bluuebunny/crossref_metadata_2025 huggingface dataset:
Some international differences in treatment and survival in breast cancer
Authors: Morrison Alan S. , Lowe C. Ronald , Macmahon Brian , Ravnihar Bozena , Yuasa Shu
Published: February 2007

In a recent study, 5‐year survival rates for breast cancer patients in Boston (Massachusetts), Glamorgan (Wales), Slovenia (Yugoslavia) and Tokyo (Japan) were 57.3%, 49.5%, 41.9% and 74.9%, respectively. In this report, data are presented on the types of treatment used in the four areas and on the relationship of differences in treatment practices to the differences in survival rates. Generally, surgically treated patients who also had radiotherapy had lower survival rates than patients in the same area who had similar operations without radiotherapy. In each area, the survival rate was higher for patients who had radical mastectomy than for those who had simple mastectomy. The Japenese patients had the highest survival rate within nearly every treatment and extent‐treatment category. Thus, the high survival rate of these patients was not explained by the variables considered. Survival differences between Boston, Glamorgan and Slovenia were largely explained by differences in extent of disease and type of treatment. As the nature of the treatment—survival trends was consistent with the interpretation that treatment tended to be selected according to apparent prognosis, the degree to which treatment customs were determinants of the differences in survival rate among the three areas is uncertain.
Fluidity difference in the surface membrane lipid core of human lymphoblastoid and lymphoma cell lines
Authors: Inbar Michael , Ben‐Bassat Hanna
Published: February 2007

Twenty‐five human hematopoietic cell lines established from patients with malignant and non‐malignant diseases have been studied for membrane fluidity. The degree of fluidity in the surface membranes was quantitatively monitored by fluorescence polarization analysis of the fluorescence probe, 1,6‐diphenyl 1,3,5‐hexatriene, when embedded in the lipid region of the surface membrane of intact cells. The results have shown that cells derived from malignant diseases have a more fluid lipid layer in their surface membrane than cells derived from non‐malignant disorders. It is, therefore, suggested that a quantitative analysis of fluidity differences in the cell surface membrane lipid core can be of value to the studies on basic differences between normal and malignant cell lines established from the human hematopoietic system.
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

Mechanical 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

Regressing 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

A 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

The 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

The 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

The 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

The 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

Benzo(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

Normal 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

Lung 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

By 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

A 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

The 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

The 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

A 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.
Agglutination reactions of spontaneous canine tumour cells, induced by concanavalin a, demonstrated by an isotopic assay
Authors: Betton G. R.
Published: February 2007

Quantitative assessment of the agglutination of 51Cr labelled canine cell suspensions to canine kidney cell monolayers has been performed over a range of concanavalin A concentrations. Agglutination was observed with all cell cultures tested, comprising four spontaneous canine melanomas, two canine mammary carcinomas, a benign mammary tumour and a contact‐inhibited kidney cell line. The melanomas tested showed strong specific inhibition of concanavalin A agglutination by 10−2 M α‐methyl‐D‐glucopyranoside. Inhibition of agglutination of mammary tumour and kidney cells was weaker and less specific. Agglutination was inhibited at 4°C. Reduced agglutination to glutaraldehyde‐fixed monolayers was observed in the case of mammary tumours but was absent when contact‐inhibited kidney cells were tested. The specificity of the reaction for transformed cells and the parameters involved are discussed.
Mast cells and tumor angiogenesis
Authors: Kessler David A. , Langer Robert S. , Pless Naomi A. , Folkman Judah
Published: February 2007

Tumor angiogenesis factor (TAF) elicits a strong vasoproliferative response when implanted upon the chorioallantoic membrane (CAM) of the chick embryo. This response is first observed stereomicroscopically 2–3 days after implantation. A 40‐fold increase in mast cell density is observed within the vicinity of this implant by 24 h. Mast cells that have been isolated from retired breeder Sprague‐Dawley rats fail to evoke a vascular reaction when implanted on the CAM. An intermediate role for the mast cell in tumor angiogenesis is suggested.
Histologic specificity of the effect of age at birth of first child on breast cancer risk
Authors: Morrison Alan S.
Published: February 2007

Slides of 531 breast cancers from Glamorgan, Wales, were classified according to the presence or absence of each of three histologic characteristics: stromal infiltration by linear strands of tumor cells, areas of intraductal carcinoma, and areas of lobular carcinoma in situ. The proportion of tumors with each of these characteristics was positively associated with age at first child‐birth. Increasing age at first birth had a strong positive effect on the incidence risk of tumors with any of these features, but only a small effect on risk of tumors with none. For porous women, the rate of breast cancer with or without linear strands, with or without areas of intraductal cancer, and without areas of lobular carcinoma in situ was lower than for nulliparous women. Parity appeared not to reduce the risk of tumors with areas of lobular carcinoma in situ.
Oncornavirus‐like particles in malignant melanoma and control biopsies
Authors: Parsons P. G. , Klucis E. , Goss P. D. , Pope J. H. , Little J. H. , Davis N. C.
Published: February 2007

Tests for the presence of oncornavirus‐like particles in human biopsies were made by the Spiegelman simultaneous assay for 70S RNA and RNA‐dependent DNA polymerase and by detection of 600–900S particles, incorporating 3H‐uridine, produced by cultured biopsy cells. Thirty‐one malignant melanoma biopsies from 29 patients were studied. Using the simultaneous assay, evidence of virus‐like particles was found in 15/26 (58%) of melanoma biopsies, 0/3 naevi pool, 1/4 samples of skin adjacent to melanoma, 0/3 samples of normal adult skin and 0/3 prepuces. The velocity sedimentation technique was shown to be a useful screening test for oncornaviruses in studies of two virus‐producing mouse cell lines (TKL‐5 and WEHI‐22), and was positive with 7/9 melanoma biopsies. Overall, these results are compatible with the earlier findings of similar virus‐like particles in malignant melanoma cell lines, but the exact nature of the particles remains to be defined.
The immunospecificity of altered initial arrest patterns of circulating cancer cells in tumor‐bearing mice
Authors: Weiss L. , Glaves D.
Published: February 2007

The early arrest patterns of a methylcholanthrene‐induced fibrosarcoma were determined after injection of 125IUdR‐labelled cells into the systemic circulation of mice bearing transplanted lymphosarcomas, and of normal animals. Similar experiments were performed using radiolabelled lymphosarcoma cells and normal or fibrosarcoma‐bearing mice. The results showed that shifts in normal distribution patterns previously observed in tumor‐bearing animals injected with cells of the same type as that borne by the animal, were not detectable when cells of a different tumor type were injected. Peritoneal exudate cell migration inhibition assays showed little immunologic cross‐reactivity between the two tumors and, together with the results of the distribution studies, indicated that alterations of early arrest patterns in mice sensitized to their tumor is an immunologically specific phenomenon.
Membrane‐associated antigen from the SV40‐induced hamster fibrosarcoma, para‐7. I. Role in immune complex fcrmation and effector cell blockade
Authors: Prather Suzanne O. , Lausch Robert N.
Published: February 2007

PARA‐7 membrane‐associated antigen was prepared by treatment of the tumor cells with PH 9.4 glycine buffer, or by concentration of spent cell culture medium. When admixed with sensitized effector cells, both preparations could specifically block cellular cytotoxicity for PARA‐7 target cells. Pretreatment of target cells with antigen did not result in blocking. Incubation of antigen extract with simian virus 40 (SV40) anti‐serum caused neutralization of antibody‐dependent cellular cytotoxicity (ADCC) with concomitant formation of a factor which blocked at the target cell level but not at the effector cell level. Serum from tumor‐bearing hamsters exhibited blocking characteristics comparable to those of the antigen‐SV40 antiserum preparation. Washing experiments indicated that PARA‐7 antigen was more efficient than PARA‐7 antigen‐antibody complexes in blocking cell‐mediated immunity in vitro. Material extracted from untransformed hamster embryo fibroblasts either by itself or when admixed with SV40 antiserum exhibited no significant blocking activity. These observations support the concept that loss of serum ADCC during progressive tumor growth is due to immune complex formation.
Leukaemias in BN/a and BN/b mice after prolonged treatment with antilymphocyte globulin
Authors: Szkudlarek Jerzy , Radzikowski Czeslaw , Czarnomska Alina , Dux Kazimierz , Bartoszewicz Wadysaw
Published: February 2007

The influence of prolonged treatment with anti‐lymphocyte globulin on tumour incidence in BN/a and BN/b mice was studied. One ALG sample appeared to be highly leukaemogenic in two independent experiments. All treated mice developed, after a short latency period, non‐thymic lymphomas with involvement of abdominal lymph nodes and spleen resulting in ascites. Three established ascites leukaemia cell lines were examined for the presence of MuLV. In all lines viral C‐type particles, soluble viral gs‐1 antigen and cell surface antigen related to Gross virus were demonstrated. The mechanism of induction of these tumours remains obscure. The hypothetical role of immunosuppression, stimulation of lymphoid cells and activation of leukaemogenic virus is discussed.
Leukemogenic activity of murine type C viruses after long‐term passage in vitro
Authors: Buchhagen Dorothy L. , Pincus Theodore , Stutman Osias , Fleissner Erwin
Published: February 2007

Cloned stocks of several murine leukemia viruses (MuLVs) were shown to be leukemogenic for susceptible mice after more than nine years of in vitro passaging in mouse embryo fibroblasts. Tissue culture‐grown Rauscher (R‐) MuLVs injected into newborn or young adult BALB/c mice induced lymphocytic leukemias in 100% of the animals beginning 80 days post‐inoculation. No erythroblastic leukemia was observed even after passaging the tissue‐culture‐grown R‐MuLVs twice through mice, indicating that the component responsible for that disease had been lost or attenuated during growth in fibroblasts. The tissue‐culture‐grown stock of Moloney (M‐) MuLVs likewise induced lymphocytic leukemias in 94% of injected newborn BALB/c mice, and the tissue culture‐grown Gross (G‐) MuLVs induced lymphocytic leukemias in 42% of injected newborn C3Hf mice. The host range and neutralization characteristics of viruses recovered from animals that became leukemic after injection with the tissue‐culture‐maintained MuLVs were found to be identical with those of the injected viruses. These data implicate the injected MuLVs in the induction of the leukemias and suggest that the capacity to induce the disease is stably inherited as part of the viral genome even in the absence of expression.
Chemical‐viral co‐carcinogenesis: Requirement for leukemia virus expression in accelerated transformation
Authors: Mishra Nirmal K. , Pant Kamala J. , Thomas Francina O. , Price Paul J.
Published: February 2007

The essential role of Rauscher leukemia virus (RLV) multiplication in viral—chemical co‐carcinogenesis was investigated by the use of ethidium bromide (EtBr) as an inhibitor of viral complementary DNA (cDNA) integration in the host genome. EtBr inhibited co‐carcinogenic transformation when present at the time of RLV inoculation but was ineffective when added to preinfected cells. Inhibitors of protein synthesis, puromycin and cyclohexamide also inhibited co‐carcinogenic transformation of chronically infected cells. Purified rat interferon used at a concentration which inhibited 85% of RLV production did not modify the course of co‐carcinogenic transformation. The implications of these observations in terms of the possible role of the virus‐specific protein(s) in the co‐carcinogenic process are discussed.
Reactivity of peripheral blood leukocytes against human foetal cells. II. Cytotoxic potential of preparations enriched or depleted of different leukocyte populations
Authors: Vose B. M. , Moore M.
Published: February 2007

Leukocytes separated initially by Ficoll‐Triosil sedimentation from the peripheral blood of 62 healthy donors and 64 patients with a variety of cancers were tested for cytotoxicity against cells from a single human foetal lung, by means of a microplate technique based on visual enumeration of surviving target cells. Under these conditions cytotoxicity was primarily observed to be a function of the granulocyte content of the preparations, which was extremely variable (range 0–60%). When the influence of these cells was greatly diminished through depletion by adherence, residual cytotoxicity was still detectable in the majority of samples tested. Complete abrogation of this cytotoxicity by pretreatment with carrageenan implicated cells of the monocyte‐macrophage series, which persisted as a small minority (about 2%) in the already depleted effector cell populations. However some cytotoxicity could also be demonstrated in populations, purified by passage through columns containing nylon fibre or Degalan‐coated (human Ig‐anti Ig) beads, which consisted almost exclusively (about 98%) of lymphocytes, mainly of thymus (T)‐dependent type (⩾80%). Under these conditions and those in which T‐cells were concentrated by formation of spontaneous E rosettes, cytotoxicity appeared to decline with T cell enrichment, suggesting that the cytolytic effects were attributable to cells of the non‐T compartment which were present to a variable extent in the different T‐cell‐enriched populations. Although the absolute identity of these cells was not established, the experiments illustrate potential sources of non‐specific cytotoxicity among different effector cell populations against target cells expressing antigens to which the majority of leukocyte donors —in health or disease—were presumably non‐sensitized. As such these data have several implications for the interpretation of in vitro cytotoxicity tests against human neoplasms.
Detection of human c‐type “helper” viruses in human leukemic bone marrow with murine sarcoma virus‐transformed human and rat non‐producer cells
Authors: Nooter Kees , Bentvelzen Peter , Zurcher Chris , Rhim Johng
Published: February 2007

Bone‐marrow cells from two leukemic children were co‐cultivated with the canine thymus cell line A 7573. In early passages, C‐type oncornaviruses were released as detected by extracellular reverse transcriptase assay. Co‐cultivation of the infected canine cells with the non‐producing cell lines R‐970‐5 (human) or K‐NRK (rat) both transformed by Kirsten mouse sarcoma virus (MSV) yielded a new pseudotype of MSV that could transform rat embryo, rabbit SIRC and human kidney cells but not mouse embryo cells. The focus formation could be inhibited by an antiserum to the simian sarcoma virus but not by a serum directed against murine leukemia virus. A cell line derived from a focus of transformed cells became a high virus producer. By immunofluorescence it could be established that the virus is related to the simian sarcoma virus. It is concluded that the leukemic bone‐marrow cells produce a C‐type oncornavirus that can serve as a helper virus to the defective MSV.
Detection of early antigens in nuclei of cells infected with cytomegalovirus or herpes simplex virus type 1 and 2 by anti‐complement immunofluorescence, and use of a blocking assay to demonstrate their specificity
Authors: Giraldo G. , Beth E. , Hämmerling U. , Tarro G. , Kourilsky F. M.
Published: February 2007

Skin fibroblasts exposed to cytosine arabinoside (Ara C) were infected with either cytomegalovirus (CMV) or herpes simplex virus (HSV) type 1 and 2. Herpesvirus‐determined early antigens (HV‐EA), detected by anti‐complement immunofluorescence (ACIF), occurred primarily in the nuclei, and the specificity of these results was established by an ACIF blocking reaction using F(ab')2 fragments of human and hyperimmune reference sera. Direct tests with selected sera and cross‐blocking experiments between early antigenic systems of CMV, HSV‐1 and the Epstein‐Barr virus (EBV) did not demonstrate common HV‐EA.
Development of hemangiosarcomas in B6C3F1 mice fed 2‐methyl‐1‐nitroanthraquinone
Authors: Krishna Murthy A. S. , Baker J. R. , Smith E. R. , Wade G. G.
Published: February 2007

Subcutaneous hemangiosarcomas developed in 97% of 172 B6C3F1 mice of both sexes fed either 0.03% or 0.06% 2‐methyl‐1‐nitroanthraquinone in the diet. There was no significant relationship to dose or sex. In addition, similar vascular tumors occurred in the mesentery of 14 mice. 2‐Methyl‐1‐nitro‐anthraquinone is carcinogenic in B6C3F1 mice when given in food. One of 97 control mice had a splenic hemangiosarcoma.
Dna binding and its relationship to carcinogenesis by different polycyclic hydrocarbons
Authors: Huberman Eliezer , Sachs Leo
Published: February 2007

Five different polycyclic hydrocarbons with different degrees of carcinogenicity in vivo were tested for their metabolism to water‐soluble products and their binding to DNA, RNA and protein in normal embryonic hamster and BHK cells. The compounds studied were 7,12‐dimethyl‐benz(a)anthracene, benzo(a)pyrene, 20‐methyl‐cholanthrene, dibenz(a,h)anthracene and dibenz‐(a,c)anthracene. All five compounds were metabolized to water‐soluble products in both types of cells and treatment of cells with aminophylline enhanced this metabolism. After and not before this enhancement of metabolism by aminophylline, there was a relationship between the degree of carcinogenicity and binding to DNA. There was no such relationship with binding to RNA or protein. The results, indicating a relationship between the degree of carcinogenicity and binding to DNA under appropriate conditions of metabolism, support the suggestion that DNA is the target for carcinogenesis by such carcinogens.
Long‐term administration of ddt or phenobarbital‐na in wistar rats
Authors: Rossiz Lorenzo , Ravera Marina , Repetti Giuliana , Santi Leonardo
Published: February 2007

In lifespan studies, outbred male and female Wistar rats were given either technical DDT mixed into the diet at a dose of 500 parts per million (ppm) or phenobarbital‐sodium dissolved in drinking water at a dose of 500 ppm. Liver‐cell tumors developed in treated animals but not in controls. The incidence of liver tumors was 45% in the DDT‐treated group and 44% in the phenobarbital‐sodium‐group. When evaluated by sex, DDT‐treated females and males had incidences of 56% and 35%, respectively, while in the phenobarbital‐sodium group, the respective incidences were 32% and 59% in females and males. These data show a varying susceptibility between the sexes, with regard to induction of liver‐cell tumors by the two compounds. In both treated groups, the number of nodular tumors per rat and the average size increased with age and were greater in females. None of these tumors had metastasized. Histologically, the liver tumors were nodular growths, which compressed surrounding parenchyma but did not infiltrate it. The total incidence of extrahepatic tumors was higher in controls than in treated animals. In this connection, we must mention the apparent, but not significant, reduction of adrenal tumors in treated rats compared to the controls.
Gross‐virus‐induced lymphoma in the rat. V. Natural cytotoxic cells are non‐t cells
Authors: Shellam G. R.
Published: February 2007

The cytotoxic cells from the spleens of normal rats, which lyse Gross‐virus‐induced lymphoma target cells in a short‐term 51Cr release test, are predominantly small to medium‐sized cells sedimentng at 4–5 mm/h as shown by velocity sedimentation analysis. Their cytotoxic activity is relatively resistant to γ‐radiation, 50% surviving 1,000 rads and 30% remaining after 5,000 rads, and to heat, since 20 min incubation at 48–51° C is required for its abolition. In these properties the natural killer (NK) cells are very similar to the cytotoxic T cells from tumour‐immune rats, and they share in addition a requirement for Ca++ ions for cytolysis. They differ in that they are non‐T cells as defined by their resistance to anti‐T‐cell antiserum and complement, and by their presence in T‐cell‐deprived rats. They lack detectable surface Ig, Fc receptors and phagocytic or adherence properties and belong therefore to that small proportion of lymphoid cells lacking the surface markers of T or B lymphocytes, as do the comparable NK cells of mice. Cytotoxicity appears to involve an autonomous, papain‐sensitive recognition structure on the surface of NK cells, rather than acquired cytophilic antibody operating through an antibody‐dependent mechanism.
Effects of ethylnitrosourea administration during pregnancy on three subsequent generations of bdvi rats
Authors: Tomatis L. , Ponomarkov V. , Turusov V.
Published: February 2007

A single dose of 40 mg/kg of N‐nitrosoethylurea (ENU) was administered to BDVI rats on the 16th day of pregnancy. The first generation descendants (F1) were mated on a brother‐to‐sister system to produce a second generation (F2) which was then mated to produce a third generation. A high incidence of nervous tissue tumors and a few kidney tumours were observed in F1 descendants. A few nervous tissue tumours were observed in F3 but not in F2 descendants. These results partially confirm previous observations obtained with 7,12‐dimethylbenz(a)anthracene in mice and nitrosomethylurea in rats and indicate that prenatal exposure to a chemical carcinogen may result in an increased cancer risk which can persist for more than one generation.
Mouse mammary tumor virus production stimulated by hormones and polyamines in cells grown in semi‐synthetic in vitro conditions
Authors: Svec Juraj , Links Jan
Published: February 2007

Hormonal regulation of mouse mammary tumor virus (MMTV) synthesis was studied in the CCL‐51‐SF cell subline derived from the Sykes' mammary tumor cell line CCL‐51 and adapted to grow in semisynthetic in vitro conditions. The virus was quantitated by measuring the supernatant reverse transcriptase activity in exogenous reaction using poly (rA) · oligo (dT) and poly (rC) · oligo (dG) as template/primers. The cells produced a low but significant amount of virus in the absence of any hormones and serum proteins. The synthetic glucocorticoid dexamethasone increased production considerably, up to 100‐fold. Pretreatment of CCL‐51‐SF cells with serum or 5‐bromodeoxyuridine, BrdUrd, partly reduced the stimulation by dexamethasone of MMTV production. Insulin and prolactin alone or in combination had no stimulating effect on spontaneous MMTV synthesis and cell growth. Prolactin, and more efficiently the prolactin‐insulin combination, enhanced the MMTV production stimulated with dexamethasone. Insulin alone remained without effect. The polyamine spermidine, but not spermine, increased the MMTV production over the control by a factor of 2. Polyamines did not influence cell replication at the concentrations used.
Detergent solubilization and partial purification of tumor specific surface and transplantation antigens from SV40‐virus‐transformed mouse cells
Authors: Chang Chungming , Pancake Samuel J. , Luborsky Samuel W. , Mora Peter T.
Published: February 2007

A solubilization technique employing 0.5% Triton X‐100 was developed to obtain both SV40 virus (SV40)‐induced tumor‐specific surface antigen(s) (TSSA) from SV40‐transformed mouse cells, as determined by a serum‐mediated microcytolytic assay, and tumor‐specific transplantation antigen(s) (TSTA), as determined by in vivo experiments. High yields (˜50%) of TSSA were obtained in whole‐cell extracts and also after ammonium sulfate fractionation. Additional fractionation of a 30–50% ammonium sulfate fraction by gel exclusion chromatography on Sephadex G‐150 resulted in two pooled fractions which contained TSSA activity. The first eluted close to the void volume, and the second in the 45,000 molecular weight region. The various TSSA active fractions were also active in in vivo TSTA tests. Detergent solubilization provides a suitable technique to recover the SV40‐induced antigens in good yield, and apparently in intact form.