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Biomedical subjects

R C Bast

Publications and source records attributed to R C Bast.

At least 253 records · Page 14Linked to original sources
PubMed1983

Monocyte chemotaxis mediated by formyl-methionyl-leucyl-phenylalanine conjugated with monoclonal antibodies against human ovarian carcinoma.

Availability of a chemically defined chemoattractant (fMLP) and of appropriate monoclonal antibodies may permit local manipulation of the inflammatory response to human tumors. fMLP has been conjugated with two monoclonal antibodies (OC125 and OC133) which react with human ovarian carcinomas. Conjugates retained the ability to bind to a human ovarian carcinoma line (OVCA433) judged by indirect immunofluorescence and by radioimmunoassay. The fMLP conjugate was maximally chemotactic for human blood monocytes and human peritoneal macrophages at protein concentrations of 300-900 micrograms/ml. Conjugates stimulated chemotaxis rather than chemokinesis. After incubation with an fMLP-antibody conjugate, antigen positive OVCA433 cells released chemotactic activity and attracted monocytes in vitro, whereas an antigen-negative ovarian cell line failed to do so. As monocytes can be important effectors of antibody dependent cell mediated cytoxicity, fMLP conjugates might increase monocyte concentrations at tumor sites and potentiate serotherapy for certain human neoplasms.

Antibodies, Monoclonal↗
PubMed1983

Immunopathologic characterization of a monoclonal antibody that recognizes common surface antigens of human ovarian tumors of serous, endometrioid, and clear cell types.

A murine monoclonal antibody, OC125, reacts with a surface component of ovarian tumor cells from humans, but fails to react with normal adult ovarian cells. The spectrum of reactivity of OC125 in ovarian tumors from humans was defined by testing cryostat tissue sections from 60 selected ovarian tumors by indirect immunofluorescence. OC125 stained 7/7 benign, and borderline serous ovarian tumors, 19/23 (83%) serous adenocarcinomas, 2/2 mixed serous and endometrioid carcinomas, 2/3 endometrioid carcinomas, 1/4 clear cell carcinomas, and 2/2 undifferentiated carcinomas. No reactivity was found in eight mucinous ovarian tumors or any of the other 11 epithelial sex cord, germ cell, on hematopoietic tumors tested. In neoplastic cysts, papillae, and glands, the staining was most intense on the luminal surface or in subjacent cytoplasm. Cells in solid sheets also showed peripheral staining. Within a reactive tumor, both negative and positive cells could be found, intimately intermixed. There were no differences in these staining patterns between tissues from primary and metastatic sites. The expression of the OC125 antigen was not related to the degree of malignancy as judged by pathologic criteria. Although mucinous tumors lacked reactivity with OC125, seven of eight mucinous adenomas and adenocarcinomas bound a monoclonal antibody against carcinoembryonic antigen (CEA). Thus, OC125 recognizes a common antigen in some but not all ovarian tumors of serous, clear cell, endometrioid, or undifferentiated type. OC125 may prove useful in the pathologic and cytologic identification of certain types of ovarian tumor cells. Its lack of reactivity with mucinous tumors suggests these belong in a distinct subgroup of ovarian epithelial tumors.

Adenocarcinoma↗
PubMed1983

Tissue distribution of a coelomic-epithelium-related antigen recognized by the monoclonal antibody OC125.

OC125, a murine monoclonal antibody, recognizes an antigenic determinant (CA125) that is associated with greater than 80% of epithelial ovarian neoplasms of serous, endometrioid, clear cell, and undifferentiated types. In the present report, a sensitive biotin-avidin immunoperoxidase technique was used to determine reactivity of OC125 with normal adult and fetal tissues, as well as with neoplasms of nonovarian origin. In fetal tissues, the antibody reacted with amnion and with derivatives of the coelomic epithelium, i.e., the müllerian epithelium and the lining cells of the peritoneum, pleura, and pericardium. Among adult tissues, OC125 reacted with the epithelium of fallopian tubes, endometrium, and endocervix. The CA125 determinant was also detected on mesothelial cells in the adult pleura, pericardium, and peritoneum, particularly in areas of inflammation and adhesion. Curiously, the surface epithelium of normal fetal and adult ovaries, thought to be derived from coelomic epithelium, did not express the determinant, except in inclusion cysts, areas of metaplasia, and papillary excrescences. Of neoplastic tissues of nonovarian origin, OC125 reacted consistently only with adenocarcinomas of the endocervix, endometrium, and fallopian tube, and with mesotheliomas. Only seven of 64 nongynecological tumors tested reacted with OC125. Thus, OC125 detects a differentiation antigen shared by fetal coelomic epithelium and its derivatives in the fetus and the adult. Apparently, this antigen disappears early in the course of formation of the ovarian epithelium and is reexpressed in certain reactive and neoplastic lesions, a process that could be termed "molecular metaplasia."

Adenocarcinoma↗
PubMed1983

Elimination of leukemic cells from human bone marrow using monoclonal antibody and complement.

Human leukemic cells which bear the common acute lymphoblastic leukemia antigen can be lysed with a murine monoclonal antibody (J-5) in the presence of rabbit complement. Conditions have been defined for eliminating 51Cr-labeled common acute lymphoblastic leukemia antigen-positive NALM-1 cells or cryopreserved leukemic lymphoblasts from a 100-fold excess of human bone marrow. Optimal lysis is obtained with treatment for a total of 90 min. Three treatments for 30 min are more effective than two treatments for 45 min or one treatment for 90 min. Separation of marrow on a Ficoll:diatrizoate gradient does not permit more effective elimination of leukemic cells. Tumor cell lysis is inhibited by high concentrations of common acute lymphoblastic leukemia antigen-positive cells (2 X 10(7)/ml) and by high concentrations of bone marrow (10(8)/ml). Under optimal conditions, greater than 99% of 51Cr-labeled leukemic lymphoblasts can be eliminated from a 100-fold excess of human marrow. Selective removal of leukemic cells from human bone marrow in vitro should facilitate trials of autologous marrow transplantation.

Antibodies, Monoclonal↗
PubMed1983

Enhanced arachidonic acid lipoxygenation by K562 cells stimulated with 12-O-tetradecanoylphorbol-13-acetate.

The arachidonic acid lipoxygenase products released into culture supernatants by the human myeloid cell line K562 were quantitated by high-performance liquid chromatography. During 2 hr of incubation, K562 cells spontaneously released a mean of 9 ng of 15-monohydroxyeicosatetraenoic acid, 35 ng of 5-monohydroxyeicosatetraenoic acid, and 87 ng of a partially resolved mixture of 11- and 12-monohydroxyeicosatetraenoic acid per 10(7) cells. The addition of 50 micrograms of arachidonic acid per ml to the cell cultures increased the quantities of monohydroxyeicosatetraenoic acids generated after 2 hr of incubation by 10- to 100-fold; changes in the ratios of these lipoxygenase products occurred over 24 hr of incubation. The tumor promoter 12-O-tetradecanoylphorbol-13-acetate, at concentrations of 5 to 25 ng/ml increased arachidonic acid lipoxygenation 1- to 2-fold in cultures containing 50 micrograms of arachidonic acid per ml, and up to 20-fold in cultures not supplemented with arachidonic acid. The lipoxygenation of arachidonic acid was enhanced 2- to 9-fold for up to 24 hr after a 2-hr exposure of K562 cells to 12-O-tetradecanoylphorbol-13-acetate. Nordihydroguaiaretic acid, a lipoxygenase inhibitor, blocked the effects of 12-O-tetradecanoylphorbol-13-acetate, suggesting that the monohydroxyeicosatetraenoic acids are the products of specific lipoxygenases rather than of nonenzymatic oxidative reactions. The capacities of phorbol esters to promote tumors in the mouse skin model corresponded to their respective capacities to enhance the lipoxygenation of arachidonic acid to 15- and 5-monohydroxyeico-satetraenoic acid but not to 11- and 12-monohydroxyeico-satetraenoic acid.

Arachidonate Lipoxygenases↗
PubMed1983

Intraperitoneal immunotherapy of human ovarian carcinoma with Corynebacterium parvum.

Corynebacterium parvum has been administered i.p. to 14 patients with advanced ovarian cancer. Two patients had responded completely to cytoreductive surgery and combination chemotherapy prior to immunotherapy, and one patient with residual disease had received only a single course of C. parvum due to i.p. catheter malfunction. Among the 11 patients with residual disease evaluable for response, from three to eight i.p. treatments with C. parvum produced surgically confirmed tumor regression in five patients (45%) with three partial responses and two complete responses of 5 and 12 months duration. All responders had (a) multiple tumor nodules less than 0.5 cm at the initiation of immunotherapy, and (b) severe abdominal pain and fever after C. parvum injection. Overall, 58 courses of immunotherapy were associated with abdominal pain (91%), fever (67%), nausea (52%), vomiting (31%), and hypotension that responded promptly to i.v. infusion of fluids (10%). Use of i.p. cathethers was associated with two episodes each of infection and intraabdominal bleeding. Administration of C. parvum i.p. has augmented the ability of human peritoneal cells to lyse human ovarian carcinoma cell lines in the presence of specific rabbit heteroantiserum. C. parvum administered i.p. has inhibited the growth of human ovarian carcinoma and may prove useful for modulating the activity of human effectors for antibody-dependent cell-mediated cytotoxicity.

Adult↗
PubMed1982

Autologous bone-marrow transplantation in CALLA-positive acute lymphoblastic leukemia after in-vitro treatment with J5 monoclonal antibody and complement.

A monoclonal antibody (J5) specific for the common acute-lymphoblastic-leukaemia antigen (CALLA) was used for in-vitro pre-treatment of bone-marrow before autologous transplantation in four patients with CALLA-positive acute lymphoblastic leukaemia (ALL) in relapse, who did not have HLA-compatible donors. After remission induction and intensification, bone-marrow cells were harvested, treated with J5 antibody and rabbit complement, and cryopreserved in liquid nitrogen. Patients received ablative chemotherapy and total-body irradiation before reinfusion of autologous J5-treated bone marrow. The transplantation protocol was well tolerated, and engraftment of normal myeloid cells occurred in all for patients. Two patients have continued in unmaintained remission with complete haematopoietic reconstitution for more than 1 year after autologous transplantation.

Antibodies, Monoclonal↗
PubMed1981

Reactivity of a monoclonal antibody with human ovarian carcinoma.

A murine monoclonal antibody (OC125) has been developed that reacts with each of six epithelial ovarian carcinoma cell lines and with cryopreserved tumor tissue from 12 of 20 ovarian cancer patients. By contrast, the antibody does not bind to a variety of nonmalignant tissues, including adult and fetal ovary. OC125 reacts with only 1 of 14 cell lines derived from nonovarian neoplasms and has failed to react with cryostat sections from 12 nonovarian carcinomas.

Animals↗
PubMed1981

Absence of common ALL antigen on normal bipotent myeloid, erythroid, and granulocyte progenitors.

The presence of the common acute lymphoblastic leukemia antigen (CALLA) on leukemic cells from the great majority of patients with non-T cell acute lymphoblastic leukemia and chronic myelogenous leukemia in blast crisis suggests that CALLA could be differentiation antigen expressed by normal lymphoid and myeloid stem cells. Treatment with a murine monoclonal anti-CALLA antibody and complement lysed CALLA-positive leukemic cells quantitatively, whereas similar treatment of nucleated cells from peripheral blood and bone marrow failed to affect the expression, in semisolid culture, of CFU-G/E, BFU-E, CFU-E, or CFU-C. These data suggest that CALLA is not a normal differentiation antigen of the myeloid bipotent cell or its committed progenitors.

Acute Disease↗
PubMed1981

Elimination of leukemic cells from rat bone marrow using antibody and complement.

An animal model has been developed that utilizes antibody and complement to eliminate a transplantable cloned line of Wistar/Furth acute nonlymphocytic leukemia (CI-3) from syngeneic Wistar/Furth bone marrow. The CI-3 leukemia grows progressively from an i.v. inoculum of 10(1) to 10(2) cells. Antiserum has been raised in rabbits following multiple injections of CI-3. Using optimal concentrations of absorbed antibody and complement, approximately 3 logs of tumor could be destroyed in vitro, judged by the number of cells required to produce progressive growth in vivo. Similar incubation with antibody and complement did not affect the ability of Wistar-Furth marrow to reconstitute rats that had received lethal total-body irradiation (950 R). Each of the 33 irradiated rats that received mixtures of 10(4) CI-3 and 1.6 X 10(8) nucleated bone marrow cells succumbed to leukemia within 65 days, whereas 16 of 33 rats (48%) receiving similar inocula that had been treated with antibody and complement survived greater than 180 days without evidence of tumor growth. Repeated treatment of contaminated marrow with antibody and complement following removal of mature granulocytes and erythrocytes on density gradients permitted elimination of 10(5) CI-3.

Animals↗
PubMed1981

Aryl hydrocarbon (benzo[a]pyrene) hydroxylase in guinea pig lymphoid tissue.

Aryl hydrocarbon hydroxylase (AHH) activity was detected in a variety of guinea pig lymphoid tissues and was increased by intradermal or ip administration of 3-methylcholanthrene AHH levels were generally greater in spleen than in lymph node, bone marrow, or thymus. Similar AHH activities were observed in lymphoid tissues from Sewall-Wright inbred strain 2 and strain 13 guinea pigs. Greater AHH activities were associated with peritoneal and alveolar macrophages than with lymph nodes lymphocytes in the absence of mitogens.

Animals↗
PubMed1981

HL-A antigen frequency distribution in patients with gestational choriocarcinoma and their husbands.

HL-A (A,B,C, and DR) antigen frequency distribution was determined in 29 patients with choriocarcinoma and in their husbands, as well as in a matched control population of 21 healthy couples. All 29 patients had achieved complete sustained remission with chemotherapy. The HL-A antigen frequency distribution was normal in the choriocarcinoma patients and in their husbands and there was no abnormal HL-A antigen sharing between patients and their husbands. This study does not exclude the possibility that the pathogenesis of resistant choriocarcinoma may be dependent upon tumour-host histocompatibility.

Choriocarcinoma↗
PubMed1980

High dose methotrexate with leucovorin rescue. Rationale and spectrum of antitumor activity.

Methotrexate (MTX) in high doses (3 to 7.5 g/m2) with leucovorin rescue (HDMTX-LCV) can be delivered on a weekly basis in a setting of proper pharmacologic monitoring. Myelosuppression occurs in 28 per cent of the patients and in 8 per cent of the courses and usually results from delayed MTX excretion secondary to mild reversible nephrotoxicity. The incidence of tumor regression was 50 per cent in head and neck cancer; 59 per cent in non-Hodgkin's lymphoma; 40 per cent in small cell lung cancer; 24 to 50 per cent in breast cancer and 50 per cent in osteogenic carcinoma, for an over-all response rate of 39 per cent (70 of 178) in patients with disseminated cancer. HDMTX-LCV is not recommended for the conventional treatment of metastatic cancer because of the potential for toxicity and the fact that the response rates cited are probably not superior to those which can be achieved by conventional doses of MTX. However, the relative lack of myelosuppression and mucositis, when compared to conventional unrescued MTS, and the achievement of therapeutic concentrations of MTX in the central nervous system with the HDMTX-LCV program have led to its incorporation into clinical trials of combination chemotherapy.

Adult↗
PubMed1980

Specificity of heteroantisera developed against purified populations of intact murine ovarian carcinoma cells.

Antisera were raised in New Zealand White rabbits against purified populations of murine ovarian carcinoma (MOT) cells that were freed from contaminating host leukocytes and erythrocytes. In contrast to other antisera raised against this tumor, heteroantisera from rabbits immunized with purified tumor cell suspensions consistently retained antitumor activity after exhaustive absorption with syngeneic (C3HeB/FeJ) adult and fetal tissues. Absorbed antisera inhibited tumor growth in vivo and reacted with MOT cells in vitro as judged by indirect immunofluorescence, binding of staphylococcal protein A, and complement-mediated cytotoxicity. Appropriately absorbed antisera failed to bind to fetal tissues or to adult spleen, ovary, and kidney cells. Antisera with similar specificity could be obtained with the use of populations purified on a fluorescence-activated cell sorter or on discontinuous rabbit serum albumin gradients. Optimal titers against tumor were raised with multiple injections of 5 x 10(5) gradient-purified MOT cells.

Animals↗
PubMed1979

Immunotherapy of a murine ovarian carcinoma with Corynebacterium parvum and specific heteroantiserum. I. Activation of peritoneal cells to mediate antibody-dependent cytotoxicity.

Immunotherapy with a combination of Corynebacterium parvum and specific heteroantiserum is significantly more effective than treatment with either single agent in prolonging the survival of mice that have recevied an i.p. injection of syngeneic murine ovarian carcinoma (MOT) cells. Invitro, a combination of C. parvum-activated peritoneal cells and specific heteroantiserum has proven significantly more effective than either single component in destroying 51Cr-labeled MOT cells in the absence of complement. Activation of peritoneal cells to produce lysis of tumor in the presence specific antiserum peaked 3 to 7 days after a single injection of C. parvum and declined to baseline over 3 to 4 weeks. With repeated i.p. injections of C. parvum at appropriate intervals, activation of peritoneal cells could be prolonged and augmented. Among the routes tested, only i.p. administration of C. parvum was effective, although activation of peritoneal cells for cooperation with heteroantiserum was observed over a broad range of i.p. dosage (0.45 to 4.20 mg). These data suggest that the administration of C. parvum by appropriate doses, routes, and schedules can attract and activate a population of peritoneal effectors that mediate antibody-dependent cytotoxicity more effectively than resident peritoneal cells.

Animals↗