The expression of CCAAT/enhancer binding protein (C/EBP) in the human ovary in vivo: specific increase in C/EBPbeta during epithelial tumour progression. (1/127)

The CCAAT/enhancer binding protein (C/EBP) family of transcription factors is involved in metabolism and differentiation of cells, especially in rodent liver cells and adipocytes. Their roles in vivo and in particular during pathophysiological conditions in humans are largely unknown. We have investigated the presence of C/EBPalpha, -beta, -delta and -zeta in normal ovaries and in epithelial ovarian tumours of different stages. Immunohistochemical experiments demonstrated that C/EBPalpha and C/EBPbeta were preferentially expressed in epithelial/tumour cells irrespective of stage or grade of the tumour. C/EBPbeta was located in the nuclei of the cells, in contrast to C/EBPalpha, which was present only in the cytoplasm of these cells. The nuclear localization of C/EBPbeta indicates an active role of this transcription factor in tumour cells, whereas the cytoplasmic distribution suggests a more passive function of C/EBPalpha. C/EBPdelta and -zeta demonstrated a more diverse distribution with predominant localization to epithelial cells, but stromal distribution was also noted. The intracellular distribution was confined to both the nucleus and the cytoplasm for C/EBPdelta and -zeta. Western blotting demonstrated that C/EBPalpha, -beta, -delta and -zeta were present in a majority of the samples. The amount of C/EBPbeta increased markedly with malignancy, i.e. with degree of dedifferentiation, while the other members of the C/EBP family displayed a more constant expression level. These results demonstrate an association between the expression of members of the C/EBP family and the formation of epithelial ovarian tumours, with C/EBPbeta as a potential marker for these tumours. As C/EBPbeta is known to be expressed during proliferation of cells in vitro, it may participate in the proliferative process of ovarian epithelial tumour cells in vivo and play a central role in tumour progression.  (+info)

In vitro estrogen-binding by human breast carcinomas. (2/127)

Patients whose breast carcinomas possess only low concentrations of a receptor molecule that binds estrogens with high affinity are unlikely to respond to hormonal manipulative therapy when the disease recurs. The estrogen-binding capacity of 106 breast carcinomas was measured by an in vitro method and was expressed per milligram wet weight and in some cases related to the concentration of deoxyribonucleic acid (DNA) of the tumours. The ability of tumors to bind 3H-estradiol ranged from 0 to 1.3 fm/mg in pre- and perenopausal women, and from 0 to 16.8 fm/mg in postmenopausal women. Menopausal status or serum concentrations of endogenous estrogen, or both, should therefore be considered when tumours are classified into low and high estrogen-binding capacity. It is not necessary to carry out Scatchard analysis for every tumour, and expressing estradiol binding on the basis of DNA concentration may be preferable to expressing in on a wet-weight basis.  (+info)

Serous adenocarcinofibroma of the ovary--report of two cases and review of the literature. (3/127)

We investigated the clinical and histologic characteristics of patients with ovarian serous adenocarcinofibroma. Because the tumors in both cases contained fibroma components; they were hard and clinically indistinguishable from uterine myoma, even by computed tomography. Both patients experienced relapses associated with tumors that originated outside the abdominal cavity (the subcutaneous abdominal wall in case 1, and the inguinal lymph nodes in case 2). The serum level of CA125 was normal or only moderately elevated at the first onset and relapse. The present cases suggest that the diagnostic features and clinical course differ between ovarian serous adenocarcinoma and serous adenocarcinofibroma.  (+info)

Alterations in the expression of the DNA repair/redox enzyme APE/ref-1 in epithelial ovarian cancers. (4/127)

The DNA base excision repair pathway is responsible for the repair of alkylation and oxidative DNA damage. A crucial step in the base excision repair pathway involves the cleavage of an apurinic/apyrimidinic (AP) site in DNA by an AP endonuclease (APE). The major AP endonuclease in mammalian cells is APE/ref-1, a multifunctional enzyme that acts not only as an AP endonuclease but as a redox-modifying factor for a variety of transcription factors. The purpose of this study was to determine the expression of APE/redox factor-1 (ref-1) in ovarian tissues, particularly ovarian cancers. Formalin-fixed, paraffin-embedded specimens of ovarian tissues (normal, various benign conditions, and epithelial cancers) were studied using both polyclonal and monoclonal antibodies to APE/ref-1. The relationship between APE/ref-1 protein levels and DNA repair activity was studied in ovarian Hey and Hey-C2 cell lines using Western blot and a specific AP-site oligonucleotide cleavage assay. Hey and Hey-C2 cells were fractionated, and the nuclear and cytoplasmic extracts were quantitated for protein levels and assessed for APE/ref-1 with Western blot. Normal ovarian tissues consistently demonstrated strong nuclear staining of the surface epithelium, epithelial inclusions, corpora lutea and albicantia, and stroma. Cytoplasmic staining was absent. A similar pattern was seen for benign conditions including endometriosis. Low malignant potential ovarian cancers stained in a pattern similar to normal ovarian and nonneoplastic tissues; however, two specimens also had areas of cytoplasmic staining. Epithelial ovarian cancers were remarkably different from all other ovarian tissues studied. Both nuclear and cytoplasmic staining of the malignant epithelium were seen and ranged from strong to weak, often with considerable staining heterogeneity within the same tumor. The AP-site oligonucleotide cleavage assay indicated that APE/ref-1 protein levels correlate well with DNA repair activity. The increased levels of APE/ref-1 in the Hey-C2 cells was mainly attributable to increased cytoplasmic enzyme. APE/ref-1 immunoreactivity is altered in malignant ovarian tumors. Further studies will determine whether the altered expression and subcellular location reflect changes in redox regulatory functions.  (+info)

Accumulation of collagen in ovarian benign tumours. (5/127)

Extracellular matrix components of benign ovarian tumours (cystadenoma, adenofibroma, cystadenofibroma) were analysed. The investigated tumours contained twice as much collagen than control ovarian tissues. Significant alterations in mutual quantitative relationships between collagens of various types were observed. The proportion of type I collagen decreased and that of type III collagen increased. The accumulation of collagen was accompanied by a reduction in sulphated glycosaminoglycan content whereas the amount of hyaluronic acid was not changed. Dermatan sulphate was the most abundant glycosaminoglycan component. It is suggested that the accumulation of collagen (natural barrier to the migration of tumour cells) and underexpression of glycosaminoglycans/proteoglycans (binding some growth factors and interleukins) may exert an inhibitory effect on tumour growth.  (+info)

Contrast-enhanced sonography in the examination of benign and malignant adnexal masses. (6/127)

Our objective was to characterize the properties of an intravascular ultrasonographic contrast agent in examination of adnexal masses and to compare contrast agent properties between benign and malignant adnexal tumors. Fifty-eight consecutively examined women with suspected ovarian tumors were examined preoperatively by power Doppler ultrasonography, first without and then with contrast agent enhancement (Levovist). Fourteen women had ovarian cancer, 3 had borderline ovarian tumors, 18 had benign ovarian neoplasms, and 23 had functional adnexal cystic masses or endometriomas. The effect of the contrast agent was evaluated visually and by using computerized power Doppler signal intensity measurements. In visual evaluation, the brightness of the power Doppler signal and the amount of recognizable vascular areas increased in each tumor after contrast agent administration. The number of vessels in power Doppler ultrasonograms, both before and after contrast agent enhancement, was significantly higher in malignant than in benign adnexal masses, as also was the increase in the number of recognizable vessels after contrast agent administration. Contrast agent uptake time was significantly shorter in malignant than in benign tumors. No significant differences were found in the power Doppler signal intensities or their changes between benign and malignant tumors. In conclusion, use of sonographic contrast agent facilitates imaging of tumor vessels. For differentiation of benign and malignant tumors, the kinetic properties of the contrast agent, such as uptake and washout times, may have more potential than the use of the contrast agent in anatomic imaging of the tumor vessels.  (+info)

Apparent rat strain-related sensitivity to phorbol promotion of mammary carcinogenesis. (7/127)

It has been reported that twice-weekly i.p. injections of 4 mg phorbol for 10 weeks, after a single feeding of 6 mg dimethylbenz(a)anthracene (DMBA) in female Wistar rats, led to a significant augmentation of mammary adenocarcinoma incidence and of lymphatic leukemia incidence as compared to 6 mg DMBA alone. In an experiment reported here, in female Sprague-Dawley rats, using the same doses of DMBA and phorbol and the same injection schedule, phorbol given after DMBA did not augment mammary adenocarcinoma incidence or lymphatic leukemia incidence as compared to DMBA given alone. It thus appears that there is a strain-related sensitivity between Wistar and Sprague-Dawley rats with regard to the promoting activity of phorbol when phorbol treatment follows DMBA treatment, and mammary adenocarcinoma incidence and lymphatic leukemia incidence are studied. Further, in Sprague-Dawley rats, phorbol did not promote mammary fibroadenoma incidence in DMBA-treated rats, mammary adenocarcinoma incidence in procarbazine-treated rats, and mammary adenocarcinoma incidence or mammary fibroadenoma incidence in X-ray-treated rats. DMBA and procarbazine, with or without phorbol, tended to induce more mammary neoplasms in the anterior (thoracic) than in the posterior (abdominal) mammary glands. X-irradiation tended to induce mammary neoplasms in approximately equal numbers in the anterior and posterior mammary glands. It was suggested that regional differences in chemically induced mammary carcinogenesis were due to a difference in the transport and delivery of the chemical carcinogens to the regions rather than a difference in the amount of mammary gland tissue in the regions. An analysis of the numbers of Sprague-Dawley rats that developed either no mammary neoplasms, or only mammary adenocarcinomas, or only mammary fibroadenomas, or both mammary adenocarcinomas and mammary fibroadenomas in response to DMBA, procarbazine, and X-ray, suggested that the development of a mammary adenocarcinoma or the development of a mammary fibroadenoma are independent processes.  (+info)

Sonographic features of ovarian cystadenofibromas: spectrum of findings. (8/127)

OBJECTIVE: To describe the sonographic characteristics of ovarian cystadenofibromas. METHODS: We conducted a retrospective study of 23 ovarian tumors histopathologically confirmed as ovarian cystadenofibromas that were preoperatively evaluated by transvaginal color Doppler sonography. RESULTS: In all cases the mass was predominantly cystic. Septations appeared in 30.4% of the tumors. Papillary projections or solid nodules appeared in 56.5% of the cases. The most frequent appearance was a unilocular complex cystic mass. In 47.8% of the tumors, vascularization was detected, having a typical pattern of peripheral vascularization with scattered vessels of high blood flow impedance. CONCLUSIONS: We have described the sonographic spectrum of findings of ovarian cystadenofibromas. The most frequent appearance was a unilocular cystic mass with gross papillary projections or solid nodules. In almost half of the tumors, vascularization could be detected.  (+info)

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