Fibronectin plasma levels in gynecological cancers.

PURPOSE: Fibronectin (FBN) is involved in the motility and migration of malignant cells. The purpose of this study was to investigate FBN plasma levels in gynecological cancers patients and in healthy women. METHODS: The study took place between 1998 and 2003. One hundred women with histologically diagnosed cancer of gynecological organs (cervix, ovary, endometrium, breast) formed the study group (group A), whereas the control group (group B) consisted of 100 healthy women. FBN plasma levels were measured with the radial immunodiffusion method. RESULTS: The average age of group A patients was 42.08 years (range 33-77), and of group B it was 41.1 years (range 32-65). Both groups were compared with the Student's-t test. The median plasma value of FBN in all gynecological malignancies was 258.4 mg/l (standard deviation/SD 163.9, p=0.0066, t-statistics: 2.768, (t95): 1.984, 95% CI: 225.4-290.9). The plasma levels were significantly elevated when compared to the control group (median=213 mg/l). The distribution of values showed a statistically important "tail" in high plasma levels (FBN >400 mg/l). Plasma levels of FBN were more increased in breast and cervical malignancies when compared to ovarian and endometrial cancers. CONCLUSION: FBN plasma levels were significantly increased in the total of group A patients, but not significantly increased in the endometrial and ovarian subgroup. Whether or not FBN could reliably be a marker for gynecological cancers should be confirmed in studies with larger number of patients.

The cardiovascular effects of selective estrogen receptor modulators.

Coronary artery disease (CAD) is the main contributor of mortality among postmenopausal women. Menopause-associated estrogen deficiency has both metabolic and vascular consequences that increase the risk for CAD. Hormone therapy (HT) has been reported to have a beneficial effect on metabolic and vascular factors influencing the incidence of CAD. Although observational studies have reported that HT reduces significantly the risk for CAD, randomized clinical trials (WHI, HERS, ERA) have questioned the efficacy of HT in primary and secondary CAD prevention despite confirming the lipid-lowering effect of HT. In the aftermath of the WHI, increased interest has been given to the action of selective estrogen receptor modulators (SERMs) and their effect on the cardiovascular system. The chemical structure of SERMs, either triphenylethilyn (tamoxifen) or benzothiophene (raloxifene) derivatives, differs from that of estrogens. SERMs are nonsteroidal molecules that bind, with high affinity, to the ER. SERMs induce conformational changes to the ligand-binding domain of the ER that modulate the ability of the ER to interact with coregulator proteins. The relative balance of coregulators within a cell determines the transcriptional activity of the receptor-ligand complex. SERMs therefore may express an estrogen-agonist or estrogen-antagonist effect depending on the tissue targeted. SERMs express variable effects on the metabolic and vascular factors influencing the incidence of CAD. SERMs have been reported to modulate favorably the lipid-lipoprotein profile. Toremifene expresses the most beneficial effect followed by tamoxifene and raloxifene, while ospexifene and HMR-3339 have the least effect and may even increase triglycerides. Raloxifene and tamoxifene decrease serum homocysteine levels and C-reactive proteins (CRP), which are both markers of CAD risk. Raloxifene has been reported to increase the nitric oxide (NO)-endothelin (ET)-1 ratio and, thus, contribute to proper endothelial function and vasodilation. Toremifene has no effect on the NO-ET-1 ratio. Finally, raloxifene decreases the vascular cell adhesion molecules and the inflammatory cytokines TNF-alpha and IL-6. Of the SERMs, raloxifene has had the most extensive evaluation regarding the effect on the vascular wall of endothelium. Although not confirmed by large clinical trials, raloxifene has been reported to have an effect on the cohesion of the intercellular junction (VE-cadherin) and the synthesis-degradation of extracellular matrix (MMP-2). The Multiple Outcomes Raloxifene Evaluation (MORE) study has reported that raloxifene may have a cardioprotective effect when administered to postmenopausal women at high risk for CAD disease.