本文關(guān)鍵詞： 新生血管抑制劑 Vasostation TRAIL 重組表達(dá) 抗腫瘤 融合蛋白　出處：《第二軍醫(yī)大學(xué)》2005年碩士論文　論文類型：學(xué)位論文

【摘要】：新生血管的形成(angiogenesis)是從已有血管生成新血管的重要生理和病理過(guò)程,其可發(fā)生在胚胎形成、子宮內(nèi)膜周期性變化、傷口愈合和腫瘤生長(zhǎng)等環(huán)節(jié)。新生血管形成是一個(gè)復(fù)雜的過(guò)程,受到一系列正負(fù)生長(zhǎng)因子的調(diào)控。一旦這些正負(fù)調(diào)控因子失去平衡,就可能造成不正常的新生血管形成,導(dǎo)致腫瘤的生長(zhǎng)轉(zhuǎn)移、心肌梗塞和糖尿病等疾病。與正常細(xì)胞一樣,腫瘤細(xì)胞的代謝和營(yíng)養(yǎng)需要從血液中獲取氧氣和養(yǎng)料,運(yùn)走代謝產(chǎn)生的物質(zhì)。如果沒有這些充足的營(yíng)養(yǎng)供應(yīng),一個(gè)腫瘤塊就只能長(zhǎng)到2mm~3那么大。血管生成除了供給腫瘤生長(zhǎng)必需的養(yǎng)分外,也是腫瘤轉(zhuǎn)移的必要的條件之一,腫瘤細(xì)胞進(jìn)入血液循環(huán)從而向其他組織器官浸潤(rùn)轉(zhuǎn)移。如果抑制新生血管形成,腫瘤細(xì)胞將發(fā)生凋亡或壞死。這就為抗腫瘤治療提供了一條新思路,目前臨床上已有多種抑制新生血管的藥物用于抗腫瘤治療。 Vasostatin是最近發(fā)現(xiàn)的一個(gè)血管生成抑制因子,最初是從經(jīng)EB病毒轉(zhuǎn)化的B細(xì)胞系VDS-O的培養(yǎng)上清液中提純,是鈣網(wǎng)蛋白(calreticulin)的N-端1～180個(gè)氨基酸組成的結(jié)構(gòu)域片段。Vasostatin可有效且專一的抑制內(nèi)皮細(xì)胞的增生,使新生血管無(wú)法生成,進(jìn)而抑制腫瘤的生長(zhǎng)。將Vasostatin注射于無(wú)胸腺小鼠中,可明顯抑制Burkitt淋巴瘤和人結(jié)腸癌的生長(zhǎng)。Vasostatin通過(guò)抑制血管內(nèi)皮細(xì)胞的增殖、遷移和抑制新生血管的形成,從而抑制腫瘤生長(zhǎng)。當(dāng)前的研究表明Vasostatin具有抗腫瘤效果明顯、毒副作用低等特點(diǎn),但尚不知Vasostatin片段是通過(guò)何種途徑作用于細(xì)胞,近期的研究表明可能與細(xì)胞表面因子Laminin有關(guān)。 1995年,國(guó)外報(bào)道從人表達(dá)標(biāo)簽序列文庫(kù)(expressed sequence tag,EST)中篩選到一種編碼抗腫瘤蛋白質(zhì)的基因,該基因編碼的蛋白質(zhì)稱為腫瘤壞死因子相關(guān)凋亡誘導(dǎo)配體(tumor necrosis factor-related apoptosis-inducing ligand,TRAIL),又稱凋亡素2配體(apoptotin-2 ligand,簡(jiǎn)稱Apo-2L),是腫瘤壞死因子(tumornecrosis factor,TNF)家族成員之一,其通過(guò)啟動(dòng)細(xì)胞固有的凋亡程序,可有效地誘導(dǎo)腫瘤和轉(zhuǎn)化細(xì)胞凋亡,而對(duì)正常細(xì)胞無(wú)影響。人TRAIL基因的編碼序列有843個(gè)核苷酸,編碼的蛋白質(zhì)TRAIL由281個(gè)氨基酸組成。研究表明TRAIL是典型
[Abstract]:Angiogenesis is an important physiological and pathological process of angiogenesis from existing blood vessels. It may occur in embryo formation and endometrial periodic changes. Wound healing and tumor growth. Neovascularization is a complex process regulated by a series of positive and negative growth factors. It can cause abnormal angiogenesis, leading to tumor growth and metastasis, myocardial infarction and diabetes. Just like normal cells, the metabolism and nutrition of tumor cells require oxygen and nutrients from the blood. Remove metabolites. Without these sufficient nutrients, a tumor can only grow to the size of 2 mm. Angiogenesis provides only the nutrients necessary for the growth of the tumor. It is also a necessary condition for tumor metastasis, when tumor cells enter the blood circulation to infiltrate and metastasize to other tissues and organs, if angiogenesis is inhibited. Apoptosis or necrosis will occur in tumor cells, which provides a new idea for anti-tumor therapy. At present, there are many anti-angiogenic drugs used in anti-tumor therapy. Vasostatin is a recently discovered angiogenesis inhibitor which was initially purified from the supernatant of B cell line VDS-O transformed by EB virus. Vasostatin, a 1-180 amino acid domain of calreticulin (calreticulin), can effectively and specifically inhibit the proliferation of endothelial cells. Vasostatin was injected into thymus-free mice by preventing neovascularization, which in turn inhibited tumor growth. Vasostatin can significantly inhibit the growth of Burkitt lymphoma and human colon cancer. Vasostatin inhibits the proliferation, migration and angiogenesis of vascular endothelial cells. In order to inhibit tumor growth. Current studies show that Vasostatin has obvious anti-tumor effect, low toxicity and other characteristics. However, it is not known how the Vasostatin fragment acts on cells, and recent studies have shown that it may be related to the cell surface factor Laminin. In 1995, a gene encoding antitumor protein was screened from human expression tag library expressed sequence tagESTs. The protein encoded by the gene is called tumor necrosis factor-related apoptosis-inducing ligand (TNF- related apoptosis-inducing ligand). Tumor necrosis factor-related apoptosis-inducing ligand. Trail, also known as apoptotin-2 ligand (Apo-2L). TNFs is a member of the tumor necrosis factor TNFs family, which initiates the inherent apoptosis process of the cells. It can effectively induce apoptosis of tumor and transformed cells, but has no effect on normal cells. The coding sequence of human TRAIL gene has 843 nucleotides. The protein TRAIL is composed of 281 amino acids. Studies show that TRAIL is a typical protein.
【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2005
【分類號(hào)】：R346

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