To determine whether phenotypic field changes occur in tissues adjacent to carcinoma, we assayed, by immunohistochemistry, the expression of HER-2, p53, Fas, and FasL in 72 breast cancers (BC) and multiple autologous peritumoral tissues (PTTs) sampled up to 5 cm distance and in 44 benign breast tumors (BBTs). About 5% and 3% of the PTTs and 4.5% and 6.8% of BBTs showed alterations in HER2 and p53 expression, respectively. Of interest, gene amplification was observed in 50% of HER2 positive PTTs, but not in any HER2 positive BBTs. Fas, highly expressed in BBTs and downregulated in BC, maintained its expression in PTTs, whereas FasL, usually negative in BBTs, was upregulated in BC as well as in the PTTs closest (1 cm) to the invasive lesion. Our data suggest that FasL could be a potential novel biomarker of transformation, which may identify, along with HER2 and p53, precursor lesions in a genetically altered breast tissue.
Asian ginseng (Panax ginseng C. A. Meyer) has been used in Chinese medicine for two thousand years. The root of ginseng contains several saponins (ginsenosides) which are biologically active compounds. Individual ginsenosides suppress tumor cell growth, induce cell differentiation, regulate apoptosis and inhibit metastasis formation. The aim of this study was to evaluate its chemo-preventive effects in an animal test model, through its regulatory effects on apoptosis and the cell cycle.The expression of genes (Bcl-2, Bcl-x and Cyclin D1) which affect apoptosis were examined, in different organs of animals which had consumed a ginseng-containing diet in the presence of a known carcinogen (DMBA). The pattern of gene expression was determined by Q-RT-PCR. The increase of antiapoptotic gene expression after carcinogenic exposure was suppressed by consumption of ginseng which promoted apoptosis.The population is exposed to numerous physical and chemical insults in the modern environment and these include compounds which are known carcinogens. Research has shown that it is possible to interfere with the multi-step process of carcinogenesis through the use of compounds with chemo-preventive effects, such as the inhibition of the activation of antiapoptotic genes.These results support the efficacy of ginseng-containing diets and dietary supplements in the prevention of cancerous diseases.
The male proband reported here was born with appropriate anthropometric parameters at term as the second child of healthy nonconsanguineous parents. His only clinical symptom was bilateral congenital cataracts with strabismus at birth, and both lenses were removed surgically at the age of 8 months. The perinatal and infantile period thereafter was clinically uneventful and his psychomotor development appeared almost normal. At the age of 6 years he was hospitalized for slight muscle weakness, minor ptosis, nystagmus and decreased physical activity. Soon after, his general condition worsened, gait ataxia presented, dysphagia and difficulty of speech followed by rapidly progressive generalized ataxia, and myopathy developed. Typical progressive gray matter degeneration with focal necrosis in the basal ganglia characteristic of the Leigh type of neuropathology could be detected by cranial MRI, the muscle histology showed ragged-red fibers. At the age of 7.5 years, unexpected left side hemiparesis with speech disability resembling that seen in MELAS syndrome developed, from which he recovered within 1.5 days. The mtDNA of the patient showed single 6.7 kb large-scale deletion harboring between 7817 and 14 536 bp. This case represents the first report of a verified mtDNA mutation associated with congenital cataracts as the first clinical sign of a later developing progressive neuromuscular disease presented with a combination of Leigh neuropathology, ragged-red fiber histopathology and stroke-like attack.
Hungarians are unique among the other European populations because according to history, the ancient Magyars had come from the eastern side of the Ural Mountains and settled down in the Carpathian basin in the 9th century AD. Since variations in the human mitochondrial genome (mtDNA) are routinely used to infer the histories of different populations, we examined the distribution of restriction fragment length polymorphism (RFLP) sites of the mtDNA in apparently healthy, unrelated Hungarian subjects in order to collect data on the genetic origin of the Hungarian population. Among the 55 samples analyzed, the large majority belonged to haplogroups common in other European populations, however, three samples fulfilled the requirements of haplogroup M. Since haplogroup M is classified as a haplogroup characteristic mainly for Asian populations, the presence of haplogroup M found in approximately 5% of the total suggests that an Asian matrilineal ancestry, even if in a small incidence, can be detected among modern Hungarians.
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