^99mTc—MDP骨扫描在前列腺癌骨转移诊断中的价值

目的：探讨^99mTc-MDP骨扫描在前列腺痛骨转移诊断中的价值。方法：对明确诊断为前列腺癌的527例患者行^99mTc-MDP骨扫描,骨扫描不能确诊为骨转移者再经MRI、CT和病理检查等最后确诊有无骨转移。结果：在527例前列腺癌^99mTc-MDP骨扫描中,阳性显像331例,阴性显像196例;最后确诊骨转移者318例,占前列腺癌总例数的60．34％（318／527）．无骨转移者209例,占前列腺癌总例数的39．66％（209／527）。^99mTc-MDP骨扫描诊断前列腺癌骨转移的灵敏度为84．59％（269／318）,特异度为70．33％（147／209）,误诊率为29．67％（62／209）．漏诊率为15．4l％（49/318）．阳性预测值为81．27％（269／331）,阴性预测值为75．00％（147／l96）。随着^99mTc-MDP骨扫描诊断前列腺癌骨转移病灶数量级别从I级增至Ⅱ级和Ⅲ级时,其诊断前列腺癌骨转移的准确度越来越高。结论：^99mTc-MDP骨扫描诊断前列腺癌骨转移具有微高的灵敏度、特异性、阳性预测值和阴性预测倩,误诊率和漏诊率低。随骨转移病灶级别的增加,其诊断前列腺癌有无骨转移的价值越来越大。     

Stimulation of human prostate cancer cell lines by factors present in human osteoblast-like cells but not in bone marrow

Secondary deposits of prostate tumours are frequently found in the skeleton where they produce osteoblastic lesions. In this study both osteoblast-like cells and bone marrow from the proximal femur have been cultured to determine whether or not they can release factors which could support the growth of secondary prostate tumours. Media conditioned by both osteoblast-like cells (OBCM) and bone marrow were examined for their potential to stimulate prostate carcinoma cell lines. Whilst the results obtained demonstrated that OBCM could enhance the growth of both the hormone sensitive (LNCaP) and hormone unresponsive (PC-3 and DU-145) prostate carcinoma cell lines, no proliferative effect could be shown on cell lines derived from cancers of the breast, bladder, and liver. Significantly, media conditioned by either bone marrow or human skin fibroblasts also had no effect on the growth of prostate carcinoma cell lines. This study supports the possibility that the proliferation of prostate cancer cells at secondary skeletal sites, in vivo, may be due to osteoblast derived factors. © 1995 Wiley-Liss, Inc.     

Intraosseous growth of human prostate cancer in implanted adult human bone: relationship of prostate cancer cells to osteoclasts in osteoblastic metastatic lesions

BACKGROUND: More than 80% of patients with advanced prostate cancer have skeletal involvement, but the biology of bone metastasis is poorly understood. This study investigated the in vivo formation and progression of bone metastases under conditions that resembled the human bone environment as closely as possible. METHODS: Adult human bone fragments were implanted subcutaneously into 120 male NOD/SCID mice. Four weeks later, 1 x 10(7) LNCaP prostate cancer cells or phosphate-buffered saline were injected intravenously into 80 or 40 mice, respectively. The implanted bone fragments were removed from 20 to 10 mice in each group at 2, 4, 6, and 8 weeks after injection. RESULTS: LNCaP colonized the bone marrow blood vessels within 2 weeks, and then gradually expanded into the entire medullary cavity. An osteoblastic response often occurred at the edges of metastatic foci (intertrabecular bone metaplasia). In addition, new bone formation was observed adjacent to mature lamellar bone (appositional bone formation). These two processes appeared to occur through different mechanisms, but might similarly cause osteosclerosis. Osteoclasts showed a marked increase in numbers at sites of early tumor invasion, whereas few osteoclasts were observed at sites where tumor invasion was complete. CONCLUSIONS: The predominance of osteoblastic change with resorption may lead to bone remodeling in metastatic lesions, and osteoclasts may play an important role in bone metastasis from prostate cancer.     

Clinical usefulness of bone markers in prostate cancer with bone metastasis

Bone metastases occur in approximately 70% of patients with advanced prostate cancer. Skeletal‐related events have been correlated with reduced survival and quality of life of patients with prostate cancer. Biochemical markers of bone metabolism (e.g. bone formation, bone resorption, osteoclastogenesis) might meet an unmet need for useful, non‐invasive and sensitive surrogate information for following patients' skeletal health. Recently, zoledronic acid and denosumab have been proven to have the potential for preventing skeletal‐related events among prostate cancer patients with bone metastasis. An improved understanding of the mechanisms underlying bone metastasis has also led to the recognition of multiple molecular targets and advances in therapy. However, estimating the efficacy of these agents is difficult. A clinical trial for castration‐resistant prostate cancer is currently underway based on the definition of The Prostate Cancer Clinical Trials Working Group, and bone turnover markers are being used as conventional end‐points for the clinical trial. Bone turnover markers are useful surrogate markers reflecting the effect of new therapeutic drugs and prognosis, as well as assessment of bone metastases. In particular, N‐terminal cross‐linked telopeptide of type 1 collagen and bone‐specific alkaline phosphatase are widely used bone metabolism markers, and offer reliable surrogate markers to detect bone metastatic spread and to predict prognosis for prostate cancer patients with bone metastases.     

Osteoblasts produce soluble factors that induce a gene expression pattern in non-metastatic prostate cancer cells, similar to that found in bone metastatic prostate cancer cells

BACKGROUND: Progressive prostate cancer typically metastasizes to bone where prostate cancer cells gain an osteoblast-like phenotype and induce osteoblastic metastases through unknown mechanisms. To investigate the biology of prostate cancer skeletal metastases, we compared gene expression between the non-metastatic LNCaP cell line and its derivative cell line C4-2B that metastasizes to bone. METHODS: Total RNA from LNCaP and C4-2B cell lines was isolated and used to probe membrane-based gene arrays (Comparison 1). Additionally, LNCaP cells were incubated in the absence or presence of conditioned media (CM) from a human osteoblast-like cell line (HOBIT) and total RNA from these cells was used to probe gene arrays (Comparison 2). Differential expression of genes was confirmed by RT-PCR. RESULTS: Of the 1,176 genes screened, 35 were differentially expressed between LNCaP and C4-2B cells (Comparison 1). HOBIT-CM induced differential expression of 30 genes in LNCaP cells (Comparison 2). Interestingly, 19 genes that were differentially expressed in C4-2B vs. LNCaP also displayed a similar expression pattern in LNCaPs grown in HOBIT-CM. These genes are primarily involved in motility, metabolism, signal transduction, tumorigenesis, and apoptosis. CONCLUSIONS: These results suggest that osteoblasts produce soluble factors that contribute to the progression of prostate cancer skeletal metastases, including their transition to an osteoblast-like phenotype. Additionally, these data provide targets to explore for further investigations towards defining the biology of skeletal metastases.     

Kallikrein 4 is a potential mediator of cellular interactions between cancer cells and osteoblasts in metastatic prostate cancer

BACKGROUND: Prostate cancer (PCa) and bone cell interactions are critical in the metastatic phase. Kallikrein 4 (KLK4/hK4) is expressed in both PCa and mineralized tissues. We determined if KLK4/hK4 expression was associated with, and influenced by, the bone environment of metastatic PCa. METHODS: Immunohistochemistry, in vitro co-culture, cell migration, and attachment assays. RESULTS: hK4 was localized to tumor cells and osteoblasts in bone metastases. KLK4/hK4 increased in LNCaP and PC3 cells co-cultured with SaOs2 cells; SaOs2 KLK4/hK4 was unchanged. Co-culture did not affect cell proliferation but altered alkaline phosphatase activity/mRNA levels in SaOs2 cells. KLK4-transfected PC3 cells had increased migration towards SaOs2 conditioned medium and greater attachment to the bone-matrix proteins, collagens I and IV. CONCLUSIONS: hK4 expression and interaction with both tumor cells and osteoblasts suggests a role for hK4 in PCa bone metastasis. Whether this observation is unique to bone metastasis or reflects a role for hK4 in PCa metastasis generally is yet to be established.     

Osteocalcin: Is it a useful marker of bone metastasis and response to treatment in advanced prostate cancer?

Serum osteocalcin (OC) is derived largely from new cellular synthesis. It is a marker for bone formation and a noninvasive specific marker of osteoblastic activity. The clinical significance of OC in monitoring prostatic cancer bone metastases was evaluated. Pretreatment serum OC levels were determined with a radioimmunoassay kit in a total of 63 patients with prostate cancer (8 with stage B, 12 with stage C, 12 with stage D1, and 31 with metastatic bone disease). The OC levels in patients with skeletal metastasis were significantly higher than those in patients without bony lesions (P less than 0.01). The pattern of the initial changes in OC levels were analyzed in patients with skeletal metastasis who received endocrine treatment. The pretreatment OC value is of little use in predicting the response to treatment. The patients whose OC level initially increased and remained high tended to have a shorter interval to disease progression. On the other hand, the pattern of initial changes in OC varied according to the regimen of endocrine treatment. Our study suggests that OC seem to reflect the response to treatment and might lead to the improvement in follow-up procedures. However, the clinical significance of OC as a marker of the response of bone metastasis should be carefully discussed with regard to the direct hormonal effect on bone metabolism.     

Prediction of bone metastases by combination of tartrate-resistant acid phosphatase, alkaline phosphatase and prostate specific antigen in patients with prostate cancer

Objective:   The clinical value of serum tartrate-resistant acid phosphatase (TRACP), prostate specific antigen (PSA), alkaline phosphatase (ALP), and prostatic acid phosphatase (PACP) for the prediction of bone metastases in prostate cancer were investigated.
Methods:   TRACP, PACP, ALP, and PSA serum levels were measured in 215 patients with prostate cancer, including 160 without and 55 with bone metastases. Correlation of serum marker levels with bone metastases was assessed using receiver operating characteristics (ROC) analysis. Sensitivity, specificity, accuracy, positive and negative predictive values were calculated for each serum marker. Multivariate stepwise logistic regression analysis was used to identify independent predictors for the presence of bone metastasis.
Results:   Mean serum TRACP, PACP, ALP, and PSA levels were significantly elevated in patients with bone metastases compared with those without ( P  < 0.05). PSA and PACP levels increased significantly with clinical stage of the disease, whereas TRACP and ALP levels only increased significantly in stage D2. Serum TRACP levels correlated significantly with extent of disease on bone scans. ROC analyses showed no significant differences in area under the curve for these markers. Logistic regression analysis demonstrated that PSA, ALP, and TRACP were significant predictors of bone metastasis. Predicted and observed risks of bone metastasis were well correlated when TRACP, ALP, and PSA were combined and bone scan could have been omitted in 70% of patients by assessing these three markers.
Conclusions:   Serum TRACP can be considered a useful predictor of bone metastases in prostate cancer. A combination of TRACP, ALP, and PSA can obviate the need for a bone scan in 70% of cases.     

前列腺癌骨转移血清蛋白质组学研究

目的:应用蛋白质组学双向凝胶电泳和质谱技术筛选前列腺癌骨转移血清标志物。方法:收集前列腺癌伴骨转移、不伴骨转移各5例血清样本。血清样品用除白蛋白试剂盒除去血清中的白蛋白后进行双向凝胶电泳,ImageMaster 2D Platinum软件分析,有意义的差异蛋白质点行基质辅助激光解析离子化飞行时间质谱(MALDI-TOF-MS)鉴定。结果:双向凝胶电泳显示,前列腺癌骨转移组血清蛋白中有15个斑点与前列腺癌无骨转移组有显著差异,前列腺癌骨转移患者血清中10个蛋白质表达水平显著增加,5个蛋白质表达水平显著下降。5个差异蛋白点进行胶内原位酶解,肽质量指纹图谱分析成功得到了3个蛋白质肽质量指纹图谱,并查询数据库初步鉴定了该3个蛋白质分别为锌α2糖蛋白、结合珠蛋白和载脂蛋白CⅢ。结论:双向凝胶电泳结合质谱鉴定是血清差异蛋白质组学研究的可靠平台和有力工具。所鉴定出的蛋白质与前列腺癌骨转移的发生、发展有关,可能是前列腺癌骨转移潜在的血清标志物。     

前列腺癌骨转移研究进展

骨骼是最常见的前列腺癌转移靶器官,前列腺癌骨转移是一系列复杂而有序的过程,其发生机制可能涉及多个方面。现就从解剖学、病理学、分子生物学等方面对前列腺癌骨转移机制的研究现状作一综述。     

Molecular mechanisms of metastasis in prostate cancer

Prostate cancer （PCa） preferentially metastasizes to the bone marrow stroma of the axial skeleton. This activity is the principal cause of PCa morbidity and mortality. The exact mechanism of PCa metastasis is currently unknown, although considerable progress has been made in determining the key players in this process. In this review, we present the current understanding of the molecular processes driving PCa metastasis to the bone.     

泉安方治疗晚期前列腺癌骨转移痛初探(附18例报告)

目的 探讨泉安方治疗晚期前列腺癌的疗效。方法 18例晚期前列腺癌以自拟泉安方治疗，疗程为6个月。结果 治疗后在改善患者生活质量方面特别是缓解骨转移痛症状取得了明显的效果。结论 泉安方对晚期前列腺癌骨转移痛有较好的疗效。