bluuebunny/crossref_metadata_2025_split huggingface dataset:
Localized Pelvic Neuroblastoma: Excellent Survival and Low Morbidity With Tailored Therapy—The 10-Year Experience of the French Society of Pediatric Oncology
Authors: Leclair Marc-David , Hartmann Olivier , Heloury Yves , Fourcade Laurent , Laprie Anne , Mechinaud Françoise , Munzer Caroline , Rubie Herve 
Published: April 2004

Purpose To assess the results and morbidity of treatment of children with localized pelvic neuroblastoma (NB). Patients and Methods All consecutive cases of localized pelvic NB registered in the French multicenter prospective studies NBL90 and NBL94 between 1990 and 1999 were reviewed. Resectability was decided on the basis of clinical and radiologic evaluation. In unresectable tumors, primary chemotherapy (combinations of carboplatin-etoposide and vincristine-cyclophosphamide-doxorubicine) was administered before surgery. Results Forty-seven children (with 26 resectable tumors and 21 unresectable) were included in this study. At the end of treatment, 31 children were in complete remission (66%). Long-term neurologic sequelae were observed in seven patients (15%), directly attributable to surgery in three cases. After a median follow-up of 48 months (range, 13 to 129 months), 44 patients are alive. Six children experienced local relapse; four of these children achieved subsequent remission. The projected overall survival and event-free survival (EFS) rates at 5 years are, respectively, 93% ± 4% and 84% ± 5%. Survival of children treated with preoperative chemotherapy are similar to those treated by primary surgery (80% and 88% respectively). The extent of surgical resection seemed to have no influence on the outcome (EFS rates 76% and 89% in case of gross residue and complete resection or microscopic residue, respectively). Conclusion Our data confirm the excellent survival of localized pelvic NBs. Considering the efficacy of preoperative chemotherapy, patients with pelvic NB should be carefully screened for primary surgery. The risk of neurologic impairment during radical excision should be balanced with the good survival of children with minimal residual disease.
Individuals With an Increased Risk of Colorectal Cancer: Perceived Benefits and Psychological Aspects of Surveillance by Means of Regular Colonoscopies
Authors: Liljegren A. , Lindgren G. , Brandberg Y. , Rotstein S. , Nilsson B. , Hatschek T. , Jaramillo E. , Lindblom A. 
Published: April 2004

Purpose To evaluate the psychological consequences of genetic counseling followed by a surveillance program using colonoscopy among individuals with increased risk of colorectal cancer. Patients and Methods Two hundred sixty-five individuals, participating in a surveillance program with colonoscopy, were mailed a survey questionnaire that assessed their experience of the surveillance program and their perception of the risk of colorectal cancer. The Hospital Anxiety and Depression scale and the Swedish Short Form-36 Health Survey was also included. Results Two hundred forty individuals completed the questionnaire and were divided into the following risk groups: risk group 1, an individual with a mutation in hMLH1 or hMSH2 and a lifetime colorectal cancer risk of 80% (n = 28); risk group 2, a lifetime colorectal cancer risk of 40% (n = 129); and risk group 3, a lifetime colorectal cancer risk of 20% (n = 83). Among all individuals, the mean for perceived benefit was 8.0, and the perception of discomfort was 3.3 on the visual analog scale (1-10). In risk group 1, 61% underestimated personal risks as being 40% or less. Approximately 50% of the subjects in risk groups 2 and 3 either under- or overestimated their lifetime risk. According to the Swedish Short Form-36 Health Survey and the Hospital Anxiety and Depression scale, the study sample resembled the reference population. Conclusion A majority of the study sample understood why they were under surveillance, and regular colonoscopies were well-tolerated. The wide range of risk perception as well as low-risk perception in mutation positive subjects is acceptable, as long as these individuals adhere to surveillance programs and do not demonstrate increased levels of anxiety or depression.
Incidence of BRCA1 and BRCA2 Mutations in Young Korean Breast Cancer Patients
Authors: Choi Doo Ho , Lee Min Hyuk , Bale Allen E. , Carter Darryl , Haffty Bruce G. 
Published: April 2004

Purpose The prevalence of BRCA-associated breast carcinoma in the Korean population has not been evaluated extensively. Methods Sixty Korean women who developed breast cancer by age 40 years were studied. Lymphocyte specimens from peripheral blood were processed for BRCA1 and BRCA2 by complete sequencing. Family history through three generations was obtained. Available paraffin-embedded tissue blocks were processed for immunohistochemical staining. Results In the cohort of 60 patients, nine patients with 11 deleterious mutations (six in BRCA1 and five in BRCA2) and seven missense mutations of unknown significance were found. Two patients had deleterious mutations in both BRCA1 and BRCA2 (double mutant). One half of the mutations were novel, and no founder mutations were observed in this cohort. Most of the BRCA-associated patients had no family history of breast and/or ovarian cancer. The expression of HER-2/neu, cyclin D1, and hormone receptors was less common, and p53 overexpression was more common in BRCA-associated tumors. Conclusion The prevalence of BRCA1 and BRCA2 mutations in Korean women with breast cancer at a young age was high. However, the penetrance, as evidenced by the low frequency of breast and ovarian cancers in family members, appears to be low. These data suggest that there may be different genetic and etiologic factors affecting transmission and penetrance of the BRCA genes in Korean patients with breast cancer diagnosed at a young age.
Phase II Trial of Trastuzumab Followed by Weekly Paclitaxel/Carboplatin As First-Line Treatment for Patients With Metastatic Breast Cancer
Authors: Burris Howard , Yardley Denise , Jones Suzanne , Houston Gerry , Broome Catherine , Thompson Dana , Greco F. Anthony , White Melissa , Hainsworth John 
Published: April 2004

Purpose To determine the response rate of trastuzumab as first-line therapy in patients with HER-2 overexpressing metastatic breast cancer. To assess the feasibility and toxicity of weekly paclitaxel/carboplatin with or without trastuzumab following initial treatment with trastuzumab. Patients and Methods Sixty-one patients received trastuzumab (8 mg/kg followed by 4 mg/kg/wk) for 8 weeks. Responding patients received 8 additional weeks of trastuzumab (4 mg/kg/wk), and then proceeded to receive trastuzumab (2 mg/kg) in combination with paclitaxel 70 mg/m2 and carboplatin (area under the curve, 2) weekly for 6 weeks followed by 2 weeks rest. Stable patients after the initial 8 weeks of trastuzumab proceeded to treatment with trastuzumab, paclitaxel, and carboplatin. Patients with disease progression during the initial 8 weeks had the trastuzumab discontinued and were treated with weekly paclitaxel/carboplatin. Results Weekly paclitaxel/carboplatin with or without trastuzumab was well tolerated. Fifty-two patients were assessable for response and all 61 patients were assessable for survival. Seventeen (33%) of 52 patients experienced a minor/partial response to single-agent trastuzumab and received 8 additional weeks of single-agent trastuzumab. Fifteen (29%) of 52 patients had stable disease and proceeded to receive paclitaxel/carboplatin/trastuzumab. Thirty-one patients with measurable disease were assessable for response after initial single-agent trastuzumab followed by paclitaxel/carboplatin/trastuzumab. An overall response rate of 84% (eight complete responses/18 partial responses), median time to progression of 14.2 months, and median overall survival of 32.2 months was reported with the triplet combination. In the patients treated with paclitaxel/carboplatin alone after disease progression on initial single-agent trastuzumab, an overall response rate of 69% (one complete response/10 partial responses), median time to progression of 8.3 months, and median overall survival of 22.2 months was reported. Median time to progression for all 61 patients is 10 months and the median overall survival is 26.7 months. Conclusion This trial confirms the activity and tolerability of weekly paclitaxel/carboplatin alone or in combination with trastuzumab in women with HER-2 overexpressing metastatic breast cancer.
Association of Preoperative Plasma Levels of Vascular Endothelial Growth Factor and Soluble Vascular Cell Adhesion Molecule-1 With Lymph Node Status and Biochemical Progression After Radical Prostatectomy
Authors: Shariat Shahrokh F. , Anwuri Veronica A. , Lamb Dolores J. , Shah Nina V. , Wheeler Thomas M. , Slawin Kevin M. 
Published: April 2004

Purpose Angiogenesis is a critical process for cancer progression. We tested whether elevated circulating levels of the angiogenesis-related markers vascular endothelial growth factor (VEGF) and/or soluble vascular cell adhesion molecule-1 (sVCAM-1) are associated with prostate cancer diagnosis, stage, progression, and metastasis. Patients and Methods Plasma levels of VEGF and sVCAM-1 were measured on frozen, archival plasma obtained preoperatively from 215 consecutive patients who underwent radical prostatectomy for clinically localized disease, nine men with untreated prostate cancer metastatic to bones, and 40 healthy men without cancer. Results Plasma levels of both VEGF and sVCAM-1 were highest in patients with bone metastases (P < .001). VEGF levels were higher in patients with clinically localized disease than in healthy controls (P < .001). VEGF levels were elevated in patients with biopsy and final Gleason sum ≥ 7 (P = .036 and P = .020, respectively) and extraprostatic extension (P = .047). Higher preoperative VEGF was independently associated with metastases to lymph nodes (P < .001). Both VEGF and sVCAM-1 were independently associated with biochemical progression after adjustment for the effects of standard preoperative features (P = .014 and P = .039, respectively). VEGF remained independently associated with biochemical progression after adjustment for standard postoperative features (P = .019). Conclusion Plasma levels of VEGF increased incrementally from healthy controls to patients with clinically localized disease to patients with lymph node and skeletal metastases. Higher preoperative VEGF was independently associated with metastases to lymph nodes and biochemical progression after surgery in both pre- and postoperative models. Plasma sVCAM-1 was elevated in men with bone metastases and was associated with biochemical progression in a preoperative model.
Prognostic Value of Proliferation, Apoptosis, Defective DNA Mismatch Repair, and p53 Overexpression in Patients With Resected Dukes' B2 or C Colon Cancer
Authors: Garrity Megan M. , Burgart Lawrence J. , Mahoney Michelle R. , Windschitl Harold E. , Salim Muhammad , Wiesenfeld Martin , Krook James E. , Michalak John C. , Goldberg Richard M. , O'Connell Michael J. , Furth Alfred F. , Sargent Daniel J. , Murphy Linda M. , Hill Eunice , Riehle Darren L. , Meyers Cecelia H. , Witzig Thomas E. 
Published: April 2004

Purpose Molecular studies of colon cancer have provided insights into pathogenesis, yet it is unclear how important these markers are in predicting prognosis. This study investigated the prognostic significance of TUNEL, bcl-2, p53, proliferation marker Ki-67 and DNA mismatch repair (MMR) status in patients with Dukes' stage B2 and C colorectal adenocarcinomas. Patients and Methods Tumor tissue from 366 patients (75% Dukes' C, 25% Dukes' B2) from four randomized North Central Cancer Treatment Group phase III surgical adjuvant trials were used. Eighty-one percent of patients received adjuvant treatment, which was primarily fluorouracil (FU) based (90%). Tumor location was predominantly (87%) the colon. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), Ki-67, p53, bcl-2, and MMR were assayed using immunohistochemistry. Stage, grade, MMR, Ki-67, and previously determined flow cytometry markers (ploidy and S phase) were explored for associations with each other and with overall survival (OS) and disease-free survival (DFS). Results Univariately, stage B2, low grade, diploid, Ki-67 more than 27%, normal p53, and FU-based adjuvant treatment were significantly associated with improved OS and DFS (P < .05). After adjusting for stage, grade, and ploidy in multivariate analysis, Ki-67 remained significantly related to both OS and DFS (P < .01). Active FU-based adjuvant treatment was significant only for OS in this multivariate model. Neither bcl-2 nor TUNEL were significant. Conclusion This retrospective study indicates that Ki-67 and ploidy may have stronger prognostic impact on OS and DFS than other parameters investigated after adjusting for stage and tumor grade. Prospective studies to elucidate the mechanism and prognostic significance of these findings are necessary.
Survivin Expression Predicts Poorer Prognosis in Anaplastic Large-Cell Lymphoma
Authors: Schlette Ellen J. , Medeiros L. Jeffrey , Goy Andre , Lai Raymond , Rassidakis George Z. 
Published: April 2004

Purpose Survivin, a member of the inhibitor of apoptosis (IAP) family, is not detected in normal adult tissues but is overexpressed in various cancers, including some types of lymphoma. The frequency and prognostic significance of survivin expression in anaplastic large-cell lymphoma (ALCL) is unknown. Materials and Methods We assessed for survivin expression in 62 ALCL tumors (30 anaplastic lymphoma kinase [ALK]-positive and 32 ALK-negative) obtained before doxorubicin-based chemotherapy. Given that survivin is a target of the STAT3 signaling pathway and STAT3 is activated in ALCL, survivin expression was also correlated with STAT3 activation. Results Survivin was expressed in 34 tumors (55%) and did not correlate with ALK. A significant association between survivin expression and STAT3 activation was observed (P = .007, Fisher's exact test). For the ALK-positive group, the 5-year failure-free survival (FFS) was 34% for patients with survivin-positive ALCL compared with 100% for patients with survivin-negative ALCL (P = .009, log-rank test). For the ALK-negative group, the 5-year FFS was 46% for patients with survivin-positive tumors compared with 89% for patients with survivin-negative tumors (P = .03, log-rank test). Overall survival was similarly worse for patients with survivin-positive tumors in both the ALK-positive and ALK-negative groups. Furthermore, multivariate analysis confirmed the independent prognostic value of survivin expression, along with age older than 60 years and Ann Arbor stage III or IV. Conclusion Survivin is expressed in approximately half of ALCL tumors and independently predicts unfavorable clinical outcome. Modulation of survivin expression or function may provide a novel target for experimental therapy in patients with ALCL.
First-Line Chemotherapy With Cisplatin Plus Fractionated Temozolomide in Recurrent Glioblastoma Multiforme: A Phase II Study of the Gruppo Italiano Cooperativo di Neuro-Oncologia
Authors: Brandes Alba A. , Basso Umberto , Reni Michele , Vastola Francesca , Tosoni Alicia , Cavallo Giovanna , Scopece Luciano , Ferreri Andres J. , Panucci Maria G. , Monfardini Silvio , Ermani Mario 
Published: April 2004

Purpose Cisplatin and temozolomide (TMZ) are active in glioblastoma multiforme (GBM), with different profiles of toxicity. A bid regimen of TMZ achieves a strong inhibition of O6-alkylguanine DNA-alkyl transferase (AGAT), and cisplatin reduces AGAT activity in vitro, suggesting a possible synergic interaction. The primary end point of the present multicenter phase II study was progression-free survival (PFS) at 6 months (PFS-6); secondary end points included response, toxicity, and overall survival. Patients and Methods Chemotherapy-naive patients with GBM who experienced disease recurrence or progression after surgery and standard radiotherapy were eligible. Chemotherapy cycles consisted of cisplatin 75 mg/m2 on day 1, TMZ 130 mg/m2 bolus followed by nine doses of 70 mg/m2 every 12 hours (total of 5 days) from day 2 every 4 weeks. In the absence of hematologic toxicity, TMZ was escalated to 1,000 mg/m2 in 5 days. Results A total of 50 patients (median age, 53.4 years; range, 27 to 70 years; median Karnofsky performance status, 80; range, 60 to 100) were accrued in the study. PFS-6 was 34% (95% CI, 23% to 50%), and PFS-12 was 4% (95% CI, 0.3% to 16%). Median PFS was 18.4 weeks (95% CI, 13 to 25.9 weeks). Among 49 assessable patients, one complete response and nine partial responses were obtained, with an overall response rate of 20.4% (95% CI, 7.7% to 33%). Among 203 treatment cycles delivered, the most common grade 3 or grade 4 events included granulocytopenia in 7.9% of cycles, thrombocytopenia in 4%, and neurologic toxicity in three patients (6%). Conclusion The new cisplatin plus bid TMZ regimen appears active in chemotherapy-naive patients with recurrent GBM and incurs an acceptable toxicity.
Trypanocidal and antifungal activities of p-hydroxyacetophenone derivatives from Calea uniflora (Heliantheae, Asteraceae)
Authors: do Nascimento Andréa Mendes , Salvador Marcos José , Candido Regina Celia , de Albuquerque Sérgio , de Oliveira Dionéia C. R. 
Published: April 2004

Abstract
The dichloromethane extract of underground parts of Calea uniflora (Heliantheae, Asteraceae) exhibited trypanocidal and antifungal activities. Four p-hydroxyacetophenone derivatives were isolated as the main compounds: 2-senecioyl-4-(hydroxyethyl)-phenol (1), 2-senecioyl-4-(angeloyloxy-ethyl)-phenol (2), and two new derivatives, 2-senecioyl-4-(methoxyethyl)-phenol (3) and 2-senecioyl-4-(pentadecanoyloxyethyl)-phenol (4). 1 and 4 were active towards Trypanosoma cruzi trypomastigotes, reducing their number by 70 and 71% at 500 μg mL−1, whereas 2 and 3 were inactive. All the compounds tested showed antifungal activity with minimal inhibitory concentration values between 500 and 1000 μg mL−1 against pathogenic Candida spp. and dermatophytes. The isolation, structure elucidation, NMR spectral assignments and bioactivity results of these compounds are reported.
Disposition kinetics of taxanes after intraperitoneal administration in rats and influence of surfactant vehicles
Authors: Yokogawa Koichi , Jin Mingji , Furui Naho , Yamazaki Masaru , Yoshihara Hiromi , Nomura Masaaki , Furukawa Hiroyuki , Ishizaki Junko , Fushida Sachio , Miwa Kouichi , Miyamoto Ken-ichi 
Published: April 2004

Abstract
Rats were intraperitoneally administered 40 mg kg−1 of paclitaxel or docetaxel dissolved in various drug solutions. The drug solutions were prepared using 20 mL of saline, adding 4.2% Cremophor EL (crEL) for paclitaxel (TXL), and 1.5% Polysorbate-80 (PS-80) (TXT), 7.5% PS-80 (TXT+PS-80) or 4.2% crEL (TXT+crEL) for docetaxel. The apparent first-order absorption rate constant from the peritoneal cavity (ka) of TXL was about one-twentieth of that of TXT. The ratio of the area under the concentration-time curve of drug in plasma over that in ascites for TXL was about one-third of that of TXT. The values of the above ratio and the ka of TXT+PS-80 and TXT+crEL were similar to those of TXL. After intraperitoneal administration, the values of the blood-to-plasma concentration ratio in the four groups were similar and independent of time. In the in-vitro study, PS-80 and crEL caused similar, concentration-dependent decreases of drug permeation into red blood cells after a 15-min incubation of rat blood with 10 μg mL−1 of TXL. We demonstrated that the disposition kinetics of taxanes after intraperitoneal administration to rats was strongly influenced, in a concentration-dependent manner, by the surfactant vehicle used, crEL or PS-80.
Biodegradable microspheres for prolidase delivery to human cultured fibroblasts
Authors: Lupi A. , Perugini P. , Genta I. , Modena T. , Conti B. , Casado B. , Cetta G. , Pavanetto F. , Iadarola P. 
Published: April 2004

Abstract
Prolidase deficiency (PD) is a rare autosomal recessive disorder caused by inadequate levels of the cytosolic exopeptidase prolidase (E.C. 3.4.13.9), for which there is not, as yet, a resolutive cure. We have investigated whether biodegradable microspheres loaded with prolidase could release active enzyme inside cells, to consider this system as a possible therapeutic approach for prolidase deficiency. Poly(lactide-co-glycolide) microspheres were prepared, modifying the classical double emulsion solvent evaporation method to mitigate the burst effect of the enzyme from the microspheres. Ex-vivo experiments were performed, by incubating microencapsulated prolidase with cultured fibroblasts from PD patients and from controls, to determine the amount of active enzyme delivered to the cells. The microparticulate drug delivery system described carried small amounts of active prolidase inside fibroblasts, ensuring a response to the intracellular accumulation of X-Pro dipeptides, the mechanism that is supposed to be responsible for the development of clinical manifestations of this disorder in man. A positive result of the presence of active enzyme inside cells was an improvement in fibroblast shape.
Owner-occupation, social mix and neighbourhood impacts
Authors: Atkinson Rowland , Kintrea Keith 
Published: April 2004

English
There is interest within the social exclusion debate about the extent to which people in deprived social housing estates are socially isolated and their material disadvantages reinforced by exclusion from job opportunities and inward-looking and negative social norms. One approach to this problem has been the introduction of a social mix through the development of new housing for owneroccupation. Through interviews with and diaries kept by residents in three Scottish estates this article charts residents’ networks and assesses the potential for owner-occupation to ‘reconnect’ existing residents with society beyond the local neighbourhood. The article concludes that owners and renters in regeneration areas largely inhabit different social worlds and that the introduction of owner-occupation makes little difference to renters’ networks. Policy implications include the need to meet the housing aspirations of homeowners in these areas, and the effects of promoting largescale commercial developments based on heavy car use in towns and cities.