnik, Faikah Gueler, Nelli Shushakova, Melanie Albrecht, Anna-Maria Dittrich, Sibylle von Vietinghoff, Jan Ulrich Becker, Anette Melk, Andrea Bohlmann, Sonja Reingruber, Peter Petzelbauer, Hermann Haller, Roland Schmitt
Journal: Journal of the American Society of Nephrology (2011)

Renal ischemia-reperfusion contributes to reduced renal allograft survival. The peptide Bβ(15-42), a breakdown product of fibrin, attenuates inflammation induced by ischemia-reperfusion in the heart by competitively blocking the binding of leukocytes to endothelial VE-cadherin, but whether it could improve outcomes in renal transplantation is unknown. Here, we tested the ability of Bβ(15-42) to ameliorate the effects of renal ischemic injury during allogenic kidney transplantation in mice. In our renal transplantation model (C57BL/6 into BALB/c mice), treatment with Bβ(15-42) at the time of allograft reperfusion resulted in significantly improved survival of recipients during the 28-day follow-up (60% versus 10%). Bβ(15-42) treatment decreased leukocyte infiltration, expression of endothelial adhesion molecules, and proinflammatory cytokines. Treatment significantly attenuated allogenic T cell activation and reduced cellular rejection. Moreover, Bβ(15-42) significantly reduced tubular epithelial damage and apoptosis, which we reproduced in vitro. These data suggest that Bβ(15-42) may have therapeutic potential in transplant surgery by protecting grafts from ischemia-reperfusion injury.