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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A major goal of tumor immunotherapy is the induction of tumor-specific T cell responses that are effective in eradicating disseminated tumor, as well as mounting a persistent tumor-protective immunity. We demonstrate here that a genetically engineered fusion protein consisting of human/mouse chimeric anti-ganglioside GD2 antibody and human interleukin-2 is able to induce eradication of established B78-D14 melanoma metastases in immunocompetent syngeneic C57BL/6J mice. This therapeutic effect is mediated by host immune cells, particularly CD8+ T cells and is associated with the induction of a long-lived immunity preventing tumor growth in the majority of animals when challenged up to four months later with B78-D14 cells. This effect was tumor-specific, since no cross-protection against syngeneic, ganglioside GD2+ EL-4 thymoma cells was observed. Furthermore, this tumor-specific protection can be transmitted horizontally to naive, syngeneic SCID mice by passive transfer of CD8+ T lymphocytes derived from immune animals. These results suggest that antibody-targeted delivery of cytokines provides a means to elicit effective immune responses against established tumors in the immunotherapy of neoplastic disease.
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PMID:Long-lived and transferable tumor immunity in mice after targeted interleukin-2 therapy. 898 27

We investigated whether local production of macrophage colony-stimulating factor (M-CSF), responsible for migration and activation of monocytes/macrophages at a tumor growth site, affected the metastatic pattern of lung cancer. For this, highly metastatic human squamous (RERF-LC-AI) or small (H69/VP) cell lung carcinoma cells were transduced with the human M-CSF gene inserted into pRc/CMV-MCSF to establish M-CSF-producing clones (MCSF-AI-9-18, MCSF-AI-9-24, and MCSF-VP-5). M-CSF gene transduction had no effect on the expression of surface antigen or on in vitro proliferation. After s.c. injection into SCID mice, the growth rates of M-CSF-producing cells were slower than those of parent or mock-transduced cells. In the metastatic model in SCID mice depleted of natural killer cells, RERF-LC-AI cells formed metastases mainly in the liver and kidneys, whereas H69/VP cells metastasized mainly to the liver and systemic lymph nodes. The numbers of metastatic colonies of MCSF-AI-9-18 and MCSF-AI-9-24 cells in the liver but not the kidneys were significantly reduced. The development of lymph node metastases of MCSF-VP-5 cells was also less than that of parent or mock-transduced cells. Treatment of SCID mice with anti-human M-CSF antibody resulted in a significant increase in liver metastases of their M-CSF gene transfectants. No significant differences were observed in the distributions in mice or in the in vitro invasive potentials of MCSF-AI-9-18 cells and Neo-AI-3 cells. These findings indicate that the antimetastatic effect of M-CSF may be specific to particular organs, suggesting the influence of heterogeneity of organ microenvironments on the metastasis of lung cancer.
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PMID:Macrophage colony-stimulating factor gene transduction into human lung cancer cells differentially regulates metastasis formations in various organ microenvironments of natural killer cell-depleted SCID mice. 904 61

The success of solid tumor growth and metastasis is dependent upon angiogenesis. Neovascularization within the tumor is regulated, in part, by a dual and opposing system of angiogenic and angiostatic factors. We now report that IP-10, a recently described angiostatic factor, as a potent angiostatic factor that regulates non-small cell lung cancer (NSCLC)-derived angiogenesis, tumor growth, and spontaneous metastasis. We initially found significantly elevated levels of IP-10 in freshly isolated human NSCLC samples of squamous cell carcinoma (SCCA). In contrast, levels of IP-10 were equivalent in either normal lung tissue or adenocarcinoma specimens. The neoplastic cells in specimens of SCCA were the predominant cells that appeared to express IP-10 by immunolocalization. Neutralization of IP-10 in SCCA tumor specimens resulted in enhanced tumor-derived angiogenic activity. Using a model of human NSCLC tumorigenesis in SCID mice, we found that NSCLC tumor growth was inversely correlated with levels of plasma or tumor-associated IP-10. IP-10 in vitro functioned as neither an autocrine growth factor nor as an inhibitor of proliferation of the NSCLC cell lines. Reconstitution of intratumor IP-10 for a period of 8 wk resulted in a significant inhibition of tumor growth, tumor-associated angiogenic activity and neovascularization, and spontaneous lung metastases, whereas, neutralization of IP-10 for 10 wk augmented tumor growth. These findings support the notion that tumor-derived IP-10 is an important endogenous angiostatic factor in NSCLC.
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PMID:Interferon-gamma-inducible protein 10 (IP-10) is an angiostatic factor that inhibits human non-small cell lung cancer (NSCLC) tumorigenesis and spontaneous metastases. 906 58

We have previously shown that four markers spanning the 3p24-p21.3 region, THRB, AP20R, D3S1029, and D3S32, were regularly eliminated from three human chromosome 3 (chr3)/mouse microcell hybrids (MCHs) during tumor growth in SCID mice. In an attempt to narrow down the eliminated region, we have studied 22 new SCID mouse tumors derived from 5 MCH lines carrying human chr3. They were analyzed by fluorescence in situ hybridization (FISH), Southern blotting, and polymerase chain reaction (PCR). MCHs that carried human chr1, chr8, chr13, and chr17 were examined as controls. We could identify a common eliminated region (CER) at 3p21.3, bordered distally by D3S1260 and proximally by D3S643/D3F15S2. Eight of 53 chr3-specific PCR markers, AP20R, D3S966, D3S3559, D3S1029, WI-7947, D3S2354, AFMb362wb9, and D3S32. were localized within the CER. This finding is consistent with the notion that a tumor suppressor gene may be located in this area, as suggested by frequent loss of heterozygosity (LOH) within this region observed in several types of solid tumors.
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PMID:A 3p21.3 region is preferentially eliminated from human chromosome 3/mouse microcell hybrids during tumor growth in SCID mice. 907 73

Prostate cancer mortality results from metastasis to bone and hormone-independent tumor growth. Models to study these progressive changes are lacking. Here we describe the propagation of advanced human prostate cancer by direct transfer of surgical samples from patients into immune-deficient male SCID mice. Explants from six of eight patients formed prostate tumors and two showed unique cytogenetic, biologic and molecular features that were retained through six or more passages. One grew in an androgen-independent fashion, whereas the second formed tumors that regressed following castration then regrew. Micrometastatic disease was detected in the hematopoietic tissues of half of the recipient mice. Thus selected specimens of advanced human prostate cancer can be propagated in SCID mice in a manner that recapitulates the clinical transition from androgen-sensitive to androgen-independent growth, accompanied by micrometastasis.
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PMID:Progression of metastatic human prostate cancer to androgen independence in immunodeficient SCID mice. 909 73

S 16020-2, a new olivacine derivative selected on the basis of its cytotoxicity in vitro and antitumor activity in vivo, was evaluated against the human A549 and the murine Lewis lung tumor models implanted s.c. and i.v. Against Lewis lung carcinoma implanted s.c., S 16020-2 was found to be curative, with an activity and therapeutic index (Ti = 4) similar to that of cyclophosphamide. S 16020-2 administered weekly demonstrated a high therapeutic efficacy against A549 non-small cell lung carcinoma implanted s.c. in nude mice and induced tumor regression at 80 mg/kg. When A549 tumor cells were injected i.v. in SCID mice, experimental metastases rapidly developed and the progressive invasion of the lung tissue by tumor preceded the death of animals. In this model, S 16020-2 administered at 40 mg/kg i.v. following an early (days 8, 18 and 28) or delayed (days 20, 30 and 40) treatment schedule prolonged the survival of tumor-bearing mice with T/C values of 150 and 145%, respectively. Against the i.v. Lewis lung carcinoma, S 16020-2 was also highly active since when administered at 60 mg/kg on days 5, 9 and 13 it totally inhibited tumor growth and cured up to 89% of mice. When administered on days 11, 15 and 19 to animals with established tumors, S 16020-2 was still active but not curative. In the presented studies, S 16020-2 antitumor activity was superior to that of adriamycin and comparable or superior to cyclophosphamide (used as reference compounds). Our results demonstrate the efficacy of S 16020-2 against these highly aggressive and chemoresistant tumor models.
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PMID:Antitumor activity of S 16020-2 in two orthotopic models of lung cancer. 909 33

The presence of heat shock proteins (HSPs) on the surface of tumor cells suggested the possibility of using stress proteins as immunological target for specific immunotoxins (ITs). Flow cytometry analysis showed that U937 cells constitutively express both 28 and 60 kDa HSP in vitro, while the HPC-4 cells only express surface HSPs when grown in vivo, i.e. explanted from SCID mice. Incubation of U937 cells with monoclonal antibodies against 28 or 60 kDa HSP, and then with an immunotoxin consisting of a goat anti-mouse antibody linked to the ribosome inactivating protein Saporin-6 specifically inhibits cell proliferation in vitro. Moreover, an anti-HSP60 immunotoxin prepared by direct linking of the specific monoclonal antibody (MoAb) ML30 to saporin was able to inhibit the proliferation of the U937 line in vitro, and tumor growth in SCID mice bearing the human pancreatic carcinoma line HPC-4 in vivo. Finally, low expression of HSPs on the membrane of peripheral blood mononuclear cells, and their resistance to the toxic effect exerted by anti-HSP immunotoxins, suggest further evaluation of the possible applications of anti-HSP immunotoxins for HSP+tumors.
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PMID:In vitro and in vivo efficacy of heat shock protein specific immunotoxins on human tumor cells. 912 34

The regulation of tumor growth by cytokine-induced alterations in host effector cell recruitment and activation is intimately associated with leukocyte adhesion and angiogenic modulation. In the present study, we have developed a novel tumor model to investigate this complex series of events in response to cytokine administration. Gelatin sponges containing recombinant human basic fibroblast growth factor (rhFGFb) and B16F10 melanoma cells were implanted onto the serosal surface of the left lateral hepatic lobe in syngeneic C57BL/6 mice. The tumor model was characterized by progressive tumor growth initially localized within the sponge and the subsequent development of peritoneal carcinomatosis. Microscopic examination of the sponge matrix revealed well developed tumor-associated vascular structures and areas of endothelial cell activation as evidenced by leukocyte margination. Treatment of mice 3 days after sponge implantation with a therapeutic regimen consisting of pulse recombinant human interleukin-2 (rhIL-2) combined with recombinant murine interleukin-12 (rmIL-12) resulted in a marked hepatic mononuclear infiltrate and inhibition of tumor growth. In contrast to the control group, sponges from mice treated with rhIL-2/rmIL-12 demonstrated an overall lack of cellularity and vascular structure. The regimen of rhIL-2 in combination with rmIL-12 was equally effective against gelatin sponge implants of rhFGFb/B16F10 melanoma in SCID mice treated with anti-asialo-GM1 in the absence of a mononuclear infiltration, suggesting that T, B, and/or NK cells were not the principal mediators of the anti-tumor response in this tumor model. The absence of vascularity within the sponge after treatment suggests that a potential mechanism of rhIL-2/rmIL-12 anti-tumor activity is the inhibition of neovascular growth associated with the establishment of tumor lesions. This potential mechanism could be dissociated from the known activities of these two cytokines to induce the recruitment and activation of host effector cells. Moreover, this model provides a unique opportunity to study the cellular and molecular mechanism(s) underlying both tumor angiogenesis and leukocyte recruitment to metastatic lesions.
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PMID:Regulation of local host-mediated anti-tumor mechanisms by cytokines: direct and indirect effects on leukocyte recruitment and angiogenesis. 913 9

Rhizoxin is an antineoplastic drug that inhibits tubulin polymerization. In this study, we demonstrated that rhizoxin was approximately twice as active in vitro against a human small-cell lung cancer cell line with non-P-glycoprotein-mediated resistance to vindesine, H69/VDS, as against its parental line, H69. Tubulin polymerization in H69/VDS, demonstrated by Western blot analysis, was inhibited markedly by rhizoxin compared with that in H69, in a concentration-dependent manner. A drug-accumulation study showed that the intracellular rhizoxin level in H69/VDS was 15% lower than that in H69, whereas efflux from H69/VDS was enhanced slightly. These results indicate that enhanced inhibition of tubulin polymerization rather than increased intracellular drug concentration accounted for the higher sensitivity of H69/VDS to rhizoxin. In an experiment using mice with severe combined immunodeficiency and inoculated subcutaneously with H69/VDS, in vivo tumor growth was reduced markedly by three intermittent intraperitoneal doses of rhizoxin compared with that in mice inoculated with H69. Three weeks after the last rhizoxin dose, the relative treated/untreated tumor volumes were 0.29 for H69, but only 0.06 for H69/VDS, indicating that H69/VDS regrowth was minimal even after a 3-week treatment-free period. In conclusion, rhizoxin conquers vindesine resistance of a human small-cell lung cancer cell line in vitro and in vivo.
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PMID:In vitro and in vivo modulation by rhizoxin of non-P-glycoprotein-mediated vindesine resistance. 917 91

We demonstrate that from the CaSki cervical cancer cell line, integrated HPV-16 genome was amplified and viral-like particles were generated in an in vivo SCID mouse model. The in vivo tumor growth of several HPV-containing cell lines and 2 HPV-negative cell lines was examined in SCID mice. Tumor growth was noted with the HeLa, CaSki, ME-180, and MS751 cell lines within 2 months after subcutaneous injection. Squamous differentiation was appreciated in focal areas of tumors derived from CaSki and ME-180. In the CaSki tumors, DNA in situ hybridization revealed homogeneous staining of nuclei in some cells in the differentiated areas, suggesting HPV genomic amplification. In contrast, punctate or speckled patterns of hybridization were identified in the less differentiated areas, suggesting continued integration of the HPV genome. Immunocytochemical staining for HPV-16 L1 capsid protein showed it to be concentrated in cells from the differentiated areas, correlating with the results of hybridization. Electron microscopic studies revealed 50 nm uniform particles, consistent with HPV viral-like particles, in the nuclei of some cells in well-differentiated areas. Furthermore, Southern transfer and hybridization of the Hirt's extract from the CaSki tumors was positive for HPV-16 DNA, indicating non-integrated, low molecular weight HPV-16 DNA. Our results show HPV genomic amplification of integrated viral DNA and generation of HPV viral-like particles in CaSki cancer cells in SCID mice and that viral DNA amplification and the formation of viral-like particles are coupled to cellular differentiation. This experimental model provides a potential system for studying the molecular pathogenesis of HPV infections.
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PMID:Demonstration of human papillomavirus (HPV) genomic amplification and viral-like particles from CaSki cell line in SCID mice. 918 53


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