内皮素-1及受体基因在良性前列腺增生组织中的表达及意义

目的　探讨内皮素 1(ET 1)及受体A、B(ETAR、ETBR)在良性前列腺增生 (BPH)组织中的表达及意义。　方法　应用免疫组化和RT PCR方法检测前列腺组织ET 1及ETAR、ETBRmRNA的表达 ,并与患者临床参数行相关分析。　结果　ET 1、ETARmRNA和ETBRmRNA在BPH组织中的表达 (吸光度A值分别为 0 .94± 0 .0 8、0 .6 4± 0 .0 8、0 .97± 0 .0 8)与正常前列腺组织(0 .5 7± 0 .0 6、0 .37± 0 .0 5、0 .5 1± 0 .0 4 )相比 ,差别均有显著性意义 ,P均 <0 .0 5 ,其中ET 1、ETARmRNA与IPSS、前列腺体积、前列腺尿道长度、前列腺尿道压、最大尿道压呈正相关 ,与最大尿流率、平均尿流率呈负相关。　结论　ET 1和ETAR在BPH中的表达量与膀胱出口梗阻严重程度密切相关。     

雌二醇对去势前列腺癌患者LH脉冲分泌的抑制作用

３例前列腺癌施行双侧睾丸节除术后２－１２周的患，每天肌注苯甲酸雌二醇１ｍｇ，ｄ。治疗前后分别每１０ｍｉｎ采血一次，作７ｈ ＬＨ脉冲分析。结果表明，３例患平均血清ＬＨ水平分别由１７７．５８±３．２０，１３８．３０±５．８３和１４５．８８±３．８２ＩＵ／ＬＧＨＢＴＧＣ １７４．９０±７．６０，１３２．０２±５．７７和１４２．８０±３．６５ＩＵ／Ｌ（Ｐ均＜０．０１），但ＬＨ脉冲幅度和频率无明显变化（     

良性前列腺增生组织中一氧化氮合酶活性的变化

为探讨一氧化氮（ＮＯ）与良性前列腺增生（ＢＰＨ）发病的关系，应用双波长分光光度法测定１５例正常前列腺及２５例ＢＰＨ组织中一氧化氮合酶（ＮＯＳ）活性，并比较不同年龄组的正常前列腺及ＢＰＨ组织中ＮＯＳ活性水平。结果：ＢＰＨ组织中ＮＯＳ活性（９６．７７±２８．０２ｐｍｏｌ．ｍｇ－１．ｍｉｎ－１）明显低于正常前列腺者（２９０．９９±１３０．６８ｐｍｏｌ．ｍｇ－１．ｍｉｎ－１），Ｐ＜０．００１。不同年龄组的正常前列腺组织中ＮＯＳ活性水平与年龄无相关关系。而在５０岁、６０岁和≥７０岁三个年龄组之间的ＢＰＨ组织中ＮＯＳ活性水平有显著性差异，Ｐ＜０．０１，ＢＰＨ组织中ＮＯＳ活性水平随年龄增大呈下降趋势。结果提示前列腺组织中ＮＯＳ活性水平与ＢＰＨ有相关关系，ＮＯＳ活性降低可能是ＢＰＨ的年龄依赖性发病原因之一。     

Repeated quantitative bone scintigraphy in patients with prostatic carcinoma treated with orchiectomy

Bone scintigraphy was performed in 16 men with newly diagnosed prostatic carcinoma before orchiectomy as well as 2 weeks and 2 months after operation. The uptake in the lower thoracic and lumbar vertebrae was registered up to 240 min after injection of ^99mTc-MDP and was then calculated for each patient and vertebra. The relative standard deviation in measured uptake due to measuring technique was estimated to be±7%. In eight patients, who had normal bone scintigraphies before orchiectomy, there were no changes in the uptake values after operation. The remaining eight patients had widespread metastatic involvement prior to treatment. Six of these patients showed a so called flare phenomenon in the abnormal vertebrae which means an initial increase in uptake after operation followed by a decreased uptake in response to therapy. One patient had a continuously increased uptake in all the abnormal vertebrae which correlated well with the clinical progression of the disease, while in another patient both reactions were seen. Thus, repeated quantitative bone scintigraphies using ^99mTc-MDP can be made in a reproducible way and can be a useful tool to follow a patient's response to treatment.     

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.     

20q13.2 Amplification in intraductal hyperplasia adjacent to in situ and invasive ductal carcinoma of the breast

The 20q13 region harboring recently described putative oncogenes is frequently amplified in invasive ductal carcinoma (IDC). The aim of this study was to examine the 20q13 copy number in intraduct hyperplasia (IH), atypical duct hyperplasia (ADH), and ductal carcinoma in situ (DCIS) adjacent to IDC. In 5 patients, comparative genomic hybridization (CGH) after laser microdissection revealed 20q13 amplification in four of five cases of IH, in all of three cases of IH with atypia, all five of DCIS, and all five of IDC. Fluorescence in situ hybridization (FISH) confirmed the amplification at 20q13.2 in IH in the two specimens analyzed. The amplification rate, however, was higher in DCIS and IDC. In phenotypically normal ductal epithelium normal values were found for 20q13 copy number by FISH (n=2) and CGH (n=5). Although the number of cases presented here is small, our results suggest that mutations in the 20q13.2 region in IH may be associated with accelerated proliferation and hyperplasia of the ductal epithelium. Progression to DCIS and ICD is accompanied by a further increase in the 20q13.2 copy number. Received: 17 March 1999 / Accepted: 22 June 1999     

Early (Stage A) prostatic cancer

Summary This study was performed in order to elucidate some of the problems of incidence, morphology and natural history concerned with Stage A prostatic cancer or prostatic microcarcinoma (PMC).The prostates of 100 patients, treated by subtotal prostatectomy for benign prostatic hyperplasia (BPH), were studied by comparing both routine and step-section techniques. The incidence of PMC was 41% by the former and 86% by the latter technique. Assessment of the size of PMC, as measured by the sum of the two main diameters, resulted in three groups: A₁, A₂, A₃. The last of these may represent a frankly malignant condition, judged by size and the histological appearance. Radical prostatectomy is strongly suggested as appropriate therapy for this group.Supported in part by a Grant from the Ministry of Education (art. 286 T.U., 1977/78)     

Numerical chromosomal aberrations in prostate cancer: correlation with morphology and cell kinetics

Eleven routinely processed radical prostatectomy specimens were studied for the presence of numerical chromosomal aberrations by means of in situ hybridization with nucleic acid probes specific for chromosomes 7, 10, 17, X, and Y. Cytogenetic information was correlated with morphology, tumour stage and volume as well as with cell kinetics, the latter being assessed by immunohistochemistry with antibodies raised against the proliferative cell nuclear antigen (PCNA) and against a formalin-resistant epitope of the Ki-67 antigen, MIB 1. In 5 of 11 cases, numerical aberrations of at least one chromosome were found. The cases with normal chromosome numbers were those with the smallest volumes of Gleason grade 4 and/or 5 tumour (mean 0.5 cm³) and represented tumours restricted to the prostate. Tumours with aberrations in the number of detected chromosomes showed advanced stages and large volumes of high-grade tumour (mean 12.5 cm³). All 4 tumours with positive surgical margins were recruited from a group with marked local heterogeneity in chromosome numbers. Immunostaining with MIB 1 and PCNA was most intense in areas of high-grade tumour and was positively correlated with the emergence of chromosomal aberrations. The data suggest that the appearance of numerical chromosomal aberrations in prostate cancer coincides with aggressive tumour behaviour and could be used as an additional prognostic marker.This work is part of E.K.'s doctoral thesis     

Allele-specific PCR and Next-generation sequencing based genetic screening for Congenital Adrenal Hyperplasia in India

Genetic screening of Congenital Adrenal Hyperplasia (CAH) is known to be challenging due to the complexities in CYP21A2 genotyping and has not been the first-tier diagnostic tool in routine clinical practice. Also, with the advent of massive parallel sequencing technology, there is a need for investigating its utility in screening extended panel of genes implicated in CAH. In this study, we have established and utilized an Allele-Specific Polymerase Chain Reaction (ASPCR) based approach for screening eight common mutations in CYP21A2 gene followed by targeted Next Generation Sequencing (NGS) of CYP21A2, CYP11B1, CYP17A1, POR, and CYP19A1 genes in 72 clinically diagnosed CAH subjects from India. Through these investigations, 88.7% of the subjects with 21 hydroxylase deficiency were positive for eight CYP21A2 mutations with ASPCR. The targeted NGS assay was sensitive to pick up all the mutations identified by ASPCR. Utilizing NGS in subjects negative for ASPCR, five study subjects were homozygous positive for other CYP21A2 variants: one with a novel c.1274G>T, three with c.1451G>C and one with c.143A>G variant. One subject was compound heterozygous for c.955C>T and c.1042G>A variants identified using ASPCR and NGS. One subject suspected for a Simple Virilizing (SV) 21 hydroxylase deficiency was positive for a CYP19A1:c.1142A>T variant. CYP11B1 variants (c.1201-1G>A, c.1200+1del, c.412C>T, c.1024C>T, c.1012dup, c.623G>A) were identified in all six subjects suspected for 11 beta-hydroxylase deficiency. The overall mutation positivity was 97.2%. Our results suggest that ASPCR followed by targeted NGS is a cost-effective and comprehensive strategy for screening common CYP21A2 mutations and the CAH panel of genes in a clinical setting.