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991.
Boron neutron capture therapy (BNCT) for glioblastoma multiforme: A phase II study evaluating a prolonged high-dose of boronophenylalanine (BPA) 总被引:1,自引:0,他引:1
Roger Henriksson Jacek Capala Annika Michanek Sten-ke Lindahl Leif G. Salford Lars Franzn Erik Blomquist Jan-Erik Westlin A. Tommy Bergenheim 《Radiotherapy and oncology》2008,88(2):183-191
BACKGROUND AND PURPOSE: To evaluate the efficacy and safety of boron neutron capture therapy (BNCT) for glioblastoma multiforme (GBM) using a novel protocol for the boronophenylalanine-fructose (BPA-F) infusion. PATIENT AND METHODS: This phase II study included 30 patients, 26-69 years old, with a good performance status of which 27 have undergone debulking surgery. BPA-F (900mg BPA/kg body weight) was given i.v. over 6h. Neutron irradiation started 2h after the completion of the infusion. Follow-up reports were monitored by an independent clinical research institute. RESULTS: The boron-blood concentration during irradiation was 15.2-33.7mug/g. The average weighted absorbed dose to normal brain was 3.2-6.1Gy (W). The minimum dose to the tumour volume ranged from 15.4 to 54.3Gy (W). Seven patients suffered from seizures, 8 from skin/mucous problem, 5 patients were stricken by thromboembolism and 4 from abdominal disturbances in close relation to BNCT. Four patients displayed 9 episodes of grade 3-4 events (WHO). At the time for follow-up, minimum ten months, 23 out of the 29 evaluable patients were dead. The median time from BNCT treatment to tumour progression was 5.8 months and the median survival time after BNCT was 14.2 months. Following progression, 13 patients were given temozolomide, two patients were re-irradiated, and two were re-operated. Patients treated with temozolomide lived considerably longer (17.7 vs. 11.6 months). The quality of life analysis demonstrated a progressive deterioration after BNCT. CONCLUSION: Although, the efficacy of BNCT in the present protocol seems to be comparable with conventional radiotherapy and the treatment time is shorter, the observed side effects and the requirement of complex infrastructure and higher resources emphasize the need of further phase I and II studies, especially directed to improve the accumulation of (10)B in tumour cells. 相似文献
992.
A phase I study of dose-escalated chemoradiation with accelerated intensity modulated radiotherapy in locally advanced head and neck cancer. 总被引:1,自引:0,他引:1
Teresa Guerrero Urbano Catharine H Clark Vibeke N Hansen Elizabeth J Adams Roger A'Hern Elizabeth A Miles Helen McNair Margaret Bidmead Alan P Warrington David P Dearnaley Kevin J Harrington Christopher M Nutting 《Radiotherapy and oncology》2007,85(1):36-41
BACKGROUND AND PURPOSE: Intensity modulated radiotherapy (IMRT) allows the delivery of higher and more homogeneous radiation dose to head and neck tumours. This study aims to determine the safety of dose-escalated chemo-IMRT for larynx preservation in locally advanced head and neck cancer. METHODS: Patients with T2-4, N1-3, M0 squamous cell carcinoma of the larynx or hypopharynx were treated with a simultaneous-boost IMRT. Two radiation dose levels (DL) were tested: In DL 1, 63 Gy/28F was delivered to primary tumour and involved nodes and 51.8 Gy/28F to elective nodes. In DL 2, the doses were 67.2 Gy/28F and 56 Gy/28F, respectively, representing a 9% dose escalation for the primary. All patients received 2 cycles of neoadjuvant cisplatin and 5-fluorouracil, and concomitant cisplatin. Acute (NCICTCv.2.0) and late toxicity (RTOG and modified LENTSOM) were collected. RESULTS: Thirty patients were entered, 15 in each dose level. All patients completed the treatment schedule. In DL 1, the incidences of acute G3 toxicities were 27% (pain), 20% (radiation dermatitis), 0% (xerostomia) and 67% required gastrostomy tubes. For DL 2 the corresponding incidences were 40%, 20%, 7%, and 87%. G3 dysphagia and pain persisted longer in DL 2. With regard to mucositis, a prolonged healing time for DL 2 was found, with prevalence of G2 of 58% in week 10. No acute grade 4 toxicity was observed. At 6 months, 1 patient in DL 2 had G3 late toxicity (dysphagia). No dose limiting toxicity was found. Complete response rates were 80% in DL 1, and 87% in DL 2. CONCLUSION: Moderately accelerated chemo-IMRT is safe and feasible with good compliance and acceptable acute toxicity. Dose escalation was possible without a significant difference in acute toxicity. Longer follow-up is required to determine the incidence of late radiation toxicities, and tumour control rates. 相似文献
993.
Morgan Rouprêt Vincent Hupertan David R Yates James W F Catto Ishtiaq Rehman Mark Meuth Sylvie Ricci Roger Lacave Géraldine Cancel-Tassin Alexandre de la Taille Fran?ois Rozet Xavier Cathelineau Guy Vallancien Freddie C Hamdy Olivier Cussenot 《Clinical cancer research》2007,13(6):1720-1725
PURPOSE: The diagnosis of localized prostate cancer is difficult due to a lack of cancer-specific biomarkers. Many patients require repeat prostate biopsies to diagnose the disease. We investigated whether aberrant promoter hypermethylation in prostatic fluid could reliably detect prostate cancer. EXPERIMENTAL DESIGN: Urine samples were collected after prostate massage from 95 patients with localized prostate cancer undergoing radical prostatectomy (63 pT(1), 31 pT(2), and 1 pT(3)) and from 38 control patients. Ten genes (GSTP1, RASSF1a, ECDH1, APC, DAPK, MGMT, p14, p16, RARbeta2, and TIMP3) were investigated using quantitative real-time methylation-specific PCR. Receiver operator curves were generated. RESULTS: The frequency of gene methylation ranged from 6.3% (p14) to 83.2% (GSTP1) in prostate cancer patients. At least one gene was hypermethylated in 93% of cancer patients. The specificity of methylation was 0.74. Methylation was significantly more frequent (P < 0.05) in cancer than control patients for all genes except p14 and p16. According to receiver operator curve analysis, the four-gene combination of GSTP1 (0.86), RASSF1a (0.85), RARbeta2 (0.80), and APC (0.74) best discriminated malignant from nonmalignant cases. The sensitivity and accuracy of this four-gene set were 86% and 89%, respectively. CONCLUSIONS: The presence of aberrant methylation in urinary cells obtained after prostate massage is significantly associated with prostate cancer. A panel of four genes could stratify patients into low and high risk of having prostate cancer and optimize the need for repeat prostatic biopsies. 相似文献
994.
995.
Mutational analysis of a highly conserved proline residue in MRP1, MRP2, and MRP3 reveals a partially conserved function. 总被引:1,自引:0,他引:1
Isabelle J Létourneau Andrew J Slot Roger G Deeley Susan P C Cole 《Drug metabolism and disposition》2007,35(8):1372-1379
The ATP-binding cassette multidrug resistance protein 1 MRP1 (ABCC1) mediates the cellular efflux of organic anions including conjugated metabolites, chemotherapeutic agents, and toxicants. We previously described a mutation in cytoplasmic loop 7 (CL7) of MRP1, Pro1150Ala, which reduced leukotriene C(4) (LTC(4)) transport but increased 17beta-estradiol 17beta-d-glucuronide (E(2)17betaG) and methotrexate (MTX) transport. Vanadate-induced trapping of [alpha-(32)P]8N(3)ADP by the Pro1150Ala mutant in the absence of substrate was also greatly reduced compared with wild-type MRP1 suggesting an uncoupling of ATP hydrolysis and transport activity. To determine whether the functional importance of MRP1-Pro(1150) is conserved, the analogous Pro(1158) and Pro(1147) residues in the MRP2 and MRP3 transporters, respectively, were mutated to Ala. Expression levels of the three mutants were unaffected; however, the vesicular transport activity of at least one organic anion substrate was significantly altered. As observed for MRP1-Pro1150Ala, LTC(4) transport by MRP2-Pro1158Ala was decreased. However, E(2)17betaG and MTX transport was comparable with that of wild-type MRP2 rather than increased as was observed for MRP1-Pro1150Ala. In the case of MRP3-Pro1147Ala, LTC(4) transport was increased, whereas E(2)17betaG transport was unaffected. MTX transport by MRP3-Pro1147Ala was also increased but to a lesser extent than for MRP1-Pro1150Ala. In contrast, all three mutants showed a marked reduction in levels of vanadate-induced trapped [alpha-(32)P]8N(3)ADP. We conclude that MRP1-Pro(1150), MRP2-Pro(1158), and MRP3-Pro(1147) in CL7 differ in their influence on substrate specificity but share a common role in the nucleotide interactions of these transporters. 相似文献
996.
[目的]了解艾滋病综合防治示范区和非示范区群众艾滋病自愿咨询检测相关的知识、态度和经历,为开展艾滋病自愿咨询检测项目提供依据。[方法]采用与规模大小成比例(PPS)的两阶段抽样法在示范区和非示范区分别抽取了500名和512名居民,由调查员对调查对象进行一对一的问卷调查。[结果]示范区和非示范区普通群众对艾滋病自愿咨询检测的认识水平不高,态度有待转变,有过艾滋病检测和咨询经历的人很少。[结论]应进一步加大针对艾滋病和自愿咨询检测的宣传力度,采取多种模式共存的检测与咨询策略,以更多地发现感染者。 相似文献
997.
998.
Denise D Walker Roger A Roffman Joseph F Picciano Robert S Stephens 《Substance abuse treatment, prevention, and policy》2007,2(1):2
Countless barriers come between people who are struggling with substance abuse and those charged with providing substance
abuse treatment. The check-up, a form of motivational enhancement therapy, is a harm reduction intervention that offers a
manner of supporting individuals by lowering specific barriers to reaching those who are untreated. The check-up was originally
developed to reach problem drinkers who were neither seeking treatment nor self-initiating change. The intervention, marketed
as an opportunity to take stock of one's experiences, involves an assessment and personalized feedback delivered with a counseling
style termed motivational interviewing. Check-ups can be offered in care settings to individuals who, as a result of screening,
manifest risk factors for specific disorders such as alcoholism. They can also be free-standing and publicized widely to the
general public. This paper will discuss illustrations of in-person, computerized, in-school, and telephone applications of
the free-standing type of check-up with reference to alcohol consumers, adult and adolescent marijuana smokers, and gay/bisexual
males at risk for sexual transmission of HIV. The paper's major focus is to highlight how unique features of each application
have the potential of reducing barriers to reaching specific at-risk populations. Also considered are key policy issues such
as how check-up services can be funded, which venues are appropriate for the delivery of check-up interventions, pertinent
competency criteria in evaluating staff who deliver this intervention, how marketing can be designed to reach contemplators
in untreated at-risk populations, and how a check-up's success ought to be defined. 相似文献
999.
Raffaella Villa Maria Grazia Daidone Rosita Motta Lorenza Venturini Cinzia De Marco Alberto Vannelli Shigeki Kusamura Dario Baratti Marcello Deraco Aurora Costa Roger R Reddel Nadia Zaffaroni 《Clinical cancer research》2008,14(13):4134-4140
PURPOSE: This study aims to investigate the prevalence of the two known telomere maintenance mechanisms, telomerase activity (TA) and alternative lengthening of telomeres (ALT), and to assess their prognostic relevance in diffuse malignant peritoneal mesothelioma (DMPM). EXPERIMENTAL DESIGN: In 44 DMPM specimens obtained from 38 patients, TA was determined using the telomeric repeat amplification protocol and ALT was detected by assaying ALT-associated promyelocytic leukemia nuclear bodies. The prognostic significance of telomere maintenance mechanisms was analyzed by Cox regression in the overall series and in a subset of 29 patients who underwent a uniform treatment regimen consisting of cytoreductive surgery and hyperthermic i.p. chemotherapy. RESULTS: Telomere maintenance mechanisms were detectable in 86.4% of DMPM: ALT or TA alone was found in 18.2% or 63.6% of lesions, respectively, whereas two cases (4.6%) were ALT+/TA+. TA and ALT proved to be inversely associated (P = 0.002). In the overall series, TA was prognostic for 4-year relapse (TA+ versus TA-, hazard ratio, 3.30; 95% confidence interval, 1.23-8.86; P = 0.018) and cancer-related death (TA+ versus TA-, hazard ratio, 3.56; 95% confidence interval, 1.03-12.51; P = 0.045), whereas ALT failed to significantly affect clinical outcome. These results held true also in the subset of patients submitted to uniform treatment with cytoreductive surgery and hyperthermic i.p. chemotherapy. CONCLUSIONS: Our results indicate that both known telomere maintenance mechanisms, TA and ALT, are present in DMPM and differentially affect patient prognosis. 相似文献
1000.
Sbastien Salas Jean-Laurent Deville Roch Giorgi Thierry Pignon Danielle Bagarry Karine Barrau Michel Zanaret Antoine Giovanni Aude Bourgeois Roger Favre Florence Duffaud 《Radiotherapy and oncology》2008,87(2):195-200
BACKGROUND AND PURPOSE: This study sought to evaluate nutritional prognostic factors before treatment in patients with unresectable head and neck cancer treated by concomitant radio-chemotherapy. METHODS AND MATERIALS: Seventy-two consecutive patients were treated. We studied the potential effects of CRP, Alb, preAlb, orosomucoid, weight, weight history, BMI, PINI, OPR and NRI on response to treatment, Event-Free Survival (EFS) and Overall Survival (OS). Effects of potential risk factors on OS and on EFS were analyzed by computing Kaplan-Meier estimates, and curves were compared using the log-rank test. RESULTS: All biological nutritional factors were statistically correlated with the response to radio-chemotherapy. In multivariate analysis, only CRP (p=0.004) remained statistically significant. A statistical correlation was found between Alb and EFS in multivariate analysis (p=0.04). The factors influencing OS in univariate analysis were Alb (p=0.008), CRP (p=0.004), orosomucoid (p=0.01) and NRI (p=0.01), response to radio-chemotherapy (p<0.001) and staging (p=0.04). In multivariate analysis, only the response to radio-chemotherapy (p<0.001) remained significant. CONCLUSIONS: This study illustrates the prognostic value of nutritional status. CRP and Alb may be useful in the assessment of advanced head and neck cancer patients at diagnosis and for stratifying patients taking part in randomized trials. 相似文献