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)

Seven patients completed couses of immunotherapy using neuraminidase-altered autochthonous cells. Their response to therapy was monitored by a cytotoxicity assay using 3H-proline-tagged tumor cells from the patient's own cultured tumor in a strictly autologous system. Serum effects were measured by exposing the tumor target cells to serum to see whether this impeded (blocked) or augmented (potentiated) lymphocyte cytotoxicity. Three of the seven patients developed increasing degrees of serum blocking effect and all died within six months of completing therapy. Four of the seven showed rapidly decreasing blocking and three eventual potentiation. Three patients are living, improved, and free of evidence of tumor. There was an increase in average serum immunoglobulins in patients developing potentiation, and a decrease in those showing blocking. In any immunotherapy program attention must be given to in vitro monitoring studies, and such studies should include attention to the serum factors influencing host response.
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PMID:Neuraminidase immunotherapy: serum potentiation of lymphocyte cytotoxicity related to immunoglobulin levels. 94 5

A lactam analog of actinomycin D (AMD) has been synthesized as a potential antitumor chemotherapeutic agent. Both L-threonine residues were replaced by L-alpha,beta-diaminopropionic acid. Starting with Nalpha-benzyloxycarbonyl-Nbeta-tert-butyloxycarbonyl-L-alpha,beta-diaminopropionic acid methyl ester hydrochloride the linear intermediate Nalpha-benzyloxycarbonyl-Nbeta-(tert-butyloxycarbonylsarcosyl-L-N-methylvalyl)-L-alpha,beta-diaminopropionyl-D-valyl-L-proline p-nitrophenyl ester was prepared by conventional methods of peptide synthesis in solution. Selective cleavage of the Nbeta-tert-butyloxycarbonyl group and lactam formation afforded the desired cyclic pentapeptide derivative. The chromophore precursor, Nalpha-(2-nitro-3-benzyloxy-4-methylbenzoyl) substituent, was introduced via its symmetric anhydride. Catalytic reduction followed by ferricyanide-mediated phenoxazinone formation provided the lactam analog, [di(1'-L-alpha,beta-diaminopionic acid)]actinomycin D ([Dpr1]2-AMD). Its binding to natural and synthetic DNA and that of an analogous L-threo-alpha,beta-diaminobutyric acid containing lactam ([Dbu1]2-AMD) compared with the binding of AMD (in which the peptides are in lactone form) was studied by circular dichroic (CD) spectroscopy. The visible and uv CD spectra of free AMD differed from those of the free lactam analogs, indicating that the asymmetric environment of the pentapeptide rings in the region of the chromophore differs in free actinomycin lactone and lactams. In the presence of calf thymus DNA, PM2 DNA, and the synthetic d(A-T)-like copolymers containing 2,6-diaminopurine (DAP), poly[d(DAP-T)], and poly[d(DAP-A-T)], the rotational strengths of the optically active transitions in the visible region of the actinomycins increased, and the CD spectra in the presence of the various DNA duplexes were qualitatively similar. The CD spectra of bound actinomycin lactams resembled the spectrum of bound AMD. This suggests that the lactone and lactam actinomycins acquire a similar environment when bound to DNA. [Dpr1]2-AMD was less cytotoxic than AMD in antibacterial assays but exhibited somewhat higher toxicity in mice than AMD. At optimal dose levels the lactam analog had little or no antitumor activity in three murine tumor systems.
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PMID:Synthesis and some properties and antitumor effects of the actinomycin lactam analog, (di(1-L-alpha, beta-diaminopropionic))actinomycin D1. 95 Jun 43

An in vitro lymphocyte-mediated cytotoxicity assay using [3H]proline-labeled target cells is described. The assay, modified from an original procedure of Bean et al., assesses the release of [3-H]proline by filtering the total culture fluid containing both trypsinized tumor cells and effector cells. Filtration is performed with a semiautomatic harvesting device using low suction pressure and large-diameter glass filters. Pretreatment of filters with whole serum diminishes adsorption of cell-free radioactive material considerably and thus increases the sensitivity of the assay. Nearly 100% of the radioactivity could be recovered with this harvesting device. The technique allowed the detection of cytolytic activities of lymphocytes after 6 h of incubation. Lymphocytes from patients with primary malignant melanoma showed a significantly higher cytolytic reactivity (P less than 0.001) than normal donors' lymphocytes against three different melanoma cell lines. In a series of parallel experiments on 36 patients and 18 normal donors, this modification of the [3H]proline test was compared with three different assays: the conventional microcytotoxicity test of Takasugi and Klein, the original [3H]proline microcytotoxicity test of Bean et al., and the viability count of tumor cells.
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PMID:Cell-mediated cytotoxicity for melanoma tumor cells: detection by a (3H) proline release assay. 95 79

Activities of hydrolytic enzymes on the surface of monkey kidney, canine kidney, L. FM3A and various tumor cells were determined and compared with those in the cell homogenate. Although aminopeptidase (EC 3.4.11.-) activities were always detected on the surface membrane in mammalian cells, trypsin, chymotrypsin and elastase activities were not detected while slight glycosidase activity was detected in a suspension of cultured cells. The activities of alanine-, leucine-, methionine- and phenylalanine-aminopeptidases were rather high but aminopeptidase A, proline-, valine-, glycyl propline dipeptidyl-and glycyl propyl leucine-tripeptidyl-aminopeptidases showed relatively low activities. Aminopeptidase activity was also demonstrated in the isolated membrane fractions. The specific activities of enzymes in these membrane fractions were not significantly greater than in cell homogenate so it was concluded that these enzyme activities were rather loosely bound to the cell membrane. Further evidence for the localization of the aminopeptidase activities on the cell surface was obtained by using glass-bead-bound substrate and detecting the release of the terminal residues. When bestatin, a specific inhibitor against aminopeptidase B and leucine aminopeptidase, was included in the assay system for the enzyme activities on the cell surface, the enzymes were commonly inhibited in all types of cells.
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PMID:Aminopeptidase activities on the surface of mammalian cells. 99 Mar 9

A sensitive assay for antibody-dependent cell-mediated cytotoxicity (ADCMC) was developed utilizing serum from a patient with gestational choriocarcinoma and the 3H-proline microcytotoxicity test for detection fo destruction of monolayer target cells. Conditions for optimal expression of ADCMC were investigated using serum from this patient and skin fibroblasts from her husband and daugther as target cells with semi-purified blood leukocytes from normal donors as effector cells. Factors critical for optimal expression of ADCMC in this assay are the selection of effector cell donors possessing high levels of activity in the presence of serum with known lymphocyte-dependent antibody. (LDA), the effector cell preparative technique, and incubation for up to 40 h. Tris-NH4Cl lysis of red blood cells was found significantly to reduce effector cell activity. Under optimal conditions, the LDA titer of this patient's serum was greater than 10(-4). The sensitivity of the assay was confirmed by the detection of LDA activity of an anti-blood-group antibody at dilutions not demonstrating hemagglutination, and by the induction of ADCMC for blood group A antigen-bearing target cells by normal sera of B and O blood groups. In a preliminary study of sera from 16 melanoma patients on the corresponding antologous tumor target cells, four had significant LDA. Further studies are under way to determine specificty, incidence, and relationship of LDA-positive autologous sera to course of disease.
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PMID:Antibody-dependent cell-mediated cytotoxicity for human monolayer target cells bearing blood group and transplantation antigens and for melanoma cells. 108 Jul 51

A microcytoxicity assay with 3H-proline prelabeled target cells was used for the detection of sensitized lymphoid spleen cells from STU inbred mice inoculated with Moloney sarcoma virus (MSV-M) or ascitic MSV-M tumor cells. The target cell line was derived from ascitic MSV-M tumor cells. With regard to the specificity of the assay nonimmune slpeen cells displayed no or only a weak cytotoxicity against these cells, and this was also the case when 3H-proline-labeled secondary cultures of syngeneic mouse embryo cells were exposed to both sensitized and nonimmune spleen cells. The time-course pattern of the development of cytotoxic lymphoid spleen cells in STU mice inoculated intramuscularly either with MSV-M or ascitic MSV-M tumor cells was studied. At the stages of tumor development, peak tumor size, and tumor regression the lymphoid spleen cell preparations were found to have relatively strong cytotoxic activity independent of whether the tumor was induced by MSV-M inoculation or tumor cell transplantation. However, in the latter case effector cells appeared earlier and were demonstrable for a longer period than in MSV-M-inoculated mice. Anti-theta serum treatment of lymphoid spleen cells taken at the stage of peak tumor size abrogated the cytotoxic activity or diminished it considerably indicating a T-lymphocyte response.
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PMID:Detection of cytotoxic lymphoid spleen cells from STU-mice with Moloney sarcoma by a 3H-proline microcytotoxicity assay. 108 60

The participation of B cells in cell-mediated cytotoxicity (CMC) for allogeneic and syngeneic murine sarcoma cells induced with 3-methylcholanthrene was investigated. Primed nonadherent peritoneal cells (NAPC) were treated with antisera against lymphocyte surface antigens and complement, and residual CMC activity was measured with the [3H]proline microassay. The antisera (anti-PC.1 and various anti-Ig sera) used for this purpose were highly reactive with B cells according to established serologic criteria. Elimination of cells that carried PC.1 or Ig on their surface did not diminish CMC of NAPC for allogeneic or syngeneic tumor cells. Exposure of cytotoxic NAPC to various anti-Ig antisera (without complement) before and during the CMC assay did not inhibit CMC either. We conclude that under these conditions CMC is not mediated by B cells, nor is it dependent on their presence. In addition, our findings do not implicate any of the usual classes and types of Ig covered by the Ig antisera used in this study as constituting specific receptors on the effector T cells of CMC.
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PMID:Surface phenotype of nonadherent peritoneal cells effecting cell-mediated cytotoxicity in vitro for allogeneic and syngeneic murine sarcoma cells. 108 82

A lymphocyte cytotoxicity (CTX) test with 3-H-proline-prelabeled target cells was used to detect the immune response of murine lymphoid cells to H-2 and tumor antigens. The specificity of the reaction was determined by simultaneous tests on unrelated target cells and, for reactions directed against H-2 antigens, by blocking experiments with alloantiserum directed against the H-2 antigens of the target cells. After a single intraperitoneal (ip) injection of allogeneic spleen cells, CTX of unfractionated peritoneal cellswas strong, with a sharp peak on day 5. Repeated ip immunization markedly increased the CTX of unfractionated peritoneal cells. The reaction was strongest when the test was done at 37 degrees C. Sometimes CTX should be detected after as little as 6 hours' incubation. CTX depended primarily on the absolute number of effector or target cells per area rather than on the ratio of effector to target cells. Both nonadherent and adherent peritoneal cells destroyed target cells specifically. The CTX of nonadherent peritoneal cells was increased by 2-mercaptoethanol. The CTX reaction depended on effector cells bearing Tyl-1. Destruction of "innocent bystander" target cells was seen with one of four combinations of unfractionated and nonadherent peritoneal cells from hyperimmune animals.
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PMID:Cytotoxic reactions of murine lymphoid cells studied with a tritiated proline microcytotoxicity test. 111 24

Chick embryo collagen-synthesizing polysomes were isolated by differential centrifugation. RNA extracted from these particles was chromatographed in oligo(dT)-cellulose solumns and the mRNA thus obtained characterized as collagen mRNA by its electrophoetical mobility in acrylamide gels (equivalent to 1.05 x 10-6 daltons) and its effect upon a cell-free system derived from Krebs ascites tumor cells. The incorporation of 3H-proline was markedly dependent upon rabbit reticulocyte initiation factors and inhibited by initiation inhibitors such as aurintricaboxilate and pyrocatechol violet. The incorporation product was characterized as collagen by its lack of tryptophan, digestibility by purified bacterial collagenase, and by its co-chromatography with unlabled chick collagen in Sephadex G-200 and CM-cellulose columns.
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PMID:Isolation and characterization of collagen messenger RNA*. 114 59

In vitro cell-mediated cytotoxicity (CMC) assays have been carried out in human melanoma system with blood effector lymphocytes on [3H]proline-labeled target cells in a 48-hr microcytotoxicity technique. Three lymphocyte purification procedures (Ficoll:Hypaque gradient, plasma gel sedimentation followed by nylon column incubation, and plasma gel sedimentation followed by separation with nylon powder and glass beads) are compared in parallel experiments for characteristic effector cell composition and cytotoxic potential against target cells of dissimilar histology. The cytotoxicity is defined by the loss of target cell 3H cpm as measured by residual target cell 3H cpm in individual microwell following incubation with lymphocytes. Target cell 3H cpm loss by test lymphocytes is compared with target cell 3H cpm loss by several age and sex matched control lymphocytes (from normal donors and unrelated cancer patients); further comparison between the various control lymphocytes is also made in each assay. As control for target cells, autologous fibroblasts and homologous tumor cells of dissimilar histology are always included in each assay. Specific cytotoxicity is defined as statistically significant and selective destruction of only melanoma cells by the test lymphocytes as compared to the control lymphocytes. Significant but nonselective destruction of 2 or more target cells of unrelated histology is regarded as nonspecific cytotoxicity, while no destruction of any target cells signifies no cytotoxicity. The Ficoll:Hypaque preparations consistently exhibit the highest nonlymphocytic cell contamination (8 to 16%); the nonlymphocytic cells are, almost exclusively, monocytes. They also produce relatively high percentage of thymus independent (B) cells (8 to 15%). The ultimate cell composition of the 2 plasma gel-nylon preparations is essentially identical. In either plasma gel-nylon preparations, the nonlymphocytic contamination is minimal (0 to 4%) and thymus-dependent (T) cell percentage is considerably higher (92 to 99%) with none or few B cells.
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PMID:Variables and specificity of in vitro lymphocyte-mediated cytotoxicity in human melanoma. 119 30


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