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)

Microcell hybrid lines of A9 mouse fibrosarcoma containing complete or partially deleted human chromosomes 3 (chr. 3) were inoculated into SCID mice. Cell lines derived from the tumors were examined by fluorescent in situ hybridization for the status of the transferred human chromosome and by PCR for marker loss. The SCID tumors arising after the inoculation of 10(5) cells were passaged serially in vivo and regularly showed loss of four markers; D3S1029 (3p21.3-21.2), AP20R (3p22-21.3, D3S32 (3p21.3-p21.2), and THRB (3p24). This regularly deleted region is bordered by markers GNA12 (3p21.1-p21.3) and VHL (3p25) that were maintained in a fraction of tumors. Fragments derived from the long arm of chromosome 3 and corresponding markers in the 3q26-q28 region were retained in all tumors. Our findings may be related to the postulated presence of tumor suppressor genes in the 3p24-p21 region as indicated by the frequent deletion of this region in renal and small cell lung carcinomas and other solid tumors. The technically cumbersome identification of suppressor genes may be supplemented by an "elimination test" based on analogous principles.
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PMID:Nonrandom loss of human chromosome 3 fragments from mouse-human microcell hybrids following progressive growth in SCID mice. 753 27

The alpha 5 beta 1 integrin (CD49e/CD29), a heterodimeric membrane protein, is the "classical" fibronectin receptor on many cell types. During B-cell ontogeny, expression of the alpha 5-subunit is developmentally regulated. The alpha 5 beta 1 is decisive for migration on fibronectin substrate and very likely cooperates with other adhesion molecules in transvascular trafficking. To test whether alpha 5 beta 1 influences local growth vs. disseminative spread of neoplastic B-cells in vivo, human B-cell lines mimicking different maturational stages were transferred s.c. into severe combined immunodeficiency (SCID) mice and examined for alpha 5 beta 1 expression and for adherence on fibronectin substrate in vitro and ex vivo. All cell lines were locally tumorigenic. Dissemination was observed in all animals carrying Nalm-6 tumors, in one animal with a BL 60 and in 2 mice carrying a Raji tumor. By contrast, Daudi, BJAB and U266 tumors did not disseminate. As evidenced by immunohistochemistry and flow cytometry, all lines and their tumors were to various extents beta 1-positive but showed considerable differences in alpha 5 expression. The functional surface expression of alpha 5 beta 1 correlated with fibronectin adherence of the lines. Daudi expressed alpha 5 beta 1 in a non-functional configuration which was rendered functional only upon applying high concentrations of Mg++ and Mn++. B-cell lines functionally expressing alpha 5 beta 1 at high or moderate levels disseminated in SCID mice while alpha 5-negative lines and Daudi did not. These results support the conclusion drawn from an earlier in situ analysis of human B-cell lymphomas/leukemias that the alpha 5 beta 1 integrin contributes to the disseminative phenotype of malignant B cells.
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PMID:The capacity of human malignant B-lymphocytes to disseminate in SCID mice is correlated with functional expression of the fibronectin receptor alpha 5 beta 1 (CD49e/CD29). 753 50

Tumor dormancy can be induced in a murine B cell lymphoma (BCL1) by immunizing BALB/c mice with the tumor immunoglobulin (Ig) before tumor cell challenge. In this report, we have investigated the immunological and cellular mechanisms underlying the induction of dormancy. BCL1 tumor cells were injected into SCID mice passively immunized with antibody against different epitopes on IgM or IgD with or without idiotype (Id)-immune T lymphocytes. Results indicate that antibody to IgM is sufficient to induce a state of dormancy. Antibodies against other cell surface molecules including IgD and CD44 (Pgp1) had no effect on tumor growth. Id-immune T cells by themselves also had no effect on tumor growth in SCID mice. However, simultaneous transfer of anti-Id and Id-immune T cells enhanced both the induction and duration of the dormant state. In vitro studies indicated that antibody to IgM induced apoptosis within several hours and cell cycle arrest by 24 h. Hyper cross-linking increased apoptosis. The Fc gamma RII receptor played little or no role in the negative signaling. Antibodies that did not negatively signal in vitro did not induce dormancy in vivo. The results suggest that anti-IgM plays a decisive role in inducing tumor dormancy to BCL1 by acting as an agonist of IgM-mediated signal transduction pathways.
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PMID:Tumor dormancy and cell signaling. II. Antibody as an agonist in inducing dormancy of a B cell lymphoma in SCID mice. 753 41

Purification of human hematopoietic stem cells (HSC) may be useful clinically for preparation of tumor-free grafts to be used for autologous transplantation and as targets for gene therapy. To analyze the phenotype of the human HSC, assays were used that measure the unique properties of stem cells, i.e., their long-term repopulating ability and their multilineage potential. These assays include: (1) an in vitro long-term hematopoietic culture system, using the murine bone marrow stromal cell line SyS1, which supports both B lymphopoiesis and myelopoiesis; (2) fetal human bone grafts implanted in SCID-hu mice, in which maintenance of CD34+ cells and B and myeloid differentiative capacity of candidate stem cell populations may be measured; (3) fetal human thymus grafts in SCID-hu mice, which allow the analysis of in vivo T-cell potential of a candidate stem cell population. Stem cells in adult bone marrow (ABM) or cytokine-mobilized peripheral blood (MPB) are thought to express CD34 but lack expression of markers indicating lineage commitment. This CD34+ Lineage- (Lin-) subpopulation has been isolated by fluorescence-activated cell sorting and tested for activity in the assays described here. CD34+ Lin- cells from both ABM and MPB demonstrated long-term engraftment in the SCID-hu bone model. This CD34+ Lin- population can be subfractionated further using an antibody to Thy-1. The Thy-1+ subset of CD34+Lin- cells is enriched for both long-term culture-initiating cells (LTC-1C) and has the ability to engraft in vivo.
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PMID:Analysis of human hematopoietic stem cell populations. 753 40

The interaction between B7-1 and CD28 provides costimulatory signals not only for T cells but also for natural killer (NK) cells. Highly metastatic mouse T lymphoma cells (BW-Li) can escape from NK cell-mediated killing by expressing H-2Dk molecules that negatively regulate NK lytic activity. We have analyzed whether B7-1:CD28 overrules the MHC class I-mediated inactivation of NK cells by transfecting BW-Li with the gene coding for B7-1. Expression of B7-1 rendered BW-Li cells sensitive toward NK cells. The experimental metastatic capacity of the B7-1 transfectants was drastically reduced in both syngeneic AKR and SCID mice but could be restored in SCID-bg mice. These results provide direct evidence that B7-1 expression leads to NK-mediated elimination of metastasizing, NK-resistant tumor cells.
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PMID:Expression of B7-1 by highly metastatic mouse T lymphomas induces optimal natural killer cell-mediated cytotoxicity. 754 Sep 48

Mice, homozygous for the mutation severe combined immunodeficiency (scid) and also segregating for the mutation hypogonadal (hpg), were tested for their potential use as an in vivo model system for studying the growth of human prostate cancer and benign hyperplastic prostate tissue grafts. Fresh human prostate cancer or benign hyperplastic prostate tissue was implanted subcutaneously into androgen-replete C.B. 17 scid/scid males, and into androgen-deficient hpg/hpg scid/scid or androgen-replete +/? scid scid males. The tissue grafts grew in both androgen-replete and androgen-deficient host mice. When dihydrotestosterone (DHT) was administered at tissue grafting, both the incidence and size of the tissue grafts increased. Histology of tissue from tumors in the androgen-deficient hpg/hpg scid/scid host showed either undifferentiated tumors or adenocarcinomas with few glandular structures. These data suggest the androgen deficient environment selected for growth of androgen-independent tumor tissue. Finally, when interleukin-2 (IL-2)-activated tumor-infiltrating lymphocytes were injected into scid/scid hosts, the cells were found to survive and could be identified in the spleen of the recipient mice. These results indicate that growth of human prostate tissues and IL-2-activated lymphocytes in scid/scid mice is a viable model system for in vivo studies of prostatic disease.
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PMID:Survival of human prostate carcinoma, benign hyperplastic prostate tissues, and IL-2-activated lymphocytes in scid mice. 754 29

Human prostatic cancer cells have a remarkably low rate of proliferation even when they have metastasized to the bone and have become androgen independent (Berges et al., Clin. Cancer Res., 1:473-480, 1995). Due to this low proliferation, patients with such androgen-independent metastatic prostatic cancer cells are rarely treated successfully with the presently available chemotherapeutic agents. Therefore, new approaches are urgently needed which are not dependent on the rate of cancer cell proliferation for their effectiveness. One such approach is to inhibit the angiogenic response within localized and metastatic cancer deposits, since the resultant hypoxia-induced tumor cell death does not require cell proliferation. We have previously demonstrated that the quinoline-3-carboxamide, linomide, is an p.o. active agent which inhibits tumor angiogenesis and thus blood flow in a variety of rat prostatic cancers independent of their growth rate, androgen sensitivity, or metastatic ability. Because of its antiangiogenic effects, linomide treatment induces the hypoxic death of rat prostatic cancer cells, thus inhibiting their net growth and metastases. To determine whether human prostatic cancer cells are similarly sensitive to hypoxia-induced death caused by linomide inhibition of tumor angiogenesis, androgen-independent TSU and PC-3 human prostatic cancer cells were xenotransplanted into SCID mice that were either untreated or treated p.o. with linomide. These studies demonstrated that linomide treatment decreases microvessel density in both androgen-independent human prostatic cancers. Microvessel density was decreased from 1.8 +/- 0.4% of the total area in control tumors to 1.0 +/- 0.2% in linomide-treated TSU tumors [i.e., a 44% decrease in microvessel density (P < 0.05)]. Similarly, a 56% decrease (P < 0.05) was observed in the microvessel density of PC-3 tumors (i.e., 2.7 +/- 0.8% of the area in control tumor versus 1.2 +/- 0.2% in the linomide-treated tumors). This inhibition of angiogenesis increased cell death in both TSU and PC-3 cancer cells. This is reflected in both an increase in the area of necrosis and an increase in the apoptotic index in non-necrotic areas. In untreated TSU tumors, 40 +/- 2% of tumor volume was necrotic. Linomide treatment increased this necrotic percentage to 59 +/- 2% [i.e., 48% increase (P < 0.05)]. Linomide therapy also increased apoptotic cell death in non-necrotic tumor areas. In the untreated TSU tumors, 2.9 +/- 0.6% of tumor cells were apoptotic in the non-necrotic areas, and in the linomide-treated TSU tumors this percentage increased to 3.6 +/- 0.4% [i.e., 24% increase (P < 0.05)].(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Human prostatic cancer cells are sensitive to programmed (apoptotic) death induced by the antiangiogenic agent linomide. 754 15

Bis-indolyl-(seco)-1,2,9a-tetrahydrocyclopropa[c]benz[e]indol-4-on e compounds are synthetic analogues of CC-1065 that are highly cytotoxic toward a broad spectrum of tumor cell lines. One of these compounds, called DC1, was conjugated to antibodies via novel cleavable disulfide linkers. Conjugates of DC1 with murine mAbs anti-B4 and N901 directed against tumor-associated antigens CD19 and CD56, respectively, proved to be extremely potent and antigen selective in killing target cells in culture. DC1 conjugates with humanized versions of anti-B4 and N901 antibodies were also constructed and demonstrated to be as cytotoxic and selective as the respective murine antibody conjugates. The anti-B4-DC1 conjugate showed antitumor efficacy in an aggressive metastatic human B-cell lymphoma survival model in SCID mice and completely cured animals hearing large tumors. Anti-B4-DC1 was considerably more effective in this tumor model than doxorubicin, cyclophosphamide, etoposide, or vincristine at their maximum tolerated doses.
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PMID:Enhancement of the selectivity and antitumor efficacy of a CC-1065 analogue through immunoconjugate formation. 754 85

The therapeutic effect of TNF gene-transduced mouse fibrosarcoma cells (Meth-A: C5) on pre-inoculated parental cells (Meth-A: M0) was studied. Subcutaneous (s.c.) transplantation of M0 cells into one flank of syngeneic BALB/c mice was followed by s.c. injection of irradiated MO or C5 into the opposite flank 1 week later. The initial M0 tumor (T-MO) completely regressed in C5-vaccinated mice, whereas in M0-vaccinated mice continuous growth of T-M0 was observed. When a similar experiment was carried out in SCID mice, no regression of T-MO was observed, suggesting that the tumor regression in BALB/c mice was not due to direct anti-tumor activity of TNF secreted from C5, but to systemic immunity. Regression of the rechallenged M0 tumor was observed in mice which had shown T-MO regression by C5 vaccination, but rechallenged Colon 26 cells (syngeneic to BALB/c mice) continued to grow, indicating a specific immunity to Meth-A cells). The systemic immunity evoked in C5-vaccinated mice was directly demonstrated by enhanced killer activities of LAK and CTL with a proliferation of T-cell population in their splenocytes. Abrogation of the therapeutic effect of C5 vaccination with anti-Thy 1 and anti-Lyt 2 also demonstrates the involvement of cellular immunity in tumor regression.
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PMID:Efficacy of TNF-alpha gene-transduced tumor cells in treatment of established in vivo tumor. 755 41

Angiogenesis plays a fundamental role in human breast tumor progression. In fact, recent findings indicate that vascular density is a prognostic indicator of breast cancer disease status. Evidence is presented that the integrin alpha v beta 3 is not only a marker of human breast tumor-associated blood vessels, but that it plays a significant role in human angiogenesis and breast tumor growth. To assess the role of alpha v beta 3-dependent angiogenesis in the progression of human breast cancer, we examined a SCID mouse/human chimeric model with transplanted full thickness human skin containing alpha v beta 3-negative human breast tumor cells. This tumor induced a human angiogenic response as measured by vascular cell immunoreactivity with monoclonal antibodies LM609 and P2B1 directed to human alpha v beta 3 and CD31, respectively. Intravenous administration of LM609 either prevented tumor growth or markedly reduced tumor cell proliferation within the microenvironment of the human skin. These LM609-treated tumors not only contained significantly fewer human blood vessels but also appeared considerably less invasive than tumors in control animals. These findings demonstrate that alpha v beta 3 antagonists may provide an effective antiangiogenic approach for the treatment of human breast cancer.
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PMID:Antiintegrin alpha v beta 3 blocks human breast cancer growth and angiogenesis in human skin. 756 59


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