Influence of Cranial Radiotherapy on Outcome in Children With Acute Lymphoblastic Leukemia Treated With Contemporary Therapy.

Purpose: We sought to determine whether cranial radiotherapy (CRT) is necessary to prevent relapse in any subgroup of children with acute lymphoblastic leukemia (ALL).

Patients And Methods: We obtained aggregate data on relapse and survival outcomes for 16,623 patients age 1 to 18 years old with newly diagnosed ALL treated between 1996 and 2007 by 10 cooperative study groups from around the world. The proportion of patients eligible for prophylactic CRT varied from 0% to 33% by trial and was not related to the proportion eligible for allogeneic stem-cell transplantation in first complete remission.

A point mutation of zebrafish c-cbl gene in the ring finger domain produces a phenotype mimicking human myeloproliferative disease.

Controlled self-renewal and differentiation of hematopoietic stem/progenitor cells (HSPCs) are critical for vertebrate development and survival. These processes are tightly regulated by the transcription factors, signaling molecules and epigenetic factors. Impaired regulations of their function could result in hematological malignancies.

Exit from dormancy provokes DNA-damage-induced attrition in haematopoietic stem cells.

Haematopoietic stem cells (HSCs) are responsible for the lifelong production of blood cells. The accumulation of DNA damage in HSCs is a hallmark of ageing and is probably a major contributing factor in age-related tissue degeneration and malignant transformation. A number of accelerated ageing syndromes are associated with defective DNA repair and genomic instability, including the most common inherited bone marrow failure syndrome, Fanconi anaemia.

Genomic classification of serous ovarian cancer with adjacent borderline differentiates RAS pathway and TP53-mutant tumors and identifies NRAS as an oncogenic driver.

Purpose: Low-grade serous ovarian carcinomas (LGSC) are Ras pathway-mutated, TP53 wild-type, and frequently associated with borderline tumors. Patients with LGSCs respond poorly to platinum-based chemotherapy and may benefit from pathway-targeted agents. High-grade serous carcinomas (HGSC) are TP53-mutated and are thought to be rarely associated with borderline tumors.

Role of the registered nurse in primary health care: meeting health care needs in the 21st century.

There is widespread interest in the redesign of primary health care practice models to increase access to quality health care. Registered nurses (RNs) are well positioned to assume direct care and leadership roles based on their understanding of patient, family, and system priorities. This project identified 16 exemplar primary health care practices that used RNs to the full extent of their scope of practice in team-based care.

Altered cytokine and chemokine profiles in multiple myeloma and its precursor disease.

Currently, no reliable biomarkers are available to predict transformation from smoldering myeloma (SMM) to multiple myeloma (MM). Using an ultrasensitive enzyme-linked immunosorbent assay (ELISA) we assessed the levels of a broad range of cytokines and chemokines in the peripheral blood (PB) and bone marrow (BM) supernatant collected from 14 SMM and 38 MM patients and compared to healthy donors. We found significantly increased levels of key cytokines, in particular CXCL8 (IL-8), associated with progressive disease state (controls→SMM→MM).

Genetic inhibition of hepatic acetyl-CoA carboxylase activity increases liver fat and alters global protein acetylation.

Lipid deposition in the liver is associated with metabolic disorders including fatty liver disease, type II diabetes, and hepatocellular cancer. The enzymes acetyl-CoA carboxylase 1 (ACC1) and ACC2 are powerful regulators of hepatic fat storage; therefore, their inhibition is expected to prevent the development of fatty liver. In this study we generated liver-specific ACC1 and ACC2 double knockout (LDKO) mice to determine how the loss of ACC activity affects liver fat metabolism and whole-body physiology.

REST and stress resistance in ageing and Alzheimer's disease.

Human neurons are functional over an entire lifetime, yet the mechanisms that preserve function and protect against neurodegeneration during ageing are unknown. Here we show that induction of the repressor element 1-silencing transcription factor (REST; also known as neuron-restrictive silencer factor, NRSF) is a universal feature of normal ageing in human cortical and hippocampal neurons. REST is lost, however, in mild cognitive impairment and Alzheimer's disease.

PIM kinases are essential for chronic lymphocytic leukemia cell survival (PIM2/3) and CXCR4-mediated microenvironmental interactions (PIM1).

Overexpression of the CXCR4 receptor is a hallmark of chronic lymphocytic leukemia (CLL) and is important for CLL cell survival, migration, and interaction with their protective microenvironment. In acute myelogenous leukemia (AML), PIM1 was shown to regulate the surface expression of the CXCR4 receptor. Here, we show that PIM (proviral integration site for Moloney murine leukemia virus) kinases 1-3 are overexpressed and that the CXCR4 receptor is hyperphosphorylated on Ser339 in CLL compared with normal lymphocytes.

Anticancer effect of fucoidan in combination with tyrosine kinase inhibitor lapatinib.

Background. Despite a number of in vitro and in vivo studies reporting the efficacy of fucoidan in treating various cancers, few studies have measured the efficacy of dietary fucoidan (DF) in combination with cancer drugs. Thus, we examined the sensitivity of DF in combination with the EGFR/ERBB2-targeting reagent lapatinib on cancer cells.

Clinical trial participation as part of end-of-life cancer care: associations with medical care and quality of life near death.

Context: Clinical trials are a common therapeutic option for patients with advanced incurable cancer.

Objectives: To examine the associations between trial participation and end-of-life (EOL) outcomes, including aggressive care and quality of life (QOL).

Methods: Coping with Cancer, a multicenter prospective cohort study of patients with metastatic cancer, progressed after at least first-line chemotherapy.

Pivotal role of augmented αB-crystallin in tumor development induced by deficient TSC1/2 complex.

Tuberous sclerosis complex 1 (TSC1) and TSC2 are suppressors of mechanistic target of rapamycin (mTOR). mTOR is the major component of two protein complexes: mTOR complex 1 (mTORC1) and mTORC2. Inactive mutation of either TSC1 or TSC2 unleashes mTOR signaling and consequently causes TSC, a benign tumor syndrome affecting multiple organs.

An adaptive two-stage dose-response design method for establishing proof of concept.

We propose an adaptive two-stage dose-response design where a prespecified adaptation rule is used to add and/or drop treatment arms between the stages. We extend the multiple comparison procedures-modeling (MCP-Mod) approach into a two-stage design. In each stage, we use the same set of candidate dose-response models and test for a dose-response relationship or proof of concept (PoC) via model-associated statistics.

Personalized cancer care conference.

The Oslo University Hospital (Norway), the K.G. Jebsen Centre for Breast Cancer Research (Norway), The Radiumhospital Foundation (Norway) and the Fritz-Bender-Foundation (Germany) designed under the conference chairmen (E.

Optimal parameters for clinical implementation of breast cancer patient setup using Varian DTS software.

Digital tomosynthesis (DTS) was evaluated as an alternative to cone-beam computed tomography (CBCT) for patient setup. DTS is preferable when there are constraints with setup time, gantry-couch clearance, and imaging dose using CBCT. This study characterizes DTS data acquisition and registration parameters for the setup of breast cancer patients using nonclinical Varian DTS software.

Automation of clip localization in Digital Tomosynthesis for setup of breast cancer patients.

The objective of this study is to develop an automatic clip localization procedure for breast cancer patient setup based on Digital Tomosynthesis (DTS) and to characterize its performance with respect to the overall registration accuracy and robustness. The study was performed under an IRB-approved protocol for 12 breast cancer patients with surgical clips implanted around the tumor cavity. The registration of DTS images to planning CTs was performed using an automatic algorithm developed to overcome specific challenges of localization and registration of clips in the breast setup images.

Tobacco use cessation and weight management among motor freight workers: results of the gear up for health study.

Objectives: To present the results of a study of a worksite-based intervention to promote tobacco use cessation and improve weight management among motor freight workers.

Methods: This study used a pre-test/post-test, non-randomized design to assess the effectiveness of a four-month intervention that addressed the social context of the work setting. We evaluated 7-day tobacco quit prevalence among baseline tobacco users, and successful weight management, defined as no weight gain in workers with BMI <25 at baseline and any weight loss among overweight and obese workers.

Pharmacotherapy of neuroblastoma.

Importance Of The Field: Neuroblastoma, a tumor of the sympathetic nervous system, is the most common extracranial solid tumor of early life. High risk disease in older children remains a therapeutic challenge, despite high-intensity therapy with correspondingly significant short- and long-term toxicities.

Areas Covered In This Review: We have reviewed therapy for neuroblastoma over the last three decades.

Impact of medical Qigong on quality of life, fatigue, mood and inflammation in cancer patients: a randomized controlled trial.

Background: Substantial numbers of cancer patients use complementary medicine therapies, even without a supportive evidence base. This study aimed to evaluate in a randomized controlled trial, the use of Medical Qigong (MQ) compared with usual care to improve the quality of life (QOL) of cancer patients.

Patients And Methods: One hundred and sixty-two patients with a range of cancers were recruited.

P-glycoprotein structure and evolutionary homologies.

Analysis of multidrug resistant cell lines has led to the identification of the P-glycoprotein multigene family. Two of the three classes of mammalian P-glycoproteins have the ability to confer cellular resistance to a broad range of structurally and functionally diverse cytotoxic agents. P-glycoproteins are integral membrane glycoproteins comprised of two similar halves, each consisting of six membrane spanning domains followed by a cytoplasmic domain which includes a nucleotide binding fold.

Ras-MAPK signaling promotes trophectoderm formation from embryonic stem cells and mouse embryos.

In blastocyst chimeras, embryonic stem (ES) cells contribute to embryonic tissues but not extraembryonic trophectoderm. Conditional activation of HRas1(Q61L) in ES cells in vitro induces the trophectoderm marker Cdx2 and enables derivation of trophoblast stem (TS) cell lines that, when injected into blastocysts, chimerize placental tissues. Erk2, the downstream effector of Ras-mitogen-activated protein kinase (MAPK) signaling, is asymmetrically expressed in the apical membranes of the 8-cell-stage embryo just before morula compaction.

Molecular diversity of Dscam: recognition of molecular identity in neuronal wiring.

Our understanding of how the enormously complex task of interconnecting millions of nerve cells is accomplished remains rudimentary. What molecular mechanisms control its exquisite specificity? Can we pinpoint single molecular interactions that might help to explain some of the specificity requirements that underlie neuronal wiring? A series of recent studies on the molecular diversity of the Drosophila melanogaster cell-surface receptor Down syndrome cell-adhesion molecule (Dscam) provide one exceptional example of a novel mechanistic model of neuronal-wiring specificity, progressing from structural studies of single protein-protein interactions to biochemical analysis in vitro and to an understanding of complex neuronal differentiation at the single-cell or tissue levels.

Primary effusion lymphoma.

Primary effusion lymphoma (PEL) is a rare HIV-associated non-Hodgkin's lymphoma (NHL) that accounts for approximately 4% of all HIV-associated NHL. PEL has a unique clinical presentation in having a predilection for arising in body cavities such as the pleural space, pericardium, and peritoneum. PEL cells are morphologically variable with a null lymphocyte immunophenotype and evidence of human herpesvirus (HHV)-8 infection.

Effect of 1 mg/day finasteride on concentrations of serum prostate-specific antigen in men with androgenic alopecia: a randomised controlled trial.

Background: Use of 5 mg/day finasteride (Proscar) for benign prostatic hyperplasia is known to affect serum concentrations of prostate-specific antigen (PSA). When men taking this treatment undergo screening for prostate cancer, a compensatory adjustment of the PSA concentration (to multiply the value by two) is recommended. Whether this recommendation should apply to men taking 1 mg/day finasteride (Propecia) for the treatment of androgenic alopecia is unknown.