External doppler monitoring of free flaps through negative pressure dressings

The negative pressure dressing is a highly effective modality for coverage and bolstering of skin grafts in the early postoperative period. In the situation of a skin graft over a free flap, the surgeon might be inclined to avoid this modality out of concern that the dressing would deleteriously effect flap survival or impede flap monitoring. This case series supports the safety of the negative pressure dressing and demonstrates a technical modification that permits external Doppler monitoring of the flap through the dressing. Thus, this technique provides an ideal environment for skin graft healing while maintaining the ability to monitor the flap in a straightforward manner and also simplifies nursing care.     

Significance for the diagnosis of iron overload of histochemical and chemical iron in the liver of control subjects

Storage iron was examined in surgical liver biopsy specimens in 43 haematologically normal and otherwise healthy adult individuals. These patients had no history of unphysiological iron losses nor of unphysiological iron intake. Histochemical iron was estimated in parenchymal and Kupffer cells and graded from 0 to 4+. Stainable iron of grade 1+ or more was present in parenchymal cells in 23 of the 27 men. Six of them had a 3+ grade. In nine cases iron was also visible in Kupffer cells. Visible iron was absent in most of the menstruating women. The mean total nonhaemin iron concentration for the male group was 80·2 (19·4 to 227·0), for the postmenopausal women 50·7 (19·3 to 106·6), and for the menstruating women 23·5 (5·5 to 65·9) mg./100 g. dry weight. The mean value for the women was significantly lower than the mean value for the men. There was a significant correlation between the histochemical grades of iron and chemically determined nonhaemin iron, but the degree of overlapping was considerable.     

Polynucleotide kinase as a potential target for enhancing cytotoxicity by ionizing radiation and topoisomerase I inhibitors

The cytotoxicity of many antineoplastic agents is due to their capacity to damage DNA and there is evidence indicating that DNA repair contributes to the cellular resistance to such agents. DNA strand breaks constitute a significant proportion of the lesions generated by a broad range of genotoxic agents, either directly, or during the course of DNA repair. Strand breaks that are caused by many agents including ionizing radiation, topoisomerase I inhibitors, and DNA repair glycosylases such as NEIL1 and NEIL2, often contain 5'-hydroxyl and/or 3'-phosphate termini. These ends must be converted to 5'-phosphate and 3'-hydroxyl termini in order to allow DNA polymerases and ligases to catalyze repair synthesis and strand rejoining. A key enzyme involved in this end-processing is polynucleotide kinase (PNK), which possesses two enzyme activities, a DNA 5'-kinase activity and a 3'-phosphatase activity. PNK participates in the single-strand break repair pathway and the non-homologous end joining pathway for double-strand break repair. RNAi-mediated down-regulation of PNK renders cells more sensitive to ionizing radiation and camptothecin, a topoisomerase I inhibitor. Structural analysis of PNK revealed the protein is composed of three domains, the kinase domain at the C-terminus, the phosphatase domain in the centre and a forkhead associated (FHA) domain at the N-terminus. The FHA domain plays a critical role in the binding of PNK to other DNA repair proteins. Thus each PNK domain may be a suitable target for small molecule inhibition to effectively reduce resistance to ionizing radiation and topoisomerase I inhibitors.     

Cationic polymer‐mediated small interfering RNA delivery for P‐glycoprotein down‐regulation in tumor cells

BACKGROUND:

Among the treatment options that have been developed for cancer, chemotherapy remains 1 of the leading clinical approaches. Chemotherapy can usually control tumor growth at the onset of disease, but its effectiveness becomes limited by the overexpression of transporter proteins responsible for drug efflux, leading to multidrug resistance (MDR). To overcome this obstacle, the authors explored the feasibility of down‐regulating the main drug transporter, P‐glycoprotein (P‐gp), by using nonviral small interfering RNA (siRNA) delivery as means to enhance the accumulation of chemotherapeutic agents in drug‐resistant cancer cells.

METHODS:

Several cationic carriers capable of siRNA complexation were investigated for P‐gp down‐regulation in the MDA435/LCC6 cell line and, consequently, increased cellular uptake of the chemotherapeutic agents doxorubicin and paclitaxel.

RESULTS:

Efficient siRNA delivery into tumor cells was demonstrated particularly using a palmitic‐acid substituted poly(L‐lysine), with no apparent differences in siRNA delivery between the wild type (WT)‐expressing and P‐gp‐expressing phenotype (MDR1) of the cells. Efficient siRNA delivery led to approximately 40% to 50% P‐gp suppression (based on the average expression level of the protein), an approximately 3‐fold increased DOX uptake, and increased cytotoxicity in MDR1 cells.

CONCLUSIONS:

The authors concluded that effective siRNA delivery with nonviral carriers can reduce the level of P‐gp on cell surfaces and enhance the efficiency of chemotherapeutic agents in vitro. Cancer 2010. © 2010 American Cancer Society.     

Interleukins,laminin and epstein - barr virus latent membrane protein 1 (EBV LMP1) Promote metastatic phenotype in nasopharyngeal carcinoma

Background  

Nasopharyngeal carcinoma (NPC) is a type of neoplasm that is highly prevalent in East Asia and Africa with Epstein-Barr virus (EBV), genetic, and dietary factors implicated as possible aetiologic factors. Previous studies suggested the association of certain cytokines with the invasion and metastatic properties of NPC. The present study examined the roles of EBV latent membrane protein-1 (LMP1), interleukin-6 (IL-6), interleukin-10 (IL-10), transforming growth factor-beta 1 (TGF-β1) and laminin in the regulation of matrix-metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) in NPC. The effects of these factors on bmi-1, an oncogene, and ngx6, a tumour suppressor gene, were also investigated.