Relationship of preoperative serum CA-125 to survival in epithelial ovarian carcinoma

BACKGROUND: Epithelial carcinoma of the ovary has the highest death rate of any gynecologic malignancy in the developed world. The antigen CA-125 has been used over the past decade as a tumor marker for epithelial ovarian cancer and other cancers of coelomic epithelium. The object of this study was to see if the degree of elevation of preoperative CA-125 was related to length of survival in patients with epithelial ovarian carcinoma. METHODS: Eighty-two consecutive patients diagnosed with epithelial ovarian carcinoma were evaluated for their initial preoperative CA-125 level, time to recurrence, length of survival and level of primary debulking as well as International Federation of Gynecologists and Obstetricians stage, grade and histology. Ovarian tumors of low malignant potential were not included in the study. All patients had their initial surgery performed by one surgeon. RESULTS: Decreased length of survival was related to the degree of elevation of CA-125 prior to initial exploratory laparotomy (P = .047). The mean initial CA-125 for patients surviving five years or more (15 patients) was 899 U/mL, with an SD of +/- 1,880 U/mL, while the CA-125 for patients surviving less than five years (67 patients) was 1,978 U/mL, with an SD of +/- 1,852 U/mL (P = .02). Increased stage of disease at initial laparotomy showed a relationship to increased CA-125 (P < .0001). CONCLUSION: In epithelial ovarian carcinoma, high preoperative serum levels of CA-125 predict decreased length of survival.     

Presence of activin, inhibin, and follistatin in epithelial ovarian carcinoma

Activin induces proliferation in epithelial ovarian carcinoma cell lines, whereas follistatin (FS), an activin binding protein, inhibits this action. To test the hypothesis that activin production, in excess of inhibin and FS, results in cell proliferation in epithelial ovarian tumors, messenger RNA (mRNA) expression of the activin family of proteins, FS, and activin type I and II receptors was examined in 25 primary epithelial ovarian tumors and tumor epithelium in culture (n = 7) using RT-PCR. Activin A was measured in the serum of ovarian cancer patients, and activin A, total inhibin, and FS protein secretion was measured from primary epithelial tumors in vitro. The effect of activin and FS on cell proliferation was assessed by measuring [3H]thymidine incorporation. All results were compared with normal ovarian epithelium. All epithelial ovarian tumors expressed mRNA for the alpha, beta A, and beta B subunits; FS 288 and 315; and the activin type IA, IB, II, and IIB receptors. beta A mRNA expression, as assessed using semiquantitative RT-PCR, was 3-fold greater in cultured tumor epithelium than in primary tumors (band density 0.86 +/- 0.17 vs. 0.28 +/- 0.09; P < 0.01). In addition, beta A mRNA was abundantly expressed in normal epithelium in culture (n = 2), whereas only trace amounts were seen in 2/9 primary epithelial samples. Activin protein was secreted by 24/25 primary epithelial ovarian tumors (range 0.2-155.8 ng/mL). In contrast, total inhibin was secreted by only 2/25 (range 0.01-0.92 ng/mL), whereas free FS was not detectable in the medium of any tumor (< 0.5 ng/mL). Treatment with activin or FS did not consistently affect cell growth. Measurement of serum activin A in a subset of subjects and in 27 additional subjects with epithelial ovarian carcinoma (n = 33) revealed preoperative activin A levels > 3 SD above the mean for pre- and postmenopausal women in 13/33 (39%) subjects. We conclude that in epithelial ovarian cancer: 1) beta A subunit mRNA is expressed, 2) activin protein is secreted more frequently than inhibin and in greater quantities than FS, 3) beta A subunit mRNA expression is greater in neoplastic and normal epithelium in culture than in the primary tissue, 4) the majority of tumors in culture do not respond to activin or FS treatment with proliferation, and 5) serum activin levels may reflect tumor secretion in some patients. Thus, activin A appears to be available as an autocrine/paracrine factor in epithelial ovarian tumors and may contribute to circulating levels, but its role in tumorigenesis has yet to be defined.     

Cytogenetic studies in reproductive loss

On the basis of the two years investigations carried on the green pea (var. Delis 11 fold), it was confirmed that blanching and freezing decrease the content of albumen and amino acids. The sterilizing belongs to the most drastic process. It was also confirmed that methionine limits the content of albumen.     

Cytogenetic studies of acute promyelocytic leukemia

Translocation t(15;17) is reported in bone marrow cells from six of seven patients with active acute promyelocytic leukemia (APL). One patient who showed t(15;17) at final relapse did not show it in directly prepared or cultured cells taken from a previous relapse. Bone marrow samples from two patients showed only cells with a normal karyotype in the direct preparation, whereas more than 60% of cells cultured for 24 hr showed t(15;17). R-Banding, G-banding, and an attempt at high-resolution banding indicated the break points t(15;17)(q24;21) for one of our patients.     

Management of early-stage epithelial ovarian cancer

"Early" epithelial ovarian carcinoma encompasses a spectrum of patients with diseases that have markedly different survivals, ranging from indolent lesions truly confined to the ovary to high-grade lesions that have a significant chance of occult metastasis at the time of diagnosis. The basic principles of management rest on an adequate primary surgical procedure that removes all gross disease and accurately assesses the sites at risk for metastasis with a comprehensive staging laparotomy. After a comprehensive staging laparotomy, patients can be stratified into low-risk and high-risk groups. Those with low-risk disease have such a low risk of recurrence that the toxicity of adjuvant therapy is not warranted. Although patients with high-risk disease have a high enough of a risk of recurrence to justify consideration of adjuvant therapy, their ultimate prognosis may be determined more by an accurate determination of the stage of disease rather than by currently available, marginally effective or ineffective therapy. Patients who are thought to have early stage disease on the basis of inadequate staging procedures either should undergo a restaging laparotomy or receive therapy for the possibility of occult advanced disease.     

Chemotherapy of ovarian carcinoma

The relative reproducibility of two widely used arbitrary face-bow transfer systems, the Denar Slidematic and the Dentatus type AEB, was assessed for use in orthognathic surgery planning. A novel method was also developed to determine any variation in three-dimensional spatial position and orientation of the maxillary cast. This envelope of movement enabled realistic comparisons to be made for each face-bow system, operator, and skeletal type. The overall face-bow/articulator procedure showed poor reproducibility. However, the Denar Slidematic face-bow was better (P < 0.001) than the Dentatus type AEB standard face-bow, and the errors were higher in the anteroposterior and lateral directions than the vertical direction. There was no significant difference between operators for each system.     

Update of ovarian carcinoma

Correct histopathologic diagnosis of ovarian carcinoma is essential, because biological behavior of the disease varies by the histologic subtype and its grade of differentiation. The standard treatment modality of advanced ovarian carcinoma has consisted of an initial maximal surgical effort and subsequent platinum-based chemotherapy, followed by a secondary surgery. "Maximal surgical effort" is a convenient term but it does not define a surgical procedure. In USA, since 1996, paclitaxel/cisplatin had become a 1st-line regimen. Introduction of other potent agents including topotecan/CPT-11 and previous evidence of the efficacy of doxorubicin have made it difficult to decide which regimen is the most potent. A maximal effort should be made at the second surgical attempt after completing a planned 1st regimen. Finally, we should obtain a pathologically complete response with the combined use of surgery and chemotherapy to achieve long-term survival in patients with advanced ovarian carcinoma.     

Distribution pattern and risk factors of pelvic and para-aortic lymph node metastasis in epithelial ovarian carcinoma

The distribution of lymph node metastasis and the clinicopathologic risk factors for nodal involvement in ovarian carcinoma need to be clarified based on systematic lymph node dissection. We studied 115 patients with ovarian carcinoma who underwent systematic pelvic and para-aortic lymph node dissection between 1987 and 1997. The incidence and distribution of lymph node metastasis are described and the clinico-pathologic risk factors for nodal involvement are investigated. Based on the occurrence of lymph node metastasis in the early stages, the incidence of solitary node involvement and the distribution of lymph node metastasis, we conclude that the primary site of nodal involvement in ovarian carcinoma is the para-aortic node (PAN), especially PAN superior to the inferior mesenteric artery (IMA). By univariate analysis, clinical stage, histologic type (mucinous vs. others), grade, multiple peritoneal metastases, peritoneal cytology, volume of ascites and serum CA125 level were correlated with overall incidence of lymph node metastasis. By performing a multivariate analysis with the clinical stage excluded, it was revealed that grade and peritoneal cytology were independent factors for PAN metastasis (p < 0.0025 and < 0.001, respectively) and that multiple peritoneal metastases and PAN metastasis were significant predictors of pelvic node metastasis (p < 0.01 and < 0.005, respectively). In conclusion, the PANs superior and inferior to IMA should be explored in staging of ovarian carcinoma that appears to be confined to the ovaries. To determine accurately the extent of disease, both the para-aortic and pelvic areas may need to be sampled or dissected in the case of ovarian carcinoma involving the peritoneal surfaces.     

Light dosimetry for intraperitoneal photodynamic therapy in a murine xenograft model of human epithelial ovarian carcinoma

This study aims (i) to ascertain whether oxidative-stress-induced disturbances in chromosomal distribution in the metaphase-II spindle of mouse oocytes can be counteracted by supplementing culture medium with antioxidants; and (ii) to determine whether supplemental intake of antioxidants neutralizes the disturbing effects of maternal ageing on segregation of chromosomes during the first meiotic division and distribution of chromosomes in the metaphase-II spindle. (i): Germinal vesicle oocytes from unstimulated 10-12 week old mice were matured in vitro in the presence or absence of diamide and/or dithiothreitol. Metaphase-II oocytes were fixed and stained with 4',6-diamidino-2-phenylindole (DAPI) to detect abnormalities in chromosomal distribution. The percentage of oocytes arrested in metaphase I (12.9% vs 28.4%; P < or = 0.05) or with a telophase-I chromosome configuration (0.0% vs 8.2%; P < or = 0.0005) was decreased in diamide-DTT-treated oocytes when compared to diamide-treated oocytes. (ii): Mice were fed, from the first day of weaning until their death, a diet supplemented or not with an antioxidant mixture of vitamin C and vitamin E. Ovulated oocytes were fixed and stained with DAPI or C-banded for chromosome analysis. The percentage of abnormal (chromosome scattering and nulloploidy) or asynchronous (anaphase I or telophase I) oocytes was 2.7-fold higher in controls than in females fed an antioxidant diet (24.4% vs 8.9%, P < or = 0.05). Furthermore, the percentage of aneuploidy (2.2% vs 0.0%; P < or = 0.01) and diploidy (5.8% vs 1.7%; P < or = 0.05) was significantly higher in controls than in females fed an antioxidant diet. These findings support Tarin's oxidative stress hypothesis of aneuploidy and have clinical implications for preventing both laboratory-induced and maternal-age-associated aneuploidy in human beings.     

Quantitative studies of the kallikrein-prokallikrein system in mixed saliva in oral squamous epithelial carcinoma

We report a 3-year-old girl with the association of spondyloepiphyseal dysplasia, nephrotic syndrome, and signs of defective cellular immunity. The findings are similar to those reported by Spranger et al., which have become known as Schimke immunoosseous dysplasia.     

Cytogenetic analysis in transitional cell carcinoma of the bladder

The potential use of numerical chromosomal abnormalities as predictive factors for the clinical behaviour of transitional cell carcinoma (TCC) was investigated. The effects on survival and progression-free survival were measured in 91 patients with TCC treated by transurethral resection. The survival rate of patients having tumours with a diploid chromosomal modal number was significantly better than that of patients having tumours with a hyperdiploid chromosomal modal number. The survival rate of patients having TCC with diploid cells only was also significantly better than that of patients having TCC with both diploid and hyperdiploid cells. Progression-free survival was significantly higher in patients having TCC with a diploid modal number of chromosomes than in patients with a hyperdiploid modal number. Simultaneous evaluation of the modal chromosome number or chromosomal range, histological grade, category and mitotic index of the tumour, and the patient's age and sex as prognostic factors in multivariate analyses showed that the category of bladder carcinomas was the most important factor in predicting the survival rate. In patients with superficial tumours (category Ta and T1) the modal chromosome number was the most important factor in predicting survival. For progression-free survival, the modal chromosome number appeared to be the most important factor. It was concluded that the modal chromosome number in TCC was useful in predicting survival in patients with superficial tumours and in predicting progression-free survival in patients with tumours of all categories.     

Biological characterization of human epithelial ovarian carcinoma cells in primary culture: the insulin-like growth factor system

Current hypotheses for explaining which sex cares for offspring assume a relationship between the mode of fertilization and the sex showing parental care. In general, it is hypothesized that maternal care should be concentrated in taxa with internal fertilization, and paternal care should be concentrated in taxa with external fertilization. Studies have supported this relationship; however, new comparative techniques and new data on parental care and the frequency of internal fertilization in anurans suggest that the relationship should be re-evaluated. I examined the relationship between mode of fertilization and sex providing parental care in 334 taxa of anurans using concentrated changes tests and in 396 taxa of anurans using a method developed by Ridley (1983. The Explanation of Organic Diversity. The Comparative Method and Adaptations of Mating. Oxford: Clarendon). The results of the concentrated changes tests showed that both female and male parental care are randomly distributed among taxa with respect to mode of fertilization. However, using Ridley's method, I found significant relationships between mode of fertilization and sex providing parental care. The observed and expected numbers of transitions from external fertilization and no parental care to external fertilization and male parental care or to internal fertilization and female parental care are not qualitatively different. Therefore, the results of my analyses suggest that current hypotheses for explaining the occurrence of maternal versus paternal care in anurans should be reconsidered. Copyright 1998 The Association for the Study of Animal Behaviour.     

Cytogenetic studies of the effects of 5-fluorouracil in vivo

Cytogenetic analysis was carried out of the culture of peripheral blood lymphocytes of 10 healthy donors and 40 patients with malignant tumours of digestive tract treated with 5-fluorouracil. The frequency of cells with chromosome aberrations in the lymphocyte culture of the patients before the treatment was significantly higher than that in the healthy donors. The difference in the frequency of the aberrant metaphases between treated and intact patients was statistically insignificant.     

Neurologic complications of ovarian carcinoma

1. Hyperbaric or hyperoxic or both conditions may affect the disposition of drugs by (1) changes in the catalytic activity of drug metabolizing enzymes, (2) hemodynamic changes and (3) changes in membrane permeability, affecting drug distribution. 2. In isolated microsome preparations from rat liver, the metabolism rate of aniline, but not of amidopirin, is reduced by hyperoxia. In vivo, the clearance of salicylic acid is enhanced in the dog at 2.8 ATA and 100% O2, but not at 6 ATA and air, for reasons that are still unknown. The disposition of theophylline, pentobarbital or pethidine is not affected in dogs by hyperbaric or hyperoxic conditions. 3. In human volunteers, hyperbaric or hyperoxic or both conditions do not affect the disposition of gentamycin (2.4 bar, 100% O2), caffeine or lidocaine (2.5 bar, 100% O2). 4. In conclusion, a single exposure to hyperbaric or hyperoxic conditions does not seem to affect single-dose pharmacokinetics of drugs eliminated by the kidney (gentamycin) or by the liver with a capacity-limited clearance (pentobarbital, theophylline, caffeine) or with a perfusion-limited clearance (pethidine, lidocaine). The enhancement of salicylic acid clearance in dogs under hyperoxic conditions remains unclear.     

Segregation analysis of epithelial ovarian cancer in Finland

Epithelial ovarian cancer is known to aggregate in families. The dominantly inherited ovarian cancer predisposing genes, BRCA1, BRCA2 and genes involved in the hereditary non-polyposis colorectal cancer (HNPCC) syndrome, have recently been identified. However, in the majority of families with more than one case of ovarian cancer, dominant inheritance cannot be recognized. We investigated familial clustering of epithelial ovarian cancer in a population-based sample of 663 Finnish ovarian cancer patients. A segregation analysis with the POINTER software was conducted on the 937 nuclear families from these 663 pedigrees. The major gene model was favoured, and the sporadic and multifactorial models were strongly rejected. In the studied population, the best fitting model was a recessive mode of inheritance, and 8% of ovarian cancer patients were estimated to be homozygous for the deleterious genotype. This evidence for recessively inherited ovarian cancer predisposition should be interpreted cautiously, as the analysis is subject to certain errors, which are discussed in the article. Results of this analysis, however, strongly emphasize the role of genetic factors in all familial aggregation of epithelial ovarian cancer.