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At least 343 records · Page 19Linked to original sources
PubMed2006

African-American race is associated with a poorer overall survival rate for breast cancer patients treated with mastectomy and doxorubicin-based chemotherapy.

BACKGROUND: African-American (AA) race has been associated with a worse outcome in breast cancer. It is unclear whether this is due to biological factors, socioeconomic factors, or both. METHODS: The records from 2 independent cohorts of breast cancer patients treated on institutional protocols with mastectomy and adjuvant (n = 1456) or neoadjuvant (n = 684) doxorubicin-based chemotherapy were retrospectively reviewed. RESULTS: The adjuvant (Adj) chemotherapy cohort included 1142 Caucasian (CA), 186 Hispanic (HI), and 128 (AA) patients. The neoadjuvant (Neo) chemotherapy protocols included 448 CA, 114 HI, and 122 AA patients. In both groups, AA patients had later-stage tumors (Adj P = .017; Neo P = .051), a higher rate of estrogen receptor (ER)-negative disease (Adj P = .054; Neo P = .039), and a worse 10-year actuarial overall survival rate than CA or HI patients (Adj, 52%, 62%, and 62%, respectively, P = .009; Neo, 40%, 50%, and 56%, respectively, P = .015). In multivariate analyses, AA race remained independently associated with a poorer overall survival rate in both cohorts (Adj, hazard ratio = 1.39, P = .018; Neo, hazard ratio = 1.37, P = .02). CONCLUSIONS: The data suggest that AA race is associated with less favorable biological tumor features, such as an increased likelihood of ER-negative disease, than those found in CA and HI patients. Such differences in tumor biology, as well as previously described socioeconomic factors, likely contribute to the lower rate of survival in the AA breast cancer population.

Adolescent↗
PubMed1992

High amounts of circulating interleukin (IL)-6 in the form of monomeric immune complexes during anti-IL-6 therapy. Towards a new methodology for measuring overall cytokine production in human in vivo.

A patient with plasma cell leukemia was treated with anti-interleukin (IL)-6 monoclonal antibodies (mAb) for 2 months. Using chromatography on protein A-Sepharose, anti-murine-IgG-Sepharose, anti-IL-6-mAb-Sepharose and gel filtration at pH 2.3, we have demonstrated that the anti-IL-6 mAb, by preventing the binding of IL-6 to its cell membrane receptor and its renal elimination, has induced huge amounts of IL-6 to circulate in the form of monomeric immune complexes. By using this observation, we have developed a mathematical modelling that allows the determination of the overall daily production of IL-6 in this patient, which was in the range of 15 micrograms per day. Overall in vivo production of cytokines has never been evaluated in animals or in humans before.

Antibodies, Monoclonal↗
PubMed2004

Overall versus socioeconomic health inequality: a measurement framework and two empirical illustrations.

This paper outlines a framework for comparing empirically overall health inequality and socioeconomic health inequality. The framework, which is developed for both individual-level data and grouped data, is illustrated using data on malnutrition amongst Vietnamese children and on health utility amongst Canadian adults. In both cases, the degree of socioeconomic inequality is estimated at around 25% of overall inequality.

Adult↗
PubMed2002

DNA topoisomerase IIalpha predicts progression-free and overall survival in pediatric malignant non-brainstem gliomas.

Malignant non-brainstem glioma (MNBG) is a rare pediatric brain tumor. The prognosis for children harboring this lesion remains largely unpredictable. Assessment of histologic features alone only provides a marginal insight into the biologic behavior of these lesions. Hence, the identification of novel molecular markers capable of characterizing these lesions more accurately with respect to their biologic aggressiveness is definitely needed. Our current study examined the expression of nuclear DNA topoisomerase IIalpha (TIIalpha), a novel marker of cell cycle turnover and a determinant of tumor cell resistance to chemotherapy, in a series of 17 archival pediatric MNBGs. TIIalpha expression was found to extend over a wide range in the study cohort (3.9-69.1%). A cutoff labeling index of 12% was found to define 2 prognostic subgroups (TIIalpha <12 vs. >or=12) with profoundly different 5-year progression-free survival (60% vs. 8%; p = 0.0108, log-rank test) and overall survival (100% vs. 8%; p = 0.0038) rates. TIIalpha expression was significantly linked to MIB-1 antibody labeling of the Ki-67 nuclear antigen (R = 0.919, p < 0.001). A high TIIalpha labeling index remained associated with short progression-free survival (p = 0.022) and overall survival (p = 0.022) in multivariate analysis (Cox regression). In conclusion, considering that TIIalpha expression was not related to histopathologic grade, biological characteristics as assessed by TIIalpha labeling may complement the information obtained by tumor morphology as a means of improving the accuracy of patient prognosis prediction.

Adolescent↗
PubMed2007

Does high-dose carmustine increase overall survival in supratentorial high-grade malignant glioma? An EBMT retrospective study.

Radiotherapy plus concomitant and adjuvant temozolomide have demonstrated improved survival for glioblastoma. However, prognosis remains poor. High-doses chemotherapy with carmustine is another way to improve response and survival by increasing the dose delivered. Myelotoxicity imposes autologous stem cell rescue. European Group for Blood and Marrow Transplantation experience of this treatment in patients with high-grade glioma was reported here. A retrospective analysis of 217 patients from European Group for Blood and Marrow Transplantation database was realized. Ninety-six patients underwent complete surgical resection while the 121 others had partial resection or only biopsy and were evaluable for an antitumor effect. Patients received 800 mg/m2 of carmustine intravenously at least 1 month after neurosurgery. Forty-eight to 72 hr after chemotherapy, 108 patients received autologous hematopoietic stem cells from bone marrow harvest and 109 patients autologous hematopoietic stem cells from peripheral blood. Radiotherapy was started approximately 40 days after transplantation. Ten deaths were related to the treatment. Of the 121 patients evaluable for tumor response, 64 (53%) presented an objective response. This protocol appear feasible, but with toxicity-related mortality of 4.5%. Median overall survival was 20 months and median time to treatment failure was 7 months. Overall survival and time to treatment were correlated with age, quality of resection and histological subtypes. In glioblastoma multiforme, age and surgery quality appeared to be prognostic factors. Compared with Stupp et al.'s recent study, this study did not favor high-dose carmustine for patients with glioblastoma multiforme with complete surgical resection.

Adolescent↗
PubMed2007

Less aggressive treatment and worse overall survival in cancer patients with diabetes: a large population based analysis.

The purpose of this study was to document the prevalence of diabetes among newly diagnosed cancer patients and to evaluate the influence of diabetes on stage at diagnosis, treatment and overall survival. We performed a population-based analyses of all 58,498 cancer patients newly diagnosed between 1995 and 2002 in the registration area of the Eindhoven Cancer Registry. Stage of cancer, cancer treatment and comorbidities were actively collected by hospital medical records review. Follow-up of all patients was completed until January 1, 2005. Nine percent of all cancer patients had diabetes at the time of cancer diagnosis. The prevalence of diabetes was highest among patients with cancer of the pancreas (19%), uterus (14%) and among young men with kidney cancer (8%). Colon, breast and ovarian cancer patients with diabetes were more often diagnosed with a higher tumour stage (p < 0.05). Patients with diabetes and cancer of the oesophagus, colon, breast and ovary were treated less aggressively compared to those without diabetes (p < 0.05). During the follow-up period 3,902 of 5,555 cancer patients with diabetes died and 29,909 of 52,943 cancer patients without diabetes died. For all cancers combined, in a multivariate cox-regression model, adjusting for age, gender, stage, treatment and cardiovascular disease, patients with diabetes experienced a significant increase in overall mortality (HR = 1.44, 95% CI 1.40-1.49), ranging however from 0 to 40% for different types of cancer, compared to those without diabetes. In conclusion, diabetic cancer patients frequently were treated less aggressively and had a worse prognosis compared to those without diabetes.

Adult↗
PubMed1995

Overall and site-specific risk of malignant melanoma associated with nevus counts at different body sites: a multicenter case-control study of the German Central Malignant-Melanoma Registry.

A large number of benign melanocytic nevi is the major risk factor for malignant melanoma (MM). In a multicenter case-control study, the number of common (CN) and clinically atypical (AN) nevi were counted separately at individual sites in 278 melanoma patients and 278 age- and gender-matched non-melanoma controls. Relative risk (RR) adjusted for age and sex was calculated. In men as well as women, the number of CN on the legs was the best predictor of overall melanoma risk. In men, RR for developing MM when > or = 1 AN were present on the trunk was 4-fold (vs. none). In women, presence of AN on the arms increased RR 9.5-fold. For men and women combined, after adjusting for age and gender, the RR for developing MM on the trunk and on the legs was best predicted by counts of CN at the respective body region. However, high counts of CN on the arms were associated with high melanoma risk on the legs (somewhat lower on the trunk). For AN, no site-specificity of melanoma risk was found. Our data suggest that nevus counts of the legs are the best predictor of overall melanoma risk if total body nevus counts are not feasible. Although high counts of CN on the trunk and legs are associated with a higher risk of developing MM at the respective site than at another site, our data do not unequivocally support a direct site-specific melanoma risk.

Arm↗
PubMed1984

Ca2+ and hormones interact synergistically to stimulate rapidly both prolactin production and overall protein synthesis in pituitary tumor cells.

Effects of Ca2+ and hormones on short-term protein synthesis were examined utilizing intact Ca2+-depleted and Ca2+-restored GH3 pituitary tumor cells as a model system. Amino acid incorporation by cells in complete growth medium during short incubations was markedly reduced by EGTA concentrations in excess of Ca2+. Thyrotropin-releasing hormone (TRH) rapidly enhanced amino acid incorporation and prolactin production, with both effects being reserved by EGTA in excess of extracellular Ca2+ or prevented by cellular Ca2+ depletion. Epidermal growth factor and phorbol myristate acetate (PMA) also stimulated amino acid incorporation and prolactin production; absolute increases in protein synthesis provided by these agents were significantly greater in Ca2+-restored than in Ca2+-depleted preparations. TRH and PMA concentrations which raised prolactin production were identical to those increasing the rate of amino acid incorporation into overall protein. The extracellular Ca2+ concentration dependencies of amino acid incorporation and prolactin production were similar and were unchanged by hormone. PMA, the most efficacious of the agents tested, and Ca2+ promoted incorporation of amino acid into the same spectrum of proteins. Stimulation of protein synthesis by hormones was not attributable to alterations in amino acid uptake, attachment to substrata, hormone binding, protein catabolism or transcription. Trifluoperazine selectively prevented the stimulation by Ca2+ of amino acid incorporation and prolactin production. Unlike total prolactin, the total protein content of GH3 cells during these short incubations was not altered by Ca2+, hormones or trifluoperazine. It is proposed that hormones and Ca2+, which have been demonstrated to regulate prolactin secretion and prolactin mRNA transcription in GH3 cells, also exert translational controls which serve to facilitate the overall expression of the prolactin gene.

Amino Acids↗
PubMed2001

On tests of the overall treatment effect in meta-analysis with normally distributed responses.

For the meta-analysis of controlled clinical trials or epidemiological studies, in which the responses are at least approximately normally distributed, a refined test for the hypothesis of no overall treatment effect is proposed. The test statistic is based on a direct estimation function for the variance of the overall treatment effect estimator. As outcome measures, the absolute and the standardized difference between means are considered. In simulation studies it is shown that the proposed test keeps the prescribed significance level very well in contrast to the commonly used tests in the fixed effects and random effects model, respectively, which can become very liberal. Furthermore, just for using the proposed test it is not necessary to choose between the fixed effects and the random effects approach in advance.

Amlodipine↗
PubMedDate not supplied

Molecular heterogeneity of glucose-6-phosphate dehydrogenase deficiency in Mexico: overall results of a 7-year project.

Several years ago, a project aiming to determine (i) the molecular basis of G-6-PD deficiency, (ii) the distribution of four different mutant alleles previously detected, and (iii) the whole of polymorphic alleles that account for the overall prevalence of G-6-PD deficiency in Mexico was implemented. Nearly 5000 individuals-from the general population and patients with hemolytic anemia-belonging to at least 14 States were screened for G-6-PD deficiency. Seventy-six G-6-PD-deficient subjects were detected and the prevalence of G-6-PD deficiency in 4777 individuals from the general population was 0.71%. Screening for both mutations associated with enzyme deficiency and silent polymorphisms at the G-6-PD gene was performed in the enzyme-deficient individuals by PCR-SSCP combined with restriction enzyme analysis; the silent polymorphisms as well as the nondeficient variant G-6-PD A(376G) were also investigated in 366 G-6-PD normal individuals from the general population. In 88% of the enzyme-deficient individuals it was possible to define the mutation responsible and the type G-6-PD A- variants were the more common in both individuals from the general population and patients with hemolytic anemia. G-6-PD deficiency is heterogeneous at the DNA level in Mexico and up to date 10 different variants-8 in the present project and 2 previously-have been observed: G-6-PD A(-202A/376G), G-6-PD A(-376G/968C), G-6-PD Santamaria(376G/542T), G-6-PD Vanua Lava(383C), G-6-PD Tsukui(del561-563), G-6-PD "Mexico City"(680A), G-6-PD Seattle(844C), G-6PD Guadalajara(1159T),G-6-PD Nashville(1178A), and G-6-PD Union(1360T). The G-6-PD A(-) variants have a relatively homogeneous distribution and along with G-6-PD Santamaria(376G/542T), they account for 82% of the overall prevalence of G-6-PD deficiency in Mexico; all other seven variants represent 9% of the mutant alleles examined, and in the rest of the chromosomes the mutation responsible for the enzyme deficiency remains to be defined. Several of the variants observed in Mexico are common in Africa, South Europe, and Southeast Asia. The prevalence for the variant G-6-PD A(376G) was 1.64%. From 256 possible haplotypes only 14 were observed and haplotype analysis suggests that some of the G-6-PD variants probably were imported to Mexico by population flow from South Europe, Africa, and Southeast Asia. This work (i) identified the G-6-PD variants prevalent in Mexico, (ii) defines their geographical distribution, (iii) contributes to the knowledge of the genetic structure of the Mexican population, and (iv) will facilitate the molecular analysis of the G-6-PD gene in enzyme-deficient Mexican individuals.

DNA Mutational Analysis↗
PubMed2002

The combined evaluation of p27Kip1 and Ki-67 expression provides independent information on overall survival of ovarian carcinoma patients.

OBJECTIVE: Considering the limited and controversial information on the significance of the cyclin-dependent kinase inhibitor p27Kip1 in ovarian cancer, we conducted a retrospective investigation to clarify the relationships of this protein to proliferation rate, clinicopathologic variables, and prognosis of epithelial ovarian tumors. METHODS: Paraffin-embedded tissue from 43 ovarian tumors of low malignant potential (LMP) and 80 primary ovarian adenocarcinomas was stained immunohistochemically for p27Kip1, Ki-67 antigen (a marker of cell proliferation), and p53 protein. Expression of these markers was correlated with clinicopathologic features and with overall survival of patients with adenocarcinomas. RESULTS: p27Kip1 levels were significantly higher in LMP tumors as well as in low-grade, early-stage, slowly proliferating adenocarcinomas and those associated with minimal residual disease (P < 0.001). Decreased p27Kip1 expression was related to poor overall survival on its own (P = 0.0304) and, when combined, to increased proliferation rate (P = 0.0232). More importantly, in multivariate analysis, p27Kip1/Ki-67 status was independently related to survival (P = 0.040) along with histologic type and FIGO stage. CONCLUSION: Decreased p27Kip1 expression is related to several clinicopathologic indicators of aggressiveness in ovarian adenocarcinomas and is a major player in cell cycle control in these neoplasms. On the contrary, deregulation of the protein does not seem to participate in the pathogenesis of LMP tumors. Furthermore, combined p27Kip1/Ki-67 expression is a better prognostic marker than expression of p27Kip1 or Ki-67 alone and supplements the prognostic information gained from traditional prognosticators.

Adenocarcinoma↗
PubMed1998

1.8 A crystal structure of the major NAD(P)H:FMN oxidoreductase of a bioluminescent bacterium, Vibrio fischeri: overall structure, cofactor and substrate-analog binding, and comparison with related flavoproteins.

We have solved the crystal structure of FRase I, the major NAD(P)H:FMN oxidoreductase of Vibrio fischeri, by the multiple isomorphous replacement method (MIR) at 1.8 A resolution with the conventional R factor of 0.187. The crystal structure of FRase I complexed with its competitive inhibitor, dicoumarol, has also been solved at 2.2 A resolution with the conventional R factor of 0.161. FRase I is a homodimer, having one FMN cofactor per subunit, which is situated at the interface of two subunits. The overall fold can be divided into two domains; 80% of the residues form a rigid core and the remaining, a small flexible domain. The overall core folding is similar to those of an NADPH-dependent flavin reductase of Vibrio harveyi (FRP) and the NADH oxidase of Thermus thermophilus (NOX) in spite of the very low identity in amino acid sequences (10% with FRP and 21% with NOX). 56% of alpha-carbons of FRase I core residues could be superposed onto NOX counterparts with an r.m.s. distance of 1.2 A. The remaining residues have relatively high B-values and may be essential for defining the substrate specificity. Indeed, one of them, Phe124, was found to participate in the binding of dicoumarol through stacking to one of the rings of dicoumarol. Upon binding of dicoumarol, most of the exposed re-face of the FMN cofactor is buried, which is consistent with the ping pong bi bi catalytic mechanism.

Amino Acid Sequence↗
PubMed1999

Role of Salmonella enterotoxin in overall virulence of the organism.

In this study, the Salmonella enterotoxin gene (stn) was mutated by marker exchange mutagenesis, and the overall virulence of the organism was evaluated. Salmonella marker exchange mutants evoked significantly less fluid secretion in mouse intestinal loops compared to that seen with wild-type S. typhimurium. Salmonella mutants were as invasive as wild-type bacteria for HeLa cells; however, their capacity to cause destruction of the intestinal mucosa was impaired, when compared with wild-type bacteria by electron microscopy. Upon oral challenge of mice, the LD(50)of the Salmonella mutants was greater than that for the wild-type bacteria. The fluid secretory potential, as well as a reduction in the LD(50)of these mutants was restored when the mutated stn gene was replaced by the native stn gene sequence. These mutations had no effect on the aerobic growth of these bacteria in minimal or complete medium; anaerobic growth was also not affected. With these studies, we demonstrated that the presence of an intact stn gene contributed significantly to the overall virulence of S. typhimurium in a murine model.

Animals↗
PubMed1989

The overall fractionation effect of isotopic oxygen molecules during oxygen transport and utilization in humans.

The aim of the study was to clarify (1) whether fractionation effects of isotopic oxygen molecules due to respiratory processes can be neglected in tracer studies, (2) whether additional information about respiratory processes can be obtained from measuring isotope fractionations. Experiments were performed on 7 healthy humans at rest. Samples were taken from inspiratory and expiratory gas. After having removed the carbon dioxide from the samples, the oxygen was completely burnt with graphite to CO2, and the 16O18O/16O2 ratio of the CO2 generated was analysed by mass spectrometry. The 16O18O/16O2 ratio of the expiratory gas was 0.21 +/- 0.07% greater than that of the inspiratory air. The overall rate constant for uptake, subsequent transport and utilization was higher for 16O2 by 0.91 +/- 0.24% than for 16O18O. These results together with model calculations including data from literature suggest: (1) the fractionation effects between 16O18O and 16O2 as well as between 18O2 and 16O2 are small enough for both isotopic species to be considered appropriate labels in the investigation of respiratory processes, (2) the effect measured could be due to limitations of oxygen transport by utilization, (3) additional processes such as the reaction of oxygen with hemoglobin could be involved in forming the overall fractionation effect.

Carbon Dioxide↗
PubMed1982

Overall prognosis of patients with diagnosed chronic organic solvent intoxication.

The prognosis of 87 patients (mean age 38.6 years) was examined who had been diagnosed 3-9 years earlier as having chronic organic solvent intoxication due to trichloroethylene, perchloroethylene, or a mixture of solvents. The methods comprised an interview, a clinical neurological examination, neurophysiological examinations (EEGs and electroneuromyographs), and a psychological examination. In order to assess the prognosis, the patient's condition at the time of diagnosis was evaluated from the hospital records, and the condition upon reexamination was compared to that at the time of diagnosis. At the time of diagnosis, 31 patients had objective clinical signs in the neurological examination, whereas the remaining 56 had only subjective symptoms and neurophysiological or psychological findings attributed to the slight solvent intoxication. Upon reexamination, 42 patients had clinical neurological signs. Based on the clinical overall evaluation, the condition of 21 patients had deteriorated during the follow-up period, the condition of 23 had improved, and that of 43 had remained unchanged. The prognoses of the results of the separate examinations correlated poorly with each other. No statistically significant correlation was found between the overall prognosis and age, sex, the duration and the level of exposure, the termination of exposure after diagnosis, the presence of other diseases, or the use of alcohol.

Adult↗
PubMed1988

No relevant influence on overall survival time in patients with metastatic breast cancer undergoing combination chemotherapy.

The results of clinical studies dealing with first and second line chemotherapy of metastatic breast cancer published between 1975 and early 1986 which involved 9350 women were reviewed. Our special aim was to evaluate combination chemotherapy and its influence on overall survival in late stage breast cancer patients. No significant improvement in overall survival times was found in this selected group of patients who were treated with intense palliative chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

Overall open-loop gain of rapidly acting arterial pressure control system in rabbits.

We estimated the overall open-loop gain of the rapidly acting arterial pressure control system without surgically or pharmacologically opening the reflex loop in rabbits. Animals anesthetized by intravenous injection of Nembutal (27.5 mg X kg-1 body weight) and heparinized were bled by 2 ml X kg-1 body weight within 1-2 s through a catheter inserted into the aortic arch. Arterial pressure change after the quick mild hemorrhage was monitored via a catheter placed in the right subclavian artery for more than 2 min. The overall open-loop gain of the lumped arterial pressure control system determined from the mean arterial pressure response to the hemorrhage was 7.3. It was almost constant over the range between 12.9 and 22.2 kPa systemic pressure.

Animals↗
PubMed1988

Synonymous nucleotide substitution rates of beta-tubulin and histone genes conform to high overall genomic rates in rodents but not in sea urchins.

Sea urchin and rodent genomes have been posited to evolve rapidly as indicated by divergences in single copy nuclear DNA sequences. We have examined whether the synonymous substitution rates of three highly conserved genes, beta-tubulin, histone H4, and histone H3, adhere to these high genomic substitution rates by comparing sequences between two sea urchins, Strongylocentrotus purpuratus and Lytechinus pictus, and between rodents and humans. Whereas the rate of change between the 3' untranslated regions of the beta-tubulin cDNA of S. purpuratus (Sp-beta 1), sequenced in this study, and of L. pictus (Lp-beta 3) was consistent with the overall rate of change estimated from previous DNA hybridization results between these species, the synonymous substitution rates for the carboxyl domains of these beta-tubulins, as well as for the late histones H4 and H3, were significantly depressed. In contrast, synonymous nucleotide substitution rates between rodents and between rodent and human for the carboxyl domain proper of identical beta-tubulin isotypes and for histone H4 and H3.1 did not differ from the overall rate of change for the rodent genomes. Moreover, an analysis of paralogous human and mouse beta-tubulin sequences supported the conclusion that the synonymous substitution rates in the mouse were higher than those in the human. Differences in constraint on evolutionary change were not evident strictly from the conserved amino acid sequences and base compositions of these genes. Other constraining influences seemed more relevant to the departure of the synonymous substitution rates of the sea urchin beta-tubulin and histone coding regions from the average genomic rate.

Amino Acid Sequence↗