Modulation of drug resistance in homoharringtonine-resistant C-1300 neuroblastoma cells with cyclosporine A and dipyridamole.

The development of resistance accounts for therapy failure in the majority of advanced cases of neuroblastoma in children. A new transplantable murine C-1300 neuroblastoma cell line was developed in vitro, by repeated exposure of a sensitive cell line to increasing, but sublethal, doses of Homoharringtonine (HHT). The ED50 of the highly resistant cells for HHT, using a standard agar colony assay, is 480 ng/ml, compared with 13 ng/ml for the sensitive parental line. The resistant cells have cross-resistance to a number of other agents, including adriamycin, vinca alkaloids, melphalan, and CCNU. Western blot analysis revealed progressive increases in P-glycoprotein, parallel to the graded development of resistance with a 29-fold elevation in the highest resistant cells. High-performance liquid chromatography (HPLC) indicated that resistant cells have a significantly lower uptake of HHT than parental sensitive cells. cyclosporine A (CsA) and dipyridamole (DPM) could modulate the acquired resistance and completely restore the cytotoxic effects of HHT and adriamycin as determined by the clonogenic assay. The reversal of resistance by CsA and DPM was dose dependent. With the relative low toxicity of dipyridamole and CsA in doses required for modulation of resistance, these agents may be candidates for clinical utilization in chemotherapy of resistant neuroblastoma.     

Past stem cells and finally in transit: SLC1A3 instructs skin niche coupling

During postnatal growth of the skin and homeostatic hair cycling, different proliferative compartments contribute to tissue expansion and establishment of a functional epidermis. A new study by Reichenbach et al ( 2018 ) reports coordinated proliferation of three distinct epithelial stem cell niches and a role for glutamate transporter Slc1a3 in synchronisation of activated stem and progenitor cells.     

The prevalence of goitre and cretinism in a population of the west Ivory Coast

Iodine deficiency is a major public health problem in developing countries. The main areas where goitre is prevalent have been identified, but the different degrees of severity and the populations affected have not. Most countries are now attempting to obtain reliable and more extensive data. A pilot study was carried out in the Ivory Coast in order to improve epidemiological knowledge of iodine deficiency and collect the information required to set up an elimination programme. The aim of this study was to assess the prevalence of goitre and cretinism and to measure the main biochemical indicators of thyroid function (T3, T4 and TSH). The study involved 1433 people identified from a census. The prevalence of goitre was 50.3%. There was a significant difference between the examined ethnic groups: 52.7% of the Yacouba and 28.6% of the non-Yacouba had goitre. The most affected age group was 15-45 year. The predominance of women demonstrated the susceptibility of women at child-bearing age to develop the condition. The prevalence of cretinism was approximately 1.5%. Through the assessment carried out using a grid of clinical indicators, it was possible to identify 10 cases of laboratory proven myxedematous cretinism due to hypothyroidism. The concentration of iodine in foodstuffs was below the limit of detection (< 7.5 micrograms/kg) and iodine could not be detected in the water (< 1 microgram.l) The biological profile of the population was affected to a very limited extent, with a mean value (+/- standard deviation) for TSH of 1.93 (+/- 1.56) mIU/l (0.1-4.0) and a free T4 value of 10 (+/- 3.46) pmol/l (8.2-20). These initial results confirm the high prevalence of endemic goitre and the low iodine content of the soil, water and food in the investigated region. The study will be complemented by a nutritional investigation to improve the understanding of iodine balance, after which an appropriate action plan will be proposed.     

Peptides with Dual Antimicrobial-Anticancer Activity Derived from the N-terminal Region of H. pylori Ribosomal Protein L1 (RpL1)

International Journal of Peptide Research and Therapeutics - Whereas the traditional approaches of cancer therapy including radiotherapy, chemotherapy, and immunotherapy have failed to properly...     

TB trifusion antigen adsorbed on calcium phosphate nanoparticles stimulates strong cellular immunity in mice

Among various vaccine candidates, subunit vaccines play an important role in immune protection against tuberculosis (TB). Calcium phosphate (CP) is considered as a strong inorganic adjuvant due to its great potential in increasing immune responses. The purpose of this study was to evaluate specific immune responses following the administration of trifusion-CP nanoparticles. The physiochemical properties of these nanoparticles, including morphology, particle size, zeta potential and adsorption rate, were measured in vitro. Subcutaneous immunization was performed three times on days 0, 14, and 28. Two weeks after the last administration, IFN-gamma, IL-4, and TGF-beta levels were measured by indirect enzyme linked immunosorbent assay (ELISA). The trifusion protein was successfully adsorbed onto calcium phosphate nanoparticles. The mean sizes of the resultant trifusion- CPN and CPN were 97.84 ± 12.08 and 67 ± 11.85 nm, respectively. CPN containing trifusion had stronger ability to induce IFN-gamma than the control groups. IL-4 and TGF-beta secretions in trifusion and trifusion-CPN groups were higher than those in the PBS group. However, there was no significant (p > 0.05) difference in IL-4 and TGFbeta concentrations between trifusion group and trifusion- CPN group. Therefore, calcium phosphate nanoparticles are good candidates for immunization against TB because antigen can be easily adsorbed onto CPN and strong cellular immune responses against CPN-antigen can be stimulated.     

Bimodal behaviour of interfollicular epidermal progenitors regulated by hair follicle position and cycling

Interfollicular epidermal (IFE) homeostasis is a major physiological process allowing maintenance of the skin barrier function. Despite progress in our understanding of stem cell populations in different hair follicle compartments, cellular mechanisms of IFE maintenance, in particular, whether a hierarchy of progenitors exists within this compartment, have remained controversial. We here used multicolour lineage tracing with Brainbow transgenic labels activated in the epidermis to track individual keratinocyte clones. Two modes of clonal progression could be observed in the adult murine dorsal skin. Clones attached to hair follicles showed rapid increase in size during the growth phase of the hair cycle. On the other hand, clones distant from hair follicles were slow cycling, but could be mobilized by a proliferative stimulus. Reinforced by mathematical modelling, these data support a model where progenitor cycling characteristics are differentially regulated in areas surrounding or away from growing hair follicles. Thus, while IFE progenitors follow a non‐hierarchical mode of development, spatiotemporal control by their environment can change their potentialities, with far‐reaching implications for epidermal homeostasis, wound repair and cancer development.