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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three intraperitoneal human ovarian cancer xenografts (OS, HU, and LA) were used to assess the antitumour activity of intraperitoneal therapy with liposome encapsulated MTP-PE. MTP-PE led to significant prolongation of survival in all three xenograft models, but with varying efficacy. In one tumour model (OS), 80% of mice were cured of tumour by twice weekly therapy for 4 weeks, whereas in another xenograft model (LA), the median survival time was approximately doubled compared to PBS injected and placebo liposome injected controls (median survivals: 30 vs 62.5 days respectively). The antitumor efficacy of MTP-PE did not correlate with the extent of peritoneal neutrophil infiltration after intraperitoneal therapy. Combined therapy with liposome encapsulated MTP-PE and recombinant murine granulocyte-macrophage colony stimulating factor led to increased survival of mice bearing the LA and HU xenografts, compared to tumour bearing mice treated with either agent singly.
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PMID:Therapy of human ovarian cancer xenografts with intraperitoneal liposome encapsulated muramyl-tripeptide phosphoethanolamine (MTP-PE) and recombinant GM-CSF. 200 80

Overexpression of HER-2/neu has been demonstrated in human ovarian cancer and correlated with poor prognosis. We previously found that the adenovirus type 5 early region 1A (E1A) gene product can repress overexpression and suppress the tumorigenic potential of the HER-2/neu-overexpressing cancer cells. To develop an efficient HER-2/neu-targeting gene therapy with E1A, a replication-deficient adenovirus containing the E1A gene, Ad.E1A(+), was used to transduce the HER-2/neu-overexpressing human ovarian cancer cell line SK-OV3.ip1. Tumor cell growth in vitro and colony formation in soft agarose were greatly inhibited by Ad.E1A(+) transduction. To test therapeutic efficacy in vivo, tumor-bearing mice were established by i.p. injection with ovarian cancer cells and treated by i.p. injection of 10(8) PFU viral solution containing either replication-deficient Ad.E1A(+); control virus Ad.E1A(-) which is the same adenovirus as Ad.E1A(+) except for E1A deletion, or just PBS. Ad.E1A(+) significantly prolonged survival in treated mice for 1 year (80%) whereas in control groups, all mice died of cancer within 4.5 months. Immunohistochemistry analysis indicated that Ad.E1A protein was expressed in tumor tissue and expression of HER-2/neu p185 protein was suppressed in vivo. As a control, another ovarian cancer cell line 2774, in which HER-2/neu is expressed at a basal level, was also inoculated i.p. following the same therapeutic procedure. Ad.E1A(+) could not prolong survival of 2774 cells, indicating that Ad.E1A(+) specifically targeted HER-2/neu-overexpressing tumor cells and functioned as an antitumor agent.
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PMID:HER-2/neu-targeting cancer therapy via adenovirus-mediated E1A delivery in an animal model. 776 Oct 95

Ovarian cancer is one of the significant and deadly disease. Since 1980 when cisplatin was introduced in the chemotherapy, about 30% of the patients with advanced disease have achieved 5-year survival. However, remaining patients have had progressive disease or recurrence after achieving NED. Forty-seven% of recurrent disease was discovered as distant metastasis, while at initial therapy. In the recurrent disease, distantly metastatic lesions were encountered more frequently than those in primary disease. In the recurrent tumor, expression of immunohistochemical markers of malignancy, such as p53 protein and CD44v6 antigen were increased. These clinical data suggest that recurrent ovarian cancer which are exposed to anticancer agents attain increased metastatic potential. In order to assure that anticancer agent contribute to this increment, an experimental system using two human ovarian cancer cell lines (HRA, KF) and nude mice in which cancer cells were exposed to cisplatin in vivo was introduced. Cancer cells exposed to cisplatin in vivo (treated cells) made spontaneously more metastatic nodules in the mouse lung than those exposed to PBS (untreated cells). This result suggest that cisplatin induce the increase of metastatic potential of cancer cells in vivo. Treated cells showed higher invasiveness compared with untreated cells when inoculated in the footpad. Three major factors which were generally proposed to be necessary for cancer cell to give rise to invasion, such as attachment to extracellular matrix, production of proteolytic enzyme, and cellular mobility. For all of these factors, treated cells were superior to untreated cells. These results obtained suggests that cisplatin could increase the metastatic potential of cancer by enhancing potential of invasion. To investigate the mechanism of this phenomenon from the standpoint of genetic mutation, clonal analysis of experimental cancer in vivo was performed using southern blot method. Cancer cells before inoculation to the mice consisted of multiple clones. In 5 week after inoculation, tumor was wholely occupied by only one clone which showed one band on the lane. At this point cisplatin were administered. In 6 week, new single clone appeared with different band pattern from that of the clone at the administration of cisplatin. Furthermore, the cisplatin-induced new clone metastasized to the lung, while no metastasis was observed in the mouse with PBS-treated tumor during the same period. These data suggest that increased metastatic potential after cisplatin treatment is due not to selection but to creation of highly metastatic clone caused by potential of genetic mutation of cisplatin. In conclusion, chemotherapeutic agent has a potential to create highly malignant cancer cells as well as a potential to kill cancer cells.
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PMID:[Alteration of metastatic potential of ovarian cancer in clinical course]. 880 28

The HER-2/neu proto-oncogene is frequently amplified or overexpressed in human breast and ovarian cancers, and is significantly correlated with shorter survival. We have previously reported that the adenovirus type 5 early region 1A (E1A) gene product can repress HER-2/neu overexpression by repressing HER-2/neu promoter activity, and suppress the tumorigenic potential of HER-2/neu-overexpressing ovarian cancer cells. To examine E1A tumor suppressor function in breast cancer, we transduced E1A in vitro by adenovirus into both HER-2/neu-overexpressing and low expressing human breast cancer cell lines. In HER-2/neu-overexpressing cells, E1A greatly inhibited tumor cell growth in vitro. However, in HER-2/neu low expressing cancer cell lines, E1A had no significant effect on cell growth in culture medium. To test the therapeutic efficacy of E1A, we used both adenovirus-mediated and cationic liposome-mediated E1A gene delivery systems in an orthotopic breast cancer animal model. An advanced breast cancer model was established by inoculation of HER-2/neu-overexpressing human breast cancer cells in mammary fat pad and treated by local injections of either replication-deficient adenovirus expressing E1A, Ad.E1A(+) or a liposome-E1A DNA complex. As controls, mice bearing tumors were also treated with Ad.E1A(-) which is virtually the same adenovirus as Ad.E1A(+) except that E1A is deleted, a liposome-E1A frame-shift mutant DNA complex, or just PBS. In mice bearing a HER-2/neu-overexpressing breast cancer cell line, E1A delivered either by adenovirus or liposome significantly inhibited tumor growth and prolonged mouse survival compared with the controls. In fact, 60-80% of E1A-treated mice lived longer than 2 years versus only 0-20% of control mice (P<0.05). Western blot analysis showed that E1A protein was expressed in tumor tissue and immunohistochemical analysis showed that HER-2/neu p185 protein expression was suppressed. Taken together, our results indicated that both adenovirus and cationic liposome delivery systems were effective in transfering E1A gene for tumor suppression in a HER-2/neu-overexpressing breast cancer model.
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PMID:The tumor suppression activity of E1A in HER-2/neu-overexpressing breast cancer. 905 54

The purpose of this study was to determine the efficacy of adenovirus-based p53 gene therapy in the treatment of ovarian cancer using an intraperitoneal microscopic tumor animal model system. Adenovirus-mediated wild-type p53 gene was introduced into the NIH:OVCAR-3 human ovarian cancer cell line in vitro and in vivo. In order to study microscopic intraperitoneal tumor, athymic nude mice were inoculated intraperitoneally (i.p.) with 1 x 107 OVCAR-3 cells and observed for tumor growth. Three days after inoculation with OVCAR-3 cells, the mice were divided into 3 treatment groups. One group received three daily i.p. injections of 1 x 108 pfu Ad-CMV-p53, a second group received three daily i.p. injection of 1 x 108 pfu of the control adenovirus construct expressing beta galactosidase (Ad-CMV-betagal) and a third group received three daily i.p. injections of normal saline. Adenovirus-mediated introduction of the wild-type p53 gene in the ovarian cancer cell line resulted in transient high levels of p53 protein for 24-48 h. Cell cycle analysis revealed G1 arrest, as well as the appearance of apoptosis. In vitro cell growth assays showed growth inhibition of cancer cells infected with Ad-CMV-p53 compared to cells infected with Ad-CMV-betagal or normal saline. There was a significant increase in survival in the Ad-CMV-p53 adenovirus treated animals compared to the PBS treated animals (P = 0.004). Likewise, the survival in Ad-CMV-p53 treated mice was also significantly greater than mice treated with Ad-CMV-betagal (P < 0.0001). These results demonstrated that Ad-CMV-p53 treatment is effective in inhibiting tumor growth and prolonging survival in this microscopic cancer xenograft model. The results of this study constitute a step in translating promising in vitro and in vivo data from an adenovirus-based gene therapeutic model system into practical and scientifically based human cancer therapeutic trials.
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PMID:Efficacy of intraperitoneal adenovirus-mediated p53 gene therapy in ovarian cancer. 1124 Jul 95

The aim of this study was to investigate therapeutic efficacy of adenovirus-mediated E1a gene therapy for ovarian cancer in vitro and in vivo. Recombinant replication-deficient adenoviral vectors were prepared by superinfection of 293 cells, and then purified. The efficacy of the adenovirus vector system to infect ovarian cells was tested using different multiplicity of infection (MOI) and different times (1-4) of Ad.RSVlacZ. SKOV-3 cells (10(3) per well) were infected once with 2 x 10(4) adenovirus. The cells were harvested and counted on different days for 7 days to generate the in vitro growth curve. Tumor-bearing mice were injected intraperitoneally with ovarian cancer cells and treated by intraperitoneal injection of 100 microl (2.5 x 10(8) PFU) viral solution containing either replication-deficient Ad.E1a(+); control virus Ad.E1a(-) which is the same adenovirus as Ad.E1a(+) except for E1a deletion, or just phosphate buffered solution. The transduction efficacy increased with higher MOI and reached a plateau at the 20:1 ratio. When Ad.E1a(+) was used to transduce the HER-2/neu overexpressing human ovarian cancer cell line SKOV-3, tumor cell growth in vitro was greatly inhibited by E1a transduction. Also, Ad.E1a+ greatly inhibited tumor growth of SKOV-3-bearing mice. Immunohistochemistry analysis indicated that Ad.E1a protein was expressed in tumor tissue and expression of HER-2/neu p185 protein was suppressed. Very strong beta-gal staining was detected in tumors, and beta-gal activity in small intestine, lung, heart, stomach, liver, and kidney was detected. No beta-gal activity was detected in the tumor and other organs in control mice injected with Ad.E1a(-) or PBS. Adenovirus-type 5 E1a gene can efficaciously inhibit HER-2/neu-overexpressing ovarian cancer, and this promising procedure could greatly benefit ovarian cancer patients with high expression of HER-2/neu.
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PMID:Adenovirus 5 E1a-mediated gene therapy for human ovarian cancer cells in vitro and in vivo. 1128 29

We evaluated the antitumor activity of the Bax gene and green fluorescent protein/tumor necrosis factor-related apoptosis-inducing ligand (GFP/TRAIL) fusion gene driven by the human telomerase reverse transcriptase promoter both separately and combined in the human ovarian cancer lines SKOV3ip and DOV13 and human lung cancer line H1299. In vitro study showed that both TRAIL- and Bax-expressing vectors elicited significant cell killing in H1299 and SKOV3ip cells, but only the GFP/TRAIL gene elicited significant cell killing in DOV13 cells. Combined TRAIL and Bax therapy also produced more profound cell killing in SKOV3ip and H1299 cells, but not DOV13 cells without escalation of the vector doses. To further evaluate the combined effects of Bax and TRAIL, abdominally spread tumors were established in nude mice via intraperitoneal inoculation of SKOV3ip cells followed by that of adenoviral vectors. Tumor growth, ascites formation, survival duration and toxicity were evaluated after treatment. We found that treatment using the Bax- or TRAIL-expressing vector alone significantly suppressed tumor growth and ascites formation, and prolonged animal survival when compared with that of using PBS or a control vector. Combined TRAIL and Bax therapy further prolonged survival significantly when compared with therapy using the TRAIL or Bax gene alone. Transgene expression and apoptosis induction were not detected in normal human ovarian epithelial cells in vitro or normal mouse tissues in vivo after intraperitoneal vector administration. Also, liver toxicity was not detected after either treatment. Thus, combined TRAIL and Bax gene therapy may be useful for treatment of abdominally spread tumors.
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PMID:Combined TRAIL and Bax gene therapy prolonged survival in mice with ovarian cancer xenograft. 1236 3

Localized and sustained delivery of anti-cancer agents to the tumor site has great potential for the treatment of solid tumors. A chitosan-egg phosphatidylcholine (chitosan-ePC) implant system containing PLA-b-PEG/PLA nanoparticles has been developed for the delivery of paclitaxel to treat ovarian cancer. Production of volumes of ascites fluid in the peritoneal cavity is a physical manifestation of ovarian cancer. In vitro release studies of paclitaxel from the implant were conducted in various fluids including human ascites fluid. A strong correlation (r2=0.977) was found between the release of paclitaxel in ascites fluid and PBS containing lysozyme (pH 7.4) at 37 degrees C. The drug release mechanism for this system was proposed based on swelling, degradation and morphology data. In addition, in vitro release of paclitaxel was found to be a good indicator of the in vivo release profile (correlation between release rates: r2=0.965). Release of paclitaxel was found to be sustained over a four-week period following implantation of the chitosan-ePC system into the peritoneal cavity of healthy Balb/C mice. Also, the concentrations of paclitaxel in both plasma and tissues (e.g. liver, kidney and small intestine) were found to be relatively constant.
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PMID:Drug release mechanism of paclitaxel from a chitosan-lipid implant system: effect of swelling, degradation and morphology. 1816 31

Epithelial ovarian cancer (EOC) is the fifth most common cancer in women and is characterized by a low 5-year survival rate. One strategy that can potentially improve the overall survival rate in ovarian cancer is the use of antitumor agents such as ABT-510. ABT-510 is a small mimetic peptide of the naturally occurring antiangiogenic compound thrombospondin-1 and has been shown to significantly reduce tumor growth and burden in preclinical mouse models and in naturally occurring tumors in dogs. This is the first evaluation of ABT-510 in a preclinical model of human EOC. Tumorigenic mouse surface epithelial cells were injected into the bursa of C57BL/6 mice that were treated with either 100 mg/kg ABT-510 or an equivalent amount of PBS. ABT-510 caused a significant reduction in tumor size, ascites fluid volume, and secondary lesion dissemination when compared with PBS controls. Analysis of the vasculature of ABT-510-treated mice revealed vascular remodeling with smaller diameter vessels and lower overall area, increased number of mature vessels, and decreased tissue hypoxia. Tumors of ABT-510-treated mice had a significantly higher proportion of apoptotic tumor cells compared with the PBS-treated controls. Immunoblot analysis of cell lysates revealed a reduction in vascular endothelial growth factor, vascular endothelial growth factor receptor-2, and proliferating cell nuclear antigen protein expression as well as expression of members of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase survival pathways. In vitro, ABT-510 induced tumor cell apoptosis in mouse and human ovarian cancer cells. This study shows ABT-510 as a promising candidate for inhibiting tumor growth and ascites formation in human EOC.
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PMID:ABT-510 induces tumor cell apoptosis and inhibits ovarian tumor growth in an orthotopic, syngeneic model of epithelial ovarian cancer. 1913 14

A 10-fold improvement in the signal-to-noise (S/N) ratio of an optically encoded silica particle-based immunoassay was achieved through incorporating a protein resistant poly(ethylene glycol) (PEG) surface layer and optimizing antibody immobilization conditions. PEG was activated using 2,2,2-trifluoroethanesulfonyl chloride (tresyl) and required a minimum reaction time of 1.5 h. The activated PEG had a reactive half-life of approximately 5 h when stored in acidified dimethyl sulfoxide (DMSO). By increasing the protein incubation time and concentration, a maximum antibody loading on the particle surface of 1.6 x 10(-2) molecules per nm(2) was achieved. The assay S/N ratio was assessed using a multiplexed multicomponent optically encoded species-specific immunoassay. Encoded particles were covalently grafted or nonspecifically coated with either bovine or mouse IgG for the simultaneous detection of complementary anti-IgG "target" or uncomplementary anti-IgG "noise". The versatility and potential as a serum-based assay platform was demonstrated by immobilizing either a polyclonal antibody or an engineered single-chain variable fragment (scFv) capture probe on particles for the detection of the ovarian cancer biomarker, mesothelin (MSLN). The MLSN antigen was spiked into PBS buffer or 50% human serum. Both capture probe orientations, and media conditions showed similar low level detection limits of 5 ng/mL; however, a 40% decrease in maximum signal intensity was observed for assays run in 50% serum.
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PMID:Antifouling surface layers for improved signal-to-noise of particle-based immunoassays. 1992 44


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