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101.
Expression of senescence-associated beta-galactosidase in enlarged prostates from men with benign prostatic hyperplasia 总被引:8,自引:0,他引:8
Choi J Shendrik I Peacocke M Peehl D Buttyan R Ikeguchi EF Katz AE Benson MC 《Urology》2000,56(1):160-166
OBJECTIVES: Cellular senescence is a unique cellular response pathway thought to be closely associated with the aging process. The senescent phenotype is characterized by the loss of a cell's ability to respond to proliferative and apoptotic stimuli even while normal metabolic activity and vitality is maintained. Recently, a novel biomarker, senescent-associated beta-galactosidase (SA-beta-gal), was found to identify cells with the senescent phenotype. In the present study, we examined whether human prostatic epithelial cells adopt a senescence-associated phenotype after prolonged culture and analyzed a series of human benign prostatic hyperplasia (BPH) specimens to determine whether the cellular senescence process might be a factor in the development of BPH. METHODS: A primary culture of epithelial cells was established from the normal tissue of the peripheral zone of a radical prostatectomy specimen and was serially passaged until senescence. Forty-three human prostate specimens were obtained subsequent to radical prostatectomy or transrectal ultrasound-guided biopsy. The cultured cells and tissue specimens were histochemically stained to reveal the expression of SA-beta-gal, the cellular senescence biomarker. RESULTS: As has been reported for other types of cultured cells, human prostatic epithelial cells demonstrated widespread expression of the cellular senescence marker, SA-beta-gal, on prolonged culture. In our survey of hypertrophied human prostate tissues, 17 specimens (40%) of the 43 analyzed demonstrated positive staining for SA-beta-gal. In these tissues, SA-beta-gal expression was noted only in the epithelial cells. No statistical correlation (P = 0.42) between the chronologic age of the patient donor and SA-beta-gal expression was found. However, a high prostate weight (greater than 55 g) was found to correlate strongly with the expression of the SA-beta-gal biomarker (P = 0. 0001). CONCLUSIONS: Cultured prostatic epithelial cells expressed SA-beta-gal on reaching replicative senescence in vitro. The survey of human BPH specimens for the senescent marker showed that prostatic epithelial cells in patients with BPH with more advanced enlargement of the prostate (greater than 55 g prostate weight) expressed SA-beta-gal, and the prostates from patients with BPH that weighed less than 55 g tended to lack senescent epithelial cells. On the basis of these results, we propose that the accumulation of senescent epithelial cells may play a role in the development of the prostatic enlargement associated with BPH. 相似文献
102.
Dafoe-Lambie JC Abel LJ Blatt HJ Fuscardo JA Stipetich RL Lief JH Dorsey AT Butler WM Benson ML Merrick GS 《The West Virginia medical journal》2000,96(1):357-360
Over the past decade, prostate brachytherapy has been increasingly utilized as definitive management for early stage carcinoma of the prostate gland. One risk of the procedure is pulmonary seed embolization. In this article we report the incidence and timing of seed migration. Pulmonary embolization of radioactive seeds occurs in approximately 20% of patients undergoing prostate brachytherapy. To date, no acute or delayed detrimental effects have been reported which are attributable to the pulmonary embolization of the seeds; nevertheless, it is imperative that patients and health care providers be cognizant of this possible event. 相似文献
103.
Darrell J Gaskin Kevin P Weinfurt Liana D Castel Venita DePuy Yun Li Andrew Balshem Al Benson Caroline B Burnett Sandra Corbett John Marshall Elyse Slater Daniel P Sulmasy David Van Echo Neal J Meropol Kevin A Schulman 《Medical decision making》2004,24(6):614-624
OBJECTIVE: The authors sought to empirically test whether relative health stock, a measure of patients' sense of loss in their health due to illness, influences the treatment decisions of patients facing life-threatening conditions. Specifically, they estimated the effect of relative health stock on advanced cancer patients' decisions to participate in phase I clinical trials. METHOD: A multicenter study was conducted to survey 328 advanced cancer patients who were offered the opportunity to participate in phase I trials. The authors asked patients to estimate the probabilities of therapeutic benefits and toxicity, their relative health stock, risk preference, and the importance of quality of life. RESULTS: Controlling for health-related quality of life, an increase in relative health stock by 10 percentage points reduced the odds of choosing to participate in a phase I trial by 16% (odds ratio = 0.84, 95% confidence interval = 0.72, 0.97). CONCLUSION: Relative health stock affects advanced cancer patients' treatment decisions. 相似文献
104.
105.
Ennis RD Petrylak DP Singh P Bagiella E O'Toole KM Benson MC Olsson CA 《The Journal of urology》2000,163(5):1413-1418
PURPOSE: Trials have demonstrated decreased relapse with perioperative methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) chemotherapy in patients with muscle invasive bladder cancer. We evaluated whether the benefit of chemotherapy correlates with its effects on distant or pelvic relapse. MATERIALS AND METHODS: We retrospectively evaluated the records of all 107 patients who underwent cystectomy for muscle invasive bladder cancer at our institution between 1988 and 1994. Factors predicting relapse were identified and used to group patients at high or low risk. The outcome in each group with and without M-VAC chemotherapy was then analyzed in terms of overall, metastatic and pelvic relapse. Univariate analysis was performed using the Kaplan-Meier method and log rank statistic, and multivariate analysis was done using the Cox proportional hazards model. Median survival was 29 months for patients free of disease. RESULTS: Pathological stage T3 or greater according to the American Joint Committee on Cancer, tumor greater than 3 cm. and creatinine greater than 1.5-fold normal were independent poor prognostic factors in patients treated with cystectomy only. Patients with any of these factors or metastatic involvement of the pelvic lymph nodes were considered at high risk. All 35 low risk patients were treated with cystectomy only and had an excellent outcome with a 3-year relapse-free survival plus or minus standard error of 93% +/- 5%. The 3-year rates in 52 and 20 high risk patients treated without and with chemotherapy, respectively, were 42% +/- 8% versus 57% +/- 13% for relapse-free survival (p = 0.17), 38% +/- 9% versus 8% +/- 8% for pelvic failure (p = 0.02) and 39% +/- 9% versus 38% +/- 13% for distant metastases (not significant). Multivariate analysis of patients who underwent pelvic lymphadenectomy revealed that perioperative chemotherapy improved relapse-free survival and pelvic control but not metastatic control (p = 0.03, 0.02 and 0.31, respectively). CONCLUSIONS: Low risk patients have excellent disease control when treated with cystectomy only. Those with high risk features are at substantial risk for pelvic failure (38% at 3 years) after cystectomy only. Perioperative M-VAC chemotherapy has a profound impact on pelvic but not on metastatic failure. 相似文献
106.
Michael D Benson Hiroshi Kobayashi Lakshman R Sehgal Hidekazu Oi Elaine I Haney 《The journal of maternal-fetal & neonatal medicine》2006,19(1):31-34
OBJECTIVES: To assess the relationship, if any, between complement, fetal antigen, and shaking rigors during labor and delivery. METHODS: We recruited 13 volunteers for serial blood sampling during labor and childbirth. RESULTS: Complement levels had a small but significant drop (11-15%) immediately following childbirth but had no association with fetal antigen levels or shaking rigors. Fetal antigen levels failed to show any consistent relationship with shaking rigors or the labor and delivery process. CONCLUSION: Shaking rigors do not appear to be associated with changes in either complement or fetal antigen levels. Complement levels remain stable during labor but drop immediately following birth. 相似文献
107.
108.
G P H Gui D J Joubert R Reichert A Ward S Lakhani P Osin A Nerurkar R A'Hern K Benson S R Underwood 《European journal of surgical oncology》2005,31(7):707-714
INTRODUCTION: Sentinel lymph node biopsy (SLNB) has become increasingly accepted as a diagnostic method to stage the axilla in breast cancer, selecting women with a positive sentinel node for completion axillary clearance. As SLNB became established, many surgeons supplemented SLNB to sample a minimum of four lymph nodes, on the assumption that the four-node technique is supported by randomised trial data. We hypothesised that the practice of undirected sampling to supplement SLNB adds little information to the status of the residual axilla. METHODS: One hundred and sixty-five patients with early breast cancer were studied. Following successful identification of the sentinel node, 84 women had completion axillary dissection and 81 women had an axillary sample with at least four nodes available for pathological assessment. RESULTS: Following successful identification of the sentinel node in 165 patients, the false negative rate (FNR) was 2/44=4.5% (95% CI 0.6-15.5), sensitivity 42/44=95.5% (84.5-99.4) and negative predictive value (NPV) 121/123=98.4% (94.2-99.8). In the axillary dissection cohort, the FNR was 2/26=7.7% (0.9-25.1), sensitivity 24/26=92.3% (74.9-99.1) and NPV 58/60=96.7% (88.5-100). In the axillary sample group, the FNR was 0/18=0% (0-18.5), sensitivity 18/18=100% (81.5-100) and NPV 63/63=100% (94.3-100). The SLNB was the only positive node in 12/26 (46.2%) in the axillary dissection group and 10/18 (55.6%) in the axillary sampling group. There was no patient in the axillary sampling group where the sample node was positive and the sentinel node negative. CONCLUSION: Once SLNB is validated within the multidisciplinary unit, undirected sampling of the axilla following identification of the sentinel node(s) is unnecessary. The additional sampling of non-sentinel nodes has no role to play either in the assessment of a potential false negative SLNB nor as predictive information on the status of the residual axillary nodes. 相似文献
109.
American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer. 总被引:28,自引:0,他引:28
Gary H Lyman Armando E Giuliano Mark R Somerfield Al B Benson Diane C Bodurka Harold J Burstein Alistair J Cochran Hiram S Cody Stephen B Edge Sharon Galper James A Hayman Theodore Y Kim Cheryl L Perkins Donald A Podoloff Visa Haran Sivasubramaniam Roderick R Turner Richard Wahl Donald L Weaver Antonio C Wolff Eric P Winer 《Journal of clinical oncology》2005,23(30):7703-7720
PURPOSE: To develop a guideline for the use of sentinel node biopsy (SNB) in early stage breast cancer. METHODS: An American Society of Clinical Oncology (ASCO) Expert Panel conducted a systematic review of the literature available through February 2004 on the use of SNB in early-stage breast cancer. The panel developed a guideline for clinicians and patients regarding the appropriate use of a sentinel lymph node identification and sampling procedure from hereon referred to as SNB. The guideline was reviewed by selected experts in the field and the ASCO Health Services Committee and was approved by the ASCO Board of Directors. RESULTS: The literature review identified one published prospective randomized controlled trial in which SNB was compared with axillary lymph node dissection (ALND), four limited meta-analyses, and 69 published single-institution and multicenter trials in which the test performance of SNB was evaluated with respect to the results of ALND (completion axillary dissection). There are currently no data on the effect of SLN biopsy on long-term survival of patients with breast cancer. However, a review of the available evidence demonstrates that, when performed by experienced clinicians, SNB appears to be a safe and acceptably accurate method for identifying early-stage breast cancer without involvement of the axillary lymph nodes. CONCLUSION: SNB is an appropriate initial alternative to routine staging ALND for patients with early-stage breast cancer with clinically negative axillary nodes. Completion ALND remains standard treatment for patients with axillary metastases identified on SNB. Appropriately identified patients with negative results of SNB, when done under the direction of an experienced surgeon, need not have completion ALND. Isolated cancer cells detected by pathologic examination of the SLN with use of specialized techniques are currently of unknown clinical significance. Although such specialized techniques are often used, they are not a required part of SLN evaluation for breast cancer at this time. Data suggest that SNB is associated with less morbidity than ALND, but the comparative effects of these two approaches on tumor recurrence or patient survival are unknown. 相似文献
110.
Mace L Rothenberg Bonnie LaFleur Donna E Levy Mary Kay Washington Sherry L Morgan-Meadows Ramesh K Ramanathan Jordan D Berlin Al B Benson Robert J Coffey 《Journal of clinical oncology》2005,23(36):9265-9274
PURPOSE: The clinical objective of this trial was to evaluate gefitinib in patients with metastatic colorectal cancer that had progressed despite prior treatment. Serial tumor biopsies were performed when possible and analyzed for activation of the epidermal growth factor receptor (EGFR) signaling pathway. Serial serum samples were measured for amphiregulin and transforming growth factor-alpha (TGFalpha). PATIENTS AND METHODS: One hundred fifteen patients were randomly assigned to receive gefitinib 250 or 500 mg orally once a day. One hundred ten patients were assessable for clinical efficacy. Biologic evaluation was performed on paired tumor samples from 28 patients and correlated with clinical outcome. RESULTS: Median progression-free survival was 1.9 months (95% CI, 1.8 to 2.1 months) and 4-month progression-free survival rate was 13% +/- 5%. One patient achieved a radiographic partial response (RR = 1%; 95% CI, 0.01% to 5%). Median survival was 6.3 months (95% CI, 5.1 to 8.2 months). The most common adverse events were skin rash, diarrhea, and fatigue. In the biopsy cohort, expression of total or activated EGFR, activated Akt, activated MAP-kinase, or Ki67 did not decrease following 1 week of gefitinib. However, a trend toward decreased post-treatment levels of activated Akt and Ki67 was observed in patients with a PFS higher than the median, although these did not reach the .05 level of significance. CONCLUSION: Gefitinib is inactive as a single agent in patients with previously treated colorectal cancer. In tumor samples, gefitinib did not inhibit activation of its proximal target, EGFR. Trends were observed for inhibition of downstream regulators of cellular survival and proliferation in patients achieving longer progression-free survival. 相似文献