重组人血管内皮抑素(恩度)联合放射治疗治前列腺癌骨转移瘤临床研究

目的观察重组人血管内皮抑素(恩度)联合放疗对前列腺癌骨转移瘤患者的疗效及安全性。方法对30例前列腺癌骨转移瘤患者进行随机分组研究,单纯放疗组(RT)14例,血管内皮抑素(恩度)联合放疗组(RT+E)16例。观察近期疗效和毒副反应。结果近期临床疗效:RT组显效4例(28.57%),有效3例(21.43%),无效7例(50%),有效率(50%);RT+E组显效9例(56.25%),有效5例(31.25%),无效2例(12.5%),有效率(87.5%)。两组毒副反应轻,均可以耐受。结论重组人血管内皮抑素(恩度)同步放疗可提高前列腺癌骨转移近期疗效,毒性反应没有增加。     

配体RANKL-受体RANK信号在前列腺癌细胞生存和转移中扮演重要角色(英文)

目的:前列腺癌在病情加重期和疾病晚期普遍发生的骨转移已成为当代医学治疗的一大难题和研究热点。愈来愈多的证据显示,破骨细胞和成骨细胞共同参与了前列腺癌的骨转移,调节破骨细胞和成骨细胞的细胞因子影响前列腺癌细胞的发展与转移。RANKL-RANK信号在破骨细胞的形成、分化、存活及骨的改建中发挥着不可缺少的重要作用。本实验对配体RANKL在前列腺癌细胞和成骨细胞中表达、产生,受体RANK在前列腺癌细胞中的表达、产生,以及配体RANKL促进前列癌细胞的增殖、侵袭活动进行了研究。方法:本研究采用了细胞培养,条件培养基(MediumConditioning),反转录-聚合酶链式反应(RT-PCRAnalysis),WesternBlot分析,增值分析(Proliferationas-say),迁移分析(Migrationassay)以及荧光报告基因分析(Luciferasereporterassay)等方法。结果:受体RANK在多数前列腺癌细胞中表达,而在正常的前列腺上皮细胞中无表达。前列腺癌细胞可刺激成骨细胞产生配体RANKL。外加配体RANKL或与成骨细胞共培养可刺激前列腺癌细胞的增殖与迁移,而这种作用是通过信号系统传递的。结论:配体RANKL-受体RANK信号在前列腺癌细胞生存和转移中扮演不可缺少的重要角色,为前列腺癌等的骨转移治疗和研究开辟了一条新途径。     

人N-myc下游调节基因与前列腺癌分化程度及转移的关系

目的探讨人N-myc下游调节基因（NDRG1）在前列腺癌组织中的表达及其与分化程度和转移的关系。方法用免疫组化LSAB法检测86例不同Gleason级别的前列腺癌和30例良性前列腺增生组织中NDRG1的表达情况。结果NDRG1在前列腺癌和良性前列腺增生组织中均呈高表达，阳性率分别为73．3％和70．0％，两者差异无统计学意义（P〉0．05）；前列腺癌Gleason分级从2～4分→6～7分→8～10分，NDRG1的表达逐渐下降，差异有统计学意义（P〈0．05）；NDRG1的阳性表达率在有淋巴结或骨转移的前列腺癌组织低于无淋巴结或骨转移的前列腺癌组织，两者呈负相关；NDRG1的表达与患者的年龄无关（P〉0．05）。结论NDRG1参与了前列腺癌的发生发展，并与前列腺癌的分化程度相关，有望成为一个早期预测肿瘤转移及预后的有用标志物。     

The role of cholesterol in prostate cancer

PURPOSE OF REVIEW: Experimental and epidemiological evidence suggests that cholesterol may play a promotional role in prostate cancer development and progression. This review seeks to provide an overview of established links between cholesterol and prostate cancer, with an emphasis on very recent scientific contributions supporting a role of cholesterol in prostate cancer etiology. RECENT FINDINGS: Elevated cholesterol levels in prostate cancer cells have been found to result from aberrant regulation of cholesterol metabolism. Recent studies have identified Akt/protein kinase B and sterol response element binding proteins as major players regulating cholesterol biosynthesis and feedback regulation. It has also become apparent that prostate cancer cells process critical cell survival cues via specialized membrane microdomains that are dependent on cholesterol for signal transduction. These findings converge to support a scenario in which abnormal cholesterol metabolism influences signal transduction events at the membrane in a manner that promotes tumor cell growth, inhibits apoptotic signals and potentially stimulates other malignant cellular behaviors. SUMMARY: Recent experimental evidence has invigorated the discussion of a role for cholesterol in prostate cancer. The identification of cholesterol as a critical component in signal transduction events in prostate cancer cells has not only provided new mechanistic insights but also opened up new avenues for chemotherapeutic intervention.     

基于SEER 数据库构建前列腺癌术后生存率预测模型

目的 探讨前列腺癌患者术后总生存率的影响因素,构建术后总生存率的列线图预测模型,预测患者术后1、3及6年总生存率,并进行该模型的临床获益分析 。方法 通过 SEER stat 软件提取Surveillance,Epidemiology,and End Results Program(SEER)数据库2012年1月至2017年12月经病理学诊断的48 486例前列腺癌患者一般临床资料和随访数据。将年龄、肿瘤转移情况、gleason评分、PSA、有无骨转移和肿瘤分化程度等6个因素纳入研究中,通过Cox回归,分析影响患者术后总生存率的因素,采用逐步回归法选择对总生存率影响最大的因素,并构建列线图。通过校准图、ROC曲线和C指数对模型进行评估。通过决策曲线对列线图预测模型的临床获益预测的准确性进行评估。结果 年龄(=3 535.714,P<0.001)、肿瘤分化程度(=2 127.478,P<0.001)、转移情况(=2 020.823,P<0.001)、有无骨转移(=33.409,P<0.001)、PSA(=3 197.936,P<0.001)和gleason评分(=9 257.727,P<0.001)等均是影响前列腺癌患者术后总生存率的独立危险因素,通过逐步回归法筛选出肿瘤分化程度、gleason评分、转移情况、有无骨转移和年龄与前列腺癌患者术后生存率关联最紧密,使用这些因素构建列线图预测模型。训练集和验证集的一致性指数分别为0.622(95%CI:0.618～0.625)和0.617(95%CI:0.614～0.620),训练集和验证集样本的1、3、6年ROC 曲线下面积(AUC)均为0.6左右。校准图表示该模型的预测值和实际值之间具有较好的一致性。结论 基于肿瘤分化程度、gleason评分、有无骨转移、转移情况和年龄5个因素构建的前列腺癌患者术后总生存率列线图预测模型具有一定的参考价值,有助于医师正确的评估患者的术后总生存率,对患者诊疗和预后评价提供参考依据。     

NDRG1在前列腺癌中的表达及意义

目的探讨NDRG1在前列腺癌中的表达及其意义,以及NDRG1的表达与前列腺癌分化的关系。方法收集2002年1月～2011年12月广州市第一人民医院手术切除的前列腺癌标本154例,其中伴转移16例(骨转移标本9例,淋巴结转移的标本7例)。所有患者术前未行放疗和化疗。观察前列腺癌病理形态特征,并用免疫组织化学EnVison法检测NDRG1的表达。结果 NDRG1在前列腺癌中低表达,肿瘤的分化程度越低表达越低(p<0.05),在前列腺癌转移的患者中NDRG1的表达明显下降。结论 NDRG1在前列腺癌中低表达,并且随着肿瘤的发生发展,表达量明显降低。NDRG1可能对前列腺癌起着抑制作用,提示该基因可望作为一个候选的转移抑制基因和早期预测肿瘤转移的分子生物学指标之一,并对前列腺癌的预防和治疗提供一定的帮助。     

Inorganic arsenic and human prostate cancer

OBJECTIVE: We critically evaluated the etiologic role of inorganic arsenic in human prostate cancer. DATA SOURCES: We assessed data from relevant epidemiologic studies concerning environmental inorganic arsenic exposure. Whole animal studies were evaluated as were in vitro model systems of inorganic arsenic carcinogenesis in the prostate. DATA SYNTHESIS: Multiple studies in humans reveal an association between environmental inorganic arsenic exposure and prostate cancer mortality or incidence. Many of these human studies provide clear evidence of a dose-response relationship. Relevant whole animal models showing a relationship between inorganic arsenic and prostate cancer are not available. However, cellular model systems indicate arsenic can induce malignant transformation of human prostate epithelial cells in vitro. Arsenic also appears to impact prostate cancer cell progression by precipitating events leading to androgen independence in vitro. CONCLUSION: Available evidence in human populations and human cells in vitro indicates that the prostate is a target for inorganic arsenic carcinogenesis. A role for this common environmental contaminant in human prostate cancer initiation and/or progression would be very important.     

乌鲁木齐维吾尔族与汉族前列腺癌骨转移患者 差异性研究

摘要:目的　探究乌鲁木齐地区维吾尔族（维族）与汉族前列腺癌患者的骨转移特点。方法　分别对75例维族和82例汉族前列腺癌患者采用SPECT进行全身核素骨显像,放射免疫法分析法测定血清骨钙素（BGP）水平,化学发光免疫分析法测血清白介素-6（IL-6）、游离前列腺特异抗原（F-PSA）和血清总前列腺特异抗原（T-PSA）水平及其比值（F/T）。结果　骨显像阳性率维族为54.67%（75例）,低于汉族76.83%（82例）,血清骨钙素和IL-6水平维族均低于汉族,差异均有统计学意义（P＜0.05）;血清F-PSA和T-PSA水平,两民族间差异无统计学意义（P＞0.05）,但其比值（F/T）维族明显高于汉族（P＜0.05）。结论　乌鲁木齐地区维族与汉族前列腺癌患者骨转移不同,汉族患者更容易发生骨转移,且肿瘤代谢指标活跃,累及范围较广,预后差。     

多参数MRI成像技术用于前列腺癌病理和分期的预测价值研究

目的 评价多参数MRI成像技术用于前列腺癌病理和分期的预测价值。方法 以2016—2021年收治的80例前列腺癌患者作为研究对象，全部患者均接受多参数MRI成像扫描。以根治性前列腺切除术后病理切片结果作为金标准，评价多参数MRI成像用于显著性前列腺癌、包膜外侵犯、主要病灶部位和淋巴结转移的预测价值。结果 多参数MRI用于鉴别显著性前列腺癌的敏感性为96%、特异性为60%、阳性预测值为97.3%、阴性预测值为50%；鉴别主要病变与根治性前列腺切除术后病理切片结果一致性为75%；检测包膜外侵犯敏感性为40%、特异性为91.4%、阳性预测值为85.7%、阴性预测值为54.2%；检测淋巴结转移的准确性为16.7%。结论 多参数MRI成像用于鉴别显著性前列腺癌的敏感性和阳性预测值及检测前列腺癌主要病变的准确度均较高，对于制定前列腺癌治疗方案、评估预后等均具有重要价值。     

综合治疗中晚期前列腺癌的疗效分析

目的探讨一种对中晚期前列腺癌较理想的治疗方法。方法回顾性分析2001年3月~2005年1月收治的前列腺癌临床病例78例,采用综合治疗:经尿道等离子束腔内微创手术加双侧睾丸白膜下切除去势,术后应用抗雄激素药物阻断治疗,对伴有骨转移者同时行核素89Sr内放射治疗。与同期用单纯膀胱造瘘加双侧睾丸切除的45例病人进行比较。结果随访3~48个月,综合治疗后下尿路梗阻症状明显改善,血清PSA水平下降,骨痛缓解,生活质量显著提高,生存时间明显延长。结论对于中晚期前列腺癌采取积极的综合治疗可取得较好的疗效,是一种较为理想的治疗手段。     

Bisphosphonates' use in metastatic bone disease

Bisphosphonates already have an established role in the management of the skeletal complications of metastatic bone disease. The development of new, highly potent compounds has led to investigation into their use as preventive agents in the adjuvant setting. The aim of the paper is to evaluate the evidence for their use in prevention and treatment.     

前列腺癌患者外周血PSA、IL-6、TNF-ɑ及IL-17A的表达水平及临床意义

目的:探讨前列腺癌(PCa)患者肿瘤标志物及相关细胞因子的表达水平及其临床意义.方法:选取在医院泌尿外科行PCa筛查的77例PCa患者,将其纳入观察组,另选同期健康体检的30名男性为健康对照组,分别测定两组总前列腺特异性抗原(tPSA)、游离前列腺特异性抗原(fPSA)、游离前列腺特异性抗原与总前列腺特异性抗原比值(f...     

影响前列腺癌内分泌治疗有效时间的临床因素分析

目的 评估影响前列腺癌患者内分泌治疗有效时间的临床相关因素.方法 回顾性分析432例诊断为前列腺癌并接受单纯内分泌治疗患者的临床资料.研究终点定义为内分泌治疗失效,即前列腺特异抗原（PSA）从最低值连续2次增加,并超过0.2μg/L.纳入分析的变量包括年龄、临床分期、淋巴转移情况、骨转移情况、Gleason评分、初始PSA水平以及PSA最低值,通过Cox回归模型检测其与内分泌治疗有效时间的相关关系.结果 432例患者发病年龄57 ～88 （73.70±7.28）岁.初始PSA水平10.30～588.10（27.15±75.90）μg/L.内分泌治疗有效时间3～62（27.01±13.10）个月.单因素分析表明,初始PSA水平、临床分期、Gleason评分、PSA最低值、淋巴结转移和骨转移与内分泌治疗有效时间存在显著相关关系（P＜0.01）.多因素分析中,仅Gleason评分与内分泌治疗有效时间存在显著相关关系（P=0.001）.与Ghason评分≤3＋4分相比,≥4＋3分患者的内分泌治疗失效风险增加2.49倍,95％ CI 1.44～4.30.结论 在不同分期的前列腺癌患者中,Gleason评分与内分泌治疗有效时间具有显著的相关性,Gleason评分≥4＋3分患者显示出更短的内分泌治疗有效时间.     

1α,25-Dihydroxyvitamin D Inhibits the Metastatic Capability of MCF10CA1a and MDA-MB-231 Cells in an In Vitro Model of Breast to Bone Metastasis

Breast cancer metastasis to the bone continues to be a major health problem, with approximately 80% of advanced breast cancer patients expected to develop bone metastasis. Although the problem of bone metastasis persists, current treatment options for metastatic cancer patients are limited. In this study, we investigated the preventive role of the active vitamin D metabolite, 1α,25-dihydroxyvitamin D (1,25(OH)₂D), against the metastatic potential of breast cancer cells using a novel three-dimensional model (rMET) recapitulating multiple steps of the bone metastatic process. Treatment of MCF10CA1a and MDA-MB-231 cells inhibited metastasis in the rMET model by 70% (±5.7%) and 21% (±6%), respectively. In addition, 1,25(OH)₂D treatment decreased invasiveness (20 ± 11% of vehicle) and decreased the capability of MCF10CA1a cells to survive in the reconstructed bone environment after successful invasion through the basement membrane (69 ± 5% of vehicle). An essential step in metastasis is epithelial–mesenchymal transition (EMT). Treatment of MCF10CA1a cells with 1,25(OH)₂D increased gene (2.04 ± 0.28-fold increase) and protein (1.87 ± 0.20-fold increase) expression of E-cadherin. Additionally, 1,25(OH)₂D treatment decreased N-cadherin gene expression (42 ± 8% decrease), a marker for EMT. Collectively, the present study suggests that 1,25(OH)₂D inhibits breast cancer cell metastatic capability as well as inhibits EMT, an essential step in the metastatic process.     

上皮细胞间质转化与肿瘤转移

多种研究表明上皮细胞间质转化(EMT)与上皮细胞恶性肿瘤的发生和发展关系密切。EMT是上皮细胞获得迁移能力的有效方式,在成体中成为占恶性肿瘤90%以上的上皮细胞癌浸润转移的一个重要途径。目前体内和体外实验证据都表明,EMT在乳腺癌、结肠癌、肺癌、前列腺癌、肝癌、胰腺癌等多种癌症的原发性浸润和继发性转移中起着举足轻重的作用。本研究从EMT的分类、生物标记物以及与恶性肿瘤浸润和转移的关系等方面进行综述。     

The place of estramustine in the treatment of prostate cancer

INTRODUCTION/AIMS: Prostate cancer is a dynamic disease. Androgen ablation is palliative, and does not cure advanced prostate cancer. The hormone-sensitive cells die, and the hormone-resistant cells come into excess; the disease then progresses, which results in a deterioration of the condition of the patient. The theoretical basis of the curing strategy is the fact that the prostate tumour itself changes during the progression; the molecular determinants of the resistance are present in the varying stages of the disease. The treatment of advanced prostate cancer remains unsolved; it is a well-known fact that a hormone-resistant state develops after the primary treatment forms (androgen withdrawal). The drug of choice for the secondary treatment is estramustine. This can be utilized as monotherapy or in combination. METHODS: In the present study, the results of estramustine treatment of 79 patients with advanced prostate cancer were evaluated. The preparation, known and clinically applied for more than 20 years, was studied in 12 centres. RESULTS: The mean prostate-specific antigen level improved for 6 months, but rose from the 9th month on. The improvement in the subjective condition of the patients paralleled the change in the prostate-specific antigen level. The shortness of the improvement was a consequence of the very high prostate-specific antigen level and the poor general condition. CONCLUSIONS: Estramustine administration is recommended when the prostate-specific antigen level becomes more than doubled following the primary treatment. At a starting prostate-specific antigen level of >100 ng/ml, the treatment leads to total androgen blockade. If the prostate-specific antigen level has not decreased after treatment for 3 months, the secondary strategy is to apply chemotherapy.     

A High-Fat Diet Containing Lard Accelerates Prostate Cancer Progression and Reduces Survival Rate in Mice: Possible Contribution of Adipose Tissue-Derived Cytokines

To examine the effects of high-fat diet (HFD) containing lard on prostate cancer development and progression and its underlying mechanisms, transgenic adenocarcinoma mouse prostate (TRAMP) and TRAMP-C2 allograft models, as well as in vitro culture models, were employed. In TRAMP mice, HFD feeding increased the incidence of poorly differentiated carcinoma and decreased that of prostatic intraepithelial neoplasia in the dorsolateral lobes of the prostate, which was accompanied by increased expression of proteins associated with proliferation and angiogenesis. HFD feeding also led to increased metastasis and decreased survival rate in TRAMP mice. In the allograft model, HFD increased solid tumor growth, the expression of proteins related to proliferation/angiogenesis, the number of lipid vacuoles in tumor tissues, and levels of several cytokines in serum and adipose tissue. In vitro results revealed that adipose tissue-conditioned media from HFD-fed mice stimulated the proliferation and migration of prostate cancer cells and angiogenesis compared to those from control-diet-fed mice. These results indicate that the increase of adipose tissue-derived soluble factors by HFD feeding plays a role in the growth and metastasis of prostate cancer via endocrine and paracrine mechanisms. These results provide evidence that a HFD containing lard increases prostate cancer development and progression, thereby reducing the survival rate.     

A strontium-89 injection: a simple treatment of painful bone metastases in patients with prostate cancer unresponsive to hormonal treatment]

Four patients (men aged 75, 67, 65 and 69 years) with painful osseous metastases from prostate cancer were treated by intravenous radionuclide therapy using Strontium-89. All had secondary progression after initially successful hormonal treatment. Three of these four had good responses lasting from 5 to 9 months. One patient with rapidly progressive disease did not respond. Second and third injections were successful in two patients. Mild bone marrow suppression was observed in all, but was not clinically significant. The 70-80% chance of long-lasting pain alleviation through a single injection of Strontium-89 is a valuable addition in the treatment of painful bone metastases from prostate cancer, and probably also in such metastases from breast cancer.     

血小板源性生长因子-D与肿瘤相关性研究进展

血小板源性生长因子(PDGF)是1987年从人的血管中分离出来的促血管生成因子,也是一种刺激结缔组织生长的常见肽类调节因子,在纤维化、组织修复、免疫应答、肿瘤细胞增殖等过程中起重要作用.PDGF主要包括血小板源性生长因子-A(PDGF-A)、血小板源性生长因子-B(PDGF-B)、血小板源性生长因子-C(PDGF-C)...     

Community attitudes towards the early detection of cancer in Victoria, Australia

OBJECTIVES: To describe people's attitudes towards early detection of cancer. METHODS: We conducted a telephone survey of Victorian adults aged 18+ years, during April-May 2005, using a market research company. RESULTS: 1,502 (41%) people participated; 80% of respondents believed that detecting cancer early meant that treatment saved lives most of the time or always; 88% believed finding cancer early enabled more effective treatment most of the time or always; and 70% indicated they would want to be tested for a cancer even if no treatment were available. Two-thirds or more of adults considered survival would be very much improved by early detection for breast, melanoma and prostate cancers; 49% for bowel cancer, and 30% for lung cancer. CONCLUSIONS AND IMPLICATIONS: Community support for the early detection of cancer was evident even in the absence of effective treatment. There was a lower perceived survival benefit for the early diagnosis of bowel cancer, compared with breast or prostate cancer or melanoma. An education campaign is required that focuses on the gains associated with early detection and benefits of screening for bowel cancer.