There is a growing body of evidence that HER2 status can change during disease recurrence or progression in breast cancer patients. In this context, re-evaluation of HER2 status by assessment of HER2 expression on circulating tumor cells (CTCs) is a strategy with potential clinical application. The aim of this trial was to determine the HER2 status of CTCs in metastatic breast cancer patients comparing two CTC assays. A total of 254 patients with metastatic breast cancer from nine German university breast cancer centers were enrolled in this prospective study. HER2 status of CTCs was assessed using both the FDA-approved CellSearch® assay and AdnaTest BreastCancer™. Using the CellSearch assay, 122 of 245 (50%) patients had ≥5 CTCs, and HER2-positive CTCs were observed in 50 (41%) of these patients. Ninety of 229 (39%) patients were CTC positive using AdnaTest BreastCancer, and HER2 positivity rate was 47% (42 of 90). The rate of breast cancer patients with HER2-negative primary tumors but HER2-positive CTCs was 32% (25 of 78) and 49% (28 of 57) using the CellSearch assay and AdnaTest BreastCancer, respectively. Considering only those patients who had CTCs on both tests (n = 62), concordant results regarding HER2 positivity were obtained in 50% of the patients (31/62) (P = 0.96, κ = -0.006). HER2-positive CTCs can be detected in a relevant number of patients with HER2 negative primary tumors. Therefore, it will be mandatory to correlate the assay-dependent HER2 status of CTCs to the clinical response on HER2-targeted therapies.

The dimension of invasive ductal carcinomas, small and low grading tumors is significantly better to estimate. Concerning treatment decisions, we propose a combination of all three modalities, as the best predictive value was seen for the complementary use of mammography, ultrasound and clinical examination.

Tip60 was originally identified as cellular HIV-Tat interacting protein and has been shown to augment Tat-dependent transcription. It has also been shown to interact with various cellular transcription factors and to belong to the nuclear histone acetyltransferase (HAT) family. To further elucidate the function of Tip60 and its HAT domain in transcription regulation, we compared Tip60 activity in HeLa and Jurkat T lymphoma cells. Here we show that Tip60 augments the HIV-1 Tat activity at the HIV-LTR promoter in HeLa but inhibits it in Jurkat cells. Moreover, we isolated two new variants of the Tip60 protein (Tip60Delta1, Tip60Delta2) from Jurkat cells. The Tip60Delta2 variant lacks the entire HAT domain but modulates HIV-1 Tat activity like full-length Tip60. In addition, Tip60 and the transcriptional repressor ZEB (zinc finger E box binding protein) interact specifically in the yeast two-hybrid system and additively inhibit the CD4 enhancer/promoter activity in Jurkat cells. Thus, Tip60 may function as corepressor of the ZEB protein. In summary, these data show that Tip60 functions as a cell-type-specific transcriptional regulator and that the HAT domain is not required for either transcriptional activation or inhibition. This indicates that Tip60 may function by recruiting additional cell-type-specific cofactors.

Physicians are the most important source of recommendations for oncological patients. From the marketing point of view, intensive involvement of local private-practice physicians is necessary. The availability of certified perinatal centers does not currently play any part in patients' choice of hospital.

ZEB, an E-box binding transcriptional repressor, is an important regulator of T cell and muscle development. Targeted disruption of ZEB in mice resulted in a strong reduction of thymocytes and the few T cells that reached the mature stage were predominantly CD4(+). CD4 expression during the various stages of T cell differentiation is controlled at the transcriptional level by a complex array of regulatory elements in the CD4 gene locus, consisting of at least three enhancers, one promoter and one silencer. Here we present evidence that CD4 gene expression is negatively regulated by ZEB. We show that ZEB binds to the 5'E-box in the CD4-3 element of the proximal CD4 enhancer in competition with the transcriptional activators E12 and HEB, thereby reducing CD4 expression on CD4 single-positive but not CD4/CD8 double-positive T cells. The conversion of the CD4 proximal enhancer into a potential silencer element by the transcriptional repressor ZEB offers an additional concept of CD4 gene regulation in T cells.

No abstract

Several factors can influence individual perceptions of the expected benefit of recommended adjuvant treatment for breast cancer. This study investigated differences between patients and physicians with regard to the required efficacy of treatment and the factors influencing patients' and physicians' willingness to accept different therapeutic options. A total of 9,000 questionnaires were distributed to patients with breast cancer, and 6,938 questionnaires were distributed to physicians treating breast cancer patients. The patients were asked for personal information and about their medical history and experiences during treatment. The physicians were asked about personal information and their specialty and work environment. The treatment efficacy required by the two groups was assessed using six virtual cases of breast cancer and the treatment regimens proposed, with specific benefits and side effects. A total of 2,155 patients and 527 physicians responded to the questionnaire (return rates of 23.9 and 7.6 %). Significantly different ratings between patients and physicians with regard to the expected benefit of certain treatment options were observed. The differences were noted not only for chemotherapy but also for antihormonal and antibody treatments. Whereas physicians had a quite realistic view of the expected treatment benefits, the patients' expectations were varied. Approximately one-fifth of the patients were willing to accept treatment regimens even with marginal anticipated benefits, whereas one-third required unrealistic treatment benefits. Several influencing factors that were significantly associated with the quality rating of treatment regimens in the groups of breast cancer patients and physicians were also identified. In contrast to physicians, many breast cancer patients required treatment benefits beyond what was realistically possible, although a large group of patients were also satisfied with minimal benefits. Individual factors were also identified in both groups that significantly influence thresholds for accepting adjuvant treatment, independently of risk estimates and therapy guidelines.

Total laparoscopic hysterectomy using the Hohl instrument simplifies the surgical procedure. The technique reported here is safe and effective in preventing ureteral complications during TLH, even in a university training program.