Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00790 (PGA)
 2,475 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polymer polyglycolic acid is biocompatible in the body. A needle-shaped long-acting anti-cancer preparation (F-PGA needle) was prepared by compounding polyglycolic acid and the anti-cancer drug 5-Fluorouracil (5-FU). The release of 5-FU from the needle was maintained for about 10 days, and the needle disappeared after one year. A clinical study with the F-PGA needle was made on patients with terminal carcinomas. Shrinkage of tumors and tumor necrosis were observed in two patients with metastatic liver carcinomas. The F-PGA needle supplies high-dose 5-FU locally for a long time with fewer side effects by embedding it into the tumor tissue. Therefore the F-PGA needle can be said to be promising in the treatment of unresectable cancer as a topical application of chemotherapy.
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PMID:[Studies on the new long-acting anti-cancer preparation, 5-fluorouracil-polyglycolic acid composite]. 608 66

The purpose of these studies was to characterize the effect of the new anticancer preparation, 5-fluorouracil-polyglycolic acid-composite (F-PGA needle), on experimental tumors and in patients with solid tumors. The formative composite in a F-PGA needle was found to easily dissociate in physiologic saline resulting in the release of 5-fluorouracil (5-FU). The aspect of 5-FU release was observed to be relative to 5-FU content in the needle, but not to the length of the needle. When a F-PGA needle of 10mm in length and 30% in 5-FU content was subcutaneously or intrahepatically implanted in healthy rats, the release of 5-FU was maintained for 9 days in each case. Pathophysiologic examination of the liver following the implantation of a F-PGA needle revealed an increase in severe necrosis and/or degeneration and infiltration of small-round cells with the increase in release of 5-FU. Implantation of F-PGA needles into tumor mass of AH 130-bearing rats resulted in an increased 5-FU level in tumor tissue reaching the maximum level of 16.00 +/- 1.98 micrograms/g after 24 hours, and in a marked inhibition of the tumor growth indicating 2.4% of T/C (tested/controlled) at 10 days after implantation of the needle. A study of the F-PGA needle was made for 10 patients with terminal carcinomas and in 5 of these were verifiable. Of these 5 patients, shrinkage of tumors or improvement of symptoms was observed in 3 cases. From these results, the F-PGA needle is promising in the treatment of unresectable cancer as a long-acting chemotherapy.
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PMID:[Studies on the new anticancer preparation, 5-fluorouracil-polyglycolic acid-composite and its therapeutic evaluation]. 609 6

Prostaglandins (PGs) are bioregulatory substances and are widely distributed in a variety of tissues. Numerous facts have been described in relation to cancer biology with PGs. The purpose of our study lies in the creation of anti-tumor PGs. We have described that PGD2 has strong cell growth inhibitory activity; furthermore, we discovered that PGJ2, 9-deoxy-delta 9-PGD2, has 3 times stronger activity than the mother compound, PGD2. In vivo experiments showed that only PGA2 and PGJ2 exert antitumor activity. Thus, cyclopentenone ring structure in PG seems to be an essential moiety for cytotoxicity of PG. On the basis of the above facts, we propose tha name of antineoplastic PGs for PGA and PGJ derivatives which have cyclopentenone ring. Recently, we developed several antineoplastic PGs which showed IC50 value less than 0.3 microgram/ml against L1210 leukemia cells, and these compounds also showed antitumor activity against Ehrlich ascites tumor in vivo comparable to that of cyclophosphamide. The action mechanism seems to be in its alkylation activity of the cyclopentenone structure and not in receptor-cAMP route. Spectrum of anti-tumor activity and its toxicity in vivo are now under investigation. In this brief review, mainly our recent approaches in this field are discussed.
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PMID:[Development of antineoplastic prostaglandins]. 657 12

This study was designed to test the sensitivity and specificity of serum anti-Helicobacter pylori IgG antibodies and the ratio of serum pepsinogen A to pepsinogen C (PGA:PGC) in detecting chronic atrophic gastritis (CAG) and intestinal metaplasia. Parallel gastric biopsies and a serum sample were collected from a series of 87 patients aged 20-69 years attending a routine upper endoscopy clinic. The seroprevalence (> 10 micrograms IgG/ml) of anti-H. pylori antibodies was 42.7%, and of a low PGA:PGC ratio (< 1.5) was 17.7%. A positive H. pylori IgG antibody level was more sensitive than the level of PGA:PGC in diagnosing CAG (71.4% and 25.0%, respectively), moderate CAG (86.7% and 26.7%, respectively), and intestinal metaplasia (90.9% and 50.0%, respectively). Anti-H. pylori IgG antibody levels were less specific than PGA:PGC levels in diagnosing CAG (90.9% and 93.9%, respectively), moderate CAG (78.3% and 89.1%, respectively), and intestinal metaplasia (72.6% and 92.2%, respectively). A combination of anti-H. pylori antibodies and a low PGA:PGC ratio for the detection of CAG resulted in a specificity of 100%, but the sensitivity was 21.4%.
Cancer Epidemiol Biomarkers Prev
PMID:Serum anti-Helicobacter pylori IgG antibodies and pepsinogens A and C as serological markers of chronic atrophic gastritis. 846 46

Prostaglandins of the A type (PGAs) function as signals for heat shock protein (hsp) synthesis in mammalian cells. In human K562 erythroleukemic cells, PGA1 induces the synthesis of a M(r) 70,000 hsp (hsp70) by cycloheximide-sensitive activation of heat shock transcription factor (HSF). Induction of hsp70 has been associated recently with the ability of PGA to protect K562 cells from thermal injury, establishing a thermotolerant state; however, the role of hsp70 in thermotolerance is still controversial. Because quercetin was shown to modulate hsp70 expression after heat shock in K562 cells, we have investigated the effect of this flavonoid on HSF activation, hsp70 synthesis, and thermotolerance in human K562 cells after induction with PGA1. Quercetin was found to inhibit hsp70 synthesis for a period of 3-6 h after PGA1 treatment. This transient block was exerted at the transcriptional level and was not due to the loss of HSF DNA-binding activity. After the initial delay, hsp70 synthesis reached the same rate as the PGA1-treated control, and it was actually prolonged in the presence of quercetin. In PGA1-treated cells, quercetin suppressed PGA1-induced thermotolerance completely if the heat shock was applied at a time (6 h) when hsp70 synthesis was inhibited, whereas it could not prevent the establishment of a thermotolerant state if the heat challenge was applied 24 h after treatment, when hsp70 synthesis was not affected. These results support strongly the hypothesis that hsp70 is involved in the establishment of thermotolerance in human cells.
Cancer Res 1996 Jan 01
PMID:Modulation of prostaglandin A1-induced thermotolerance by quercetin in human leukemic cells: role of heat shock protein 70. 854 66

Cytotoxicity of trimetrexate (TMQ), a lipophilic dihydrofolate reductase inhibitor, was examined in antifolate-resistant human T-cell leukemia cell lines developed in oxidized or reduced folate. An approximately 60-fold methotrexate (MTX)-resistant subline was developed in oxidized folate (pteroylglutamic acid: PGA) (CCRF-CEM/MTX60-PGA) from human T-cell leukemia cell line CCRF-CEM; this line exhibited impaired membrane transport of the drug. Further enhancement of MTX resistance resulted in selection of an approximately 5000-fold MTX-resistant subline (CCRF-CEM/ MTX5000-PGA), which showed increased dihydrofolate reductase activity due to gene amplification in addition to further impairment of MTX transport. An approximately 140-fold MTX-resistant subline, and then a 1500-fold MTX-resistant subline were developed in reduced folate (10 nM leucovorin) (CCRF-CEM/MTX140-LV and CCRF-CEM/MTX1500-LV); they exhibited increased dihydrofolate reductase due to gene amplification accompanied by increased intracellular drug accumulation of MTX. While CCRF-CEM/MTX140-LV and CCRF-CEM/MTX1500-LV cells showed cross-resistance to TMQ, CCRF-CEM/MTX60-PGA and CCRF-CEM/MTX5000-PGA cells were at least as sensitive to TMQ as the parent cells. TMQ was more potent against approximately 200-fold N10-propargyl-5,8-dideazafolic-acid (CB3717)-resistant human T-cell leukemia MOLT-3 sublines developed in PGA (MOLT-3/CB3717(200)-PGA) or leucovorin (MOLT-3/CB3717(200)-LV), as compared to the parent cells; MOLT-3/CB3717(200)-PGA and MOLT-3/CB3717(200)-LV cells were resistant to CB3717 by virtue of impaired transport, only the former possessing gene amplification of thymidylate synthase. The cytotoxicity of TMQ in both MOLT-3/CB3717(200)-PGA and MOLT-3/CB3717(200)-LV cells was reduced by addition of leucovorin in a dose-dependent manner, suggesting intracellular folate deficiency as a cause of TMQ sensitivity. These results demonstrate that TMQ overcomes transport-impaired antifolate resistance, irrespective of gene amplification of dihydrofolate reductase or thymidylate synthase. Types of folate used during the development of antifolate resistance seem to be important in relation to the mechanism of TMQ responsiveness as well as that of antifolate resistance.
Jpn J Cancer Res 1997 Sep
PMID:Cytotoxicity of trimetrexate against antifolate-resistant human T-cell leukemia cell lines developed in oxidized or reduced folate. 936 39

The relationship of the production of interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF-alpha) and interleukin-2 (IL-2) to the pattern and etiology was studied in patients with pulmonary tuberculosis (n = 74) and nontuberculous lung diseases (n = 28). There was an inverse correlation between the production of the proinflammatory cytokines IL-1 beta and TNF-alpha and the main T-cellular immunity IL-2. An exacerbation of a tuberculous process is accompanied by an increase in IL-1 beta and TNF-alpha productions and by a decrease in inducted IL-2 synthesis. With favourable changes, there was, on the contrary, a reduction in the levels of IL-1 beta and TNF-alpha and a rise in IL-2. There were differences in the rate of cytokine synthesis in pulmonary tuberculosis, lung cancer, and pneumonia. Patients with cancer are most typified by the spontaneous mononuclear production of serum TNF-alpha and by the low level of IL-2 when PGA is stimulated. On the contrary, the least TNF-alpha synthesis and pronounced IL-2 production in pneumonia. A combination of the high production of PPD-induced IL-1 beta and PGA-stimulated IL-2 is more specific to patients with infiltrative pulmonary tuberculosis.
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PMID:[Production of cytokines in different forms of pulmonary tuberculosis]. 969 96

Prostaglandin A(2) (PGA(2)), an experimental chemotherapeutic agent, causes growth arrest associated with decreased cyclin D1 expression in several cancer cell lines. Here, using human non-small-cell lung carcinoma H1299 cells, we investigated the mechanisms whereby PGA(2) down-regulates cyclin D1 expression. Transcription rates of the cyclin D1 gene, studied using a cyclin D1 promoter-luciferase construct and nuclear run-on assays, were not affected by PGA(2) treatment. Instead, the cyclin D1 mRNA was rendered unstable after exposure to PGA(2). Since the stability of labile mRNA is modulated through binding of proteins to specific mRNA sequences, we sought to identify protein(s) recognizing the cyclin D1 mRNA. In electrophoretic mobility-shift assays using radiolabeled RNA probes derived from different regions of cyclin D1 mRNA, we observed that (i) lysates prepared from PGA(2)-treated cells exhibited enhanced protein-cyclin D1 RNA complex formation; (ii) the kinetics of complex formation correlated closely with that of cyclin D1 mRNA loss; and (iii) binding occurred within a 390-base cyclin D1 3' untranslated region (UTR) (K12). This binding activity could be cross-linked, revealing proteins ranging from 30 to 47 kDa. The RNA-binding protein AUF1, previously associated with the degradation of target mRNAs, bound cyclin D1 mRNA, because anti-AUF1 antibodies were capable of supershifting or immunoprecipitating cyclin D1 mRNA-protein complexes. Finally, insertion of K12 in the 3'UTR of reporter genes markedly reduced the expression and half-life of the resulting chimeric mRNAs in transfected, PGA(2)-treated cells. Our data demonstrate that PGA(2) down-regulates cyclin D1 expression by decreasing cyclin D1 mRNA stability and implicates a 390-base element in the 3'UTR in this regulation.
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PMID:Down-regulation of cyclin D1 expression by prostaglandin A(2) is mediated by enhanced cyclin D1 mRNA turnover. 1102 61

Radiation therapy for cancer in the head and neck region leads to a marked loss of salivary gland parenchyma, resulting in a severe reduction of salivary secretions. Currently, there is no satisfactory treatment for these patients. To address this problem, we are using both tissue engineering and gene transfer principles to develop an orally implantable, artificial fluid-secreting device. In the present study, we examined the tissue compatibility of two biodegradable substrata potentially useful in fabricating such a device. We implanted in Balb/c mice tubular scaffolds of poly-L-lactic acid (PLLA), poly-glycolic acid coated with PLLA (PGA/PLLA), or nothing (sham-operated controls) either beneath the skin on the back, a site widely used in earlier toxicity and biocompatibility studies, or adjacent to the buccal mucosa, a site quite different functionally and immunologically. At 1, 3, 7, 14, and 28 days postimplantation, implant sites were examined histologically, and systemic responses were assessed by conventional clinical chemistry and hematology analyses. Inflammatory responses in the connective tissue were similar regardless of site or type of polymer implant used. However, inflammatory reactions were shorter and without epithelioid and giant cells in sham-operated controls. Also, biodegradation proceeded more slowly with the PLLA tubules than with the PGA/PLLA tubules. No significant changes in clinical chemistry and hematology were seen due to the implantation of tubular scaffolds. These results indicate that the tissue responses to PLLA and PGA/PLLA scaffolds are generally similar in areas subjacent to skin in the back and oral cavity. However, these studies also identified several potentially significant concerns that must be addressed prior to initiating any clinical applications of this device.
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PMID:Tissue compatibility of two biodegradable tubular scaffolds implanted adjacent to skin or buccal mucosa in mice. 1220 4

For the regeneration of injured peripheral nerves, we have devised a PGA-tube that is composed of a tube of polyglycolic acid containing collagen sponge. This PGA-tube was applied clinically to reconstruct a peripheral nerve that had been resected during extended surgical resection of for intrapelvic recurrent rectal cancer. Four months after the surgical resection, the function of the left hip joint has improved remarkably, whereas the function had been lost just after the operation. It is suggested that the PGA-tube will be useful for regeneration of peripheral nerves that are resected during operation for intrapelvic malignancy.
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PMID:[Clinical application of PGA-tube for regeneration of intrapelvic nerves during extended surgery for intrapelvic recurrent rectal cancer]. 1248 37


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