CT-guided I implantation of tumor cell apoptosis and related genes

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1、 CT-guided 125I implantation of tumor cell apoptosis and related genes Keywords: tumor; iodine radioisotopes; close-therapy; apoptosis; gene; Radiology Radiation therapy is one of the primary means of treating cancer, began in the late 19th century, interstitial brachytherapy radioactive particles h

2、ave nearly 100 years ago the history of 1, but because the production of radioactive particles are mostly high-energy radionuclides, The release of -ray radionuclides, quite difficult to deal with protection of patients and health care workers caused serious injury, coupled with no precise positioni

3、ng system and the treatment planning system and quality certification system, the treatment greatly reduced the accuracy and clinical application of slow progress. the past 20 years , with the new, low-energy particles of radioactive 125I successful development of the computer the emergence of three

4、-dimensional treatment planning system and the ultrasound, CT guided the development of positioning systems, so that the technology of radioactive particles in treatment of cancer has gained new vigor. particle implantation in radiology treatment of tumors with high precision, minimally invasive and

5、 efficacy of certain other advantages, clinical application shows a broad prospect. But for the 125I treatment of cancer of the mechanism of particle and related experimental research at home and abroad are not reported more on this area is Research reviewed. 1, CT guided positioning system CT guida

6、nce technology as a safe, accurate and efficient diagnosis and treatment 2, more and more clinical and radiologists attention. CT scan for high-density resolution, shows cross-sectional intuitive, can well Show lesion and the surrounding anatomy organs, especially from gas, the interference of bone

7、and adipose tissue can be used as various parts of the body-oriented devices. recent years, with 64-slice spiral CT and ultra-fast CT scanners used in clinical gradually began to reduce the operating time of CT guidance, reducing the radiation dose, especially the new system can be configured to pin

8、point three-dimensional positioning of the needle path and the simulated robot manipulation, improved accuracy and success rate of puncture, and position of some small tumors deep tumor has obvious advantages, but also to avoid damage vital organs, reduce complications, compared with the surgery is

9、a safe, reliable, minimally invasive, simple method of treatment 3. 2, CT guided three-dimensional treatment planning system 90 20th century, three-dimensional CT guided treatment planning system (TPS and quality verification system began to be used clinically. TPS treatment planning system is to ch

10、eck the image through the CT scanner into the computer software system, the reconstruction of three-dimensional image displayed on the screen, calculated according to the tumor target volume radioactive particles in the tumor lesion and the surrounding area of ​​space dose distribution,

11、development of the prescription dose, calculate the number and activity of radioactive particles to calculate the location of radioactive particles from the sensitive organizations and put forward to avoid the security-sensitive organizations or vital organs near the tumor in the best way. After the

12、 implantation of particles enter the TPS CT scan image quality verification system, based on the actual particle distribution, depicts the actual dose distribution curve, the quality certification, a clear risk of tumors and organs around the tumor the dose actually received. 3,125 I particle effect

13、s on tumor cell apoptosis 125I brachytherapy interstitial implantation particles, the apoptosis is the main form of cell death of tumor 4. Szostak MJ 5 of 76 T1-2 prostate cancer patients with tumors implanted 125I particles, before treatment and After treatment, 7-23 months (median 12 months, biops

14、y of tumor tissue was found after brachytherapy than before radiation significantly increased apoptotic index (3.1% vs 2%, P <0.05, and the tumor in the follow-up disappearance of the tumor in patients with persistent compared to patients with biopsy apoptosis index also increased significantly (

15、3.4% vs 1.8%, P = 0.02. Song Jinlong et al 6 125I seed implantation in hepatocellular carcinoma in nude mice, irradiation 48 hours after the apoptosis index (7.31 + - 1.41)% in the control group (0.69 + -0.14)%, confirming 125I brachytherapy for cancer cells. In Petraki CD 7 of prostate cancer, Keme

16、ny-Beke A 8 on the context layer of melanoma, Zlobec I 9 on the colorectal cancer study of brachytherapy also confirmed the existence of a large number of apoptotic cells. 4, 125I particles implantation in tumor tissue P53 gene regulation p53 gene is a tumor suppressor gene, located on the short arm

17、 of human chromosome 17, encoding phosphoprotein p53 (wild type found in the nucleus, is a nuclear binding protein 10. normal P53 protein in DNA damage or hypoxia When activated, so dependent on the CDK inhibitor P21 and P53 DNA repair gene transcription regulation, cell growth arrest in the G1 phas

18、e appears to carry out DNA repair. If successful repair, the cell into S phase, such as the repair fails, then through the activation of bax gene the cells into apoptosis, in order to ensure the genetic stability of the genome 11-12 .125 I particles implantation in two ways induced by DNA damage (a

19、direct effect: -ray of the tumor cell nuclear DNA double-strand breaks, single strand fracture. (2 indirect effects: ray ionization of the water molecules to produce free radicals (H., OH. and the interaction of biological macromolecules, and then act on the DNA chain, causing DNA damage. to increas

20、e the expression of wild-type p53 gene, increased Inhibition of tumor. Ishikawa H 13 38 B for cervical squamous cell carcinoma of the endometrium within a short distance outside the radiotherapy combined with radiotherapy, the results of 22 (58% of patients after radiotherapy showed high expression

21、rate of P53. In the following study 14 He also found that mutation of P53 gene is highly associated with tumor recurrence, but also the type of P53 in the relapse free survival and local control rates are also statistically significant (P = 0.02 and P = 0.03, and therefore that B P53 can serve as a

22、squamous cell cervical radiotherapy of endometrial cancer as a predictor. Oka k 15 to give 40 cervical squamous cell carcinoma of 27Gy dose brachytherapy, radiotherapy was significantly higher than that before radiotherapy P53 . Sur M 16 Early on 10 patients with lower esophageal brachytherapy, eigh

23、t patients after radiotherapy P53 gene showed strong positive, so that brachytherapy can be anti-P53 gene containing wild-type cells, but tumor edge Area P53 gene variant with no cell killing effect. Brantley MA Jr 17 of 12 patients with choroidal melanoma, brachytherapy, six (50% of the patients an

24、d the P53 gene showed strong positive correlation with the recent highly radiotherapy (P = 0.04. Lo Kai Yuan 18 nude mouse model of colorectal cancer research organizations found that implantation of 125I particles can cause increased expression of P53 gene, apoptotic cells increased. 5, 125I partic

25、les implantation in tumor tissue expression of bcl-2 gene In apoptosis regulatory genes related to research, Bcl-2 gene is the most in-depth study, the most extensive one of the apoptosis regulatory genes 19. Bcl-2 gene was originally follicular non-Hodgkins separate B-cell lymphoma, which is in the

26、 14 and 18 on the chromosome translocation breakpoints were found. Bcl-2 gene encodes a 25-26KD protein, the C terminal hydrophobic amino acids 21 an extension of The chain structure. the chain into the cell membrane to the structure, the structural features and Bcl-2 regulation of apoptosis is rela

27、ted to the manner and capacity 20. Bcl-2 gene belongs to a new class of cancer gene family members, through the effective inhibition of many different types of apoptotic stimuli-induced apoptosis, prolonged cell viability and exerts its biological effect on cell cycle progression does not occur 21.

28、Many scholars study found that nearly from radiation therapy can reduce the level of bcl-2 gene, thus shortening the life span of tumor cells, accelerated apoptosis. Lang X 22 to 80 artificial vascular graft model mice were randomly divided into two groups: control group and the brachytherapy group

29、(20Gy After 3 days, 1 week, 2 weeks, 4 weeks, respectively, the tissue immunohistochemistry results showed that brachytherapy group of bcl-2 gene was significantly lower at 2 weeks (t = 9.783, P <0.05. Shaowen Bo 23 12 nude mice bearing human hepatocellular carcinoma BEL-7402 model is divided int

30、o treatment group and the control group 6. xenografts in nude mice per treatment group implanted an activity for the 33.3MBq of 125I particles in the control group .3 weeks without intervention Immunohistochemistry showed that bcl-2 gene therapy group than the control group. Szostak MJ 5 of 76 patie

31、nts with early prostate cancer, interstitial implantation of 125I particles were followed up for 7-23 months ( After a median of 12 months showed that bcl-2 gene in a more effective treatment in patients with treatment failure was significantly higher than patients (30.5% vs 13.1%, P <0.05.Zlobel

32、 I 9 of 62 patients with rectal cancer to surgery before brachytherapy and postoperative radiotherapy in the tumor bed on the assessment of pathology, found that 85% bcl -2 gene radiotherapy in patients with negative effective. Ishikawa H 13 of 38 B squamous cell carcinoma of the cervix in patients

33、and outside combined with radiotherapy, although there are 15 (39% of patients with high bcl-2 gene expression, but bcl-2 gene and that the local recurrence free survival rate and no correlation. 6, 125I particles implantation in Bax gene expression in tumor tissue The physiological function of Bax

34、proteins promote apoptosis, its mechanism is not itself a direct role. The one hand, overexpression of its apoptosis signal start, on the other hand, performance in the inhibition of Bcl-2 protein, which is Bax The main mechanism for regulating apoptosis. Bax protein Bcl-2 protein is an important in

35、hibitory factor, when the Bax protein dimer protein or Ba x dominant, the cells can be induced to apoptosis when Bcl-2 protein and Bcl-2 protein II dominant polymer When apoptosis was inhibited. Bax and Bcl-2 can form heterodimers, thus inhibiting the function of Bcl-2 24 .125 I particles after impl

36、antation in tumor tissue, Bax gene level may rise high, thus inducing apoptosis. Harima Y 25 37 B for cervical cancer to pelvic external radiotherapy in patients with pelvic radiotherapy combined with brachytherapy and hyperthermia, better tumor control by Bax gene increased. Lang X 22 in the mouse

37、model of artificial blood vessel transplantation experiments confirmed that 2 weeks after brachytherapy Bax gene was significantly higher (t = 9.783, P <0.05. Shaowen Bo 23 In nude mice bearing human hepatocellular carcinoma BEL-7402 Model 125I particles found in interstitial implantation experim

38、ents 3 weeks after the experimental group was significantly higher than in the control group Bax. Links to free paper download 7, 125I particles implantation in tumor tissue VEGF expression and regulation Tumor growth, invasion and metastasis of affected and restricted by many factors, angiogenesis

39、is an important factor. Tumor blood vessels required for tumor growth not only provides nutrition, but also a way to spread cancer cells 26. Vascular endothelial growth factor (vasocular endothelial growth factor, VEGF is the most potent known angiogenic factors promote. VEGF by stromal cells in tum

40、or tissue and tumor cells in the majority of solid tumor tissue was highly expressed, it is not only can promote the proliferation of tumor vascular endothelial cells and vascular endothelial growth factor and other obvious synergies there promote angiogenesis 27-28. brachytherapy by eliminating the

41、 role of VEGF and inhibit the formation and migration of endothelial cells, inhibit basement membrane degradation mechanism to achieve anti-tumor. Missotten GS 29 of 74 patients with choroidal melanoma brachytherapy and found that VEGF-A concentration range of factors 18-826pg/ml, which has been con

42、trolled in 30 cancer patients, VEGF was significantly lower (average 50.1pg/ml (p <0.001). Zlobel I 9 of 62 patients with rectal cancer during preoperative radiotherapy, 10 patients without VEGF complete response to radiotherapy, 85% VEGF and bcl-2 negative patients respond to radiotherapy, so th

43、at preoperative VEGF can be used as a predictor of radiation sensitivity. In animal experiments 18,30, also confirmed brachytherapy can reduce the level of VEGF . In conclusion, CT guided interstitial implantation of 125I tumor particles in the country is a new treatment, the P53 gene and by activat

44、ion of Bax gene, Bcl-2 gene and inhibition of VEGF to induce tumor cell apoptosis and other . Although brachytherapy on the classic tumor suppressor gene and its function is still controversial, the opinions of apoptosis related genes is not uniform, however, CT-guided 125I seed implantation is a tu

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