Epidermal growth factor as a biologic switch in hair growth cycle

The hair growth cycle consists of three stages known as the anagen (growing), catagen (involution), and telogen (resting) phases. This cyclical growth of hair is regulated by a diversity of growth factors. Although normal expression of both epidermal growth factor and its receptor (EGFR) in the outer root sheath is down-regulated with the completion of follicular growth, here we show that continuous expression of epidermal growth factor in hair follicles of transgenic mice arrested follicular development at the final stage of morphogenesis. Data from immunoprecipitation and immunoblotting showed that epidermal growth factor signals through EGFR/ErbB2 heterodimers in skin. Furthermore, topical application of tyrphostin AG1478 or AG825, specific inhibitors of EGFR and ErbB2, respectively, completely inhibited new hair growth in wild type mice but not in transgenic mice. When the transgenic mice were crossed with waved-2 mice, which possess a lower kinase activity of EGFR, the hair phenotype was rescued in the offspring. Taken together, these data suggest that EGFR signaling is indispensable for the initiation of hair growth. On the other hand, continuous expression of epidermal growth factor prevents entry into the catagen phase. We propose that epidermal growth factor functions as a biologic switch that is turned on and off in hair follicles at the beginning and end of the anagen phase of the hair cycle, guarding the entry to and exit from the anagen phase.postprin

Dichlorodiphenyltrichloroethane specifically depletes dopaminergic neurons in primary cell culture

Toxicity of dichlorodiphenyltrichloroethane (DDT) to dopaminergic neurons in primary cell culture was investigated in the present study. Developing neurons from the substantia nigra of neonatal rats were cultured. After treatments with different concentrations of DDT (5-12.5 μM), specific cell death of tyrosine-hydroxylase-immunoreactive dopaminergic neurons was observed in the culture by flow cytometric analysis. More than 60% of dopaminergic neurons were depleted after treatments with 10 and 12.5 μM of DDT. In addition, significant reductions of intensity levels of tyrosine hydroxylase immunofluorescence were observed in dopaminergic neurons after DDT treatments even at low concentrations of DDT. The present findings indicate that dopaminergic neurons are more susceptible to DDT toxicity than other types of neurons in the primary cell culture. Moreover, it is shown that the synthesis of dopamine in dopaminergic neurons is also depressed. Previous studies have demonstrated that perinatal exposure of DDT causes neurons to be more susceptible to neurotoxic damages in later adult life. The present findings thus provide evidence that dopaminergic neurons that are undergoing growth and development are targets of DDT neurotoxic effects. Exposure to DDT from contaminated environments is therefore a potential risk of onset of Parkinson's disease. Copyright © 2003 S. Karger AG, Basel.published_or_final_versio

Preventing cervical cancer: primary and secondary measures

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Down-regulation of Sox7 is associated with aberrant activation of Wnt/b-catenin signaling in endometrial cancer

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Simulation, visualization and dosimetric validation of scatter radiation distribution under fluoroscopy settings

2015-2016 > Academic research: refereed > Refereed conference paperVersion of RecordPublishe

Molecular and cellular aspects of plasticity after neural injury

This review focuses on our effort to address plasticity of the nervous system after neural injury. We have used different animal models to examine cellular mechanisms of plasticity underlying the pathological and repair processes. After severance of sensory input from one inner ear, topographic representations of spacecentered coordinates in the brain undergo plastic changes. During vestibular compensation, tissue plasticity constitutes an important component for functional recovery of neuronal network. In Parkinsonian animals, modulation of signaling via glutamatergic synapses, neurotrophins and neurokinins contributes to the protection of basal ganglion neurons from degeneration, thereby delaying deterioration of motor functions. With the use of animal models of neural injury, we further overcome the molecular restriction at the glial scar to enhance neural regrowth and remyelination, pointing to the possibility of developing new therapeutic strategies to stimulate neural plasticity and repair in the adult nervous system.published_or_final_versio

Current concepts in the management of endometrial carcinoma

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Ultra-radical (extensive) surgery versus standard surgery for the primary cytoreduction of advanced epithelial ovarian cancer

BACKGROUND: Ovarian cancer is the sixth most common cancer among women and the leading cause of death in women with gynaecological malignancies. Opinions differ regarding the role of ultra-radical (extensive) cytoreductive surgery in ovarian cancer treatment. OBJECTIVES: To evaluate the effectiveness and morbidity associated with ultra-radical/extensive surgery in the management of advanced stage ovarian cancer. SEARCH STRATEGY: We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 4), MEDLINE and EMBASE (up to November 2010). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) or non-randomised studies, analysed using multivariate methods, that compared ultra-radical/extensive and standard surgery in adult women with advanced primary epithelial ovarian cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed whether potentially relevant studies met the inclusion criteria, abstracted data and assessed the risk of bias. One non-randomised study was identified so no meta-analyses were performed. MAIN RESULTS: One non-randomised study met our inclusion criteria. It analysed retrospective data for 194 women with stage IIIC advanced epithelial ovarian cancer who underwent either ultra-radical (extensive) or standard surgery and reported disease specific overall survival and perioperative mortality. Multivariate analysis, adjusted for prognostic factors, identified better disease specific survival among women receiving ultra-radical surgery, although this was not statistically significant (Hazard ratio (HR) = 0.64, 95% confidence interval (CI): 0.40 to 1.04). In a subset of 144 women with carcinomatosis, those who underwent ultra-radical surgery had significantly better disease specific survival than women who underwent standard surgery (adjusted HR = 0.64, 95% CI 0.41 to 0.98). Progression-free survival and quality of life (QoL) were not reported and adverse events were incompletely documented. The study was at high risk of bias. AUTHORS' CONCLUSIONS: We found only low quality evidence comparing ultra-radical and standard surgery in women with advanced ovarian cancer and carcinomatosis. The evidence suggested that ultra-radical surgery may result in better survival. It was unclear whether there were any differences in progression-free survival, QoL and morbidity between the two groups. The cost-effectiveness of this intervention has not been investigated. We are, therefore, unable to reach definite conclusions about the relative benefits and adverse effects of the two types of surgery.In order to determine the role of ultra-radical surgery in the management of advanced stage ovarian cancer, a sufficiently powered randomised controlled trial comparing ultra-radical and standard surgery or well-designed non-randomised studies would be required.link_to_subscribed_fulltex

Experience of using bevacizumab in epithelial ovarian, fallopian tube and primary peritoneal cancers in a single centre

Objectives: To review the use of bevacizumab in epithelial ovarian, fallopian tube and primary peritoneal cancers in our centre. Methods: Patients receiving bevacizumab for epithelial ovarian, fallopian tube and primary peritoneal cancer at the Division of Gynaecological Oncology, Queen Mary Hospital, The University of Hong Kong between January 2011 and December 2015 were included. A retrospective chart review was performed. Main outcome measures were adverse events and progression-free survival. Results: Overall, 41 patients received bevacizumab for epithelial ovarian, fallopian tube or primary peritoneal cancer, of which 24 were for primary treatment and 17 for recurrent disease. Of 24 patients who received bevacizumab as primary treatment, the median age was 52 years, and 12.5% of the patients had early-stage high-risk disease, 87.5% had FIGO stage III or IV disease, 45.8% had a serous adenocarcinoma, and 54.2% had residual disease after debulking surgery. Of 17 patients who received bevacizumab for recurrent disease, the median age was 52 years, and 94.1% of the patients were having their first recurrence, 64.7% had platinum-sensitive disease and 41.2% had a serous adenocarcinoma. Grade 2 or higher hypertension and proteinuria occured in 24.4% and 12.2% of patients, respectively. Bevacizumab was discontinued in 7.3% of patients due to adverse events and 31.7% due to inadequate therapeutic response. The median progression free survival was 18.0 months (95% CI 13.6 to 22.4) for primary treatment and 11.0 months (95% CI 8.4 to 13.6) for recurrent disease. Conclusions: With acceptable toxicity, combination of bevacizumab and chemotherapy may be considered as treatment modality in newly diagnosed suboptimally debulked stage III or stage IV ovarian cancer as well as in recurrent ovarian cancer.postprin

Downregulation of the Gli Transcription Factors Regulator Kif7 Facilitates Cell Survival and Migration of Choriocarcinoma Cells

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