Long-term follow-up of women with ovarian cancer after positive second-look laparotomy

OBJECTIVE: Previous reports indicate that cytoreduction and salvage therapy with P32 or whole abdominal radiation may improve survival in patients with positive findings at second-look laparotomy (SLL). The aim of this investigation was to determine whether these findings held true with extended follow-up and a larger patient cohort. METHODS: From 1977 (the year platinum-based chemotherapy was introduced to our institution) to 1989, 150 patients had persistent disease at SLL. Relevant clinical information was extracted through retrospective chart review. RESULTS: One hundred forty-five patients were followed until death, with a median follow-up of 15.4 years for the 5 living patients. Median actuarial survival from the time of SLL was 18 months. Tumor grade (P = 0.003) and pre- and post-SLL tumor size (P < 0.0001) were significant determinants of survival by univariate analysis. Patients with microscopic disease or those with < or =1 cm disease rendered microscopic at SLL had improved survival relative to those with < or =1 cm and macroscopic disease following SLL (P = 0.03) (median survivals of 3.3, 2.5, and 1.4 years, respectively). In contrast, median survival of those with >1 cm disease cytoreduced to microscopic disease was no different than those with macroscopic residual, even if < or =1 cm (1.3 and 1.0 years, respectively). After adjusting for tumor size, salvage treatment was not a significant predictor of survival. CONCLUSION: With long-term follow-up there was no suggestion that the type of salvage therapy (e.g., P32 or WART) influenced survival. Rather, low-grade disease and low tumor burdens following cytoreduction were associated with improved survival on multivariate analysis.     

Hepatic resection for metachronous metastases from ovarian carcinoma

OBJECTIVE: Hepatic resection for recurrent ovarian carcinoma is controversial because of the paucity of relevant published data. The principles of cytoreduction before chemotherapy suggest that resection of measurable liver lesions in properly selected patients would be beneficial. To determine the effect of resection of metachronous liver metastases on morbidity and survival, we reviewed our experience with this treatment. METHODS: Medical records were reviewed retrospectively for all patients who had anatomic hepatic resection for metachronous parenchymal liver metastases from ovarian carcinoma (epithelial or malignant mixed Müllerian tumors) at Mayo Clinic from 1976 to 1999. RESULTS: We identified 26 patients (median age at hepatic resection, 62 years; range, 39-75 years) who had hepatic resection requiring complete segmentectomies or more extensive hepatic surgery for recurrent ovarian carcinoma. Cytoreduction was optimal (extrahepatic and hepatic residual disease 相似文献   

Hematogenous dissemination in corpus cancer

OBJECTIVE: The aim of this study was to assess the predictors of hematogenous dissemination (HD) in corpus cancer. METHODS: In 612 corpus cancer patients managed surgically, we defined HD as tumor spread to the lung, liver, or other sites via hematogenous routes. RESULTS: We observed 142 instances of tumor spread-71 nonhematogenous and 42 hematogenous to the lung, 9 to the liver, 5 to other sites (adrenals, breast, brain, bone, skin), 3 to both liver and lung, 1 to both lung and bone, and 11 to sites unknown. Stage IV disease, positive adnexae, deep myometrial invasion, primary tumor diameter, tumor involving the whole uterine cavity, positive peritoneal cytology, adjuvant radiotherapy, adjuvant chemotherapy, grade 3 histology, histologic subtype, and lymph-vascular invasion significantly (P < or = 0.01) correlated with HD. However, deep myometrial invasion was the only independent predictor of HD. Only 5% of patients with < or = 50% myometrial invasion had HD compared with 23% with > 50% myometrial invasion. Considering separately recurrence in the lung and in the liver and recurrence in other sites, the only independent predictors of lung recurrence were stage IV disease and myometrial invasion, whereas independent predictors of HD to the liver/other sites were age and histologic grade. Considering only the 60 patients with a known site of HD, 67% with lung recurrence were > 65 years old compared with 17% with HD to the liver/other sites. Furthermore, grade 1-2 disease was observed in 65% of patients with lung recurrence compared with 27% with HD to the liver/other sites. CONCLUSIONS: The presence of deep myometrial invasion was the strongest predictor of HD in corpus cancer, and, together with stage IV disease, it independently predicted lung recurrence. Recurrence in the lung was more frequent in older patients with well or moderately differentiated tumors, whereas HD to the liver/other sites was more frequent in patients < or = 65 years of age harboring grade 3 tumors.     

Neurotoxic nitric oxide rapidly depolarizes and permeabilizes mitochondria by dynamically opening the mitochondrial transition pore

Exposure of SH-SY5Y neuroblastoma or rat cortical neurons to diethylenetriamine-NO (DETA-NO) rapidly depolarized mitochondria. In SH-SY5Y DETA-NO activated caspase 3 and produced cell death. Mitochondrial depolarization in SH-SY5Y was visualized both with JC-1 accumulation and as dequenching of calcein fluorescence in mitochondria initially loaded with calcein-AM and tetramethylrhodamine methyl ester (TMRM). Calcein/TMRM-visualized mitochondrial depolarization was prevented by cyclosporin A (CsA) or approximately two-fold increased levels of BclXL protein. Dynamic imaging of mitochondrial potential (Deltapsi M) with TMRM showed that DETA-NO induced cycles of mitochondrial depolarization/repolarization ("flickering"). Fifteen-30 min of DETA-NO exposure caused high-frequency flickering with small peak size; 2 h of DETA-NO produced large peaks with prolonged depolarization. NO-induced flickering but not that from Bax was blocked by the calcium uniporter antagonist Ru360. Our findings show rapid-onset, dynamic regulation of Deltapsi M by NO, implying that neuroprotective therapies for brain ischemia target cell death processes downstream of effects of NO on mitochondria.     

Genetic analysis of early- versus late-stage ovarian tumors

In the United States, ovarian cancer is the fourth most common cause of cancer-related deaths among women. The most important prognostic factor for this cancer is tumor stage, or extent of disease at diagnosis. Although women with low-stage tumors have a relatively good prognosis, most women diagnosed with late-stage disease eventually succumb to their cancer. In an attempt to understand early events in ovarian carcinogenesis, and to explore steps in its progression, we have applied multiple molecular genetic techniques to the analysis of 21 early-stage (stage I/II) and 17 advanced-stage (stage III/IV) ovarian tumors. These techniques included expression profiling with cDNA microarrays containing approximately 18,000 expressed sequences, and comparative genomic hybridization to address the chromosomal locations of copy number gains as well as losses. Results from the analysis indicate that early-stage ovarian cancers exhibit profound alterations in gene expression, many of which are similar to those identified in late-stage tumors. However, differences observed at the genomic level suggest differences between the early- and late-stage tumors and provide support for a progression model for ovarian cancer development.     

Molecular and cytokinetic pretreatment risk assessment in endometrial carcinoma

OBJECTIVE: Our objective was to determine whether cytokinetic and molecular analyses of curettage specimens can provide a mechanism for triage of patients with endometrial cancer before initiating definitive surgical treatment. METHODS: Pretreatment analysis consisted of flow cytometric determination of ploidy, S-phase fraction (SPF), and proliferative index (PI) and immunohistochemical determination of expression of proliferating cell nuclear antigen, HER-2/neu, and p53 in curettage specimens from 134 patients with endometrial carcinoma who subsequently had surgical staging and definitive surgical treatment. Fisher's exact test or chi(2) was used to examine the association between pretreatment variables and traditional surgical-pathologic indices. The log-rank test was used for univariate survival analysis. Cox proportional hazards identified the most important molecular factors. RESULTS: Nondiploid status, SPF >/=9%, and PI >/=14% were associated with the traditional posttreatment prognostic indices, stage, grade, and histologic subtype. Univariate survival analysis demonstrated a correlation between nondiploid status, SPF >/=9%, PI >/=14%, and p53 overexpression and decreased progression-free survival (PFS) and disease-related survival (DRS). Stepwise Cox regression analysis identified p53 overexpression and SPF >/=9% as the most significant pretreatment molecular risk factors. A model stratifying patients according to whether none, one, or both of these two pretreatment factors were present showed that when both factors are present the risk for recurrence was higher (RR = 7.07; 95% confidence interval [CI], 3.06-16.38; P < 0.01) and death due to disease was higher (RR = 9.93; 95% CI, 3.92-25.19; P < 0.01) than when no factors are present. In the group with both factors, 5-year PFS and DRS estimates were 41 and 44%, respectively, compared with 86 and 86% and 90 and 92% for the "none" and "one" groups, respectively. CONCLUSION: When observed simultaneously, increased SPF and p53 overexpression defined a group of patients at high risk for rapid recurrence and death due to disease. Pretreatment molecular analysis of curettage specimens could provide a mechanism of triage that could be applied before definitive surgical treatment.     

Organization, structure and evolution of the CYP2 gene cluster on human chromosome 19.

The cytochrome P450 superfamily of mixed-function oxygenases has been extensively studied due to its many critical metabolic roles, and also because it is a fascinating example of gene family evolution. The cluster of genes on human chromosome 19 from the CYP2A, 2B, and 2F subfamilies has been previously described as having a complex organization and many pseudogenes. We describe the discovery of genes from three more CYP2 subfamilies inside the cluster, and assemble a complete map of the region. We comprehensively review the organization, structure, and expression of genes from all six subfamilies. A general hypothesis for the evolution of this complex gene cluster is also presented.     

普鲁卡因选择性涂丝电极稳定性的研究

涂丝电极的应用已很广泛,但其稳定性差限制了它的进一步推广应用。本文找出普鲁卡因涂丝电极稳定性差的原因,制备了以聚乙烯醇(含盐酸普鲁卡因)为内参的Ag-Agcl丝涂(PVC)膜电极,其稳定性大为提高,并有良好的响应性能。     

Biosynthesis and secretion of factor VII, protein C, protein S, and the Protein C inhibitor from a human hepatoma cell line

Using specific radioimmunoassays, 8 day cultures of Hep G2 cells were shown to contain in their supernatants 16, 74, and 828 ng/mL and in their cell lysates, 8, 55, and 48 ng/2 X 10(8) cells of factor VII, protein C, and protein S, respectively. These proteins and the protein C inhibitor were functionally active, and each of these activities was neutralized by their respective polyclonal antibodies. Although vitamin K had a modest effect, warfarin decreased the activity of secreted factor VII, protein C, and protein S by 50% to 90%. Protein C and protein S antigens were reduced three- to fourfold by warfarin. The protein C inhibitor antigen and activity were unaffected by vitamin K or warfarin treatment. Intrinsic labeling and immunoprecipitation indicated that factor VII, protein S, and the protein C inhibitor were secreted as 52,000, 77,000, and 58,000 molecular weight (mol wt) proteins, respectively. Protein C was secreted as a single-chain protein of about 65,000 mol wt, indicating that all of the vitamin K- dependent proteins are translated and secreted as single-chain molecules. Each of the four proteins studied represented their plasma protein counterparts structurally, functionally, and immunochemically. Thus, all of the known soluble components of the protein C pathway are produced by liver parenchymal cells.