Targeting of preexisting and induced breast cancer stem cells with trastuzumab and trastuzumab emtansine (T-DM1).

The antibody trastuzumab (Herceptin) has substantially improved overall survival for patients with aggressive HER2-positive breast cancer. However, about 70% of all treated patients will experience relapse or disease progression. This may be related to an insufficient targeting of the CD44(high)CD24(low) breast cancer stem cell subset, which is not only highly resistant to chemotherapy and radiotherapy but also a poor target for trastuzumab due to low HER2 surface expression. Hence, we explored whether the new antibody-drug conjugate T-DM1, which consists of the potent chemotherapeutic DM1 coupled to trastuzumab, could improve the targeting of these tumor-initiating or metastasis-initiating cells. To this aim, primary HER2-overexpressing tumor cells as well as HER2-positive and HER2-negative breast cancer cell lines were treated with T-DM1, and effects on survival, colony formation, gene and protein expression as well as antibody internalization were assessed. This revealed that CD44(high)CD24(low)HER2(low) stem cell-like breast cancer cells show high endocytic activity and are thus particularly sensitive towards the antibody-drug conjugate T-DM1. Consequently, preexisting CD44(high)CD24(low) cancer stem cells were depleted by concentrations of T-DM1 that did not affect the bulk of the tumor cells. Likewise, colony formation was efficiently suppressed. Moreover, when tumor cells were cocultured with natural killer cells, antibody-dependent cell-mediated cytotoxicity was enhanced, and EMT-mediated induction of stem cell-like properties was prevented in differentiated tumor cells. Thus our study reveals an unanticipated targeting of stem cell-like breast cancer cells by T-DM1 that may contribute to the clinical efficacy of this recently approved antibody-drug conjugate.

[Acute foeto-foetal transfusion syndrome--case report and review of the literature]. / Akutes fetofetales Transfusionssyndrom--Fallbericht und Literaturübersicht.

The perinatal morbidity and mortality risk in monochorionic twin pregnancies are 3-5-fold increased compared to those of dichorionic twin pregnancies. Partially, this is due to the higher rate of preterm delivery but also to the twin-to-twin transfusion syndrome (TTTS). Caused by unidirectional blood flow via placental anastomoses, the TTTS leads to weight differences of more than 20% between monochorial twins. The blood donor often shows oligohydramnios, whereas the recipient shows polyhydramnios. Lewi et al. demonstrated, in a study with 202 monochorionic twin pregnancies, a 9% rate of severe TTTS. The mortality of this complication is about 90% when untreated. In contrast to the chronic TTTS, little is known about the acute intrapartal one, which is characterised by anaemia and hypovolaemia of the donor and polyglobulia of the recipient without significant weight differences between the two. In most cases, anaemia occurred after normal delivery of the first twin. Still, there are no means or signs for early detection. We describe the case of a 30-year-old primigravida with a monochorionic diamniotic twin pregnancy. During pregnancy, no evidence of TTTS could be detected. At 37 + 1 weeks gestation labour was induced with prostaglandin-containing gel. Both foetuses showed cephalic presentation. The CTG of the first twin showed a conspicuous heart rate. After labour the first twin presented with anaemia and hypovolaemic shock, the APGAR was 2/7/8. The infant's haemoglobin was 13.7 g/dL. After delivery, the second twin with APGAR 10/10/10 showed a haemoglobin of 19.6 g/dL, which is in the upper normal range. Their birth weights differed by merely 10.4%. Acute TTTS is frequently characterised by anaemia and hypovolaemia of the second twin. In our case of a monochorionic twin delivery with acute TTTS the donor was born first. Early diagnosis and neonatal intervention is essential for reducing postnatal morbidity and mortality.

Continent urinary diversion and the ileal cecal pouch with appendostomy: a review with nursing care.

Creation of a continent urinary reservoir has become the procedure of choice when the bladder is removed for either malignant or nonmalignant disease. The continent urinary reservoir provides the patient with a manageable and socially acceptable bladder replacement. It is important for the ET nurse to have a basic understanding of the surgical principles of continent urinary diversion, including the antireflux and continence mechanism, and segment of bowel used. Such an understanding facilitates competent patient care and appropriate instruction, both before and after operation. The basic principles of continent urinary diversion are discussed in this article, along with a brief description of the most common continent urinary reservoirs. In addition, a recent form of urinary diversion, the ileocecal pouch with appendostomy, is described, and relevant preoperative and postoperative care is outlined.

Energy and labor in the construction sector.

An energy input-output model was used to investigate energy and employment in the construction industry. The model covered nearly 400 industrial sectors and was used to determine the impact of construction activities on total national energy consumption in 1967 and to study the patterns of total energy use and employment within various construction categories. For the construction of new buildings, total energy consumption could be reduced by 20 percent by selecting less energy-intensive building materials and assemblies for fixed programmatic requirements, by expending energy in construction to minimize the total lifetime energy cost of buildings, and by energy conservation in industries that supply direct and indirect inputs to the construction sector of the economy.