Human prostate cancer stem cells： new features unveiled

Cancer stem cells （CSCs） are a rare subpopulation of phenotypically distinct cancer cells exhibiting stem cell characteristics. They are tumourigenic, meanwhile capable of self-renewal and forming differentiated progenies. CSCs are believed to be resistant to the standard therapeutics, and provide the cell reservoir for tumour initiation.1 Understanding CSCs or in another word, tumour-initiating cells, is of critical therapeutic importance.

GIT1 enhances neurite outgrowth by stimulating microtubule assembly

GIT1,a G-protein-coupled receptor kinase interacting protein,has been reported to be involved in neurite outgrowth.However,the neurobiological functions of the protein remain unclear.In this study,we found that GIT1 was highly expressed in the nervous system,and its expression was maintained throughout all stages of neuritogenesis in the brain.In primary cultured mouse hippocampal neurons from GIT1 knockout mice,there was a significant reduction in total neurite length per neuron,as well as in the average length of axon-like structures,which could not be prevented by nerve growth factor treatment.Overexpression of GIT1 significantly promoted axon growth and fully rescued the axon outgrowth defect in the primary hippocampal neuron cultures from GIT1 knockout mice.The GIT1 N terminal region,including the ADP ribosylation factor-GTPase activating protein domain,the ankyrin domains and the Spa2 homology domain,were sufficient to enhance axonal extension.Importantly,GIT1 bound to many tubulin proteins and microtubule-associated proteins,and it accelerated microtubule assembly in vitro.Collectively,our findings suggest that GIT1 promotes neurite outgrowth,at least partially by stimulating microtubule assembly.This study provides new insight into the cellular and molecular pathogenesis of GIT1-associated neurological diseases.

Transcriptional repression by androgen receptor: roles in castration-resistant prostate cancer

Androgen receptor (AR), a hormonal transcription factor, plays important roles during prostate cancer progression and is a key target for therapeutic interventions. While androgen-deprivation therapies are initially successful in regressing prostate tumors, the disease ultimately comes back as castration-resistant prostate cancer (CRPC) or at the late stage as neuroendocrine prostate cancer (NEPC). CRPC remains largely dependent on hyperactive AR signaling in the milieu of low androgen, while NEPC is negative of AR expression but positive of many AR-repressed genes. Recent technological advances in genome-wide analysis of transcription factor binding sites have revealed an unprecedented set of AR target genes. In addition to its well-known function in activating gene expression, AR is increasingly known to also act as a transcriptional repressor. Here, we review the molecular mechanisms by which AR represses gene expression. We also summarize AR-repressed genes that are aberrantly upregulated in CRPC and NEPC and represent promising targets for therapeutic intervention.

Novel double-layer Silastic testicular prosthesis with controlled release of testosterone in vitro, and its effects on castrated rats

Testicular prostheses have been used to deal with anorchia for nearly 80 years. Here, we evaluated a novel testicular prosthesis that can controllably release hormones to maintain physiological levels of testosterone in vivo for a long time. Silastic testicular prostheses with controlled release of testosterone （STPT） with different dosages of testosterone undecanoate （TU） were prepared and implanted into castrated Sprague-Dawley rats. TU oil was applied by oral administration to a separate group of castrated rats. Castrated untreated and sham-operated groups were used as controls. Serum samples from every group were collected to measure the levels of testosterone （T）, follicle-stimulating hormone and luteinizing hormone （LH）. Maximum intracavernous penile pressure （ICPmax） was recorded. The prostates and seminal vesicles were weighed and subjected to histology, and a terminal dexynucleotidyl transferase-mediated UTP nick end labeling （TUNEL） assay was used to evaluate apoptosis. Our results revealed that the weights of these tissues and the levels of T and LH showed significant statistical differences in the oral administration and TU replacement groups compared with the castrated group （P 〈 0.05）. Compared with the sham-operated group, the ICPmax, histology and TUNEL staining for apoptosis, showed no significant differences in the hormone replacement groups implanted with medium and high doses of STPT. Our results suggested that this new STPT could release TU stably through its double semi-permeable membranes with excellent biocompatibility. The study provides a new approach for testosterone replacement therapy.

Generation of functional organs from stem cells

We are now well entering the exciting era of stem cells.Potential stem cell therapy holds great promise for the treatment of many diseases such as stroke,traumatic brain injury,Alzheimer’s disease,Parkinson’s disease,amyotrophic lateral-sclerosis,myocardial infarction,muscular dystrophy,diabetes,and etc..It is generally believed that transplantation of specific stem cells into the injured tissue to replace the lost cells is an effective way to repair the tissue.In fact,organ transplantation has been successfully practiced in clinics for liver or kidney failure.However,the severe shortage of donor organs has been a major obstacle for the expansion of organ transplantation programs.Toward that direction,generation of transplantable organs using stem cells is a desirable approach for organ replacement and would be of great interest for both basic and clinical scientists.Here we review recent progress in the field of organ generation using various methods including single adult tissue stem cells,a blastocyst complementation system,tissue decellularization/recellularization and a combination of stem cells and tissue engineering.