Gabit Alipov

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.

Overexpression of Ets‐1 proto‐oncogene in latent and clinical prostatic carcinomas

Aims : The high incidence of clinically diagnosed prostatic cancer is exceeded by the frequency of tumours detected at autopsy. The Ets‐1 proto‐oncogene is expressed by a variety of malignant and normal tissues. Therefore, in this study, expression of Ets‐1 protein was investigated in ‘latent’ prostatic cancer detected at autopsy, compared with benign prostatic hyperplasia, normal prostatic tissues and clinical prostatic cancer.

Expression of parathyroid hormone-related peptide (PTHrP) in gastric tumours.

Parathyroid hormone‐related peptide (PTHrP) is produced by various neoplasms. It has been suggested that it acts as a cytokine for cell proliferation and tumour progression. The purpose of this study was to evaluate PTHrP expression in gastric cancers by immunohistochemistry. PTHrP was expressed in 71 of 92 (77·2 per cent) gastric adenocarcinomas without humoral hypercalcaemia. In contrast, one case (5 per cent) out of 20 adenomas and none of the background non‐neoplastic epithelium showed PTHrP immunoreactivity. In carcinomas, PTHrP immunoreactivity was higher in moderately differentiated adenocarcinomas (21/22; 95·5 per cent) and poorly differentiated adenocarcinomas (34/34; 100 per cent) than in well‐differentiated adenocarcinomas (10/23; 43 per cent). Furthermore, PTHrP expression was more intense in the deeply invasive portions than in the mucosal carcinomas. High percentages of metastatic tumour cells in regional lymph nodes were immunopositive. PTHrP mRNA expression was confirmed by in situ hybridization in gastric adenocarcinomas. Reverse transcription‐polymerase chain reaction (RT‐PCR) studies of normal gastric mucosa and four human gastric cancer cell lines detected PTHrP transcription in NUGC‐1 (poorly differentiated) and NUGC‐3 (poorly differentiated) but not in normal gastric mucosa, MKN‐1 (well differentiated), and KATO‐III (signet ring cell). These findings suggest that overexpression of PTHrP may be involved in the malignant transformation and progression of gastric carcinomas.

Gastric cancer associated with overexpression of parathyroid hormone-related peptide (PTHrP) and PTH/PTHrP receptor in relation to tumor progression

Parathyroid hormone-related peptide (PTHrP) is involved in cell proliferation in both neoplastic and non-neoplastic tissues. We describe an autopsy case of gastric cancer in a patient who showed serum hypercalcemia and overexpression of PTHrP and PTH/PTHrP receptor in the metastatic tumor cells. The primary gastric tumor was poorly differentiated adenocarcinoma, and multiple metastases were present in the bone, multiple visceral organs, peritoneum, and lymph nodes. PTHrP and its mRNA were detected only in the metastatic tumor cells, but not in primary gastric tumor. PTH/PTHrP receptor was also demonstrated immunohistologically in metastatic tumor cells. This case suggests that the expression of PTHrP is related to tumor progression and the poor prognosis in tumors associated with humoral hypercalcemia.

Transient activation of c-Jun NH2-terminal kinase by growth factors influences survival but not apoptosis of human thyrocytes.

Activation of c-Jun NH2-terminal kinase (JNK), a member of the mitogen-activated protein kinase (MAPK) family, is involved in apoptosis or cell proliferation. We have previously demonstrated that ionizing radiation or thyroid-stimulating hormone activated JNK without linking to thyroid cell apoptosis. To clarify the involvement of JNK activation in thyroid cell survival, we investigated the effects of various growth factors on induction of JNK activation in cultured human thyroid cells. JNK activation was observed at 30 minutes after fetal bovine serum (FBS) stimulation and returned to basal level at 240 minutes. Epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta) and hepatocyte growth factor (HGF) also induced JNK activation, but did not trigger apoptotic cell death. Furthermore, we observed high basal activation of JNK in four of five human thyroid cancer cell lines. Overexpression of c-Met, an HGF receptor, was observed in two of the four cell lines with high basal JNK activity. Our results suggest that JNK activation does not induce apoptosis but is associated with survival or transformation of human thyroid cells.

Ret proto-oncogene rearrangement in thyroid cancer around Semipalatinsk nuclear testing site

About 50 years ago, on August 29, 1949, the first nuclear device was exploded at the Semipalatinsk nuclear testing site located in the northern part of the Republic of Kazakhstan in the former USSR. Here we describe the first evidence of ret proto-oncogene rearrangement of thyroid cancer tissues around the site.

EXPRESSION OF PARATHYROID HORMONE (PTH)‐RELATED PEPTIDE (PTHrP) AND PTH/PTHrP RECEPTOR IN GIANT CELL TUMOUR OF TENDON SHEATH

The giant cell tumour of tendon sheath (GCTTS) is mainly composed of mononucleated stromal cells (SC) and multinucleated giant cells (GC), so‐called osteoclast‐like GC. It is thought that GC are derived from SC, but their precise relationship is not fully understood. Parathyroid hormone (PTH)‐related peptide (PTHrP) is now considered to be a cytokine for cell differentiation, which may stimulate osteoclast‐like cell formation in haematopoietic cells. Five cases of GCTTS were evaluated immunohistochemically, using a variety of antibodies against PTHrP, PTH/PTHrP receptor, KP‐1 as a histiocytic phenotypic antigen, fibronectin as a fibroblastic phenotypic antigen, and proliferating cell nuclear antigen (PCNA). In situ hybridization and immunohistochemistry revealed that in all cases both SC and GC expressed PTHrP. PTH/PTHrP receptor was observed only in histiocytic SC and GC, but not in fibroblastic SC. Almost all GC showed histiocytic features. PCNA immunoreactivity was detected only in the nuclei of SC, and not in GC. Moreover, SC with PTH/PTHrP receptor immunoreactivity were negative for PCNA. These results suggest that GC are derived from histiocytic SC expressing PTH/PTHrP receptor and losing proliferative activity in the process of transition from mononuclear to multinucleated. PTHrP produced by SC and GC may be involved in the formation of osteoclast‐like cells in GCTTS by acting in an autocrine/paracrine fashion.

Morphological investigation of thyroid and parathyroid glands of the population living around the Semipalatinsk Nuclear Test Site

Abstract The results of a long-term investigation of morphological conditions of endocrine glands in the Semipalatinsk region, a site of nearly 500 nuclear weapon tests from 1949 to 1989, are presented in relation to its ecological and medico-social-demographical situations. A significant relationship was demonstrated between tumor development in the thyroid gland and the mortality rate for inhabitants of the Semipalatinsk region, many of whom had received accumulated radiation doses exceeding 50 cSv.