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)

Earlier studies from this laboratory revealed that killer lymphocyte lineages are inactivated in the tumor-bearing host by macrophage-derived PGE2. In this study, we examined whether tumor bearing causes a change in the density or affinity of PGE2 receptors on lymphocytes, making them more vulnerable to PGE2 action, and whether it enhances PGE2 production by host macrophages. PGE2 receptors were examined on both unfractionated and monocyte-macrophage-depleted splenocytes of normal or tumor-bearing C3H/HeJ mice (at 25 days following s.c. transplantation of 10(6) C3 mammary adenocarcinoma cells) using a [3H]PGE2 binding assay in the presence of increasing (up to 10(4)-fold) concentrations of unlabeled PGE2 (or PGA or PGF2 alpha as specificity controls) followed by a Scatchard analysis. PGE2 production by splenic macrophages was measured with a radio-immunoassay. Results revealed that splenocytes in normal and tumor-bearing mice bear specific receptors for PGE2, since splenocyte binding of [3H]PGE2 (10(-9) M) was inhibited in the presence of excess unlabeled PGE2, but not 10(-4)-fold excess PGA or PGF2 alpha. Tumor-bearing did not appear to cause an appreciable change in the affinity or density of these receptors, since Kd and Bmax values for PGE2 binding were similar for normal and tumor-bearing mice. However, specific PGE2-binding by splenocytes in vitro was reduced in tumor-bearing mice. Three types of evidence indicate that this resulted from a partial occupation of PGE2 receptors on lymphocytes with PGE2 produced by splenic macrophages of tumor-bearing hosts. First, depletion of monocyte-macrophages from the splenocyte population improved this binding in tumor-bearing but not normal mice.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:PGE2 receptors on murine splenic lymphocytes: effects of tumor bearing. 166 31

The syntheses and cytotoxic activities of substituted N-phenylacetamido derivatives of doxorubicin and melphalan are described. The derivatives were designed as prodrugs which could be activated in a site-specific manner by monoclonal antibody-penicillin-G amidase (mAb-PGA) conjugates. N-(Phenylacetamido)doxorubicin (2) and N-(phenylacetyl)melphalan (6) were found to be 10- and 20-fold less cytotoxic against H2981 lung adenocarcinoma cells than doxorubicin and melphalan, respectively. When incubated with PGA, the cytotoxicity of 2 and 6 increased and became equivalent to that of the corresponding drugs from which they were made. The poor solubility characteristics of 2 in aqueous solutions provided the basis for the development of the more soluble doxorubicin derivatives, N-(4-aminophenylacetyl)doxorubicin (3) and N-(4-phosphonooxy)phenylacetyl)-doxorubicin (4). In vitro cytotoxicity assays indicated that 3 and 4 were at least 1000-fold less toxic than doxorubicin against H2981 cells. PGA and the mAb conjugate L6-PGA were able to effect the activation of 3 and 6 on H2981 cells (L6-antigen positive). Hydrolysis of the phosphate group of 4 was required prior to activation with PGA or L6-PGA. This was achieved using alkaline phosphatase, or by exposing 4 to phosphatases present in cell culture medium. The activation of 3, 4, and 6 on H2981 cells by L6-PGA occurred in an immunologically specific manner, since activation could be blocked by saturating cell surface antigens with L6 prior to treatment with L6-PGA. These results demonstrate that 3, 4, and 6 are prodrugs that can be specifically activated to release clinically approved anticancer agents by a mAb-PGA conjugate.
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PMID:Prodrugs of doxorubicin and melphalan and their activation by a monoclonal antibody-penicillin-G amidase conjugate. 846 46

The ability of poly(lactic-co-glycolic acid) (PLGA, 50:50 PLG/PGA, wt%) nanotopographies to decrease lung epithelial carcinoma cell functions (including adhesion, proliferation, apoptosis and vascular endothelial growth factor (VEGF) secretion) has been previously reported. Specifically, results demonstrated decreased lung epithelial carcinoma cell VEGF synthesis on 23 nm surface-featured PLGA compared to traditional nanosmooth PLGA. However, clearly, different cell lines could have different behaviors on similar biomaterials. Thus, to investigate the universality of nanopatterned PLGA substrates to inhibit numerous cancer cell functions, here, breast epithelial adenocarcinoma cell (MCF-7) adhesion, proliferation, apoptosis and VEGF secretion were determined on different PLGA nanometer surface topographies. To isolate surface nanotopographical effects from all other surface properties, PLGA surfaces with various nanotopographies but similar chemistry and hydrophobicity were fabricated here. Atomic force microscopy (AFM) verified the varied nanotopographies on the PLGA surfaces prepared in this study. Importantly, results demonstrated for the first time significantly decreased breast adenocarcinoma cell functions (including decreased proliferation rate, increased apoptosis and decreased VEGF synthesis) on 23 nm featured PLGA surfaces compared to all other PLGA surface topographies fabricated (specifically, nanosmooth, 300 and 400 nm surface-featured PLGA surfaces). In contrast, healthy breast epithelial cells proliferated more (24%) on the 23 nm featured PLGA surfaces compared to all other PLGA samples. In summary, these results provided further insights into understanding the role PLGA surface nanotopographies can have on cancer cell functions and, more importantly, open the possibility of using polymer nanotopographies for a wide range of anticancer regenerative medicine applications (without resorting to the use of chemotherapeutics).
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PMID:Poly-lactic-glycolic-acid surface nanotopographies selectively decrease breast adenocarcinoma cell functions. 2243 63

Gastric and duodenal adenomas exhibit a significant morphological and phenotypical diversity and are classified into intestinal-type, foveolar-type and pyloric gland adenomas. We analysed the mutations in GNAS, KRAS, BRAF and CTNNB1 and the expressions of mismatch repair (MMR) proteins in 80 gastric and 32 duodenal adenomas with histologically distinct subtypes, as well as in 71 gastric adenocarcinomas. Activating GNAS mutations were found in 22 of the 35 pyloric gland adenomas (PGAs; 63%) but in none of the foveolar-type or intestinal-type adenomas or the adenocarcinomas. Fourteen PGAs (41%), two foveolar-type adenomas (9%), five intestinal-type adenomas (9%) and one adenocarcinoma (1%) had KRAS mutations. BRAF mutations were absent in all the adenomas and adenocarcinomas that were examined. CTNNB1 mutations were only found in two intestinal-type adenomas (4%). Notably, 13 of the 14 KRAS-mutated gastric and duodenal PGAs had concurrent GNAS mutations. The loss of the MMR proteins, which is indicative of microsatellite instability, was observed in one PGA (3%), 12 foveolar-type adenomas (52%), one intestinal-type adenoma (2%) and five adenocarcinomas (7%). These observations indicate that each histological subtype of gastric and duodenal adenomas has a distinct genetic background. In particular, the present study identified the frequent presence of activating GNAS mutations, which are often associated with KRAS mutations, as a characteristic genetic feature of PGAs of the stomach and duodenum.
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PMID:Frequent GNAS and KRAS mutations in pyloric gland adenoma of the stomach and duodenum. 2320 52

The aim of this case report was to evaluate the usefulness of a grafting with polyglycolic acid sheet and a fibrin glue spray (PGA sheet grafting) after resection of a cervical skin tumor. A 61-year-old woman presented with left cervical skin tumor resistance to chemo-radiotherapy. She had been undergoing multimodal therapy for ovarian serous papillary adenocarcinoma for the previous six years. Although she had a poor general condition and a cervical skin tumor of 9cm in diameter, which was painful and easy bleeding, had offensive smell, she hoped to return to her job. Under local anesthesia, resection was performed, and PGA sheet grafting were used to shield the skin defect. After resection, she was relieved from pain, and could stay home without daily wound treatment. One and half months after resection, the wound was almost epithelialized. The PGA sheets consist of soft, elastic, nonwoven fabric made of PGA. In recent years, PGA sheet grafting has been widely used in the reconstruction and was chosen to shield the skin defect for this case. PGA sheet grafting after resection of cervical skin tumor can be an acceptable method for palliative care to relieve pain, bleeding, offensive smell, and ugly appearance.
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PMID:A case grafted with polyglycolic acid sheets and fibrin glue for protection after temporary resection of a metastatic cervical skin tumor. 2862 27