Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

TAG72 is a well-characterized, human tumor-associated antigen present in > 85% of human colonic cancers. In this study, we established an animal model of hepatic metastases of human colonic carcinoma. The high-mucin variant cell line, designated HM7, was derived from the human colonic carcinoma cell line LS174T. Following intrasplenic injection, HM7 was able to induce much greater hepatic metastases in SCID mice compared to its parental cell line LS174T. Numerous hepatic metastases were evident 18 days subsequent to the intrasplenic injection of tumor cells. Using the chimeric anti-TAG72 antibody ccM4, immunohistochemistry demonstrated strong expressions of the TAG72 antigen in these metastases. Our biodistribution and imaging data also showed that the radiolabelled ccM4 antibody was able to localize hepatic metastases in the SCID mice. Based upon these findings, w anticipate that the herein described SCID mouse model will prove most useful in studying hepatic metastases of human colonic carcinoma by using anti-TAG72 therapeutic immunoreagents.
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PMID:Immunolocalization of hepatic metastases of human colonic cancer by chimeric anti-TAG72 antibody in SCID mice. 774 73

Malignant cells possess a high degree of proteolytic activity in which the plasminogen activator system plays an important role. An increased expression of urokinase type plasminogen activator (uPA) is of significance for degradation of the extracellular tumor matrix, facilitating invasiveness and growth. Inhibition of the active site of uPA makes it possible to evaluate the significance of uPA in tumor growth. We report here experiments on a uPA-producing human prostate xenograft (DU 145) using a competitive inhibitor of uPA, p-aminobenzamidine. In vitro experiments with DU 145 cells showed that p-aminobenzamidine caused a dose-dependent inhibition of uPA activity. DU 145 cells were inoculated s.c. in SCID mice and, once tumors were established, treatment with p-aminobenzamidine added to drinking water was started and lasted for 23 days. Mice receiving 250 mg/kg/day of p-aminobenzamidine showed a clear decrease in tumor-growth rate compared to the non-treated mice, resulting in 64% lower final tumor weight. In addition, uPA-antigen levels in the membrane fractions of DU 145 tumors from p-aminobenzamidine-treated mice were found to be decreased by 59%. We also show that p-aminobenzamidine has an anti-proliferative effect in cell culture at low cell number, correlating with a dose-dependent decrease in uPA production. In conclusion, we show that a low-molecular-weight uPA-inhibitor, p-aminobenzamidine, has a growth-inhibitory effect on a solid uPA-producing tumor.
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PMID:The urokinase inhibitor p-aminobenzamidine inhibits growth of a human prostate tumor in SCID mice. 775 60

WERI-Rb27 human retinoblastoma cells were reconstituted with an intact RB gene by retrovirus-mediated gene transfer, in order to study the phenotypic effects of the protein in vitro and in vivo. Extensive morphological changes were observed, dominated by the formation of multinucleated giant cells. Six weeks after retroviral infection, the giant cells began to die and small cells emerged, resembling the parental non-reconstituted line. They expressed RB and continued to grow, although they showed an increased sensitivity to serum starvation. The original RB-negative cells grew progressively after subcutaneous inoculation into SCID mice, whereas the reconstituted cells failed to grow. RB-positive cells grew progressively in the corpus vitreum of the eye and in the brain, however. The RB-reconstituted cells grew more slowly and were less invasive than the parental cells and cells infected with a firefly luciferase (LUX) gene carrying retrovirus, used as controls. RB-reconstituted cells re-explanted from the intraocular and intracranial tumors continued to express full-length RB protein. RBeye2, an RB-positive cell line established from an eye tumor, was still unable to grow subcutaneously. The reduced tumorigenicity of the RB-reconstituted cells in the subcutaneous space may be due to the influence of locally acting growth-controlling signals or the absence of microenvironment-specific trophic factors. Alternatively, it may reflect the action of residual immune effectors in the SCID mice. If this is the case, these would have to be more effective at the subcutaneous site than in the eye or brain.
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PMID:RB-reconstituted human retinoblastoma cells form RB-positive intraocular and intracerebral but not subcutaneous tumors in SCID mice. 776 42

This study investigates a new approach to adoptive therapy of glioblastoma using as antitumor effector a potent major histocompatibility complex nonrestricted killer clone (TALL-104) established from a patient with acute T-lymphoblastic leukemia. The human glioblastoma cell line U-87 MG could be successfully engrafted in mice with severe combined immunodeficiency using the i.p., intracerebral, and s.c. routes. The latter model was elected to evaluate therapy based on its high reproducibility. Tumor growth in mice engrafted s.c. was proportionally associated with splenomegaly and leukocytosis. Multiple transfers of lethally irradiated (non-proliferating) TALL-104 cells at the tumor site resulted in about 50-70% inhibition of tumor growth as compared to untreated mice, with concomitant reduction of splenomegaly and leukocytosis. The antitumor effects were inversely proportional to the size of the tumor at initiation of therapy, 90-100% inhibition occurring in severe combined immunodeficiency mice treated from the day of U-87 MG challenge. Neither splenomegaly nor leukocytosis developed in animals in which tumor growth was completely blocked. Stimulation of TALL-104 cells with either interleukin 2 or interleukin 12 prior to irradiation and adoptive transfer increased the antitumor efficacy of the killer cells to about the same extent. The potential usefulness of irradiated TALL-104 cells in adjuvant therapy against glioblastomas and other well-localized tumors is discussed.
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PMID:Treatment of experimental glioblastoma with a human major histocompatibility complex nonrestricted cytotoxic T cell line. 780 48

In vivo screening models of a cisplatin (CDDP)-resistant human small-cell lung cancer cell (SCLC) line, H69/CDDP, and a non-small-cell lung cancer cell (NSCLC) line, PC-14/CDDP, were evaluated. The transplantability of the tumor xenografts to SCID mice was more than 90%. Tumor xenografts of H69/CDDP and PC-14/CDDP showed CDDP resistance during in vivo treatment. The novel anticancer agent 254-S showed only a partial effect on the growth of H69/CDDP and PC-14/CDDP while ormaplatin showed no cross resistance to CDDP. The in vivo results correlated well with the results of the in vitro MTT assay. In this in vivo sensitivity test, H69/CDDP and PC-14/CDDP were more sensitive to ormaplatin than its parental cell lines. In vivo sensitivity testing using SCID mice bearing transplanted CDDP-resistant tumors was shown to be useful for evaluating the effects of new anti-cancer drugs, especially those that might overcome CDDP resistance.
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PMID:In vivo screening models of cisplatin-resistant human lung cancer cell lines using SCID mice. 780 77

Despite advances in conventional therapy, many lives continue to be lost to common forms of B-cell cancers, including leukemias, lymphomas and multiple myeloma. We propose a novel approach to therapy of such cancers using controlled expression of a diphtheria toxin gene (DT-A) to kill malignant cells. We have previously demonstrated selective killing of various cell types, in vitro and in vivo, by cell-specific, transcriptionally controlled expression of this gene. Organ-specific ablation in otherwise healthy transgenic mice has convincingly demonstrated the exquisite specificity achievable by this technique. In the studies now described, DT-A was delivered in vitro and in vivo using a novel gene delivery system employing DNA physically attached to the exterior of adenovirus. After demonstrating the efficacy of gene delivery to Epstein-Barr virus transformed human B-cells in vitro, in vivo work was performed using a SCID mouse model for B-cell lymphoma, in which protection against tumor was observed. The concepts of tissue-regulated toxin gene therapy, and this novel adenovirus gene delivery system are discussed.
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PMID:Gene therapy for B-cell lymphoma in a SCID mouse model using an immunoglobulin-regulated diphtheria toxin gene delivered by a novel adenovirus-polylysine conjugate. 781 62

EBV has been associated with several malignancies in humans. EBV can also infect marmoset B lymphocytes, which, as opposed to human B cells, are permissive for lytic Epstein-Barr viral replication. Mice with a severe combined immunodeficiency phenotype (SCID mice) are extremely susceptible to EBV-induced lymphomagenesis when inoculated with EBV-infected lymphocytes. We inoculated SCID mice with human and marmoset lymphoblastoid cells infected with the same EBV isolates. The marmoset cells never gave rise to lymphomas, even after the administration of acyclovir or an anti-natural killer cell antibody and observation periods of up to 16 wk. In contrast, the human lymphoblastoid cells nearly always gave rise to lymphomas within 8 wk. Furthermore, human lymphoblastoid cells genetically engineered to permit lytic EBV replication also readily formed tumors in the SCID mouse. Thus, in this system, it is the cellular milieu that is crucial in determining whether a given lymphoblastoid cell will give rise to a tumor, not the EBV isolate harbored by the cell or whether the virus is permitted to undergo lytic replication.
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PMID:Epstein-Barr virus-infected marmoset cells do not form lymphomas in mice with severe combined immunodeficiency. 781 20

A metastatic human melanoma cell line that produces urokinase-type plasminogen activator was stably transfected with cDNA encoding human plasminogen activator inhibitor 2 (PAI-2). Transfected clones expressed PAI-2 at levels two to nine times higher than both the parental cell line and mock transfectants, as detected by ELISA of cell lysates and conditioned medium. The clone with the highest PAI-2 expression exhibited complete inhibition of soluble and cell-surface-bound plasminogen activator activity. The level of PAI-2 overexpression in these clonal cell lines correlated positively with the inhibition of their ability to degrade extracellular matrix in vitro. Parental, mock-transfected, and PAI-2-transfected cell lines produced rapidly growing tumors when injected s.c. into the skin of mice with severe combined immunodeficiency. The tumors producing the highest levels of PAI-2 were surrounded by a dense tumor capsule. Both parental cells and mock-transfected cells invariably metastasized from s.c. tumors to lymph nodes and lungs of mice. PAI-2-transfected cell lines produced significantly less or no metastases. Taken together, these data indicate a critical role for plasminogen activator activity in melanoma invasion and metastasis.
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PMID:Overexpression of plasminogen activator inhibitor 2 in human melanoma cells inhibits spontaneous metastasis in scid/scid mice. 781 18

Magainin peptides and model amphipathic peptides exhibit antibiotic activity and are also cytolytic for transformed human cells. Here we demonstrate in vitro that MSI-511 (an all-D amino-acid model magainin peptide) and MSI-130 (a margainin analogue) were more lytic for 17 human melanomas than for normal melanocytes. Melanomas established s.c. in athymic nude mice and then injected once with the peptide MSI-511 completely disappeared in 6 out of 9 animals, whereas a control peptide had no effect. Murine skin at the tumor injection site was initially affected, but healed within 2 weeks with minimal scarring. Similarly, accelerated healing was seen in human skin grafted to SCID mice and injected with MSI-511. Our results indicate that lytic magainin peptides can be used for local tumor therapy with minimal long-term damage to normal tissues.
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PMID:Experimental local therapy of human melanoma with lytic magainin peptides. 782 29

Recent studies have suggested that ICAM-1 (CD54) is involved in the pathogenesis of human multiple myeloma. A monoclonal antihuman CD54 antibody has been generated by immunizing BALB/c mice with human myeloma cell lines. SCID mice injected with human ARH-77 myeloma cells develop disseminated myeloma which is similar in several respects to multiple myeloma in humans. The mice have monoclonal gammopathy and succumb to hind leg paralysis caused by infiltration of tumor cells into the thoracolumbar vertebrae, resulting in compression of the spinal cord. In the absence of treatment, the mean paralysis time of the SCID/ARH-77 mice is 29 days. When the SCID/ARH-77 mice received four consecutive daily i.v. injections of anti-CD54 mAb commencing 1 day after tumor inoculation, they survived for 150 days, at which time the experiment was terminated. Histopathological analyses indicated that prior to death all control SCID/ARH-77 mice had myeloma cells in the vertebrae and skull. At this time, the anti-CD54-treated mice had no evidence of tumor. High levels of human immunoglobulin were detected in the sera of control, but not treated mice. F(ab')2 fragments of the anti-CD54 antibody also had similar, albeit, slightly less antitumor activity in vivo, suggesting that antibody effector function may account for some, but not all the antitumor activity of anti-CD54. In vitro studies indicate that anti-CD54 does not inhibit homotypic adhesion, the binding of myeloma cells to murine bone marrow stromal cells, or cell proliferation. By exclusion, we propose that the CD54-mediated homing of these ARH-77 cells to certain anatomical sites is crucial for their growth in vivo.
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PMID:Anti-CD54 (ICAM-1) has antitumor activity in SCID mice with human myeloma cells. 783 32


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