Overexpression/amplification of HER-2/neu is uncommon in hepatocellular carcinoma

BACKGROUND： Hepatocellular carcinoma （HCC） is one of the most prevalent fatal cancers in the world. Despite advances in early diagnosis and improvements in surgical techniques, the survival of patients with HCC even after resection is poor because of the high incidence of recurrences. Therefore, the identification of prognostic factors may be helpful in the development of new treatment protocols. AIMS： To investigate HER-2/neu status in HCC by immunohistochemistry （IHC） and fluorescence in situ hybridisation （FISH）, and to explore the possibility of using trastuzumab in the treatment of HCC. METH ODS： Eight hundred and sixty eight surgical samples from patients with primary HCC were examined for their HER-2/neu status. IHC for HER-2/neu was performed with the HercepTest kit; FISH analysis was performed with the PathVysion HER-2 DNA probe kit. The correlations between HER-2/neu overexpression and clinicopathological characteristics were analysed statistically. RESULTS： HER-2/neu overexpression was detected in 21 （2.42%） of the 868 primary HCCs. Only one specimen showed HER-2/neu gene amplification by FISH. No significant associations were found between HER-2/neu overexpression and the clinicopathological parameters. CONCLUSIONS： There is a low frequency of HER-2/neu overexpression/amplification in HCC. There appears to be no role for HER-2/neu as a prognostic marker and no benefit of anti-HER-2/neu trastuzumab treatment in patients with HCC.     

Epididymal cystadenomas in von Hippel-Lindau disease

Objectives. Epididymal cystadenomas (ECs) are frequently found in association with von Hippel-Lindau disease (VHL), but little has been reported about their sonographic appearance. We review the sonographic appearance of ECs, the relationship of ECs to other manifestations of VHL, and the specific genetic mutations associated with ECs.Methods. Fifty-six male patients with VHL were examined with scrotal sonography and physical examination as part of a larger screening program for VHL. The head of the epididymis was measured in two planes on sonography and compared with age-matched normal controls. All VHL patients with palpable epididymal abnormalities or enlargement (more than two standard deviations) of the head of the epididymis on ultrasound were considered positive for EC.Results. Thirty of 56 (54%) male patients with VHL demonstrated a unilateral (n = 10; 33%) or bilateral (n = 20; 67%) solid abnormality in the head of the epididymis suggestive of EC. Sonographic appearances ranged from a solid mass with multiple tiny cysts to an almost completely solid mass. The most common appearance was a 15- to 20-mm solid mass with small cystic components. Dilated efferent ductules were seen within the testicle in 7 men, evidently a result of chronic obstruction. There was no association between the clinical subtype of VHL and the presence of ECs (P >0.10, chi square). Mutations resulting in a truncated gene product were associated with the development of ECs but the association did not reach statistical significance (P = 0.06).Conclusions. ECs are a common manifestation of VHL in men and exhibit a range of appearances on ultrasound. Sonography can be used to identify ECs and determine the extent of cystic dilation of the rete testes. The benign course of ECs and the usual absence of clinical symptoms favor a conservative approach to their management.     

Suramin inhibits bone resorption and reduces osteoblast number in a neonatal mouse calvarial bone resorption assay.

The antineoplastic properties of suramin, a polyanionic agent with demonstrated antigrowth factor activity, are under evaluation in vitro, in vivo, and in clinical trials. Suramin has been shown to have antitumor activity in patients with advanced, hormone refractory prostate cancer. During these trials, significant resolution of osseous pain was observed in nearly three quarters of the patients treated with suramin. To evaluate the effect of suramin on bone cells, we studied the effect of suramin on bone resorption in a neonatal mouse calvarial assay. Suramin inhibited bone-resorbing activity in a dose-related fashion and had an additive effect with calcitonin. Calvaria pretreated with suramin had less bone-resorbing activity, fewer attached osteoblasts, and less medium alkaline phosphatase activity than control calvaria. Suramin also inhibited osteoclastic release of tritiated proline from labeled bone in a dose-dependent fashion. The effect of metastatic prostate carcinoma on bone is incompletely understood, but may be moderated by tumor-produced factors and/or cytokines. The effects of several such agents, therefore, were examined in combination with suramin. Bone resorption induced by PTH, epidermal growth factor, tumor necrosis factor, and a tumor-produced factor, PTH related-protein, was blocked by suramin. The ability of suramin to inhibit the bone-resorbing effects of several cytokines suggests that its mechanism may involve direct action on bone metabolism. Autoradiography performed on calvaria treated with labeled suramin demonstrated heavy deposition of suramin on the outer surface of the matrix, adjacent to osteoblasts and osteoclasts lining the outer table, suggesting that bone cells may be subject to high local concentrations of the drug, in keeping with this hypothesis.     

中西医结合医院单病种的质量管理及其作用

针对中西医结合医院单病种质量评定没有现成的、规范的标准的现状,就中西医结合单病种的质量管理方法及其在中西医结合医院建设中的作用进行了论述。     

Expression microdissection: operator-independent retrieval of cells for molecular profiling.

Tissue microdissection is an important method for the study of disease states. However, it is difficult to perform high-throughput molecular analysis with current techniques. We describe here a prototype version of a novel technique (expression microdissection) that allows for the procurement of desired cells via molecular targeting. Expression microdissection (xMD) offers significant advantages over available methods, including an increase in dissection speed of several orders of magnitude. xMD may become a valuable tool for investigators studying cancer or other disease states in patient specimens and animal models.     

Human ovarian granulosa cells and follicular fluid indices: the relationship to oocyte maturity and fertilization in vitro

The study investigates the correlation between oocyte maturity and fertilization and a variety of hormonal parameters in follicular fluid and ovarian granulosa cells. A methodology for purification of granulosa cells from contaminating blood cells is also established. A total of 63 follicular aspirates were collected at oocyte retrieval from 30 women superovulated using the long luteinizing hormone- releasing hormone (LHRH analogue)/human menopausal gonadotrophin regimen. Oestradiol, progesterone, testosterone and human chorionic gonadotrophin (HCG) were quantified in follicular fluid and granulosa cells were immunostained for human chorionic gonadotrophin. Immunopurification of granulosa cells from contaminating blood cells was performed. HCG in follicular fluid was significantly high in follicles yielding immature (grade 3) oocytes (P=0.002); there was no correlation with fertilization. Aspirates from follicles containing mature (grade 1) oocytes and oocytes that subsequently fertilized had significantly more granulosa cells immunobound to HCG (P < 0.001, P=0.02). Moreover, the immunomagnetic purification technique provided >98% pure population of granulosa cells. The data demonstrate that HCG in follicular fluid and on granulosa cells may help to predict oocyte maturity and fertilization. Furthermore, immunomagnetic beads provide a reliable procedure for the purification of ovarian granulosa cells.      

Patterns of aneuploidy in stage IV clear cell renal cell carcinoma revealed by comparative genomic hybridization and spectral karyotyping

We report the use of spectral karyotyping (SKY) and comparative genomic hybridization (CGH) to describe the numerous genomic imbalances characteristic of stage IV clear cell renal cell carcinoma (CCRCC). SKY and CGH were performed on 10 cell lines established from nephrectomy specimens, and CGH on uncultured material from five of the primary renal tumors. The mutational status of VHL (3p25) and MET (7q31), genes implicated in renal carcinogenesis, were determined for each case. Each case showed marked aneuploidy, with an average number of copy alterations of 14.6 (+/-2.7) in the primary tumors and 19.3 (+/-4.6) in the cell lines. Both whole-chromosome and chromosome-segment imbalances were noted by CGH: consistent losses or gains included +5q23-->ter (100%), -3p14-->ter (80%), and +7 (70%). All VHL mutations and 83% of the genomic imbalances found in the primary tumors were also found in the cell lines derived from them. SKY showed many complex structural rearrangements that were undetected by conventional banding analysis in these solid tumors. All cases with VHL inactivation had 3p loss and 5q gain related primarily to unbalanced translocations between 3p and 5q. In contrast, gains of chromosome 7 resulted primarily from whole-chromosome gains and were not associated with mutations of MET. SKY and CGH demonstrated that genomic imbalances in advanced RCC were the result of either segregation errors [i.e., whole chromosomal gains and losses (7.8/case)] or chromosomal rearrangements (10.7/case), of which the majority were unbalanced translocations.