大鼠放射性皮肤溃疡组织中c-Fos、Rb蛋白表达研究

为研究大鼠放射性溃疡组织中ｃ－Ｆｏｓ、Ｒｂ表达。采用１４０只Ｗｉｓｔａｒ大鼠进行局部照射（γ射线）制备放射性皮肤溃疡动物模型,观察病变１年,然后采用ｃ－Ｆｏｓ、Ｒｂ多克隆抗体及免疫组化方法检测溃疡组织中ｃ－Ｆｏｓ、Ｒｂ的表达情况。结果表明：ｃ－Ｆｏｓ、Ｒｂ的表达阳性率分别为４５．８％（３３／７２）、６３．９％（４６／７２）,两者阳性部位主要见于增生肥大的鳞状上皮细胞胞核、增生的间质成纤维细胞胞质及     

抗胃癌基因产物的IgY抗体的研究

将人胃癌细胞系MGC803细胞中,由癌基因编码的P_(110)蛋白提纯作为抗原免疫产卵母鸡,从该鸡所产卵的卵黄中提出一种对人胃癌具有特异性的IgY抗体。该抗体与人胃癌组织的免疫组化反应率为80％,明显高于其他癌组织及正常胃组织。将该抗体与蓖麻毒素A链交连成IgY-Riein A,分别攻击培养中的人胃癌及其他癌细胞,结果IgY-RicinA对人胃癌细胞的TCID_(50)为0.01mg/ml,明显低于其他癌细胞。表明所制备的IgY是一种较好的抗肿瘤多克隆抗体。     

Effect of Nitro Orientation on Ras -Protooncogene Mutation in Liver Tumors from 7-Nitrodibenz[ a,h ]anthracene-Treated Mice

Dibenz[ a,h ]anthracene (DB[ a,h ]A) and 7-nitrodibenz[ a,h ]anthracene (7-NDB[ a,h ]A) induced liver tumors when administered to neonatal B6C3F 1 mice. For protooncogene analysis, RNA was isolated from each of the liver tumors from treated mice and reverse-transcribed into cDNA. Portions of the K- and H- ras protein coding sequences were then amplified and analyzed for DNA sequence alterations. DB[ a,h ]A-induced liver tumors had a 100% (23/23) frequency of ras -protooncogene mutation, with 83% (19/23) occurring at the first base of K- ras codon 13 and resulting in G GC M C GC transversion; the remaining 17% (4/23) of the mutations were located at the second base of H- ras codon 61. In contrast, only four of nine (44%) of 7-NDB[ a,h ]A-induced liver tumors had ras -protooncogene mutations, with two each at K- ras codon 13 and H- ras codon 61. Combined with previous observations, the results indicate that the nitro substituent perpendicular to the aromatic moiety alters the chemical-induced protooncogene activation frequency and mutational pattern in liver tumors of B6C3F 1 mice.     

辐射诱发白血病初期过程的细胞和分子遗传学研究

以小鼠为实验模型，通过对经Ｘ射线照射后１２￣３２ｄ的小鼠染色体Ｇ带核型分析，发现与白血病发生有密切关系的特异性染色体畸变是１５ 染色体三体和１２号染色体Ｅ－Ｆ区的易位。在细胞遗传学分析基础上，用ＰＣＲ－ＳＳＣＰ方法检测了与特异性染色体畸变的受照射小鼠ｃ－ｍｙｃ原癌基因和ｐ５３抑癌基因的结构变化。选用ｃ－ｍｙｃ基因ＰＣＲ－ＳＳＣＰ试剂盒对正常和受照射小鼠进行了分析，实验结果未发现特异性改变。用ＰＣＲ     

低剂量电离辐射对小鼠胸腺细胞Fos蛋白表达的影响

应用免疫组织化学、图像分析定量法及流式细胞术分别观察７５ｍＧｙ全身照射后不同时间小鼠胸腺细胞Ｆｏｓ蛋白的变化。结果发现,照射后胸腺细胞Ｆｏｓ蛋白的表达明显增高,２４ｈ达峰值,以后逐渐恢复至假照水平。与以往的低剂量电离辐射全身照射后小鼠胸腺细胞ｃ－ｆｏｓｍＲＮＡ转录水平的变化在时程上一致。提示,低剂量电离辐射可使免疫细胞的活性增强。     

癌基因及其检测方法研究进展

肿瘤的发生是与肿瘤相关基因的行为有很大的关系。本文综述了癌基因和抑癌基因的定义,原癌基因的最新发现,抑癌基因的研究进展,以及现阶段对肿瘤相关基因检测方法。其中总结了关于甲基化检测作为肿瘤标志物的研究情况。     

Twenty years of transgenic animals: Are some inventions SO important as to NOT be entitled to full patent protection?

Transgenic animals have been known for 30 years but the first transgenic mammal patent dates from 1988. This first patent, for the Oncomouse which has been created to be susceptible to developing tumors, has generated large revenues for its licensee, DuPont. Equivalent patents were only granted in Canada and Europe after litigation and amendment of the patent. DuPont has strictly enforced its patent rights but this has led to debate over whether it is impeding research.     

Targeting the “undruggable” cancer driver genes: <i>Ras</i>, <i>myc</i>, and <i>tp53</i>

The term “undruggable” is to describe molecules that are not targetable or at least hard to target pharmacologically. Unfortunately, some targets with potent oncogenic activity fall into this category, and currently little is known about how to solve this problem, which largely hampered drug research on human cancers. Ras, as one of the most common oncogenes, was previously considered “undruggable”, but in recent years, a few small molecules like Sotorasib (AMG-510) have emerged and proved their targeted anti-cancer effects. Further, myc, as one of the most studied oncogenes, and tp53, being the most common tumor suppressor genes, are both considered “undruggable”. Many attempts have been made to target these “undruggable” targets, but little progress has been made yet. This article summarizes the current progress of direct and indirect targeting approaches for ras, myc, two oncogenes, and tp53, a tumor suppressor gene. These are potential therapeutic targets but are considered “undruggable”. We conclude with some emerging research approaches like proteolysis targeting chimeras (PROTACs), cancer vaccines, and artificial intelligence (AI)-based drug discovery, which might provide new cues for cancer intervention. Therefore, this review sets out to clarify the current status of targeted anti-cancer drug research, and the insights gained from this review may be of assistance to learn from experience and find new ideas in developing new chemicals that directly target such “undruggable” molecules.