Detection of amyloid β oligomers toward early diagnosis of Alzheimer's disease.

Amyloid β (Aβ) peptide accumulation in the brain is considered to be one of the hallmarks of Alzheimer's disease. Here, we compare two analytical techniques for detecting neurotoxic Aβ oligomers - Quartz Crystal Microbalance with Dissipation (QCM-D) and Single Molecule Array (Simoa). Both detection methods exploit a feature of the monoclonal antibody bapineuzumab, which targets N-terminal residues 1-5 of Aβ with high affinity and use it as both a capture and detection reagent.

Oncogenic drives invasion and maintains metastases in colorectal cancer.

Human colorectal cancer (CRC) is a major cause of cancer mortality and frequently harbors activating mutations in the gene. To understand the role of oncogenic in CRC, we engineered a mouse model of metastatic CRC that harbors an inducible oncogenic allele ( ) and conditional null alleles of and (iKAP). The iKAP model recapitulates tumor progression from adenoma through metastases.

From the Cover: Neutralization of terminal differentiation in gliomagenesis.

An immature state of cellular differentiation--characterized by stem cell-like tendencies and impaired differentiation--is a hallmark of cancer. Using glioblastoma multiforme (GBM) as a model system, we sought to determine whether molecular determinants that drive cells toward terminal differentiation are also genetically targeted in carcinogenesis and whether neutralizing such genes also plays an active role to reinforce the impaired differentiation state and promote malignancy. To that end, we screened 71 genes with known roles in promoting nervous system development that also sustain copy number loss in GBM through antineoplastic assay and identified A2BP1 (ataxin 2 binding protein 1, Rbfox1), an RNA-binding and splicing regulator that is deleted in 10% of GBM cases.

Antitelomerase therapy provokes ALT and mitochondrial adaptive mechanisms in cancer.

To assess telomerase as a cancer therapeutic target and determine adaptive mechanisms to telomerase inhibition, we modeled telomerase reactivation and subsequent extinction in T cell lymphomas arising in Atm(-/-) mice engineered with an inducible telomerase reverse transcriptase allele. Telomerase reactivation in the setting of telomere dysfunction enabled full malignant progression with alleviation of telomere dysfunction-induced checkpoints. These cancers possessed copy number alterations targeting key loci in human T cell lymphomagenesis.