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Abstract Background The SRY-related HMG-box family of transcription factors member SOX2 has been mainly studied in embryonic stem cells as well as early foregut and neural development. More recently, SOX2 was shown to participate in reprogramming of adult somatic cells to a pluripotent stem cell state and implicated in tumorigenesis in various organs. In breast cancer, SOX2 expression was reported as a feature of basal-like tumors. In this study, we assessed SOX2 expression in 95 primary tumors of postmenopausal breast cancer patients. Methods Samples from 95 patients diagnosed and treated at the University of Tuebingen Institute of Pathology and Women's Hospital were analyzed by immunohistochemistry for SOX2 expression in the primary tumor samples and in corresponding lymph node metastasis, where present. Furthermore, SOX2 amplification status was assessed by FISH in representative samples. In addition, eighteen fresh frozen samples were analyzed for SOX2, NANOG and OCT4 gene expression by real-time PCR. Results SOX2 expression was detected in 28% of invasive breast carcinoma as well as in 44% of ductal carcinoma in situ (DCIS) lesions. A score of SOX2 expression (score 0 to 3) was defined in order to distinguish SOX2 negative (score 0) from SOX2 positive samples (score 1-3) and among latter the subgroup of SOX2 high expressors (score 3 > 50% positive cells). Overall, the incidence of SOX2 expression (score 1-3) was higher than previously reported in a cohort of lymph node negative patients (28% versus 16.7%). SOX2 expression was detected across different breast cancer subtypes and did not correlate with tumor grading. However, high SOX2 expression (score 3) was associated with larger tumor size (p = 0.047) and positive lymph node status (0.018). Corresponding metastatic lymph nodes showed higher SOX2 expression and were significantly more often SOX2 positive than primary tumors (p = 0.0432). Conclusions In this report, we show that the embryonic stem cell factor SOX2 is expressed in a variety of early stage postmenopausal breast carcinomas and metastatic lymph nodes. Our data suggest that SOX2 plays an early role in breast carcinogenesis and high expression may promote metastatic potential. Further studies are needed to explore whether SOX2 can predict metastatic potential at an early tumor stage.

Objectives: The influence of the new antiepileptic drug losigamone (CAS 11285644-7 / 123783-52-8) on the pharmacokinetics of a combined oral contraceptive containing ethinylestradiol (CAS 57-63-6) and levonorgestrel (CAS 797-63-7) was investigated in 16 healthy women. Methods: This phase I study consisted of 3 periods with an uncontrolled first period and a double-blind, placebo-controlled, cross-over design in the second and third period. All subjects received a single dose of 200 mg losigamone (1 tablet) in period 1 (on day 14) as well as multiple doses of losigamone (3 tablets = 600 mg per day) or placebo for 15 days in periods 2 and 3. During all three periods an oral contraceptive containing 30 µg ethinylestradiol and 150 µg levonorgestrel was given. Single-dose pharmacokinetics was investigated on day 14 of period 1. Multiple-dose pharmacokinetic investigations were performed on day 15 of periods 2 and 3. The samples were assayed to derive pharmacokinetic data of ethinylestradiol and levonorgestrel. In addition, the concentrations of losigamone racemate (AO-33) and its enantiomers AO-242 and AO-294 were determined in these samples. Results: The mean values of the pharmacokinetic parameters AUC and Cmax of ethinylestradiol and levonorgestrel after multiple-dose treatment with losigamone or placebo were quite similar and met the criteria for bioequivalence. The 90% confidence intervals of the logtransformed ratios of the geometric means of the primary pharmacokinetic variables were included in the respective acceptance ranges of 80% to 125% (AUC) and 70% to 143% (Cmax). Conclusions: The study demonstrated that multiple doses of losigamone did not influence the multiple dose kinetics of ethinylestradiol and levonorgestrel. The single- and multiple-dose kinetics of 200 mg losigamone and its enantiomeres did not differ from each other in a significant way. The combination of losigamone and the combined oral contraceptive was well tolerated and no serious adverse events occurred. It can be stated that the antiepileptic drug losigamone and the combined contraceptive do not interact each others metabolism. [ABSTRACT FROM AUTHOR]

We present the case of a 22-year-old female patient with chondroblastoma in the right humeral head. To allow a gentle and anatomic resurfacing of the humeral joint surface and to avoid total joint arthroplasty in our young patient with high functional requirements, we implanted a HemiCAP® after intralesional curettage of the chondroblastoma. Our patient's excellent short-term functional outcome shows that our approach can be considered a very good therapeutic option.