ABSTRACT
The effects of vaginal bleeding during first and second trimester on pregnancy outcomes was assessed in a hospital-based population of 268 non-diabetic women. The group of non-bleeders comprised 173 females whereas, there were 71 females with first and 24 with second trimester bleeding. Fetal loss (abortion) occurred in 34% of first trimester and 25% of second trimester bleeders. Low birth weight and preterm delivery were significantly associated with second trimester haemorrhage. The results suggest that first and second trimester vaginal bleeding correlates with adverse infant outcomes.
Subject(s)
Infant, Low Birth Weight , Infant, Premature , Pregnancy Complications, Cardiovascular/epidemiology , Pregnancy Outcome/epidemiology , Uterine Hemorrhage/epidemiology , Abortion, Spontaneous/epidemiology , Adolescent , Adult , Case-Control Studies , Chi-Square Distribution , Female , Humans , Infant Mortality , Infant, Newborn , Pakistan/epidemiology , Pregnancy , Pregnancy Trimester, First , Pregnancy Trimester, Second , Retrospective StudiesABSTRACT
Transforming growth factor beta-1 (TGF-beta 1) has been proposed as a mediator of tumour growth in a number of tumours and cell lines including prostate, and in a recent study was shown to be up-regulated in the stroma of breast cancer tissue following treatment with the anti-oestrogen tamoxifen. Immunolocalisation of the intracellular form of TGF-beta 1 confirmed that the source of the stromal TGF-beta 1 was the peritumoral fibroblasts. We present here the results of a study in which five patients with hormonally unresponsive prostatic carcinoma and seven patients responding to a luteinising hormone-releasing hormone analogue had prostate biopsies taken before and during treatment. These were stained for TGF-beta expression prior to treatment and at either relapse or 3 months later respectively. Six of seven clinically responding tumours and three of five relapsed tumours showed up-regulation of extracellular TGF-beta 1, again primarily in the stroma, with no apparent up-regulation of intracellular TGF-beta 1, TGF-beta 2 or TGF-beta 3. These data illustrate that the epithelial growth inhibitor TGF-beta 1 can be induced by hormonal manipulation in prostate cancer in vivo, and may continue to be up-regulated even after relapse. This suggests that relapse of hormonally treated prostate cancer may be associated with a failure of the epithelium to respond to stromal TGF-beta 1.
Subject(s)
Diethylstilbestrol/therapeutic use , Leuprolide/therapeutic use , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/metabolism , Transforming Growth Factor beta/biosynthesis , Androgens/pharmacology , Biopsy , Extracellular Space/metabolism , Humans , Immunohistochemistry , Male , Neoplasms, Hormone-Dependent/drug therapy , Neoplasms, Hormone-Dependent/metabolism , Orchiectomy , Prostatic Neoplasms/pathology , Transforming Growth Factor beta/metabolism , Up-Regulation/drug effects , Up-Regulation/physiologyABSTRACT
Previous studies have shown that in the breast there are multiple forms of the enzyme oestradiol dehydrogenase (E2DH), responsible for the interconversion of oestrone (E1) to oestradiol (E2). We have now re-examined oestrogen metabolism in the breast cancer cell lines (T47D and MCF-7) and have shown that steroids previously shown to inhibit the conversion of E1 to E2 in normal breast tissue failed to do so when added to growing monolayers of these malignant cells. In contrast to earlier estimates in normal breast tissues, the apparent Km for this conversion in monolayers of these malignant cells is shown here to be considerably lower, at around 50 nM. Cell free studies on these cell lines have revealed the presence of a high affinity (for E1) form of this enzyme of Mw approximately 80 kDa. The ability to detect this enzyme in soluble cell fractions appears to be critically dependent on buffer composition. Normal breast epithelial cells and adipose tissue appear to be devoid of this form of E2DH. As this form of E2DH has the highest affinity for the substrate E1 of all the forms in the breast, it is probable that this 80 kDa enzyme is responsible for the conversion of E1 to E2 in cell monolayers. If the observation holds that the 80 kDa enzyme is absent in the normal tissues, then the possibility arises that this E2DH may be linked with the neoplastic process in some breast tumours containing malignant epithelial cells of a similar type as studied here.
Subject(s)
Breast Neoplasms/metabolism , Estradiol Dehydrogenases/metabolism , Estradiol/biosynthesis , Estrone/metabolism , Adipose Tissue/enzymology , Breast/enzymology , Cell-Free System , Epithelium/enzymology , Estradiol Dehydrogenases/isolation & purification , Female , Humans , Kinetics , Molecular Weight , Tumor Cells, CulturedABSTRACT
We have investigated the ability of tamoxifen to regulate members of the transforming growth factor beta (TGF-beta) family in human breast cancers in vivo. Using immunohistochemical techniques, we find that 3 months of tamoxifen treatment causes a consistent induction of extracellular TGF-beta 1 in breast cancer biopsies, compared with matched pretreatment samples from the same patient. The induced TGF-beta is localized between and around stromal fibroblasts and appears to be derived from these cells. Lower levels of TGF-beta 1,-beta 2, and -beta 3 seen in epithelial cells were not altered by tamoxifen treatment. The increased stromal staining of TGF-beta 1 occurred in estrogen receptor-negative as well as estrogen receptor-positive tumors. These results provide in vivo evidence for a novel, estrogen receptor-independent mechanism of action for tamoxifen, involving the stromal induction of a potent growth inhibitor for epithelial cells.
