It is generally accepted that local growth of solid tumors and their ability to establish distant metastases are dependent on the formation of new blood vessels arising from preexisting ones (angiogenesis). The angiogenic response of the host is mediated by angiogenic molecules that are released from cancer and normal stroma cells, especially fibroblasts. The goal of the present study was to quantitatively compare the expression of the two most important angiogenic growth factors (VEGF, angiogenin) of cervical cancer cells (HeLa and Me-180) with that of cervical cancer-derived fibroblasts (from one tumor/patient) under defined normoxic and hypoxic conditions in vitro. The growth kinetics of cervical cancer cells (HeLa and Me-180) and tumor-derived fibroblasts were evaluated in vitro under normoxic and hypoxic conditions. Growth factor concentrations in the cell culture medium were measured by ELISA and the secretion rates per cell were calculated. Under normoxic conditions, both the cervical cancer cells as well as the tumor-derived fibroblasts released VEGF and angiogenin. The secretion rate of both angiogenic factors was significantly higher in the stroma cells than in the tumor cells (P < 0.05). VEGF and angiogenin secretion is significantly higher in the stroma cells under hypoxia than in the tumor cells investigated (P < 0.05). The presented data support the concept that in cervical cancer non-neoplastic fibroblasts could play a pivotal role in the complex process of tumor angiogenesis.

Cell Division↗

PubMedDate not supplied

Multivariate independent prognostic factors in endometrial carcinoma: a clinicopathologic study in 181 patients: 10 years experience at the Department of Obstetrics and Gynecology of the Mainz University.

The aim of this study was to evaluate the biologic outcome of endometrial carcinomas as compared to clinical and pathologic parameters and to identify multivariate independent prognostic factors. Charts were abstracted from patients with endometrial carcinoma from 1985 to 1995. Data on clinicopathologic variables, adjuvant treatment, site of recurrence, and survival were collected. chi2 test was used to test association between variables. Kaplan-Maier method was used for survival analysis and Cox proportional hazards model for multiple regression analysis. Univariate analysis revealed that FIGO stage, tumor grade, depth of myometrial invasion, biochemical analysis of progesterone receptor status, age, additional diabetes mellitus, lymph node metastasis, and type of tumor were significantly associated with the overall-survival. For disease-free interval, FIGO stage, tumor grade, depth of myometrial invasion, biochemical analysis of progesterone receptor status, lymph node metastasis, and type of tumor were also significantly associated. Multivariate analysis revealed that FIGO stage, tumor grading, tumor type, depth of myometrial invasion, and biochemically measured progesterone receptor status were associated significantly with overall survival. A significant correlation as independent prognostic factors were also seen for recurrence free interval for FIGO stage, tumor grade, and biochemical progesterone receptor status. In multivariate statistical analysis we identified FIGO stage, tumor type, tumor grade, biochemical analysis of progesterone receptor status, and depth of myometrial invasion as independent prognostic factors for overall survival, and FIGO stage, biochemical analysis of progesterone receptor status, and tumor grade as independent prognostic factors for recurrence-free interval.

Adenocarcinoma↗

PubMedDate not supplied

CD8+CD45RA+CD27-CD28-T-cell subset in PBL of cervical cancer patients representing CD8+T-cells being able to recognize cervical cancer associated antigens provided by HPV 16 E7.

OBJECTIVE: In response to antigenic stimulation, naive MHC-class I restricted and antigen-specific CD8+CD45RA+CD28+T-cells undergo clonal expansion and differentiate into CD8+CD45RO+ memory T-cells. Upon re- encounter with the nominal antigen, CD45RO+ T-cells are able to convert to CD8+CD45RA+CD28-T-cells displaying potent immune effector functions, including TNF-alpha production. This T-cell subpopulation constitutes a minor population in healthy individuals. In the present study we are currently evaluating whether this particular T-cell subset in PBL represents CD8+T-cells which may be able to recognize cervical cancer associated antigens provided by HPV 16 E7. MATERIAL AND METHODS: Flow-cytometric cell sorted CD8+CD45RA+CD28- and CD8+CD45RA+CD28-T-cells were obtained from patients with cervical cancer and tested for recognition of HLA-A2 restricted peptides derived from the human papillomavirus (HPV)16-E7 gene product using ELISA. HPV DNA in tumor tissue was detected by PCR. RESULTS: We show that the effector CD8+CD45RA+CD28-T-cell subset is expanded in peripheral blood lymphocytes (PBL) from patients with cervical cancer, but also in PBL from patients with an acute mycobacterial infection. CD8+T-cells from 3/6 cancer patients showed a peptide-specific immune response which could be segregated in peptide epitopes which elicited either a strong TNF-alpha production, or GM-CSF and IL-2 secretion. Peptide-reactivity could exclusively be detected in the ex vivo freshly isolated CD8+CD45RA+CD28-T-cell population. A similar situation was found to be true for HLA-A2 presented peptide epitopes derived from M. tuberculosis-associated antigens presented to T-cells obtained from patients with tuberculosis. CONCLUSIONS: The sorting of CD8+CD45RA+CD28-T-cells enables to determine the fine specificity of CD8+ effector T-cells without the need for in vitro manipulation and aids to define the most appropriate target epitopes for novel vaccine designs.

Amino Acid Sequence↗

PubMedDate not supplied

[Circadian blood pressure rhythm in preeclampsia as a predictor of maternal and obstetrical outcome].

BACKGROUND: Preeclampsia is a pregnancy-induced multiorganic disease. The incidence is 5 - 7 % in all pregnant women. To assess the value of circadian blood pressure rhythm in preeclamptic women, 24-hour blood pressure monitoring might be useful. The purpose of this study was to determine the predictive value of circadian blood pressure rhythm for the maternal and obstetrical outcome in patients with mild preeclampsia. PATIENTS AND METHODS: Sixty-six patients with mild preeclampsia underwent 24-hour blood pressure monitoring between 29 and 39 weeks gestation. Twenty-eight patients with normal circadian blood pressure rhythm were compared with thirty-eight patients with suspended circadian blood rhythm. RESULTS: There was no difference in age, body mass index, gravidity, parity, miscarriage, or fetal outcome between the two groups. The rate of secondary caesarean section was 39.5 % in the suspended circadian blood pressure group and 21.4 % in the normal circadian blood pressure group, respectively (P = 0.03). CONCLUSIONS: In patients with mild preeclampsia, the circadian blood pressure rhythm appears to be unsuitable as a screening test. Further research is required for more etiological and pathophysiological insights into the development of clinically useful tools with predictive value.

Adolescent↗

PubMedDate not supplied

Sonographic prognostic factors in prenatal diagnosis of SCT.

OBJECTIVE: A subset of fetuses with sacrococcygeal teratomas (SCT) develops hydrops caused by high-output heart failure. Identification of fetuses at risk for hydrops is important because surgical intervention may reverse the pathophysiology of the disease. The aim of this study was to evaluate sonographic prognostic factors regarding tumor morphology and vascularity associated with the development of hydrops in utero. METHODS: Over a 10-year period, we identified 7 fetuses with SCT diagnosed antenatally and managed at the University of Mainz. We retrospectively reviewed the charts of mothers and infants and recorded data on prenatal diagnosis, tumor size and localization, perinatal management, neonatal care, and fetal outcome. RESULTS: The diagnosis of SCT was made in all cases by ultrasound. The median gestational age at the time of initial diagnosis was 23 weeks. In 3 cases, signs of fetal heart failure were detected by ultrasound. Pathological blood flow in the venous system was further noted in 2 cases. One fetus developed hydrops. The mean gestational age at delivery was 35 weeks, depending on the presence or absence of maternal or fetal complications. Six infants were delivered by cesarean section, and 1 by vaginal delivery. After fetal stabilization, surgery was performed in 5 of 7 cases. Inadequate ventilation secondary to prematurity was a contributing factor to death in 1 fetus. One fetal intrauterine death occurred at 27 weeks of gestation. CONCLUSION: Pregnancies with antenatally diagnosed fetal SCT necessitate frequent monitoring to ensure the detection of fetal/maternal complications by ultrasound and Doppler ultrasound. The most important prognostic criteria were cardiomegaly, fetal hydrops, and increased preload indexes of the fetal venous system as sign of fetal heart failure. Many studies show that the occurrence of pulsations in the umbilical vein of a hydropic fetus correlates with a poor fetal outcome. The decision on the optimal time of delivery should therefore be made by a multidisciplinary team of specialists.

Diagnosis, Differential↗

PubMedDate not supplied

PAF receptor. 2. Quantitative hydrophobic contribution of the agonist's etheroxid chain.

In order to undertake a quantitative assessment of the contribution of the hydrophobic effect of the etheroxid chain to agonistic activity, it was necessary to include in the calculated data a highly lipophilic platelet-activating factor (PAF) analogue. The synthesis of such a compound--racemic 1-O-docosyl-2-O-acetylglycero-3-phosphocholine (C22 PAF)--is described. The regression analysis performed with data of 14 etheroxid analogues (reviewed by Godfroid et al., 1987), combined with data obtained with C22 PAF, is significant with respect to a parabolic evolution between lipophilicity of the chain and the logarithm of relative platelet stimulation. This result is characteristic of a hydrophobic interaction between the agonist and the PAF receptor.

Animals↗

PubMedDate not supplied

[Parietal chondrosarcoma arising after excision and irradiation of breast adenocarcinoma].

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Adenocarcinoma↗

PubMedDate not supplied

[Pseudo-ovarian primary peritoneal carcinosis. Apropos of a case].

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Aged↗