Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A polyethylene glycol (PEG) precipitation F(ab')2 anti-C3 ELISA for the detection of complement-fixing IgG circulating immune complexes (CIC) is described. For this assay, test sera were treated with 3.5% PEG and then measured with F(ab')2 anti-C3 ELISA. The lower detection limit was 4 micrograms/ml of heat aggregated human IgG (HAHG). Intra-assay coefficient of variation (CV) was 4.9-8.3%. High levels of CIC are found in the sera of patients with systemic lupus erythematosus (SLE), hepatitis B and stomach cancer.
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PMID:Detection of circulating immune complexes with polyethylene glycol precipitation F(ab')2 anti-C3 ELISA. 227 58

Immune complexes (IC) were measured in 66 gastric cancer patients, using the 3.5 percent polyethylene glycol (PEG) precipitation method. Preoperatively, the IC values in patients with advanced gastric cancer (stages III and IV) were significantly higher than in normal subjects (p less than 0.01). In the presence of 3.5 percent PEG-precipitated IC from sera of gastric cancer patients, the mitogen responses of normal peripheral blood lymphocytes was inhibited; the PHA response revealed a significant negative correlation with the concentration of IC (p less than 0.01). Our data suggest that IC may be a major serum factor exerting immunosuppressive effect in cancer hosts.
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PMID:Circulating immune complexes in gastric cancer patients and their effect on lymphocyte mitogenesis (the first report). 653 Aug 48

In 47 patients with an endoscopic-bioptic reliable gastric cancer two prognostic groups (good/poor) were set up by the help of clinical TNM-determination (gastroscopy, laparoscopy, operation), histology (bioptate and resectate) and long-term observation. In order to determine their prognostic significance 37 clinical, morphological and immunological parameters were recorded and analysed by the help of a multivariate analysis of variance and discriminance. The TNM-stage, erythrocyte sedimentation rate, the acid mucopolysaccharides in the tumour, circulating, complement binding immuncomplexes, B-cells, IgM, C3 and C4, IgE, gastritic degree and the infiltration of the tumour by neutrophile granulocytes and lymphocytes prove to be prognostic-discriminatoric significant. The parameters allowed a retrogradually-mathematically reliable classification of the patients into one of the both prognostic groups. The remaining features (age, sex, duration of the case history, Rohrer-index, tumour superficial spread, histological differentiation, neutral mucopolysaccharides, gastric activity, plasma cells and macrophages as stroma cells, IgG, IgA, auto-antibodies, dysproteinaemies, PEG-precipitate, T-cells, LAI-test, haemoglobin, total leucocyte count and total protein) prove to be redundant, i.e. they are unnecessary for calculation of the prognosis.
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PMID:[Relevant prognostic results in stomach cancer (analysis of variance and discriminance with clinical, morphologic and immunologic features)]. 660 1

This review deals with the current status of newly developed pendant-type PEG-immunoliposomes (Type C), carrying monoclonal antibodies or their fragments (Fab') at the distal ends of the PEG chains. In terms of target binding of Type C, two different anatomical compartments are considered. They are mouse lung endothelium as a readily accessible site via the intravascular route and the implanted solid tumor as a much less accessible target site reached via extravasation. Distearoyl phosphatidylethanolamine derivatives of PEG with a carboxyl group (DSPE-PEG-COOH) and dipalmitoyl phosphatidylethanolamine derivatives of PEG with a maleimidyl group (DPPE-PEG-Mal) at the PEG terminus were newly synthesized. Small unilamellar liposomes (90-130 nm in diameter) were prepared from phosphatidylcholine and cholesterol (2 : 1, m/m) containing 6 mol% of DSPE-PEG-COOH or DPPE-PEG-Mal. For targeting to the vascular endothelial surface in the lung, 34A antibody, which is highly specific to mouse pulmonary endothelial cells, was conjugated to PEG-liposomes (34A-Type C). The degree of lung binding of 34A-Type C in BALB/c mouse was significantly higher than that of 34A-Type A, which is an ordinary type of immunoliposome (without PEG derivatives). For targeting to solid tumor tissue, 21B2 antibody (anti-human CEA) and its Fab' fragment were used. The targeting ability of Fab'-Type C was examined by using CEA-positive human gastric cancer strain MKN-45 cells inoculated into BALB/c nu/nu mice. Fab'-Type C showed low RES uptake and a long circulation time, and enhanced accumulation of the liposomes in the solid tumor was seen. The small Fab'-Type C predominantly passed through the leaky tumor endothelium by passive convective transport. These studies offer important insights into the potential of Type C liposomes for target-specific drug delivery.
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PMID:In vivo targeting by liposomes. 1091 54

cis-Diamminedichloroplatinum (II) (cisplatin, CDDP), a potent anticancer agent, was bound to the aspartic acid residues of poly(ethylene glycol)-poly(aspartic acid) (PEG-P(ASP)) block copolymer by ligand substitution reaction at the platinum atom of CDDP. The polymeric drug thus obtained was observed to form a micelle structure in aqueous medium, showing excellent water solubility. In the present study, in vitro and in vivo antitumor activity against several human tumor cell lines, toxicity and pharmacokinetic characteristics in rodents of CDDP-incorporated polymeric micelles (CDDP / m) were evaluated in comparison with those of CDDP. In vitro, CDDP / m exhibited 10 - 17% of the cytotoxicity of CDDP against human tumor cell lines. CDDP / m given by intravenous (i.v.) injection yielded higher and more sustained serum levels than CDDP. In vivo CDDP / m treatment resulted in higher and more sustained levels in tumor tissue than CDDP, and showed similar antitumor activity to CDDP against MKN 45 human gastric cancer xenograft. CDDP / m treatment caused much less renal damage than CDDP. These results indicate that CDDP / m treatment can reduce CDDP-induced nephrotoxicity without compromising the anticancer cytotoxicity of CDDP.
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PMID:Cisplatin-incorporated polymeric micelles eliminate nephrotoxicity, while maintaining antitumor activity. 1126 44

Peritoneal dissemination in gastric cancer is a common fatal clinical condition with few effective therapies available. We studied the therapeutic effect of a tumor-targeting drug delivery system that uses cisplatin-encapsulated and Tf-conjugated PEG liposomes (Tf-PEG liposomes) in nude mice with peritoneal dissemination of human gastric cancer cells. Small unilamellar Tf-PEG, PEG or DSPC/CH liposomes (bare liposomes) encapsulating cisplatin were prepared by reverse-phase evaporation followed by extrusion. Electron microscopic studies revealed that Tf-PEG liposomes were internalized into tumor cells by receptor-mediated endocytosis. To examine the biodistribution of each liposome and cisplatin level, nude mice were inoculated i.p. with 10(7) MKN45P human gastric tumor cells. On the fourth day after tumor inoculation, (3)H-CHE-labeled and cisplatin-encapsulated Tf-PEG, PEG or bare liposome were inoculated i.p. The Tf-PEG liposome-administered group maintained high liposome and cisplatin levels in ascites and showed a prolonged residence time in the peripheral circulation. Uptake of Tf-PEG liposomes into the liver and spleen was significantly lower than that of bare liposomes. Uptake of Tf-PEG liposomes in disseminated tumor cells of ascites and the greater omentum was significantly higher than that of PEG or bare liposomes and a significant increase in cisplatin levels was observed in these tumor cells. Mice receiving Tf-PEG liposomes 1 and 4 days after the day of tumor inoculation showed significantly higher survival rates compared with those receiving PEG liposomes without Tf, bare liposomes or free cisplatin solution. These results suggest that cisplatin-encapsulated Tf-PEG liposomes may be useful as a new intracellular targeting carrier for treatment of gastric cancer with peritoneal dissemination.
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PMID:Intracellular targeting therapy of cisplatin-encapsulated transferrin-polyethylene glycol liposome on peritoneal dissemination of gastric cancer. 1194 4

This review deals with the current status of newly developed pendant-type PEG-immunoliposomes (Type C), carrying monoclonal antibodies or their fragments (Fab') at the distal ends of the PEG chains. In terms of target binding of Type C, two different anatomical compartments are considered. They are mouse lung endothelium as a readily accessible site via the intravascular route and the implanted solid tumor as a much less accessible target site reached via extravasation. Small unilamellar liposomes (90-130 nm in diameter) were prepared from phosphatidycholine and cholesterol (2:1, m/m) containing 6mol.% of DSPE-PEG-COOH or DPPE-PEG-Mal. For targeting to the vascular endothelial surface in the lung, 34A antibody, which is highly specific to mouse pulmonary endothelial cells, was conjugated to PEG-liposomes (34A-Type C). The degree of lung binding of 34A-Type C in BALB/c mouse was significantly higher than that of 34A-Type A, which is an ordinary type of immunoliposome (without PEG derivatives). For targeting to solid tumor tissue, 21 B2 antibody (anti-human CEA) and its Fab' fragment were used. The targeting ability of Fab'-Type C was examined by using CEA-positive human gastric cancer strain MKN-45 cells inoculated into BALB/c nu/nu mice. Fab'-Type C showed low RES uptake and a long circulation time, and enhanced accumulation of the liposomes in the solid tumor was seen. The small Fab'-Type C predominantly passed through the leaky tumor endothelium by passive convective transport. These studies offer important insights into the potential of Type C liposomes for target-specific drug delivery.
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PMID:PEG-immunoliposome. 1242 3

There is increasing incidence of adenocarcinoma of the esophagastric junction (EGJ) especially in young white men (+35% in 30 years). The reasons for this are not yet well known, however one of the main causes is gastro-esophageal-reflux disease (GERD). The differentiation of a EGT carcinoma in three subtypes is important for therapy: adenocarcinoma of the distal esophagus (type I), cardia carcinoma (type II) and subcardial gastric carcinoma (type III). The most important risk-factor for type I-cancers is "barrett's metaplasia" resulting from GERD over years. The risks for the type II- and type III-carcinomas may be obesity and high caloric and fat intake. The role of Helicobacter pylori infection and adenocarcinoma of the subcardia is unproven. Preoperative tumor staging is difficult and tumor-stage is most often underestimated (esp. in the case of a high-grade dysplasia where in 43% carcinomas one already established). Therapy for all three types of EGJ tumors is surgical. Transhiatal (rarely transthoracic) esophagectomy with lymphadenectomy and proximal gastrectomy is performed for type-I-tumors, type-II and III-tumors are treated like a gastric cancer with total gastrectomy, lymphadenectomy and distal esophagectomy. Lymph-node metastases and advanced tumor-stage are bad prognostic factors, complete tumor resection (R0 resection) with extended lymphadenectomy will improve prognosis. The results of a preoperative combined-modality therapy are encouraging, but have not yet shown a definitive benefit. In case of distant metastases, radio-chemotherapy combined with gastroenterologic treatments (e.g. esophageal prostheses, PEG, etc.) will be used as a palliative treatment option.
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PMID:[Carcinomas of the esophago-gastric junction: surgical strategies]. 1281 32

Lipophilic photosensitizers hold potential for cancer photodynamic therapy. We sought to develop a novel photosensitive stealth liposome (PSSL) which incorporating a lipophilic photosensitizer into its lipid bilayer and to examine its photoactivity. We prepared PSSL composed of lipophilic chlorin e6 (Ce6) ester, dilauroylphosphatidylcholine, dioleoylphosphatidylethanolamine and distearoyl-phosphoethanolamine-N-[poly (ethylene glycol) 2000] and evaluated its photodynamic effect against gastric cancer cell lines and tumor-bearing nude mice models. In gastric cancer cell lines, LC(80) of PSSL was a maximum of 53 times as low as that of Ce6 sodium salt (Ce6-Na). PSSL completely destroyed all tumors in animal models and tumor recurrence levels were minimal (1.5 +/- 0.9%). PSSL achieved greater photodynamic effects in gastric cancer cell lines and in murine models than Ce6-Na. PSSL holds promise for photodynamic therapy for gastric cancer.
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PMID:Enhanced photodynamic antitumor effect on gastric cancer by a novel photosensitive stealth liposome. 1508 31

The development of protocols for the ex vivo generation of dendritic cells (DCs) has led to intensive research of their potential use in immunotherapy. Accumulating results show the efficacy of this treatment on melanomas which are highly immunogenic. However, its efficacy remains unclear in other tumors. In this study, allogeneic gastric cancer cell-DC hybrids were used to determine the efficacy of this type of immunotherapy in gastric cancer. Fusion cells of DC and allogeneic gastric cancer cells were generated by polyethylene glycol (PEG) and electrofusion. These hybrids were used to induce tumor associated antigen (TAA) specific cytotoxic T lymphocytes (CTLs). The DCs were successfully fused with the allogeneic gastric cancer cells resulting in hybrid cells. These hybrid cells were functional as antigen-presenting cell because they induced allogeneic CD4(+) T cells proliferation. CD8(+) T cells stimulated by the MKN-45-DC hybrid cells were able to kill MKN-45 when used for immunization. The CTLs killed another gastric cancer cell line, MKN-1, as well as a melanoma cell line, 888mel, suggesting the recognition of a shared tumor antigen. MKN-45 specific CTLs can recognize carcinoembryonic antigen (CEA), indicating that the killing is due to tumor antigens as well as alloantigens. This approach suggests the possible use of allogeneic gastric cancer cell-DC hybrids in DC based immunotherapy for gastric cancer treatment.
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PMID:Allogeneic gastric cancer cell-dendritic cell hybrids induce tumor antigen (carcinoembryonic antigen) specific CD8(+) T cells. 1589 83


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