bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II Trial of Temozolomide in Patients With Progressive Low-Grade Glioma
Authors: Quinn Jennifer A. , Reardon David A. , Friedman Allan H. , Rich Jeremy N. , Sampson John H. , Provenzale James M. , McLendon Roger E. , Gururangan Sridharan , Bigner Darell D. , Herndon James E. , Avgeropoulos Nicholas , Finlay Jonathan , Tourt-Uhlig Sandra , Affronti Mary Lou , Evans Brandon , Stafford-Fox Valerie , Zaknoen Sara , Friedman Henry S. 
Published: February 2003

Purpose: Temozolomide (Temodar; Schering-Plough Corp, Kenilworth, NJ) is an imidazole tetrazinone that undergoes chemical conversion to the active methylating agent 5-(3-methyltriazen-1yl)imidazole-4-carboximide under physiologic conditions. Previous studies have confirmed activity of Temodar in the treatment of progressive and newly diagnosed malignant gliomas. We have extended these results, and now we report results of a phase II trial of Temodar for patients with progressive, low-grade glioma. Patients and Methods: Temodar was administered orally once a day for five consecutive days (in a fasting state) at a starting dose of 200 mg/m2/d. Treatment cycles were repeated every 28 days following the first daily dose of Temodar. Response criteria used a combination of magnetic resonance imaging and physical examination to evaluate activity. Results: Forty-six patients with low-grade glioma have been treated to date. The objective response rate was 61% (24% complete response and 37% partial response), with an additional 35% of patients having stable disease. Median progression-free survival (PFS) was 22 months (95% confidence interval [CI], 15 to ∞ months) with a 6-month PFS of 98% (95% CI, 94% to 100%) and a 12-month PFS of 76% (95% CI, 63% to 92%). Toxicity observed during the study was limited to only six patients. Three patients experienced grade 3 neutropenia, with a duration greater than 3 weeks in one patient, and two patients experienced grade 3 thrombocytopenia. One patient experienced ≥ grade 4 toxicity, with intracerebral hemorrhage, neutropenia, thrombocytopenia, sepsis, and death. Conclusion:Initial results indicate that Temodar may be active in the treatment of low-grade glioma, and thus, further evaluation of this agent in the treatment of these tumors is warranted.
Vaccination With Irradiated Autologous Tumor Cells Engineered to Secrete Granulocyte-Macrophage Colony-Stimulating Factor Augments Antitumor Immunity in Some Patients With Metastatic Non–Small-Cell Lung Carcinoma
Authors: Salgia Ravi , Lynch Thomas , Skarin Arthur , Lucca Joan , Lynch Cathleen , Jung Ken , Hodi F. Stephen , Jaklitsch Michael , Mentzer Steve , Swanson Scott , Lukanich Jean , Bueno Raphael , Wain John , Mathisen Douglas , Wright Cameron , Fidias Panos , Donahue Dean , Clift Shirley , Hardy Steve , Neuberg Donna , Mulligan Richard , Webb Iain , Sugarbaker David , Mihm Martin , Dranoff Glenn 
Published: February 2003

Purpose: We demonstrated that vaccination with irradiated tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates potent, specific, and long-lasting antitumor immunity in multiple murine models and patients with metastatic melanoma. To test whether this vaccination strategy enhances antitumor immunity in patients with metastatic non–small-cell lung cancer (NSCLC), we conducted a phase I clinical trial.Patients and Methods: Resected metastases were processed to single-cell suspension, infected with a replication-defective adenoviral vector encoding GM-CSF, irradiated, and cryopreserved. Individual vaccines consisted of 1 × 106, 4 × 106, or 1 × 107cells, depending on overall yield, and were administered intradermally and subcutaneously at weekly and biweekly intervals.Results: Vaccines were successfully manufactured for 34 (97%) of 35 patients. The average GM-CSF secretion was 513 ng/106cells/24 h. Toxicities were restricted to grade 1 to 2 local skin reactions. Nine patients were withdrawn early because of rapid disease progression. Vaccination elicited dendritic cell, macrophage, granulocyte, and lymphocyte infiltrates in 18 of 25 assessable patients. Immunization stimulated the development of delayed-type hypersensitivity reactions to irradiated, dissociated, autologous, nontransfected tumor cells in 18 of 22 patients. Metastatic lesions resected after vaccination showed T lymphocyte and plasma cell infiltrates with tumor necrosis in three of six patients. Two patients surgically rendered as having no evidence of disease at enrollment remain free of disease at 43 and 42 months. Five patients showed stable disease durations of 33, 19, 12, 10, and 3 months. One mixed response was observed.Conclusion: Vaccination with irradiated autologous NSCLC cells engineered to secrete GM-CSF enhances antitumor immunity in some patients with metastatic NSCLC.
Effect of Lymphatic Mapping on the New Tumor-Node-Metastasis Classification for Colorectal Cancer
Authors: Bilchik Anton J. , Nora Dean T. , Sobin Leslie H. , Turner Roderick R. , Trocha Steven , Krasne David , Morton Donald L. 
Published: February 2003

Purpose: Sensitive detection methods and accurate reporting are necessary to determine the prognostic significance of micrometastases (MM) and isolated tumor cells (ITCs) in lymph nodes that drain colorectal cancers (CRCs). This study examined the role of lymphatic mapping (LM) in the application of the new tumor-node-metastasis (TNM) classification for MM and ITC. Patients and Methods: All patients at the John Wayne Cancer Institute underwent LM immediately before standard resection of primary CRC between 1996 and 2001. Sentinel nodes (SNs) were identified using blue dye and/or radiotracer and were examined by hematoxylin-eosin (H&E) staining, cytokeratin immunohistochemistry, and multilevel sectioning. The comparison group comprised 370 patients whose primary CRCs were resected without LM during the same period at the same institution. Results: LM was successfully performed in 115 of 120 (96%) patients and correctly predicted the tumor status of the nodal basin in 110 of 115 (96%) patients. Thirty-seven patients (32%) were lymph node-positive by H&E; ITC and MM were found in 23 patients (29.4%) whose lymph nodes were negative by H&E. Tumor deposits were found in the SN only in 29 patients (50%). Nodal involvement was identified for 14.3%, 30%, 74.6%, and 83.3% of T1, T2, T3, and T4 tumors, respectively, in the study group, and for 6.8%, 8.5%, 49.3%, and 41.8% of T1, T2, T3, and T4 tumors, respectively, in the comparison group. The study group had a higher percentage of nodal metastases (53% v 36%; P < .01) and a higher incidence of MM and ITC (29.4% v 1.9%; P < .0001). The mean number of lymph nodes found in the study group (14) was also significantly more than the number found in the comparison group (10; P < .00001). Conclusion: Conventional examination of lymph nodes for CRC is inadequate for the detection of MM and ITC as described in the new TNM classification. Thus, LM and focused SN analysis should be considered to fully stage CRC.
Pregnancy Outcome of Partners of Male Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study
Authors: Green Daniel M. , Whitton John A. , Stovall Marilyn , Mertens Ann C. , Donaldson Sarah S. , Ruymann Frederick B. , Pendergrass Thomas W. , Robison Leslie L. 
Published: February 2003

Purpose: This study was undertaken to determine the effect, if any, on pregnancy loss, live births, and birthweight of treatment for cancer diagnosed during childhood or adolescence. Patients and Methods: We reviewed pregnancy outcome among sexually active male Childhood Cancer Survivor Study (CCSS) participants who responded to a questionnaire before February 3, 2000. Medical records of all members of the cohort were abstracted to obtain chemotherapeutic agents administered, the cumulative dose of drug administered for several drugs of interest, and the doses, volumes, and dates of administration of all radiotherapy. Results: There were 4,106 sexually active males; 1,227 reported they sired 2,323 pregnancies (69% live births, 1% stillbirths, 13% miscarriages, 13% abortions, 5% unknown or in gestation). The male-to-female ratio of the offspring of the partners of the male survivors was significantly different from that of the offspring of the partners of the male siblings of the survivors (1.0:1.03 v 1.24:1.0) (P = .016). The proportion of pregnancies of the partners of male survivors that ended with a liveborn infant was significantly lower than for the partners of the male siblings of the survivors who were the control group for comparison (relative risk = 0.77, P = .007). There were no significant differences in pregnancy outcome by treatment. Conclusion: This large study did not identify adverse pregnancy outcomes for the partners of male survivors treated with most chemotherapeutic agents. The reversal of the sex ratio and the association observed for procarbazine warrant further investigation.
Health-Related Quality-of-Life Parameters as Independent Prognostic Factors in Advanced or Metastatic Bladder Cancer
Authors: Roychowdhury D.F. , Hayden A. , Liepa A.M. 
Published: February 2003

Purpose: This retrospective analysis examined prognostic significance of health-related quality-of-life (HRQoL) parameters combined with baseline clinical factors on outcomes (overall survival, time to progressive disease, and time to treatment failure) in bladder cancer. Patients and Methods: Outcome and HRQoL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30) data were collected prospectively in a phase III study assessing gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in locally advanced or metastatic bladder cancer. Prespecified baseline clinical factors (performance status, tumor-node-metastasis staging, visceral metastases [VM], alkaline phosphatase [AP] level, number of metastatic sites, prior radiotherapy, disease measurability, sex, time from diagnosis, and sites of disease) and selected HRQoL parameters (global QoL; all functional scales; symptoms: pain, fatigue, insomnia, dyspnea, anorexia) were evaluated using Cox’s proportional hazards model. Factors with individual prognostic value (P < .05) on outcomes in univariate models were assessed for joint prognostic value in a multivariate model. A final model was developed using a backward selection strategy. Results: Patients with baseline HRQoL were included (364 of 405, 90%). The final model predicted longer survival with low/normal AP levels, no VM, high physical functioning, low role functioning, and no anorexia. Positive prognostic factors for time to progressive disease were good performance status, low/normal AP levels, no VM, and minimal fatigue; for time to treatment failure, they were low/normal AP levels, minimal fatigue, and no anorexia. Global QoL was a significant predictor of outcome in univariate analyses but was not retained in the multivariate model. Conclusion: HRQoL parameters are independent prognostic factors for outcome in advanced bladder cancer; their prognostic importance needs further evaluation.
Hereditary Breast-Ovarian Cancer at the Bedside: Role of the Medical Oncologist
Authors: Lynch Henry T. , Snyder Carrie L. , Lynch Jane F. , Riley Bronson D. , Rubinstein Wendy S. 
Published: February 2003

Purpose: To provide practical considerations for diagnosing, counseling, and managing patients at high risk for hereditary breast cancer. Design: We have studied 98 extended hereditary breast cancer (HBC)/hereditary breast-ovarian cancer (HBOC) families with BRCA1/2 germline mutations. From these families, 1,315 individuals were counseled and sampled for DNA testing. Herein, 716 of these individuals received their DNA test results in concert with genetic counseling. Several challenging pedigrees were selected from Creighton University’s hereditary cancer family registry, as well as one family from Evanston/Northwestern Healthcare, to be discussed in this present report. Results: Many obstacles were identified in diagnosis, counseling, and managing patients at high risk for HBC/HBOC. These obstacles were early noncancer death of key relatives, perception of insurance or employment discrimination, fear, anxiety, apprehension, reduced gene penetrance, and poor compliance. Other important issues such as physician culpability and malpractice implications for failure to collect or act on the cancer family history were identified. Conclusion: When clinical gene testing emerged for BRCA1 and BRCA2, little was known about the efficacy of medical interventions. Potential barriers to uptake of testing were largely unexplored. Identification and referral of high-risk patients and families to genetic counseling can greatly enhance the care of the population at the highest risk for cancer. However, because premonitory physical stigmata are absent in most of these syndromes, an HBOC diagnosis may be missed unless a careful family history of cancer of the breast, ovary, or several integrally associated cancers is obtained.
Barriers to Hospice Care Among Older Patients Dying With Lung and Colorectal Cancer
Authors: McCarthy Ellen P. , Burns Risa B. , Davis Roger B. , Phillips Russell S. 
Published: February 2003

Purpose: To identify factors associated with hospice enrollment and length of stay in hospice among patients dying with lung or colorectal cancer. Methods: We used the Linked Medicare-Tumor Registry Database to conduct a retrospective analysis of the last year of life among Medicare beneficiaries diagnosed with lung or colorectal cancer at age ≥ 66 years between January 1, 1973, and December 31, 1996, in the Surveillance, Epidemiology, and End Results Program who died between January 1, 1988, and December 31, 1998. Our outcomes of interest were time from cancer diagnosis to hospice enrollment and length of stay in hospice care. We used Cox proportional hazards regression to adjust for demographic and clinical information. Results: We studied elderly patients dying with lung cancer (n = 62,117) or colorectal cancer (n = 57,260). Overall, 27% of patients (n = 16,750) with lung cancer and 20% of patients (n = 11,332) with colorectal cancer received hospice care before death. Median length of stay for hospice patients with lung and colorectal cancer was 25 and 28 days, respectively. Overall, 20% of patients entered hospice within 1 week of death, whereas 6% entered more than 6 months before death. Factors associated with later hospice enrollment include being male; being of nonwhite, nonblack race; having fee-for-service insurance; and residing in a rural community. Many of these factors also were associated with shorter stays in hospice. Conclusion: Although use of hospice care has increased dramatically over time, specific patient groups, including men, patients residing in rural communities, and patients with fee-for-service insurance continue to experience delays in hospice enrollment.
Phase III Study of Concurrent Chemoradiotherapy Versus Radiotherapy Alone for Advanced Nasopharyngeal Carcinoma: Positive Effect on Overall and Progression-Free Survival
Authors: Lin Jin-Ching , Jan Jian-Sheng , Hsu Chen-Yi , Liang Wen-Miin , Jiang Rong-San , Wang Wen-Yi 
Published: February 2003

Purpose: Nasopharyngeal carcinoma (NPC) is a radiosensitive and chemosensitive tumor. This randomized phase III trial compared concurrent chemoradiotherapy (CCRT) versus radiotherapy (RT) alone in patients with advanced NPC. Patients and Methods: From December 1993 to April 1999, 284 patients with 1992 American Joint Committee on Cancer stage III to IV (M0) NPC were randomly allocated into two arms. Similar dosage and fractionation of RT was administered in both arms. The investigational arm received two cycles of concurrent chemotherapy with cisplatin 20 mg/m2/d plus fluorouracil 400 mg/m2/d by 96-hour continuous infusion during the weeks 1 and 5 of RT. Survival analysis was estimated by the Kaplan-Meier method and compared by the log-rank test. Results: Baseline patient characteristics were comparable in both arms. After a median follow-up of 65 months, 26.2% (37 of 141) and 46.2% (66 of 143) of patients developed tumor relapse in the CCRT and RT-alone groups, respectively. The 5-year overall survival rates were 72.3% for the CCRT arm and 54.2% for the RT-only arm (P = .0022). The 5-year progression-free survival rates were 71.6% for the CCRT group compared with 53.0% for the RT-only group (P = .0012). Although significantly more toxicity was noted in the CCRT arm, including leukopenia and emesis, compliance with the combined treatment was good. The second cycle of concurrent chemotherapy was refused by nine patients and was delayed for ≥ 1 week for another nine patients. There were no treatment-related deaths in either arm. Conclusion: We conclude that CCRT is superior to RT alone for patients with advanced NPC in endemic areas.
Expression of Aryl Hydrocarbon Receptor and Aryl Hydrocarbon Receptor Nuclear Translocator Messenger Ribonucleic Acids and Proteins in Rat and Human Testis
Authors: Schultz Rüdiger , Suominen Janne , Värre Tanja , Hakovirta Harri , Parvinen Martti , Toppari Jorma , Pelto-Huikko Markku 
Published: February 2003

Dioxins, e.g. 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), use the aryl hydrocarbon receptor (AHR)/aryl hydrocarbon receptor nuclear translocator (ARNT) receptor complex to mediate their toxic actions. In addition to interaction with environmental pollutants, several transcription factors, steroid receptors, and growth factors are capable interacting with the AHR/ARNT complex, which suggests a constitutive role for the receptor complex.The testis has been reported to be among the most sensitive organs to TCDD exposure. Our experiments revealed a complex distribution of AHR and ARNT mRNAs and proteins in rat and human testis. AHR and ARNT immunoreactivities could be detected in the nuclei of interstitial and tubular cells. The incubation of seminiferous tubules in a serum-free culture medium resulted in up-regulation of AHR mRNA, which could be depressed by adding FSH to the culture medium. Furthermore, the incubation of tubular segments with a solution of 1 or 100 nm TCDD resulted in a 2- to 3-fold increase in apoptotic cells. Thus, up-regulation of AHR in cultured tubular segments and consecutive depression by FSH suggest a role for AHR in controlled cell death during spermatogenesis. We suggest that AHR and ARNT mediate effects by direct action on testicular cells in the rat and human testis.
Fatigue strength of PMMA bone cement mixed with gentamicin and barium sulphate vs pure PMMA
Authors: Baleani M , Cristofolini L , Minari C , Toni A 
Published: February 2003

Barium sulphate is added to polymethylmethacrylate (PMMA) bone cement as a radio-pacifier. Gentamicin is an antibiotic added to bone cement to treat or prevent infection in arthroplasty. This study investigated the combined effect of barium sulphate and gentamicin sulphate on the fatigue strength of PMMA bone cement. Three different formulations were studied: pure PMMA, PMMA with barium sulphate added and PMMA with barium sulphate and gentamicin sulphate added. Before testing all specimens were stored in water at 37°C for at least 15 days to season the PMMA and to elute the antibiotic. Fatigue tests were performed following a previously validated procedure. The slope part of the Wöhler diagram was obtained and a rough endurance limit was estimated for all three formulations. The experimental data showed that the addition of barium sulphate to PMMA bone cement affected the fatigue strength of the material, whereas addition of gentamicin sulphate to the radiopaque PMMA had no effect on the fatigue properties of the bone cement. While PMMA with barium sulphate added was confirmed to have a reduced fatigue strength when compared with plain PMMA, no detrimental effect was found for the addition of gentamicin sulphate to radiopaque PMMA.
Higher α-Olefin Polymerization Behavior of a Bis(Phenoxy-Imine)Titanium Complex/i-Bu3Al/Ph3CB(C6F5)4 Catalyst System
Authors: Saito Junji , Suzuki Yasuhiko , Fujita Terunori 
Published: February 2003

Abstract
Catalytic behavior of a bis(phenoxy-imine)Ti complex/i-Bu3Al/Ph3CB(C6F5)4 catalyst system for higher α-olefin polymerization was investigated. The catalyst system exhibited higher activities towards α-olefins having larger molecular sizes and formed ultra-high molecular weight poly(higher α-olefin)s.
Doubly N-Confused Porphyrins as Efficient Sensitizers for Singlet Oxygen Generation
Authors: Araki Koiti , Engelmann Fábio M , Mayer Idemar , Toma Henrique E , Baptista Maurício S , Maeda Hiromitsu , Osuka Atsuhiro , Furuta Hiroyuki 
Published: February 2003

Abstract
The high singlet oxygen quantum yield (ca. 0.8) for the Ag(III) complex of doubly N-confused porphyrin, a potential PDT photosensitizer, was observed according to its favourable intersystem crossing and the triplet lifetime characteristics.
Selective One-pot Synthesis of Facial Tris-ortho-metalated Iridium(III) Complexes Using Microwave Irradiation
Authors: Konno Hideo , Sasaki Yoshiyuki 
Published: February 2003

Abstract
We report on a novel synthesis method for the production of two facial tris-ortho-metalated iridium(III) complexes, fac-[Ir(ppy)3] (1a; ppyH = 2-phenylpyridine) and fac-[Ir(tpy)3] (1b; tpyH = 2-(p-tolyl)pyridine), by the reaction of IrCl3·3H2O with a large excess of the corresponding 2-arylpyridine under microwave irradiation. The method does not require a dehalogenating reagent such as AgCF3SO3, and facial tris-ortho-metalated iridium(III) complexes can be obtained rapidly, selectively and efficiently.