bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective Exploratory Analysis of the Association Between Tumor Response, Quality of Life, and Expenditures Among Patients Receiving Paclitaxel Monotherapy for Refractory Metastatic Breast Cancer
Authors: Modi Shanu , Panageas Katherine S. , Duck Elaine T. , Bach Ariadne , Weinstock Nancy , Dougherty James , Cramer Laura , Hudis Clifford , Norton Larry , Seidman Andrew 
Published: August 2002

PURPOSE: To prospectively evaluate the association between tumor response, change in quality of life (QoL), and hospital expenditures in patients with metastatic breast cancer (MBC) receiving single-agent paclitaxel. PATIENTS AND METHODS: Eligible patients had bidimensionally measurable MBC and any number of previous therapies, excluding taxane chemotherapy. Paclitaxel was administered by various different infusion schedules. QoL measures were evaluated for each patient at baseline and serially using the Memorial Symptom Assessment Scale (MSAS)-Global Distress Index (GDI) and Functional Assessment of Cancer Therapy–Breast (FACT-B) instruments. Patients were assessed for early (first 6 weeks) and ever changes in QoL parameters. Charges were monitored through the hospital’s centralized computer billing system and converted to cost ratios for the analysis. Correlations between response and improvement in QoL were assessed by Fisher’s exact test statistic. Associations between improvements in QoL with cost ratios were assessed by logistic regression and likewise between response and cost ratios. RESULTS: Of the 59 patients treated, 50 had sufficient data for comparative analyses. The overall response rate was 24% (all partial responses). Minor responses were observed in 17% of patients, 25% had stable disease, and 29% had progression. Responding patients had significant improvement in QoL as assessed by MSAS-GDI (P = .004) and FACT-B (P = .028). The mean total cost/month ratios for patients experiencing improved GDI QoL scores was 1.31 versus 1.56 for those without QoL benefit (P = .52) and 1.05 versus 1.76 for responders versus nonresponders, respectively (P = .07). CONCLUSION: Patients with evidence of tumor response on paclitaxel had a QoL benefit not observed in nonresponders, and this response was associated with a trend for lower overall costs.
Correlation of Smoking History and Other Patient Characteristics With Major Complications of Pelvic Radiation Therapy for Cervical Cancer
Authors: Eifel Patricia J. , Jhingran Anuja , Bodurka Diane C. , Levenback Charles , Thames Howard 
Published: August 2002

PURPOSE: The purpose of this study was to identify patient-related factors that influence the risk of serious late complications of pelvic radiation therapy.PATIENTS AND METHODS: The records of 3,489 patients treated with radiation therapy for International Federation of Gynecology and Obstetrics stage I or II carcinoma of the cervix were reviewed for information about patient characteristics, treatment details, and outcomes. Any complication occurring or persisting more than 3 months after treatment that required hospitalization, transfusion, or an operation or caused severe symptoms or the patient’s death was considered a major late complication. Complication rates were calculated actuarially. The median duration of follow-up was 85 months, and 99% of patients were followed for at least 3 years or until they died.RESULTS: Heavy smoking was the strongest independent predictor of overall complications (multivariate hazard ratio, 2.30; 95% confidence interval [CI], 1.84 to 2.87). The most striking influence of smoking was on the incidence of small bowel complications (hazard ratio for smokers of one or more packs per day, 3.25; 95% CI, 2.21 to 4.78). Hispanics had a significantly lower rate of small bowel complications than whites, and blacks had higher rates of bladder and rectal complications than whites. Thin women had an increased risk of gastrointestinal complications, and obese women were more likely to have serious bladder complications.CONCLUSION: Complications of pelvic radiation therapy are strongly correlated with smoking, race, and other patient characteristics. These factors should be considered before the results of clinical studies are generalized to different cultural and racial groups.
Randomized Comparative Study of Tegafur/Uracil and Oral Leucovorin Versus Parenteral Fluorouracil and Leucovorin in Patients With Previously Untreated Metastatic Colorectal Cancer
Authors: Carmichael James , Popiela Tadeusz , Radstone David , Falk Stephen , Borner Markus , Oza Amit , Skovsgaard Torben , Munier Stephane , Martin Christophe 
Published: August 2002

Purpose: This phase III study compared the time to progression (TTP) of an oral regimen of dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine composed of a fixed combination of tegafur and uracil in a 1:4 molar ratio (UFT) and leucovorin (LV) to intravenous (IV) fluorouracil (5-FU) and LV in previously untreated metastatic colorectal carcinoma (CRC) patients. Secondary end points were survival, tumor response, safety, and quality of life. Patients and Methods: Between May 1996 and July 1997, 380 patients were randomized to receive either UFT (300 mg/m2/d) and LV (90 mg/d), administered for 28 days every 35 days, or 5-FU (425 mg/m2/d) and LV (20 mg/m2/d), given IV for 5 days every 35 days. Results: No statistically significant difference in TTP was observed between treatments. With 320 events assessed, the median TTP was 3.4 months (95% Confidence interval [CI], 2.6 to 3.8) on UFT/LV and 3.3 months (95% CI, 2.5 to 3.7) on 5-FU/LV (P = .591, stratified log-rank test). There were no statistically significant differences in survival, tumor response, duration of response, and time to response. Substantial safety benefits were observed in patients treated with UFT/LV. They experienced significantly less stomatitis/mucositis (P < .001) and myelosuppression, resulting in fewer episodes of febrile neutropenia (P < .001) and less documented infection (P = .04). Concomitant medication usage was significantly greater on 5-FU/LV (P = .010). With respect to quality of life, after correcting for baseline imbalances, there were no significant differences between treatments for any scale, except diarrhea. Conclusion: The oral UFT/LV regimen failed to achieve improved TTP; however, the study confirms significant safety improvements compared with bolus IV 5-FU/LV for the first-line treatment of metastatic CRC.
Communication in End-of-Life Cancer Care: A Comparison of Team Assessments in Three European Countries
Authors: Higginson Irene J. , Costantini Massimo 
Published: August 2002

PURPOSE: To compare team assessments of end-of-life communication in three European countries, and to identify factors associated with problematic communication. PATIENTS AND METHODS: Three prospective cohort studies used similar standardized procedures, and included patients referred to palliative care services in the United Kingdom, Ireland, and Italy. Palliative team care staff assessed three components of communication in the last week of the patient’s life—between the patient and family (or those close to them), between professionals and patient and family, and between professionals—using a validated measure. Univariate and multivariate analyses explored the data and tested for relationships between possible explanatory variables and communication. RESULTS: Data were collected on 1,326 patients, 416 in the United Kingdom, 411 in Ireland, and 499 in Italy. Mean age was 68 years (range, 19 to 95 years), 55% were male, and almost two thirds were married. Team members assessed that communication between patient and family was a moderate or severe problem in the last week of life for 30% to 40% of patients; 10% to 20% had moderate or severe problems recorded for the other two communication items. Problematic communication was associated with respiratory and breast cancers, a shorter time in care, and hospice death. It was also associated with greater spiritual need, need for care planning, and poorer patient and family insight (Spearman’s ρ > 0.4), but not especially with pain and symptom control, in both univariate and multivariate analyses, both within countries and for all data combined. CONCLUSION: Severe communication problems were reported by team assessments in up to 40% of patients at the end of life. A multiprofessional approach is needed to recognize and improve this.
Racial Variation in CAG Repeat Lengths Within the Androgen Receptor Gene Among Prostate Cancer Patients of Lower Socioeconomic Status
Authors: Bennett Charles L. , Price Douglas K. , Kim Simon , Liu Dachao , Jovanovic Borko D. , Nathan Derek , Johnson Margaret E. , Montgomery Jeffrey S. , Cude Kelly , Brockbank Justin C. , Sartor Oliver , Figg William D. 
Published: August 2002

PURPOSE: To evaluate (1) whether there were racial differences in the androgen receptor gene CAG repeat length and in clinical or laboratory attributes of prostate cancer at the time of diagnosis; (2) whether there were differences in race, Gleason score, prostate-specific antigen (PSA) level, and stage at diagnosis by androgen receptor gene CAG repeat length; and (3) whether sociodemographic, clinical, and laboratory based factors might be associated with advanced-stage prostate cancer. To our knowledge, our study is the first to report on CAG repeat lengths in a cohort of prostate cancer patients, which includes large numbers of African-American men. METHODS: CAG repeat lengths on the androgen receptor gene were evaluated for 151 African-American and 168 white veterans with prostate cancer. The χ2 test, t test, and logistic regression analyses were used to evaluate the associations between CAG repeat lengths and race, stage, histologic grade, and PSA levels at diagnosis. RESULTS: The mean age of the cohort at the time of diagnosis was 68.7 years. At presentation, 42.0% had stage D prostate cancer, 26.5% had Gleason scores of 8 to 10, and 53.0% had PSA levels ≥ 10 ng/dL. Mean androgen receptor gene CAG repeat length for white veterans was 21.9 (SD, 3.5) versus 19.8 (SD, 3.2) for African-American veterans (P = .001). Men with shorter CAG repeats were more likely to have stage D prostate cancer (P = .09) but were not more likely to have a higher PSA concentration or Gleason score. CONCLUSION: In this cohort of men with prostate cancer, short CAG repeat length on the androgen receptor gene was associated with African-American race and possibly with higher stage but not with other clinical or pathologic findings.
Palliative Chemotherapy or Watchful Waiting? A Vignettes Study Among Oncologists
Authors: Koedoot C.G. , de Haes J.C.J.M. , Heisterkamp S.H. , Bakker P.J.M. , de Graeff A. , de Haan R.J. 
Published: August 2002

PURPOSE: To determine the preferences of oncologists for palliative chemotherapy or watchful waiting and the factors considered important to that preference. METHODS: Sixteen vignettes (paper case descriptions), varying on eight patient and treatment characteristics, were designed to assess the oncologists’ preferences. Their strength of preference was rated on a 7-point scale. An orthogonal main effects design provided a subset of all possible combinations of the characteristics, allowing estimations of the relative weights of the presented characteristics. A written questionnaire was sent to a random sample of oncologists (N = 1,235). RESULTS: The response rate was 67%, and 697 questionnaires were available for analysis. Eighty-one percent of the respondents were male. The mean age was 46 years. We found considerable variation among the oncologists. No major associations between physician characteristics and preferences were found. Of the patient and treatment characteristics affecting treatment preference, age was the strongest predictor, followed by the patient’s wish to be treated and the expected survival gain. Other patient and treatment characteristics had a limited effect on preferences, except for psychologic distress, which had no independent impact. CONCLUSION: Patients will encounter different decisions depending on their oncologists’ preferences and their own personal background. Therefore, to ensure adequate information for decision-making processes, decision aids are proposed.
Paclitaxel Plus Carboplatin Versus Gemcitabine Plus Paclitaxel in Advanced Non–Small-Cell Lung Cancer: A Phase III Randomized Trial
Authors: Kosmidis Paris , Mylonakis Nick , Nicolaides Costas , Kalophonos Charalabos , Samantas Epaminontas , Boukovinas John , Fountzilas George , Skarlos Dimosthenis , Economopoulos Theophanis , Tsavdaridis Dimitrios , Papakostas Pavlos , Bacoyiannis Charalabos , Dimopoulos Meletios 
Published: August 2002

PURPOSE: We conducted this randomized study comparing the activity and toxicity of paclitaxel and gemcitabine (PG) and paclitaxel and carboplatin (PC) combinations for the treatment of advanced non–small-cell lung cancer (NSCLC).PATIENTS AND METHODS: Chemotherapy-naive patients were randomized to paclitaxel 200 mg/m2on day 1 plus either carboplatin at an area under the concentration-time curve of 6 on day 1 (group A) or gemcitabine 1,000 mg/m2on days 1 and 8 (group B) every 3 weeks. A retrospective cost analysis was conducted using Student’s t test to compare independent samples between groups.RESULTS: A total of 509 patients (group A, 252 patients; group B, 257 patients) were enrolled; all characteristics were well balanced. The median survival time was 10.4 months (95% confidence interval [CI], 8.8 to 12 months) for group A and 9.8 months (95% CI, 8.0 to 11.7 months) for group B (P = .32). Respective 1-year survival rates were 41.7% and 41.4%. The response rate for group A was 28.0% (2% complete response [CR], 26% partial response [PR] [95% CI, 22% to 34%]), and the response rate for group B was 35.0% (5% CR, 30% PR) [95% CI, 29% to 41%]) (P = .12). Toxicity was mild. Grades 3/4 neutropenia, thrombocytopenia, and anemia for groups A and B were seen in 15% and 15%, 2% and 1%, and 5% and 2%, respectively. The mean total cost (outpatient clinic visits plus chemotherapy drug fee) for group A (€ 7,612.64) versus group B (€ 7,484.77) was not statistically significant (P < .66).CONCLUSION: The PG combination is as equally active and well tolerated as the PC combination in patients with advanced NSCLC.
Dose-Dense Anthracycline-Based Chemotherapy for Node-Positive Breast Cancer
Authors: Ellis Georgiana K. , Livingston Robert B. , Gralow Julie R. , Green Stephanie J. , Thompson Tove 
Published: August 2002

PURPOSE: Theoretical considerations and clinical experience suggest that dose-dense chemotherapy may be superior to other approaches using the same drugs. We studied a dose-dense combination of doxorubicin and cyclophosphamide, with or without fluorouracil, as adjuvant therapy. PATIENTS AND METHODS: Patients with resected breast cancer were treated if they were node-positive and estrogen receptor–negative, positive for overexpression of Her-2-neu, or had four or more involved nodes. Doxorubicin was given weekly to a total dose of 480 mg/m2. Cyclophosphamide 60 mg/m2 was given daily by mouth during the period of doxorubicin treatment. The first 30 patients received fluorouracil at 300 mg/m2/wk intravenously concurrently with doxorubicin administration. In the last 22, it was omitted because of symptomatic hand-foot syndrome in the majority of patients. Filgrastim (granulocyte colony-stimulating factor [G-CSF]) was administered during chemotherapy every day except the day of intravenous administration and continued until 1 week after the completion of the chemotherapy. RESULTS: Between October 20, 1992, and June 10, 1997, we enrolled 52 patients. The mean delivered dose-intensity for doxorubicin was 18.6 mg/m2/wk. Hospitalization was required in 6% of patients for reversible febrile neutropenia. There were no acute treatment-related deaths, but one patient subsequently died of acute leukemia with a characteristic translocation for anthracycline-related exposure. At 5 years, the event-free survival was 86% for all patients (95% confidence interval, 75% to 95%). CONCLUSION: Continuous dose-dense chemotherapy with G-CSF support produced encouraging results, which seem to be superior to those expected with “standard” doxorubicin and cyclophosphamide chemotherapy. It deserves a test in the form of a randomized trial where this approach to anthracycline-based treatment is compared with intermittent administration.
Functional Insulin Receptors on Human Epithelial Ovarian Carcinoma Cells: Implications for IGF-II Mitogenic Signaling
Authors: Kalli Kimberly R. , Falowo Oluwole I. , Bale Laurie K. , Zschunke Michael A. , Roche Patrick C. , Conover Cheryl A. 
Published: August 2002

AbstractThe insulin receptor mediates a proliferative response in certain transformed cells, but little is known about its function in ovarian cancer. We used human epithelial ovarian carcinoma cell lines and lifespan-extended normal ovarian surface epithelial (OSE) cells to examine 125I-insulin binding and mitogenic responses to insulin. All cancer cell and OSE cultures specifically bound 125I-insulin. Except for OV202, the carcinoma lines had elevated insulin binding compared with OSE cells. All carcinoma lines except OV202 expressed insulin receptor as detected by flow cytometry and increased 3H-thymidine incorporation or cell number in response to 0.1–10 nm insulin. Interestingly, similar concentrations of IGF-II also induced proliferation of the insulin-responsive cancer cell lines and displaced 125I-insulin binding. Direct binding of 125I-IGF-II to the insulin receptor was visualized by cross-linking and immunoprecipitation. Binding of IGF-II to the insulin receptor and a proliferative effect of insulin suggest the presence of insulin receptor isoform A. Real-time PCR analyses confirm that insulin receptor isoform A expression predominates over isoform B expression in the ovarian carcinoma cell lines. This report suggests that the insulin receptor may play a role in the regulation of ovarian cancer cell growth.
Estrogen Receptor-Related Receptor α Impinges on the Estrogen Axis in Bone: Potential Function in Osteoporosis
Authors: Bonnelye Edith , Kung Vanessa , Laplace Catherine , Galson Deborah L. , Aubin Jane E. 
Published: August 2002

Abstract
The orphan nuclear estrogen receptor-related receptor α (ERRα) is expressed by osteoblastic cells and plays a functional role in osteoprogenitor proliferation and differentiation. To dissect further the role of ERRα in bone, we investigated the effects of estrogen (E2) on ERRα both in vitro and in vivo. Chronic treatment of fetal rat calvaria cells with E2-stimulated bone nodule formation and up-regulated ERRα mRNA expression at early (10 h and d 8) but not later times in culture, suggesting a link between ERRα and E2 during osteoprogenitor proliferation. ERRα mRNA levels were significantly lower in ovariectomized adult rat bones vs. those of sham-operated rats early (1 d and 1 wk) post surgery, but levels returned to control levels thereafter. ERRα is also expressed in osteoclasts (tartrate-resistant acid phosphatase + multinucleated cells) in vivo and in vitro (RAW 264.7 cells) and ovariectomization lowered the OPG/receptor activator of nuclear factor κB ligand expression ratio. Down-regulation of ERRα expression via antisense treatment of rat calvaria cells not only inhibited osteogenesis but also increased adipocyte colony formation and changed the OPG/receptor activator of nuclear factor κB ligand ratio. These data suggest that ERRα is regulated by estrogen in bone in which it may play a functional role at several levels (osteoblasts, adipocytes, and osteoclasts) in E2 deficiency diseases such as osteoporosis.
Hepatocyte Growth Factor/Scatter Factor Facilitates Migration of GN-11 Immortalized LHRH Neurons
Authors: Giacobini P. , Giampietro C. , Fioretto M. , Maggi R. , Cariboni A. , Perroteau I. , Fasolo A. 
Published: August 2002

AbstractThe molecular cues regulating the migratory process of LHRH neurons from the olfactory placode into the brain are not well known, but gradients of chemotropic and chemorepellent factors secreted by the targets are likely to play a key role in guidance mechanisms.Hepatocyte growth factor/scatter factor (HGF/SF) is a pleiotropic cytokine inducing cell migration. It is involved in a variety of developmental processes through interaction with its receptor c-Met. Here we show that c-Met-antibody labels LHRH migrating neurons in the olfactory mesenchyme of E12 mouse and analyze the potential chemotropic effect of HGF/SF on two immortalized LHRH cell lines, GT1-7 and GN11, isolated from tumors developed in the hypothalamus and in the olfactory bulb, respectively.By RT-PCR analysis, Western blotting, and immunocytochemistry, we provide evidence for a high level of c-Met expression in GN11, but not in GT1-7, cells. In addition, HGF/SF treatment promotes specific migratory activity of GN11 cells, as demonstrated by collagen gel assay, time-lapse video microscopy, and Boyden’s chamber experiments. Such promotion is inhibited by the neutralizing antibody.The data reported here represent the first direct evidence of a chemotactic effect of HGF/SF on immortalized LHRH neurons.
Minireview: A Novel Pathway of Prostacyclin Signaling—Hanging Out with Nuclear Receptors
Authors: Lim Hyunjung , Dey Sudhansu K. 
Published: August 2002

AbstractProstacylin (PGI2), one of the major prostaglandins, is derived from arachidonic acid by the action of the cyclooxygenase (COX) system coupled to PGI2 synthase (PGIS). The presence of the COX-2/PGIS at the nuclear and endoplasmic reticular membrane suggests differential signaling pathways of PGI2 actions involving both cell surface and nuclear receptors. Although the signaling of PGI2 via its cell surface receptor, prostacyclin receptor (IP), is well documented in vascular biology, its action via nuclear receptors in other physiological responses is gradually being more appreciated. Peroxisomal proliferator-activated receptors (PPARs), PPARα, PPARγ, and PPARδ, though initially cloned as a family of orphan receptors, are now known for their ligand promiscuity. The ligands range from free fatty acids and their derivatives produced by the cyclooxygenase or lipoxygenase pathway to certain hypolipidemic drugs. The predisposition of PPARs to use a wide spectrum of ligands is well explained by their unusually large ligand-binding pocket. The promiscuous ligand usage by PPARs is also reflected by their involvement in various pathophysiological events. Several recent independent reports show that endogenously produced PGI2 indeed activates PPARδ in vivo, indicating that a novel signaling mechanism for this abundant eicosanoid is operative in certain systems. This review attempts to cover recent developments in nuclear actions of PGI2 in diverse biological functions.