首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 15 毫秒
1.

Introduction

Tissue cryoablation is a potential curative option for solid malignancies, including radiation recurrent prostate cancer (RRPC). Case series of salvage cryotherapy (SCT) in RRPC have reported promising disease free survival (DFS) outcomes and acceptable toxicity profile. While many men receive SCT, no predictive factors for treatment induced side effects are known. The aim of this study is to validate the oncologic outcome of SCT in a large multi-centre patient cohort and to identify potential parameters associated with an increased risk of micturition symptoms.

Patients and Methods

In this retrospective analysis, we studied 283 consecutive patients with RRPC treated by SCT in three independent U.K. centres (between 2001 and 2011). Two freeze-thaw cycles of transperineal cryotherapy were performed under transrectal ultrasound guidance by a single surgeon in each of the 3 sites. We analysed clinico-pathological factors against tumour response. Functional outcomes were assessed by continence status and IPSS questionnaire. Predictive factors for SCT-induced micturition symptoms were analysed in a sub-group (n = 42) of consecutive cases.

Results

We found that nadir post-SCT PSA levels strongly associated with DFS. The DFS rates at 12- and 36-month were 84% and 67% for the ≤1 ng/ml group and 56% and 14% for the >1 ng/ml group, respectively (p<0.001). Correlative analysis revealed highly significant association between patients'' post-SCT micturition status with prostate gland and iceball lengths following SCT. Finally, in a reduction model, both gland length and maximal length of iceball were highly associated with patients'' IPSS outcome (p<0.001).

Conclusion

We report the largest European patient cohort treated with SCT for RRPC. Oncologic outcome guided by nadir PSA of <1 ng/ml is consistent with earlier single-centre series. For the first time, we identified physical parameters to predict micturition symptoms following SCT. Our data will directly assist on-going and future trial design in cryotherapy in prostate cancer.  相似文献   

2.

Purpose

Accurate analysis of the correlation between deformation of the prostate and displacement of its center of gravity (CoG) is important for efficient radiation therapy for prostate cancer. In this study, we addressed this problem by introducing a new analysis approach.

Method

A planning computed tomography (CT) scan and 7 repeat cone-beam CT scans during the course of treatment were obtained for 19 prostate cancer patients who underwent three-dimensional conformal radiation therapy. A single observer contoured the prostate gland only. To evaluate the local deformation of the prostate, it was divided into 12 manually defined segments. Prostate deformation was calculated using in-house developed software. The correlation between the displacement of the CoG and the local deformation of the prostate was evaluated using multiple regression analysis.

Results

The mean value and standard deviation (SD) of the prostate deformation were 0.6 mm and 1.7 mm, respectively. For the majority of the patients, the local SD of the deformation was slightly lager in the superior and inferior segments. Multiple regression analysis revealed that the anterior-posterior displacement of the CoG of the prostate had a highly significant correlation with the deformations in the middle-anterior (p < 0.01) and middle-posterior (p < 0.01) segments of the prostate surface (R2 = 0.84). However, there was no significant correlation between the displacement of the CoG and the deformation of the prostate surface in other segments.

Conclusion

Anterior-posterior displacement of the CoG of the prostate is highly correlated with deformation in its middle-anterior and posterior segments. In the radiation therapy for prostate cancer, it is necessary to optimize the internal margin for every position of the prostate measured using image-guided radiation therapy.  相似文献   

3.
4.
Although endothelial cell apoptosis participates in the tumor shrinkage after single high-dose radiotherapy, little is known regarding the vascular response after conventionally fractionated radiation therapy. Therefore, we evaluated hypoxia, perfusion and vascular microenvironment changes in an orthotopic prostate cancer model of conventionally fractionated radiation therapy at clinically relevant doses (2 Gy fractions, 5 fractions/week). First, conventionally fractionated radiation therapy decreased tumor cell proliferation and increased cell death with kinetics comparable to human prostate cancer radiotherapy. Secondly, the injection of Hoechst 33342 or fluorescent-dextrans showed an increased tumor perfusion within 14 days in irradiated tumors, which was correlated with a clear reduction of hypoxia. Improved perfusion and decreased hypoxia were not explained by increased blood vessel density, size or network morphology. However, a tumor vascular maturation defined by perivascular desmin+/SMA+ cells coverage was clearly observed along with an increase in endothelial, zonula occludens (ZO)-1 positive, intercellular junctions. Our results show that, in addition to tumor cell killing, vascular maturation plays an uncovered role in tumor reoxygenation during fractionated radiation therapy.  相似文献   

5.

Background

In prostate cancer, tumour expression of cannabinoid CB1 receptors is associated with a poor prognosis. One explanation for this association comes from experiments with transfected astrocytoma cells, where a high CB receptor expression recruits the Akt signalling survival pathway. In the present study, we have investigated the association between CB1 receptor expression and the Akt pathway in a well-characterised prostate cancer tissue microarray.

Methodology/Principal Findings

Phosphorylated Akt immunoreactivity (pAkt-IR) scores were available in the database. CB1 receptor immunoreactivity (CB1IR) was rescored from previously published data using the same scale as pAkt-IR. There was a highly significant correlation between CB1IR and pAkt-IR. Further, cases with high expression levels of both biomarkers were much more likely to have a more severe form of the disease at diagnosis than those with low expression levels. The two biomarkers had additive effects, rather than an interaction, upon disease-specific survival.

Conclusions/Significance

The present study provides data that is consistent with the hypothesis that at a high CB1 receptor expression, the Akt signalling pathway becomes operative.  相似文献   

6.
Despite continuing research and the development of alternate therapeutic options, prostate cancer remains problematic. Chemotherapy has played a minor role as a treatment option due to its lack of efficacy. Whereas cryotherapy has received renewed attention as a treatment modality, it too fails to offer an absolute curative option. Previously, we reported on the utilization of a therapeutic model, which, in combination, increases cell death in a canine renal cell model. Based upon that study, we investigated a combination therapy model as an alternative for the treatment modality for prostate cancer. We hypothesized that the combination of chemotherapy and cryosurgery would result in enhanced cell death, thereby presenting a more effective treatment of prostate cancer. A human prostate cancer cell (PC-3) model was exposed to 5-fluorouracil (5-FU) for 2 and 4 days (prefreeze), freezing (-5 to -100 degrees C), or a combination of the two treatments, and each was assessed for effectiveness over a 2-week posttreatment period. Additionally, investigation into the mechanisms of cell death initiated by the respective therapies was performed through DNA cleavage analysis. For chemotherapy, cultures exposed to 5-FU (2-4 days) yielded a 15-25% loss in cell survival. For cryotherapy, cultures exposed to a temperature window of -5 to -20 degrees C yielded an initial 5-70% loss of viability but cells propagated over time. Cultures exposed to temperatures of -25 to -80 degrees C yielded a 90-99% (+/-4.5%) initial loss in viability with repopulation observed by 12 days postthaw. Cells frozen to -100 degrees C yielded 100% (+/-0.3%) loss of viability and exhibited no signs of propagation. For chemo-cryo therapy, combination treatment at milder temperatures (-5 to -25 degrees C) resulted in an enhanced loss of cell viability compared to that for either treatment alone. Combination treatment at lower temperatures (-40 to -80 degrees C) resulted in a complete loss of cell viability. DNA fragmentation analysis at 48 h posttreatment revealed that dead (detached) cells treated with 5-FU died primarily through apoptosis, whereas dead cells from freezing (-15 degrees C) alone died primarily through freeze-rupture and necrosis. Detached cell analysis from combination treatment at -15 degrees C revealed the presence of apoptotic, necrotic, and freeze-rupture cell death. Scanning electron micrographs of cells exposed to freezing contributing to cell death. These data demonstrate that the combination of 5-FU at sublethal doses and freezing temperatures improves human prostate cancer cell death efficacy. Further, we suggest that chemo-cryo therapy offers a potential alternative treatment for the control and eradication of prostate cancer.  相似文献   

7.
8.

Objectives

The aim of this study was to investigate the expression of two commonly altered genes ERG and PTEN in prostate cancer (PC) and evaluate their prognostic significance. Despite conflicting published results, TMPRSS2-ERG gene fusion and PTEN loss are generally considered unfavorable markers for PC progression.

Materials and Methods

Of the 762 prostatic adenocarcinoma specimens obtained from radical prostatectomy, 613 without neoadjuvant hormone therapy were included in tissue microarrays for quantitatively assessment of ERG and PTEN expression via immunohistochemistry. Statistical analysis of the association between such expression and clinicopathological parameters, including clinical prognosis, was performed with a p-value of <0.05 considered significant.

Results

During a median follow-up period of 44.0 months, 132 (21.5%) patients developed biochemical recurrence (BCR). ERG overexpression and PTEN loss were observed in 145 (23.7%) and 253 (41.3%) cases, respectively. BCR-free survival was significantly better in patients with ERG overexpression (p=0.005), but unfavorable among those with PTEN loss (p=0.142). Sub-group analysis revealed that patients with PTEN loss and negative ERG expression had the worst BCR-free survival outcome (p=0.021). Furthermore, multivariate analysis identified prostate-specific antigen level (≥10 ng/mL), Gleason score (>6), pathologic T stage (≥T3), positive surgical margin, and extraprostatic capsule extension as significant risk factors for BCR (p<0.05).

Conclusions

Our results indicated that ERG overexpression was associated with favorable BCR-free survival after radical prostatectomy for PC, whereas PTEN loss was with unfavorable outcomes.  相似文献   

9.
Radiation therapy (RT) continues to be one of the most popular treatment options for localized prostate cancer (CaP). The purpose of the study was to investigate the in vitro effect of LBH589 alone and in combination with RT on the growth and survival of CaP cell lines and the possible mechanisms of radiosensitization of this combination therapy. The effect of LBH589 alone or in combination with RT on two CaP cell lines (PC-3 and LNCaP) and a normal prostatic epithelial cell line (RWPE-1) was studied by MTT and clonogenic assays, cell cycle analysis, western blotting of apoptosis-related and cell check point proteins, and DNA double strand break (DSB) repair markers. The immunofluorescence staining was used to further confirm DSB expression in treated CaP cells. Our results indicate that LBH589 inhibited proliferation in both CaP and normal prostatic epithelial cells in a time-and-dose-dependent manner; low-dose of LBH589 (IC20) combined with RT greatly improved efficiency of cell killing in CaP cells; compared to RT alone, the combination treatment with LBH589 and RT induced more apoptosis and led to a steady increase of sub-G1 population and abolishment of RT-induced G2/M arrest, increased and persistent DSB, less activation of non-homologous end joining (NHEJ)/homologous recombination (HR) repair pathways and a panel of cell cycle related proteins. These results suggest that LBH589 is a potential agent to increase radiosensitivity of human CaP cells. LBH589 used either alone, or in combination with RT is an attractive strategy for treating human CaP.  相似文献   

10.
Manganese superoxide dismutase (MnSOD) is the most effective antioxidant enzyme in mitochondria and protects cells from reactive oxygen species‐induced oxidative damage. The aim of this study was to investigate the association between MnSOD Ala‐9Val gene polymorphism and prostate cancer (PCa) risk in Turkish men with prostate cancer. 33 patients with PCa and 81 control individuals were included in the study. We observed an association between MnSOD Ala/Ala frequency and a higher PCa risk. In addition, we found that the increased risk of early‐onset PCa (under age of 65) in the men homozygous for Ala allele was higher than the men homozygous for Val allele. However, we determined that MnSOD Ala‐9Val genotype was not associated with the aggressiveness of the disease. The results of our study suggest that MnSOD Ala/Ala genotype may influence on early‐onset of PCa patients, but no effect on subsequent development of the disease in Turkish men. However, our study has a limitation that is small numbers of individuals for cases and controls. Therefore, the presented study limited our statistical power to fully investigate the gene polymorphism on cancer risk. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:213‐218, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.21472  相似文献   

11.
《Epigenetics》2013,8(4):183-186
Up to 30% of men with clinically localized disease who receive radical prostatectomy develop a biochemical recurrence. Gene methylation in tumor tissue may distinguish men with aggressive cancer. This study evaluated methylation of GSTP1, RARβ2, CD44 and PTGS2 with biochemical recurrence among 60 patients who underwent radical prostatectomy using logistic regression and Kaplan Meier time to event analysis. Methylation of GSTP1 and RARβ2 was not associated with recurrence, however, CD44 and PTGS2 methylation were significant predictors. In multivariate models adjusting for Gleason grade, methylation profile of CD44 and PTGS2 combined was an independent predictor of biochemical recurrence (associated with 9-fold increased risk). In addition, Kaplan Meier analysis showed CD44 and PTGS2 methylation was associated with shorter time to recurrence. CD44 and PTGS2 methylation may predict biochemical recurrence in prostate cancer patients undergoing radical prostatectomy and if validated in larger studies, may identify patients with aggressive cancer.  相似文献   

12.

Background

No meta-analysis is yet available for the risk of metabolic syndrome (MetS) following androgen deprivation therapy (ADT) for men with prostate cancer. To summarize the evidence for the link between ADT and MetS or its components quantitatively with a meta-analysis including all studies published to date.

Methods

PubMed and Embase were searched using predefined inclusion criteria to perform meta-analyses on the association between metabolic syndrome, hyperglycemia, diabetes, hypertension, dyslipidemia or obesity and androgen deprivation therapy in patients with prostate cancer. Random effects methods were used to estimate pooled relative risks (RRs) and 95% confidence intervals (CI).

Results

A total of nine studies was included. There was a positive association between ADT and risk of MetS (RR: 1.75 (95% CI: 1.27–2.41)). Diabetes was the only MetS component present in more than 3 studies, and also showed an increased risk following ADT (RR: 1.36 (95% CI: 1.17–1.58)).

Conclusion

This is the first quantitative summary addressing the potential risk of MetS following ADT in men with PCa. The positive RRs indicate that there is a need to further elucidate how type and duration of ADT affect these increased risks of MetS and diabetes as the number of men with PCa treated with ADT is increasing.  相似文献   

13.
PurposeTo evaluate the influence of timing of salvage and adjuvant radiation therapy on outcomes after prostatectomy for prostate cancer.MethodsUsing the Surveillance, Epidemiology, and End Results-Medicare linked database, we identified prostate cancer patients diagnosed during 1995–2007 who had one or more adverse pathological features after prostatectomy. The final cohort of 6,137 eligible patients included men who received prostatectomy alone (n = 4,509) or with adjuvant (n = 894) or salvage (n = 734) radiation therapy. Primary outcomes were genitourinary, gastrointestinal, and erectile dysfunction events and survival after treatment(s).ResultsRadiation therapy after prostatectomy was associated with higher rates of gastrointestinal and genitourinary events, but not erectile dysfunction. In adjusted models, earlier treatment with adjuvant radiation therapy was not associated with increased rates of genitourinary or erectile dysfunction events compared to delayed salvage radiation therapy. Early adjuvant radiation therapy was associated with lower rates of gastrointestinal events that salvage radiation therapy, with hazard ratios of 0.80 (95% CI, 0.67–0.95) for procedure-defined and 0.70 (95% CI, 0.59, 0.83) for diagnosis-defined events. There was no significant difference between ART and non-ART groups (SRT or RP alone) for overall survival (HR = 1.13 95% CI = (0.96, 1.34) p = 0.148).ConclusionsRadiation therapy after prostatectomy is associated with increased rates of gastrointestinal and genitourinary events. However, earlier radiation therapy is not associated with higher rates of gastrointestinal, genitourinary or sexual events. These findings oppose the conventional belief that delaying radiation therapy reduces the risk of radiation-related complications.  相似文献   

14.
Focal therapy has been proposed in recent years as a means of bridging the gap between radical prostatectomy and active surveillance for treatment of prostate cancer. The rationale for focal therapy comes from its success in treating other malignancies. One of the challenges in applying such an approach to the treatment of prostate cancer has been the multifocal nature of the disease. This review addresses the selection of potentially ideal candidates for focal therapy and discusses which modalities are currently being used and proposed for focal therapy. Setting and meeting guidelines for oncologic efficacy is a challenge we must embrace to safely deliver this potentially revolutionary approach to treating men with prostate cancer.Key words: Focal therapy, Photodynamic therapy, Prostatic neoplasms, Prostate-specific antigen, Prostatectomy, Ultrasound, high-intensity focused, transrectal, CryosurgeryWith the advent of prostate-specific antigen (PSA) screening there has been a stage migration, with radical prostatectomy (RP) being performed with increasing frequency in men with low-risk disease.1 Whole gland treatment of prostate cancer carries a significant risk of incontinence and sexual dysfunction. Even in the most experienced centers, the rate of potency following RP is approximately 60%.24 Stage migration has led many to recommend active surveillance (AS) as a means to decrease the number of men who may be overtreated; however, AS has been slow to gain acceptance in the United States.An analysis of over 5300 men from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) National Prostate Cancer Registry5 showed that only 7% of men with clinically localized prostate cancer chose AS as an initial option. Aside from the anxiety that stems from not treating a diagnosed cancer, the greater difficulty with AS lies in selection of candidates and appropriate parameters for surveillance, allowing prompt intervention without compromising cure rates.Focal therapy has been proposed in recent years as a means of bridging the gap between whole gland treatment and AS. Many believe that for patients with low-risk disease, focal therapy is the ideal option for maximizing quality of life by avoiding the effects of whole gland radiation or surgery while alleviating the anxiety and uncertainty of AS. The definition of focal therapy itself is not well established and includes lesion-targeted therapy (LAT), hemiablative therapy (HAT), or subtotal gland therapy (STAT), sparing at least 1 neurovascular bundle.6The rationale for focal therapy comes from its success in treating other malignancies. In breast cancer treatment, for example, radical mastectomy has been replaced in many instances by local excision and Mohs surgery has led to less radical surgery for the treatment of melanoma.7 In our own field, the push for nephron-sparing surgery has led to the favoring of partial nephrectomy in tumors less than 7 cm, with oncologic outcomes similar to those of radical nephrectomy.8The challenge in applying such an approach to the treatment of prostate cancer has been the multifocal nature of prostate cancer and the fact that most cancers are detected without identifying a lesion on palpation or imaging studies.9,10In this review, we revisit the current status of focal therapy in the treatment of prostate cancer. We discuss whether there are ideal candidates for focal therapy; we then discuss how these candidates should be selected. We review which modalities are currently being used and proposed for focal therapy. Finally, we discuss potential definitions of successful treatment. As this article shows, there are still many aspects of focal therapy that are yet to be defined, that warrant a great need for further research.  相似文献   

15.
目的:探讨国人前列腺癌患者前列腺体积与肿瘤分级之间的关系。方法:回顾我院及武汉大学人民医院2005年1月-2011年10月70例确诊为前列腺癌并行根治性前列腺切除术(RP)患者的临床病理资料,采用SPSS13.0软件总结并分析前列腺癌患者前列腺体积与肿瘤分级之间的关系。结果:经直肠前列腺穿刺活检获得肿瘤病理分级与根治性前列切除术获得最终病理分级具有显著差异(P=0.003);在活检及根治性前列腺切除标本中,前列腺体积与高级别肿瘤发生率均呈负相关(P<0.05);小前列腺与阳性手术切缘、前列腺外侵犯及高级别肿瘤在单变量分析中具有相关性(P<0.05),而与精囊腺侵犯及淋巴结侵犯则无相关性(P>0.05);在校正了年龄、体重指数及术前前列腺特异性抗原水平后,前列腺体积与阳性手术切缘、前列腺外侵犯、精囊腺侵犯及高级别肿瘤发生率均呈负相关(OR<1,P<0.05),而与淋巴结侵犯则无相关性(P>0.05)。结论:前列腺体积是高级别前列腺癌的重要预测因子,利用其对高级别肿瘤风险的预测能力可帮助选择最佳治疗方案并进一步提高治疗效果。  相似文献   

16.
BackgroundDuring the period 1985-2000 the breast cancer incidence rates increased 50% in the age group invited to mammography screening in Norway and Sweden. Simultaneously, use of hormone replacement treatment therapy (HT) increased 5 times. Several influential observational studies showed that HT was associated with 50% to 100% increased risk of breast cancer and most for those using combined (estrogen plus progestin) hormone replacement therapy (CHT). In contrast, the randomized WHI trial reported that CHT increased the risk by 10% for those not having previously used hormones and 24% when including previous users in the analyses. In another randomized trial, estrogen use only was not associated with any increased risk at all. After the WHI trial was published in 2003, use of HT dropped 70% within 5 years in Norway and Sweden while breast cancer rates were essentially unchanged. After 2008, HT use has dropped further and breast cancer incidence rates have started increasing again. The study objective is to calculate and to explain potential bias in the observational study design.ConclusionsWe suggest that the mechanism causing higher hazard ratio of breast cancer (compared to the observational studies) is the time-varying effect of CHT on the breast cancer risk and selective retrospective reporting of hormone use. Other risk factors for the increase in breast cancer risk in the age group 50-69 years should be considered, for example, overdiagnosis.  相似文献   

17.
Taxane based chemotherapy is the standard of care treatment in castration resistant prostate cancer (CRPC). There is convincing evidence that taxane therapy affects androgen receptor (AR) but the exact mechanisms have to be further elucidated. Our studies identified c-jun as a crucial key player which interacts with AR and thus determines the outcome of the taxane therapy given. Docetaxel (Doc) and paclitaxel (Pac) agents showed different effects on LNCaP and LNb4 evidenced by alteration in the protein and mRNA levels of c-jun, AR and PSA. Docetaxel-induced phophorylation of c-jun occurred before JNK phosphorylation which suggests that c-jun phosphorylation is independent of JNK pathways in prostate cancer cells. A xenograft study showed that mice treated with Pac and bicalutamide showed worse outcome supporting our hypothesis that upregulation of c-jun might act as a potent antiapoptotic factor. We observed in our in vitro studies an inverse regulation of PSA- and AR-mRNA levels in Doc treated LNb4 cells. This was also seen for kallikrein 2 (KLK 2) which followed the same pattern. Given the fact that response to taxane therapy is measured by PSA decrease we have to consider that this might not reflect the true activity of AR in CRPC patients.  相似文献   

18.
Prostate cancer is the most frequent and second most lethal cancer in men in the United States. Innate immunity and inflammation may increase the risk of prostate cancer. To determine the role of innate immunity and inflammation in advanced prostate cancer, we investigated the association of 320 single nucleotide polymorphisms, located in 46 genes involved in this pathway, with disease risk using 494 cases with advanced disease and 536 controls from Cleveland, Ohio. Taken together, the whole pathway was associated with advanced prostate cancer risk (P = 0.02). Two sub-pathways (intracellular antiviral molecules and extracellular pattern recognition) and four genes in these sub-pathways (TLR1, TLR6, OAS1, and OAS2) were nominally associated with advanced prostate cancer risk and harbor several SNPs nominally associated with advanced prostate cancer risk. Our results suggest that the innate immunity and inflammation pathway may play a modest role in the etiology of advanced prostate cancer through multiple small effects.  相似文献   

19.
20.
Despite dramatic and recently accelerated advances in the reduction of morbidity linked to radical prostatectomies, significant short- and long-term morbidity is still associated with this surgical procedure. Currently both surgical and nonsurgical minimally invasive options are available for men with clinically localized prostate cancer, including laparoscopic and robotic radical prostatectomy, brachytherapy, and cryosurgical ablation of the prostate, with others, such as high intensity focused ultrasound, under investigation. In continued efforts to improve patient outcomes and to tailor treatment options to individual patient circumstances, nomograms have been developed and are increasingly being used by physicians and patients, alike, to guide therapeutic choices at each stage of disease. This tool predicts the possibility of successful treatment for the patient based on factors such as prostate-specific antigen levels, clinical stage of disease, and biopsy results. The current and future development, design, availability, and use of nomograms is described along with the historic and newer minimally invasive treatment options for prostate cancer.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号