Matched unrelated donor allogeneic transplantation provides comparable long-term outcome to HLA-identical sibling transplantation in relapsed diffuse large B-cell lymphoma.

The objective of this retrospective analysis was to compare outcomes of patients with diffuse large B-cell lymphoma (DLBCL) who received either a matched sibling (sib) or an unrelated donor (URD) allogeneic hematopoietic cell transplantation (allo-HCT). Long-term outcome of 172 DLBCL patients receiving URD-HCT between 2000 and 2007 and reported to the European Group for Blood and Marrow Transplantation, was compared with that of 301 subjects, allografted from sib-HCT. With a median follow-up of 45 months, 3-year PFS approached 35% for both groups; overall survival (OS) was 42% for sib-HCT versus 37% for URD (NS).

Depletion of a putatively druggable class of phosphatidylinositol kinases inhibits growth of p53-null tumors.

Here, we show that a subset of breast cancers express high levels of the type 2 phosphatidylinositol-5-phosphate 4-kinases α and/or β (PI5P4Kα and β) and provide evidence that these kinases are essential for growth in the absence of p53. Knocking down PI5P4Kα and β in a breast cancer cell line bearing an amplification of the gene encoding PI5P4K β and deficient for p53 impaired growth on plastic and in xenografts. This growth phenotype was accompanied by enhanced levels of reactive oxygen species (ROS) leading to senescence.

PKM2 isoform-specific deletion reveals a differential requirement for pyruvate kinase in tumor cells.

The pyruvate kinase M2 isoform (PKM2) is expressed in cancer and plays a role in regulating anabolic metabolism. To determine whether PKM2 is required for tumor formation or growth, we generated mice with a conditional allele that abolishes PKM2 expression without disrupting PKM1 expression. PKM2 deletion accelerated mammary tumor formation in a Brca1-loss-driven model of breast cancer.

Immunostimulatory activity of murine keratinocyte-derived exosomes.

It has long been known that keratinocytes influence cutaneous immunity through secretion of soluble factors. Exosomes, small membrane vesicles of endocytotic origin, have been implicated in intercellular communication processes such as the transfer of tumor cell antigens and the activation of recipient dendritic cells (DC). However, little is known about immunomodulatory functions of keratinocyte-derived exosomes.

High-resolution HLA matching in hematopoietic stem cell transplantation: a retrospective collaborative analysis.

To validate current donor selection strategies based on previous international studies, we retrospectively analyzed 2646 transplantations performed for hematologic malignancies in 28 German transplant centers. Donors and recipients were high resolution typed for HLA-A, -B, -C, -DRB1, and -DQB1. The highest mortality in overall survival analysis was seen for HLA-A, -B, and DRB1 mismatches.

A novel selective small-molecule PI3K inhibitor is effective against human multiple myeloma in vitro and in vivo.

Developing effective therapies against multiple myeloma (MM) is an unresolved challenge. Phosphatidylinositol-3-kinase (PI3K) activation may be associated with tumor progression and drug resistance, and inhibiting PI3K can induce apoptosis in MM cells. Thus, targeting of PI3K is predicted to increase the susceptibility of MM to anticancer therapy.

The effect of acute exercise on pistol shooting performance of police officers.

Previous studies indicate that rifle shooting performance while standing is compromised when fatigued. Apprehension of suspects by police officers may involve foot pursuit and firing a weapon from a standing position. The purpose of the current study was to investigate pistol shooting performance in police officers under similar conditions of physical fatigue.

Intracellular ATP-binding cassette transporter A3 is expressed in lung cancer cells and modulates susceptibility to cisplatin and paclitaxel.

Patients with advanced-stage bronchial cancer benefit from systemic cytostatic therapy, in particular from regimens integrating cisplatin and taxanes. However, eventual disease progression leads to a fatal outcome in most cases, originating from tumor cells resisting chemotherapy. We here show that the intracellular ATP-binding cassette transporter A3 (ABCA3), previously recognized as critical for the secretion of surfactant components from type 2 pneumocytes, is expressed in non-small-cell lung cancer (NSCLC) cells.

Closing escape routes: inhibition of IL-8 signaling enhances the anti-tumor efficacy of PI3K inhibitors.

The phosphoinositide 3-kinase (PI3K) pathway serves as a relay where signals that emanate from the cell membrane are received and converted into intracellular signals that promote proliferation and survival. Inhibitors of PI3K hold promise for the treatment of breast cancer because activation of this pathway is highly prevalent. However, as is increasingly observed with inhibitors of cell signaling, there appear to be mechanisms of primary and secondary resistance.

Tyrosinekinase inhibition facilitates cooperation of transcription factor SALL4 and ABC transporter A3 towards intrinsic CML cell drug resistance.

Although BCR-ABL1 tyrosine kinase inhibitors reliably induce disease remission for patients with chronic myeloid leukaemia (CML), unlimited extension of therapy is necessary to prevent relapse from persistent leukaemic cells. Here, we analysed model cell lines and primary CML cells for the expression and functions of the ABC transporter A3 (ABCA3) as well as the embryonic stem cell-associated transcription factor SALL4. ABCA3 protected leukaemic cells from the cytotoxic effects of the tyrosine kinase inhibitors imatinib, dasatinib, and nilotinib.

Iron overload impairs proliferation of erythroid progenitors cells (BFU-E) from patients with myelodysplastic syndromes.

In patients with myelodysplastic syndromes (MDS) iron overload caused by long-term red blood cell transfusions is an important factor for comorbidity especially in low-risk MDS. In this report we present the results of a comparative study based on colony formation assays of hematopoietic cells in MDS patients with and without iron overload. We demonstrate that iron overload suppresses the proliferation of erythroid progenitors cells (BFU-E), while the myeloid compartment (CFU-GM) was not found to be affected.

Self-controlled learning: the importance of protecting perceptions of competence.

Recent studies examining the role of self-controlled feedback have shown that learners ask for feedback after what they believe was a "good" rather than "poor" trial. Also, trials on which participants request feedback are often more accurate than those without feedback. The present study examined whether manipulating participants' perception of "good" performance would have differential effects on learning.

Infectious mononucleosis and risk of breast cancer in a prospective study of women.

Purpose: The association between infectious mononucleosis (IM) and risk of breast cancer is unclear; no prospective studies have examined this relationship. We examined self-reported history and age at IM in relation to risk of invasive breast cancer.

Methods: Self-reported history and age at IM were examined in relation to risk of invasive breast cancer in a large cohort of women, the Nurses' Health Study II (81,807 women followed from 1989 to 2007).

Combining a PI3K inhibitor with a PARP inhibitor provides an effective therapy for BRCA1-related breast cancer.

Unlabelled: There is a need to improve treatments for metastatic breast cancer. Here, we show the activation of the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways in a MMTV-CreBrca1(f/f)Trp53(+/-) mouse model of breast cancer. When treated with the pan-class IA PI3K inhibitor NVP-BKM120, tumor doubling was delayed from 5 to 26 days.

Dual-task practice enhances motor learning: a preliminary investigation.

Practicing a motor task under dual-task conditions can be beneficial to motor learning when the secondary task is difficult (Roche et al. in Percept Psychophys 69(4):513-522, 2007) or when it engages similar processes as the primary motor task (Hemond et al. in J Neurosci 30(2):650-654, 2010).

Feedback about more accurate versus less accurate trials: differential effects on self-confidence and activation.

One purpose of the present study was to examine whether self-confidence or anxiety would be differentially affected byfeedback from more accurate rather than less accurate trials. The second purpose was to determine whether arousal variations (activation) would predict performance. On day 1, participants performed a golf putting task under one of two conditions: one group received feedback on the most accurate trials, whereas another group received feedback on the least accurate trials.

Comparative study of human-induced pluripotent stem cells derived from bone marrow cells, hair keratinocytes, and skin fibroblasts.

Aims: Induced pluripotent stem cells (iPSCs) provide a unique opportunity for the generation of patient-specific cells for use in disease modelling, drug screening, and regenerative medicine. The aim of this study was to compare human-induced pluripotent stem cells (hiPSCs) derived from different somatic cell sources regarding their generation efficiency and cardiac differentiation potential, and functionalities of cardiomyocytes.

Methods And Results: We generated hiPSCs from hair keratinocytes, bone marrow mesenchymal stem cells (MSCs), and skin fibroblasts by using two different virus systems.

3-Ethenyl-1-(4-methyl-phenyl-sulfon-yl)-1H-indole.

Two independent but very similar mol-ecules comprise the asymmetric unit of the title compound, C(17)H(15)NO(2)S. The mol-ecules have L-shapes with the dihedral angles between the fused-ring system (r.m.

An external focus of attention enhances motor learning in children with intellectual disabilities.

Background: The present study examined whether the learning benefits of an external focus of attention (i.e., on the movement effect) relative to an internal focus (i.

Self-controlled feedback enhances learning in adults with Down syndrome.

Background: One factor that has consistently been shown to enhance learning in typical participants is self-controlled practice.

Objectives: The purpose of the present study was to examine whether the learning benefits of self-controlled feedback found previously in non-disabled adults would also be found in adults with Down syndrome.

Methods: Participants with Down syndrome practiced a linear positioning task.

[B symptoms, lymphadenopathy and signs of systemic disease in a 21-year-old female].

Sarcoidosis is a multi-systemic disease. A 21-year-old female patient was admitted to our department with lymphadenopathy, B symptoms, erythema nodosum and joint pain. Sarcoidosis showed a very atypical course, lacking any pulmonary symptoms or typical laboratory values.

Enhanced expectancies improve movement efficiency in runners.

We followed up on recent findings demonstrating that enhancing performers' expectancies can improve their performance. Specifically, we examined whether providing experienced runners with positive feedback regarding their movement efficiency would increase running efficiency. Two groups of experienced runners ran on a treadmill at 75% of their maximum oxygen consumption (VO(2max)) for 10 min.

Amyloid precursor protein is a biomarker for transformed human pluripotent stem cells.

Increasing evidence suggests an important function of the β-amyloid precursor protein (APP) in malignant disease in humans; however, the biological basis for this evidence is not well understood at present. To understand the role of APP in transformed pluripotent stem cells, we studied its expression levels in human testicular germ cell tumors using patient tissues, model cell lines, and an established xenograft mouse model. In the present study, we demonstrate the cooperative expression of APP with prominent pluripotency-related genes such as Sox2, NANOG, and POU5F1 (Oct3/4).

Enhanced expectancies improve performance under pressure.

Beyond skill, beliefs in requisite abilities and expectations can affect performance. This experiment examined effects of induced perceptions of ability to perform well under generic situations of challenge. Participants (N = 31) first completed one block of 20 trials on a throwing accuracy task.