Effect of zoledronic acid on acro-osteolysis and osteoporosis in a patient with Hajdu-Cheney syndrome

Hajdu-Cheney syndrome is a rare, autosomal dominant skeletal dysplasia marked by acro-osteolysis of the distal phalanges and severe osteoporosis. Although there are more than 60 reports published to date, proper treatment and subsequent outcome have been scarce. Herein, we report a progress of anti-resorptive therapy with zoledronic acid, in a woman with Hajdu-Cheney syndrome. Results suggest that anti-resorptive therapy may be important in delaying the progress of osteoporosis and preventing fractures, but not necessarily acro-osteolysis itself.     

前列腺癌患者血清T-PSA、F-PSA水平和F/T比值变化及临床意义

目的:观察前列腺癌患者(PCa)血清总前列腺特异抗原(T-PSA)、游离前列腺特异抗原(F-PSA)和F-PSA/T-PSA比值(F/T值)变化,探讨其临床意义。方法: 用MEIA法检测121例PCa患者和554例良性前列腺增生(BPH)患者术前及其中82例PCa患者和396例BPH患者术后血清T-PSA、F-PSA水平,并计算F/T值。结果: 术前PCa患者T-PSA与F-PSA明显高于BPH患者,F/T比值明显低于BPH患者,两组间差异均显著(P＜0.01)。术后两组患者T-PSA、F-PSA水平较术前明显降低,F/T值则明显升高,与术前结果比较,差异均显著(P＜0.01)。在T-PSA＜10.0 μg/L范围,PCa患者占33.9%,BPH患者占85.5%,两组患者结果存在交叉。F/T值＜0.16时,PCa患者占83.5%,BPH患者占6.5%,两组差异显著(P＜0.01),F/T值＜0.16时诊断的灵敏度、特异性、阳性预示值、阴性预示值分别为83.5%、86.7%、81.1%、88.2%。结论: PCa和BPH患者手术前后血清T-PSA、F-PSA水平及F/T值均有明显变化。以F/T比值＜0.16作为PCa诊断临界值,可有效提高早期PCa诊断的特异性和敏感性,减少不必要的活检。     

前列腺癌脊柱转移瘤治疗进展

肿瘤脊柱转移是前列腺癌常见的并发症之一,脊柱转移瘤引起的骨相关事件(SRE)严重影响患者生活质量,增加死亡风险。临床上对于前列腺癌脊柱转移的治疗尚无统一标准。本文简述了放疗、外科手术及护理、骨靶向制剂在前列腺癌脊柱转移瘤治疗上的进展。笔者认为脊柱转移瘤的治疗策略应当是个体化、多学科联合。     

Vascular endothelial growth factor expression in untreated and androgen-deprived patients with prostate cancer

The aim of the study was to investigate immunohistochemically the expression of vascular endothelial growth factor (VEGF) in untreated and androgen-deprived patients with prostate cancer. The study included 20 patients with prostate cancer who had undergone transurethral prostatectomy due to infravesical obstruction. All patients had been receiving androgen deprivation therapy for at least 3 months. Transurethral prostatectomy specimens were examined for VEGF expression after androgen deprivation, and the biopsy samples of the same patients were used for the evaluation of VEGF expression before androgen deprivation. VEGF expression was analyzed using immunohistochemistry. Staining patterns determined by the staining scores were compared before and after treatment. The correlation of VEGF expression with PSA, Gleason score, and the percent change in PSA after treatment was also investigated. Eligible biopsy specimens were available in 15 of the 20 patients, allowing for the evaluation of VEGF expression before treatment. All prostate cancer specimens were positive. VEGF was localized mainly in the cytoplasm or on the membrane of carcinoma cells. Staining was strong in 86.7% of patients before androgen deprivation. Heterogeneous staining (strong in 25%, moderate in 35%, and weak in 40%) was observed after treatment. Staining scores were significantly higher in patients before androgen deprivation and showed a significant decrease after androgen deprivation (p = 0.007). Tumor staining correlated with Gleason score. No significant correlation was determined between VEGF expression and pre-treatment PSA and percent change of PSA after treatment. Immunohistochemical results indicate that VEGF expression is downregulated by androgen deprivation therapy. VEGF may be a potential target for therapeutic intervention in prostate cancer.     

Detection of prostate cancer by sialic acid level in patients with non-diagnostic levels of prostate-specific antigen

Introduction

Ideally, there will be reproducible markers easily and non-invasively available to test for malignancy, or alternative procedures when there is no accurate marker available. For prostate cancer, one of the most common cancers in men, levels of prostate-specific antigen (PSA) lack specificity and sensitivity for the determination of malignancy when they fall within a range of values termed the ‘grey zone’.

Objective

To examine the predictive value of sialic acid in prostate neoplasms.

Study design

In our study of diagnostic accuracy we recruited 70 men complaining of urinary symptoms who presented in the urology department as outpatients or inpatients. All patients were checked with biopsy and pathology in order to relate benign and malignant lesions of the prostate to levels of sialic acid, a member of a family of acetylated products of neuraminic acid, which has so far proved to be a very sensitive and accurate marker of malignancy.

Results

The sialic acid level was found to be elevated in patients with prostate cancer (mean 75.06 ± 10.4 mg/dl) and reduced in patients with benign prostate hyperplasia (mean 57.086 ± 8.7 mg/dl) (p < 0.01); it had a sensitivity of 86% and specificity of 84% in diagnosing malignancy.

Conclusion

Sialic acid can be used as an adjunct in predicting prostate malignancy when PSA values fall in the grey zone.     

A systematic review of psychosocial interventions for men with prostate cancer and their partners

Objective

To systematically review interventions aiming to improve adjustment in men with prostate cancer and their partners.

Methods

Medline, EMBASE, CINAHL and PsycINFO databases were searched. Inclusion criteria were: randomized controlled trials; relevant to specified clinical questions; included men who had prostate cancer (at least 80% prostate cancer patients or prostate cancer sub-group analysis); published in English between December 1999 and December 2009. Trial quality was assessed.

Results

21 studies met inclusion criteria. Trial quality was low; had not improved over the study timeframe; men with advanced disease were not targeted; minority groups were seldom included. Group cognitive-behavioral and psycho-education interventions appear helpful in promoting better psychological adjustment and QOL for men with prostate cancer; coping skills training for patient–spouse dyads improved QOL for partners.

Conclusion

There are limitations in the research on effective ways to improve adjustment for men with prostate cancer of any stage and their partners; and scant research targeting minority groups and the concerns of men with advanced disease.

Practice implications

Interventions for men with advanced prostate cancer could usefully target the implications of advancing disease and caregiver burden. There is an urgent need for researchers to focus efforts specifically on such men and their families.     

45例人前列腺癌雄激素受体基因B~H外显子的突变研究

目的和方法：为探讨雄激素受体（ＡＲ）与前列腺癌（ＰＣ）发生发展及内分泌治疗不敏感的关系，我们首先建立了用ＰＣ的穿刺和石蜡切片组织检测ＡＲ基因突变的ＰＣＲ－ＳＳＣＰ（双链构象多态性）－双链ＤＮＡ循环测序法。并用上述方法检测了４５例国人前列腺癌组织ＡＲ基因Ｂ￣Ｈ我显子的突变。结果：在６例２的癌组织中证实有７个ＳＳＣ溘 变位片段（其中一患者有两个外显子异常）。这６例 ４例为低分化腺癌，其中２例已有远处转     

Comparison of pelvic phased-array versus endorectal coil magnetic resonance imaging at 3 Tesla for local staging of prostate cancer

Purpose

Several studies have demonstrated the superiority of endorectal coil magnetic resonance imaging (MRI) over pelvic phased-array coil MRI at 1.5 Tesla for local staging of prostate cancer. However, few have studied which evaluation is more accurate at 3 Tesla MRI. In this study, we compared the accuracy of local staging of prostate cancer using pelvic phased-array coil or endorectal coil MRI at 3 Tesla.

Materials and Methods

Between January 2005 and May 2010, 151 patients underwent radical prostatectomy. All patients were evaluated with either pelvic phased-array coil or endorectal coil prostate MRI prior to surgery (63 endorectal coils and 88 pelvic phased-array coils). Tumor stage based on MRI was compared with pathologic stage. We calculated the specificity, sensitivity and accuracy of each group in the evaluation of extracapsular extension and seminal vesicle invasion.

Results

Both endorectal coil and pelvic phased-array coil MRI achieved high specificity, low sensitivity and moderate accuracy for the detection of extracapsular extension and seminal vesicle invasion. There were statistically no differences in specificity, sensitivity and accuracy between the two groups.

Conclusion

Overall staging accuracy, sensitivity and specificity were not significantly different between endorectal coil and pelvic phased-array coil MRI.     

Slow zoledronic acid releasing testis prostheses in the treatment of prostate cancer patients with bone metastases

Surgical castration is still considered the ‘gold standard’ for androgen deprivation therapy which have become the mainstay for the management of advanced prostate cancer. The main drawback of this safe operation is that it may have a negative psychological effect, thus, in recent years, a decline in the utilization of bilateral orchiectomy which is the most cost-effective form of androgen deprivation therapy can be witnessed. Testicular prostheses have been shown to reduce the psychological impact resulting from loss or absence of a testicle in those patients. Besides, patients with advanced prostate cancer are at risk of skeletal complications and bisphosphonates are used in treatment. Zoledronic acid is the only bisphosphonate agent demonstrated to effectively reduce skeletal related events in patients with advanced prostate cancer metastatic to bone. Therefore, zoledronic acid releasing testicular prostheses can be used in the treatment of prostate cancer patients with bone metastases after bilateral orchiectomy. This technology has the potential to become the preferred clinical management tool for prostate cancer patients with bone metasthases after bilateral orchiectomy.     

雄激素受体在人类前列腺癌发展中的作用研究

目的:研究雄激素受体在前列腺癌雄激素非依赖性生长中的作用。方法:通过连续传代培养,建立雄激素非依赖性前列腺癌细胞模型。用Western blot方法检测AR和PSA在上述过程中的表达情况。结果:连续传代培养后,LNCaP C-33细胞(传代次数少于33次)生物学行为发生改变。同C-33和C-51(传代次数介于33次和80次之间)细胞相比,C-81细胞(传代次数大于80次)表现出更强生长能力和更低雄激素依赖性。C-81细胞分泌高水平PSA,且DHT对其分泌作用的影响比C-33细胞小。3种LNCaP细胞总AR表达水平相同,但C-81表现为特征性AR-B表达丢失和AR-A表达增加。结论:前列腺癌进展是多因素作用的结果,其中包括AR亚型的差异性表达。     

血管生成及其抑制剂在前列腺癌中的研究进展

Angiogenesis plays a key role in progression of prostate cancer. Antigiogenesis becomes a new treament target for prastate cancer. In this review, we focus on the current knowledge of angiogenesis and tumor angiogenesis inhibitor in prastate cancer.     

低剂量唑来膦酸对去势拔牙大鼠破骨及成骨细胞的影响

文题释义：去势大鼠：即通过去势法建立骨质疏松动物模型,该模型建造方法主要有3种：去势法、维甲酸灌胃法和糖皮质激素肌注法,而去势法是目前最常用、最成熟的造模方法,主要是通过去除大鼠双侧卵巢至少3个月,构建骨量少、骨显微结构退化而引起骨脆性增加及骨折发生率升高的一种全身性骨病,即骨质疏松疾病模型。 TUNEL细胞凋亡检测：用于检测细胞在凋亡过程中细胞核DNA的断裂情况,其原理是生物素标记的dUTP在脱氧核糖核苷酸末端转移酶的作用下,可以连接到凋亡细胞中断裂DNA的3’-OH末端,并可与连接辣根过氧化酶的链霉亲和素特异结合,在显色剂DAB的存在下,产生很强的颜色反应(呈深棕色),特异准确定位正在凋亡的细胞。 背景：目前唑来膦酸虽能有效地预防绝经后妇女的骨丢失,但其对下颌骨的影响及其机制尚不清楚。 目的：观察去势大鼠经低剂量唑来膦酸作用后下颌骨组织病理学改变,探讨RANKL/RANK/OPG信号系统在唑来膦酸抑制骨吸收过程中的调控效应与机制。 方法：取36只雌性SD大鼠随机分为对照组、模型组和治疗组,后2组大鼠行两侧卵巢切除术,建立骨质疏松模型;对照组行假手术去除同等质量卵巢周围的脂肪。去卵巢3个月后,治疗组皮下一次性注射唑来膦酸20 μg/kg,对照组和模型组皮下注射相应剂量的盐水;用药1周后拔除大鼠左侧下颌磨牙,拔牙后4周麻醉动物取出拔牙侧下颌骨组织。通过影像学X 射线大致观察大鼠拔牙窝剩余牙槽骨状况,苏木精-伊红染色检测下颌骨皮质和骨松质的病理结构改变,TUNEL凋亡实验检测凋亡的成骨细胞数量,利用免疫组织化学技术检测下颌牙槽骨内细胞核因子κB受体活化因子配基(RANKL)、骨保护素、细胞核转录因子(NF-κB)的表达情况,最后Western blot检测核因子κB受体活化因子配基、细胞核转录因子蛋白的表达。 结果与结论：①拔牙4周后,治疗组相较模型组牙槽骨骨吸收减少,拔牙窝底有新骨形成;②苏木精-伊红染色可见,模型组的骨皮质变薄,骨小梁结构变细,甚至出现断裂,大量骨吸收陷窝,成骨细胞较少;治疗组骨皮质增厚,骨小梁结构正常,只有少量骨吸收陷窝,成骨细胞增多;③治疗组的成骨细胞凋亡数目显著低于模型组(P < 0.001);④免疫组织化学染色可见,治疗组RANKL蛋白、NF-KB p65蛋白表达显著低于模型组(P < 0.001,P < 0.002),骨保护素蛋白表达显著高于模型组(P < 0.001);⑤Western Blot结果显示,与对照组相比较,模型组的RANKL、NF-κB蛋白高表达,治疗组其表达量显著降低(均P < 0.001);⑥结果说明,唑来膦酸可通过下调细胞核转录因子信号通路抑制破骨细胞的分化,同时调控成骨细胞的凋亡。 ORCID: 0000-0002-0300-0460(程余婷) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Docetaxel chemotherapy of Korean patients with hormone- refractory prostate cancer:comparative analysis between 1st-line and 2nd-line docetaxel

Purpose

This study was undertaken to investigate the outcomes associated with docetaxel treatment of Korean patients with hormone-refractory prostate cancer (HRPC) and to compare its clinical efficacies in 1st and 2nd-line settings.

Materials and Methods

This study was retrospectively performed and included 47 patients with HRPC. The 1st-line group consisted of 19 patients who had not undergone prior chemotherapy, and the 2nd-line group consisted of 28 patients who underwent prior chemotherapy. All patients were treated with 75 mg/m² IV docetaxel every 3 weeks and 5 mg of prednisone twice daily with a continuous androgen blockade.

Results

Of 47 study subjects, 14 patients (29.8%) had ≥ 50% PSA decline from baseline. PSA response was more common in the 1st-line group, but this was not statistically different (42.1% vs. 21.4%, p = 0.114). After a median follow up of 11 months (range, 6 - 24 months), the 1st-line group showed a longer time to PSA progression (4 vs. 2 months, p = 0.015) and survival (17 vs. 10 months, p = 0.037) than the 2nd-line group. In terms of toxicities, no difference was apparent between the 2 groups.

Conclusion

In a 1st-line setting, docetaxel is an effective and tolerable agent for Korean HRPC patients, and that its efficacy is limited, although 2nd-line docetaxel is tolerable.     

Analysis of NKX3.1 expression in prostate cancer tissues and correlation with clinicopathologic features

This study aimed to analyze NKX3.1 expression in tissue samples of benign prostate hyperplasia (BPH) and in three different prostate cancer categories. The correlation of NKX3.1 expression with clinical and pathologic features of patients having undergone radical prostatectomy also was investigated. NKX3.1 expression was determined in tissue samples obtained from four different histopathological categories: (1) from patients treated with transurethral prostatectomy for BPH (n = 26), (2) localized prostate cancer patients subjected to radical prostatectomy (n = 38), (3) biopsy samples from prostate cancer patients who were metastatic at the initial admission (n = 10), and (4) tissue samples of prostate cancer patients administered antiandrogens, but who had undergone transurethral prostatectomy for infravesical obstruction (n = 11). Standard immunohistochemical staining was performed using an antiserum raised against recombinant human NKX3.1. Staining was seen in all categories of prostatic tissues. Immunohistochemistry staining scores were lower in prostate cancer patients. The staining scores were significantly higher in patients with BPH compared to metastatic or localized prostate cancer patients. Staining scores of patients with BPH and of those under antiandrogen therapy were similar. No significant correlation was found between NKX3.1 expression and tumor volume, Gleason sum scores, the presence of extraprostatic extension, tumor stage, or serum PSA. NKX3.1 expression is significantly decreased in prostate cancer patients when compared to BPH. However, the decline of NKX3.1 expression was not correlated with prostate cancer progression and was not associated with advanced stage. Thus, NKX3.1 expression is not a clinically valuable prognostic factor.     

Nomogram to predict insignificant prostate cancer at radical prostatectomy in Korean men: a multi-center study

Purpose

Due to the availability of serum prostate specific antigen (PSA) testing, the detection rate of insignificant prostate cancer (IPC) is increasing. To ensure better treatment decisions, we developed a nomogram to predict the probability of IPC.

Materials and Methods

The study population consisted of 1,471 patients who were treated at multiple institutions by radical prostatectomy without neoadjuvant therapy from 1995 to 2008. We obtained nonrandom samples of n = 1,031 for nomogram development, leaving n = 440 for nomogram validation. IPC was defined as pathologic organ-confined disease and a tumor volume of 0.5 cc or less without Gleason grade 4 or 5. Multivariate logistic regression model (MLRM) coefficients were used to construct a nomogram to predict IPC from five variables, including serum prostate specific antigen, clinical stage, biopsy Gleason score, positive cores ratio and maximum % of tumor in any core. The performance characteristics were internally validated from 200 bootstrap resamples to reduce overfit bias. External validation was also performed in another cohort.

Results

Overall, 67 (6.5%) patients had a so-called "insignificant" tumor in nomogram development cohort. PSA, clinical stage, biopsy Gleason score, positive core ratio and maximum % of biopsy tumor represented significant predictors of the presence of IPC. The resulting nomogram had excellent discrimination accuracy, with a bootstrapped concordance index of 0.827.

Conclusion

Our current nomogram provides sufficiently accurate information in clinical practice that may be useful to patients and clinicians when various treatment options for screen-detected prostate cancer are considered.     

TMPRSS2-ERG融合基因在转移性前列腺癌中的表达

目的 检测转移性前列腺癌中TMPRSS2-ERG基因融合的发生率,探讨ERG基因重排在前列腺癌进展中的作用.方法 收集32例由细针穿刺诊断的转移性前列腺癌,穿刺部位包括盆腔及远处淋巴结、肝、骨、甲状腺等,回顾相关临床病理学资料.免疫组织化学采用EnVision法标记前列腺特异性抗原、突触素和嗜铬粒素A.运用ERG分离断...     

用逐步回归探讨影响鼻咽癌转移的主要因素

目的：探讨与非角化性鼻咽癌（ｎａｓｏｐｈａｒｙｎｇｅａｌｃａｒｃｉｎｏｍａ，ＮＰＣ）转移有关的主要因素。方法：采用逐步回归的方法，对８３例非角化性ＮＰＣ１５项可能与转移有关的因素进行筛选。结果：在不同的Ｆ值水平下筛选出与ＮＰＣ转移发生最相关的因素，它们是癌内血管密度，血管壁上层粘蛋白（ＬＮ）表达异常，癌巢内淋巴细胞（ＬＣ）浸润量，癌细胞间变程度与患者年龄。这５个因素包括在逐步回归方程中（Ｙ＝１．４７６８－０．０９５７Ｘ１＋２．６６５Ｘ３＋０．００３１Ｘ９－０．２９４８Ｘ１３－０．３１０Ｘ１５，ＭＲ＝０．７０７４ｓｘ＝０．６４８９Ｆ＝１５．４２４７Ｐ＜０．０１），进而用方程进行回顾性推断８３例ＮＰＣ转移率为７３．４９％，明显高于临床记录发现的转移率（５９．０４％）。结论：逐步回归方程的建立为临床正确判断ＮＰＣ转移，以确定治疗提供有价值的参考依据     

婆罗双树样基因4在人前列腺癌细胞和组织中的表达及其与临床预后之间的关系

 目的：评估婆罗双树样基因4（SALL4）在人前列腺癌细胞系和前列腺癌组织中的表达情况,并明确其表达水平和临床病理学参数间的关系。方法：用免疫荧光技术、RT-PCR和Western blotting检测SALL4在LNCaP、DU145、PC-3细胞系和RWPE-1正常前列腺上皮细胞系中的表达。同时用免疫组化方法检测SALL4在前列腺增生及前列腺癌组织中的表达,并探讨其与Gleason评分等临床病理参数的关系。结果： SALL4蛋白在细胞中主要表达于胞浆,在3种前列腺癌细胞株中SALL4蛋白表达水平要明显高于正常前列腺上皮细胞RWPE-1（P＜005）,而SALL4 mRNA表达水平在4种细胞系中无明显差异（P＞0.05）。免疫组化结果显示SALL4在前列腺癌组织中的表达水平明显高于增生和正常前列腺组织（P＜0.01）。SALL4蛋白表达水平与Gleason评分、前列腺癌临床分期、预后及组织前列腺特异抗原（PSA）表达密切相关,而与患者年龄、治疗前血清总PSA水平、前列腺体积及组织雄激素受体表达无明显相关性。结论：SALL4蛋白在前列腺癌中高表达,提示其在前列腺癌的发生、发展过程中可能起重要作用,有可能成为诊断前列腺癌新的肿瘤标志物及评估其恶性程度、进展和预后的参考指标。     

Preoperative nomograms for predicting extracapsular extension in Korean men with localized prostate cancer: a multi-institutional clinicopathologic study

We developed a nomogram to predict the probability of extracapsular extension (ECE) in localized prostate cancer and to determine when the neurovascular bundle (NVB) may be spared. Total 1,471 Korean men who underwent radical prostatectomy for prostate cancer between 1995 and 2008 were included. We drew nonrandom samples of 1,031 for nomogram development, leaving 440 samples for nomogram validation. With multivariate logistic regression analyses, we made a nomogram to predicts the ECE probability at radical prostatectomy. Receiver operating characteristic (ROC) analyses were also performed to assess the predictive value of each variable alone and in combination. The internal validation was performed from 200 bootstrap re-samples and the external validation was also performed from the another cohort. Overall, 314 patients (30.5%) had ECE. Age, Prostate specific antigen (PSA), biopsy Gleason score, positive core ratio, and maximum percentage of biopsy tumor were independent predictors of the presence of ECE (all P values <0.05). The nomogram predicted ECE with good discrimination (an area under the ROC curve of 0.777). Our nomogram allows for the preoperative identification of patients with an ECE and may prove useful in selecting patients to receive nerve sparing radical prostatectomy.     

前列腺癌组织中人腺体激肽释放酶2基因表达值与Gleason评分的相关性分析

目的探讨人腺体激肽释放酶(hK)2基因表达值与前列腺癌的Gleason评分的相关性及临床意义.方法运用实时荧光定量(FQ)PCR方法检测40例已知Gleason评分前列腺癌病理组织中hK2的基因表达值.结果前列腺癌组织中hK2基因表达值在不同的Gleason评分中有差异,随Gleason评分值升高而升高.结论前列腺癌组织中hK2基因表达值与Gleason评分呈正相关;hK2有望成为前列腺癌早期诊断,恶性程度评估以及预后判断的重要指标.