Usefulness of tumor markers in veterinary medicine

为了显示肿瘤标志物在兽医学中的有用性，我们在小动物实践中测量了患有肿瘤疾病的狗和猫的各种肿瘤标志物。在本研究的2年期间，我们调查了分为6类的肿瘤标志物的有用性：（1）血清（血浆）肿瘤标志物;（2）细胞内端粒酶和端粒酶逆转录酶;（3）P-53和MDM 2表达及p53基因突变;（4）细胞克隆性;（5）染色体畸变;（6）与多药耐药相关的P-糖蛋白（P-gp）。本研究的主要结果如下：1.我们检测了犬乳腺肿瘤的端粒长度和细胞内端粒酶活性，发现端粒酶活性可以作为一种肿瘤标志物; 2.我们检测了犬和猫自然发生的肿瘤中p53基因的序列，发现大约50%的犬肿瘤中p53基因发生突变，因此，发现p53基因突变可导致B 关于我们 e用作狗的肿瘤标记物。此外，在犬肿瘤组织中发现了MDM 2的高表达，MDM 2是一种抑制P-53蛋白的蛋白质，可能成为一种新的肿瘤标志物。3.应用外源性猫白血病病毒（FeLV）对犬肿瘤组织、骨髓和淋巴结进行了Southern印迹分析。结果表明，在肿瘤性疾病（白血病和骨髓增生异常综合征，MDS）中检测到了单克隆或寡克隆细胞群，并发现细胞克隆性可作为FeLV感染猫的一种新的肿瘤标志物。4.测定了犬和猫mdr（multidrug resistance，多药耐药）基因编码P-gp的核苷酸序列。采用逆转录聚合酶链反应（RT-PCR）和免疫组化方法检测肿瘤细胞中mdr RNA和P-gp蛋白的表达。通过联合使用抗肿瘤药物和P-gp抑制剂治疗，显示对化疗的反应得到改善。少

In order to show the usefulness of tumor markers in veterinary medicine, we measured a variety of tumor markers in dogs and cats with neoplastic diseases in small animal practice. During the 2 years for the present study, we investigated the usefulness of tumor markers classified into 6 categories : (1) serum (plasma) tumor marker, (2) intracellular telomerase and telomerase reverse transcriptase, (3) expression of P-53 and MDM2 and mutation of p53 gene, (4) cell clonarity, (5) chromosome abberation, and (6) P-glycoprotein (P-gp) associated with multidrug resistance. Major results of the present study are as follows.1.We measured the telomere length and intracellular telomerase activity in canine mammary tumors and found that telomerase activity could be used as a tumor marker.2.We examined the sequence of p53 gene in naturally occurring tumors in dogs and cats and found that p53 gene was mutated in approximately 50% of the dog tumors, therefore, found that mutation of p53 gene could b … More e used as a tumor marker in dogs. Moreover, a large number of dog tumors were shown to have an overexpression of MDM2 (a protein inhibiting P-53) which could be a candidate of new tumor marker.3.Southern blot analysis using exogenous feline leukemia virus (FeLV) was carried out in the peripheral blood samples and biopsy specimens of tumors, bone marrows and lymph modes. As a result, monoclonal or oligoclonal cell population was detected in neoplastic deseases (leukemia and myelodysplastic syndrome, MDS) and it was found that the cell clonality could be used as a new tumor marker in FeLV-infected cats.4.Nucleotide sequences of canine and feline mdr (multidrug resistance) genes that encodes P-gp were determined. Expressions of mdr RNA and P-gp protein were examined by RT-PCR and immunohistochemistry using a monoclonal antibody directed P-gp (C219), respectively, in tumor cells. By the treatment with antineoplastic drugs in conjunction with P-gp inhibitor, response to the chemotherapy was shown to be improved. Less