Drug discovery by targeting the protein-protein interactions involved in autophagy

Autophagy is a cellular process in which proteins and organelles are engulfed in autophagosomal vesicles and transported to the lysosome/vacuole for degradation. Protein-protein interactions (PPIs) play a crucial role at many stages of autophagy, which present formidable but attainable targets for autophagy regulation. Moreover, selective regulation of PPIs tends to have a lower risk in causing undesired off-target effects in the context of a complicated biological network. Thus, small-molecule regulators, including peptides and peptidomimetics, targeting the critical PPIs involved in autophagy provide a new opportunity for innovative drug discovery. This article provides general background knowledge of the critical PPIs involved in autophagy and reviews a range of successful attempts on discovering regulators targeting those PPIs. Successful strategies and existing limitations in this field are also discussed.

Stereotactic excision of benign breast lesions using the Mammotome system / 中国微创外科杂志

Objective To discuss the clinical value of u ltrasound-guided stereotactic biopsy and excision using the Mammotome system in the treatment of benign breast lesions. Methods A retrospecti ve analysis was made on the efficacy of ultrasound-guided Mammotome biopsy and e xcision in the management of 61 patients clinically diagnosed as having benign b reast lesions between October 2001 and October 2002. Results T he lesions were histologically confirmed as fibroadenoma in 51 patients and mast opathia in 10 patients. The operative time was 20.6?4.1 min. All procedures w ere performed smoothly. Of the 61 patients, no infection or breast deformity occ urred on short-term follow-up examinations (1 month) except for mild subcutaneou s hemorrhage in 3 patients, and no obvious scarring was seen on long-term follow -up (2 years). Recurrence was found in only 2 patients. Conclusions Treatment of benign breast diseases by the Mammotome system can offer comp lete excision of the lesion, minimal invasion, a low recurrence rate, and good c osmetic outcomes.

Expression of Mcm2 protein in colorectal neoplasm / 第二军医大学学报

Objective:To determine the expression of Mcm2(a member of MCMs family) in colorectal neoplasm and to assess the relationship between Mcm2 expression and clinicopathological characteristics of colorectal neoplasm.Methods: Immunohistochemical staining was used to detect the expression of Mcm2 in normal colorectal mucosa(n=23),adenoma(n=33),and cancer(n=69) tissues,and the results were quantified by calculating the labelling index(LI).Results: Mcm2 expression in normal colorectal mucosa was confined to the 1/3-1/2 of colonic crypts basal;there was no expression in coloncytes surface.In colorectal adenoma and cancer,Mcm2 expression was seen throughout epithelium,including the coloncytes surface.The median(range) LI of Mcm2 in these 3 tissues were 18%(5%-37%),35%(15%-75%),66%(41%-90%),respectively.The differences between normal mucosa,adenoma and cancer were statistically significant(P