新西兰护理代写 胰腺癌给药系统

2020-05-25 02:21

本项目旨在结合多种策略设计一种有效的胰腺癌给药系统。胰腺癌发生的遗传和积累交替(1、2)。众所周知,最常见的基因突变异常在胰腺腺癌是kras突变(3)。在70 - 90%的情况下k - ras基因点突变发生在基因,绝大多数发生在致癌基因的密码子12 (4、5)。因此,人们正在努力确定Ras在正常细胞和病变细胞中的功能,并将Ras作为癌症治疗的靶点。KRAS作为一个GTPase被GTP激活,被GDP停用。活化的Kras结合并激活RAF家族激酶、BRAF、ARAF和RAF1(6)。活化的RAFs负责磷酸化和激活ERK1和ERK2激酶。随后ERK磷酸化了细胞核和细胞质转录因子,如ELK1和c-JUN,导致细胞增殖。因此,导致K-ras基因活化的突变导致细胞不受控制的生长,最终导致癌症的发生和扩散(7)。SiRNA将作为一种治疗药物来抑制KRAS的表达。小干扰rna介导的表达减少这种突变喀斯特的胰腺细胞可以减少细胞增殖从而减少肿瘤的生长(8、9)。因此,确保核将优先目标癌症组织而不是正常组织,癌症特异性抗体可用于定位的目的。癌症的特征之一是细胞表面的某些蛋白受体过度表达。胰腺癌细胞具有高表达的表皮生长因子受体(EGFR),可作为抗胰腺癌细胞株的药物传递靶点。因此,靶向部分(抗egfr抗体)将附着在脂质体表面,以靶向特定的癌细胞递送。
新西兰护理代写 胰腺癌给药系统
This project aims to design an effective drug delivery system for pancreatic cancer combining multiple strategies. Pancreatic cancer arises because of the genetic and accumulated alternations (1, 2). It is well known that the most common type of genetic mutation abnormality in pancreatic adenocarcinomas is the kras mutation (3). In 70-90% of the cases point mutation occur in k-ras gene, the majority occurring at codon 12 of oncogene (4,5). Therefore, efforts have been made to define the function of Ras in normal and diseased cells and to target ras for cancer therapy.KRAS being a GTPase is activated by GTP and deactivated by GDP. The activated Kras binds and thus activates the RAF family kinases, BRAF, ARAF and RAF1(6). Activated RAFs is responsible for phosphorylating and activating ERK1 and ERK2 kinases. Later ERK phosphorylates nuclear and cytoplasmic transcription factors like ELK1 and c-JUN which leads to cell proliferation. Therefore, the mutation which causes the activation of K-ras leads to uncontrolled cell growth which eventually leads to cancer development and spreading (7). SiRNA will be used as a therapeutic drug to suppress KRAS expression. This siRNA mediated reduction in the expression of mutated KRAS in the pancreatic cells can reduce cell proliferation thus reducing the tumor growth (8, 9). Thus, to make sure that siRNA will preferentially target the cancer tissues rather than the normal tissues, cancer-specific antibody can be used for targeting purpose. One of the trait seen in cancer is that there is an overexpression of certain protein receptors on the cell surface. Pancreatic cancer cells have high expression of Epidermal Growth Factor Receptor (EGFR), which can be used as a drug delivery target against pancreatic cancer cell lines. Hence, the targeting moiety (anti-EGFR antibody) will be attached on the surface of liposomes to target specific cancer cell delivery.
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