Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fifty patients with primary localized lung cancer were tested at the time of surgery for the ability of their lymphocytes to kill autologous, freshly isolated tumor cells, and the assay was evaluated for prognostic significance. Peripheral blood lymphocytes of 27 patients (54%) demonstrated significant autologous tumor-killing activity in 6-hour 51Cr-release assays. Twenty-three of the 27 patients with autologous tumor-killing activity remained tumor free and survived more than 5 years after curative surgery, while all 23 who were negative for autologous tumor-killing activity relapsed by 18 months after surgery and died within 42 months after surgery. The differences in survival curves for the two groups were highly significant (P less than .00003). Autologous tumor-killing activity was not correlated with natural killer (NK) cell activity against K562 human myeloid leukemia cells or proliferation of lymphocytes stimulated with autologous, freshly isolated tumor cells in mixed culture. There were no differences in total survival between patients with positive results and those with negative results in tests of NK cell activity and autologous mixed lymphocyte-tumor culture reaction. These results indicate that autologous tumor-killing activity is a meaningful prognostic indicator and provide evidence for immunological control of tumor growth and metastasis. According to our preliminary data, it is unlikely that lung cancer patients who remain tumor free after 60 months of follow-up will develop recurrence or die from the disease. We are conducting a study to determine whether induction of autologous tumor-killing activity before surgery, by treatment with biological response modifiers,can improve the clinical outcome in patients who do not naturally have this potential.
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PMID:Prediction of postoperative clinical course by autologous tumor-killing activity in lung cancer patients. 223 57

Antitumor synergism occurs with two drugs in sequence when the second drug is given at the time of maximal regrowth of residual leukemia and peak humoral stimulatory activity (HSA). To determine if this enhancement relates to a host derived HSA, studies were conducted in Lewis x brown Norway F1 rats bearing brown Norway myelocytic leukemia. A significant cure rate was observed in rats treated initially with 1-beta-D-arabinofuranosylcytosine and then given injections of 10(6) leukemia cells and treated with a second 2-day course of 1-beta-D-arabinofuranosylcytosine in every-8-h s.c. injections in the 6-day period after the initial drug. No effect on survival of the initial drug or of the second drug given at intervals after day 6 was noted. This result is consistent with the efficacy of treatment at the time of peak HSA and tumor growth. The direct effect of HSA on tumor sensitivity to 1-beta-D-arabinofuranosylcytosine was evaluated by 18-h incubations of leukemia and HSA, followed by bioassay. Increased survival and high cure rates were observed when compared with cultured cells in normal serum. These studies support the notion that host derived factors operative during drug induced aplasia stimulate tumor growth and thereby, if the drugs are properly timed, increase sensitivity to cycle active agents.
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PMID:Drug induced host factors which stimulate growth of residual leukemia in Lewis x Brown Norway F1 (LEW-BN) rats. 348 14

Diets high (17.7 cal%) and low (3.3 cal%) in linoleic acid were given to groups of Brown Norway female rats before and after inoculation of syngeneic tumor models with different characteristics, with regard to tumor spread, malignancy, immunogenicity, growth rate, rat strain, and histopathological features. Despite the differences in characteristics, in most tumor models, tumor growth was identical in both experimental groups. However, in 2 tumor models, an adrenal cortical carcinoma and a myeloid leukemia, differences in growth were noted. In rats given the diet low in linoleic acid, growth of the cortical carcinoma was significantly increased, whereas the opposite effect was seen in rats with myeloid leukemia.
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PMID:Influence of the linoleic acid content of the diet on tumor growth in transplantable rat tumor models. 396 48

Daily injections of somatostatin into mice with myeloid leukemia retarded the tumor growth. This myeloid leukemia is an insulin-dependent tumor (in that it grows more slowly in hypoinsulinemic diabetic mice than in nondiabetic animals). Since somatostatin decreased the level of immunoreactive insulin in mice with myeloid leukemia, and since the treatment with insulin abrogated the antileukemic effect of somatostatin, we attribute retarded growth of this leukemia to decreased secretion of insulin, caused by somatostatin.
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PMID:Somatostatin suppresses growth of murine myeloid leukemia in vivo. 611 Apr 47

Cells from the established human myeloid cell lines KG-1, KG-1a, and HL-60, transplanted subcutaneously (sc) into nude mice, developed discrete tumors (myelosarcomas). These myelosarcomas had a host's age-associated pattern of growth identical to that of experimental tumors produced by sc transplantation of cells derived from malignant solid neoplasias. Thus, leukemia cells yielded either localized myelosarcomas at the site of inoculation or a disseminated neoplastic growth after inoculation in adult (more than 4 weeks old) or newborn (1-3 days old) nude mice, respectively. Human myeloid leukemia cells proliferating in the nude mice preserved the human karyotype and a surface antigenic determinant and did not influence the hematopoietic tissues of the host. The KG-1 and HL-60 cell lines consistently attained varying degrees of differentiation along the myeloid series in vitro, and these features were maintained during proliferation in the mice. Furthermore, cells of the variant subline KG-1a, which had a blastic morphology, developed signs of differentiation that were not seen in culture. The presence of readily identifiable markers, such as cytoplasmic granules containing myeloperoxidase, in the cell lines tested makes these models particularly useful for studying the influence of a biological environment on cell differentiation and its influence on tumor growth. These experimental systems are also suitable for investigating the mechanism(s) of metastases and for in vivo experimental therapeutic trials.
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PMID:Local and metastatic growth and in vivo differentiation of human myeloid leukemia cells transplanted in nude mice. 632 81

omega-3 fatty acids are associated with reduced growth and incidence of certain cancers, and in this report we demonstrate that a fish oil diet (rich in omega-3 fatty acids) enhances the longevity of mice bearing the myeloid leukemia T27A. We have proposed that the omega-3 fatty acid docosahexaenoic acid (DHA, 22:6 delta 4,7,10,13,16,19) may induce structural changes in tumor cell plasma membranes resulting in reduced tumor growth in vitro. Here, we test whether liposomes containing DHA (18:0, 22:6 PC) have antitumor effects in vivo, leading to enhanced longevity of the tumor-bearing host. Male BALB/c mice (6-8 weeks old) were inoculated intraperitoneally with a T27A tumor dose known to cause 100% mortality of syngeneic (BALB/c) mice in less than 2 weeks. Small unilamellar vesicles (liposomes) were prepared, composed of phosphatidylcholine (PC) with 18:0 in the sn-l position and one of the following fatty acids in the sn-2 position: 18:0, 18:1 omega 9 (oleic), 18:3 omega 3 (alpha-linolenic), 20:4 omega 6 (arachidonic), 22:6 omega 3 (docosahexaenoic). The liposomes were injected intraperitoneally into tumor-bearing mice at various times: concurrently with the tumor inoculum, at select times during tumor growth, and when the mice were moribund. Mouse survival was then charted. DHA-containing lipid vesicles (18:0, 22:6 PC) caused a statistically significant increase in survival of the tumor-bearing mice when compared with 18:0, 18:1 PC. Lipid vesicles of 18:0, 18:0 PC showed no benefit, and 18:0, 20:4 PC was not significantly different than 18:0, 18:1 PC. Lipid vesicles containing a different omega-3 fatty acid, 18:0, 18:3 PC, also effectively enhanced tumor-bearing mouse survival. The greatest benefit was achieved if either the liposome treatments were spaced throughout the tumor growth period, or if the tumor inoculum was suspended in the liposome preparation (without further liposome treatments). Neither lipid peroxidation nor prolonged inflammatory responses appeared to be pertinent, leaving membrane structural changes as a feasible mode of liposome action. With antitumor properties of their own, omega-3 fatty acid-containing lipid vesicles may offer an important new avenue in combination cancer therapies.
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PMID:Omega-3 fatty acid-containing liposomes in cancer therapy. 853 60

A leukemia-selective immunotoxin was constructed by linking recombinant gelonin (rGel), a single chain ribosome inhibitory protein, to recombinant humanized M195 antibody (HuM195), which recognizes the cell-surface protein designated CD33. CD33 is an antigen found on myeloid leukemia blasts as well as myeloid progenitor cells but it is not expressed in detectable amounts on the ultimate hematopoietic progenitor stem cell. Our previous studies indicated that a non-recombinant humanized immunotoxin displayed specific, potent toxicity towards CD33-positive cells but not to CD33-negative cells in vitro. In the current study, a recombinant humanized immunotoxin, HuM195-rGel, was evaluated in vivo in a nude mouse model of human myeloid leukemias. HuM195-rGel was found to target leukemia cells rapidly in vivo and was subsequently internalized into the cells. For trials in vivo, nude mice were injected (ip) with 10(7) log-phase HL60 human leukemia cells 10 days prior to the start of i.p. HuM195-rGel treatments. HuM195-rGel demonstrated significant tumor suppressive activity in this model. While all mice treated with either saline, rGel alone, or HuM195 plus unconjugated rGel (at 10 or 14 days after transplantation) had rapid tumor growth or early deaths, 50% of mice treated with HuM195-rGel failed to develop leukemic tumors for 5 months and the 50% had significantly retarded tumor growth after treatment with HuM195-rGel. Mice treated at later times (28 days after transplantation of leukemia cells) also showed delayed leukemia cell growth, but no cures. These data show that HuM195-rGel can target leukemia cells in vivo and can result in pronounced anti-leukemic effects.
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PMID:Antileukemic activity of recombinant humanized M195-gelonin immunotoxin in nude mice. 863 41

Tumor cells are eradicated by several systems, including Fas ligand-Fas and tumor necrosis factor (TNF)-tumor necrosis factor receptor (TNFR). In the previous study, we purified an apoptosis-inducing factor (AIF) to homogeneity from a medium conditioned by PDBu-treated HL-60 cells. N-terminal sequence analysis showed that AIF is identical to endothelial interleukin-8 (IL-8). A novel apoptosis system, in which endothelial cells participate via endothelial IL-8 release, is identified here. Human umbilical vein cells (VE cells) produce and secrete IL-8 by stimulation of IL-1alpha and TNF-alpha. Endothelial IL-8, which is secreted from VE cells by stimulation of IL-1alpha and TNF-alpha , induces apoptosis in myelogenous leukemia cell line K562 cells. Monocyte-derived IL-8 could not induce apoptosis in K562 cells. Moreover, interaction between VE cells and K562 cells induces the release of endothelial IL-8 from VE cells, and the attached K562 cells undergo apoptosis. Moreover, interactions between VE cell and other cell lines, such as HL-60, U937, Jurkat, and Daudi, induce the secretion of endothelial IL-8 and the induction of apoptosis in cell lines. Endothelial IL-8 significantly inhibits tumor growth of intraperitoneal and subcutaneous tumor mass of K562 cells and induces apoptosis in their cells in vivo. Endothelial IL-8 plays an important role in apoptosis involving endothelial cells, which may provide us with a new therapy for hematological malignancies.
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PMID:Activated endothelial cells induce apoptosis in leukemic cells by endothelial interleukin-8. 976 49

Allogeneic bone marrow transplantation (BMT) induces 2 closely associated immune responses: graft-versus-tumor (GVT) activity and graft-versus-host disease (GVHD). We have previously shown that pretransplant immunization of allogeneic BMT donors with a recipient-derived tumor cell vaccine increases both GVT activity and lethal GVHD because of the priming of donor T cells against putative minor histocompatibility antigens (mHAgs) on the tumor vaccine cells. The work reported here tested the hypothesis that tumor cell vaccination after BMT would produce an increase in GVT activity without exacerbating GVHD. C3H.SW donor bone marrow and splenocytes were transplanted into major histocompatibility complex-matched, mHAg-mismatched C57BL/6 recipients. One month after BMT, recipients were immunized against either a C57BL/6 myeloid leukemia (C1498) or fibrosarcoma (205). Immunized recipients had a significant increase in survival and protection against tumor growth in both tumor models, and significant tumor protection was seen even in recipients with preexisting micrometastatic cancer before immunization. Alloreactivity appeared to contribute to the in vitro anti-tumor cytolytic activity, but in vivo immunity was tumor specific, and no exacerbation of GVHD was observed. Although the immunodominant mHAg B6(dom1) was shown to be expressed by all B6 tumors tested and was largely responsible for the alloreactivity resulting from tumor immunization of donors, the in vitro alloreactivity of immune recipients was more restricted and was not mediated by recognition of B6(dom1). In conclusion, post-transplant tumor immunization of allogeneic BMT recipients against either a leukemia or a solid tumor can increase GVT activity and survival without exacerbating GVHD.
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PMID:Immunization of allogeneic bone marrow transplant recipients with tumor cell vaccines enhances graft-versus-tumor activity without exacerbating graft-versus-host disease. 1073 17

Bcl-2 is a potent suppressor of apoptosis, and its overexpression contributes to tumorigenesis in many types of human cancers. To test the possibility of modulating Bcl-2 function as an anticancer strategy, a cell permeable Bcl-2 binding peptide, cell permeable moiety (cpm)-1285, was designed by chemically attaching a fatty acid to a peptide derived from the proapoptotic protein Bad. cpm-1285 entered HL-60 tumor cells, bound Bcl-2 protein, and induced apoptosis in vitro. In contrast, cpm-1285 had little effect on normal human peripheral blood lymphocytes. Furthermore, cpm-1285 had in vivo activity in slowing human myeloid leukemia growth in severe combined immunodeficient mice. These results demonstrate a novel approach for therapeutic intervention of tumor growth in vivo with small molecule inhibitors of Bcl-2.
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PMID:Cell permeable Bcl-2 binding peptides: a chemical approach to apoptosis induction in tumor cells. 1074 11


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