Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0031154 (peritonitis)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cell suspensions of chemically induced tumors (rhabdomyosarcoma) were transplanted into the peritoneal cavities of Lewis rats. In normal animals, the greater omentum was the main site of tumor growth, and transdiaphragmatic metastases to regional lymph nodes in the mediastinum were few and small. In animals during the healing phase of a chemical peritonitis, the greater omentum was fibrotic, shrunken, and inactivated. The loss of the scavenging function of the omentum was associated with wide dissemination of the tumor in the peritoneal cavity and increased access of the tumor to the lymphatic stomata on the peritoneal surface of the diaphragm. Number and size of transdiaphragmatic metastases in draining lymph nodes were greatly increased in this postinflammatory state.
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PMID:Lymphatic metastases from the peritoneal cavity are increased in the postinflammatory state. 222 16

We had demonstrated that the NK cell mediated cytotoxicity of murine spleen cells could be augmented by in vivo priming and subsequent in vitro challenge with a streptococcal preparation OK432, and the cell surface phenotype of induced killer cells was Thy-1+, asialo GM1+, suggesting that the activated cells were of NK lineage (OK-NK cell). We had also clarified that IL-2 played a major role in inducing the OK-NK cells via the production of IFN-gamma. In this study, we examined the effect of adoptive transfer of OK-NK cells on syngeneic tumors in mice. Mice were implanted with SP2 myeloma cells intraperitoneally (i.p.), or C26 colon adenocarcinoma cells subcutaneously to make the models of peritonitis carcinomatosa or solid tumor, and the OK-NK cells were transferred i.p. or intratumorally, adoptively. By the adoptive transfer of OK-NK cells, 92% of mice bearing SP2-tumor had be cured. The tumor growth of C26-solid tumor was inhibited, and the survival rate of mice bearing C26-tumor was significantly increased. The intratumoral remnants of 125I-labelled OK-NK cells were 61, 27 and 8% at 4, 12 and 36h after intratumoral transfer, respectively. By multiple transfer of OK-NK cells, the antitumor effect was more effectively augmented than that of a single transfer. Results in this study suggested that OK-NK cells could be useful for the therapy of cancer patients.
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PMID:Successful adoptive immunotherapy with OK432-inducible activated natural killer cells in tumor-bearing mice. 240 Jun 28

We had demonstrated that the NK cell mediated cytotoxicity of murine spleen cells could be augmented by in vivo prime and subsequent in vitro challenge with the streptococcal preparation OK432, and the cell surface phenotype of induced killer cells was Thy 1+, asialo GM1+, suggesting the activated NK cells (OK-NK cell). The culture supernatants of spleen cells with OK432 possessed the activity of IL-2 and IFN-gamma, and the IL-2 played a major role to induce the OK-NK cells via the production of IFN-gamma. In this study, we examined the effect of adoptive transfer of OK-NK cells on tumor-bearing mice. The mice were implanted SP2 myeloma cells intraperitoneally (i.p.), or C26 colon adenocarcinoma cells subcutaneously (s.c.) to make the models of peritonitis carcinomatosa or solid tumor, and the OK-NK cells were transferred i.p. or i.t., adoptively. By the adoptive transfer of OK-NK cells, the 92% of mice bearing SP2-tumor had be cured. The tumor growth of C26-solid tumor was inhibited, and the survival rate of mice bearing C26-tumor was increased, significantly. The intratumoral remnants of 125I-labelled OK-NK cells were 61.27 and 8% after intratumoral transfer, respectively. By multiple transfer of OK-NK cells the anti-tumor effect was more augmented than that of a single transfer. Thus we recognized the anti-tumor effect of adoptive transfer of OK-NK cells on tumor-bearing mice, and suggested that OK-NK cells could be useful for the therapy of cancer patients.
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PMID:[Successful adoptive immunotherapy with OK432-inducible activated natural killer cells on tumor-bearing mice]. 261 90

In humans, treatment of malignant ascites with bolus TNF leads to resolution of the ascites. In an experimental model NMRI nude mice were inoculated intraperitoneally with human NIH-OVCAR3 adenocarcinoma cells, resulting in production of ascites and intraperitoneal tumor growth. Ascites formation and tumor growth after IP injection of recombinant human TNF was determined. Depending on the treatment schedule, a dual effect of TNF on the development of ascites was seen. Doses of TNF (1-10 micrograms/g) given once per week completely prevented ascites production, whereas the same doses of TNF given on a daily schedule induced enhanced ascites formation in an inverse TNF dose relationship. The area of tumor cell-covered peritoneal lining corresponded to these findings, indicating a correlation of tumor mass with ascites production. In an attempt to prevent renewal of ascites after drainage, neither inhibition nor enhancement in ascites production was seen when TNF was given five times per week. However, doses of 10 micrograms/g of TNF once per week led to almost complete inhibition of ascites reappearance. Histological examination of animals that received repeated TNF treatment demonstrated chronic peritonitis with strong stromal proliferation, angiogenesis, and increased adhesion of tumor cells to the peritoneum.
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PMID:Tumor necrosis factor effects on ascites formation in an experimental tumor model. 872 81

Recent studies suggest that drug induced apoptosis relates to the sensitivity. p53 gene, which has a pivotal role in inducing apoptosis, frequently mutates in ovarian cancer. Therefore, p53 gene status and chemosensitivity in epithelial ovarian cancer is discussed. Nonresponders to chemotherapy had mutations of the p53 gene more frequently (83% for nonresponders vs. 16% for responders) in patients with epithelial ovarian cancer undergoing platinum-base chemotherapy. Apoptotic index was significantly greater in tumors with wild-type p53 gene than those without the gene. p53 gene transduction markedly enhanced the sensitivity to cisplatin (CDDP) and CDDP-induced apoptosis, but did not affect the sensitivity to paclitaxel (PTX) nor PTX-induced apoptosis in ovarian cancer cells without p53 gene. The combination treatment with a recombinant adenovirus carrying a wild-type p53 gene (AxCAp53) and CDDP significantly suppressed tumor growth of ovarian cancer cells with and without p53 gene, compared with a single treatment of either AxCAp53 or CDDP in ovarian cancer xenograft. Apoptotic index was significantly higher and proliferating cell nuclear antigen labeling index was relatively lower in an ovarian cancer xenograft without p53 gene receiving combination treatment, compared with a single treatment of either CDDP or AxCAp53, suggesting that the transduction of p53 gene induces apoptosis, but does not enhance the DNA repair system. A significant survival advantage was observed in the combination treatment compared with other treatments in carcinoma peritonitis models. In conclusion, p53 gene status contributes the sensitivity to CDDP in ovarian cancer. Additionally, combination treatment of p53 gene transduction and CDDP may be an effective therapeutic modality for ovarian cancer without wild-type p53 gene.
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PMID:p53 gene status and chemosensitivity in ovarian cancer. 1177 36

In a previous study, we demonstrated that calponin h1 suppressed tumor growth of transformed cells and that the peritonitis carcinomatosa induced by mouse B16-F10 melanoma (F10) cells was more extensive in calponin h1-deficient (CN(-/-)) mice with fragility of mesothelial (MS) cells than in their calponin h1-wild (CN(+/+)) counterparts. In our study, we assessed the therapeutic effect of calponin h1 on peritoneal dissemination. F10 cells were overlaid on the cultured CN(+/+) or CN(-/-) MS cells and the effect of calponin h1 on retraction of MS cells was evaluated. Then, an adenoviral vector with the calponin h1 gene (AdGFP-CN) inserted was constructed and was applied to CN(-/-) MS cells or CN(-/-) mouse peritoneum to investigate its suppressive effect on the peritoneal dissemination caused by F10 cells. Greater retraction and invasion of F10 cells were observed in CN(-/-) MS than in CN(+/+) cells in vitro, while down-regulation of calponin h1 was observed in CN(+/+) MS cells prior to the invasion of F10 cells. Infecting CN(-/-) MS cells with AdGFP-CN prevented their retraction and the invasion of F10 cells. Peritoneal dissemination was prominently suppressed in AdGFP-CN-infected CN(-/-) mice, and the survival of those mice was significantly prolonged. Thus, calponin h1 functioned to protect host MS cells from the invasion of F10 cells.
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PMID:Suppression of peritoneal dissemination through protecting mesothelial cells from retraction by cancer cells. 1452 Jun 92

The number of published studies on peritoneal dissemination of scirrhous gastric carcinoma is very small as a result of the unavailability of highly reproducible animal models. Orthotopic implantation of HSC-44PE and HSC-58 (scirrhous gastric carcinoma-derived cell lines) cells into nude mice led to dissemination of the tumor cells to the greater omentum, mesenterium, peritoneum and so on, and caused ascites in a small number of animals. Cycles of isolation of the ascitic tumor cells and orthotopic inoculation of these cells were repeated in turn to animals. This was to isolate highly metastatic cell lines with a strong capability of inducing the formation of ascites (44As3 from HSC-44PE; 58As1 and 58As9 from HSC-58). All three cell lines induced tumor formation at the site of orthotopic injection, and caused fatal cancerous peritonitis and bloody ascites in 90-100% of the animals approximately 3-5 weeks after the inoculation. When the parent cells were implanted, the animals became moribund in approximately 12-18 weeks, however, none of the animals developed ascites. Complementary DNA microarray and immunohistochemical analyses revealed differences in the expression levels of genes coding for the matrix proteinase, cell adhesion, motility, angiogenesis and proliferation between the highly metastatic- and parent-cell lines. The usefulness of this model for the evaluation of drugs was assessed by analyzing the stability of the metastatic potential of the cells and the reproducibility. Animals intravenously treated with CPT-11 and GEM showed suppressed tumor growth and significantly prolonged survival. The metastatic cell lines and the in vivo model established in the present study are expected to serve as a model of cancerous peritonitis developing from primary lesions, and as a useful means of clarifying the pathophysiology of peritoneal dissemination of scirrhous gastric carcinoma and the development of drugs for its treatment.
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PMID:Development and biological analysis of peritoneal metastasis mouse models for human scirrhous stomach cancer. 1595 54

In order to facilitate the discovery and investigation of anti-cancer therapeutics under physiological conditions, we have engineered the ovarian cancer cell line, HM-1/luc, in mice. This cell stably expresses firefly luciferase and produces light that can be detected using an in vivo imaging system (IVIS). Parental HM-1 cells cause severe carcinomatous peritonitis to B6C3F1 mice, but not to C57BL6 mice. Established HM-1/luc cells showed pathologically similar findings to HM-1 cells. HM-1/luc cells were injected into the peritoneal cavity of B6C3F1 mice and IVIS 2000 was conducted weekly after inoculation to monitor intra-peritoneal tumor growth. The mice were divided into three groups: non-CDDP-treated (control) and CDDP-treated (0.2 and 0.4 mg). A disease-suppressive effect of the CDDP was reflected by the significantly prolonged survival of the CDDP-treated mice (control 23 +/- 1.9 days, CDDP 0.2 mg 29.6 +/- 2.9 days; p < 0.05); the total photon and area of flux were decreased. The optical imaging of intraperitoneal tumors via in vivo bioluminescence is effective for noninvasive monitoring and semi-quantitative analysis. Our syngeneic mouse model has the relevant clinical features of ovarian cancer, which makes it a useful model for developing new ovarian cancer therapies.
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PMID:Generation of a syngeneic mouse model to study the intraperitoneal dissemination of ovarian cancer with in vivo luciferase imaging. 1971 87

Sunitinib and sorafenib are broad-spectrum tyrosine kinase inhibitors (TKI) targeting, for example, VEGF1-3, PDGFRb, RET, FLT3, CD117 (c-KIT) and CSF-1R cell membrane receptors thus suppressing tumor angiogenesis and cancer cell growth. Recently it has been suggested that the kinases targeted by Sunitinib and/or Sorafenib regulate leukocyte transmigration, which might in part be responsible for the often-observed reduction in tumor-associated myeloid derived suppressor cells and regulatory T cells. The aim of the current study is to determine whether sunitinib or sorafenib inhibit leukocyte extravasation. Sunitinib, sorafenib, or vehicle treated animals did not show any difference in leukocyte trafficking either in peritonitis or in vivo homing experiments, although sunitinib treatment effectively inhibited growth of B16 melanoma tumors in WT, SCID and SCID beige mice. Inhibition of tumor growth was associated with an increased number of infiltrating CD11b+ cells in the tumor, while the numbers of CD8, Gr-1 and F4/80 expressing cells were unchanged. In conclusion, the findings suggest that despite multiple targets with a potential role in leukocyte extravasation, neither sunitinib nor sorafenib effectively inhibits this process in vivo. Thus, the observed specific effect on CD11b cells among tumor infiltrating leukocytes is most likely an indirect effect.
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PMID:Leukocyte trafficking is not affected by multikinase inhibitors sunitinib or sorafenib in mice. 2745 81

Hepatocellular carcinoma (HCC) is a common malignant tumor in the digestive tract with limited therapeutic choices. Although sorafenib, an orally administered multikinase inhibitor, has produced survival benefits for patients with advanced HCC, favorable clinical outcomes are limited due to individual differences and resistance. The application of immunotherapy, a promising approach for HCC is urgently needed. Macrophage infiltration, mediated by the CCL2/CCR2 axis, is a potential immunotherapeutic target. Here, we report that a natural product from Abies georgei, named 747 and related in structure to kaempferol, exhibits sensitivity and selectivity as a CCR2 antagonist. The specificity of 747 on CCR2 was demonstrated via calcium flux, the binding domain of CCR2 was identified in an extracellular loop by chimera binding assay, and in vivo antagonistic activity of 747 was confirmed through a thioglycollate-induced peritonitis model. In animals, 747 elevated the number of CD8+ T cells in tumors via blocking tumor-infiltrating macrophage-mediated immunosuppression and inhibited orthotopic and subcutaneous tumor growth in a CD8+ T cell-dependent manner. Further, 747 enhanced the therapeutic efficacy of low-dose sorafenib without obvious toxicity, through elevating the numbers of intra-tumoral CD8+ T cells and increasing death of tumor cells. Thus, we have discovered a natural CCR2 antagonist and have provided a new perspective on development of this antagonist for treatment of HCC. In mouse models of HCC, 747 enhanced the tumor immunosuppressive microenvironment and potentiated the therapeutic effect of sorafenib, indicating that the combination of an immunomodulator with a chemotherapeutic drug could be a new approach for treating HCC.
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PMID:A Natural CCR2 Antagonist Relieves Tumor-associated Macrophage-mediated Immunosuppression to Produce a Therapeutic Effect for Liver Cancer. 2875 4


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