The Influence of Alpha-fetoprotein on Natural Suppressor Cell Activity and Ehrlich Carcinoma Growth.

The influence of alpha-fetoprotein (AFP) on the bone marrow (BM) natural suppressor (NS) cells of intact Ehrlich carcinoma -bearing CBA mice was studied. Bone marrow NS cells were fractionated into three fractions by isopycnic centrifugation on percoll gradients: NS1 (rho=1.080 g/ml), NS2 (rho=1.090 g/ml) and NS3 (1.100>rho>1.090 g/ml). These fractions were highly different in their sensitivity to known NS cell inductors (interleukin (IL)-2, IL-3 or histamine). None of the NS fractions isolated from the intact mice spontaneously produced antiproliferative activity, however, they showed a high level of NS (antiproliferative and natural killer cell inhibitory) activity under the influence of AFP. A single injection of AFP to intact mice led to an increase of spontaneous NS activity and the inhibition of natural killer cell activity. NS activity, especially NS2, was increased in when tumor cells were subcutaneously inoculated three days after AFP injection. In the AFP-treated mice, the tumor mass at 14 days was 60% larger than that in the untreated mice. Our data confirmed that AFP is a tumor marker that can inhibit cancer immunity and plays a role in cancer pathogenesis.

Expression of apoptotic epithelial cells in biopsy specimens of patients with colitis.

We postulated that nuclear dust within the lamina propria beneath the basement membrane of the epithelium in colonic mucosal biopsies of patients with colitis is a form of apoptotic epithelial cells and that its expression correlates with clinical severity. Our aim was to determine the origin of nuclear dust and to explore the correlation between nuclear dust expression and clinicopathologic parameters of colitis. we examined 228 specimens with colitis and 18 normal specimens. The expression rates of nuclear dust were 11.1% (2/18) and 83.8% (191/228) in normal colonic mucosa and colitis, respectively. Cells showing double positive staining with cytokeratin and TdT-mediated uUTP-biotin nick-end labeling technique were apoptotic cells derived from epithelial cells. Nuclear dust expression correlated significantly with inflammation, eosinophil infiltration, edema, and congestion. Our results suggest that interventions directed toward the apoptotic process may be beneficial in the treatment of colitis.

Expression of Ets-1 proto-oncoprotein in gastrointestinal stromal tumors, leiomyomas and schwannomas.

AIM: Gastrointestinal stromal tumors (GISTs) are rare. GISTs differ from other mesenchymal tumors of the gastrointestinal tract (e.g. leiomyomas and schwannomas). The purpose of this study was to investigate the role of Ets-1 in the growth and differentiation of GISTs. METHODS: Twenty-eight GISTs, nine leiomyomas and six schwannomas were examined by immunohistochemical staining method for Ets-1 in this study. Specimens were selected from surgical pathology archival tissues at Nagasaki University Hospital. RESULTS: Ets-1 protein was expressed in the cytoplasm of cells in all of these tumors. Immunohistochemical staining revealed that 27 GISTs (96.4%), six leiomyomas (66.7%), and five schwannomas (83.3%) were positive for Ets-1. Ets-1 expression was statistically different between GISTs and leiomyomas (P<0.005). However, there was no correlation between Ets-1 expression and clinical risk categories. CONCLUSION: Ets-1 plays an important role in the growth and differentiation of GISTs, leiomyomas and schwannomas.

A SNP in the ABCC11 gene is the determinant of human earwax type.

Human earwax consists of wet and dry types. Dry earwax is frequent in East Asians, whereas wet earwax is common in other populations. Here we show that a SNP, 538G --> A (rs17822931), in the ABCC11 gene is responsible for determination of earwax type. The AA genotype corresponds to dry earwax, and GA and GG to wet type. A 27-bp deletion in ABCC11 exon 29 was also found in a few individuals of Asian ancestry. A functional assay demonstrated that cells with allele A show a lower excretory activity for cGMP than those with allele G. The allele A frequency shows a north-south and east-west downward geographical gradient; worldwide, it is highest in Chinese and Koreans, and a common dry-type haplotype is retained among various ethnic populations. These suggest that the allele A arose in northeast Asia and thereafter spread through the world. The 538G --> A SNP is the first example of DNA polymorphism determining a visible genetic trait.

Epstein-Barr virus-associated gastric carcinoma in Kazakhstan.

AIM: To investigate the incidence of Epstein-Barr virus-associated gastric cancer (EBV-GC) in Kazakhstan and to compare it with that in Russia, Western and Asian countries in order to evaluate the significance of epidemiopathologic and ethnic factors. METHODS: In situ hybridization (ISH) of EBV-encoded small RNA-1 (EBER-1) was used to identify the presence of EBER-1 signal in 139 formalin-fixed and paraffin-embedded GC tissues from Kazakhstan. RESULTS: EBER-1 expression was observed in the nuclei of 10% of the cases of GC (14/139), but not in the surrounding normal mucosa. The incidence of the diffuse type of EBV-GC was significantly higher in Kazakhstan (14%, 13/91) than that of the intestinal type (2%, 1/48). Furthermore, the incidence was significantly higher in males (14%, 12/89) than in females (3.7%, 2/53) from all countries. The overall incidence of EBV-GC increased from 6.7% in Asian countries to 8.7% in Russia, 10.1% in Kazakhstan and 16% in Western countries. CONCLUSION: Geographical differences in the incidence of EBV-GC may reflect the epidemiologic factors and/or dietary habits independent of histological type and sex.

Loss of heterozygosity on chromosome 9q22.3 in microdissected basal cell carcinomas around the Semipalatinsk Nuclear Testing Site, Kazakhstan.

A high incidence of skin cancers has been noted around the Semipalatinsk Nuclear Testing Site (SNTS) in Kazakhstan. Recently, basal cell carcinoma (BCC) susceptibility genes, human homolog of the Drosophila pathed gene (PTCH), and the xeroderma pigmentosa group A-complementing gene (XPA), have been cloned and localized on chromosome 9q22.3. To clarify the effect of low-dose irradiation on the occurrence of BCC, we used microdissection and polymerase chain reaction to identify loss of heterozygosity (LOH) at 9q22.3 using BCC samples obtained from this region. Ten Japanese samples were analyzed as controls. LOH with at least 1 marker was identified in 5 of 14 cases from around SNTS, whereas only 1 case with 1 marker was identified among the 10 Nagasaki cases. The total number of LOH alleles from SNTS (8 of 45) was significantly higher than the number from Nagasaki (1 of 26) (P = 0.03). The higher incidence of LOH on 9q22.3 in BCC from around SNTS suggests involvement of chronic low-dose irradiation by fallout from the test site as a factor in the cancers.

No evidence of radiation risk for thyroid gland among schoolchildren around Semipalatinsk Nuclear Testing Site.

To assess thyroid status among the schoolchildren around Semipalatinsk Nuclear Testing Site (SNTS), Kazakhstan, and to evaluate the current status of iodine deficiency in this area, we performed medical screening of schoolchildren in two villages, Kaynar and Karaul villages, East Kazakhstan Region, Republic of Kazakhstan, located within 100 km of SNTS. A total of 196 schoolchildren were chosen at random. Control groups comprised 250 schoolchildren from Nagasaki, an iodine-rich area, and 100 schoolchildren from Gomel, an iodine-deficient area contaminated by the Chernobyl Nuclear Power Plant accident. Ultrasound screening of thyroid revealed three cases of benign thyroid disease (two cases of goiter and one single cyst), but no cases suspicious of malignancy. The urinary iodine (UI) concentrations of subjects in Kaynar and Karaul ranged from 21.8 to 735.8 microg/L, 4.3% of whom showed low UI concentrations (<50 microg/L), compared with 0% in the Nagasaki group and 52% in the Gomel group. The median UI concentration in Kaynar and Karaul was 153.2 microg/L, which was significantly lower than that in Nagasaki (366.3 microg/L, p<0.0001) but higher than that in Gomel (47.3 microg/L, p<0.0001). In conclusion, there was a low incidence of morphological abnormalities in the thyroid, and no evidence for severe iodine deficiency among the Kazakhstani children studied. These results suggest that there is no transgenerational risk for schoolchildren born from parents irradiated as a result of tests carried out in SNTS.