Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies have indicated the efficacy of adoptive immunotherapy utilizing recombinant interleukin-2 (rIL-2) and lymphokine-activated killer (LAK) cells in the treatment of advanced neoplastic disease. However, this therapeutic approach is associated with considerable toxicity, primarily due to the systemic administration of rIL-2. The present study was undertaken to determine the efficacy of a newly developed water-soluble glucan, when administered in combination with LAK cells, in the therapy of experimental hepatic metastases. Mice were challenged subcutaneously (1 X 10(4) cells) with reticulum cell sarcoma M5076 on day 0. Therapy was initiated on day 15, when a palpable primary tumor mass and hepatic micrometastases were evident, and continued at 3-day intervals up to day 54. Sarcoma-bearing mice received glucan (250 mg/kg) intravenously, either alone or in combination with LAK cells (1 X 10(7)/mouse). Control mice received 5% (wt/vol) dextrose in water. Glucan-LAK cell therapy significantly suppressed primary tumor growth, inhibited the progression of hepatic metastases and prolonged survival in sarcoma-bearing mice. Splenocytes, incubated with rIL-2 for 72 h, exhibited significant natural killer (NK) cell activity and were cytotoxic to sarcoma cells in vitro. Glucan-LAK cell administration resulted in significant increases in splenic NK cell activity and Kupffer cell-mediated tumoricidal activity. In addition, bone marrow proliferation was enhanced following the co-administration of glucan and LAK cells. Due to its nontoxic nature and immunostimulating properties, soluble glucan may prove to be an attractive biological response modifying agent for utilization in adoptive immunotherapy of advanced neoplastic disease.
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PMID:Soluble glucan and lymphokine-activated killer (LAK) cells in the therapy of experimental hepatic metastases. 328 99

Previous studies from our laboratory have demonstrated that particulate glucan is efficacious in the therapy of a syngeneic murine reticulum cell sarcoma (M5706), which specifically metastasizes from its primary site to the liver. The present study was undertaken to examine the therapeutic efficacy of a newly developed soluble glucan, in combination with cyclophosphamide in the treatment of hepatic metastatic disease. Male C57Bl/6J mice were injected subcutaneously on Day 0 with 1 x 10(4) sarcoma cells. Glucan (200 mg per kg i.v.), cyclophosphamide (45 mg per kg i.p.) or glucan and cyclophosphamide were administered beginning on Day 20, when hepatic metastases were evident, and continued at 3-day intervals up to Day 50. Combined therapy with glucan and cyclophosphamide resulted in reduction of hepatic metastatic lesions on Day 36, compared to control. Survival data revealed that the combination of glucan and cyclophosphamide significantly (p less than 0.001) extended median survival time and the time to 100% mortality in an additive fashion, when compared to either therapy alone. Glucan-cyclophosphamide therapy was also effective in decreasing primary tumor weight to a level that was significantly (p less than 0.05) less than when therapy was initiated. In vitro studies revealed that Kupffer cell tumoricidal activity against sarcoma was increased (p less than 0.05) following glucan and cyclophosphamide. Glucan and cyclophosphamide also enhanced bone marrow proliferation and splenocyte response to mitogens in vitro. Additionally, glucan was observed to exert a direct cytostatic effect on sarcoma in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chemoimmunotherapy of experimental hepatic metastases. 331 33

Glucan, a particulate beta-1,3-polyglucose immunomodulator, was evaluated for its ability to modify hepatic metastases and survival in mice with reticulum cell sarcoma. Sarcoma M5076 cells were injected subcutaneously (1 X 10(5) cells) into syngeneic C57BL/6J male mice. On Day 20, histopathological studies indicated the presence of hepatic micrometastases. At this time, glucan (0.45 mg per mouse) or dextrose was administered intravenously. Therapy was continued at 3-day intervals up to Day 50. By Day 36 postchallenge, the glucan-treated group, when compared to the control group, showed a marked decrease in hepatic metastases, both grossly and histopathologically. A significant inhibition in the growth of the primary tumor also occurred. Plasma clearance of bromosulfophthalein measured on Day 36, denoted that glucan therapy maintained hepatic parenchymal cell functional integrity, while a 4-fold impairment in bromosulfopthalein removal was observed in control mice. Glucan-treated mice showed a 28% (p less than 0.05) long-term survival. In contrast, control mice showed a 100% mortality by Day 42 postchallenge. Studies to evaluate the mechanism of the anti-metastatic action of glucan indicated that 8 days after glucan administration, isolated hepatic macrophages were significantly more cytotoxic to sarcoma cells in vitro than were normal Kupffer cells. At this time, the cytotoxic activity of peritoneal and splenic macrophages from glucan-treated mice were unaltered. Additionally, co-incubation of particulate glucan with diverse populations of normal or tumor cells in vitro indicated that glucan exerted a direct cytostatic effect on sarcoma and melanoma cells and, in contrast, had a proliferative effect on normal spleen and bone marrow cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Therapeutic efficacy of glucan in a murine model of hepatic metastatic disease. 388 76

The effect of a glucan, Schizophyllan (SPG), on pulmonary metastases in syngeneic mice bearing Lewis lung carcinoma (3LL) was examined. As a model of pulmonary metastases, 3LL cells were implanted into the footpads of C57BL/6 mice, the resulting primary tumor was removed 9-10 days later. The inhibitory effect of SPG was evaluated from the number of pulmonary surface nodules on the lungs about 3 weeks after tumor implantation. SPG was found to have antimetastatic activity, which depended on its dose and time of injection. A single injection of 100 or 200 mg/kg or daily injections of 20 or 50 mg/kg of SPG after removal of the primary tumor markedly inhibited pulmonary metastases. Combined therapy with cyclophosphamide and SPG significantly prolonged the survival of mice with pulmonary metastases. Enhancement of the in vitro cytotoxic activity of peritoneal macrophages and bronchoalveolar or whole lung cells against 3LL cells was noted in SPG-treated mice on day 7 after a single intraperitoneal injection of 100 mg/kg SPG. Intravenous transfer of peritoneal macrophages activated with SPG inhibited the development of pulmonary micrometastases.
Invasion Metastasis 1981
PMID:Inhibition of pulmonary metastasis of Lewis lung carcinoma by a glucan, Schizophyllan. 623 52

Tumor cells (AH130 hepatoma cell originated from rat) were injected intraportally into Donryu rats to produce liver metastases 21 days later. Phagocyte cells activity was depressed by the administration of Silica, which significantly increased the number of surface liver metastases. Phagocyte cells were stimulated by beta 1-3-glucan, which significantly reduced the number of metastases. And the administration of free radical scavenger (SOD, Catalase) increased the number of metastases. Non parenchymal cells (NPC) of the liver play a main role of self defence line for portally liver metastases. Then free radical from these cells were noticed in this study. NPC were isolated, from pronase perfused rat liver. O2- production by activated NPC was measured by chemiluminescence with CLA. NPC activated by beta 1-3-glucan added sera increased the luminescence of CLA, and SOD depressed the production of chemiluminescence. SOD activity of hepatocytes and tumor cells (AH130) were measured by NBT methods. Hepatocytes had high potential production of SOD, in contrast AH130 had poor production. These results suggest that free radicals from liver NPC was important for protecting liver metastases.
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PMID:[The effect of free radicals from non-parenchymal cells (NPC) of the liver on the development of liver metastases in rat]. 823 83

Bispecific antibody (BsAb) with specificity for tumor cell surface antigen and the CD3 molecule on T cells can redirect activated T cells to lyse tumor cells. Since the ex vivo expansion and activation of T cells is impractical and ineffective for treating established tumors, we tested whether the immune stimulant beta glucan could in situ-activate T cells, which could secondarily be retargeted with BsAbs to lyse tumor cells. To test for tumor neutralization, C3H/HeN mice were injected i.v. with Cl-62 melanoma cells and immediately treated with i.p. beta glucan and/or anti-CD3 (500A2) x anti-p97 (96.5) F(ab')2 BsAb i.v. Pulmonary metastases were counted 14 days later. To test for tumor rejection and survival in a solid tumor model, mice were injected s.c. and i.p. with Cl-62 cells and 7 days later administered beta glucan i.p. and/or F(ab')2 BsAb i.v. In the neutralization model, there was a significant reduction in the number of metastases in the beta glucan + BsAb group, as compared with controls, and with beta glucan alone. In the established tumor model, beta glucan + BsAb reduced the incidence of s.c. tumors as compared with control, with BsAb alone and with beta glucan alone. It also prolonged survival of tumor-bearing mice compared with control, BsAb alone and beta glucan alone. We conclude that T cells can be activated in vivo by beta glucan and retargeted with F(ab')2 BsAb.
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PMID:Pulmonary metastases neutralization and tumor rejection by in vivo administration of beta glucan and bispecific antibody. 857 61

For antitumor x anti-CD3 bifunctional antibody (BFA) therapy to be clinically relevant in solid tumors, activated lymphocytes must be present within tumors. Toward that end, three uniquely different in vivo activation approaches were investigated in a p97 human antigen expressing syngeneic murine melanoma model. beta-Glucan (200 micrograms), staphylococcal enterotoxin B (SEB) (50 micrograms), and F(ab')2 BFA (10 micrograms) were tested for their ability to activate lymphocytes, neutralize pulmonary metastases, and treat established tumors. Systemic activation, measured as the ability of splenocytes to lyse tumor cells in vitro in the presence of BFA, was enhanced by the in vivo administration of SEB but not by beta-glucan or F(ab')2 BFA. Despite lacking a systemic effect, F(ab')2 BFA increased both direct and BFA-mediated cytotoxicity in fresh tumor infiltrating lymphocytes. beta-Glucan did not increase systemic or intratumor T cell activation. However, it significantly enhanced the ability of splenocytes to lyse NK-sensitive YAC-1 cells. When tested in a pulmonary metastases model, all three forms of immune modulation combined with F(ab')2 BFA significantly reduced the number of metastases. BFA were more effective at tumor neutralization when combined with SEB compared with adoptively transferred, in vitro-activated splenocytes. These studies demonstrate that immune modulators when combined with F(ab')2 BFA can provide effective antitumor therapy. Several clinical obstacles may be overcome by the application of these reagents.
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PMID:Bifunctional antibody retargeting in vivo-activated T lymphocytes: simplifying clinical application. 884 18

We studied the effect of macrophage stimulator water-soluble beta-(1-->3)-D-carboxymethylglucan on the efficiency of cyclophosphamide chemotherapy in Lewis lung carcinoma. Cyclophosphamide inhibited the growth of primary tumor nodes by 57%. The preparation possessed pronounced antimetastatic activity: metastases were found in 40.9% animals. Combination therapy with cyclophosphamide and (1-->3)-beta;-D-glucan inhibited the growth of intramuscular tumors by 75-89% and reduced the incidence of metastases into the lungs by 92-94%. The therapeutic effect was most pronounced after simultaneous administration of these preparations: tumor growth was suppressed by 89.3% and metastases were found in only 7.5% animals (vs. 100% in the control). The potentiating effect of beta-(1-->3)-D-carboxymethylglucan is related to accumulation of cysteine proteinase inhibitors in the tumor tissue and plasma, but not to changes in blood cell composition.
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PMID:Macrophage Stimulator beta-(1-->3)-D-carboxymethylglucan improves the efficiency of chemotherapy of Lewis lung carcinoma. 1171 68

The antitumor effects of biological response modifiers (BRMs) in an experimental mouse model using a double grafted tumor system were analyzed. Some BRMs prevented metastases by utilizing the anti-tumor immunological cascade reactions, which activate macrophages in the body. The following BRMs were analyzed: PSK was a hot water extract of cultured mycelia from Coliolus versicolor and a protein bound beta-glucan. Lentinan was purified from fruit bodies of Lentinus erodes and is a beta-glucan. The agaricus preparation was extracted from fruit bodies of Agaricus blazei and a protein-bound alpha-, beta-glucan. The M2 fraction was extracted from mycelia of Tricholoma matsutake and was a protein bound alpha-glucan. M1 fraction was purified from mycelia of T. matsutake and was an alpha-glucan. PSK cured both primary and metastatic tumors in the double grafted tumor system. Lentinan did not inhibit the growth of either primary or metastatic tumors. Agaricus preparation cured a primary tumor and inhibited the growth of a metastatic tumor. The M2 fraction prepared from Matsutake inhibited the growth of both primary and metastatic tumors. The M1 fraction did not inhibit either primary or metastatic tumors. Immunosuppressive acidic protein (IAP) is produced by activated macrophages. The PSK, Agaricus preparation and M2 fraction of the Matsutake preparation induced IAP but the lentinan and M1 fraction did not.
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PMID:[Activation of antitumor immunity by intratumor injection of biological preparations]. 1461 62

Metastases from renal cell carcinomas (RCC) are resistant to radiation and chemotherapy but are relatively immunogenic. We have investigated the possibility to eliminate human RCC micrometastases using MAb G250. G250 penetrates human micrometastases completely in a spheroid model and induces complement deposition rapidly on the outmost cell layers. However, complement dependent cytotoxicity (CDC) was barely detected using either (51)chromium release assays or confocal microscopy, due to relatively low expression of the G250 antigen and the effect of membrane bound complement regulatory proteins. Addition of blocking anti-CD59 MAbs enhanced formation of C5b-9 and consequently complement mediated lysis (13%). Complement assisted cellular cytotoxicity (CACC) was not detectable, although the iC3b ligand and CR3 receptor were present on respectively target and effector cells. Addition of soluble beta-glucan induced the killing of MAb and iC3b opsonized spheroids by effector cells (6-21%). Despite a lower affinity for G250 antigen, a bispecific anti-G250*anti-CD55 MAb enhanced cell killing in spheroids comparable to the parental G250 MAb. Our results suggest that complement-activating G250 in combination with anti-mCRP MAbs is able to kill human RCC cells in micrometastasis in vitro. For CACC the presence of CR3-priming beta-glucan seems to be obligatory. In vivo, bi-MAb may be more effective as therapeutic agent due to its increased C5a generating properties.
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PMID:Beta-glucan enhanced killing of renal cell carcinoma micrometastases by monoclonal antibody G250 directed complement activation. 1502 24


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