bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genotype of metabolic enzymes and the benefit of tamoxifen in postmenopausal breast cancer patients
Authors: Wegman Pia , Vainikka Linda , Stål Olle , Nordenskjöld Bo , Skoog Lambert , Rutqvist Lars-Erik , Wingren Sten 
Published: January 2005

Abstract
Background
Tamoxifen is widely used as endocrine therapy for oestrogen-receptor-positive breast cancer. However, many of these patients experience recurrence despite tamoxifen therapy by incompletely understood mechanisms. In the present report we propose that tamoxifen resistance may be due to differences in activity of metabolic enzymes as a result of genetic polymorphism. Cytochrome P450 2D6 (CYP2D6) and sulfotransferase 1A1 (SULT1A1) are polymorphic and are involved in the metabolism of tamoxifen. The CYP2D6*4 and SULT1A1*2 genotypes result in decreased enzyme activity. We therefore investigated the genotypes of CYP2D6 and SULT1A1 in 226 breast cancer patients participating in a trial of adjuvant tamoxifen treatment in order to validate the benefit from the therapy.

Methods
The patients were genotyped using PCR followed by cleavage with restriction enzymes.

Results
Carriers of the CYP2D6*4 allele demonstrated a decreased risk of recurrence when treated with tamoxifen (relative risk = 0.28, 95% confidence interval = 0.11–0.74, P = 0.0089). A similar pattern was seen among the SULT1A1*1 homozygotes (relative risk = 0.48, 95% confidence interval = 0.21–1.12, P = 0.074). The combination of CYP2D6*4 and/or SULT1A1*1/*1 genotypes comprised 60% of the patients and showed a 62% decreased risk of distant recurrence with tamoxifen (relative risk = 0.38, 95% confidence interval = 0.19–0.74, P = 0.0041).

Conclusion
The present study suggests that genotype of metabolic enzymes might be useful as a guide for adjuvant endocrine treatment of postmenopausal breast cancer patients. However, results are in contradiction to prior hypotheses and the present sample size is relatively small. Findings therefore need to be confirmed in a larger cohort.
Outcome Predictors for the Increasing PSA State After Definitive External-Beam Radiotherapy for Prostate Cancer
Authors: Zelefsky Michael J. , Ben-Porat Leah , Scher Howard I. , Chan Heather M. , Fearn Paul A. , Fuks Zvi Y. , Leibel Steven A. , Venkatraman E.S. 
Published: January 2005

Purpose To identify predictors of distant metastases (DM) among patients who develop an isolated prostate-specific antigen (PSA) relapse after definitive external-beam radiotherapy for clinically localized prostate cancer. Materials and Methods A total of 1,650 patients with clinical stage T1 to T3 prostate cancer were treated with high-dose three-dimensional conformal radiotherapy. Of these, 381 patients subsequently developed three consecutive increasing PSA values and were characterized as having a biochemical relapse. The median follow-up time was 92 months from the completion of radiotherapy. Results The 5-year incidence of DM after an established PSA relapse was 29%. In a multivariate analysis, PSA doubling time (PSA-DT; P < .001), the clinical T stage (P < .001), and Gleason score (P = .007) were independent variables predicting for DM after established biochemical failure. The PSA-DT for favorable-, intermediate-, and unfavorable-risk patients who developed a biochemical failure was 20.0, 13.2, and 8.2 months, respectively (P < .001). The 3-year incidence of DM for patients with PSA-DT of 0 to 3, 3 to 6, 6 to 12, and more than 12 months was 49%, 41%, 20%, and 7%, respectively (P < .001). Patients with PSA-DT of 0 to 3 and 3 to 6 months demonstrated a 7.0 and 6.6 increased hazard of developing DM or death, respectively, compared with patients with a DT more than 12 months. Conclusion In addition to clinical stage and Gleason score, PSA-DT was a powerful predictor of DM among patients who develop an isolated PSA relapse after external-beam radiotherapy for prostate cancer. Patients who develop biochemical relapse with PSA-DT ≤ 6 months should be considered for systemic therapy or experimental protocols because of the high propensity for rapid DM development.
Changes in Body Fat and Weight After a Breast Cancer Diagnosis: Influence of Demographic, Prognostic, and Lifestyle Factors
Authors: Irwin Melinda L. , McTiernan Anne , Baumgartner Richard N. , Baumgartner Kathy B. , Bernstein Leslie , Gilliland Frank D. , Ballard-Barbash Rachel 
Published: January 2005

Purpose Obese women and women who gain weight after a breast cancer diagnosis are at a greater risk for breast cancer recurrence and death compared with lean women and women who do not gain weight after diagnosis. In this population-based study, we assessed weight and body fat changes from during the first year of diagnosis to during the third year after diagnosis, and whether any changes in weight and body fat varied by demographic, prognostic, and lifestyle factors in 514 women with incident Stage 0-IIIA breast cancer. Methods Patients were participants in the Health, Eating, Activity, and Lifestyle (HEAL) study. Weight and body fat (via dual-energy x-ray absorptiometry scans) were measured during the baseline visit and 2 years later at a follow-up visit. Analysis of covariance methods were used to obtain mean weight and body fat changes adjusted for potential cofounders. Results Women increased their weight and percent body fat by 1.7 ± 4.7 kg and 2.1% ± 3.9%, respectively, from during their first year of diagnosis to during their third year of diagnosis. A total of 68% and 74% of patients gained weight and body fat, respectively. Greater increases in weight were observed among women diagnosed with a higher disease stage, younger age, being postmenopausal, and women who decreased their physical activity from diagnosis to up to 3 years after diagnosis (P for trend < .05). Conclusion Weight and body fat increased in the postdiagnosis period. Future research should focus on the effect of physical activity on weight and fat loss and breast cancer prognosis.
Molecular Classification of Tamoxifen-Resistant Breast Carcinomas by Gene Expression Profiling
Authors: Jansen Maurice P.H.M. , Foekens John A. , van Staveren Iris L. , Dirkzwager-Kiel Maaike M. , Ritstier Kirsten , Look Maxime P. , Meijer-van Gelder Marion E. , Sieuwerts Anieta M. , Portengen Henk , Dorssers Lambert C.J. , Klijn Jan G.M. , Berns Els M.J.J. 
Published: January 2005

Purpose To discover a set of markers predictive for the type of response to endocrine therapy with the antiestrogen tamoxifen using gene expression profiling. Patients and Methods The study was performed on 112 estrogen receptor–positive primary breast carcinomas from patients with advanced disease and clearly defined types of response (ie, 52 patients with objective response v 60 patients with progressive disease) from start of first-line treatment with tamoxifen. Main clinical end points are the effects of therapy on tumor size and time until tumor progression (progression-free survival [PFS]). RNA isolated from tumor samples was amplified and hybridized to 18,000 human cDNA microarrays. Results Using a training set of 46 breast tumors, 81 genes were found to be differentially expressed (P ≤ .05) between tamoxifen-responsive and -resistant tumors. These genes were involved in estrogen action, apoptosis, extracellular matrix formation, and immune response. From the 81 genes, a predictive signature of 44 genes was extracted and validated on an independent set of 66 tumors. This 44-gene signature is significantly superior (odds ratio, 3.16; 95% CI, 1.10 to 9.11; P = .03) to traditional predictive factors in univariate analysis and also significantly related with a longer PFS in univariate (hazard ratio, 0.54; 95% CI, 0.31 to 0.94; P = .03) as well as in multivariate analyses (P = .03). Conclusion Our data show that gene expression profiling can be used to discriminate between breast cancer patients with progressive disease and objective response to tamoxifen. Additional studies are needed to confirm if the predictive signature might allow identification of individual patients who could benefit from other (adjuvant) endocrine therapies.
Validation and Extension of the Memorial Sloan-Kettering Prognostic Factors Model for Survival in Patients With Previously Untreated Metastatic Renal Cell Carcinoma
Authors: Mekhail Tarek M. , Abou-Jawde Rony M. , BouMerhi Gabriel , Malhi Sareena , Wood Laura , Elson Paul , Bukowski Ronald 
Published: January 2005

Purpose To validate the Motzer et al prognostic factors model for survival in patients with previously untreated metastatic renal cell carcinoma (RCC) and to identify additional independent prognostic factors. Patients and Methods Data were collected on 353 previously untreated metastatic RCC patients enrolled onto clinical trials between 1987 and 2002. Results Four of the five prognostic factors identified by Motzer were independent predictors of survival. In addition, prior radiotherapy and presence of hepatic, lung, and retroperitoneal nodal metastases were found to be independent prognostic factors. Using the number of metastatic sites as surrogate for individual sites (none or one v two or three sites), Motzer’s definitions of risk groups were expanded to accommodate these two additional prognostic factors. Using this expanded criteria, favorable risk is defined as zero or one poor prognostic factor, intermediate risk is two poor prognostic factors, and poor risk is more than two poor prognostic factors. According to Motzer’s definitions, 19% of patients were favorable risk, 70% were intermediate risk, and 11% were poor risk; median overall survival times for these groups were 28.6, 14.6, and 4.5 months, respectively (P < .0001). Using the expanded criteria, 37% of patients were favorable risk, 35% were intermediate risk, and 28% were poor risk; median overall survival times of these groups were 26.0, 14.4, and 7.3 months, respectively (P < .0001). Conclusion These data validate the model described by Motzer et al. Additional independent prognostic factors identified were prior radiotherapy and sites of metastasis. Incorporation of these additional prognostic factors into the Motzer et al model can help better define favorable risk, intermediate risk, and poor risk patients.
Review of Exercise Intervention Studies in Cancer Patients
Authors: Galvão Daniel A. , Newton Robert U. 
Published: January 2005

PurposeTo present an overview of exercise interventions in cancer patients during and after treatment and evaluate dose-training response considering type, frequency, volume, and intensity of training along with expected physiological outcomes.MethodsThe review is divided into studies that incorporated cardiovascular training, combination of cardiovascular, resistance, and flexibility training, and resistance training alone during and after cancer management. Criteria for inclusion were based on studies sourced from electronic and nonelectronic databases and that incorporated preintervention and postintervention assessment with statistical analysis of data.ResultsTwenty-six published studies were summarized. The majority of the studies demonstrate physiological and psychological benefits. However, most of these studies suffer limitations because they are not randomized controlled trials and/or use small sample sizes. Predominantly, studies have been conducted with breast cancer patients using cardiovascular training rather than resistance exercise as the exercise modality. Recent evidence supports use of resistance exercise or “anabolic exercise” during cancer management as an exercise mode to counteract side effects of the disease and treatment.ConclusionEvidence underlines the preliminary positive physiological and psychological benefits from exercise when undertaken during or after traditional cancer treatment. As such, other cancer groups, in addition to those with breast cancer, should also be included in clinical trials to address more specifically dose-response training for this population. Contemporary resistance training designs that provide strong anabolic effects for muscle and bone may have an impact on counteracting some of the side effects of cancer management assisting patients to improve physical function and quality of life.
Molecular and Clinical Analysis of Locally Advanced Dermatofibrosarcoma Protuberans Treated With Imatinib: Imatinib Target Exploration Consortium Study B2225
Authors: McArthur Grant A. , Demetri George D. , van Oosterom Allan , Heinrich Michael C. , Debiec-Rychter Maria , Corless Christopher L. , Nikolova Zariana , Dimitrijevic Sasa , Fletcher Jonathan A. 
Published: January 2005

Purpose The cutaneous malignant tumor dermatofibrosarcoma protuberans (DFSP) is typically associated with a translocation between chromosomes 17 and 22 that places the platelet-derived growth factor–B (PDGFB) under the control of the collagen 1A1 promoter. The purpose of this study was to evaluate molecular, cytogenetic, and kinase activation profiles in a series of DFSPs and to determine whether these biologic parameters are correlated with the clinical responses of DFSP to imatinib. Patients and Methods We analyzed the objective radiologic and clinical response to imatinib at 400 mg twice daily in eight patients with locally advanced DFSP and two patients with metastatic disease. Results Each of eight patients with locally advanced DFSP had evidence of t(17;22) and showed a clinical response to imatinib. Four of these patients had complete clinical responses. The two patients with metastatic disease had fibrosarcomatous histology and karyotypes that were substantially more complex than those typically associated with localized DFSP. One patient with metastatic DFSP and an associated t(17;22) had a partial response to imatinib but experienced disease progression after 7 months of therapy. In contrast, the other patient with metastatic disease had a tumor lacking t(17;22), and there was no clinical response to imatinib. Unexpectedly, there was minimal platelet-derived growth factor receptor–beta phosphorylation in the untreated DFSP, despite the documented presence of a PDGFB autocrine mechanism. Conclusion Imatinib has clinical activity against both localized and metastatic DFSP with t(17;22). However, fibrosarcomatous variants of DFSP lacking t(17;22) may not respond to imatinib.
Evaluation of Tamoxifen and Anastrozole in the Prevention of Gynecomastia and Breast Pain Induced by Bicalutamide Monotherapy of Prostate Cancer
Authors: Boccardo F. , Rubagotti A. , Battaglia M. , Di Tonno P. , Selvaggi F.P. , Conti G. , Comeri G. , Bertaccini A. , Martorana G. , Galassi P. , Zattoni F. , Macchiarella A. , Siragusa A. , Muscas G. , Durand F. , Potenzoni D. , Manganelli A. , Ferraris V. , Montefiore F. 
Published: January 2005

Purpose To determine whether tamoxifen or anastrozole prevents gynecomastia and breast pain caused by bicalutamide (150 mg) without compromising efficacy, safety, or sexual functioning. Patients and Methods A double-blind, placebo-controlled trial was performed in patients with localized, locally advanced, or biochemically recurrent prostate cancer. Patients (N = 114) were randomly assigned to either bicalutamide (150 mg/d) plus placebo or in combination with tamoxifen (20 mg/d) or anastrozole (1 mg/d) for 48 weeks. Gynecomastia, breast pain, prostate-specific antigen (PSA), sexual functioning, and serum levels of hormones were assessed. Results Gynecomastia developed in 73% of patients in the bicalutamide group, 10% of patients in the bicalutamide-tamoxifen group, and 51% of patients in the bicalutamide-anastrozole group (P < .001); breast pain developed in 39%, 6%, and 27% of patients, respectively (P = .006). Baseline PSA level decreased by ≥ 50% in 97%, 97%, and 83% of patients in the bicalutamide, bicalutamide-tamoxifen, and bicalutamide-anastrozole groups, respectively (P = .07); and adverse events were reported in 37%, 35%, and 69% of patients, respectively (P = .004). There were no major differences among treatments in sexual functioning parameters from baseline to month 6. Elevated testosterone levels occurred in each group; however, free testosterone levels remained unchanged in the bicalutamide-tamoxifen group because of increased sex hormone–binding globulin levels. Conclusion Anastrozole did not significantly reduce the incidence of bicalutamide-induced gynecomastia and breast pain. In contrast, tamoxifen was effective, without increasing adverse events, at least in the short-term follow-up. These data support the need for a larger study to determine any effect on mortality.
Lymphatic Vessel Invasion As a Prognostic Factor in Patients With Primary Resected Adenocarcinomas of the Esophagogastric Junction
Authors: von Rahden Burkhard H.A. , Stein Hubert J. , Feith Marcus , Becker Karen , Siewert J. Rüdiger 
Published: January 2005

Purpose To evaluate the value of lymphatic vessel invasion (LVI) as a predictor of survival in patients with primary resected adenocarcinomas of the esophagogastric junction (AEG). Patients and Methods We prospectively evaluated 459 patients undergoing primary surgical resection for tumors of the esophagogastric junction at our institution between 1992 and 2000 (180 adenocarcinomas of the distal esophagus, AEG I; 140 carcinomas of the cardia, AEG II; and 139 subcardial gastric cancers, AEG III). Median follow-up was 36.8 months. The prevalence of LVI was evaluated by two independent pathologists. Univariate and multivariate analysis of prognostic factors was performed. Results The total rate of LVI was 49.9%, with a significant difference between AEG I (38.9%) and AEGII/III (57.0%, P = .0002). Univariate analysis showed a significant correlation between LVI and T category (P < .0001), N category (P < .0001), and resection status (R [residual tumor] category; P < .0001). This was shown for the group of all AEG tumors, as well as for the subgroups AEG I and AEG II/III. On multivariate analysis, LVI was identified as a significant and independent prognostic factor (P = .050) in the population of all patients and in patients with AEG II/III, but not in the subgroup with AEG I. Conclusion These data demonstrate the prognostic significance of LVI in patients with AEG tumors, with marked differences between the subgroups AEG I versus AEG II/III. The lower prevalence and lack of prognostic significance of LVI in AEG I might be explained by inflammation involved in the pathogenesis of this entity.
Individualized Predictions of Disease Progression Following Radiation Therapy for Prostate Cancer
Authors: Taylor Jeremy M.G. , Yu Menggang , Sandler Howard M. 
Published: January 2005

Purpose Following treatment for localized prostate cancer, men are monitored with serial prostate-specific antigen (PSA) measurements. Refining the predictive value of post-treatment PSA determinations may add to clinical management, and we have developed a model that predicts future PSA values and the time to future clinical recurrence for individual patients. Patients and Methods Data from 934 patients treated between 1987 and 2000 were used to develop a comprehensive statistical model to fit the clinical recurrence events and patterns of PSA data. A logistic model was used for the probability of cure, mixed models were used for serial PSA measurements, and a proportional hazards model was used for recurrences. Data available through February 2001 were fit to the model, and data collected between February 2001 and September 2003 were used for validation. Results T-stage, baseline PSA, and radiotherapy dosage are all associated with probability of cure. The risk of clinical recurrence in those not cured is strongly affected by the slope of PSA values. We show how the model can be used for individual monitoring of disease progression. For each patient the model predicts, based on baseline characteristics and all post-treatment PSA values, the probability of future clinical recurrences and future PSA values. The model accurately predicts risk of recurrence and future PSA values in the validation data set. Conclusion This predictive information on future PSA values and the risk of clinical relapse for each individual patient, which can be updated with each additional PSA value, may prove useful to patients and physicians in determining post-treatment salvage strategies.
High-Throughput Mitochondrial Genome Screening Method for Nonmelanoma Skin Cancer Using Multiplexed Temperature Gradient Capillary Electrophoresis
Authors: Girald-Rosa Willie , Vleugels Ruth A , Musiek Amy C , Sligh James E 
Published: January 2005

Abstract
Background:We explored the utility of multiplexed temperature gradient capillary electrophoresis (TGCE) as a screening tool for identifying genetic changes in the human mitochondrial genome. We examined changes in mitochondrial DNA (mtDNA) in nonmelanoma skin cancers (NMSCs), using TGCE to resolve genetic differences contained within the tumors compared with the control DNA.
Methods: The entire mtDNA from NMSC tissue samples was amplified in 17 overlapping amplicons averaging 1.1 kb in size. Fourteen of these amplicons were digested with restriction endonucleases into as many as five smaller analyzable fragments. Digested tumor mtDNA amplicons were annealed with digested amplicons from the control DNA to form heteroduplexes in regions of DNA mismatch. TGCE was performed in a 96-well parallel format to detect mtDNA changes in a high-throughput fashion.
Results: TGCE resolved heteroduplexes from homoduplexes in singlet reactions and in multiplexed assays. Using a single programmed temperature gradient, we detected 18 of 20 mtDNA changes contained within the specimens. This system was also able to detect a single nucleotide change in a fragment as large as 2 kb.
Conclusion: Multiplexed TGCE is a sensitive and high-throughput screening tool for identifying mtDNA variations.
Prediction of Liver Fibrosis and Cirrhosis in Chronic Hepatitis B Infection by Serum Proteomic Fingerprinting: A Pilot Study
Authors: Poon Terence CW , Hui Alex Y , Chan Henry LY , Ang Irene Ling , Chow Shuk Man , Wong Nathalie , Sung Joseph JY 
Published: January 2005

AbstractBackground: Most noninvasive predictive models of liver fibrosis are complicated and have suboptimal sensitivity. This study was designed to identify serum proteomic signatures associated with liver fibrosis and to develop a proteome-based fingerprinting model for prediction of liver fibrosis.Methods: Serum proteins from 46 patients with chronic hepatitis B (CHB) were profiled quantitatively on surface-enhanced laser desorption/ionization (SELDI) ProteinChip arrays. The identified liver fibrosis-associated proteomic fingerprint was used to construct an artificial neural network (ANN) model that produced a fibrosis index with a range of 0–6. The clinical value of this index was evaluated by leave-one-out cross-validation.Results: Thirty SELDI proteomic features were significantly associated with the degree of fibrosis. Cross-validation showed that the ANN fibrosis indices derived from the proteomic fingerprint strongly correlated with Ishak scores (r = 0.831) and were significantly different among stages of fibrosis. ROC curve areas in predicting significant fibrosis (Ishak score ≥3) and cirrhosis (Ishak score ≥5) were 0.906 and 0.921, respectively. At 89% specificity, the sensitivity of the ANN fibrosis index in predicting fibrosis was 89%. The sensitivity for prediction increased with degree of fibrosis, achieving 100% for patients with Ishak scores &gt;4. The accuracy for prediction of cirrhosis was also 89%. Inclusion of International Normalized Ratio, total protein, bilirubin, alanine transaminase, and hemoglobin in the ANN model improved the predictive power, giving accuracies &gt;90% for the prediction of fibrosis and cirrhosis.Conclusions: A unique serum proteomic fingerprint is present in the sera of patients with fibrosis. An ANN fibrosis index derived from this fingerprint could differentiate between different stages of fibrosis and predict fibrosis and cirrhosis in CHB infection.