Human tumor suppressor gene. The gene encodes a protein with a molecular weight of 53kDa, named P53. Inactivation of p53 gene plays an important role in tumor formation.

P53 protein is mainly concentrated in nucleolar region, which can specifically bind to DNA, and its activity is regulated by phosphorylation. The biological function of normal P53 is like "the guardian of genome". At the G 1 stage, DNA damage points were examined to monitor the integrity of the genome. In the case of injury, P53 protein prevents DNA replication, so as to provide enough time for DNA repair. If the repair fails, P53 protein will induce apoptosis. If both copies of p53 gene mutate, cell proliferation will be out of control, leading to cancer.

P53 gene therapy

Gene therapy refers to biomedical treatment based on changing human genetic material. It introduces human normal genes or therapeutic DNA into human target cells in a certain way to correct gene defects or play a therapeutic role. So gene therapy is aimed at the root of the disease-the abnormal gene itself.

Cancer is a genetic disease, which is a multi-stage and long-term evolutionary process in which many pre-oncogenes are activated and tumor suppressor genes are inactivated under the influence of external environmental factors. Cancer is a serious threat to human health and life. There are more than 2.5 million new cancer patients in China every year, and no less than 6 million patients receive treatment every year. The treatment cost exceeds 654.38+50 million yuan. At present, the main treatments for tumors are surgery, radiotherapy and chemotherapy. Although medical scientists constantly improve these three treatments, many cancer patients are still difficult to cure. People pay more and more attention to improving the cure rate of tumors through "radical cure", and gene therapy is the only way for human beings to overcome tumors in 2 1 century.

P53 gene is the most thoroughly studied and powerful tumor suppressor gene. Wild-type p53 plays a key role in cell cycle and apoptosis, especially in killing cancer cells hit by radiation, cytotoxic agents and high temperature. Its main functions are:

Inhibit and kill tumor cells; Combined with radiotherapy and chemotherapy to enhance its efficacy in killing cancer cells, so as to achieve

1+ 1 greater than 2;

Inhibit tumor angiogenesis and effectively prevent tumor recurrence and metastasis. Improve human immune function;

Domestic recombinant human p53 adenovirus injection (trade name: Zaijinsheng), under the leadership of Professor Wen from Beijing Cancer Hospital, successfully completed the second clinical trial of head and neck squamous cell carcinoma after five years of arduous clinical trials, which fully proved that it was safe and effective in the treatment of head and neck squamous cell carcinoma. On June 65438+1October 65438+June, 2003, the State Food and Drug Administration of the United States approved the new drug certificate of recombinant human p53 adenovirus injection, which means that the world's first cancer gene therapy drug was born in China, marking that China is at the forefront of the world in cancer clinical gene therapy and gene drug industrialization.

Recombinant human p53 adenovirus is a live virus modified by genetic engineering, and its structure consists of two parts: tumor suppressor gene p53 and vector. The vector is a modified adenovirus with no replication ability. Just like a rocket carrying a satellite into space, this adenovirus carrying p53 specifically infects tumor cells. It can effectively transfer p53 gene for treatment to tumor cells, but it is harmless to normal cells.

53 cases of head and neck squamous cell carcinoma were treated with radiotherapy, and the complete disappearance rate of tumor was twice as high as that of 46 cases treated with radiotherapy alone. 45 cases of nasopharyngeal carcinoma were treated with radiotherapy, and the tumor complete disappearance rate was 4 1 case higher than that of radiotherapy alone 1.7 times. Combined with radiotherapy, 4 cases of inoperable stage ⅲ cervical cancer were treated, and all the tumors disappeared completely. Combined with radiotherapy, chemotherapy or hyperthermia, all kinds of soft tissue sarcoma, digestive system adenocarcinoma and ovarian cancer have achieved certain curative effects, and these cases are all patients who failed to be treated by the three major means. Jinsheng has not found any other side effects except temporary self-limited fever in the treatment of malignant tumor. In the future, comprehensive clinical trials will be carried out in other tertiary hospitals in an orderly manner, and p53 gene therapy will move from laboratory to clinic and industrialization.

P53 gene therapy for cancer is just a good beginning, which brings new hope and dawn for mankind to conquer cancer.

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