bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammatory cells in solid murine neoplasms. I. TUMOR disaggregation and identification of constituent inflammatory cells
Authors: Russell Stephen W. , Doe William F. , Hoskins Ronald G. , Cochrane Charles G. 
Published: February 2007

AbstractMechanical and enzymatic methods of disaggregating tumors were studied with the goals of (1) minimizing cell losses while (2) maintaining functional and surface membrane markers needed to objectively identify inflammatory cells (IC)1 in resultant suspensions. Application of the principles and methods described makes accurate estimation of the percentage of each IC type present in neoplasms possible for the first time. Compared to purely mechanical means of disaggregating tumors, all enzyme mixtures tested markedly increased yields of viable cells/g neoplasm. Best results were obtained with a combination of collagenase and a protease of broader substrate range (alpha chymotrypsin, papain, pronase or trypsin). The combination of enzymes that gave the highest yields with the least effect on inflammatory cell markers was trypsin, collagenase and DNAse (TCD). Because mechanical injury appeared to be the greatest single cause of cell loss (the enzymes themselves had little direct effect), potential sources were identified and either eliminated or minimized. With TCD, depending on the tumor system, cell recovery (measured as DNA recovered in cell suspensions) was as high as 50% and yields were as much as 6.9 × 108 viable cells/g tumor. Complete disaggregation was not required to obtain representative IC populations from tumor fragments. Neutrophils, eosinophils and mast cells from disaggregated neoplasms were counted in Giemsa stained cytocentrifuge preparations based on their unique morphologic appearances. Macrophages were identified by their capacity to phagocytose zymosan, a function which proved highly resistant to the effect of enzymes. Fluorescent microscopic identification of brain associated thymus antigen (BATA) allowed quantification of T lymphocytes, since this marker was virtually unchanged by enzyme exposure. Surface immunoglobulin (Ig) was stripped from B lymphocytes most rapidly by pronase and chymotrypsin, slowly by trypsin and papain, and not at all by collagenase. Ig positive cells therefore could be quantified in suspensions generated by collagenase or very short (20 min) exposure of fragments to trypsin.
Inflammatory cells in solid murine neoplasms. II. Cell types found throughout the course of moloney sarcoma regression or progression
Authors: Russell Stephen W. , Gillespie G. Yancey , Hansen Christopher B. , Cochrane Charles G. 
Published: February 2007

AbstractRegressing and progressing Moloney sarcomas, induced in BALB/c mice by the injection of cultured sarcoma cells (MSC)1, were sampled for histologic analysis and then disaggregated using mixtures of trypsin, collagenase and DNAse or collagenase and DNAse alone. The types of inflammatory cells (IC) found in resultant cell suspensions were determined 6, 11, 14 and 18 days post inoculation. Inflammatory infiltrates were composed almost exclusively of three cell types: neutrophils, T lymphocytes and macrophages. The extent to which each was found in tumors was related to the time post inoculation. Neutrophils were part of an early acute inflammatory response seen in both developing regressing and progressing sarcomas. The onset of regression was associated histologically with the appearance within tumors of a mononuclear inflammatory infiltrate. T lymphocytes and macrophages were the principal constituents. A higher percentage of T lymphocytes was recovered at all sampling times from regressing, compared to progressing, sarcomas. During development of the mononuclear inflammatory infiltrate there were relatively more large T cells in regressing, than in progressing tumors, and the percentage of macrophages was higher. Thereafter, the proportion of macrophages in the recovered cell population was approximately the same for both types of tumor. Such equality was more apparent than real, however, since IC were restricted to the peripheries of progressing sarcomas after the acute inflammatory phase, but continued to be found throughout regressing neoplasms. The effective ratio of macrophages and T lymphocytes to tumor cells therefore was much lower in progressing sarcomas than was suggested by percentage figures. The data presented support the concept that T lymphocytes are instrumental in causing the regression of Moloney sarcomas, possibly through interactions with macrophages.
The role of 9‐hydroxybenzo(a)pyrene in the microsome mediated binding of benzo(a)pyrene to dna
Authors: King H. W. S. , Thompson M. H. , Brookes P. 
Published: February 2007

AbstractA study of the liver microsome‐mediated binding to added DNA of the phenol metabolites of benzo (a)‐pyrene (BP‐OH) and of 7,8‐dihydro‐7,8‐dihydroxybenzo (a)pyrene (BP‐7,8‐diol) suggested that as in the case of BP itself the reaction was catalysed by the enzyme aryl hydrocarbon hydroxylase. The addition of glutathione to the microsomal incubation inhibited the binding of BP and BP‐OH more than that of BP‐7,8‐diol. Analysis by LH20 chromatography of the deoxyribonucleoside products from BP‐DNA showed greater inhibition by glutathione of formation of the major product believed to result from further metabolism of BP‐OH, than of the product arising by metabolism of BP‐7,8‐diol. The chromatographic behaviour and fluorescence spectrum of this major product were consistent with its derivation from 9‐hydroxybenzo (a)pyrene (BP‐9‐OH) and furthermore suggested that BP‐9‐OH‐4,5‐oxide was the derivative whose reaction with DNA yielded this microsome‐mediated BP‐DNA product.
Increased uptake of iodide by hormone‐responsive compared to hormone‐independent mammary tumors in GR mice
Authors: Thorpe Susan M. 
Published: February 2007

AbstractThe uptake of 125‐iodide by transplanted hormone‐responsive (HR) or hormone‐independent (HI) mammary tumors, normal mammary tissue and skeletal muscle was compared in GR mice. The uptake of 125‐iodide by HR mammary tumors in mice treated with progesterone and oestrone (P+O) was about 20 times greater than the uptake of 125‐iodide by HI mammary tumors in mice not treated with P+O. This difference in uptake of 125‐iodide by HR and HI mammary tumors could not be attributed to the difference in the hormonal status of the mice since uptake of 125‐iodide was also low in HI tumors in mice receiving P+O treatment. The uptake of 125‐iodide by HR mammary tumors was greatly reduced by the simultaneous injection of either an excess of non‐radioactive iodide or of perchlorate. Uptake of 125‐iodide by normal mammary tissue and skeletal muscle was similar in all groups of tumor‐bearing mice, and was not influenced by the presence of an excess of non‐radioactive iodide or of perchlorate. The possible clinical significance of these findings is discussed.
The reaction of (±)‐7α, 8β‐dihydroxy‐9β, 10β‐epoxy‐7,8,9,10‐tetrahydrobenzo(a)pyrene with dna
Authors: Osborne M. R. , Brookes P. , Beland F. A. , Harvey R. G. 
Published: February 2007

AbstractThe reaction of (±)‐7α,8β‐dihydroxy‐9β,10β‐epoxy‐7,8,9,10‐tetrahydrobenzo(a)pyrene (BP diol epoxide) with DNA, followed by enzymatic hydrolysis and LH 20 Sephadex column chromatography, yielded products containing a purine deoxyribonucleoside linked to a 7,8,9,10‐tetrahydrobenzo(a)pyrene derivative. DNA containing tritiated adenine or pyrimidines gave little or no tritiated products, showing that reaction occurred chiefly with the guanine residues. Results with 8‐(3H)‐guanine‐labelled DNA, and studies on the protonation and ionization of the products in acid or alkaline media, led to the formulation of the main product as an N2‐substituted guanine derivative. The reaction of BP diol epoxide with deoxyadenosine and deoxyguanosine gave further nucleoside derivatives which were probably minor products in the reaction with DNA. Treatment with strong acid unexpectedly converted each of the isolated products to free guanine or adenine.
Inhibition of syngeneic tumor growth in rats immunized with allogeneic skin grafts
Authors: Hosokawa Masuo , Imamura Masahiro , Oikawa Tsuneyuki , Gotohda Eiki , Kodama Takao , Kobayashi Hiroshi , Nakayama Masayuki , Sendo Fujiro 
Published: February 2007

AbstractThe growth of a transplantable tumor (KMT‐17) in syngeneic Wistar King Aptekman/Mk (WKA) rats was inhibited by preimmunization with allogeneic normal cells from Donryu strain rats. The phenomenon is referred to as allogeneic cell immunity. A slight inhibition was observed in rats immunized with normal liver, spleen, kidney, embryonal cells, whole blood and white blood cells from allogeneic Donryu rats. A strong inhibition was observed in animals which had rejected allogeneic skin grafts, particularly from the Donryu and Kyoto rats. The inhibition was comparatively weak after immunization with skin grafts from the Long Evans, ACI, Buffalo, Fischer, Sprague Dawley or Tokyo allogeneic rat strains. This immunizing effect was dependent on the viability of the grafts and was easily abrogated by low‐dose irradiation. The mechanism of allogeneic cell immunity is considered to be a non‐specific stimulation of the immunity against antigenic tumors in the syngeneic host.
Properties of the K562 cell line, derived from a patient with chronic myeloid leukemia
Authors: Klein Eva , Vánky Farkas , Ben‐Bassat Hannah , Neumann Hava , Ralph Peter , Zeuthen Jesper , Polliack Aaron 
Published: February 2007

AbstractThe K562 cell line derived from a CML patient in blast crisis was examined for properties of B and T lymphocytes and cell lines. K562 lacks the B markers of immunoglobulin, Epstein‐Barr virus (EBV) genome and associated nuclear antigen, and receptors for EBV. A low proportion of cells form rosettes with sheep erythrocytes, the frequency of which is considerably increased after neuraminidase treatment. Unlike B lines but like T lines, K562 cells are lysed rapidly by C'/Fc receptor‐positive human blood leukocytes and do not stimulate MLC reactions. On the other hand, K562 lacks T antigen, high radiosensitivity and sensitivity to growth inhibition by thymidine. The cells do not contain N‐APase, an enzyme found in all lines derived from lymphoid cells and in lymphoproliferative diseases. By scanning electron microscopy, K562 cells were seen to be rounded and relatively smooth, with small numbers of short microvilli resembling undifferentiated leukemic cells. A few cells had narrow ridge‐like profiles and small ruffles similar to granulocytic leukemic cells. K562 is strongly positive for immunoglobulin Fc receptors and pinocytosis, but does not phagocytose or mediate antibody‐dependent phagocytosis or cytolysis. Among histochemical stains, K562 is positive for esterase, lipid, and acid phosphatase. There seems to be no doubt that K562 is not a B cell line. While it has some T cell properties, these are not exclusive. Some of its characteristics indicate that it is probably not lymphoid. Due to its low level of differentiation, its nature cannot be stated with certainty. On the basis of the possible presence of the cellular marker of chronic myeloid leukemia, the Ph chromosome, it may be regarded as belonging to the granulocytic series of cells.
Prevention of benzo(a)pyrene‐induced mutagenicity by homogeneous epoxide hydratase
Authors: Oesch F. , Bentley P. , Glatt H. R. 
Published: February 2007

AbstractBenzo(a)pyrene and benz(a)anthrancene which, in contrast to the K‐region epoxides benzo(a)pyrene 4,5‐oxide and benz(a)anthracene 5,6‐oxide, are not mutagenic to Salmonella typhimurium TA 1537 in the absence of mammalian enzyme preparations, were activated by liver microsomes from C3H mice, which had not received any pretreatment, to mutagens reverting this tester strain to histidine prototrophy. Addition of epoxide hydratase inhibitors greatly increased this mutagenicity and addition of pure epoxide hydratase reduced it by more than 95% down to the range of spontaneous mutations as observed in absence of any added mutagen. This demonstrates that the metabolic pathway responsible for the mutagenicity of both polycyclic hydrocarbons observed in this system proceeds entirely via an epoxidation pathway and that the responsible metabolites are epoxides or species arising from them. Moreover, further metabolism by epoxide hydratase does not lead to products contributing to the mutagenicity observed with the tester strain used. Finally, the epoxides relevant for the observed mutagenicity are substrates for epoxide hydratase; indeed, modest amounts of the pure enzyme can prevent the mutagenic effect.
Markers to distinguish normal and neoplastic mammary epithelial cells in vitro: comparison of saturation density, morphology and concanavalin a reactivity
Authors: Voyles Bruce A. , McGrath Charles M. 
Published: February 2007

AbstractNormal and premalignant mouse mammary epithelial cells can be prepared in high yields by collagenase dissociation of minced glands followed by a brief, differential centrifugation to remove contaminating fibroblasts and fat cells. The major difficulties in preparing pure cultures in quantity are 1) incomplete dissociation of gland material, and 2) cell death during enzymatic digestion. These problems are eliminated by careful selection of collagenases for dissociation. Normal and premalignant mammary epithelial cells are morphologically indistinguishable from malignant mouse mammary epithelial cells in primary monolayer cultures. In addition, the growth rates and saturation densities achieved by normal mammary epithelial cells are indistinguishable from those of malignant mammary epithelial cells in primary culture. In both cases, a monolayer of cells is preserved with no evidence of focal overgrowth. Malignant adenocarcinoma mammary cells can however be distinguished from normal mammary epithelial cells by virtue of differences in their surface interactions with concanavalin A. A hemadsorption assay using Con‐A‐coated erythrocytes was the most sensitive indicator for these differences. In hemadsorption assays malignant mammary epithelial cells were half‐maximally reactive with 2.5 μg/ml concanavalin A, while normal cells were completely unreactive even at concanavalin A concentrations five‐times higher. Premalignant mammary epithelial cells were as reactive as malignant mammary epithelial cells in the hemadsorption assays. Hemadsorption of malignant cells was observed in primary and secondary cultures of epithelium as well as in cell lines. Malignant cells forming mammary adenocarcinomas were as highly reactive as malignant cells forming scirrhous carcinomas. Malignant cells not releasing mammary tumor virus (MuMTV) were as reactive as cells releasing that virus. Adsorption of concanavalin‐A‐coated erythrocytes to normal mammary epithelial cells could be induced by brief treatment of cell monolayers with hyaluronidase. Exposure of active sites was not affected with either trypsin or collagenase. Our results show that while the growth of malignant cells does not serve to distinguish them from normal cells in monolayer culture, surface changes do exist which can be identified by differences in concanavalin A reactivity. Since the earliest transformants identifiable in vitro (premalignant) have undergone conversion of the surface marker, concanavalin‐A‐mediated hemadsorption provides a sensitive measure for mammary epithelial cell transformants in vitro.
Lung tumour incidence in mice treated with hydrazine sulphate
Authors: Bhide S. V. , D'souza R. A. , Ranadive Kamal J. , Sawai M. M. 
Published: February 2007

AbstractLung tumour incidence in mice fed with hydrazine sulphate (1.1 mg/day/mouse) was studied in male and female mice of Swiss, Strong “A” and F1 cross of ICRC (female) × C3H (Jax) (male), as well as in C17 males. Swiss strain mice showed 100% lung adenocarcinomas. None of the treated mice of different strains had liver tumours. Hydrazine sulphate also induced adenocarcinomas of lung in Strong “A” and F1 cross of ICRC females × C3H (Jax) males but it produced lymphomas of lung in C17 strain. Female mice of Swiss strain and F1 hybrids showed greater susceptibility to hydrazine sulphate than the males. It was interesting to observe that protein and vitamin B deficiency in the diet shortened the tumour induction period in Swiss strain mice.
Cell surface changes observed in mc‐29 virus‐infected chicken‐embryo fibroblast (cec) cultures
Authors: Podmaniczky Erzsebet , Szende B. , Lapis K. , Ferenc G. 
Published: February 2007

AbstractBy transmission and scanning electron microscopic studies of MC‐29 virus‐infected CEC cultures, C‐type virus particles were detected in the medium of infected cultures, in infected cells and in intracellular vacuoles. Virus budding was also observed. In the scanning electron microscope (SEM) so‐called blebs appeared on the surfaces of the infected cells, in a number proportional to the concentration of the virus preparation. On the basis of the size of the blebs, it could be considered that virus formation was taking place in their center. In control cells, neither viruses nor blebs were observed. This method will presumably be suitable for the titration of virus preparations.
Human thymus/leukemia‐associated antigen in normal and leukemic cells
Authors: Chechik B. E. , Pyke K. W. , Gelfand E. W. 
Published: February 2007

AbstractA saline extractable human thymus/leukemia‐associated antigen (HThy‐L) has been detected in immunodiffusion using rabbit antisera raised to human thymus extracts. HThy‐L was demonstrated in extracts of normal thymocytes, lymphocytes from E‐rosetting T‐cell lines and from the blast cells of patients with E‐rosetting acute lymphoblastic leukemia. Extracts of leukemic cells from patients with acute myeloblastic leukemia and E‐rosette‐negative acute lymphoblastic leukemia contained significantly lower quantities of HThy‐L. Only trace amounts of the antigen were detected in normal spleen, tonsil, peripheral blood, bone marrow and PHA‐induced lymphoblasts. HThy‐L appears to be an antigen associated with the intrathymic differentiation of human T cells and a marker of leukemic cells in certain forms of acute leukemia.
Inhibition of leukocyte migration by human breast‐cancer‐associated antigens
Authors: Kadish Anna S. , Marcus Donald M. , Bloom Barry R. 
Published: February 2007

AbstractThe existence of CMI to tumor‐associated antigens present in 3 M KCl extracts of breast carcinomas was demonstrated in a group of breast cancer patients by the leukocyte migration inhibition (LMI) assay. When crude KCl extracts were tested, 3 of 5 breast cancer patients gave a positive response to autologous tumor extracts. Eleven of 20 gave a positive response to allogeneic extracts as compared to 3 of 22 controls (including 6 patients with benign breast disease, 7 with non‐mammary cancers and 9 normal controls). Extracts of fibrocystic disease tissue gave positive LMI tests in 2 of 5 breast cancer patients, suggesting the presence of antigenic cross‐reactivity between benign and malignant breast disease. An extract of a medullary carcinoma of breast was fractionated on Sephadex G‐200 and the effluent pooled into three fractions. The high molecular weight fraction produced LMI in 11 of 22 breast cancer patients and in 1 of 19 controls, including patients with benign breast disease, other cancers and normal individuals. The low molecular weight fraction produced LMI in both the benign (4 of 6) and the malignant breast disease (6 of 20) patients, but not in the controls (0 of 12). A simple fractionation technique has thus separated “cancer‐specific” from “organspecific” activity. Sephadex G‐200 fractions were active at a much lower protein concentration than the crude 3 M KCl extracts.
Host immune potentiation of drug responses to a murine mammary adenocarcinoma. II. Effect of melphalan therapy on the host immune system
Authors: Radov L. A. , Korn J. H. , Haskill J. S. 
Published: February 2007

AbstractThe role of chemotherapy in influencing tumorspecific immunity to a mouse mammary adenocarcinoma was investigated. By studying different stages of tumor growth we were able to identify several factors important to drug‐induced tumor regression: (1) antibody response, (2) delayed hypersensitivity, (3) sensitivity of tumor cells to immune attack and (4) tumor burden. The presence of tumor‐specific delayed hypersensitivity and circulating antibody as well as specifically armed monocytes in the tumor mass characterize the T1699 adenocarcinoma. Successful chemotherapy had previously been shown to depend on prior establishment of the above immune responses. Treatment with alkylating agents was marked in all animals by abrogation of a humoral response to the tumor when drug was given early (day 7), and was associated with poor chemotherapeutic results. Later treatment (day 10) was associated with depression of antibody titers only in the minority of animals not responding to drug and prolongation of the delayed hypersensitivity response in all treated animals. Tumors recurring following initial drug‐induced regression were marked by lack of delayed hypersensitivity in the host, lack of drug response and suppression of humoral immunity following treatment. Successive passage of cells from these resistant tumors led to decreasing sensitivity to chemotherapy despite established immunity on the part of the host. The selection of tumor cells resistant to immune destruction rather than drug resistance per se appeared to play a role. Melphalan was thus able to affect both favorably and adversely the immune factors important to drug‐induced regression.
Effect of localization of L‐asparaginase as the concanavalin a conjugate on anti‐tumor activity
Authors: Shier W. T. , Trotter J. T. , Astudillo D. T. 
Published: February 2007

AbstractA method potentially capable of enhancing the effectiveness of therapeutic enzymes such as Lasparaginase was investigated. The method was suggested by the following properties that have been observed for lectins injected into tissues: (1) six lectins with differing specificities were retained near the site of injection in the feet of mice 10 to 100 times longer than several non‐lectin proteins. Prolonged retention of 125I‐labelled concanavalin A was also observed in other normal and malignant mouse tissues. (2) The retention of 125‐I‐labelled concanavalin A was not affected by prior immunization against concanavalin A. (3) Electrophoresis of tissue extracts on sodium dodecyl sulfate‐polyacrylamide gels followed by radioautography indicated that the 125‐I‐labelled concanavalin A retained in the tissue remained as intact in form as prior to injection. Since the therapeutic efficacy of many enzymes may be enhanced by localization at the intended site of action, in principle it should be possible to enhance the effectiveness of therapeutic enzymes by combining the tissue‐localizing properties of a lectin with therapeutic effectiveness of the enzyme. A conjugate of E. coli L‐asparaginase and concanavalin A has been prepared by covalent cross‐linking with glutaraldehyde and has been shown to be retained in mouse tissue 90 times longer than the free enzyme. However, it is completely ineffective in the treatment of the L‐asparaginase‐sensitive lymphosarcoma 6C3HED in C3H/HeJ mice. The ineffectiveness of the conjugated enzyme may be associated with the interiorization of the conjugate by the cells of the tumor.