The predictive value of steroid hormone receptor analysis in breast, endometrial and ovarian cancer

The predictive value of female sex steroid, estrogen and progesterone, receptor (ER and PR, respectively) assays in breast, endometrial and ovarian cancer is reviewed with emphasis on comparative aspects of these malignant tumors in relation to their hormone dependency. The endocrine etiology of these three tumor types seems to be at least partly different, and so is the expression of these receptors in normal and malignant tissues of the breast, endometrium and ovary. There is a tendency for decreased receptor concentrations and disappearance of these receptors in association with advancement of these malignancies. There is also a decrease in the presence and concentrations of ER and PR in relation to loss of differentiation in breast and endometrial cancer. Receptor analyses have an established position in the selection of patients with advanced breast cancer for endocrine treatment, and they give promise of a similar application in endometrial cancer and in endometrioid cancer of the ovary. It is not clear whether the disease-free interval is related to the presence or concentrations of ER or PR as such in the tumor tissue. There is better survival in breast cancer patients with receptor-positive tumors, which might be due to a response to endocrine treatment. The same seems to be true for patients with endometrial cancer. Future progress in the application of female sex steroid receptor analyses in breast, endometrial and ovarian cancer needs additional controlled clinical trials and more highly developed receptor assays.     

The effect of season on the circulating concentrations of anterior pituitary, ovarian and adrenal cortex hormones and hormone binding proteins in the subarctic area; evidence of increased activity of the pituitary-ovarian axis in spring

To evaluate the effects of season on the function of the pituitary-ovarian axis and the adrenal cortex in a northern area with great seasonal variation in the length of daylight, 10 healthy women were investigated over 1 menstrual cycle in spring (May-June), autumn (August-September), early winter (November-December) and late winter (February-March). Serum concentrations of LH, FSH, prolactin, estradiol, progesterone, total and free testosterone, cortisol, sex hormone binding globulin (SHBG) and cortisol binding globulin (CBG) were measured, and the indices of free estradiol (FEI), free androgen (FAI) and free cortisol (FCI) were calculated on cycle days 3-4, 6-7, 10-11, on the presumed day of ovulation, and 6-7 and 9-10 days after the presumed ovulation. Spring was the season that most significantly differed from the other seasons. It was characterized by a significantly decreased concentration of SHBG and an increased FAI throughout the whole menstrual cycle, an increased FSH concentration during the follicular phase, significantly increased estradiol concentration and an increased FEI, and significantly decreased concentrations of FSH and LH during the luteal phase of the cycle. The concentration of cortisol and the FCI were significantly increased in the autumn compared with late winter, both seasons having similar day-length. The present data demonstrate that spring, with a long photoperiod, seems to be associated with increased pituitary-ovarian axis activity and androgenic activity, whereas adrenal cortex function did not show any association with day-length.     

Factors related to postmenopausal muscle performance: a cross-sectional population-based study

The aim of the present study was to investigate cross-sectionally the association of postmenopausal muscle strength with simple performance tests. A random sample of 1,166 naturally postmenopausal women (born 1932–1941) was selected from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study cohort. Grip and quadriceps strength were measured with strain gauge dynamometers and reported in both absolute values (KPa and kg) and per kilogram of body mass (N cm^–2 kg^–1 and N kg^–1). In addition, two performance tests, ability to stand on one foot and ability to squat down to touch the floor were carried out. A five-category self-assessment of overall health (very good, good, moderate, bad, and very bad) was obtained by postal questionnaire. The women that were able to stand on one foot and able to squat down to touch the floor had greater grip and quadriceps strength than their counterparts (P<0.001 and P<0.03 in ANOVA, respectively). In addition, self-assessed health had a strong positive association with muscle strength in the grip and leg extensor muscles in ANOVA (P<0.001 between very good and moderate or poorer state of health) and regression model (P<0.001). Adjustment for age, duration of menopause, body mass, height, physical activity level, use of HRT, and number of diseases and medications did not change any of the main effects. Also, there were no differences in results between absolute measurement values and values reported per kilogram of body mass. According to the present study, a simple performance test may be useful in the prediction of postmenopausal muscle strength. Furthermore, self-assessed state of health is strongly associated with muscle strength in postmenopausal women.     

Type-I and type-iii procollagen metabolites and ca 125 in epithelial ovarian-cancer

The clinical courses of 24 patients with advanced epithelial ovarian cancer were monitored with serial serum CA125, PIIINP and PICP determinations before, during and after treatment. Initial serum CA125, PIIINP and PICP concentrations were pathologic in 93%, 80% and 11% of the cases, respectively. Eight patients responded to therapy with complete remission and 16 patients died of the malignancy. Initial serum PIIINP concentration, but not that of CA125 or PICP, was significantly lower in responders than in nonresponders. The pathologic serum CA125 and PIIINP levels of the responders decreased to normal within two months, whereas in patients with a poor prognosis they remained elevated. Serum CA 125 and PIIINP responded to progression with an increase and to remission with a decrease. The changes in the serum PICP concentration took place predominantly within the reference interval. In seven patients with progressive malignancy, it increased to a pathologic level during the final stage of the disease. Our results indicate that extensive ovarian malignancy strongly affects the metabolism of type I and type III collagens. The PIIINP assay is clinically useful. PIIINP and PICP determinations also have potential to increase our understanding of the mechanisms of invasion and spread of malignant tumours.     

Short DNA sequences and bacterial DNA induce esophageal,gastric, and colorectal cancer cell invasion

Toll‐like receptor 9 (TLR9) recognizes both bacterial and self‐DNA and it is abundantly expressed in the gastrointestinal tract. In this study, we investigated the influences of both bacterial DNA and specific short DNA sequences on TLR9‐mediated gastrointestinal cancer cell invasion. We assessed the effect of various DNA ligands on cellular invasion and on TLR9 and matrix metalloproteinase expression of three gastrointestinal cancer cell lines. DNA‐ligands described in this study include CpG‐ODN M362, 9‐mer (hairpin), human telomeric sequence h‐Tel22 G‐quadruplex, and bacterial DNAs from Escherichia coli and Helicobacter pylori. All of the DNAs studied were demonstrated to induce invasion in the studied cells. The DNA‐induced invasion was inhibited with a broad‐spectrum MMP inhibitor and partly also with chloroquine suggesting that it could be mediated via MMP activation, endosomal signaling, and TLR9. Interestingly, H. pylori DNA was shown to induce a more pronounced invasion in a gastric cancer cell line than in the other cell lines. Our results suggest that bacterial DNA as well as deoxynucleotides having stable secondary structures (i.e. hairpins or G‐quadruplex structures) may serve as endogenous, invasion‐inducing TLR9‐ligands and promote local progression and metastasis of cancers in the alimentary tract.     

Double versus single autotransplantation in multiple myeloma; a single center experience of 100 patients

One hundred patients with newly diagnosed multiple myeloma (MM) were treated with high-dose chemotherapy followed by single or double autologous stem cell transplantation (ASCT). Up-front treatment with a double ASCT tended to prolong progression-free and overall survival.     

Association between bone mineral density and lumbar disc degeneration

Objectives

Higher vertebral bone mineral density (BMD) has been found to be related with lumbar disc degeneration (LDD), while relationship between femoral neck BMD and LDD remains controversial. The aim of our research was to study the relationship between LDD and BMD of the lumbar spine and femoral neck.

Study design

The study population consisted of 168 postmenopausal women (aged 63.3–75.0 years, mean 68.6 years) from the prospective OSTPRE and OSTPRE-FPS study cohorts. The severity of LDD was graded from T2-weighted MRI images using the five-grade Pfirrmann classification. Four vertebral levels (L1-L4) were studied (total 672 discs). The association between lumbar BMD and Z-score and the severity of LDD was studied separately for each vertebral level with AN(C)OVA analysis, using potential confounders as covariates.

Results

Higher lumbar BMD and Z-score were associated with more severe LDD at all studied levels (L1-L4): between L4-L5 disc and L4 BMD (p = 0.044) and L4 Z-score (p = 0.052), between L2-L3 disc and L3 BMD (p = 0.001) and at all other levels (p < 0.001). The mean degeneration grade of the studied discs was associated with the mean L1-L4 BMD and Z-score (p < 0.001). Statistical significance of any result did not alter after controlling for confounding factors. There was no significant association between femoral neck BMD and LDD.

Conclusions

Higher lumbar BMD/Z-score were associated with more severe LDD. There was no significant association between femoral neck BMD and disc degeneration. Femoral neck BMD may be a more reliable measurement for diagnosing osteoporosis in postmenopausal women with degenerative changes in the lumbar spine.