tbuckley/cabot-search huggingface dataset:
Oxidative DNA Damage in Prostate Cancer Patients Consuming Tomato Sauce-Based Entrees as a Whole-Food Intervention
Authors: L. Chen, M. Stacewicz-Sapuntzakis, C. Duncan, R. Sharifi, L. Ghosh, R. v. Breemen, D. Ashton, P. E. Bowen
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: Human prostate tissues are vulnerable to oxidative DNA damage. The risk of prostate cancer is lower in men reporting higher consumption of tomato products, which contain high levels of the antioxidant lycopene. We examined the effects of consumption of tomato sauce-based pasta dishes on lycopene uptake, oxidative DNA damage, and prostate-specific antigen (PSA) levels in patients already diagnosed with prostate cancer. Methods: Thirty-two patients with localized prostate adenocarcinoma consumed tomato sauce-based pasta dishes for the 3 weeks (30 mg of lycopene per day) preceding their scheduled radical prostatectomy. Serum and prostate lycopene concentrations, serum PSA levels, and leukocyte DNA oxidative damage (ratio of 8-hydroxy-2`-deoxyguanosine [8-OHdG] to 2`-deoxyguanosine [dG]) were assessed before and after the dietary intervention. DNA oxidative damage was assessed in resected prostate tissue from study participants and from seven randomly selected prostate cancer patients. All statistical tests were two-sided. Results: After the dietary intervention, serum and prostate lycopene concentrations were statistically significantly increased, from 638 nM (95% confidence interval [CI] = 512 to 764 nM) to 1258 nM (95% CI = 1061 to 1455 nM) (P<.001) and from 0.28 nmol/g (95% CI = 0.18 to 0.37 nmol/g) to 0.82 nmol/g (95% CI = 0.57 to 1.11 nmol/g) (P <.001), respectively. Compared with preintervention levels, leukocyte oxidative DNA damage was statistically significantly reduced after the intervention, from 0.61 8-OHdG/105 dG (95% CI = 0.45 to 0.77 8-OHdG/105 dG) to 0.48 8-OHdG/ 105 dG (95% CI = 0.41 to 0.56 8-OHdG/105 dG) (P = .005). Furthermore, prostate tissue oxidative DNA damage was also statistically significantly lower in men who had the intervention (0.76 8-OHdG/105 dG [95% CI = 0.55 to 0.96 8-OHdG/105 dG]) than in the randomly selected patients (1.06 8-OHdG/105 dG [95% CI = 0.62 to 1.51 8-OHdG/105 dG]; P = .03). Serum PSA levels decreased after the intervention, from 10.9 ng/mL (95% CI = 8.7 to 13.2 ng/mL) to 8.7 ng/mL (95% CI = 6.8 to 10.6 ng/mL) (P<.001). Conclusion: These data indicate a possible role for a tomato sauce constituent, possibly lycopene, in the treatment of prostate cancer and warrant further testing with a larger sample of patients, including a control group.
Busulfan plus fludarabine as a myeloablative conditioning regimen compared with busulfan plus cyclophosphamide for acute myeloid leukemia in first complete remission undergoing allogeneic hematopoietic stem cell transplantation: a prospective and multicenter study
Authors: Hui Liu, Xiao Zhai, Zhaoyang Song, Jing Sun, Yang Xiao, Danian Nie, Yu Zhang, Fen Huang, Hongsheng Zhou, Zhiping Fan, Sanfang Tu, Yonghua Li, Xutao Guo, Guopan Yu, Qifa Liu
Journal: Journal of Hematology & Oncology (2013)

We conducted a prospective, randomized, open-label, multicenter study to compare busulfan plus fludarabine (BuFlu) with busulfan plus cyclophosphamide (BuCy) as the conditioning regimen in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia (AML) in first complete remission (CR1). Totally 108 AML-CR1 patients undergoing allo-HSCT were randomized into BuCy (busulfan 1.6 mg/kg, q12 hours, -7 ~ -4d; cyclophosphamide 60 mg/kg.d, -3 ~ -2d) or BuFlu (busulfan 1.6 mg/kg, q12 hours, -5 ~ -2d; fludarabine 30 mg/m2.d, -6 ~ -2d) group. Hematopoietic engraftment, regimen-related toxicity (RRT), graft-versus-host disease (GVHD), transplant related mortality (TRM), and overall survival were compared between the two groups. All patients achieved hematopoietic reconstitution except for two patients who died of RRT during conditioning. All patients obtained complete donor chimerism by day +30 post-transplantation. The incidence of total and III-IV RRT were 94.4% and 81.5% (P = 0.038), and 16.7% and 0.0% (P = 0.002), respectively, in BuCy and BuFlu group. With a median follow up of 609 (range, 3–2130) days after transplantation, the 5-year cumulative incidence of TRM were 18.8 ± 6.9% and 9.9 ± 6.3% (P = 0.104); the 5-year cumulative incidence of leukemia relapse were 16.5 ± 5.8% and 16.2 ± 5.3% (P = 0.943); the 5-year disease-free survival and overall survival were 67.4 ± 7.6% and 75.3 ± 7.2% (P = 0.315), and 72.3 ± 7.5% and 81.9 ± 7.0% (P = 0.177), respectively in BuCy and BuFlu group. Compared with BuCy, BuFlu as a myeloablative condition regimen was associated with lower toxicities and comparable anti-leukemic activity in AML-CR1 patients undergoing allo-HSCT.
Effect of dietary fat, carbohydrate, and protein on branched-chain amino acid catabolism during caloric restriction.
Authors: J A Vazquez, E L Morse, S A Adibi
Journal: Journal of Clinical Investigation (1985)

To assess the effect of each dietary caloric source on the catabolism of branched-chain amino acids, we investigated the rate of leucine oxidation before and after obese volunteers consumed one of the following diets for one week: (a) starvation, (b) 300 or 500 cal of fat/d, (c) 300 or 500 cal of carbohydrate/d, (d) 300 or 500 cal of protein/d, (e) a mixture of carbohydrate (300 cal/d) and fat (200 cal/d), or (f) a mixture of carbohydrate (300 cal/d) and protein (200 cal/d). Starvation significantly increased the rate of leucine oxidation (1.4 +/- 0.11 vs. 1.8 +/- 0.16 mmol/h, P less than 0.01). The same occurred with the fat and protein diets. In sharp contrast, the 500-cal carbohydrate diet significantly decreased the rate of leucine oxidation (1.3 +/- 0.13 vs. 0.6 +/- 0.09 mmol/h, P less than 0.01). The same occurred when a portion of the carbohydrate diet was isocalorically replaced with either fat or protein. The cumulative nitrogen excretion during the fat diet and starvation was not significantly different. As compared with the fat diets, the carbohydrate diets on the average reduced the urinary nitrogen excretion by 12 g/wk. Nitrogen balance was positive during the consumption of the 500-cal protein diet, but negative during the consumption of carbohydrate-protein diet. The fat diets, like the protein diets and starvation, greatly increased plasma leucine (119 +/- 13 vs. 222 +/- 15 microM, P less than 0.01) and beta-hydroxybutyrate (0.12 +/- 0.02 vs. 4.08 +/- 0.43 mM, P less than 0.01) concentrations, and significantly decreased plasma glucose (96 +/- 4 vs. 66 +/- 3 mg/dl, P less than 0.01) and insulin (18 +/- 4 vs. 9 +/- 1 microU/ml, P less than 0.05) concentrations. These changes did not occur, or were greatly attenuated, when subjects consumed carbohydrate alone or in combination with fat or protein. We conclude that during brief caloric restriction, dietary lipid and protein, unlike carbohydrate, do not diminish the catabolism of branched-chain amino acids and the decrease in branched-chain amino acid oxidation is associated with protein sparing.
Actions of Parathyroid Hormone–Related Peptide and Its Receptors
Authors: T. John Martin
Journal: New England Journal of Medicine (1996)

Building on the insight gained from their initial identification of a mutation in the receptor for parathyroid hormone (PTH) and parathyroid hormone–related peptide (PTHrP) in a patient with Jansen's metaphyseal chondrodysplasia,1 Schipani et al. provide further data on genetic abnormalities associated with the disorder in this issue of the Journal. 2 They report the same mutation in a mother and her daughter and a different mutation in another patient. Two other, less severely affected patients had no detectable mutations.The mutations cause the PTH–PTHrP receptor to be persistently activated, resulting in a state of hypercalcemia and hypophosphatemia resembling that in patients . . .
A Multilocus Technique for Risk Evaluation of Patients with Neuroblastoma
Authors: Inge M. Ambros, Bettina Brunner, Gerhard Aigner, Clare Bedwell, Klaus Beiske, Jean Bénard, Nick Bown, Valerie Combaret, Jerome Couturier, Raffaella Defferrari, Nicole Gross, Marta Jeison, John Lunec, Barbara Marques, Tommy Martinsson, Katia Mazzocco, Rosa Noguera, Gudrun Schleiermacher, Frank Speleman, Ray Stallings, Gian Paolo Tonini, Deborah A. Tweddle, Alexander Valent, Ales Vicha, Nadine Van Roy, Eva Villamon, Andrea Ziegler, Sandra Preuner, Mario Drobics, Ruth Ladenstein, Gabriele Amann, Robert J.L. Schuit, Ulrike Pötschger, Peter F. Ambros
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Precise and comprehensive analysis of neuroblastoma genetics is essential for accurate risk evaluation and only pangenomic/multilocus approaches fulfill the present-day requirements. We present the establishment and validation of the PCR-based multiplex ligation-dependent probe amplification (MLPA) technique for neuroblastoma. Experimental Design: A neuroblastoma-specific MLPA kit was designed by the SIOP Europe Neuroblastoma Biology Committee in cooperation with MRC-Holland. The contained target sequences cover 19 chromosomal arms and reference loci. Validation was performed by single locus and pangenomic techniques (n = 174). Dilution experiments for determination of minimal tumor cell percentage were performed and testing of reproducibility was checked by interlaboratory testing (n = 15). Further 156 neuroblastomas were used for establishing the amplification cutoff level. Results: The MLPA technique was tested in 310 neuroblastomas and 8 neuroblastoma cell lines (including validation and amplification cutoff level testing). Intertechnique validation showed a high concordance rate (99.5%). Interlaboratory MLPA testing (κ = 0.95, P &amp;lt; 0.01) revealed 7 discrepant of 1,490 results (0.5%). Validation by pangenomic techniques showed a single discordance of 190 consensus results (0.5%). The test results led to formulation of interpretation standards and to a kit revision. The minimal tumor cell percentage was fixed at 60%. Conclusions: The recently designed neuroblastoma-specific MLPA kit covers all chromosomal regions demanded by the International Neuroblastoma Risk Group for therapy stratification and includes all hitherto described genetic loci of prognostic interest for future studies and can be modified or extended at any time. Moreover, the technique is cost effective, reliable, and robust with a high interlaboratory and intertechnique concordance. Clin Cancer Res; 17(4); 792–804. ©2011 AACR.
Enhanced platelet accumulation onto injured carotid arteries in rabbits after aspirin treatment.
Authors: M R Buchanan, E Dejana, M Gent, J F Mustard, J Hirsch
Journal: Journal of Clinical Investigation (1981)

Prostacyclin (PGI2) is a powerful inhibitor of platelet aggregation, but its role in the pathogenesis of arterial thrombosis is uncertain. We have studied the thrombogenic effect of inhibiting PGI2 production by aspirin (ASA) in carotid arteries of rabbits given 0, 3, 10, or 100 mg ASA/kg either 1, 3, 6, or 20 h beforehand. Platelet accumulation onto injured carotid arteries was enhanced with ASA in a dose of 10 mg/kg. A higher dose of ASA (100 mg/kg) had no further effect. The enhanced thrombogenic effect of ASA persisted for at least 20 h and was associated with a decrease in vessel wall PGI2 production. There was a strong inverse correlation (r = 0.55, P less than 0.01) between PGI2 production and platelet accumulation. The findings suggest that the margin of safety in obtaining an antithrombotic effect of ASA and producing a potential thrombotic effect in arteries may not be as large as predicted by studies using cultured endothelial cells or experimentally induced thrombosis in veins.
Improved glycemic control and lipid profile and normalized fibrinolytic activity on a low-glycemic index diet in type 2 diabetic patients.
Authors: A E Järvi, B E Karlström, Y E Granfeldt, I E Björck, N G Asp, B O Vessby
Journal: Diabetes Care (1999)

OBJECTIVE: To evaluate the effects of varying the glycemic index (GI) of carbohydrate-rich foods on metabolic control in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: In a randomized crossover study, 20 patients, 5 women and 15 men, were given preweighed diets with different GIs during two consecutive 24-day periods. Both diets were composed in accordance with dietary recommendations for people with diabetes. The macronutrient composition and type and amount of dietary fiber were identical. Differences in GI were achieved mainly by altering the structure of the starchy foods. RESULTS: Peripheral insulin sensitivity increased significantly and fasting plasma glucose decreased during both treatment periods. There was a significant difference in the changes of serum fructosamine concentrations between the diets (P &amp;lt; 0.05). The incremental area under the curve for both blood glucose and plasma insulin was approximately 30% lower after the low- than after the high-GI diet. LDL cholesterol was significantly lowered on both diets, with a significantly more pronounced reduction on the low-GI diet. Plasminogen activator inhibitor-1 activity was normalized on the low-GI diet, (-54%, P &amp;lt; 0.001), but remained unchanged on the high-GI diet. CONCLUSIONS: A diet characterized by low-GI starchy foods lowers the glucose and insulin responses throughout the day and improves the lipid profile and capacity for fibrinolysis, suggesting a therapeutic potential in diabetes.
Technetium-Bevacizumab in a Patient With Bone and Lung Metastatic Colon Adenocarcinoma
Authors: Eduardo C. Noguera, Emilio Palazzo, Matias F. Mayoraz, Ana Diller, Maria V. Burgesser, Adelina Jaime, Adriana Borello, Rodolfo Avila, Juan C. Mondina
Journal: Journal of Clinical Oncology (2013)
An Essential Role for gp130 in Neointima Formation Following Arterial Injury
Authors: Dong Wang, Zhimin Liu, Quanyi Li, Manjula Karpurapu, Venkatesh Kundumani-Sridharan, Huiqing Cao, Nagadhara Dronadula, Farhan Rizvi, Arun K. Bajpai, Chunxiang Zhang, Gerhard Müller-Newen, Kevin W. Harris, Gadiparthi N. Rao
Journal: Circulation Research (2007)

Interleukin (IL)-6 induced vascular smooth muscle cell (VSMC) motility in a dose-dependent manner. In addition, IL-6 stimulated tyrosine phosphorylation of gp130, resulting in the recruitment and activation of STAT-3. IL-6-induced VSMC motility was found to be dependent on activation of gp130/STAT-3 signaling. IL-6 also induced cyclin D1 expression in a time- and gp130/STAT-3-dependent manner in VSMCs. Suppression of cyclin D1 levels via the use of its small interfering RNA molecules inhibited IL-6-induced VSMC motility. Furthermore, balloon injury induced IL-6 expression both at mRNA and protein levels in rat carotid artery. Balloon injury also caused increased STAT-3 phosphorylation and cyclin D1 expression, leading to smooth muscle cell migration from the media to the intimal region. Blockade of gp130/STAT-3 signaling via adenovirus-mediated expression of dngp130 or dnSTAT-3 attenuated balloon injury-induced STAT-3 phosphorylation and cyclin D1 induction, resulting in reduced smooth muscle cell migration from media to intima and decreased neointima formation. Together, these observations for the first time suggest that IL-6/gp130/STAT-3 signaling plays an important role in vascular wall remodeling particularly in the settings of postangioplasty and thereby in neointima formation.
Randomized trial of vitamin A versus observation as adjuvant therapy in high-risk primary malignant melanoma: a Southwest Oncology Group study.
Authors: F L Meyskens, P Y Liu, R J Tuthill, V K Sondak, W S Fletcher, W R Jewell, W Samlowski, S P Balcerzak, D J Rector, R D Noyes
Journal: Journal of Clinical Oncology (1994)

A national cooperative group trial was conducted in patients with early-stage cutaneous malignant melanoma to determine if oral vitamin A can increase disease-free survival or survival.Two hundred forty-eight patients with completely resected melanoma of Breslow's thickness greater than 0.75 mm and clinically negative lymph nodes were randomized to oral vitamin A (100,000 IU/d) for 18 months or to observation. Patients were stratified by Breslow's thickness of primary lesion (0.76 to 1.50 mm, 1.51 to 3.00 mm, or > 3.00 mm), sex, and type of therapy (excision, excision plus node dissection, excision plus perfusion, or excision plus both). The median duration of follow-up observation of living patients is greater than 8 years. The relative risk (RR) in disease-free survival and overall survival in the treatment compared with the observation group was calculated using Cox proportional hazards models.Overall, there was no difference in disease-free survival or overall survival between the two groups. Examination of treatment by stratification interactions and subset analysis did not show any treatment-effect differences based on sex or type of therapy. There was also no difference between groups in disease-free survival based on Breslow's thickness of the primary lesion. Overall, 12% of patients who received vitamin A experienced grade 3 or 4 toxicities.Based on the lack of overall survival benefit, further evaluation of vitamin A as adjuvant therapy for melanoma does not appear warranted.
Selenium and Vitamin E: Cell Type– and Intervention-Specific Tissue Effects in Prostate Cancer
Authors: Dimitra Tsavachidou, Timothy J. McDonnell, Sijin Wen, Xuemei Wang, Funda Vakar-Lopez, Louis L. Pisters, Curtis A. Pettaway, Christopher G. Wood, Kim-Anh Do, Peter F. Thall, Clifton Stephens, Eleni Efstathiou, Robert Taylor, David G. Menter, Patricia Troncoso, Scott M. Lippman, Christopher J. Logothetis, Jeri Kim
Journal: JNCI Journal of the National Cancer Institute (2009)

Secondary analyses of two randomized, controlled phase III trials demonstrated that selenium and vitamin E could reduce prostate cancer incidence. To characterize pharmacodynamic and gene expression effects associated with use of selenium and vitamin E, we undertook a randomized, placebo-controlled phase IIA study of prostate cancer patients before prostatectomy and created a preoperative model for prostatectomy tissue interrogation. Thirty-nine men with prostate cancer were randomly assigned to treatment with 200 μg of selenium, 400 IU of vitamin E, both, or placebo. Laser capture microdissection of prostatectomy biopsy specimens was used to isolate normal, stromal, and tumor cells. Gene expression in each cell type was studied with microarray analysis and validated with a real-time polymerase chain reaction (PCR) and immunohistochemistry. An analysis of variance model was fit to identify genes differentially expressed between treatments and cell types. A beta-uniform mixture model was used to analyze differential expression of genes and to assess the false discovery rate. All statistical tests were two-sided. The highest numbers of differentially expressed genes by treatment were 1329 (63%) of 2109 genes in normal epithelial cells after selenium treatment, 1354 (66%) of 2051 genes in stromal cells after vitamin E treatment, and 329 (56%) of 587 genes in tumor cells after combination treatment (false discovery rate = 2%). Validation of 21 representative genes across all treatments and all cell types yielded Spearman correlation coefficients between the microarray analysis and the PCR validation ranging from 0.64 (95% confidence interval [CI] = 0.31 to 0.79) for the vitamin E group to 0.87 (95% CI = 0.53 to 0.99) for the selenium group. The increase in the mean percentage of p53-positive tumor cells in the selenium-treated group (26.3%), compared with that in the placebo-treated group (5%), showed borderline statistical significance (difference = 21.3%; 95% CI = 0.7 to 41.8; P = .051). We have demonstrated the feasibility and efficiency of the preoperative model and its power as a hypothesis-generating engine. We have also identified cell type– and zone-specific tissue effects of interventions with selenium and vitamin E that may have clinical implications.
Attainment and Maintenance of Normal Stature with Alkali Therapy in Infants and Children with Classic Renal Tubular Acidosis
Authors: Elisabeth McSherry, R. Curtis Morris
Journal: Journal of Clinical Investigation (1978)

Growth was evaluated in a group of 10 infants and children with familial or idiopathic classic renal tubular acidosis in whom alkali therapy was initiated at ages ranging from 8 days to 9.5 yr and administered at dosage schedules documented to sustain correction of acidosis in at least four prolonged observation periods on the Pediatric Clinical Research Ward. When alkali therapy was begun, six patients (four infants and two children) were stunted (height <2.5 SD below mean). Of the four who were not, two infants were too young (<2 wk of age) to have become stunted, and two children had been documented earlier to be nonacidotic. At the start of alkali therapy, the heights of the patients correlated inversely with the maximal possible duration of prior acidosis. WITH SUSTAINED ALKALI THERAPY: (a) each patient attained and maintained normal stature; (b) the mean height of the 10 patients increased from the 1.4+/-4 to the 37.0+/-33 percentile (of a normal age- and sex-matched population); (c) the mean height reached the 69th percentile in the eight patients whose heights could be analyzed according to parental prediction (Tanner technique); (d) the rate of growth increased two- to threefold, and normal heights were attained within 6 mo of initiating alkali therapy in the stunted infants and within 3 yr in the stunted children; (e) the height attained correlated inversely with the maximal possible duration of acidosis (before alkali therapy) only in those patients in whom alkali therapy was started after 6 mo of age, and not in those treated earlier. The amount of alkali required to sustain correction of acidosis increased substantially during the course of treatment in each patient. The maximal alkali requirement ranged from 4.8 to 14.1 meq/kg per day, and in each patient its amount was determined principally by the magnitude of renal bicarbonate wasting.
Recombinant Baculovirus Containing the <i>Diphtheria Toxin A</i> Gene for Malignant Glioma Therapy
Authors: Chao-Yang Wang, Feng Li, Yi Yang, Hai-Yan Guo, Chun-Xiao Wu, Shu Wang
Journal: Cancer Research (2006)

Abstract Insect baculoviruses are capable of infecting mammalian glial cells in the central nervous system. We investigated in the current study the feasibility of using the viruses as toxin gene vectors to eliminate malignant glioma cells in the brain. We first confirmed that glioma cells were permissive to baculovirus infection, with variable transduction efficiencies at 100 viral particles per cell and ranging between 35% and 70% in seven human and rat glioma cell lines. We then developed a recombinant baculovirus vector accommodating the promoter of glial fibrillary acidic protein (GFAP) to minimize possible side effects caused by overexpression of a therapeutic gene in sensitive neurons. We placed the GFAP promoter into a baculovirus expression cassette, in which the enhancer of human cytomegalovirus immediate-early gene and the inverted terminal repeats of adeno-associated virus were employed to improve the relatively low transcriptional activity of the cellular promoter. This recombinant baculovirus significantly improved transduction in glioma cells, providing the efficiency in C6 rat glioma cells up to 96%. When used to produce the A-chain of diphtheria toxin intracellularly in a rat C6 glioma xenograft model, the baculovirus effectively suppressed tumor development. The new baculovirus vector circumvents some of the inherent problems associated with mammalian viral vectors and provides an additional option for cancer gene therapy. (Cancer Res 2006; 66(11): 5798-806)