[entrez_report] 27 citations found all 27 of these reports in format. --------------------------------------------------------------------------- Links: [124 medline neighbors] Cancer 78: 2388-2399 (1996) Metastatic phenotype correlates with high expression of membrane-associated complete beta-human chorionic gonadotropin in vivo. Acevedo HF, Hartsock RJ Department of Pathology and Laboratory Medicine, Allegheny-Singer Research Institute, Allegheny General Hospital, MCP-Hahnemann Medical School, Allegheny University of the Health Sciences, Pittsburg, Pennsylvania 15212-9986, USA. BACKGROUND: Investigations using living human cancer cells and the nude mouse model were conducted to evaluate the expression of human chorionic gonadotropin (hCG) in various cancers grown in vitro and in vivo. The aim was to determine whether membrane-associated hCG in any of its forms is a characteristic metastatic marker, and at what levels or ratios. METHODS: Human cancer cell lines known to produce tumors that metastasize spontaneously when grown in nude mice (n = 4) were compared with those that do not produce such tumors (n = 4) using analytical (quantitative) flow cytometry. Monoclonal antibodies directed to epitopes of intact hCG (hCG-holo) and its subunits, including beta-human chorionic gonadotropin with its carboxy-terminal peptide (hCG beta-CTP), allowed for the determination of hCG beta-CTP/hCG-holo ratios. RESULTS: No significant difference in hCG beta-CTP/hCG-holo ratios was found between the cultured human cancer cells that do not metastasize spontaneously (ratio = 2.39) and those that do (ratio = 2.13), and no difference was seen in their growth rate in nude mice. However, the cells isolated from tumors that do not metastasize spontaneously showed a decrease in their ratios to values less than 1. They reverted to their original values after reestablishment in culture and subsequent passages. In contrast, the ratios shown by cells isolated from tumors that metastasize spontaneously increased to 3 to 6 times their original values in culture, then reverted to their original values after reestablishment in culture and subsequent passages. CONCLUSIONS: To our knowledge, these data demonstrate the following for the first time: 1) There is a direct in vivo correlation between human cancer cells that metastasize spontaneously in nude mice and the expression of membrane-associated complete hCG beta (hCG beta-CTP); and the correlation identifies this molecule as a characteristic metastatic phenotype marker. 2) The marked ratio variations under different conditions indicate that the metastatic phenotype is an unstable event. 3) Growth and local invasion in vivo correlates with the expression of hCG-holo. MeSH Terms: * Animal * Female * Flow Cytometry * Gonadotropins, Chorionic/metabolism* * Human * Male * Membrane Glycoproteins/metabolism* * Mice * Mice, Inbred BALB C * Mice, Nude * Neoplasm Metastasis * Neoplasm Proteins/metabolism* * Neoplasms/pathology * Neoplasms/metabolism* * Phenotype * Support, Non-U.S. Gov't * Tumor Cells, Cultured * Tumor Markers, Biological/metabolism* Substances: * Tumor Markers, Biological * Neoplasm Proteins * Membrane Glycoproteins * Gonadotropins, Chorionic PMID: 8941011, MUID: 97095987 --------------------------------------------------------------------------- Links: [155 medline neighbors] Cancer 76: 1467-1475 (1995) Human chorionic gonadotropin-beta subunit gene expression in cultured human fetal and cancer cells of different types and origins Acevedo HF, Tong JY, Hartsock RJ Department of Pathology and Laboratory Medicine, Allegheny-Singer Research Institute, Allegheny General Hospital, Medical College of Pennsylvania, Pittsburgh 15212-9986, USA. BACKGROUND. The authors' previous investigations using living cultured human cancer cells and cells isolated from cancer tissues, analytical flow cytometry, and monoclonal antibodies directed to epitopes located in five different sites of the human chorionic gonadotropin (hCG) molecule, identified the presence of membrane-associated hCG, its subunits and fragments, by cells from all cancers, irrespective of type and origin, indicating that the expression of these sialoglycoproteins is a common phenotypic characteristic of cancer. Although benign neoplasms do not express these compounds, cultured human embryonic and fetal cells also express the same materials. To corroborate these findings, five fetal cell lines and 28 cancer cell lines were randomly selected from those previously studied, to determine the presence of translatable levels of hCG-beta (hCG beta) mRNA. METHODS. All cell lines were grown under identical conditions. Determination of hCG beta mRNA was made by extracting the total RNA from the cells, followed by synthesis of cDNA with RNase H- reverse transcriptase and polymerase chain reaction amplification using specific hCG beta-luteinizing hormone-beta (hLH beta) primers. The presence of amplified hCG beta cDNA was corroborated by hybridization of the product with an hCG beta-specific oligonucleotide and Southern blot analyses of the hybridization products. Gestational choriocarcinoma cells and HeLa adenocarcinoma of cervical cells, known producers of biologically active hCG, were positive control subjects, and human pituitary cells were used as negative control subjects. RESULTS. The results showed single and multiple hCG beta gene activation by the fetal cells and the different types of cancer, indicating that at any given time, there is the possibility of activation of as many as four genes of the six genes of the hCG beta-hLH beta gene cluster, even though alternative gene splicing cannot be ruled out. CONCLUSIONS. In addition to the authors' previous findings, the results of these studies support the concept that cancer is a problem of development and differentiation, and, to the authors' knowledge, prove definitively for the first time that synthesis and expression of hCG, its subunits, and its fragments, is a common biochemical denominator of cancer, providing the scientific basis for studies of its prevention and/or control by active and/or passive immunization against these sialoglycoproteins. MeSH Terms: * Base Sequence * Blotting, Southern * Cells, Cultured * Chorionic Gonadotropin, beta Subunit, Human/genetics * Chorionic Gonadotropin, beta Subunit, Human/analysis* * Fetus/cytology * Fetus/chemistry* * Gene Expression Regulation, Developmental* * Gene Expression Regulation, Neoplastic* * Human * Molecular Sequence Data * RNA, Messenger/analysis * RNA, Neoplasm/analysis * Support, Non-U.S. Gov't * Tumor Cells, Cultured/chemistry* Substances: * RNA, Neoplasm * RNA, Messenger * Chorionic Gonadotropin, beta Subunit, Human PMID: 8620425, MUID: 96223203 --------------------------------------------------------------------------- Links: [200 medline neighbors] Cancer 69: 1829-1842 (1992) Expression of membrane-associated human chorionic gonadotropin, its subunits, and fragments by cultured human cancer cells. Acevedo HF, Krichevsky A, Campbell-Acevedo EA, Galyon JC, Buffo MJ, Hartsock RJ Department of Pathology and Laboratory Medicine, Allegheny General Hospital, Pittsburgh, PA 15212. The expression of human chorionic gonadotropin (hCG), its subunits, and fragments on the cell membrane of cultured human cancer cells was investigated using a flow cytometric method. This method uses living cells; a double-antibody reaction; a flow cytometer with an argon laser, standard settings, and filters for fluorescein isothiocyanate; commercially available software; the American Type Culture Collection (ATCC) CCL 2 HeLa cell line as cell control and overall quality control; polyclonal rabbit antisera raised against the hCG dimer, its alpha subunit (hCG alpha), and its beta subunit (hCG beta); and a panel of monoclonal antibodies (MoAb) recognizing different epitopes on the intact hCG molecule, its subunits, and fragments. The purified immunoglobulin G fractions from the polyclonal antisera were used to estimate the total expression of the membrane-associated glycoproteins; the MoAb were used to detect the expression of epitopes of the hCG dimer, its subunits, and fragments. The results of the analyses done on cells from 74 established cancer cell lines of different types and origins (including 52 carcinomas, 10 sarcomas, 4 leukemias, 6 lymphomas, and 2 retinoblastomas) showed variable degrees of reactivity in a great percentage of cells in all cell lines studied with MoAb directed against different conformational epitopes of intact hCG (hCG-holo), hCG beta, hCG beta-free, the carboxy terminal peptide (CTP) of hCG beta, and an epitope of hCG alpha. The expression of the membrane-associated epitopes of hCG and its subunits was found to be a phenotypic marker characteristic of all evaluated cultured human cancer cell lines, irrespective of their type or origin. There were, however, quantitative and qualitative differences in the expression of the different epitopes. Thus, hCG beta, free and as part of hCG-holo, recognized by the MoAb against hCG beta-CTP, was expressed by a high percentage of cells of most cell lines. There was great variability in the expression of hCG-holo, recognized by MoAb B109. For this reason some groups of cancers expressed larger amounts of incompetent hCG alpha and/or hCG beta than others. Cell lines derived from adenocarcinomas of the lung were the only exception to this general finding; the expression of small amounts of hCG-holo was caused by a low degree of hCG alpha synthesis. MeSH Terms: * Antibodies, Monoclonal * Cell Membrane/physiology * Epitopes/analysis * Female * Fluorescence * Gonadotropins, Chorionic/physiology* * Gonadotropins, Chorionic/immunology * Gonadotropins, Chorionic/analysis * Human * Macromolecular Systems * Male * Neoplasms/physiopathology* * Neoplasms/pathology * Neoplasms/chemistry * Peptide Fragments/physiology* * Peptide Fragments/immunology * Peptide Fragments/analysis * Phenotype * Support, Non-U.S. Gov't * Support, U.S. Gov't, P.H.S. * Tumor Cells, Cultured Substances: * Peptide Fragments * Macromolecular Systems * Gonadotropins, Chorionic * Epitopes * Antibodies, Monoclonal PMID: 1372528, MUID: 92200333 --------------------------------------------------------------------------- Cancer 69: 1818-1828 (1992) Flow cytometry method for the analysis of membrane-associated human chorionic gonadotropin, its subunits, and fragments on human cancer cells. Acevedo HF, Krichevsky A, Campbell-Acevedo EA, Galyon JC, Buffo MJ, Hartsock RJ Department of Pathology and Laboratory Medicine, Allegheny General Hospital, Pittsburgh, PA 15212. A quantitative flow cytometry method for the analysis of membrane-associated human chorionic gonadotropin (hCG), its subunits, and fragments on human cancer cells was developed using a double-antibody reaction; a flow cytometry with a 2-W argon laser, standard settings, and filters for fluorescein isothiocyanate use; commercially available software; and the ectopic hCG producer CCL 2 HeLa cells from the American Type Culture Collection (ATCC) as a cell control to standardize the reagents and for overall quality control. Twenty-two monoclonal antibodies (MoAb) and immunoglobulin G fractions from three rabbit polyclonal antisera were tested for effects of antibody concentration (titration), reproducibility at different levels of epitope expression, and variability of epitope expression to select appropriate primary antibodies. Based on the results of the various tests, three polyclonal immunoglobulin G antibodies and a panel of nine MoAb directed to epitopes located in five different regions on the hCG molecule were selected as first antibodies. Their specificity was determined by using two unrelated MoAb of the same isotype at the same concentration to replace the primary MoAb and by a competition experiment. The unrelated MoAb also were used for the selection of the appropriate control fluorescence profile needed for the software. The unique characteristics of this method were: the use of living cells, standardized reagents, internal and external quality control, and the highest sensitivity, which could detect as few as 10(3) molecules of fluorochrome per cell. Serial analyses of the ATCC CCL 2 HeLa cells and two of its variants and of the eutopic hCG producer JEG-3 choriocarcinoma cells revealed the expression of membrane-associated epitopes of intact hCG, its subunits, and fragments by a high percentage of the cells, indicating that the expression of these sialoglycoproteins by these two different types of cancer cells is a common phenotypic characteristic. MeSH Terms: * Adenocarcinoma/pathology * Adenocarcinoma/chemistry* * Antibodies, Monoclonal * Binding, Competitive * Cell Membrane/physiology * Cell Survival/physiology * Epitopes/immunology * Epitopes/analysis * Female * Flow Cytometry/methods* * Gonadotropins, Chorionic/physiology * Gonadotropins, Chorionic/immunology * Gonadotropins, Chorionic/analysis* * Hela Cells * Human * Neoplasms/pathology * Neoplasms/chemistry* * Peptide Fragments/analysis* * Reproducibility of Results * Sensitivity and Specificity * Support, Non-U.S. Gov't * Support, U.S. Gov't, P.H.S. * Time Factors Substances: * Peptide Fragments * Gonadotropins, Chorionic * Epitopes * Antibodies, Monoclonal PMID: 1372527, MUID: 92200332 --------------------------------------------------------------------------- Links: [184 medline neighbors] J. Gen. Microbiol. 133: 783-791 (1987) Human choriogonadotropin-like material in bacteria of different species: electron microscopy and immunocytochemical studies with monoclonal and polyclonal antibodies. Acevedo HF, Pardo M, Campbell-Acevedo E, Domingue GJ Department of Laboratory Medicine, Allegheny-Singer Research Institute, Allegheny General Hospital, Pittsburgh, PA 15212. Immunocytochemical studies using antisera to whole human choriogonadotropin (hCG), to its alpha- and beta-subunits and to the COOH-terminal peptide of hCG beta, and two monoclonal antibodies to hCG beta, demonstrated expression of hCG-like material, its individual subunits and/or fragments in nine bacterial strains. Seven of these were isolated from patients with cancer and were definitely identified as Streptococcus faecalis (three strains), Staphylococcus haemolyticus (two strains) and Staphylococcus epidermidis and Escherichia coli (single strains). The other two strains were cell-wall-deficient (CWD) variants, one identified as Streptococcus bovis, isolated from the blood of a patient with a fever of unknown origin and a possible brain abscess. The other was a Gram-negative diphtheroid isolated from the urine of a pregnant woman, which during the period of study reverted to a Gram-positive Corynebacterium identified as a 'C. ulcerans' strain and expressed the hCG-like factor only during its phase as Gram-negative diphtheroid. Electron microscopy of these nine strains (including negative controls of strains of the same species subjected to the same immunocytochemical analyses and under identical cultural conditions) revealed morphological alterations in the bacterial cell walls and cytoplasmic material and/or bizarre forms of reproduction in six of the nine strains expressing hCG-like material including the two CWD variants. Collectively, these results provided evidence that (1) hCG-producing bacteria isolated from patients with overt cancer are not a new and unique species as claimed by others, and (2) there is a close resemblance between the bacterial protein and the human trophoblastic hormone, based on immunochemical recognition of different parts of the hCG molecule.( MeSH Terms: * Antibodies, Monoclonal* * Corynebacterium/ultrastructure * Corynebacterium/immunology* * Enterococcus faecalis/immunology * Escherichia coli/ultrastructure * Escherichia coli/immunology* * Human * LH/immunology* * Microscopy, Electron * Staphylococcus/ultrastructure * Staphylococcus/immunology* * Staphylococcus epidermidis/immunology * Streptococcus/ultrastructure * Streptococcus/immunology* * Support, Non-U.S. Gov't Substances: * LH * Antibodies, Monoclonal PMID: 3116165, MUID: 88009898 --------------------------------------------------------------------------- Links: [197 medline neighbors] Cancer Invest 5: 177-185 (1987) Expression of human choriogonadotropin-like material correlates with metastatic phenotype of R3230 AC rat adenocarcinoma. Acevedo HF, Kellen JA, Wong AC, Gardner HA, Szalai JP Department of Laboratory Medicine, Allegheny-Singer Research Institute, Allegheny General Hospital, Pittsburgh, Pennsylvania 15212. Human choriogonadotropin (hCG)-like material has been found in variable amounts on the surface of cells of human and animal tumors. Intravenous injection of R3230 AC rat adenocarcinoma cells, one of the models investigated, results in multiple lung foci seeding. We analyzed the phenotypic diversity of this tumor by cloning and culturing two distinct cell subpopulations from a cell culture of this tumor, hereafter called OR or original cell culture. One was obtained after repeated exposure of the OR to increasing concentrations of concanavalin A and wheat germ agglutinin. A single clone was isolated and was named lectin-resistant (LR) cell line. The LR cells did not metastasize but maintained stable tumorigenicity and morphology over at least 10 passages. A second cell line was obtained by repeated passage and injection of cells from a single metastatic node. After repeating the process five times, a single clone of cells was selected from the final variant and was called lung metastatic (LM) cell line. The LM cultured cells maintained stable tumorigenicity, morphology, and metastatic properties for no more than 10 passages. OR, LR, and LM cells were assessed by their doubling time (DT), chromosome counts, and hCG immunocytochemistry. The results demonstrated that the LM cell line had a higher chromosome count than the LR and the OR cell lines, and its DT was the shortest. Immunocytochemistry of the transplanted OR neoplasm showed scattered expression of the hCG-like material. By the same techniques a complete lack of reactivity of the LR cells was found. However, almost all cells of the LM line were strongly positive for hCG-like material. After a few passages, the great majority of the LM cells also became unreactive. Our data demonstrate: (i) the existence of marked heterogeneity of the expression of hCG-like material in the primary tumor cell population; (ii) that the expression of hCG-like material correlates with the metastasizing capacity of the cells; and (iii) that there is a phenotypic instability for the expression of hCG-like material by tumor cells when maintained in vitro. MeSH Terms: * Adenocarcinoma/pathology * Adenocarcinoma/analysis* * Animal * Cell Line * Gonadotropins, Chorionic/analysis* * Mammary Neoplasms, Experimental/pathology * Mammary Neoplasms, Experimental/analysis* * Neoplasm Metastasis * Neoplasm Transplantation * Phenotype * Rats * Support, Non-U.S. Gov't * Tumor Cells, Cultured/transplantation * Tumor Cells, Cultured/analysis* Substances: * Gonadotropins, Chorionic PMID: 3651864, MUID: 88001611 --------------------------------------------------------------------------- Links: [200 medline neighbors] Cancer Detect Prev Suppl 1: 477-486 (1987) Effects of immunization against human choriogonadotropin on the growth of transplanted Lewis lung carcinoma and spontaneous mammary adenocarcinoma in mice. Acevedo HF, Raikow RB, Powell JE, Stevens VC Department of Laboratory Medicine, Allegheny-Singer Research Institute, Allegheny General Hospital, Pittsburgh, PA 15212. We studied the effects of preimmunization with a synthetic carboxy-terminal peptide of the beta-subunit of human choriogonadotropin (hCG) conjugated to diphtheria toxoid on the growth of two tumor models, the transplantable Lewis lung carcinoma in C57BL/6J mice and the spontaneous mammary carcinoma in C3H/OuJ mice. Immunization with the conjugate prior to Lewis lung tumor implantation significantly (P less than 0.05) retarded the growth of tumors as measured by tumor weight 18 days following transplantation. The weights of Lewis lung tumors in animals preimmunized with the hCG immunogen were inversely correlated (r = 0.61) with the levels of circulating antibodies against human chorionic gonadotropin, whereas no statistical correlation was found between tumor weights and the levels of antibodies reactive to diphtheria toxoid. The number of conjugate-treated C3H/OuJ mice that developed mammary tumors was significantly (P less than 0.05) reduced compared to their vehicle-treated cohorts. Pretreatment with the synthetic muramyl dipeptide analog utilized as an adjuvant with both immunogens did not show any effect on the tumor growth in either tumor system. MeSH Terms: * Adenocarcinoma/therapy* * Adenocarcinoma/pathology * Animal * Antigens* * Cell Division * Diphtheria Toxin/immunology * Diphtheria Toxin/administration & dosage * Female * Gonadotropins, Chorionic/immunology* * Immunotherapy* * Lung Neoplasms/therapy* * Lung Neoplasms/pathology * Male * Mammary Neoplasms, Experimental/therapy* * Mammary Neoplasms, Experimental/pathology * Mice * Mice, Inbred C3H * Mice, Inbred C57BL * Support, Non-U.S. Gov't * Support, U.S. Gov't, P.H.S. * Vaccines, Synthetic* Substances: * Vaccines, Synthetic * Gonadotropins, Chorionic * Diphtheria Toxin * Antigens PMID: 3480061, MUID: 88080261 --------------------------------------------------------------------------- Tumour Biol. 6: 447-452 (1986) Lack of immunological analogy between the beta-subunits of cholera toxin and human choriogonadotropin. Acevedo HF, Kellen JA A chemical relatedness has been described between the beta-subunit of cholera toxin and that of the four dimeric glycoprotein hormones (hCG, hLH, hFSH and hTSH). However, antibodies induced by cholera toxin did not crossreact, when tested by labeled hCG binding and immunocytochemistry, with the beta-subunit of hCG. It appears that differences in the tertiary structures, as shown in this study, account for distinct epitopes. Similarities in biological activity between these two compounds, such as induction of adenyl cyclase or a protective effect against some tumors, are not based on immunological mechanisms. MeSH Terms: * Adenyl Cyclase/analysis * Animal * Cholera Toxin/immunology* * Female * Gonadotropins, Chorionic/immunology* * Human * Immune Sera/immunology * Peptide Fragments/immunology* * Rats * Rats, Inbred F344 * Support, Non-U.S. Gov't Substances: * Cholera Toxin * Peptide Fragments * Gonadotropins, Chorionic * Chorionic Gonadotropin, beta Subunit, Human * Adenyl Cyclase PMID: 2422725, MUID: 86207751 --------------------------------------------------------------------------- Links: [200 medline neighbors] Infect. Immun. 50: 860-868 (1985) Expression of human choriogonadotropin-like material in coagulase-negative Staphylococcus species. Acevedo HF, Campbell-Acevedo E, Kloos WE We identified 101 coagulase-negative Staphylococcus strains obtained from different laboratories, the American Type Culture Collection, and our collection, isolated from 23 patients with overt cancer and 34 normal individuals through Kloos and Schleifer conventional methods and the Staph-Ident staphylococcal system (Analytab Products, Plainview, N.Y.). In 40 strains, identity was further verified by DNA-DNA hybridization techniques. Identification revealed 39 S. epidermidis, 22 S. hominis, 8 S. haemolyticus, 9 S. capitis, 5 S. warneri, 5 S. cohnii, 8 S. saprophyticus, and 5 S. xylosus strains, all resident species found in humans. All bacteria were tested for the expression of human choriogonadotropin (hCG)-like material by the indirect fluorescein and peroxidase immunocytochemical labeling techniques by using specific antisera to the whole hormone, to its alpha and beta subunits, to the hCG beta COOH-terminal peptide, and to a monoclonal antibody to the hCG beta. The results demonstrated that the isolates from cancer patients were not unique bacteria, as has been postulated by others; the expression of immunoreactive hCG-like material is a strain, not a species, characteristic; not every bacterial strain isolated from a cancer patient is able to express the material; hCG-producing bacteria do not necessarily indicate the presence of active disease; 20% of the strains that we studied revealed a clonal variation of the expression of hCG-like material or its subunits or both as well as a variable expression of a single hCG epitope, an observation similar to that described for malignant cells; and a specific antiserum to the whole hormone with a high affinity and high sensitivity for immunocytochemistry can be a reliable reagent for screening purposes. MeSH Terms: * Animal * Coagulase/analysis * Epitopes/analysis * Gonadotropins, Chorionic/analysis* * Histocytochemistry * Human * Neoplasms/microbiology * Nucleic Acid Hybridization * Rabbits * Staphylococcus/enzymology * Staphylococcus/analysis* * Support, Non-U.S. Gov't Substances: * Gonadotropins, Chorionic * Epitopes * Coagulase PMID: 2415456, MUID: 86058039 --------------------------------------------------------------------------- Links: [200 medline neighbors] Antimicrob. Agents Chemother. 28: 589-596 (1985) Prevention of oncogenic viral infections in mice with CGP 11637, a synthetic muramyl dipeptide analog. Acevedo HF, Raikow RB, Acevedo HO, Delgado TF, Pardo M The efficacy of N-acetyl-nor-muramyl-L-alanyl-D-isoglutamine (nor-MDP) in controlling viral oncogenesis in mice was investigated. The tumors studied were blood cell malignancies induced by Friend leukemia virus in SJL/J mice, spontaneous mammary neoplasms in RIII/Imr and C3H/OuJ mice, and spontaneous lymphocytic leukemia in AKR/J mice. A transplantable tumor, Lewis lung carcinoma, in C57BL/6J mice was used as a nonvirally induced control model. The nor-MDP was dissolved in saline and made into an emulsion with an equal volume of squalene-Arlacel A and injected subcutaneously at 1- to 2-month intervals. Test and control mice were challenged with exogenous virus or tumor transplant 2 weeks after a second injection of nor-MDP. Administration was started at around 2 months of age in mice that develop spontaneous neoplasms. Electron microscopy studies were done on neoplastic tissues of selected test and control mice. This administration of nor-MDP prevented erythroleukemia in SJL/J mice caused by low doses of Friend leukemia virus (although erythroleukemia survivors were not protected from a late-developing lymphoma) and also delayed (possibly prevented) the development of a spontaneous mammary neoplasm in RIII/Imr mice. No antitumor effects were observed on the spontaneous neoplasms of C3H/OuJ and AKR/J mice or on the Lewis lung carcinoma implanted into C57BL/6J mice. Electron microscopic examinations of the various neoplastic tissues indicated that nor-MDP administration eliminated or reduced extracellular viruses. The results suggested that under the experimental conditions used nor-MDP appears to effect the viruses and not the malignant cells per se. MeSH Terms: * Acetylmuramyl-Alanyl-Isoglutamine/therapeutic use * Acetylmuramyl-Alanyl-Isoglutamine/analogs & derivatives* * Animal * Antiviral Agents/therapeutic use* * Female * Friend Virus * Leukemia, Erythroblastic, Acute/prevention & control * Leukemia, Erythroblastic, Acute/pathology * Leukemia, Experimental/prevention & control* * Leukemia, Experimental/pathology * Male * Mammary Neoplasms, Experimental/prevention & control * Mammary Neoplasms, Experimental/pathology * Mice * Mice, Inbred Strains * Neoplasms, Experimental/prevention & control * Neoplasms, Experimental/pathology * Spleen/ultrastructure * Support, Non-U.S. Gov't * Thymus Gland/ultrastructure * Tumor Virus Infections/prevention & control* * Tumor Virus Infections/pathology Substances: * CGP 11637 * Acetylmuramyl-Alanyl-Isoglutamine * Antiviral Agents PMID: 3867329, MUID: 86129208 --------------------------------------------------------------------------- Links: [121 medline neighbors] Infect. Immun. 31: 487-494 (1981) Choriogonadotropin-like antigen in a strain of Streptococcus faecalis and a strain of Staphylococcus simulans: detection, identification, and characterization. Acevedo HF, Koide SS, Slifkin M, Maruo T, Campbell-Acevedo EA The presence of choriogonadotropin- and alpha-subunit-like materials in two species of bacteria identified as Staphylococcus simulans and Streptococcus faecalis have been demonstrated by the indirect fluorescein-labeled and the indirect peroxidase-labeled immunocytochemical techniques, utilizing antiserum for human choriogonadotropin, for its alpha and beta-subunits and the bera-subunit COOH-terminal peptide. The bacteria were originally isolated from the urine of two patients with advanced forms of cancer. Chromatography done on the water-soluble extract of acetone powder preparations of the bacterial cultures revealed the presence of a material similar to the complete trophoblastic hormone and to its beta-subunit in the culture media of S. simulans, and to the beta-subunit in the media of S. faecalis. No free alpha-subunit was detectable. Furthermore, the choriogonadotropin-like factor demonstrated biological activity in in vivo assay systems. From the present results, it can be concluded that some species of "cancer-associated" bacteria can synthesize a human trophoblastic hormone-like glycoprotein with physicochemical properties similar to those of the human trophoblastic hormone that is biologically active and that is either released complete or as one of its subunits in the culture media. MeSH Terms: * Enterococcus faecalis/metabolism* * Gonadotropins, Chorionic/immunology * Gonadotropins, Chorionic/biosynthesis* * Gonadotropins, Chorionic/analysis * Human * Immunoenzyme Techniques * Neoplasms/microbiology * Staphylococcus/metabolism* * Support, Non-U.S. Gov't Substances: * Gonadotropins, Chorionic PMID: 6783540, MUID: 81166934 --------------------------------------------------------------------------- Links: [27 medline neighbors] Infect. Immun. 24: 920-924 (1979) Choriogonadotropin-like antigen in an anaerobic bacterium, Eubacterium lentum, isolated from a rectal tumor. Acevedo HF, Slifkin M, Pouchet-Melvin GR, Campbell-Acevedo EA Using the indirect fluorescein-labeled and indirect peroxidase-antiperoxidase-labeled immunohistochemical techniques, and utilizing both antiserum specific for the beta-subunit of choriogonadotropin and antiserum for the total hormone, we have demonstrated the presence of a choriogonadotropin-like immunoreactive material in a strain of Eubacterium lenthum that was originally isolated from a rectal tumor. In contrast, both immunohistochemical reactions were negative when applied to a strain of Corynebacterium parvum and to pathogenic and nonpathogenic strains of Agrobacterium tumefaciens. Our results demonstrate for the first time the expression of the choriogonadotropin-like antigen in an obligate anaerobe and support our previous findings that the choriogonadotropin like material appears to be expressed only in "cancer-associated bacteria" but that not all bacteria associated with the malignant neoplasms have the capacity to express the antigen, at least in amounts detectable by immunohistochemistry. MeSH Terms: * Agrobacterium/immunology * Antigens, Bacterial/immunology* * Eubacterium/immunology* * Gonadotropins, Chorionic/immunology* * Human * Propionibacterium acnes/immunology * Rectal Neoplasms/microbiology* PMID: 468380, MUID: 79238527 --------------------------------------------------------------------------- Cancer 41: 1217-1229 (1978) Immunohistochemical localization of a choriogonadotropin-like protein in bacteria isolated from cancer patients. Acevedo HF, Slifkin M, Pouchet GR, Pardo M By the use of specific antibody to human chorionic gonadotropin (CG) as well as to its beta-subunit, and the application of the indirect fluorescein-labeled and peroxidase-labeled antibody techniques, we have demonstrated the presence of a membrane (wall)-associated CG-similar immunoreactive protein in 15 strains of bacteria isolated from tissues of patients bearing malignant neoplasms. These microorganisms were classified as S. epidermidis, (12) E. coli (2), and a single strain of P. maltophilia (ATCC 13637). The absence of the CG-like antigen in other "cancer associated bacteria", Streptococcus faecalis (ATCC 12818) and Pseudomonas aeruginosa (from patient with cancer of colon), demonstrated that not every "cancer associated bacteria" has the capability to synthesize the trophoblastic-like protein. The negative results obtained with a number of "noncancer control" bacteria of known origin, obtained from ATCC and from clinical samples, strongly supported the idea that the existance of these CG-like protein producing microorganisms is not a ubiquitous finding. The demonstration of a de novo bacterial biosynthesis of a protein having similar antigenic and biophysical properties to those of the human trophoblastic hormone, has great biological implications, especially if its biosynthesis is proven only in bacterial strains growing in the presence of cancer cells in which we have already demonstrated the presence of a similar antigen. The explanation of the phenomenon is unknown. Because of their origin, the potential of "genetic exchange" with subsequent expression of the mammalian gene by the bacterial cells becomes a possibility. It is also possible that the gene coding for the CG-like protein is normally present but inactive or repressed in all bacteria. MeSH Terms: * Bacterial Proteins/isolation & purification* * Epitopes * Escherichia coli/metabolism * Female * Fluorescent Antibody Technique * Gonadotropins, Chorionic/immunology * Gonadotropins, Chorionic/biosynthesis* * Hormones, Ectopic/biosynthesis* * Human * Male * Neoplasms/microbiology* * Pseudomonas/metabolism * Staphylococcus/metabolism PMID: 76504, MUID: 78146238 --------------------------------------------------------------------------- Monograph : (1977) Identification of the beta subunit of choriogonadotropin in human spermatozoa. pp. 185-92. Acevedo HF, Slifkin M, Pouchet GR, Rakhshan M MeSH Terms: * Fluorescent Antibody Technique * Gonadotropins, Chorionic/biosynthesis* * Human * Male * Spermatozoa/metabolism* * Spermatozoa/immunology PMID: 328716, MUID: 77228888 --------------------------------------------------------------------------- Cancer 37: 2847-2857 (1976) Urinary cholesterol. VIII. Its excretion in women with ovarian neoplasms. Acevedo HF, Campbell EA, Frich JC Jr, Hayeslip DW, Gilmore J The urinary excretion of nonesterified cholesterol (NEC) has been investigated in 57 women with ovarian neoplasms and/or related nonneoplastic diseases. Twelve patients had benign tumors or lesions and 45 had malignant neoplasms of their ovaries. All patients with nonmalignant ovarian tumors or lesions had normal NEC excretion irrespective of the type of tumor or lesion or its degree of extension. In contrast, urinary NEC hyperexcretion occurred with the following frequencies in patients with active malignant ovarian neoplasms: 18 of 19 cystadenocarcinomas of the serous and/or mucinous types; one of one endometrioid carcinoma; four of four malignant granulosa cell tumors; two of two mixed malignant germ cell tumors; and one of one malignant mixed mullerian tumor. Single cases of clear cell carcinoma and of rhabdomyosarcoma had a normal NEC excretion. Urinary hyperexcretion of NEC was also found after surgery in two of seven surviving patients with apparently localized resectable disease according to their staging. It is possible that in these two patients NEC hyperexcretion was due to undetected foci of cancer (wrong staging), since neither omental and peritoneal biopsies, nor cytologic examination of peritoneal washings or free fluid were performed. A normal excretion of urinary NEC has been characteristic of 19 of 21 surviving patients treated by surgery and adjunctive therapy in whom we have performed follow-up NEC determinations. They were 16 of 18 cystadenocarcinomas malignant germ cell tumor. The 94% correlation between the presence of proven active ovarian carcinomas and urinary NEC hyperexcretion is significant. The clinical significance of this investigation is even greater when one considers that cystadenocarcinomas constitute more than 75% of all primary malignant ovarian tumors. MeSH Terms: * Adenocarcinoma/urine * Adult * Aged * Cholesterol/urine* * Cystadenoma/urine * Endometriosis/urine * Female * Granulosa Cell Tumor/urine * Human * Middle Age * Neoplasm Metastasis * Neoplasms, Germ Cell and Embryonal/urine * Ovarian Neoplasms/urine* * Ovarian Neoplasms/therapy * Rhabdomyosarcoma/urine * Support, U.S. Gov't, P.H.S. PMID: 181125, MUID: 76233668 --------------------------------------------------------------------------- Cancer 36: 1459-1469 (1975) Urinary cholesterol. VII. The significance of the excretion of nonesterified cholesterol in patients with uterine carcinomas. Acevedo HF, Campbell EA, Frich JC Jr, Merkow LP, Hayeslip D, Gilmore J The urinary excretion of nonesterified cholesterol (NEC) in 170 women with cervical and endometrial carcinomas has been investigated. Control patients (236) included: 1) women with other types of (benign and/or malignant diseases of the pelvic organs; 2) patients with non-steroid-related neoplasms; 3) patients with benign and/or malignant breast diseases other than carcinoma; and 4) patients with a variety of non-neoplastic diseases. NEC was determined by a gas-liquid chromatographic procedure. The range of NEC excretion for clinically healthy normal women (64) was previously established by this method. NEC hyperexcretion was defined as any NEC value over 1.5 mg/24 hours. The results showed NEC hyperexcretion in 65 of 68 women with active carcinoma of the cervix, including 13 patients with carcinoma in situ, and in 42 of 45 women with active carcinoma of the endometrium. In contrast, a normal excretion of NEC occurred in all the patients (77) of the first and second control groups, in 39 (80%) of the 48 patients of the third control group (high-risk group), and in 101 of the 111 patients of the fourth control group. Sequential studies performed in patients with uterine carcinomas have demonstrated an almost perfect correlation between the NEC excretion and the clinical status of the patient following surgical and/or radiation therapy. Of 57 patients (31 cervix and 26 endometrium) in which the NEC studies were started after treatment was instituted, 53 have normal NEC excretion in the multiple determination performed to date. Presently these patients have no clinical, chemical, or radiologic evidence of cancer. It is concluded that urinary NEC determination can be used as an additional diagnostic biochemical test to detect active carcinoma of the steroid-producing glands and their main target organs, and that in women with uterine carcinomas, the test can be used as an objective laboratory method to monitor the course of the disease and the response of the patient to therapy. MeSH Terms: * Breast Diseases/urine * Carcinoma in Situ/urine * Cervix Neoplasms/urine * Cholesterol/urine* * Female * Human * Ovarian Diseases/urine * Support, U.S. Gov't, P.H.S. * Uterine Diseases/urine * Uterine Neoplasms/urine* * Uterine Neoplasms/surgery * Uterine Neoplasms/radiotherapy PMID: 1175140, MUID: 76020549 --------------------------------------------------------------------------- Links: [8 medline neighbors] Cancer 34: 1727-1736 (1974) Urinary cholesterol--VI. Its excretion in women with inoperable inflammatory carcinoma of the breast. Acevedo HF, Campbell EA, Frich JC Jr, Dugan PJ, Saier EL, Merkow LP MeSH Terms: * Adenofibroma/urine * Adolescence * Adult * Age Factors * Aged * Breast Diseases/urine * Breast Neoplasms/urine* * Breast Neoplasms/radiotherapy * Carcinoma/urine* * Cholesterol/urine* * Chromatography, Gas * Comparative Study * Cysts/urine * Female * Human * Middle Age * Phyllodes Tumor/urine PMID: 4371946, MUID: 75037381 --------------------------------------------------------------------------- Links: [102 medline neighbors] Cancer 32: 196-205 (1973) Urinary cholesterol. V. Its excretion in men with testicular and prostatic neoplasms. Acevedo HF, Campbell EA, Saier EL, Frich JC Jr, Merkow LP, Hayeslip DW, Bartok SP, Grauer RC, Hamilton JL MeSH Terms: * Adenocarcinoma/urine* * Adolescence * Adult * Aged * Child * Child, Preschool * Cholesterol/urine* * Choriocarcinoma/urine* * Dysgerminoma/urine* * Human * Infant * Male * Middle Age * Prostatic Hyperplasia/urine * Prostatic Neoplasms/urine* * Teratoma/urine* * Testicular Neoplasms/urine* * Testicular Neoplasms/surgery PMID: 4123791, MUID: 73213153 --------------------------------------------------------------------------- Links: [50 medline neighbors] Obstet Gynecol 37: 425-436 (1971) Urinary cholesterol. IV. Its excretion in women with neoplasms of the genital system. Acevedo HF, Campbell EA, Hayeslip DW, Gilmore J, Merkow LP, Frich JC Jr, Grauer RC MeSH Terms: * Adenocarcinoma/urine * Adolescence * Adult * Aged * Breast Feeding * Breast Neoplasms/urine * Carcinoid Tumor/urine * Carcinoma/urine * Carcinosarcoma/urine * Cervix Diseases/urine * Cervix Neoplasms/urine * Child * Child, Preschool * Cholesterol/urine* * Choriocarcinoma/urine * Cushing's Syndrome/urine * Cystadenoma/urine * Diabetic Ketoacidosis/urine * Female * Human * Pregnancy PMID: 4993439, MUID: 71111709 --------------------------------------------------------------------------- Links: [169 medline neighbors] Steroids 16: 569-577 (1970) Urinary cholesterol. 3. Its excretion as a protein-bound complex. Acevedo HF, Campbell EA MeSH Terms: * Cholesterol/urine* * Cholesterol/metabolism * Chromatography, Gas * Female * Human * Methods * Middle Age * Protein Binding PMID: 5505292, MUID: 71141861 --------------------------------------------------------------------------- Links: [155 medline neighbors] Obstet Gynecol 35: 857-869 (1970) Urinary steroid profile in patients with hydatidiform mole. Report of 3 cases. Acevedo HF, Vela BA, Campbell EA, Gilmore J, Strickler HS, Merkow LP, Hayeslip DW, Maydak JJ, Ferraro RJ MeSH Terms: * Adolescence * Adult * Cholesterol/urine * Estrogens/urine* * Female * Glucocorticoids/urine* * Gonadotropins, Chorionic/urine * Human * Hydatidiform Mole/urine* * Ovarian Cysts/pathology * Pregnancy * Pregnancy Complications/urine* * Pregnanetriol/urine * Pregnenolone/urine * 17-Ketosteroids/urine PMID: 5446718, MUID: 70191090 --------------------------------------------------------------------------- Links: [200 medline neighbors] Am. J. Obstet. Gynecol. 105: 297-303 (1969) Urinary steroid profile during the puerperium. Acevedo HF, Vela BA, Campbell EA, Strickler HS, Gilmore J, Moraca JI, Dick BM MeSH Terms: * Adolescence * Adult * Cardiovascular Diseases * Estrogens/urine* * Female * Gestational Age * Human * Parity * Pregnancy * Pregnancy Complications/urine * Pregnancy Toxemias/urine * Pregnanediol/urine* * Pregnanetriol/urine* * Pregnenolone/urine* * Puerperium* PMID: 5810780, MUID: 69289103 --------------------------------------------------------------------------- Links: [200 medline neighbors] Am. J. Obstet. Gynecol. 104: 964-972 (1969) Urinary steroid profile in threatened abortion. Acevedo HF, Vela BA, Campbell EA, Strickler HS, Gilmore J, Moraca JI, Arras BJ MeSH Terms: * Abortion, Threatened/urine* * Abortion, Threatened/diagnosis * Autoanalysis * Chromatography, Gas * Estrogens/urine* * Female * Gestational Age * Human * Pregnancy * Pregnanediol/urine* * Pregnanes/urine* * Pregnanetriol/urine* PMID: 5794840, MUID: 69236373 --------------------------------------------------------------------------- Links: [195 medline neighbors] Am. J. Obstet. Gynecol. 102: 867-879 (1968) Urinary steroid profile as an index of fetal well-being. Acevedo HF, Strickler HS, Gilmore J, Vela BA, Campbell EA, Arras BJ MeSH Terms: * Abortion, Habitual/urine * Abortion, Threatened/urine * Chromatography * Estrogens/urine* * Female * Fetus * Human * Labor Complications/urine * Pregnancy* * Pregnancy Complications/urine* * Pregnancy Toxemias/urine * Pregnanediol/urine * Pregnanes/urine* * Pregnanetriol/urine * Pregnenolone/urine PMID: 5686905, MUID: 69027611 --------------------------------------------------------------------------- Links: [69 medline neighbors] J. Clin. Endocrinol. Metab. 25: 1675-1677 (1965) Epitestosterone: an in vitro metabolite of delta-4-androstenedione in a sclerocystic ovary. Acevedo HF, Corral-Gallardo J MeSH Terms: * Androgens/metabolism* * Chromatography, Paper * Chromatography, Thin Layer * Cysts/metabolism* * Female * Human * Hydroxysteroid Dehydrogenases/metabolism * Ovarian Diseases/metabolism* PMID: 5845866, MUID: 66045252 --------------------------------------------------------------------------- Links: [200 medline neighbors] Biochim. Biophys. Acta 111: 294-298 (1965) The metabolism of [4-14C] progesterone by hypertrophic and carcinomatous human prostate tissue. Acevedo HF, Goldzieher JW MeSH Terms: * Chromatography, Paper * Human * Hydroxysteroid Dehydrogenases * In Vitro * Male * Progesterone/metabolism* * Prostate/enzymology * Prostatic Hyperplasia/metabolism* * Prostatic Neoplasms/metabolism* PMID: 4160135, MUID: 66112066 --------------------------------------------------------------------------- Links: [182 medline neighbors] Steroids 6: 531-541 (1965) The metabolism of 4-14C-estradiol-17-beta by pheochromocytoma tissue. Acevedo HF, Beering SC MeSH Terms: * Adolescence * Adrenal Medulla/metabolism * Carbon Isotopes * Case Report * Chromatography, Paper * Chromatography, Thin Layer * Estradiol/metabolism* * Estrogens/biosynthesis* * Estrone/biosynthesis * Human * Hydroxylases/metabolism * In Vitro * Male * Oxidoreductases/metabolism * Pheochromocytoma/metabolism* PMID: 5884756, MUID: 66150538 ---------------------------------------------------------------------------