Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that anti-GnRH antibodies responses can be induced by synthetic GnRH3-hinge-MVP peptide. In this study, GnRH3-hinge-MVP of conjugation to heat shock protein 65 was used as an adjuvant-free vaccine to assess the therapeutic effects of GnRH immunoneutralisation on tumor development in the mice model. Compared with mice treated with Hsp65 and PBS, mice of the o.t. model receiving in situ treatment GnRH3-hinge-MVP-Hsp65 had significant prolongation of survival and suppression of local tumor growth. Serum levels of both testosterone and luteinizing hormone were reduced by treatment with GnRH3-hinge-MVP-Hsp65 (p<0.05). Further analyses of cell mediated immune responses showed that GnRH3-hinge-MVP-Hsp65 induced stronger lymphocyte proliferative responses and higher levels of IFN-gamma (p<0.001). The conjugation of the recombinant GnRH peptide to Hsp65 could be considered a promising approach for the development of an efficacious vaccine against the prostate cancer.
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PMID:Immunization with a recombinant GnRH vaccine conjugated to heat shock protein 65 inhibits tumor growth in orthotopic prostate cancer mouse model. 1803 58

Ultrasonically induced effects of hematoporphyrin (HPD) on cell damage and membrane protein alteration of S180 isolated tumor cells in vitro were investigated, and the potential mechanisms of sonodynamic therapy (SDT) inhibiting tumor growth were discussed. Tumor cells suspended in air-saturated PBS (pH 7.2) were exposed to ultrasound at 1.8 MHz for up to 180s in the presence and absence of HPD. The viability of cells was determined by a trypan blue exclusion test. To estimate the damage effects of SDT on plasma membrane of tumor cells primarily, membrane integral proteins (EGFR, Ras, Fas, FasL) and cell proliferation associated enzymes (adenylate cyclase and guanylate cyclase) were checked with immunochemical methods. The results indicated that the intensity threshold for ultrasonically induced cell damage at 1.8 MHz was 3 W/cm2. At this condition, the expression of the integral proteins was obviously inhibited and the activity of the enzymes was decreased post ultrasound treatment in the presence of 20 microg/ml HPD. Loss of the membrane proteins and inactivity of AC and GC post SDT was time-dependent. This paper reveals SDT can cause the loss of tumor cell membrane integral proteins and inactivity of the enzymes associated with cell proliferation which might be attributed to a sonochemical activation mechanism. The mechanisms by that tumor growth is inhibited by SDT can be understood as that the growth signaling pathway is partially interdicted and the resistance of tumor cells to the specifically activated immune cells is weakened.
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PMID:Ultrasound exposure in the presence of hematoporphyrin induced loss of membrane integral proteins and inactivity of cell proliferation associated enzymes in sarcoma 180 cells in vitro. 1827 19

Tumors are a mixture of neoplastic and host stromal cells, which establish a microenvironment that contributes to tumor progression. In this study, the contribution of tumor-associated macrophages (TAMs) to tumor growth and metastasis was examined using an orthotopic, immunocompetent murine model of diffuse malignant peritoneal mesothelioma. The expression profile of cytokines and chemokines in solid tumors was consistent with a M2-polarized, TAM-mediated immunosuppressive microenvironment. TAMs were targeted using liposome-encapsulated clodronate (CLIP). Exposure of tumor spheroids to CM-DiI-labeled CLIP in situ confirms targeting of macrophages and not mesothelioma cells. Intraperitoneal (i.p.) delivery of CLIP produced apoptosis in tumor spheroids and solid tumors in contrast to delivery of liposome-encapsulated PBS or PBS. Mice received an i.p. injection of mesothelioma cells with CLIP delivered i.p. every 5 days. This treatment protocol produces a 4-fold reduction in the number of tumors, a 17-fold reduction in the relative tumor burden, and a 5-fold reduction in invasion and metastasis when compared with mice exposed to liposome-encapsulated PBS or PBS. Following transplantation of tumor spheroids and treatment with CLIP, mice showed a 4-fold reduction in the number of tumors and a 15-fold reduction in relative tumor burden. Mice bearing established tumors showed a 2-fold reduction in the number of tumors and relative tumor burden when exposed to half the previous dose of CLIP delivered by repeated i.p. injection. These reductions in tumor burden are statistically significant and identify TAMs as an important host-derived cell that contributes to growth, invasion, and metastasis in diffuse malignant peritoneal mesothelioma.
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PMID:Targeting tumor-associated macrophages in an orthotopic murine model of diffuse malignant mesothelioma. 1837 21

The aim of study was to investigate the synergetic effect of B7-1 and CD40L co-stimulating pathway in the immunotherapy for lymphoma and to explore the effective manner of tumor vaccine for treating lymphoma. The lymphoma cell line A20 cells were inoculated into BALB/c mice as to establish A20-bearing mice model, the B7-1 and CD40L expression vector were alone or in combination directly injected into lymphoma of mice model, the PBS, vector pcDM8 and pcDNA3.1 were selected as controls so as to observe tumor growth. The pathological section and HE staining of tumor tissue were performed to observe the histological characteristics and the cell infiltration of lymphoma, the CCK-8 detection kit was used to analysis the splenic CTL cytotoxicity. The results showed that the intratumor injection of B7-1 and CD40L resulted in reduction of tumor size. Morphological observation of tumor revealed inflammatory cell infiltration in the tumors, massive necrosis and localization of tumor. CCK-8 kit detection indicated significant enhancement of splenic CTL cytotoxicity, the effect of B7-1 combined with CD40L was stronger than that of B7-1 or CD40L alone. It is concluded that B7-1 and CD40L show immunotherapeutic effect on lymphoma, and the effect becomes stronger when they are combined in treating lymphoma. Meanwhile, the intratumor injection may be considered as a safe and effective way for tumor vaccine.
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PMID:[Synergetic effect of B7-1 and CD40L in the immunotherapy for lymphoma]. 1842 56

The aim of this study was to investigate the effect of heat shock protein-70 (HSP-70) on splenocyte proliferation and nitric oxide (NO) production in the BALB/c mice fibrosarcoma tumor model. To do so, HSP-70 was induced in the lysate of heat-shocked tumor cells and WEHI-164 cells (mouse fibrosarcoma cell line) were injected subcutaneously into the right flank of inbred BALB/c mice to establish a tumor model. Three animal bearing tumor groups were applied: the test group; vaccinated with HSP-70 enriched tumor lysate; control group I, vaccinated with tumor lysate only; and control group II, which received PBS. Using immunoblot analysis, an increase of HSP-70 expression was detected in the lysate of heat-shocked cells in comparison with non-heat-shocked cells. The effect of the test lysate on NO production was measured both in vitro and in vivo in the peritoneal macrophages and splenocytes of tumor bearing mice, respectively. The result showed a significant increase in NO production both in vitro by peritoneal macrophages and in vivo after immunization with HSP-70 enriched tumor lysate. In addition, tumor growth was significantly postponed and the proliferation of splenocytes was increased in the test group. Our results indicate that the lysate of heat-shocked tumor cells was more potent than that of non-heat-shocked tumor cells in inducing anti-tumor immunity. Since production of NO by HSP-activated antigen presenting cells (APCs) is likely to affect innate immunity and tumor growth, the probable mechanism of postponing tumor growth would be NO production by innate immune cells. These findings provide a useful therapeutic model for developing novel approaches to cancer treatments.
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PMID:The effect of vaccination with the lysate of heat-shocked tumor cells on nitric oxide production in BALB/c mice with fibrosarcoma tumor. 1845 32

Gene therapy with adenoviral vectors can eliminate neoplasic cells through selective replication and/or through pro-apoptotic, immunogenic or suicide gene expression. However, an adenoviral vector may provide anti-cancerous effects even in the absence of replication or therapeutic gene expression. The present study evaluates the therapeutic effects caused by the administration of an adenoviral vector, alone, in HPV-dependent neoplasias (HPV-N). In vivo trials were carried out in two HPV-N mouse models. One model was immunocompetent and the other was immunodeficient. In both models, the effect of intratumoral administration of saline solution (PBS) was compared with administration of an adenoviral vector that had no replicative capacity or therapeutic gene (Ad-BGal). In the immunocompetent mice, Ad-BGal adenoviral vector administration significantly reduced tumor growth, compared with PBS. No differences were observed in the immunodeficient mice. In conclusion, the present study lends support to the use of adenoviral vectors in HPV-N treatment since they are capable of generating an antitumoral effect in immunocompetent individuals, even in the absence of a therapeutic gene or viral vector replication.
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PMID:Preclinical evaluation of the therapeutic effect of adenoviral vectors in human papillomavirus-dependent neoplasias. 1863 68

We examined the merits of combinatorial hMUC1 vaccination and hNIS radioiodine gene therapy and evaluated its tumoricidal effects in an animal tumor model. CMNF (CT26 expressing hMUC1, hNIS, and firefly luciferase) cells were transplanted into 28 mice, and 4 and 11 days after tumor challenge, tumor-bearing mice were immunized i.m. with pcDNA3.1 or pcDNA-hMUC1 vaccine and subsequently administered PBS or (131)I i.p. [four groups (7 mice per group): pcDNA3.1 + PBS, phMUC1 + PBS, pcDNA3.1 + (131)I, and phMUC1 + (131)I groups]. Thirty-two days after tumor challenge, we rechallenged mice in the pcDNA3.1 + (131)I and phMUC1 + (131)I groups with CMNF cells. Tumor progression and tumor-free mice (%) were monitored by bioluminescence. We investigated hMUC1-associated immune response generated by combination therapy. Marked tumor growth inhibition was observed in the phMUC1 + (131)I group by bioluminescence at 32 days after tumor challenge. Mice in phMUC1 + (131)I group showed complete hMUC1-expressing tumor suppression after tumor rechallenge, whereas mice in the pcDNA3.1 + (131)I group did not. The tumor-free mice (%) were much higher in the phMUC1 + (131)I group than in the other three groups. Levels of hMUC1-associated CD8(+)IFN-gamma(+) T cells were higher in the phMUC1 + (131)I group than in the other three groups. hMUC1-loaded CD11(+) cells in the phMUC1 + (131)I group were found to be most effective at generating hMUC1-associated CD8(+)IFN-gamma(+) T cells. The activities of hMUC1-associated cytotoxic T cells in the phMUC1 + (131)I group were higher than in the other three groups. Our data suggest that phMUC1 + (131)I combination therapy synergistically generates marked tumoricidal effects against established hMUC1-expressing cancers.
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PMID:Synergistic tumoricidal effect of combined hMUC1 vaccination and hNIS radioiodine gene therapy. 1864 34

Precise and objective measurements of tumor response have yet to be standardized in the mouse orthotopic bladder cancer model. In this study, we used image analysis and green fluorescent protein (GFP) to objectively measure tumor size in response to chemotherapy. KU-7 human bladder cancer cells transfected with GFP were intravesically inoculated into 8-week-old female nude mice. Fourteen days after tumor cell inoculation, the mice were assigned into a control (PBS) group or a doxorubicin (conc. 1.0 mg/ml) treatment group and received a single instillation of treatment. Fourteen days after treatment, the bladders were surgically exposed and fluorescent images were captured and later analyzed using image analysis. Bladders were processed for histological examination. Tumor incidence determined by GFP expression and histology was 100 and 80%, respectively, in the doxorubicin treatment group. A 9-fold (histology) vs. 12-fold (GFP expression) difference in tumor regression measured by tumor area (P<0.05) and a 5-fold (histology) vs. 9-fold (GFP expression) difference in tumor regression measured by the percent of tumor area in the bladder (P<0.001) were observed in the doxorubicin treatment group. Our findings suggest that using image analysis provides a precise, sensitive and objective means to measure tumor growth and treatment response in the mouse orthotopic bladder cancer model in lieu of histological methods. Consequently, the number of mice required in an experiment can be reduced since tissue samples are not needed for histology, thus making tissue samples readily available for additional assays in both a labor-effective and cost-effective manner.
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PMID:GFP image analysis in the mouse orthotopic bladder cancer model. 1869 4

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

CXC chemokine receptor 4 (CXCR4) has been implicated in prostate cancer metastasis and this receptor also acts as a coreceptor for HIV-1 120-kDa glycoprotein variant IIIB (gp120-IIIB). The interaction between CXCR4 and gp120-IIIB has been shown to mediate apoptosis of both immune and endothelial cells. In this study, we have examined the effects of gp120-IIIB on hormone-refractory prostate cancer cells (PC3 and DU145) in vitro and tumor growth in vivo. Normal prostatic epithelial (PrEC) and prostate cancer cell lines were treated with gp120-IIIB with or without anti-CXCR4 antibody. Caspase expression was evaluated by real-time PCR and active caspase assays. Apoptosis was determined by flow cytometry. gp120-IIIB treatment correlated with active caspase-3 and -9 expression and apoptosis of prostate cancer cells but not PrEC cells. This effect was significantly inhibited after CXCR4 blockade. PC3 and DU145 tumor-bearing mice received intraperitoneal injections of gp120-IIIB and controls received bovine serum albumin in PBS. PC3 and DU145 tumor sizes were measured over time and excised tumors were evaluated for CD44, CD34, lymphatic endothelial cell marker LYVE-1, active caspase-3, and active caspase-9 expression by immunohistochemistry. The tumor size in mice receiving gp120-IIIB was significantly smaller than compared with tumors in control mice. This regression was associated with significant decreases in CD44, CD34, and LYVE-1 and increases in active caspase-3 and -9 expression. These results suggest that gp120-IIIB induced apoptosis in prostate cancer cells and reduced tumor-associated lymphoendothelial cells.
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PMID:CXCR4-gp120-IIIB interactions induce caspase-mediated apoptosis of prostate cancer cells and inhibit tumor growth. 1913 27


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