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Objective: Aim of the study was to investigate the expression of transforming growth factor-β1 (TGF-β1), a key regulator of the extracellular matrix composition, in the uterosacral ligaments (USLs) of women with pelvic organ prolapse (POP) compared with controls. We hypothesized that the expression pattern of TGF-β1 differs between postmenopausal women with or without POP. Methods: Under ethical approval, USL samples were obtained from postmenopausal women undergoing vaginal hysterectomy for stage two or greater pelvic organ prolapse (cases, n = 70) and from postmenopausal women without pelvic organ prolapse undergoing vaginal hysterectomy for benign indications (controls, n = 30). Immunohistochemical staining was performed from paraffin embedded tissue using anti-TGF-β1 antibodies. The expression of TGF-β1 was evaluated by the pathologist, who was blinded to all clinical data. Results: The expression of TGF-ß1 was similar in patients with symptomatic POP (89 % positive) and in controls (90 % positive) without any signs of prolapse (p = 0.091). Age-adjusted analysis did not significantly alter these results. Regarding POP-Q stages, TGF-ß1 was significantly more frequently expressed in severe prolapse cases compared to moderate/mild cases (POP-Q stage IV versus POP-Q stage II and III; p = 0.001). No significant association could be detected between TGF-ß1 expression and age, BMI and parity in cases with POP (p > 0.05). As published previously, advanced patients’ age as well as early menopausal age remained independent risk factors associated with POP in multiple logistic regression analysis (p = 0.001; p = 0.02). Conclusion: Although our study detected POP-Q stage related alterations in USL composition and TGF-ß1 expression, there was no significant difference in the expression of TGF-β1 in cases with or without prolapse.

Lung cancer during pregnancy represents a rare disease. In this case report, we present a patient at advanced and metastasized stage of signet ring cell carcinoma who presented in the 22nd week of gestation.

The link between higher uptake of isoflavones and a reduced frequency of menopause-related hot flushes were first described in 1992 based on a lower incidence of hot flushes in countries with high dietary soy intake1. Since then, a number of clinical trials with different sources of isoflavones, including soy and red clover, have been performed, and in almost all studies with an appropriate design the outcome was in favour of isoflavone supplementation2. A detailed risk assessment3 revealed that a number of data in humans do not confirm the alleged adverse effect resulting from possible interaction between isoflavones and the hormone-sensitive tissues of the mammary glands, uterus and thyroid. Safety was demonstrated by long-term intake of 150 mg of isoflavones per day, which lasted at least three years. It was also found that a high intake of isoflavones prevented the occurrence of breast cancer4-7. Clinical findings indicate potential benefits of exposure to isoflavones during breast cancer treatment with tamoxifen or anastrozole.

BACKGROUND:HER-targeted tyrosine kinase inhibitors (TKIs) have demonstrated pro-apoptotic and antiproliferative effects in vitro and in vivo. The exact pathways through which TKIs exert their antineoplastic effects are, however, still not completely understood. METHODS:Using Milliplex assays, we have investigated the effects of the three panHER-TKIs lapatinib, canertinib and afatinib on signal transduction cascade activation in SKBR3, T47D and Jurkat neoplastic cell lines. The growth-inhibitory effect of blockade of HER and of JNK and STAT5 signaling was measured by proliferation- and apoptosis-assays using formazan dye labeling of viable cells, Western blotting for cleaved PARP-1 and immunolabeling for active caspase 3, respectively. RESULTS:All three HER-TKIs clearly inhibited proliferation and increased apoptosis in HER2 overexpressing SKBR3 cells, while their effect was less pronounced on HER2 moderately expressing T47D cells where they exerted only a weak antiproliferative and essentially no pro-apoptotic effect. Remarkably, phosphorylation/activation of JNK and STAT5A/B were inhibited by HER-TKIs only in the sensitive, but not in the resistant cells. In contrast, phosphorylation/activation of ERK/MAPK, STAT3, CREB, p70 S6 kinase, IkBa, and p38 were equally affected by HER-TKIs in both cell lines. Moreover, we demonstrated that direct pharmacological blockade of JNK and STAT5 abrogates cell growth in both HER-TKI-sensitive as well as -resistant breast cancer cells, respectively. CONCLUSION:We have shown that HER-TKIs exert a HER2 expression-dependent anti-cancer effect in breast cancer cell lines. This involves blockade of JNK and STAT5A/B signaling, which have been found to be required for in vitro growth of these cell lines.

Objective: To compare the efficacy and safety of mirabegron 50 mg and solifenacin 5 mg in overactive bladder (OAB) patients dissatisfied with previous antimuscarinic treatment due to lack of efficacy. Patients and methods: This randomized, double-blind, phase IIIb, noninferiority study, enrolled male and female patients aged ⩾18 years old, with symptoms of OAB for ⩾3 months, who were dissatisfied with their previous antimuscarinic drug due to lack of efficacy. A total of 1887 patients were randomized to receive mirabegron 50 mg ( n = 943) or solifenacin 5 mg ( n = 944) daily for 12 weeks. The primary efficacy endpoint was change from baseline to end of treatment in mean number of micturitions/24 h. Noninferiority was confirmed if the lower limit of the two-sided 95% confidence interval (CI) for the treatment difference between solifenacin and mirabegron was > −0.20. Secondary efficacy endpoints, which included change from baseline in mean number of incontinence episodes/24 h, urgency incontinence episodes/24 h, urgency episodes (grade 3 or 4)/24 h and nocturia episodes/24 h, were analyzed using analysis of covariance. Results: For the primary endpoint, adjusted mean treatment difference (95% CI) in mean number of micturitions/24 h was −0.18 (−0.42, 0.06) and therefore noninferiority of mirabegron to solifenacin was not demonstrated. Both treatments demonstrated clinically meaningful reductions in efficacy variables and were well tolerated, with a lower incidence of dry mouth with mirabegron. Conclusions: Noninferiority of mirabegron compared with solifenacin for reduction in micturition frequency could not be demonstrated in this population of OAB patients who were dissatisfied with previous antimuscarinic therapy due to lack of efficacy. Both mirabegron and solifenacin improved key OAB symptoms with no statistically significant differences observed between the two treatments. Both drugs were well tolerated.