Biomedical subjects

G P Tryfiates

Publications and source records attributed to G P Tryfiates.

41 records · Page 3Linked to original sources

PubMedDate not supplied

Vitamin B6 and cancer: a novel pyridoxal 5-phosphate conjugate in tumor cells and blood of cancer patients.

Studies on the metabolic transformations of labeled pyridoxine showed that its utilization by tumor animals and tumor cells differs greatly from that seen in control animals. When [3,4-14C] and/or tritium labeled pyridoxine at the 6th ring carbon is administered i.p. to tumor-bearing animals and its fate is subsequently determined at different time intervals (using HPLC separation of the labeled metabolites following acid extraction from tissues), in addition to other differences, synthesis of a novel labeled product occurs which begins with the onset of tumor growth. It is either absent or present only at minimal levels in normal animals and regenerating rat liver. It is present in all tumor sources examined to date, i.e. serum of tumor rats, a spectrum of rat hepatomas, solid human tumors, tumor cells in culture and plasma of cancer patients. The novel product is a conjugate of pyridoxal 5'-phosphate with the structure Adenosine-N6-Diethylthioether-N1- Pyridoximine-5'-phosphate. This communication reports on the occurrence and distribution of the novel product in different tumor tissues and cells as well as the blood of cancer patients with active disease and in remission, and in normal volunteers. The results show significantly higher levels of this product in the blood of patients with different malignancies and in the active state. The novel vitamin B6 compound may be a good candidate as a marker for tumor presence and/or metastasis.

Adult↗

PubMedDate not supplied

Synthesis of adenosine-N6-methyl, propylthioether-N-pyridoxamine: an analog of a novel vitamin B6 tumor product.

Studies on the time-course utilization of radiolabeled pyridoxine in rats with hepatomas led to the discovery of a novel vitamin B6 product. It is found in a spectrum of tumor lines but it is absent or occurs minimally in normal tissues. Hepatomas incorporate up to 20-30% of labeled pyridoxine into the novel product. Its structure was tentatively identified as adenosine-N6-methyl, propylthioether-N-pyridoximine-5'-PO4. However, results of tests on the incorporation of labeled precursors into the novel product by 3B3 hybridoma or HL-60 cells support an N6-diethylthioether bridge linking the adenosyl and pyridoxyl moieties. The synthesis of adenosine-N6-methyl, propylthioether-N-pyridoxamine is reported in this paper. The mass spectrum of this analog is similar to that of the tumor product as seen by its fragmentation in further support of the structure of the tumor product. Whether the latter may be part of tumor RNA is questionable. RNA was isolated for 3B3 or HL-60 cells after incubation with tritiated or 14C-pyridoxine using SDS-phenol repeated extractions in the presence of RNase inhibitors. Centrifugation of cRNA on 5-20% linear sucrose density gradients showed practically all the label at the top of the gradient. RNase treatment resulted in a labeled product which coeluted with the tumor product on reverse phase paired-ion HPLC and chromatographed as dinucleotide on paper. These results suggest that the novel tumor product may occur as a short oligonucleotide.

Adenosine↗

PubMedDate not supplied

Metabolic interconversions of pyridoxine by Morris hepatoma No. 7777 cells. Synthesis of a novel metabolite.

The metabolic transformations of labeled pyridoxine by hepatoma cells were studied. Buffalo rats were fed ad libitum a commercially prepared pyridoxine sufficient diet for 20 days at which time they were inoculated intramuscularly with hepatoma 7777 cells in both hind leg muscles. After tumor development, 50 microCi [6-3H] pyridoxine. HCl or 5 microCi [4,5-14C] pyridoxine. HCl was injected intraperitoneally per rat. Groups of animals were subsequently sacrificed at defined time intervals up to 9 days. Vitamin B6 labeled tumor metabolites were acid extracted and separated on a muBondapak C18 column by ion pairing reverse phase high performance liquid chromatography. A novel vitamin metabolite contributing up to 28.5% of extractable radioactivity was found with retention time different than any of the known vitamin B6 compounds. Its pattern of synthesis in vivo from labeled pyridoxine was PN leads to PNP leads to PLP leads to PMP leads to X. Preliminary GC-mass spectral data suggested the unknown consisted of more than one species. This communication reports on the metabolism of vitamin B6 and the isolation, synthesis in vivo and possible significance of the novel metabolite to the economy of the tumor cells.

Animals↗

PubMedDate not supplied

Vitamin B6 and cancer: adenosine-N6-diethylthioether N1-pyridoximine 5'-PO4, a circulating human tumor marker.

Studies in my laboratory on the metabolism and utilization of labeled vitamin B6 by tumor-bearing animals and tumor cells in culture have shown the production and presence in the circulation of a novel pyridoxal 5'-phosphate conjugate metabolite (1-5). Using specific radiolabeling and analytical tests, its structure was tentatively identified (now confirmed) as adenosine-N6-diethylthioether-N1-pyridoximine 5'-phosphate (4-6). The novel vitamin conjugate was isolated from the plasma of patients and control subjects following extraction with perchloric acid and separation by pair-ion HPLC. This communication reports the chromatographic separation of the novel compound and its plasma levels in control subjects, cancer patients and patients with other ailments. The results show that the novel metabolite is a circulating human tumor marker with levels of up to 4x or greater seen in cancer patients compared to controls and to subjects with other ailments. The results indicate strongly that the novel circulating vitamin B6 conjugate compound can be successfully used for the detection of different malignancies in humans by evaluating its level in circulation.

Adenosine↗

PubMedDate not supplied

Adenosine-N6-diethylthioether-N1-pyridoximine 5'-phosphate. A novel marker for human cancer detection.

The Schiff base conjugate of vitamin B6 with adenosine-N6-diethylthioether was originally reported as unknown compound B6X and considered to function as a storage form for vitamin B6 utilization by tumor cells. This novel compound is present in tumor cells in culture, the blood of normal and tumor-bearing animals, and the circulation of healthy individuals and patients with various ailments including malignancies. However, its level in the blood of cancer patients is significantly much greater -a desirable feature for cancer detection. Using HPLC pair-ion, reverse phase chromatography blood samples from patients with various malignancies and ailments were screened on a blind basis for the novel compound following its extraction at pH 4.2. The results show that the level of the vitamin B6 metabolite in the blood of cancer patients is up to 4x or higher than levels seen in the blood of normal volunteers, patients in remission or patients with other diseases. In addition, patients receiving treatment had lower levels than before treatment. Normal volunteers, cancer patients prior to treatment, cancer patients on therapy, cancer patients at remission and patients with other ailments had levels of 162.2; 601.7; 497.9; 216.5 and 179.3 (SEM range +/- 18.76-46.60), respectively. A comparison of the control, remission and other ailments groups with the cancer patient groups shows them to be significantly different (P < 0.00001) and strongly supports the use of the novel vitamin B6 conjugate metabolite for detection of human cancers.

Adenosine↗