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)

The incorporation of polyethylene glycol-6000 (PEG) into the culture media of tumor-infiltrated spleen cells (TISpC) and MOPC-315 stimulator tumor cells at a responder to stimulator cell ratio of 30/1 had been shown to lead to the appearance of CD8+ T-cells that were effective in adoptive chemoimmunotherapy (ACIT) of mice bearing a barely palpable MOPC-315 tumor (J. A. Wise, M. B. Mokyr, and S. Dray, Cancer Res., 49:3613-3619, 1989). Here we show that in the presence of substantially fewer added stimulator tumor cells (responder to stimulator cell ratio, 100/1), the inclusion of PEG in the cultures of TISpC also enhanced the appearance of cells that were highly effective in curing such mice by ACIT. Moreover, these PEG-cultured TISpC were more effective in ACIT than TISpC cultured in the presence of an optimal concentration of recombinant interleukin-2 (60 IU/ml). The potency of the tumor-eradicating activity of the PEG-cultured TISpC in ACIT was further illustrated by their ability to cause the complete regression of a large (20-22 mm) s.c. MOPC-315 tumor in conjunction with a dose of drug that by itself did not cause tumor regression. PEG-cultured TISpC that were effective against MOPC-315 tumor cells in an antigen-specific manner. In fact, PEG-cultured TISpC were more effective than recombinant interleukin-2-cultured TISpC, not only in ACIT, but also in their ability to lyse MOPC-315 tumor cells in vitro. Thus, a direct specific lytic activity against the tumor by cytotoxic T-lymphocytes is the apparent mechanism through which the complete regression of the large tumor burden is brought about by the PEG-cultured TISpC. Finally, we suggest that the incorporation of PEG to render ineffective lymphoid cells effective in ACIT may offer some advantages compared with the incorporation of recombinant interleukin-2 and may be suitable for protocols to generate human cytotoxic cells for cancer therapy when there are relatively low numbers of available tumor cells.
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PMID:Advantages of adoptive chemoimmunotherapy with polyethylene glycol-cultured, antigen-activated, tumor-infiltrated spleen cells for the complete eradication of lethal MOPC-315 plasmacytomas. 187 95

Phospholipase A2 (PLA2) can participate in the regulation of eicosanoid biosynthesis via PLA2-mediated control of the release of arachidonic acid from phospholipids. Arachidonoyl-hydrolyzing PLA2s were examined in cells from normal mouse mammary glands and mammary carcinomas. Tumor-derived cells exhibited significant PLA2 activity(ies) with arachidonoyl containing phosphatidylcholine and phosphatidylethanolamine as substrates in cell-free assays. In contrast, arachidonoyl containing phosphatidylinositol was a poor substrate. When phosphatidylcholines with varying sn-2 fatty acyl groups were tested as substrates, activity was highest with the arachidonoyl containing lipid. The pH profiles for hydrolysis of phosphatidylcholine and phosphatidylethanolamine differed; all other aspects of PLA2-mediated hydrolysis of these two substrates were similar including a Ca2+ requirement for activity. Moreover, Ca2+ affected the subcellular localization of the enzyme activity. Activity was predominately in the supernatant fraction when cells were harvested in an EGTA (ethylene glycol bis(beta-aminoethylether)-N,N,N',N'-tetraacetic acid) containing buffer and largely in the particulate fraction when cells were harvested in a buffer containing free Ca2+. The localization of activity could be modulated from the supernatant fraction to the particulate fraction by recentrifugation in the presence of Ca2+. Normal gland-derived cells contained a PLA2 activity with properties similar to those of the tumor-derived cells. There was a significant difference in the level of activity in the normal versus tumor cells, the normal gland-derived cells had less than half the PLA2 activity of the carcinoma-derived cells.
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PMID:Localization and characterization of phospholipase A2 in mouse mammary gland-derived cells. 191 Feb 88

Immunologic methods for detection of colorectal neoplasia based on examination of stool or colonic effluent are being developed. Most current oral lavage preparations contain polyethylene glycol (PEG), and if PEG adversely interferes with immunologic testing these tests may become less useful. We describe a decrease in sensitivity of ELISA for tumor-associated antigens (TAA) when effluent samples are diluted in PEG-electrolyte lavage solution, equivalent to a commonly used oral lavage solution based on PEG. Radioisotope-labeled antigen binding to plastic plates was decreased by dilution in the PEG lavage solution. Antigen binding, present in colonic effluent collected by the laxative purge method, was absent in effluent collected by PEG oral lavage from the same patient. We conclude that PEG and PEG-containing lavage solutions interfere with ELISA detection of TAA in colonic effluents. We speculate that the in vitro, and possibly the in vivo, effect occurs at the level of antigen binding to the plate either by a steric effect or alteration of charge by the nonpolar properties of PEG.
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PMID:Oral colon lavage solutions containing polyethylene glycol may interfere with ELISA detection of tumor-associated antigens in colonic effluent. 191 69

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

A more soluble formulation of recombinant interleukin-2 with a prolonged half-life would allow alternate routes or schedules of administration and enhance patient comfort. The covalent attachment of polyethylene glycol to recombinant interleukin-2 provides an analog with preclinical data suggesting those desired characteristics while maintaining biologic activity. This is the report of a phase I study in which we sought to determine the maximum tolerated dose of polyethylene glycol interleukin-2, observe biologic activity, and confirm the prolonged half-life in vivo. Sixty-six patients were entered into the study during 19 months. Polyethylene glycol interleukin-2 was administered intravenously once a week over 15 minutes. The maximum tolerated dose was 20 x 10(6) U/M2. The pattern of toxicity was quite similar to that of the parent compound. Four patients had evidence of tumor regression (three partial remission; one minor response). The pharmacokinetic data confirmed a 10- to 20-fold prolongation in half-life compared with recombinant interleukin-2. No neutralizing antibodies were detected. This study provides sufficient impetus for the ongoing phase II studies of polyethylene glycol interleukin-2.
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PMID:A phase I study including pharmacokinetics of polyethylene glycol conjugated interleukin-2. 200 24

In this prospective study, flow cytometry DNA profile of 169 stage D2 prostatic carcinomas were compared with conventional cytologic data. Two transrectal fine-needle aspiration biopsies were performed in each patient. Aspirates were immediately fixed in 2% polyethylene glycol 1500* alcoholic solution (Merck). Suspensions were mixed and studied by a conventional cytologic technique (Papanicolaou) and by flow cytometry (propidium iodide stain on isolated nuclei). A highly significant correlation was found between the DNA profile and the cytologic grade (p less than 0.001). The DNA profile was bimodal in 14% (3/21) of aspirates containing benign or atypical cells, 18% (3/17) of grade I aspirates, 30% (13/43) of grade II aspirates and 71% (24/34) of grade III aspirates. Routine cytologic evaluation of cell suspensions evaluated by flow cytometry is important in clinical practice since both falsely unimodal and falsely bimodal profiles occur. Leukocytes or benign epithelial cells can interfere with the tumor cell population. In fine-needle aspirates, the broad range of non-malignant contaminating cells limits the value of immunocytochemistry and emphasizes the usefulness of routine conventional cytologic evaluation.
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PMID:[Analysis of tumor DNA by flow cytometry on prostate cyto-aspiration product. Value of routine cytologic evaluation]. 205 20

In the last 3 years tumour antigens (TA) and immune complexes (IC) were examined in 33 respectively 83 patients with cancer of the larynx. These tests were repeated several times during treatment and during the checking period. Tumour antigens were prepared from squamous cell carcinoma of the larynx using a modification of the methods by Bloom et al. and Halliday. Immune complexes in the serum were determined by the polyethylene glycol (PEG) test. In some cases the sensitivity to antigen was changed during the observation period. Constantly elevated immune complexes speaks in favour of recurrence in most of our cases.
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PMID:Implication of tumour antigens and immune complexes in laryngeal cancer. 206 32

A carrier for a new tumor imaging agent, a bifunctional chelating agent (BCA)-coupled porphyrin (ATN-2), has been synthesized from protoporphyrin dimethyl ester in 4 steps. At first, the hydrobromination of protoporphyrin dimethyl ester is carried out to obtain a monobromo derivative. The derivative is treated with ethylene glycol. The resulting porphyrin has an ether group at the either 7- or 12-position of the ring. Metallation with GaCl3 of the porphyrin having a ethylene glycol residue affords Ga-metalloporphyrin. Final condensation of the metalloporphyrin with diethylenetriaminepentaacetic acid (DT-PA) gave BCA-coupled porphyrin (ATN-2). The chelation of ATN-2 with 111InCl3 easily afforded [111In]ATN-2. This agent was used for imaging transplantable pancreatic carcinoma in Syrian golden hamster at 72 h after postinjection. The efficacy of the new agent was compared with that of [67Ga]citrate. The images with [111In]ATN-2 were found to be clearer than those with [67Ga]citrate. Therefore, ATN-2, a carrier for 111InCl3, seems to be more useful for tumor imaging agents.
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PMID:[Studies on porphyrin related compounds and tumor tissue affinities. I. Synthesis of a carrier for tumor imaging agent, bifunctional chelating agent coupled porphyrin (ATN-2)]. 207 37

Human-human hybridomas were generated using pokeweed mitogen-stimulated lymphocytes from the regional lymph nodes of cancer patients by fusion to the LICR-2 human myeloma cell line. A total of 35 fusions, using the regional lymph node lymphocytes of cancer patients, resulted in hybrid growth in 23% of wells plated with 21 IgG ELISA positive clones, 6 of which have maintained stable human monoclonal antibody production. Mononuclear cells were separated on Ficoll-Paque and grown for 3-4 days in 1% pokeweed mitogen and fused to the LICR-2 human myeloma cell line. Human-human hybridoma producing membrane reactive IgG antibodies have been isolated and react to the following cancers: breast; melanoma. Twenty-seven fusions from 8 breast carcinoma patients resulted in 13 ELISA positive IgGs, 3 of which were stable after cloning. A total of 5,071 wells were plated after polyethylene glycol fusion with resultant hybrid growth in 1210 wells (24% hybrid growth) after hypoxanthine-aminopterin-thymidine selection. In 8 fusions using regional lymph node lymphocytes of other types of cancer, including 6 fusions using lymphocytes from malignant melanoma patients, there were 1,580 wells plated with positive growth in 20% of the wells (311 wells). Of these, 8 clones were ELISA positive and 3 stable clones all producing IgG anti-melanoma antibody were isolated. The overall hybrid frequency was 43 x 10(-7) fused lymphocytes (39 x 10(-7) non-breast and 45 x 10(-7) breast). A total of 21 IgG-producing clones were identified to crude membranes of allogeneic tumor cell lines and stable antibody production was achieved for 6 (29% stable clones).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pokeweed mitogen-stimulated human lymphocytes fused to LICR-2 (HMY2) generate human-human hybridomas producing monoclonal IgG antibodies reactive to human breast carcinoma and malignant melanoma. 210 59


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