BACKGROUND: The c-erbB-2 oncogene encodes a transmembrane tyrosine kinase receptor and its abnormal expression may be related to the prognosis of gastric cancer. Gastric cancer is relatively resistant to various drugs, including cisplatin. Cisplatin is widely used in cancer chemotherapy, but the mechanisms of drug resistance are not yet known. METHODS: We used the human gastric cancer cell lines MKN-7 and KATO-III, which express the c-erbB-2 oncogene, as a model for relative resistance to cisplatin. We investigated whether inhibition with antisense oligonucleotides against c-erbB-2 increased the sensitivity of MKN-7 and KATO-III cells to cisplatin. RESULTS: Antisense oligonucleotides for c-erbB-2 inhibited the expression of c-erbB-2 mRNA and protein and increased sensitivity to cisplatin, but not to other drugs, in MKN-7 and KATO-III cells. Cell growth was also inhibited by c-erbB-2 antisense oligonucleotides but not sense oligonucleotides. CONCLUSION: These findings indicate that c-erbB-2 expression in gastric cancer is one of the factors related to cisplatin sensitivity, and that anti-c-erbB-2 antisense oligonucleotides induced increased sensitivity to cisplatin.

Antineoplastic Agents↗

PubMedDate not supplied

The significance of measuring plasma leptin in acute myocardial infarction.

We measured leptin concentrations in patients with acute myocardial infarction (AMI, n = 21) and in 15 age-matched controls, and compared leptin concentrations with levels of other myocardial enzymes and indicators of AMI. Blood was sampled immediately after hospital admission and at 1 h, 2 h, 3 h, 6 h and 9 h, then every 12 h until 5 days post-admission. Patients were stratified into three groups according to peak leptin concentrations: hypoleptinaemia (< 3 ng/ml); normoleptinaemia (> or = 3 - < 15 ng/ml) and hyperleptinaemia (> or = 15 ng/ml). Hypoleptinaemic AMI patients had significantly increased concentrations of plasma lactate dehydrogenase compared with normoleptinaemic patients. No significant differences in other serum markers were noted between hyperleptinaemic and normoleptinaemic AMI patients. A significant negative correlation was found between the peak concentrations of leptin and interleukin 6. Leptin may play a role in the regulation of the development of cardiac damage in patients with AMI.

Aged↗

PubMedDate not supplied

Use of c-myb antisense oligonucleotides to increase the sensitivity of human colon cancer cells to cisplatin.

Human colon cancer SW480DDP and SW620DDP cells resistant to cisplatin exhibited stronger c-myb gene expression than the parent SW480 and SW620 cells. However, cell growth rates in the cisplatin-resistant cell lines remained similar to those of the parent cells. Antisense oligonucleotides to c-myb inhibited c-myb expression and induced increased sensitivity to cisplatin in SW480DDP and SW620DDP cells, but this did not occur with the control sense oligonucleotides. In contrast, the parent cell lines were not affected by antisense oligonucleotides to c-myb. These results indicate that the c-myb gene in human colon cancer is one of the factors related to cisplatin resistance, and support the need to develop anti-cancer therapeutics based on oncogene-targeted antisense oligonucleotide technology.

Adenocarcinoma↗