ABSTRACT
Objective To estimate the effect of glycoprotein (transmembrane) nonmetastatic melanoma protein B (GPNMB) on the proliferation and migration of as well as melanogenesis in melanoma cells.Methods The expression of GPNMB was detected by immunofluorescence assay in two melanoma cell lines M14 and G-361,as well as in primary human melanocytes.Then,the three kinds of cells each were classified into three groups:experimental group treated with small interfering RNA targeting GPNMB (GPNMB-siRNA),negative control group treated with the negative control siRNA,blank control group remaining untreated.Methyl thiazolyl tetrazolium (MTT) assay,transwell invasion assay and spectrophotometry were performed to evaluate cell proliferation activity,invasion potential and melanin levels,respectively.Statistical analysis was done using Student's t test.Results GPNMB was expressed in both melanoma cells and melanocytes.The transfection with GPNMB-siRNA down-regulated the mRNA and protein expressions of GPNMB in,and markedly suppressed the proliferation and migration of,melanoma cells.In detail,the proliferative activity (expressed as the absorbence value at 570 nm) of M14 and G361 cells was reduced by 35％ and 40％ respectively,the migration activity of M14 and G361 cells by 49％ and 51％ respectively,and the melanin levels in melanocytes,M14 cells and G361 cells by 73％,82％ and 69％ respectively,in the experiment group compared with those in the blank control group.Conclusions The siRNA-mediated silencing of GPNMB could effectively inhibit the proliferation of,invasion of and melanogenesis in melanoma cells,which suggests that GPNMB plays critical roles in the initiation and progression of melanoma.
ABSTRACT
Objective To reconstruct skin defects with local flaps after resection of tumors. Methods From October 2006 to December 2009, medial canthal defects in 15 patients were repaired with local flaps in the hospital. The size of the defects varied from 1 cm × 1 cm to 1.8 cm × 2.0 cm. According to the size and location of the defects, different local flaps such as glabellar flaps ,rotation flaps, advancement flaps, nasolabial flaps and combination of these local flaps were selected and designed to repair the skin defects. Results Of the 15 patients, 12 received the reconstruction of skin defects with single flap, the other 3 with two flaps; totally,18 local flaps were designed and applied. All the flaps survived with primary healing postoperatively. A followup in 11 patients for 6 to 12 months showed that the color and texture of flaps were similar to those of surrounding tissues and incision line scar was inconspicuous. Medial canthal contours were restored without distortion of surrounding structures. Satisfactory function and aesthetic outcomes were achieved. Conclusions In the repair of inner canthus skin defects, to maintain and restore the "cosmetic unit" integrity of inner canthus by using suitable local flaps would lead to a satisfying restoration of function and appearance.
ABSTRACT
Chronic myeloid leukemia (CML) is a myeloproliferative disease characterized by the overproduction of granulocytes, which leads to high white blood cell counts and splenomegaly in patients. Based on clinical symptoms and laboratory findings, CML is classified into three clinical phases, often starting with a chronic phase, progressing to an accelerated phase and ultimately ending in a terminal phase called blast crisis. Blast crisis phase of CML is clinically similar to an acute leukemia; in particular, B-cell acute lymphoblastic leukemia (B-ALL) is a severe form of acute leukemia in blast crisis, and there is no effective therapy for it yet. CML is induced by the BCR-ABL oncogene, whose gene product is a BCR-ABL tyrosine kinase. Currently, inhibition of BCR-ABL kinase activity by its kinase inhibitor such as imatinib mesylate (Gleevec) is a major therapeutic strategy for CML. However, the inability of BCR-ABL kinase inhibitors to completely kill leukemia stem cells (LSCs) indicates that these kinase inhibitors are unlikely to cure CML. In addition, drug resistance due to the development of BCRABL mutations occurs before and during treatment of CML with kinase inhibitors. A critical issue to resolve this problem is to fully understand the biology of LSCs, and to identify key genes that play significant roles in survival and self-renewal of LSCs. In this review, we will focus on LSCs in CML by summarizing and discussing available experimental results, including the original studies from our own laboratory.