ABSTRACT
Many reports have indicated that the insulin receptor (IR) causes tumorigenesis and the development of breast cancer. It has been considered a potential target for treating IR-related tumors. Traditionally, there are two categories of insulin receptor (IR) antagonists, they are small molecule antagonists and anti-IR antibodies. Here, we describe a new method (anti-idiotypic antibody strategy) for the development of IR antagonist. Hybridoma technology was employed to design and identify a series of anti-idiotypic antibodies against insulin. After repeated screening and identification, an anti-idiotypic antibody against IR (AK98) was obtained. Analysis through competitive ELISA and competitive receptor binding indicated that AK98 mimicked the receptor binding epitope of insulin. The interaction between AK98 and IR was determined using indirect immunofluorescence, immunoelectron microscopy, and Immunoprecipitation-Western (IP-WB). Further research using a tumor cell model revealed that AK98 inhibited insulin-IR binding and IR-mediated intracellular signaling pathways. Conclusively, the main purpose of this paper is that we proposed a new method (anti-idiotypic antibody strategy) to develop the insulin receptor (IR) antagonist (AK98), and a series of experiments showed that the anti-idiotypic antibody (AK98) exhibited good antagonistic activity against IR. This work suggests that the anti-idiotypic antibody may be a potential strategy to develop IR antagonists that can be used in treating breast cancer.
Subject(s)
Antibodies, Anti-Idiotypic , Antineoplastic Agents , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Drug Development/instrumentation , Drug Development/methods , Receptor, Insulin/antagonists & inhibitors , Antibodies, Anti-Idiotypic/pharmacology , Antibodies, Anti-Idiotypic/therapeutic use , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Female , Humans , Hybridomas , Insulin/metabolism , MCF-7 Cells , Protein Binding/drug effects , Receptor, Insulin/metabolism , Signal Transduction/drug effects , Signal Transduction/geneticsABSTRACT
Objective To investigate the infection status of mycoplasma in Shenzhen migrant workers′genitourinary tract and the sensitivity of 12 kinds of antibiotics for guiding rational use of drugs in clinical treatment ,through the test of specimens with 2 905 cases of mycoplasma culture and drug susceptibility test .Methods Drug sensitivity test and culture of mycoplasma were per-formed on the specimens form 2 905 new patients in five hospitals by using liquid mycoplasma culture method .Results In speci-mens of 2 905 cases ,mycoplasma positive rate was 41 .8 % (1 214 cases) ,single ureaplasma urolyticum(Uu) infection rate was 39%(1 133 cases) ,single mycoplasma hominis(Mh) infection rate was 1 .3% (37 cases) ,Uu+ Mh mixed infection rate was 1 .5% (44 cases) .The result of sensitive test show that the sensitive rate of Uu to josamycin ,doxycycline ,minocin were 88 .6% ,91 .9% , 92 .2% .Conclusion The migrant workers'mycoplasma infection rate is very high in Shenzhen area .The infection of single Uu has the highest percentage ,mycoplasma is sensitive to the minocin .
