Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We developed a porous hydroxyapatite ceramic (HAP) incorporating adriamycin (ADM), that is, ADM-HAP as a new delivery system (DDS) to release ADM gradually. We also researched the possibility of hyperthermic chemotherapy using ADM-HAP by in vitro and in vivo experiments. As for in vitro experiments, we implanted HAPs into uniform Agar-Phantom, and observed thermal distribution generated by Thermotron-RF 8 using thermography. Then we found the hot spot that the edge temperature of HAPs always at the range of 0.5-0.7 degrees C than in the other regions. On the other hand, slow constant release (1%) of ADM from ADM-HAP in PBS was recognized for 24 hrs up to 30 days. When the incubating temperature was shifted up to 42.5 degrees C or 44 degrees C from 37 degrees C, the quantity released over 24 hrs increased about 1.1-fold or 1.3-1.4-fold of the cases at 37 degrees C, respectively. In the in vivo experiment, we inoculated Sarcoma 180 cells in the leg of ddY-mice, and measured the tumor growing times by the treatment of hyperthermia+ADM (whole body), hyperthermia+ADM (tumor region) or hyperthermia+ADM-HAP (tumor region). Then we found that the effect of hyperthermia with ADM-HAP inhibited synergistically the tumor growth as compared with hyperthermia with ADM. Consequently, we succeeded in tumor growth inhibition by increasing the temperature and by limiting ADM release to only a target region using hyperthermia with ADM-HAP.
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PMID:[Fundamental study on hyperthermic chemotherapy using adriamycin-loaded hydroxyapatite]. 132 24

The anti-cancer drug, mitomycin C (MMC), was conjugated to an affinity-purified horse antibody to human alpha-fetoprotein (aAFP) via purified human serum albumin (HSA) as an intermediate carrier. The conjugate (aAFP immunoglobulin (IgG): HSA: MMC, molar ratio 1: 1.10:29.8) was 21 or 38 times as cytotoxic as free MMC or PBS at the MMC concentration of 100 ng/ml, respectively, against alpha-fetoprotein-producing human yolk sac tumor in vitro. The in vivo effects of the conjugate and various controls were also tested against human yolk sac tumor growing in nude mice. The conjugate over a total of 6 injections retarded the initial tumor growth at the concentration of MMC, containing equivalent amounts of 2 micrograms/mouse (0.1 mg/kg)/injection in the conjugate, whereas free MMC and normal horse IgG-HSA-MMC showed only slight inhibitory effects alone at non-toxic levels. These results suggest that the specific antibody-conjugate was considerably more effective than free MMC against the tumor maintained in nude mice as well as in vitro cultures.
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PMID:[Anti-tumor activity of an anti-human alpha-fetoprotein antibody-human serum albumin-mitomycin C conjugate against human yolk sac tumor maintained in vitro and in nude mice in vivo]. 242 Feb 81

The anticancer drug, DNR, was conjugated to an affinity-purified horse antibody to human AFP (aAFP) via a dextran bridge. The conjugate (immunoglobulin: DNR molar ratio, 1:50) was twice as potent as free DNR in an in vitro cytotoxicity assay against an AFP-producing human yolk sac tumor. The in vivo effect of aAFP, DNR, and the conjugate was tested against the human yolk sac tumor growing in nude mice. The conjugate, at a concentration of DNR containing the equivalent amount of 20 micrograms or 70 micrograms/mouse significantly retarded tumor growth whereas free aAFP showed only a slight inhibition of tumor growth compared to the PBS-treated control. Mice which received 20 micrograms/mouse of free DNR showed a moderate retardation of tumor growth whereas those which received 70 micrograms/mouse of DNR or a mixture of DNR and aAFP showed emaciation and early death due to acute toxicity of the drug. These results suggest that the anti-body-drug conjugate accumulated preferentially on the AFP-producing tumor cells and that cytotoxicity occurred.
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PMID:Evaluation of a conjugate of purified antibodies against human AFP-dextran-daunorubicin to human AFP-producing yolk sac tumor cell lines. 242 98

Hematoporphyrin derivative (HPD) is a photosensitizer for use in photodynamic therapy (PDT). In this paper, HPD was conjugated with monoclonal antibodies 3G9 or 3H11 for use against gastric cancer in order to enhance the photosensitive effect and reduce side effect of PDT. The biological activities of the McAb conjugates were demonstrated. The killing effect on BGC-823 cells of 3G9-HPD or 3H11-HPD conjugates plus exposure to light showed 17 fold and 8.6 fold greater cytotoxicity, respectively than free HPD at an equivalent HPD concentration in vitro. When 3G9-HPD and 3H11-HPD were used in combination at 7:3, 5:5 and 3:7 proportion, the cytotoxicity was increased 12.9, 11.8 and 9.4 fold on target cells, respectively. The results indicate that the cytotoxicity was not further enhanced by the combination scheme. When tumor-bearing nude mice were treated with the different conjugates. Significant inhibition of tumor growth was observed and the survival period of animals was markedly prolonged in comparison with PBS, free HPD and NIgG-HPD treated groups.
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PMID:[Experimental study of anti-tumor effect with conjugates of monoclonal antibodies and hematoporphyrin derivative]. 253 54

The murine monoclonal antibody (MoAb)3H11 against human gastric cancer was purified with affinity column and conjugated with Mitomycin C (MMC). The binding activity of MoAb in the conjugate retained more than 90% of the original MoAb 3H11 when the molar ratios of MMC to 3H11 was 7-8:1. The killing rate of 3H11-MMC conjugate on human gastric cancer cells BGC 823 was increased significantly than that of free MMC in vitro. The selective cytotoxicity was verified with the following results: (1) the cytotoxicity of the conjugate was much higher than that of normal mouse IgG (nMuIgG) conjugated with MMC; (2) when breast cancer cells MCF-7 was used as target cells instead of BGC 823 cells, much lower cytotoxicity of the conjugate was observed; (3) the cytotoxicity of the conjugate on BGC823 cells could be blocked when the target cells was preincubated with MoAb 3H11, but not with MoAb 3G9 which did combine with BGC823 cells at binding sites different from MoAb 3H11. Nude mice were inoculated with BGC823 cells as a model of gastric cancer and treated with conjugate 3H11-MMC, nMuIgG-MMC, MMC or PBS (ip). It was shown that the time of tumor formation and the rate of tumor growth in 3H11-MMC conjugate treated animals were significantly different from that in control groups. The rate of inhibition of tumor weights was 60.4% for the conjugate 3H11-MMC treated group which was significantly higher than for other groups.
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PMID:[The selective cytotoxicity of monoclonal antibody conjugated with mitomycin C on human gastric cancer cells]. 261 75

Monoclonal antibody (MAb) B72.3 has been linked successfully to several radionuclides forming stable complexes and analyzed in vitro and in vivo without significant loss of its immunoreactivity. Previous studies have demonstrated that radioiodinated B72.3 can selectively bind to human colorectal carcinomas grown in athymic mice. The same successful localization has been obtained more recently in clinical trials in patients with metastatic colorectal carcinomas. The high degree of selective binding of this MAb has led us to investigate its potential as a radioimmunotherapeutic agent. Athymic mice bearing human colon carcinoma xenografts were injected with either 300 or 500 microCi of 131I-B72.3 IgG to assess the effect o the radiolabeled MAb on the tumor growth as well as potential toxic side effects in vital organs. In mice treated with the 131I-B72.3 IgG, a marked inhibition of the growth of the human colon carcinoma xenografts was noticed in comparison with control mice injected with PBS or control mice that received unlabeled B72.3 IgG. The tumors from these control mice weighed 2.7 to 3.7 times more than the tumors from the treated mice at 17 days post-inoculation of the radiolabeled MAb. Autoradiographic studies demonstrated a heterogeneous distribution of radioactivity throughout the tumor mass at 11 days post-administration of MAb. With time, the periphery of the tumor contained significantly less radioactivity than the medial areas composed of predominantly nonviable tissue; these findings suggest that the more biologically active peripheral tumor zones, with higher mitotic rates, could have partially escaped the radiation effect of the single dose administered. The tumor cells could have continued dividing when the levels of circulating radiolabeled monoclonal antibody had decreased. Toxicity was readily evident in the mice injected with the high-dose regimen (500 microCi), with confirmed bone marrow aplasia that proved lethal for 2 of 10 animals. The lower dose (300 microCi) resulted in a bone marrow suppression of approx. 50% of the cells, which proved to be non-lethal. The tumors in the treated mice showed extensive necrosis caused by the lethal dose of 131I-B72.3 that irreversibly damaged the cells. Radiation-induced terminal differentiation of cells was also found as manifested by the drastically decreased mitotic count (0-2 vs. 12-14 per 10 high power fields seen in control tumors) in treated animals.
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PMID:Radioimmunotherapy of athymic mice bearing human colon carcinomas with monoclonal antibody B72.3: histological and autoradiographic study of effects on tumors and normal organs. 282 Jul 42

Monoclonal antibodies (MAbs) produced against a human colon adenocarcinoma cell line, Colo-205, were tested in antibody-dependent macrophage-mediated cytotoxicity (ADMMC) assays. The antibodies C163, C215, C245 (IgG2a isotype); C151, C239, C241, C242 (IgG1); C152 (IgG2b); and C50 (IgM) were evaluated for their ability to promote killing of Colo-205 cells by thioglycollate-elicited peritoneal mouse macrophages. The concentrations of antibodies tested in ADMMC assays ranged from 1.0 ng/ml to 100 micrograms/ml, and the concentration at which 50% of tumor cells were lysed was used to characterize each antibody. Antibodies of the IgG2a isotype promoted the strongest macrophage-mediated tumor cell lysis effects in vitro. MAbs C215, C163, and C245 were also tested in nude mice which had been inoculated with Colo-205 cells. Tumor suppression was observed in mice injected with MAbs, supporting our ADMMC findings in vitro. Animals treated with MAbs had fewer and smaller tumors, and longer periods of latency between the inoculation of tumor cells and development of tumors, compared to mice sham-treated with PBS. However, in a study of established tumors, C215 antibody did not suppress tumor growth. Serum collected from MAb-treated mice promoted lysis of Colo-205 cells in ADMMC assays while serum from sham-treated mice did not.
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PMID:Mouse monoclonal antibodies for experimental immunotherapy promotes killing of tumor cells. 319 34

We examined the ability of anti-human recombinant interleukin-2 (hu rIL-2) monoclonal antibody DMS-1.10 to increase serum half-life of hu rIL-2, and the effect of this complex on inhibition of tumor progression in a B16-F10 murine melanoma model. In C57B1/6 mice, intravenous (i.v.) injection of DMS-1.10 premixed with 1 x 10(4) units (U) of hu rIL-2 at a 1:1 molar ratio extended serum half-life greater than 10-fold (222 min) when compared to the same dose of hu rIL-2 alone (20 min). In a murine tumor model, multiple intraperitoneal (i.p.) injections of non-neutralizing DMS-1.10 premixed with hu rIL-2 at a 5:1 molar ratio reduced the growth rate of subcutaneous (s.c.) B16-F10 tumor in C57B1/6 mice by 64% when compared to PBS and irrelevant antibody treated controls. Although similar treatment with hu rIL-2 alone reduced tumor growth rate by 46%, it was significantly less effective than the premixed treatment. Results from a flow cytometry assay confirm B16-F10 does not have IL-2 receptors, precluding direct inhibition of tumor growth by hu rIL-2 treatments. We propose that therapeutic efficacy of hu rIL-2 is improved by prolonging the in vivo half-life with an anti-IL-2 antibody, thus augmenting hu rIL-2 bioactivity and enhancing the hosts immune response against tumor.
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PMID:An anti-IL-2 antibody increases serum half-life and improves anti-tumor efficacy of human recombinant interleukin-2. 785 53

Prostate cancer is the most common internal malignancy in men in the United States. Most cancers are diagnosed when they are locally advanced or metastatic and there is no effective treatment. In this study we evaluated the effectiveness of cytotoxic gene therapy in human PC-3 and DU145 prostate cancer cell lines and in a rodent cell line, RM-1, derived from the mouse prostate reconstitution model system. The cell lines were efficiently transduced in vitro by a replicative-defective recombinant adenovirus (ADV) carrying the herpes simplex virus thymidine kinase gene (HSV-tk). A virus titer-dependent sensitivity to ganciclovir (GCV) was observed. To determine a target therapeutic viral dose in vivo, subcutaneous tumors were generated by injection of RM-1 cells in syngeneic male hosts and injected with escalating doses of HSV-tk virus (5 x 10(7) to 1 x 10(9) pfu). The mice received GCV twice daily for 6 days and were sacrificed when tumor volumes exceeded 2.5 cm3 or when they appeared to be in distress. Because the two highest doses were equally as effective, further controlled studies were performed with the lower dose of 5 x 10(8) pfu with ADV/RSV-tk or a control virus containing the beta-galactosidase gene (ADV/RSV-beta-Gal) and treated with GCV or saline (PBS). The mean tumor volume in the treated animals was 16% that of control animals at 13 days. Histologically, treated tumors demonstrated necrosis and had a significantly higher apoptotic index. Survival data indicated that the treatment animals lived 7 days (21 in total) longer than the control animals, with 1 treatment animal being totally free of tumor. These results demonstrate that HSV-tk + GCV cytotoxic gene therapy can inhibit the growth of mouse and human prostate cancer cells in vitro and interrupt tumor growth of an aggressive mouse prostate cancer cell line in vivo.
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PMID:Prostate cancer gene therapy: herpes simplex virus thymidine kinase gene transduction followed by ganciclovir in mouse and human prostate cancer models. 880 Jul 46

We have examined the effect of synthetic low molecular weight glycoamine analogues on the metastasis of MDA-MB-435 human breast carcinoma xenografts growing in the mammary fat pads of nude mice. Initial in vitro screening of a panel of synthetic glycoamines was performed using a clonogenic growth assay in 0.9% agarose. Eight of nine compounds manifested a significant dose-dependent inhibition of colony formation by MDA-MB-435 cells in 0.9% agarose. The relative activity ranks of the compounds, based on ID50S independently determined for each synthetic glycoamine analogue, identified N-(1-deoxy-D-lactulos-1-yl)-L-leucine (Lac-L-Leu), N-(1-deoxy-D-fructos-1-yl)-D-leucine (Fru-D-Leu), N-(1-deoxy-D-fructos-1-yl)-L-phenylalanine, and N-(1-deoxy-D-fructos-1-yl)-L-leucine as the most effective inhibitors of colony formation. Two separate experimental treatment protocols were used to examine the effect of selected synthetic glycoamines on human breast cancer growth and metastasis in athymic nude mice. Group A mice were treated intraperitoneally daily from day 2 after injection of the breast cancer cells until the end of the experiment (17 weeks). In group B, the mice were untreated until the mean tumor diameter was 10 mm, at which time daily i.p. treatment began. After 7 days, the primary tumors were resected, and the mice were treated for an additional 4 weeks (a total of 5 weeks of treatment). The synthetic glycoamines did not have significant antitumor effects, and there was no difference in the tumor incidence or tumor growth rates in mice treated continuously with synthetic glycoamines or PBS. The significant antimetastatic activity of synthetic glycoamines was detected in both experimental treatment protocols. In mice continuously treated with synthetic glycoamines according to protocol A, the incidence of metastasis was decreased 4.6-fold (P = 0.014) and 2.7-fold (P = 0.031) in mice treated with Fru-D-Leu and Lac-L-Leu, respectively. In mice in protocol B, the incidence of pulmonary metastasis was decreased 1.9-fold (P = 0.069) and 2.5-fold (P = 0.042) in mice treated with Fru-D-Leu and Lac-L-Leu, respectively. Correspondingly, the average number of spontaneous pulmonary metastases was reduced from 37 in control mice to 0.2 (P = 0.005) and 0.9 (P < 0.02) in mice treated according to the protocol A with Fru-D-Leu and Lac-L-Leu, respectively. Treatment of mice with N-(1-deoxy-D-fructos-1-yl)-L-leucine did not have significant antimetastatic effects, and no reduction in metastasis incidence or number was noted in mice treated with this synthetic glycoamine analogue. The treated animals had no apparent toxicity from chronic daily injection (up to 17 weeks of treatment) of synthetic glycoamines, and no obvious pathology was noted in the histological slides of the livers, kidneys, or spleens of the treated mice. Therefore, we have identified two synthetic glycoamines (Fru-D-Leu and Lac-L-Leu) that were the effective inhibitors of spontaneous human breast cancer metastasis in nude mice. Potential mechanisms for antimetastatic activity of synthetic glycoamines may include the inhibition of beta-galectin-mediated homotypic cancer cell aggregation and induction of apoptosis in target cells.
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PMID:Inhibition of human breast cancer metastasis in nude mice by synthetic glycoamines. 896 76


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