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)

Two new strategies for increasing tumor uptake have been investigated. First the effect of interleukin-2 (IL-2) on tumor uptake of 125I-Lym-1 antibody in nude mice was investigated. Secondly, the use of 67Cu-labeled Lym-1 was evaluated in patients. In nude mice implanted with Raji human lymphoma, a greater than 2-fold enhancement of tumor uptake of 125I-Lym-1 was observed after administration of PEG-interleukin-2 (PEG-IL-2). The macrocycle 1,4,8,11-tetraazacylcotetradecane-N,N',N",N"'-tetraacetic acid (TETA), synthesized specifically for copper chelation, has been conjugated to Lym-1 for 67Cu labeling of the monoclonal antibody (MoAb). There was no evidence for bone or normal marrow uptake and the residence time in the tumor was prolonged. Surprisingly, a dose of 4.4 mCi that was intended for imaging induced substantial tumor regression in a patient.
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PMID:Strategies for enhancement of radioimmunotherapy. 174 86

A polyethylene glycol-modified form of recombinant human IL-2 (PEG-IL-2) was tested for murine antitumor effects in vitro and in vivo. This PEG-IL-2 was demonstrated to retain the in vitro ability to support T cell proliferation, enhance a mixed lymphocyte reaction, and generate lymphokine-activated killer (LAK) cells. It was found to have a circulating half-life in mice 25 times longer than unmodified recombinant IL-2 (RIL-2). Serum levels were detected up to 60 h after a single intravenous injection. When given as a single, intravenous administration the antitumor effect of this material was similar to multiple, repeated bolus doses of RIL-2. PEG-IL-2 was also found to support the in vivo efficacy of adoptively transferred LAK cells and tumor infiltrating lymphocytes (TIL). Using a congenic TIL (Thy 1.1), persistence of adoptively transferred TIL was found to be prolonged with PEG-IL-2 compared to repeated boluses of RIL-2. Four days after transfer, twice as many Thy 1.1 TIL were recoverable from the lungs of mice given PEG-IL-2. These studies show that PEG-IL-2 is a modified lymphokine with significant antitumor activity in murine systems and is superior to bolus RIL-2 in enhancing the survival of adoptively transferred TIL.
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PMID:Murine studies using polyethylene glycol-modified recombinant human interleukin 2 (PEG-IL-2): antitumor effects of PEG-IL2 alone and in combination with adoptive cellular transfer. 180 10

The murine monoclonal antibody A7 (Mab A7) against human colon cancer was chemically modified with methoxypolyethylene glycol (PEG) (Mr 5000). A high substitution of PEG molecules on Mab A7 produced a progressive reduction in antibody-binding activity. The pharmacokinetic and immunological properties of PEG-modified monoclonal antibody A7 (Mab A7) and the PEG-modified F(ab')2 fragment, which retained their antibody-binding activity, were assessed and compared with the parent Mab A7 and the parent F(ab')2 fragment. Blood clearance of PEG-modified antibodies appeared to be diminished by PEG modification and was fitted by a two-compartment model. Low PEG-substituted Mab A7 showed less organ uptake in the liver and spleen and similar uptake in the lung and kidney, compared with the parent Mab A7. PEG-F(ab')2 showed less uptake in the liver and kidney. Both preparations exhibited less tissue:blood ratios in all resected organs as compared with parent antibodies. Tumor localization was enhanced by PEG modification for the F(ab')2 fragment, but not by PEG modification for the whole Mab A7. Multiple i.v. administration of PEG-modified antibody to rabbit did not appear to elicit a measurable immune response to the antibody portion of the conjugate. In conclusion, PEG-modified antibodies are promising reagents as drug carriers to the target tumor.
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PMID:Chemical engineering of the monoclonal antibody A7 by polyethylene glycol for targeting cancer chemotherapy. 186 53

A 24-year-old housewife presented with weight gain of about 30 kg, constipation and pitting edema of extremity nine years after having a thyroidectomy. Hormonal examination revealed low levels of serum T3 and T4 and high levels of serum TSH and PRL. She also had enlarged pituitary gland (pituitary hyperplasia) with suprasellar extension on CT and MRI image. Thyroid replacement therapy and follow-up by MRI were performed without resort to surgery, because she had no visual disturbance. Within about 1 month after thyroid replacement therapy, serum TSH and PRL were normalized. And also thyroid function was normalized by thyronine (T3). Following this results, pituitary hyperplasia regression was seen on MRI image. About 1 year after thyroid replacement therapy, pituitary hyperplasia regression was more seen on MRI image. Prolonged hypothyroidism can result in hypertrophy of the pituitary thyrotropin-secreting cells and prolactin secreting cells. So, it can increase pituitary weight (pituitary hyperplasia). Radiological examination, abnormal sellar x-ray films suggesting intrasellar tumor are common in patients with primary hypothyroidism. Suprasellar extension of pituitary mass (pituitary hyperplasia) due to hypothyroidism was reported by radiological examination (PEG, CT and MRI image), and regression of pituitary hyperplasia was revealed by radiological examination after thyroid replacement therapy. The first choice of this type of pituitary hyperplasia is thyroid replacement therapy unless the patient has a visual disturbance. However, if this replacement therapy is not effective for diminution of the tumor, surgical removal of the tumor should be considered.
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PMID:[A case of pseudo-TSH.PRL-producing pituitary adenoma with secondary hypothyroidism]. 187 88

The values of parameters of humoral immunity, such as concentration of immunoglobulins IgG, IgA, and IgM, as well as the absorbance of patients serum at 450 nm (A4 5 0) in the presence of PEG 6000 (as a measure of the presence of immune complex in circulation, CIC) in a group of breast cancer patients stage T + N0 M0, after surgical tumor resection, and before and after various therapy phases with the leucocyte IFN therapy are given. The IFN (product of Torlak, Belgrade, or Immunological Department Zagreb) therapy was performed in four therapy phases. During the first month (first phase) 3.10(6) U IFN-alpha were administered i.m. every day, during the second month 3.10(6) U were administrated thrice weekly, during the third month 3.10(6) U IFN-alpha were administered i.m.twice weekly, and during the fourth month 3.10(6) U IFN were administered i.m. once a week. The average concentration of IgG, IgA, and IgM fall in the range of normal values during the therapy. Nevertheless, some mild stimulation of the IgG production and transient one for IgA can be noticed. The average value of A4 5 0 for patients was before therapy significantly (P less than 0.05) higher than normal value--at the end of the therapy it was in the range of normal A4 5 0.
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PMID:[Parameters of humoral immunity in patients with breast carcinoma during therapy with leukocyte interferon]. 191 52

The bacterial superantigen staphylococcal enterotoxin (SE) A (SEA) directs cytotoxic T lymphocytes (CTLs) expressing particular sequences of the T-cell receptor (TCR) beta chain to lyse tumor cells expressing major histocompatibility complex (MHC) class II molecules, which serve as receptors for SEs. We now report that chemical conjugates of SEA and the colon carcinoma-reactive monoclonal antibodies (mAbs) C215 or C242 mediate T cell-dependent destruction of colon carcinoma cells lacking MHC class II molecules. SEA was covalently linked to the mAbs C215 and C242 via a PEG-based hydrophilic spacer. The C215-SEA conjugate targeted CD4+ as well as CD8+ CTLs to lyse a panel of colon carcinoma cells lacking MHC class II molecules. T-cell recognition of mAb-SEA conjugates was SEA specific, since SEB-selective T-cell lines with potent cytotoxic activity towards Raji cells coated with SEB did not respond to the C215-SEA conjugate. Unconjugated SEA did not induce T-cell lysis of MHC class II- colon carcinoma cells but efficiently directed CTLs against MHC class II+ Raji cells and certain interferon-treated MHC class II+ colon carcinoma cells. These results suggest that SEA-mAb conjugates retain the SEA-related selectivity for certain TCR beta-chain variable region (V beta) sequences but, in contrast to unconjugated SEA, mediate the TCR interaction in a MHC class II-independent manner. The cytotoxic activity mediated by C215-SEA and C242-SEA conjugates was blocked by excess of C215 mAb and C242 mAb, respectively, showing that the specificity in the targeting of mAb-SEA conjugates is defined by the antigen reactivity of the mAb. These results demonstrate that bacterial superantigens may be successfully conjugated to mAb with preserved T cell-activating capacity. The circumvention of MHC class II binding of SEs by conjugation to mAb suggests that such conjugates may find general application as antitumor agents, taking advantage of the extreme T cell-activating potency of superantigens.
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PMID:Monoclonal antibody-targeted superantigens: a different class of anti-tumor agents. 192 93

We evaluated the effect of SOD, an oxygen-free radical scavenger, on peritumoral edema in 20 rabbits. The VX2 carcinoma was transplanted to the brains of these New Zealand white rabbits. Detection of superoxide radicals in vitro was performed by incubating the VX2 tumor cells with NBT. For evaluation of the effect of SOD on the tumor cells, they were treated with free SOD or PEG-SOD before and after incubation with NBT. The animals were separated into three groups: group 1, control group; group 2, SOD-untreated tumor group; group 3, two SOD-treated groups-group 3a, treated with 10,000 U/kg PEG-SOD on day 1 and 4 after tumor transplantation and sacrificed on day 13; group 3b, treated with 10,000 U/kg PEG-SOD on day 7 and 10 and sacrificed on day 13. Brain edema was assessed by SG measurement. Our preliminary in vitro data indicated that the VX2 carcinoma produced superoxide radicals but that free SOD and PEG-SOD could not penetrate into tumor cells nor inhibit superoxide radicals. In vivo data also indicated that PEG-SOD failed to reduce peritumoral edema. It was concluded that intracellular uptake or penetration of SOD must first be achieved before any effect on peritumoral edema can be assessed.
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PMID:Effect of superoxide dismutase in rabbits with peritumoral edema. 216 69

Immune complexes (ICs) were recovered from the ascites of a patient with stage IV endometrioid ovarian cancer by sequential precipitation with 33% saturated ammonium sulfate and 2.5% polyethylene glycol 6000 (PEG 6000), followed by affinity chromatography on protein A-Sepharose CL-4B. The IgG-containing ICs were dissociated using 8 M urea, separated by ion-exchange chromatography on Sephadex QAE-50, and subsequently analyzed for purity by immunoelectrophoresis (IEP) and radial immunodiffusion (RID). Recovered antibody was tested for reactivity by immunohistologic techniques against paraffin-embedded tumor tissue and acetone-fixed cell suspensions of epithelial tumors. The antibody which demonstrated ovarian cancer-associated activity was absorbed with antigen extracts of breast, colon, and lung cancers as well as keratin to reduce cross-reactivity. The absorbed endometrioid ovarian cancer-associated antibody (OCAAb) was used to produce an immunoadsorbent column for the recovery of tumor-associated antigens. A mouse monoclonal antibody designated FEN-1 was produced using this antigen-containing fraction, and preliminary screening has demonstrated ovarian tumor-associated reactivity. The use of autologous ICs as reagents for preparing tumor antigen-rich immunogens may provide a valuable tool in the search for tumor-associated antigens.
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PMID:Ovarian cancer-associated antibodies recovered from ascites: their use for the isolation of ovarian cancer-associated antigen to produce monoclonal antibodies. 218 6

Murine monoclonal antibody FEN-1 was derived by immunizing Balb/c mice with an affinity-purified endometrioid ovarian cancer-associated antigen recovered from ascites-derived immune complexes. Splenic lymphocytes from the immunized mouse were fused with the myeloma cells SP2/0-AG14 in the presence of PEG 1500. The hybrid cultures were screened for production of immunoglobulins reactive with an extract preparation of an endometrioid ovarian tumor by enzyme-linked immunosorbent assay and flow cytometry. One of the hybrids secretes a monoclonal antibody of the IgG3 subtype designated FEN-1, which reacts with 100% of endometrioid ovarian cancer containing adenoacanthoma by indirect immunoperoxidase on paraffin-embedded tissue. No detectable levels of antigen were found in squamous metaplasia associated with nonendometrioid tumors, and no reactivity occurred against endometrial adenocarcinomas, endometriosis, or normal ovary and endometrium. The antibody does not cross-react with mucinous tumors, nonepithelial tumors of the ovary, or gastrointestinal tissue. This antibody may be used as an aid in the diagnosis of nonmucinous ovarian carcinomas by immunohistology.
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PMID:Immunohistochemical characterization of a monoclonal antibody detecting an endometrioid ovarian cancer-associated antigen. 219 40

The F(ab')2 fragment of murine monoclonal antibody A7 was covalently bonded to polyethylene glycol (PEG, molecular weight: 5000) and the conjugate was compared to the parent F(ab')2 fragment by in vitro and in vivo studies. PEG-conjugated antibody fragment retained its antigen-binding activity in a competitive radioimmunoassay. The conjugate had a longer half-life and showed increased accumulation in tumors. Although the tumor: blood ratio for parent F(ab')2 fragment was higher than that for the conjugate, it showed higher value than whole MAb A7. The tissue: blood ratios were kept low with the conjugate, indicating that the conjugate was uptaken to normal organ with lesser extent, as compared with parent F(ab')2 fragment. Our findings indicate that this PEG-conjugated F(ab')2 fragment could be a promising carrier for use in targeting cancer chemotherapy.
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PMID:Polyethylene glycol modification of the monoclonal antibody A7 enhances its tumor localization. 222 51


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