Aplydactone, a new sesquiterpenoid with an unprecedented carbon skeleton from the sea hare Aplysia dactylomela, and its cargill-like rearrangement.
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Biomedical subjects
Publications and source records attributed to S N Fedorov.
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The report deals with a molecular-genetic study of human pepsinogen A (PGA) genetic locus. EcoRI, HindIII and BamH 1 restriction endonuclease technique were employed. The investigation involving 58 patients with stomach cancer (SC) and 18 healthy donors failed to identify any significant PGA genetic restructuring in the blood of healthy donors. However, DNA sampled from tumor tissue showed lower expression and deletion of PGA fragments as compared with those of unaltered gastric mucosa in the same patients. Such changes were identified in 27 SC patients.
An abnormally long shorter shoulder of chromosome 21 was identified in 3 out of 4 members of a family at high risk for gastric cancer. We attempted to clone the amplified fragments of DNA of one of the family members who had the same chromosomal marker. This was done after the amplified sequences were enriched by re-association in phenolic emulsion, and 52 clones were obtained. All inserts were separated and each was hybridized on filters containing Hind III DNA of patient O.L. and that of a healthy donor. Hybridization with the genome DNAs of patient O.L. and the donor failed to go through in 9 inserts. Hybridization with all genomic DNAs went through in 34 inserts. Hybrids with one or several Hind III fragments of DNAs of O.L. and the donor were formed in 9 inserts. The size of fragments with varying molecular weight in inserts 6, 9, 11, 30, 39, 43 and 44 identified in the DNA of patient O.L. was 3-10 times that in the DNA of the donor. The differences in the molecular weight and size of the detected bends seem to indicate that we succeeded in cloning at least several different amplified fragments of the genome of the patient.
The survey dedicated to the 70th anniversary of the Prof. N. N. Petrov Research Institute of Oncology, St. Petersburg, gives a basic idea of molecular pathogenesis of tumor in humans, particular emphasis being placed on the clinical and applied aspects of molecular oncology. The survey is intended for a wide audience including doctors, professors and undergraduate students majoring in medicine and biology.
The action of (20R)-cholesta-5,25-diene-3 alpha, 4 beta, 21-triol 3,21-disulfate and its 25,26-dihydroanalog from the Pacific brittle star Ophiopholis aculeata was studied on mouse cancer cells, lymphocytes and erythrocytes. The cytotoxic and hemolytic effects were not observed for both steroids at the wide range of concentrations. Both steroids inhibited 3H-Thymidine (but not 3H-Uridine) incorporation into Ehrlich carcinoma cells. It was the first time shown that some sulfated marine polyhydroxylated steroids stimulate the influx of Ca2+ into cells. (20R)-Cholesta-5,25-diene-3 alpha, 4 beta, 21-triol 3,21-disulfate was two times more active than its 25,26-dihydro-analog.
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By the restriction analysis method we established that methylation of the 5'-end cytosine in 5'-m5CC-3' duplexes had individual specific features. This genetic peculiarity did not change even in DNA from human stomach carcinomas.
A method of the restriction analysis by Msp I enzyme has been used to analyze the 12th codon of Ha-ras-1 protooncogene in 10 human carcinomas and in the stomach mucosa adjacent to them their 5 metastases into the regional lymph nodes and in 2 ulcers. No point mutation was found.
The study is concerned with the expression of src, sis, fos, myc, Ha-ras, Ki-ras, N-ras, mos, and abl proto-oncogenes in the brain, heart, liver, kidneys, lung, stomach, cross-striated muscle cells and in leukocytes. Some of these genes are shown to be actively transcribed in adult intact rats. Their expression depends on the tissue specificity. Most of the investigated proto-oncogenes are expressed in the liver and kidney weakly, and in the brain and heart--more strongly. A correlation is observed between fos and Ha-ras proto-oncogenes' expression in organs of intact rats.
Ha-ras restriction fragments' length polymorphism (RFLP) in white blood cells and stomach tissues from patients with carcinoma and ulcer of the stomach was examined. Genomic DNAs were digested with Xho I, Pvu II, Pst I, Msp I, Bcn I, Mva I, Bsp RI. No Ha-ras-1 polymorphic variants specifically associated with the cancer disease were detected. RFLP of the 3'-noncoding sequence of c-Ha-ras-1 gene had got features of the definite human population. The cells forming the tissue were examined and individual peculiarity of the methylated residues disposition seemed to influence RFLP of the 5'-noncoding sequence of c-Ha-ras-1.
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The expression of c-Ha-ras-1, Ki-ras, N-ras, abl, src, fos and myc protooncogenes was analyzed in 13 cases of human gastric carcinomas. The transcriptional activity of both fos and myc protooncogenes was found to be disturbed in 47% and 42% of cases, respectively. An overexpression of fos protooncogenes as well as an appearance in some cases of atypical foc-mRNA transcripts were established. Only an elevation of the number of myc mRNA copies was observed. In one patient with gastric carcinoma a c-Ha-ras-1 overexpression was detected due to its amplification both in tumour tissues and in regional metastasis. The expression of other protooncogenes under investigation was similar to those found in normal gastric mucose. In addition, no differences in expression in protooncogenes mentioned above plus sis protooncogene were established in unchanged, premalignant and malignant stomach tissues in the course of N-methyl-N'-nitro-N-nitrosoguanidin-induced carcinogenesis.
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Both c-myc and c-Ha-ras 1 oncogenes amplification and enhanced expression were revealed in some human mammary and thyroid carcinomas by the molecular genetic analysis. Amplification proves to be a second possible molecular mechanism of the ras family protooncogene activation besides a point mutation. The coexistence of c-myc and c-Ha-ras 1 in some human primary carcinomas suggests a multistep process of carcinogenesis.
The structural proteins and the oncogene product of the avian sarcoma virus (ASV) D6 were analyzed by the radioimmunoprecipitation. ADV D6 was obtained from the chemically induced tumour. ASV D6 contains all the structural proteins found in RSV, but some of them (p19, gp 85) differ from those of RSV. The product of ASV D6 oncogene is pp65src. The protein kinase activity of this src protein is identical to that of wt pp60src. The nature of some other proteins, which can be phosphorylated in this reaction, is discussed.
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