A review of β-amyloid neuroimaging in Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia worldwide. As advancing age is the greatest risk factor for developing AD, the number of those afflicted is expected to increase markedly with the aging of the world's population. The inability to definitively diagnose AD until autopsy remains an impediment to establishing effective targeted treatments.

GSK-3β dysregulation contributes to parkinson's-like pathophysiology with associated region-specific phosphorylation and accumulation of tau and α-synuclein.

Aberrant posttranslational modifications (PTMs) of proteins, namely phosphorylation, induce abnormalities in the biological properties of recipient proteins, underlying neurological diseases including Parkinson's disease (PD). Genome-wide studies link genes encoding α-synuclein (α-Syn) and Tau as two of the most important in the genesis of PD. Although several kinases are known to phosphorylate α-Syn and Tau, we focused our analysis on GSK-3β because of its accepted role in phosphorylating Tau and to increasing evidence supporting a strong biophysical relationship between α-Syn and Tau in PD.

Nonstructural protein 1 (NS1)-mediated inhibition of c-Abl results in acute lung injury and priming for bacterial co-infections: insights into 1918 H1N1 pandemic?

Background: Nonstructural protein 1 (NS1) proteins from avian influenza viruses like the 1918 pandemic NS1 are capable of inhibiting the key signaling integrator c-Abl (Abl1), resulting in massive cytopathic cell alterations.

Methods: In the current study, we addressed the consequences of NS1-mediated alteration of c-Abl on acute lung injury and pathogenicity in an in vivo mouse model.

Results: Comparing isogenic strains that differ only in their ability to inhibit c-Abl, we observed elevated pathogenicity for the c-Abl-inhibiting virus.

Chromatin remodelers HELLS and UHRF1 mediate the epigenetic deregulation of genes that drive retinoblastoma tumor progression.

The retinoblastoma (Rb) family of proteins are key regulators of cell cycle exit during development and their deregulation is associated with cancer. Rb is critical for normal retinal development and germline mutations lead to retinoblastoma making retinae an attractive system to study Rb family signaling. Rb coordinates proliferation and differentiation through the E2f family of transcription factors, a critical interaction for the role of Rb in retinal development and tumorigenesis.

The Prox1-Vegfr3 feedback loop maintains the identity and the number of lymphatic endothelial cell progenitors.

The mammalian lymphatic vasculature is important for returning fluids from the extracellular tissue milieu back to the blood circulation. We showed previously that Prox1 dosage is important for the development of the mammalian lymphatic vasculature. The lack of Prox1 activity results in the complete absence of lymphatic endothelial cells (LECs).

Drug withdrawal in women with progressive metastatic breast cancer while on aromatase inhibitor therapy.

Background: Acquiring resistance to endocrine therapy is common in metastatic hormone-receptor-positive breast cancer (MBC). These patients most often transition either to next-line endocrine therapy or to systemic chemotherapy. However, withdrawal of endocrine therapy and observation as is selectively practiced in prostate cancer is another potential strategy for breast cancer patients.

Access to care issues adversely affect breast cancer patients in Mexico: oncologists' perspective.

Background: Despite recently implemented access to care programs, Mexican breast cancer (BC) mortality rates remain substantially above those in the US. We conducted a survey among Mexican Oncologists to determine whether practice patterns may be responsible for these differences.

Methods: A web-based survey was sent to 851 oncologists across Mexico using the Vanderbilt University REDCap database.

High order W02-reactive stable oligomers of amyloid-β are produced in vivo and in vitro via dialysis and filtration of synthetic amyloid-β monomer.

Oligomeric forms of amyloid-β (Aβ) are thought to be responsible for the pathogenesis of Alzheimer's disease. While many oligomers of Aβ are thought to be naturally occurring in the brain of humans and/or transgenic animals, it is well known that Aβ oligomers are also readily produced in vitro in the laboratory. In recent studies, we discovered that synthetic monomeric Aβ (4.

Motor and cognitive deficits in aged tau knockout mice in two background strains.

Background: We recently reported that Parkinsonian and dementia phenotypes emerge between 7-12 months of age in tau-/- mice on a Bl6/129sv mixed background. These observations were partially replicated by another group using pure Bl6 background tau-/- mice, but notably they did not observe a cognitive phenotype. A third group using Bl6 background tau-/- mice found cognitive impairment at 20-months of age.

Iron accumulation confers neurotoxicity to a vulnerable population of nigral neurons: implications for Parkinson's disease.

Background: The substantia nigra (SN) midbrain nucleus is constitutively iron rich. Iron levels elevate further with age, and pathologically in Parkinson's disease (PD). Iron accumulation in PD SN involves dysfunction of ceruloplasmin (CP), which normally promotes iron export.

Glia and zinc in ageing and Alzheimer's disease: a mechanism for cognitive decline?

Normal ageing is characterized by cognitive decline across a range of neurological functions, which are further impaired in Alzheimer's disease (AD). Recently, alterations in zinc (Zn) concentrations, particularly at the synapse, have emerged as a potential mechanism underlying the cognitive changes that occur in both ageing and AD. Zn is now accepted as a potent neuromodulator, affecting a variety of signaling pathways at the synapse that are critical to normal cognition.

Role of metal ions in the cognitive decline of Down syndrome.

Down syndrome (DS), caused by trisomy of whole or part of chromosome 21 is the most common mental impairment. All people with DS suffer from cognitive decline and develop Alzheimer's disease (AD) by the age of 40. The appearance of enlarged early endosomes, followed by Amyloid βpeptide deposition, the appearance of tau-containing neurofibrillary tangles and basal forebrain cholinergic neuron (BFCN) degeneration are the neuropathological characteristics of this disease.

Interactions of metals and Apolipoprotein E in Alzheimer's disease.

Alzheimer's disease (AD) is the most common form of dementia, which is characterized by the neuropathological accumulation of extracellular amyloid plaques and intracellular neurofibrillary tangles (NFTs). Clinically, patients will endure a gradual erosion of memory and other higher order cognitive functions. Whilst the underlying etiology of the disease remains to be definitively identified, a body of work has developed over the last two decades demonstrating that AD plasma/serum and brain are characterized by a dyshomeostasis in a number of metal ions.

Breast cancer in China.

The health burden of cancer is increasing in China, with more than 1·6 million people being diagnosed and 1·2 million people dying of the disease each year. As in most other countries, breast cancer is now the most common cancer in Chinese women; cases in China account for 12·2% of all newly diagnosed breast cancers and 9·6% of all deaths from breast cancer worldwide. China's proportional contribution to global rates is increasing rapidly because of the population's rising socioeconomic status and unique reproductive patterns.

Poor Survival for American Indians with Head and Neck Squamous Cell Carcinoma.

Objective: To examine patient characteristics, treatment modalities, and human papillomavirus (HPV) prevalence to identify potential mediators of disparities that may lead to differences in outcomes for American Indians with head and neck squamous cell carcinoma (HNSCC).

Study Design: Historical cohort study.

Setting: Community cancer centers.

Orthotopic models of pediatric brain tumors in zebrafish.

High-throughput screens (HTS) of compound toxicity against cancer cells can identify thousands of potential new drug-leads. But only limited numbers of these compounds can progress to expensive and labor-intensive efficacy studies in mice, creating a 'bottle neck' in the drug development pipeline. Approaches that triage drug-leads for further study are greatly needed.

Long-term risk of medical conditions associated with breast cancer treatment.

Early and late effects of cancer treatment are of increasing concern with growing survivor populations, but relevant data are sparse. We sought to determine the prevalence and hazard ratio of such effects in breast cancer cases. Women with invasive breast cancer and women with no cancer history recruited for a cancer research cohort completed a mailed questionnaire at a median of 10 years post-diagnosis or matched reference year (for the women without cancer).

Prospective validation of HLA-DRB1*07:01 allele carriage as a predictive risk factor for lapatinib-induced liver injury.

Purpose: Liver injury is a serious adverse event leading to permanent discontinuation of lapatinib in affected patients. This study aimed to validate previously associated major histocompatibility complex (MHC) variants as predictors of risk of liver injury by using a large, randomized, placebo-controlled trial of lapatinib in human epidermal growth factor receptor 2-positive, early-stage breast cancer (Tykerb Evaluation After Chemotherapy [TEACH]: Lapatinib Versus Placebo In Women With Early-Stage Breast Cancer).

Patients And Methods: The frequency of ALT elevation cases was compared among four MHC variants in 1,194 patients randomly assigned to lapatinib.

Pemetrexed and gemcitabine as combination therapy for the treatment of Group3 medulloblastoma.

We devised a high-throughput, cell-based assay to identify compounds to treat Group3 medulloblastoma (G3 MB). Mouse G3 MBs neurospheres were screened against a library of approximately 7,000 compounds including US Food and Drug Administration-approved drugs. We found that pemetrexed and gemcitabine preferentially inhibited G3 MB proliferation in vitro compared to control neurospheres and substantially inhibited G3 MB proliferation in vivo.

Rescue of the Friedreich ataxia knockout mutation in transgenic mice containing an FXN-EGFP genomic reporter.

Friedreich ataxia (FRDA) is an autosomal recessive disorder characterized by neurodegeneration and cardiomyopathy. The presence of a GAA trinucleotide repeat expansion in the first intron of the FXN gene results in the inhibition of gene expression and an insufficiency of the mitochondrial protein frataxin. We previously generated BAC-based transgenic mice containing an FXN-EGFP genomic reporter construct in which the EGFP gene is fused in-frame immediately following the final codon of exon 5a of the human FXN gene.

Effects of GDNF-loaded injectable gelatin-based hydrogels on endogenous neural progenitor cell migration.

Brain repair following disease and injury is very limited due to difficulties in recruiting and mobilizing stem cells towards the lesion. More importantly, there is a lack of structural and trophic support to maintain viability of the limited stem/progenitor cells present. This study investigates the effectiveness of an injectable gelatin-based hydrogel in attracting neural progenitor cells (NPCs) from the subventricular zone (SVZ) towards the implant.

C11orf95-RELA fusions drive oncogenic NF-κB signalling in ependymoma.

Members of the nuclear factor-κB (NF-κB) family of transcriptional regulators are central mediators of the cellular inflammatory response. Although constitutive NF-κB signalling is present in most human tumours, mutations in pathway members are rare, complicating efforts to understand and block aberrant NF-κB activity in cancer. Here we show that more than two-thirds of supratentorial ependymomas contain oncogenic fusions between RELA, the principal effector of canonical NF-κB signalling, and an uncharacterized gene, C11orf95.

RB1 gene inactivation by chromothripsis in human retinoblastoma.

Retinoblastoma is a rare childhood cancer of the developing retina. Most retinoblastomas initiate with biallelic inactivation of the RB1 gene through diverse mechanisms including point mutations, nucleotide insertions, deletions, loss of heterozygosity and promoter hypermethylation. Recently, a novel mechanism of retinoblastoma initiation was proposed.

A randomized trial to increase colonoscopy screening in members of high-risk families in the colorectal cancer family registry and cancer genetics network.

Background: Individuals with a strong family history of colorectal cancer have significant risk for colorectal cancer, although adherence to colonoscopy screening in these groups remains low. This study assessed whether a tailored telephone counseling intervention can increase adherence to colonoscopy in members of high-risk families in a randomized, controlled trial.

Methods: Eligible participants were recruited from two national cancer registries if they had a first-degree relative with colorectal cancer under age 60 or multiple affected family members, which included families that met the Amsterdam criteria for hereditary non-polyposis colon cancer (HNPCC), and if they were due for colonoscopy within 24 months.

A joint test for progression and survival with interval-censored data from a cancer clinical trial.

Clinical trials often assess efficacy by comparing treatments on the basis of two or more event-time outcomes. In the case of cancer clinical trials, progression-free survival (PFS), which is the minimum of the time from randomization to progression or to death, summarizes the comparison of treatments on the hazards for disease progression and mortality. However, the analysis of PFS does not utilize all the information we have on patients in the trial.