Infrequent Mutations of the hOGG1 Gene, That Is Involved in the Excision of 8-Hydroxyguanine in Damaged DNA, in Human Gastric Cancer

DNA glycosylase, encoded by the hOGG1 gene, repairs 8-hydroxyguanine (oh⁸Gua), which is an oxidatively damaged mutagenic base. To clarify whether the DNA repair activity of hOGG1 protein is involved in gastric carcinogenesis, we examined 9 gastric cancer cell lines and 35 primary gastric cancers for mutations and genetic polymorphisms of the hOGG1 gene by polymerase chain reaction-single strand conformation polymorphism analysis. A G-to-A transition was detected in a gastric cancer cell line, MKN1. This nucleotide change caused the conversion of the amino acid from Arg to His at codon 154, which is located in a domain highly conserved among human, mouse, and yeast OGG1 proteins. No mutation was detected in primary gastric cancers. We compared the distribution of the polymorphic alleles associated with enzymatic activity (hOGG1-Ser³²⁶ vs. hOGG1-Cys³²⁶) between 35 gastric cancer patients and 42 healthy individuals. Although the frequency of the Cys³²⁶ allele, associated with low enzymatic activity, in gastric cancer patients was a little higher than that in healthy individuals, the difference did not reach statistical significance. These results suggest that low hOGG1 activity due to mutations and genetic polymorphisms is involved in the development of only a small subset of gastric cancers.     

Gastric adenosquamous carcinoma producing granulocyte-colony stimulating factor

We report a case of adenosquamous carcinoma of the stomach that produced granulocyte-colony stimulating factor (G-CSF). The patient, who had an admission diagnosis of advanced gastric cancer, had marked leukocytosis without evidence of infection. After leukemia and metastatic leukemoid reaction were excluded by bone marrow examination, a G-CSF-producing cancer was suspected as the cause of the abnormally elevated serum G-CSF level. The resected stomach tumor was histologically diagnosed as adenosquamous carcinoma; positive expression of G-CSF by tumor cells was shown with immunohistochemical detection, which confirmed the preoperative diagnosis. Recurrent disease in the liver and lymph nodes, accompanied by leukocytosis and re-elevation of serum G-CSF, developed just 3 months after the curative gastrectomy and adjuvant chemotherapy. All of the recurrent disease was resected, restoring normal levels of serum G-CSF. The patient survived for almost 2 years after the initial surgery with extensive chemotherapy, including weekly treatment with paclitaxel, before finally succumbing to liver failure secondary to extensive liver metastasis.     

Timing mechanism and effective activation energy concerned with aging and lifespan in the long-lived and thermosensory mutants of Caenorhabditis elegans

The lifespans of many poikilothermic animals, including the nematode Caenorhabditis elegans, depend significantly on environmental temperature. Using long-living, thermosensory mutants of C. elegans, we tested whether the temperature dependency of the mean lifespan is compatible with the Arrhenius equation, which typically represents one of the chemical reaction rate theories. The temperature dependency of C. elegans was the Arrhenius type or normal, but daf-2(e1370) mutants were quite different from the others. However, taking into account the effect of the thermal denaturation of DAF-2 with the temperature, we showed that our analyzed results are compatible with previous ones. We investigated the timing mechanism of one parameter (the onset of biodemographic aging (t₀)) in the lifespan equation by applying the RNAi feeding method to daf-2 mutants in order to suppress daf-16 activity at different times during the life cycle. In summary, we further deepened the biological role of two elements, t₀ and z (the inverse of the aging rate), in the lifespan equation and mean lifespan formulated by our diffusion model z² = 4Dt₀, where z is composed of t₀ and D (the diffusion constant).     

Pemphigus with thymoma improved by thymectomy: report of a case

A 53-year-old female with pemphigus vulgaris received treatment with prednisolone for 3 years. On chest computed tomography performed at follow-up, an anterior–mediastinal tumor (4 cm × 3 cm) was detected and diagnosed as a thymoma. Although amyosthenia was absent, the patient’s anti-acetylcholine-receptor antibody level was high, and she was positive for anti-desmoglein 3 antibodies. She underwent extended thymectomy in the same year, following which both the anti-acetylcholine receptor antibody and the anti-desmoglein 3 antibody levels were normalized. The patient’s skin symptoms improved, and the steroid dose was gradually lowered and finally discontinued 4 years postoperatively. Extended thymectomy may be an effective therapy for treating patients with pemphigus.