853 research outputs found
Gonadotropin-releasing hormone receptor-targeted gene therapy of gynecologic cancers
No full textThe majority of ovarian, endometrial, and breast cancers express gonadotropin-releasing hormone (GnRH) receptors. Apart from reproductive organs (ovaries, fallopian tubes, and uterus) that are normally removed during surgical therapy of ovarian or endometrial cancer, pituitary gonadotrophs also express GnRH receptors. The signal transduction pathway in tumor cells is basically different from the classic GnRH receptor signal transduction, which is known to operate in the pituitary gonadotrophs and can therefore be considered tumor specific. Other organs and hematopoetic stem cells do not express GnRH receptors. We have recently shown specific activation of nucleus factor kappaB in ovarian, endometrial, and breast cancers after treatment with GnRH agonists. Based on this tumor-specific signaling pathway and the distribution pattern of GnRH receptors, we have developed and successfully tested a gene therapy concept by using a GnRH analogue as an inducer for the transcription of a therapeutic gene in cell culture and in nude mice
Polysomy 8 in three cases of homologous malignant mixed mullerian tumors of the uterus
No full textUnique genetical gain of 8q and/or polysomy 8 identified after short-term culture are presented in three cases of malignant mixed Mullerian tumors (MMMT) of the uterus. All tumors revealed abnormal karyotypes and modal chromosome numbers in the hyperdiploid range. Two out of three cases exclusively demonstrated numerical aberrations, most prominently polysomy 8. One tumor revealed tetrasomy 8 as the sole aberration. The third tumor showed a more complex karyotype, including two unbalanced translocations, leading to partial gain of 8q. These cytogenetic findings, together with 14 previously reported cases of MMMT and 5 cell lines, suggest a distinct subgroup of endometrial MMMT characterized by gain of chromosome 8 or 8q
Predictive value of routine circulating soluble endothelial cell adhesion molecule measurements during pregnancy
No full textBackground. The present study was aimed at determining whether routine prenatal measurements of circulating soluble intercellular adhesion molecule (sICAM-1; CD54) and soluble vascular cell adhesion molecule (sVCAM-1; CD106) in midgestation have predictive value for the identification of pregnant women destined to develop preeclampsia or other complications of pregnancy during late gestation. Methods: Plasma sICAM-1 and sVCAM-1 were analyzed between weeks 22 and 29 of gestation in 1543 pregnant women and related to the outcome of pregnancy in a prospective longitudinal study. Results: Plasma sICAM-1 and sVCAM-1 in uncomplicated pregnancies were normally distributed and varied over a small range (sICAM-1, SD = 22.5%; sVCAM-1, SD = 25.5%). Of all analyzed uncomplicated pregnancies, 54 (3.95%) were identified with concentrations of sICAM-1 or sVCAM-1 above the mean + 2 SD. In contrast, of 177 pregnancies with complications (prevalence, 11.5%), 97 (55%) had sICAM-1 or sVCAM-1 concentrations above the same cutoffs weeks before the onset of disease. The sensitivities of sICAM-1 and sVCAM-1 measurements were 66% for preeclampsia and hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome), 42% for gestational hypertension, 50% for fetal retardation, 46% for preterm labor, 50% for gestational diabetes mellitus, 67% for gestational proteinuria, and 70% for infections during pregnancy. Taken together, routine prenatal sICAM-1 and sVCAM-1 measurements had an overall predictive value of 64%. Conclusions: Midgestation measurements of circulating sICAM-1 and sVCAM-1 have a high predictive value (area under the curve of combined sICAM-1 and sVCAM-1 measurements determined by ROC analysis, 0.85) and may identify up to 55% of pregnant women who will later develop a severe pregnancy-related complication. (C) 2002 American Association for Clinical Chemistry
Global, local and graphical person-fit analysis using person response functions
No full textPerson-fit statistics test whether the likelihood of a respondent’s complete vector of item scores on a test is low given the hypothesized item response theory model. This binary information may be insufficient for diagnosing the cause of a misfitting item-score vector. The authors propose a comprehensive methodology for person-fit analysis in the context of nonparametric item response theory. The methodology (a) includes H. Van der Flier’s (1982) global person-fit statistic U3 to make the binary decision about fit or misfit of a person’s item-score vector, (b) uses kernel smoothing (J. O. Ramsay, 1991) to estimate the person-response function for the misfitting item-score vectors, and (c) evaluates unexpected trends in the person-response function using a new local person-fit statistic (W. H. M. Emons, 2003). An empirical data example shows how to use the methodology for practical person-fit analysis
Predictive value of routine circulating soluble endothelial cell adhesion molecule measurements during pregnancy
No full textBackground. The present study was aimed at determining whether routine prenatal measurements of circulating soluble intercellular adhesion molecule (sICAM-1; CD54) and soluble vascular cell adhesion molecule (sVCAM-1; CD106) in midgestation have predictive value for the identification of pregnant women destined to develop preeclampsia or other complications of pregnancy during late gestation. Methods: Plasma sICAM-1 and sVCAM-1 were analyzed between weeks 22 and 29 of gestation in 1543 pregnant women and related to the outcome of pregnancy in a prospective longitudinal study. Results: Plasma sICAM-1 and sVCAM-1 in uncomplicated pregnancies were normally distributed and varied over a small range (sICAM-1, SD = 22.5%; sVCAM-1, SD = 25.5%). Of all analyzed uncomplicated pregnancies, 54 (3.95%) were identified with concentrations of sICAM-1 or sVCAM-1 above the mean + 2 SD. In contrast, of 177 pregnancies with complications (prevalence, 11.5%), 97 (55%) had sICAM-1 or sVCAM-1 concentrations above the same cutoffs weeks before the onset of disease. The sensitivities of sICAM-1 and sVCAM-1 measurements were 66% for preeclampsia and hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome), 42% for gestational hypertension, 50% for fetal retardation, 46% for preterm labor, 50% for gestational diabetes mellitus, 67% for gestational proteinuria, and 70% for infections during pregnancy. Taken together, routine prenatal sICAM-1 and sVCAM-1 measurements had an overall predictive value of 64%. Conclusions: Midgestation measurements of circulating sICAM-1 and sVCAM-1 have a high predictive value (area under the curve of combined sICAM-1 and sVCAM-1 measurements determined by ROC analysis, 0.85) and may identify up to 55% of pregnant women who will later develop a severe pregnancy-related complication. (C) 2002 American Association for Clinical Chemistry
New developments in the treatment of cervical cancer
No full textCervical cancer is world-wide the second most frequent cancer found in women and represents 12% of all female malignancies. In fact, it is the most common female cancer in developing countries. There is now sufficient evidence to recommend that women with locally advanced cervical cancer confined to the pelvis receive concurrent pelvic radiation and chemotherapy. New surgical techniques such as laparoscopically assisted radical vaginal hysterectomy and trachelectomy (a fertility-preserving radical operation technique) are being, established and have to be evaluated for their long-term safety. Causal treatment by developing multivalent antiviral drugs and vaccines is no longer a pure theoretical approach. Despite these improvements, the early diagnosis by colposcopy and gynaecological cytology remains the safest method to ensure early treatment avoiding death of cervical cancer
Expression of osteoprotegerin (OPG) and receptor activator of NFkB ligand (RANKL) in 70 breast cancer cells and effects of GnRH treatment on RANKL expression
No full textPolysomy 8 in three cases of homologous malignant mixed mullerian tumors of the uterus
No full textUnique genetical gain of 8q and/or polysomy 8 identified after short-term culture are presented in three cases of malignant mixed Mullerian tumors (MMMT) of the uterus. All tumors revealed abnormal karyotypes and modal chromosome numbers in the hyperdiploid range. Two out of three cases exclusively demonstrated numerical aberrations, most prominently polysomy 8. One tumor revealed tetrasomy 8 as the sole aberration. The third tumor showed a more complex karyotype, including two unbalanced translocations, leading to partial gain of 8q. These cytogenetic findings, together with 14 previously reported cases of MMMT and 5 cell lines, suggest a distinct subgroup of endometrial MMMT characterized by gain of chromosome 8 or 8q
Factor XII deficiency is strongly associated with primary recurrent abortions
No full textObjective: To evaluate factor XII deficiency in women with primary and secondary recurrent abortion. Design: Prospective case-control study. Setting: University hospital. Patient(s): Sixty-seven women with primary and 33 women with secondary recurrent abortion of unexplained nature and 49 healthy controls with no history of thrombotic disease or adverse pregnancy outcomes. Main Outcome Measure(s): Plasma factor XII activity, activated protein C resistance, factor V Leiden mutation analysis, protein C, protein S, antithrombin III, karyotyping, and anticardiolipin antibodies. Result(s): Ten of 67 women with primary recurrent abortion (14.9%) and 4 of 33 women (12.1%) with secondary recurrent abortion had reduced factor XII activity (<60%). These results are highly significant in the former group and showed a tendency toward significance in the latter group. All controls had normal factor XII activity. Conclusion(s): Factor XII deficiency is strongly associated with primary recurrent abortion, and women with secondary recurrent abortion show a tendency toward factor XII deficiency. (C) 2003 by American Society for Reproductive Medicine
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