Protection of CHO cells by transfer of survivin driven by ovarian-specific promoter OSP-2.

Chemotherapy is the major therapy for cancer in clinic. However, chemotherapeutic agents can harm the other tissues/organs besides cancer. Thus, there are great interests in protecting the innocents by the transfer of protective genes. There are two problems to be solved, one is the selection of protective genes and the other is the orientation of the exotic genes. Recent researches demonstrated that the principal mechanism of chemotherapeutics was through apoptosis. Hereby, introduction of anti-apoptosis genes might interrupt the processes of apoptosis to avoid side effect from chemotherapeutics. On the other hand, tissue-specific promoters, which control gene expression in a tissue-specific manner, might be an alternative tool to guarantee the location of target genes. In this research, we applied gene therapy to chemoprotection using anti-apoptosis gene survivin and ovarian-specific promoter OSP-2. The results showed that OSP-2 could specifically drive the expression of survivin in ovarian cells and survivin could protect cells via inhibiting apoptosis. This might put a light on the future of chemoprotective gene therapy.

Cloning and transcriptional activity of a novel ovarian-specific promoter from rat retrovirus-like elements.

The long terminal repeats (LTRs) are the control centers for retrovirus gene expression, which possess all of the requisite signals. It has been proved that the LTRs of Moloney murine leukemia virus (MoMLV) could constitutively activate genes in diverse cell types. Recently, a retrovirus-like element, OSP-1 (ovarian-specific promoter 1), was extracted from rat ovary according to the LTRs of MoMLV, whose name was derived from the fact of ovarian-specific transcription. It was reasonable to speculate that the tissue-specificity was acquired through mutations and that there should be abound other mutants, active or inactive. In the present study, we isolated several homologous sequences to OSP-1 and detected their function. Consequently, one of them could also drive target gene expression specifically to ovarian cell lines and was named OSP-2 which shared 98% similarity to OSP-1. On the other hand, we picked up other two closest sequences and proved them inactive, which was 97% and 95% similar to OSP-1, respectively. Sequence analysis revealed the different mutations around/within the binding sites of transcriptional factors that might play important roles in tissue-specificity. In summary, we extracted a novel ovarian-specific promoter as well as other nonfunctional mutants, which in part shed light on the study of ovarian-specific transcription. In addition, it also provided a new tool in cancer gene therapy and to create transgenic animals.

Management of intrauterine adhesions: a novel intrauterine device.

Intrauterine adhesions (IUAs) are a rare but significant cause of menstrual disturbance and infertility. Most cases are caused by uterine instrumentation. Several methods have been used to prevent IUAs in the past, which can be divided into two groups: pharmacological treatment and physical barrier. However, even with the liberal use of ancillary treatments to minimize reformation of adhesions, IUAs have a high rate of recurrence. Furthermore, medical literature of the last decades has only dedicated great attention to the restoration of normal anatomy in the uterine cavity, but not on the function of the endometrium. When the lesion of the endometrium is severe, especially intrauterine fibrosis, few basal layer is left which contains plenty stem cells to regenerate functional endometrium. Loss of endometrial stem cells directly causes the proliferation of fibrous tissue and subsequent synechiae. None of current treatments can compensate the defect of loss of stem cells. On the basis of existing researches, a novel intrauterine device (IUD) is recommended in this article. The new IUD consists of a light frame which contains two isolated drug-releasing system, one for estrogen and the other for cytokines to promote regeneration of endometrium such as growth factors, and a membrane in the middle of the frame which is also the carrier of endometrium stem cell. This device not only helps to preserve the original anatomy of the uterine cavity, but also to recover the function of endometrium. Experimental and clinical studies are now needed to testify the efficiency of the novel IUD in the prevention of IUAs. If there is a marked reduction in the IUAs and/or improvement of pregnancy success in the case group compared with the control group, our hypothesis will be confirmed.