tbuckley/cabot-search huggingface dataset:
Tamoxifen, Soy, and Lifestyle Factors in Asian American Women With Breast Cancer
Authors: Anna H. Wu, Malcolm C. Pike, Lee D. Williams, Darcy Spicer, Chiu-Chen Tseng, Mona I. Churchwell, Daniel R. Doerge
Journal: Journal of Clinical Oncology (2007)

Purpose Soy foods have been a staple in Asia for centuries but the consumption of this food in the West is recent. Intake of soy among women at high risk for or with breast cancer has become a public health concern because genistein, a major component of soy, has weak estrogenic effects on breast epithelium, and has been found to negate the benefit of tamoxifen in some animal and in vitro studies. Patients and Methods We conducted a cross-sectional study in Asian Americans with breast cancer who were tamoxifen users (n = 380) to investigate the association between soy intake and circulating levels of tamoxifen and its metabolites (N-desmethyl tamoxifen [N-DMT], 4-hydroxytamoxifen [4-OHT], and 4-hydroxy-N-desmethyl-tamoxifen [endoxifen]). Results Serum levels of tamoxifen or its metabolites were unrelated to self-reported intake of soy or serum levels of isoflavones. Blood levels of tamoxifen were 81% higher in postmenopausal women age 65 or older compared with premenopaual women age 45 or younger (P = .005); similar patterns of results were observed for the tamoxifen metabolites. Levels of N-DMT were 27% (P = .03) lower among women in the highest tertile of body mass index (BMI, &gt; 24.4 kg/m 2 ) compared with those in the lowest category (BMI ≤ 21.5). Women who used hypertensive medications had higher levels of tamoxifen (P = .02) and N-DMT (P = .04) compared with nonusers. Conclusion We found no evidence that soy intake adversely affected levels of tamoxifen or its metabolites. However, age, menopausal status, BMI, and use of hypertensive medications significantly influenced circulating levels of tamoxifen and its metabolites in this population.
Effect of MTHFR 1298A→C and MTHFR 677C→T Genotypes on Total Homocysteine, Folate, and Vitamin B12 Plasma Concentrations in Kdiney Graft Recipients
Authors: MANUELA FO[Combining Diaeresis]DINGER, HEIDI BUCHMAYER, GOTFRIED HEINZ, MENELAOS PAPAGIANNOPOULOS, JOSEF KLETZMAYR, SUSANNE RASOUL-ROCKENSCHAUB, WALTER H. HO[Combining Diaeresis]RL, GERE SUNDER-PLASSMANN
Journal: Journal of the American Society of Nephrology (2000)

Abstract. The effect of 5,10-methylenetetrahydrofolate reductase ( MTHFR ) 677C→T and 1298A→C on total homocysteine (tHcy), folate and vitamin B 12 levels was investigated in 733 kidney graft recipients. The six major genotype combinations were used as grouping variables, and age, gender, BMI, serum creatinine, and creatinine clearance and ln-folate, ln-vitamin B 12 , or logarithmus naturalis tHcy (ln-tHcy) were used as covariates in three ANCOVA and multiple stepwise linear regression models. Hyperhomocysteinemia was present in 49.7% of the patients. The allele frequency of MTHFR 677T and 1298C was 0.319 and 0.326. MTHFR genotype and all other variables were significant predictors of ln-tHcy (higher tHcy plasma levels for MTHFR 677TT/1298AA versus all other five genotype groups: P &lt; 0.05). BMI, creatinine clearance, ln-tHcy, and MTHFR genotype influenced ln-folate (lower folate levels for MTHFR 677TT/1298AA versus all other genotype groups: P &lt; 0.05). Creatinine clearance and ln-tHcy were the only predictors of ln-vitamin B 12 levels. In a prespecified subgroup analysis ( n = 496), the MTHFR genotype also influenced tHcy levels and compound heterozygous patients had significantly lower folate levels as compared with MTHFR 677CC/1298AA and 677CC/1298CC. This study shows that the MTHFR 677TT/1298AA and 677CT/1298AC genotypes are significant predictors of tHcy and folate plasma levels.
Dietary Modulation of Omega-3/Omega-6 Polyunsaturated Fatty Acid Ratios in Patients With Breast Cancer
Authors: D. Bagga, S. Capone, H.-J. Wang, D. Heber, M. Lill, L. Chap, J. A. Glaspy
Journal: JNCI Journal of the National Cancer Institute (1997)

Polyunsaturated fatty acids of the omega-6 (omega-6) class, as found in corn and safflower oils, can act as precursors for intermediates involved in the growth of mammary tumors when fed to animals, whereas polyunsaturated fatty acids of the omega-3 (omega-3) class, as found in fish oil, can inhibit these effects. The effects of dietary intervention on the ratios of these fatty acids in breast and other adipose tissues have not previously been prospectively studied.The present investigation was conducted to study the impact on the ratio of omega-3 and omega-6 polyunsaturated fatty acid in plasma and in adipose tissue of the breast and buttocks when women with breast cancer consume a low-fat diet and fish oil supplements.Twenty-five women with high-risk localized breast cancer were enrolled in a dietary intervention program that required them to eat a low-fat diet and take a daily fish oil supplement throughout a 3-month period. Breast and gluteal fat biopsy specimens were obtained from each woman before and after dietary intervention. The fatty acid compositions of specimens of plasma, breast fat, and gluteal fat were determined by gas-liquid chromatography. Statistical analysis involved use of a two-sided paired t test.After dietary intervention, a reduction in the level of total omega-6 polyunsaturated fatty acids in the plasma was observed (P<.0003); moreover, total omega-3 polyunsaturated fatty acids increased approximately three-fold (P<.0001) and the omega-3/omega-6 polyunsaturated fatty acids ratio increased approximately fourfold (i.e., mean values increased from 0.09 to 0.41; P = .0001). An increase in total omega-3 polyunsaturated fatty acids in breast adipose tissue was observed following dietary intervention (P = .04); the omega-3/omega-6 polyunsaturated fatty acid ratio increased from a mean value of 0.05 to 0.07 (P = .0001). An increase in total omega-3 polyunsaturated fatty acids was observed in gluteal adipose tissue following the intervention (P = .05); however, the ratio of omega-3 to omega-6 polyunsaturated fatty acids (mean ratio values of 0.036-0.045; P = .06) was unchanged.Short-term dietary intervention can lead to statistically significant increases in omega-3/omega-6 polyunsaturated fatty acid ratios in plasma and breast adipose tissue. Breast adipose tissue changed more rapidly than gluteal adipose tissue in response to the dietary modification tested in this study. Therefore, gluteal adipose tissue may not be a useful surrogate to study the effect of diet on breast adipose tissue.
Good Response to Gefitinib in a Lung Adenocarcinoma Harboring a Heterozygous Complex Mutation of L833V and H835L in Epidermal Growth Factor Receptor Gene
Authors: Tsung-Ying Yang, Chi-Ren Tsai, Kun-Chieh Chen, Kuo-Hsuan Hsu, Hsien-Ming Lee, Gee-Chen Chang
Journal: Journal of Clinical Oncology (2011)
Rituximab Maintenance or Retreatment After Autologous Transplantation for Relapsed Follicular Lymphoma?
Authors: Claudio Fozza
Journal: Journal of Clinical Oncology (2013)

TO THEEDITOR: Pettengel et al 1 elegantly describe a randomized trial assessing the efficacy and safety of rituximab as in vivo purging before transplantation and as maintenance treatment after high-dose chemotherapy and autologous stem-cell transplantation (HDCASCT) in patients with relapsed follicular lymphoma (FL). The authorsconcludethatrituximabmaintenanceafterHDC-ASCTshowed asatisfactorytoxicityprofileandsignificantlyprolongedprogressionfree survival (PFS) but not overall survival (OS), while rituximab in vivo purging administered before transplantation failed to improve PFS or OS. 1 Rituximab maintenance has unequivocally shown a beneficial impact on the outcome of patients with FL achieving at least a partial remission after first-line therapy. 2 However, some authors have previouslyraisedanissueconcerningthebestpotentialstrategytoexploit rituximabinsuchacontext,suggestingthatretreatmentcouldpotentiallyoffersomeadvantageswhencomparedwithmaintenance.Hainsworth et al 3 have previously evaluated maintenance (four weekly doses, repeated every 6 months for 2 years) versus retreatment (four weekly doses) at the time of disease progression in 114 patients who had received previous chemotherapy for indolent non-Hodgkin lymphoma. Interestingly, this study demonstrated no differences in OS and rituximab benefit, measured as the latency from the date of first rituximab treatment until the date for the next required treatment. Besides, a 30% reduction in rituximab use was demonstrated. 3 Similarly,Kahletal 4 havepreviouslyreportedon284naivepatientswithFL
Anemia and Blood Transfusion in Critically Ill Patients
Authors: Jean Louis Vincent
Journal: JAMA (2002)

ContextAnemia is a common problem in critically ill patients admitted to intensive care units (ICUs), but the consequences of anemia on morbidity and mortality in the critically ill is poorly defined.ObjectivesTo prospectively define the incidence of anemia and use of red blood cell (RBC) transfusions in critically ill patients and to explore the potential benefits and risks associated with transfusion in the ICU.DesignProspective observational study conducted November 1999, with 2 components: a blood sampling study and an anemia and blood transfusion study.Setting and PatientsThe blood sampling study included 1136 patients from 145 western European ICUs, and the anemia and blood transfusion study included 3534 patients from 146 western European ICUs. Patients were followed up for 28 days or until hospital discharge, interinstitutional transfer, or death.Main Outcome MeasuresFrequency of blood drawing and associated volume of blood drawn, collected over a 24-hour period; hemoglobin levels, transfusion rate, organ dysfunction (assessed using the Sequential Organ Failure Assessment score), and mortality, collected throughout a 2-week period.ResultsThe mean (SD) volume per blood draw was 10.3 (6.6) mL, with an average total volume of 41.1 (39.7) mL during the 24-hour period. There was a positive correlation between organ dysfunction and the number of blood draws (r = 0.34; P&lt;.001) and total volume drawn (r = 0.28; P&lt;.001). The mean hemoglobin concentration at ICU admission was 11.3 (2.3) g/dL, with 29% (963/3295) having a concentration of less than 10 g/dL. The transfusion rate during the ICU period was 37.0% (1307/3534). Older patients and those with a longer ICU length of stay were more commonly transfused. Both ICU and overall mortality rates were significantly higher in patients who had vs had not received a transfusion (ICU rates: 18.5% vs 10.1%, respectively; χ2 = 50.1; P&lt;.001; overall rates: 29.0% vs 14.9%, respectively; χ2 = 88.1; P&lt;.001). For similar degrees of organ dysfunction, patients who had a transfusion had a higher mortality rate. For matched patients in the propensity analysis, the 28-day mortality was 22.7% among patients with transfusions and 17.1% among those without (P = .02); the Kaplan-Meier log-rank test confirmed this difference.ConclusionsThis multicenter observational study reveals the common occurrence of anemia and the large use of blood transfusion in critically ill patients. Additionally, this epidemiologic study provides evidence of an association between transfusions and diminished organ function as well as between transfusions and mortality.
Bevacizumab in Stage II-III Colon Cancer: 5-Year Update of the National Surgical Adjuvant Breast and Bowel Project C-08 Trial
Authors: Carmen J. Allegra, Greg Yothers, Michael J. O'Connell, Saima Sharif, Nicholas J. Petrelli, Samia H. Lopa, Norman Wolmark
Journal: Journal of Clinical Oncology (2012)

The National Surgical Adjuvant Breast and Bowel Project trial C-08 was designed to investigate the safety and efficacy of adding bevacizumab to fluorouracil, leucovorin, and oxaliplatin (FOLFOX6) for the adjuvant treatment of patients with stage 2-3 colon cancer. Our report summarizes the primary and secondary end points of disease-free and overall survival, respectively, with 5 years median follow-up time.Patients received modified FOLFOX6 once every 2 weeks for a 6-month period (control group) or modified FOLFOX6 for 6 months plus bevacizumab (5 mg/kg) once every 2 weeks for a 12-month period (experimental group). The primary end point of the study was disease-free survival (DFS) and overall survival (OS) was a secondary end point.Of 2,673 analyzed patients, demographic factors were well-balanced by treatment. With a median follow-up of 5 years, the addition of bevacizumab to mFOLFOX6 did not result in an overall significant increase in DFS (hazard ratio [HR], 0.93; 95% CI, 0.81 to 1.08; P = .35). Exploratory analyses found that the effect of bevacizumab on DFS was different before and after a 1.25-year landmark (time-by-treatment interaction P value <.0001). The secondary end point of OS was no different between the two study arms for all patients (HR, 0.95; 95% CI, 0.79 to 1.13; P = .56) and for those with stage 3 disease (HR, 1.0; 95% CI, 0.83 to 1.21; P = .99).Bevacizumab for 1 year with modified FOLFOX6 does not significantly prolong DFS or OS in stage 2-3 colon cancer. We observed no evidence of a detrimental effect of exposure to bevacizumab. A transient effect on disease-free survival was observed during bevacizumab exposure in the study's experimental arm.
The effects of eccentric training on lower limb flexibility: a systematic review
Authors: Kieran O'Sullivan, Sean McAuliffe, Neasa DeBurca
Journal: British Journal of Sports Medicine (2012)

Background Reduced flexibility has been documented in athletes with lower limb injury, however, stretching has limited evidence of effectiveness in preventing injury or reducing the risk of recurrence. In contrast, it has been proposed that eccentric training can improve strength and reduce the risk of injury, and facilitate increased muscle flexibility via sarcomerogenesis. Objectives This systematic review was undertaken to examine the evidence that eccentric training has demonstrated effectiveness as a means of improving lower limb flexibility. Study appraisal and synthesis methods Six electronic databases were systematically searched by two independent reviewers to identify randomised clinical trials comparing the effectiveness of eccentric training to either a different intervention, or a no-intervention control group. Studies evaluating flexibility using both joint range of motion (ROM) and muscle fascicle length (FL) were included. Six studies met the inclusion/exclusion criteria, and were appraised using the PEDro scale. Differences in the muscles studied, and the outcome measures used, did not allow for pooled analysis. Results There was consistent, strong evidence from all six trials in three different muscle groups that eccentric training can improve lower limb flexibility, as assessed using either joint ROM or muscle FL. Conclusion The results support the hypothesis that eccentric training is an effective method of increasing lower limb flexibility. Further research is required to compare the increased flexibility obtained after eccentric training to that obtained with static stretching and other exercise interventions.
Effect of clarithromycin on rhinovirus-16 infection in A549 cells
Authors: Y. J. Jang, H-J. Kwon, B-J. Lee
Journal: European Respiratory Journal (2005)

Clarithromycin (CM) has been found to inhibit the production of the intercellular adhesion molecule (ICAM)-1 and the secretion of interleukin (IL)-6 and IL-8, which may have beneficial effects on the pathophysiological changes related to rhinovirus (RV) infection. The effect of CM on RV infection in A549 cells was therefore investigated. Cells were pre-treated with 1, 10 or 100 μM CM, either starting 3 days before infection and continuing thereafter, or by addition at the time of infection. RV titre, as measured by culture on Medical Research Council 5 cells, was reduced by CM, with the degree of reduction being greater when CM was added 3 days before infection than when it was added at the time of infection. CM treatment inhibited the RV-induced increase in ICAM-1 mRNA and protein, as well as the RV-induced secretion of IL-1β, IL-6, and IL-8. These effects were greater in cells treated with 10 μM than in those treated with 100 μM CM, and the maximum effect was observed 3 days after viral infection. In contrast, secretion of IL-8 was not inhibited significantly when CM was added at the time of viral infection. The findings of this study suggest that, in A549 cells, clarithromycin inhibits the induction of intercellular adhesion molecule-1 expression, cytokine elaboration, and viral infection.
Effect of Venous Pressure on Mean Capillary Pressure and Vascular Resistance in the Intestine
Authors: PAUL C. JOHNSON
Journal: Circulation Research (1965)

Elevation of venous pressure in the intestine increases capillary pressure by amounts that average 62% of the venous pressure increment. The relation may be expressed as P c = 9.7 + 0.62 P v , where P c represents the mean capillary pressure and P v represents venous pressure (both expressed in mm Hg). The increase of capillary pressure is less than expected for a rigid system and less than reported for skeletal muscle. This attenuation of the effect of increments of venous pressure on capillary blood pressure is due to precapillary constriction and postcapillary dilation, with the latter playing the dominant role. Measurement of resistance in a segment of the venous vasculature confirmed this and also demonstrated that most of the reduction of resistance occurs in venous vessels with diameters greater than 0.5 mm.
Atopy and Risk of Non-Hodgkin Lymphoma
Authors: Mads Melbye, Karin Ekström Smedby, Tuula Lehtinen, Klaus Rostgaard, Bengt Glimelius, Lars Munksgaard, Claudia Schöllkopf, Christer Sundström, Ellen T. Chang, Pentti Koskela, Hans-Olov Adami, Henrik Hjalgrim
Journal: JNCI Journal of the National Cancer Institute (2007)

A possible connection between allergy and cancer has been suspected, but allergy-related conditions or atopy have been inconsistently associated with reduced risks of non-Hodgkin lymphoma. We investigated this association in a population-based case–control study and in a prospective study with prediagnostic blood specimens. We carried out a population-based study of 3055 case patients with non-Hodgkin lymphoma and 3187 control subjects in Denmark and Sweden, including questionnaire information on allergy and blood specimens, and a nested case–control study within a prospective cohort of more than 400 000 Finnish women. In the second study, serum specimens from the 198 case patients who developed non-Hodgkin lymphoma within a median of 8.9 years after the blood was drawn were matched with serum specimens from 594 control subjects. In both studies, laboratory-based evidence of allergy (atopy) was determined in serum on the basis of specific IgE reactivity to common inhalant allergens. Dissemination of disease was classified by the Ann Arbor system. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by logistic regression. In the first study, ever having hay fever, but not other allergic conditions, was associated with a reduced risk of non-Hodgkin lymphoma. In particular, subjects with specific IgE reactivity in serum had a 32% (95% CI = 20% to 42%) lower risk of overall non-Hodgkin lymphoma than those without such reactivity. However, among case patients, dissemination of the disease was strongly inversely associated with specific IgE reactivity. In the second (i.e., prospective) study, no association was found between non-Hodgkin lymphoma and specific IgE reactivity, except possibly immediately before a diagnosis of non-Hodgkin lymphoma (≥10 years before diagnosis, OR = 1.00, 95% CI = 0.48 to 2.09; 5–9 years before, OR = 0.95, 95% CI = 0.50 to 1.84; 1–4 years before, OR = 0.33, 95% CI = 0.11 to 1.02; and <1 year before, OR = 0.27, 95% CI = 0.03 to 2.31). Allergy may not be causally associated with the risk of non-Hodgkin lymphoma. The inverse association observed in some case–control studies may arise because non-Hodgkin lymphoma suppresses the immunologic response to allergens.
NOTE ON THE DISCOVERY OF THE HUMAN TRYPANOSOME
Authors: C.J. Baker, T. Hood, E.Langley Hunt, RaoulF. de Boissière, G.Ivanhoe Lecesne, AubreyH. Davitt, EmmelineDa Cunha, J. Lunn, R.A. Belilios, William Fletcher, M.E. O'Dea, Taylor Hancock, Geoffrey Hungerford, M.Cameron Blair
Journal: The Lancet (1902)
Identification of Ligand-Induced Proteolytic Cleavage and Ectodomain Shedding of VEGFR-1/FLT1 in Leukemic Cancer Cells
Authors: Nader Rahimi, Todd E. Golde, Rosana D. Meyer
Journal: Cancer Research (2009)

Vascular endothelial growth factor receptor-1/fms-related tyrosine kinase 1 (VEGFR-1/FLT1) is expressed as a membrane-bound receptor tyrosine kinase and as an alternatively spliced soluble protein (sVEGFR-1) containing the 1-6 IgG-like domain of its ectodomain. sVEGFR-1 is known as a naturally occurring inhibitor of angiogenesis and as a surrogate marker for cancer progression; it is also linked to pregnancy-induced hypertension called preeclampsia and to avascularity of normal cornea. It remains an open question whether alternative mRNA splicing is the only mechanism by which sVEGFR-1 is generated. In this study, we show that in leukemic cancer cells, PlGF and VEGF-A both induce tyrosine phosphorylation of VEGFR-1 and render it susceptible to ectodomain shedding, resulting in the generation of sVEGFR-1 and an intracellular cytoplasmic fragment. Activation of protein kinase C and tumor necrosis factor-alpha-converting enzyme family metalloproteases are critically required for the occurrence of sVEGFR-1. Following the removal of the ectodomain, the remnant of VEGFR-1 remains attached to the membrane, and the activity of gamma-secretase/presenilin is required for its release from the cell membrane. We propose that sVEGFR-1 produced via ectodomain shedding plays a prominent role in the VEGF receptor system by antagonizing VEGF receptor signaling by acting as a dominant-negative form and/or forming a nonsignaling dimerizing complex with VEGF receptors.
Hepcidin and Disorders of Iron Metabolism
Authors: Tomas Ganz, Elizabeta Nemeth
Journal: Annual Review of Medicine (2010)

The hepatic peptide hormone hepcidin is the principal regulator of iron absorption and its tissue distribution. Pathologically increased hepcidin concentrations cause or contribute to iron-restrictive anemias including anemias associated with inflammation, chronic kidney disease and some cancers. Hepcidin deficiency results in iron overload in hereditary hemochromatosis and ineffective erythropoiesis. The hepcidin-ferroportin axis is the principal regulator of extracellular iron homeostasis in health and disease, and is a promising target for the diagnosis and treatment of iron disorders and anemias.