Canonical ErbB-2 isoform and ErbB-2 variant c located in the nucleus drive triple negative breast cancer growth.

Triple negative breast cancer (TNBC) refers to tumors that do not express clinically significant levels of estrogen and progesterone receptors, and lack membrane overexpression or gene amplification of ErbB-2/HER2, a receptor tyrosine kinase. Transcriptome and proteome heterogeneity of TNBC poses a major challenge to precision medicine. Clinical biomarkers and targeted therapies for this disease remain elusive, so chemotherapy has been the standard of care for early and metastatic TNBC.

Human Adult Neurogenesis: Evidence and Remaining Questions.

Renewed discussion about whether or not adult neurogenesis exists in the human hippocampus, and the nature and strength of the supporting evidence, has been reignited by two prominently published reports with opposite conclusions. Here, we summarize the state of the field and argue that there is currently no reason to abandon the idea that adult-generated neurons make important functional contributions to neural plasticity and cognition across the human lifespan.

Application of Synthetic Tumor-Specific Promoters Responsive to the Tumor Microenvironment.

Activity of endogenous promoters can be altered by including additional responsive elements (REs). These elements can be responsive to features of the tumor environment or alternatively to signaling pathways specifically activated in cancer cells. These REs incorporated into tumor-specific promoters can improve cancer targeting, the replicative capacity, and lytic activity of conditionally replicative adenovirus.

Differential inhibition onto developing and mature granule cells generates high-frequency filters with variable gain.

Adult hippocampal neurogenesis provides the dentate gyrus with heterogeneous populations of granule cells (GC) originated at different times. The contribution of these cells to information encoding is under current investigation. Here, we show that incoming spike trains activate different populations of GC determined by the stimulation frequency and GC age.

Delayed coupling to feedback inhibition during a critical period for the integration of adult-born granule cells.

Developing granule cells (GCs) of the adult dentate gyrus undergo a critical period of enhanced activity and synaptic plasticity before becoming mature. The impact of developing GCs on the activity of preexisting dentate circuits remains unknown. Here we combine optogenetics, acute slice electrophysiology, and in vivo chemogenetics to activate GCs at different stages of maturation to study the recruitment of local target networks.

Therapeutic improvement of a stroma-targeted CRAd by incorporating motives responsive to the melanoma microenvironment.

We have previously designed a conditionally replicative oncolytic adenovirus (CRAd) named Ad-F512 that can target both the stromal and the malignant melanoma cell compartments. The replication capacity of this CRAd is driven by a 0.5-Kb SPARC promoter fragment (named F512).

Requirement of adult-born neurons for hippocampus-dependent learning.

A fundamental question in the field of adult neurogenesis relies in addressing whether neurons generated in the adult dentate gyrus are needed for hippocampal function. Increasing evidence is accumulating in support of the notion that hippocampus-dependent behaviors activate new neurons and that those neurons are highly relevant for information processing. More specifically, immature new neurons under development that have unique functional characteristics begin to emerge as a highly relevant population in the dentate gyrus network.

Adult neurogenesis and the plasticity of the dentate gyrus network.

The granule cell layer (GCL) of the dentate gyrus contains neurons generated during embryonic, early postnatal and adult life. During adulthood there is a continuous production of neuronal cohorts that develop and functionally integrate in the preexisting circuits. This morphogenic process generates a stratified GCL, with the outermost layers containing dentate granule cells (DGCs) generated during perinatal life, and the innermost layers containing adult-born DGCs.

Preview. Adult neurogenesis is altered by GABAergic imbalance in models of Alzheimer's disease.

Early stages of Alzheimer's disease (AD) affect hippocampal function. In this issue of Cell Stem Cell, Li et al. (2009) and Sun et al.

Newborn granule cells in the ageing dentate gyrus.

The dentate gyrus of the hippocampus generates neurons throughout life, but adult neurogenesis exhibits a marked age-dependent decline. Although the decrease in the rate of neurogenesis has been extensively documented in the ageing hippocampus, the specific characteristics of dentate granule cells born in such a continuously changing environment have received little attention. We have used retroviral labelling of neural progenitor cells of the adult mouse dentate gyrus to study morphological properties of neurons born at different ages.

SPARC endogenous level, rather than fibroblast-produced SPARC or stroma reorganization induced by SPARC, is responsible for melanoma cell growth.

SPARC (secreted protein acidic and rich in cysteine) is a matricellular protein whose overexpression in malignant or tumor-stromal cells is often associated with increased aggressiveness and bad prognosis in a wide range of human cancer types, particularly melanoma. We established the impact that changes in the level of SPARC produced by malignant cells and neighboring stromal cells have on melanoma growth. Melanoma cell growth in monolayer was only slightly affected by changes in SPARC levels.