bluuebunny/crossref_metadata_2025 huggingface dataset:
Hormones, chemicals and proviral gene expression as contributing factors during mammary carcinogenesis in C3H/StWi mice
Authors: Smith Gilbert H. , Teramoto A. , Medina Daniel
Published: February 2007

C3H/StWi mice spontaneously lost their exogenous MMTV (MMTV‐S) in 1958 and became a low mammary cancer subline. They do not ordinarily express their endogenous MMTV provirus as virions. Virigin C3H/StWi females were exposed to chemical carcinogens, 7‐12 dimethyl(α)benzanthracene (2,6 mg) and urethane (200 mg) in the presence or absence of chronic hormonal stimulation of the mammary gland by pituitary isografts. By 10 months of age, mammary tumors developed in 40% of the females given DMBA, and in 59% of those given DMBA and carrying pituitary isografts. With urethane treatment alone, 14% of the mice developed mammary cancer during a 12‐months period; however, 74% of the mice bore mammary tumors when pituitary isografts were present. None of the females given pituitary isografts alone developed mammary cancer during the experimental period. Mammary tumors from each group were evaluated by radioimmune competition assay, immunoperoxidase and electron microscopy to determine the extent of endogenous MMTV gene expression. In addition, the mammary glands of some of the non‐tumor‐bearing mice were studied by whole mount and by histology to determine the type, extent, and number of mammary dysplasias present in each group. In general, there was no correlation between tumor incidence and the presence of mammary tumor virus antigens. Of 32 mammary tumors tested in all groups, 10 were positive at low levels for MMTV antigens. In the positive tumors, the internal MMTV gag gene antigen, p28, was prevalent. Immunoperoxidase studies on these same tumors gave quantitatively similar results. It is apparent from these observations that chemical carcinogenesis of mouse mammary glands does not require or even favor the complete expression of endogenous MMTV genes. In this study, hormonal stimulation of the glands during and after exposure to the carcinogen increases the rate of tumorigenesis, but does not seem to favor MMTV gene expression. We conclude that C3H/StWi mice are susceptible to DMBA and urethane induction of mammary cancer and to an extent this process is positively influenced by the presence of hormonal stimulation. Our results support the view that a qualitative or quantitative shift in the expression of MMTV proviral sequences does not occur during tumor development.
Experimental studies of tumor radioimmunodetection using antibody mixtures against carcinoembryonic antigen (CEA) and colon‐specific antigen‐p (CSAp)
Authors: Gaffar Shaik A. , Pant Keshab D. , Shochat Dan , Bennett Sidney J. , Goldenberg David M.
Published: February 2007

Experiments with the GW‐39 human colonic carcinoma growing in hamsters showed that injection of radioactive antibody to a colorectal‐specific, tumor‐associated antigen, CSAp, results in better tumor radiolocalization than was seen previously with radioantibodies to carcinoembryonic antigen (CEA). However, a mixture of both radioactive antibodies resulted in potentiation of CEA‐tumor radioimmunodetection without affecting CSAp‐tumor radiolocalization. Hence, multi‐marker antibody mixtures may be the method of choice in cancer radioimmunodetection.
Selective antiviral activity of human interferons on primate oncogenic and neurotropic herpesviruses
Authors: Daniel Muthiah D. , Tamulevich Ruth , Bekesi J. George , King Norval W. , Falk Lawrence A. , Silva Daniel , Holland James F.
Published: February 2007

Human lymphoblastic, leukocytic and fibroblastic interferons were found to have marked antiviral activity on the replication of Herpes virus saimiri and Herpes virus ateles when used at a concentration of 500 IU/ml or greater but only minimal activity against two neurotropic viruses, viz. Herpes‐virus platyrrhine and herpes simplex virus. All three interferons were equally effective as antiviral agents against the oncogenic herpesviruses. Pretreatment of cells with interferons before virus infection was not required as it failed to enhance or retard the antiviral action of interferon, particularly in the case of the oncogenic herpesviruses. The m.o.i. of virus ranging from 100 to 0.0002 did not alter the effectiveness of the antiviral ability of interferon which was maintained at these virus concentrations. Interferon was equally effective in suppressing the replication of the two oncogenic viruses at low and high m.o.i. (20 to 0.00002). Interferon was able to suppress the advancement of virus‐induced cell cytopathic effect of HVS‐ and HVA‐infected cell monolayers. This event could be repeated continuously over a period of several months by addition and withdrawal of interferon. Virus‐infected cell monolayers exhibiting advance (75%) of cell cytopathology could be treated with 10,000 IU/ml interferon to attain cell confluency. These treated cells subsequently could be subcultivated (if maintained on 2000 IU/ml interferon) for over 14 months and 20 subpassages with an absence of virus, viral antigens or virus particles. These same cells, if maintained in the absence of interferon during each subpassage level, will produce virus; however, from the 14th subpassaged cell cultures virus appears to have been repressed or lost in the absence of interferon, suggesting that long‐term application of interferon may have a therapeutic effect in ‘eliminating’ virus infection. Owl monkey kidney cells infected with HVS or HVA at a m.o.i. of > 1 (2 and 20) or m.o.i. < 1 (to induce a multicycle infection) were successfully treated with interferon.
Lymphoproliferative responses to autologous tumor extracts as prognostic indicators in patients with resected breast cancer
Authors: Cannon G. B. , Dean J. H. , Herberman B. , Keels M. , Alford C.
Published: February 2007

Patients with operable breast cancer were tested postoperatively to assess lymphoproliferative responses. Patients with lymphocytes capable of recognizing and proliferating in response to autologous tumor extracts had a significantly longer disease‐free interval than those with a low response to their autologous extract. In this group of patients, immunological responses to autologous tumors predicted subsequent clinical course better than pathological evaluation based on tumor presence in axillary lymph nodes. Low or negative reactivity to autologous tumor often was not accompanied by a general, impaired ability to respond in LP assays. In fact, patients with low autologous tumor response and normal MLC were at a particularly high risk for recurrence.
EBV infection of mitogen‐stimulated human B lymphocytes
Authors: Einhorn Lena , Klein Eva
Published: February 2007

B lymphocytes from human blood were treated with the mitogen Protein A (Staph. aureus), which induces DNA synthesis in, as well as differentiation of, the B lymphocytes. The cells were subsequently exposed to Epstein‐Barr virus (EBV). EBV‐infected and mitogen‐stimulated cells were detected simultaneously, by using a combination of immunofluorescence (for EBNA) and autoradiography (for DNA‐synthesis). In the initial phase (1‐2 days) after addition of the mitogen, stimulated cells were as susceptible to infection as resting cells. Thereafter, their susceptibility decreased. This suggests that, although initiation of DNA‐synthesis does not seem to limit sensitivity to the viral infection, differentiation of the B cells might do so. The intensity and pattern of EBNA‐staining in prestimulated cells differed from that of the controls.
Naturally occurring humoral immunity to endogenous xenotropic and amphotropic type‐C virus in the mouse
Authors: Kende Meir , Veronese Fulvia , Hill Dick W. , Dinowitz Marshall , Kelloff Gary J.
Published: February 2007

Natural humoral cytotoxic antibodies from 13‐ and 18‐month‐old BALB/c mice showed a virus‐specific complement‐dependent activity against target cells productively infected with xenotropic, amphotropic or ecotropic type‐C viruses. The cytotoxic activity was lowest against ecotropic virus‐shedding cells. Serum obtained from mice less than 12 months old had no such reactivity. The cytotoxic reactivity was found to reside solely in the immunoglobulin M fraction which yielded reactivity comparable to the unfractionated sera concerning both titer and relative reactivities to the target cells infected with different type‐C viruses. In hyperimmune mouse serum cytotoxic reactivity resided in IgG and IgM fractions. Examination of serum from individual, normal 18‐month‐old BALB/c mice revealed that 80–90% of them were cytotoxic against virus non‐producer mink target cells expressing gp70 or gaggene product. Absorption of sera from 18‐month‐old normal BALB/c mice with cells shedding Class II or Class III xenotropic virus, amphotropic virus, Rauscher‐MuLV, or Class I murine leukemia virus indicate a closer amphotropic‐FMR viral subtype specificity of the natural cytotoxic immune response as compared to the amphotropic‐xenotropic or amphotropic‐ecotropic specificity. The incidence and the level of measured humoral cytotoxic activity was sustained in the tumor‐bearing animal up to 28 months of age as compared to the background established in the 18‐month‐old animal. However, in the non‐tumor‐bearing animal, the incidence and level of cytotoxic reactivity declined rather rapidly with aging. The sustained cytotoxic reactivity of the serum from old tumored mice might be involved in the progression of the tumor.
Rapid hepatoma induction in rats by dipentylnitrosamine and its modification by other carcinogens
Authors: Davis William E. , Jones David C. L. , Rosen Victor J. , Sasmore Daniel P.
Published: February 2007

Dipentylnitrosamine (DPN), administered in the diet at a concentration of 2,000 ppm to Fischer‐344 rats, produced hepatomas in 27% of both males and females within 8 weeks. Bile‐duct carcinomas were also produced. All animals also showed liver nodular hyperplasia and bile‐duct cell proliferation. Feeding DPN at 1,500 ppm produced hepatomas or bile‐duct carcinomas in 7% of the males and varying degrees of nodular hyperplasia and duct cell proliferation after 8 weeks of feeding. The total cumulative dose after feeding 2,000 ppm DPN was of the order of 7,700 mg/kg body weight in males and 8,200 mg/kg in females. There was a 28% weight decrement in animals fed 2,000 ppm DPN when compared to controls but no mortality. DPN carcinogenicity was enhanced when DPN was combined with a liver carcinogen, cycasin (fed as cycad nut flour, equivalent to 160 ppm cycasin). No effect on DPN carcinogenicity was found in rats fed DPN and lasiocarpine, another known liver carcinogen with antimitotic activity. Neither was there any effect on DPN carcinogenicity in rats fed DPN and N‐butyl‐N‐(4‐hydroxybutyl) nitrosamine or N‐methyl‐N′‐nitro‐N‐nitrosoguanidine. In contrast, the trisodium salt of nitrilotriacetic acid reduced the hepatocarcinogenic action of DPN. The enhancement of DPN carcinogenicity with cycasin is compatible with the hypothesis that DPN‐induced liver cell populations (hyperplastic nodules) can resist the cytotoxic effect of cycasin and differentiate rapidly toward hepatomas, while other areas of the liver are suppressed.
Prognostic value of chromosomal findings in the blast phase of Ph1‐positive chronic myeloid leukaemia (CML)
Authors: Oláh ÉVa , Rák Kálmán
Published: February 2007

Twenty‐three patients in various cytological subgroups of blast phase of Ph1‐positive chronic myeloid leukaemia were investigated cytogenetically. The correlation between prognosis and the cytological and cytogenetic features of blast cells was studied. The best prognosis was found in the myeloid group, followed by the lymphoid, myelomonocytic, megakaryoblastic and finally the promyelocytic groups, in this order. As regards the prognostic significance of the cytogenetic finding, the survival seemed to be the longest among patients with mosaic karyotypes i.e. when further aberrations occurred in some Ph1‐positive cells. The course of the disease was the most favourable in the presence of i(17q), especially in patients whose cells had i(17q) as the only aberration. The most severe course of the disease could be found in patients with +8 and/or two Ph1. The results demonstrate the usefulness of chromosome investigations in distinguishing the different cytogenetic subgroups in terminal stages of CML, which also differ prognostically from each other.
Difference in viral binding between two epstein‐barr virus substrains to a spectrum of receptor‐positive target cells
Authors: Wells Alan , Koide Norio , Klein George
Published: February 2007

Radio‐labelled Epstein‐Barr virus (EBV) was utilized in a direct binding assay to detect the presence of EBV receptors. The sensitivity of this method was affirmed by the detection of EBV‐receptors on three EBV‐carrying cell lines that have previously been reported as receptor negative. Two laboratory substrains of EBV, derived from the cell lines B95‐8 and P3HR‐1 (designated B and P virus respectively), were tested in the binding assay. The main receptor prototype adsorbed both viral strains without apparent distinction. In contrast, two lines, a Swedish EBV‐negative B‐cell lymphoma (U698) and a virus non‐producer subline of the receptor‐negative P3HR‐1 line, adsorbed P virus selectively but failed to adsorb B virus.
Deficiency of natural killer cell activity in patients with chronic lymphocytic leukemia
Authors: Ziegler Hans‐W.(Löms) , Kay Neil E. , Zarling Joyce M.
Published: February 2007

Natural killer (NK)6 cell activity of peripheral blood lymphocytes against human leukemia cell lines was measured in patients with chronic B‐cell lymphocytic leukemia (CLL) and age‐ and sex‐matched controls. In order to remove the leukemia cells that interfere with the in vitro assay we (1) isolated lymphocytes that form rosettes with sheep red blood cells (SRBC) or (2) lysed the CLL cells with a monoclonal anti‐B cell antibody and complement. NK activity in either lymphocyte preparation from nine of 10 patients with advanced disease was not detectable and, when calculated in terms of lytic units per ml of blood, was at least seven times lower than in controls; only one of these patients exhibited activity within the control range. Two patients with early disease had measurable, but low, NK‐cell activity. Prolongation of the NK cell assay from 6 to 18h gave rise to significant killing in the CLL patients lacking NK cell activity in the 6‐h assay; however, the activity still was six times lower than in controls. Treatment of leukemia cell‐depleted lymphocytes from CLL patients with human fibroblast interferon or the interferon inducer poly I:C enhanced NK‐cell activity in the two early stage patients but this treatment was ineffective in three later stage patients. The percentage of cells with characteristics of NK cells, i.e. those with receptors for SRBC and Fc‐portion of IgG, was four times higher in CLL patients and the percentage of lymphocytes binding to NK‐sensitive target cells was equal to that in controls despite the fact that, in the majority of patients, lysis of the target cells by the lymphocytes does not ensue. The NK deficiency may be responsible for the increased incidence of secondary malignancies in CLL patients.
Host range and oncogenicity studies of the murine myeloma MOPC‐315 type‐C retrovirus
Authors: Gazit Arnona , Guthmann Daphna , Yaniv Abraham
Published: February 2007

The biological features of an endogenous type‐C RNA tumor virus released by the murine plasmacytoma MOPC‐315 were determined. The virus was found to be pure ecotropic and, according to its capability to infect both NIH/3T3 and BALB/3T3 cells, it was established as an NB tropic virus. This tropism became more pronounced as a consequence of multiple passages in BALB/3T3 cells. In view of the ability of myeloma viruses to efficiently infect BALB/c cells, their possible role in myeloma induction is considered.
Spontaneous regression of friend‐virus‐induced erythroleukemia. VII. The genetic control of regression
Authors: Dietz Michael , Fouchey Susan , Furmanski Philip
Published: February 2007

The genetic control of spontaneous regression of erythroleukemia was studied in parental and hybrid mice in which leukemia was induced by the regressing strain of Friend virus (RFV). Because in previous studies parental regressor mouse strains tested (N/PLCR, SIM, NIH Swiss) all had the Fv‐I n/n genotype and the progressor mouse strains (SIM.R, 3ALB/c) had the Fv‐I b/b genotype, we determined the influence of Fv‐I alleles on regression. Genes which influence regression were dominant and had partial penetrance in (progressor X regressor) F1 mice. Regression occurred in hybrid mice which inherited the Fv‐I b/b genes of each of the progressor mouse strains. Regression and Fv‐I alleles also segregated independently in (N/PLCR X BALB/c) F2 mice, in random‐bred Swiss mice heterozygous for the Fv‐I gene, in partially inbred Swiss recombinant progressor and regressor mouse lines, and in hybrid mice carrying the Fv‐I b/b gene of SIM.R mice. Regressor SIM and progressor SIM.R mice, which were bred to be congeneic at the Fv‐I locus, also differ with respect to recovery from viremia, suggesting that their Rfv‐3 genes differ and influence regression. Crosses of SIM and SIM.R mice with the A.BY (Rfv‐3 s/s) mouse strain confirmed that SIM and SIM.R carry Rfv‐3 r/r and Rfv‐3 s/s, respectively. We conclude that Fv‐I b/b is not inhibitory to regression nor is the Fv‐I gene a genetic determinant in the process. The data suggest that regression is influenced by several genes, including those (Rfv‐1, Rfv‐2, Rfv‐3) shown to affect recovery from leukemia in other systems.
Canine transmissible venereal sarcoma: Leukocyte adherence inhibition (LAI) reactivity of various lymphoid tissues of dogs with tumors at different stages of growth
Authors: Harding Matthew W. , Yang Tsu‐Ju (Thomas)
Published: February 2007

Leukocyte adherence inhibition (LAI) reactivity of various lymphoid tissues of dogs with canine transmissible venereal sarcoma (CTVS) at different stages of growth was determined by the tube LAI test. Tumors were classified at the time of excision into progressor, steady state, and regressor stages of growth. The LAI reactivity to CTVS antigen extract of spleen, draining and non‐draining lymph‐node cells, and peripheral blood leukocytes of regressors (non‐adherence index ‐ NAI of 172.8±46.8, 148.1±64.7, 138.7±47.3, and 172.2±60.7, respectively) was significantly greater than that of progressors (46.1±20.0, 38.5±21.5, 50.2±30.0, 24,6±37.2, respectively, p <0.001) and normal dogs (47.5±22.8, 54.6±24.6, 26.7±14.0, 50.9±22.4, respectively, p<0.001). In contrast, LAI reactivity of progressor lymphoid tissues to CTVS antigen extract did not differ significantly from that of normal dogs. LAI reactivity of lymphoid tissues from steady state tumor bearers (97.9±39.2, 80.7±47.3, 87.1±40.0, 85.1±53,9, respectively) was intermediate between and significantly different from LAI reactivities of regressor (p <0.05) and progressor (p <0.01) lymphoid tissues. Significant LAI reactivity observed in regressors suggests the presence of a functional effector cell mechanism associated with spontaneous regression of CTVS. The three distinct patterns of LAI reactivity observed in tumor‐bearing dogs appear to correlate with the clinical course of tumor growth.
In vivo formation of benzo (a) pyrene diol epoxide‐deoxyadenosine adducts in the skin of mice susceptible to benzo (a) pyrene‐induced carcinogenesis
Authors: Ashurst Stephen W. , Cohen Gerald M.
Published: February 2007

The hydrocarbon‐deoxyribonucleoside adducts formed in mouse skin DNA have been determined following topical application of an initiating dose of benzo(a)pyrene to Swiss mice, a strain shown to be susceptible to benzo(a)pyrene‐induced skin carcinogenesis. Several DNA‐bound products were formed, of which the major one (60 % of total adducts), in agreement with other workers' findings, was derived from reaction of (±) 7β, 8α‐dihydroxy‐9α, 10α‐epoxy‐7,8,9,10‐tetrahy‐drobenzo(a)pyrene (BPDE) with the exocyclic amino group of deoxyguanosine. A further product (9–10% of total adducts), previously observed only after microsomal activation of benzo(a)pyrene, was observed and co‐chromatographed with a further metabolite of 9‐hydroxybenzo(a)pyrene bound to an uncharacterized base in the DNA. Two other products (2–3 % of total adducts) were also found in the in vivo studies which co‐chromatographed with BPDE‐deoxyadenosine adducts and arose from cis and trans addition of the exocyclic amino group of deoxyadenosine to the 7R form, but not the 7S form, of BPDE. In contrast to this, the major in vitrodeoxyadenosine‐bound products, formed following reaction of BPDE with calf‐thymus DNA, were derived from the 7S form of BPDE, suggesting either stereo‐selective formation or reaction of the 7R form of BPDE in mouse skin in vivo. Similar amounts of BPDE‐deoxy‐guanosine and BPDE‐deoxyadenosine adducts, as well as those derived from further metabolism of 9‐hydroxy‐benzo(a)pyrene, were formed in three strains of mice reported to have widely differing susceptibilities to polycyclic hydrocarbon‐induced skin carcinogenesis. The relevance of these different hydrocarbon‐DNA adducts to carcinogenesis requires further investigation.
Metastasis and the reticuloendothelial system. II. Effect of triamcinolone acetonide on organ retention of malignant cells in endotoxin‐treated mice
Authors: Glaves Dorothy , Weiss Leonard
Published: February 2007

The lung retention patterns of B16 melanoma cells were determined after intravenous injection of [125I]dUrd‐labelled tumor cells into B16 melanoma‐bearing mice. Experiments were performed to assess the effects of a synthetic glucocorticoid, triamcinolone acetonide, on the retention of B16 melanoma cells arrested in the lungs of mice with endotoxin‐induced reticuloendothelial system hyperfunction. Lung clearance of malignant cells was greatly accelerated in mice treated with endotoxin alone but was markedly inhibited in mice with only triamcinolone acetonide. In mice treated with both endotoxin and subsequently triamcinolone acetonide after tumor‐cell arrest processes had occurred, the endotoxin‐induced increase in clearance was nullified. These results are discussed in terms of the mutually antagonistic activity of both pharmacologic agents upon the reticuloendothelial system and the role of the latter in regulating organ retention of disseminated malignant cells.
The effect of high doses of poly (i>poly (c) induced mouse l cell interferon on rauscher leukemia virus induced erythroleukemia in balb/c mice
Authors: Herman R. A. C. P. , Prins M. E. F. , Bosveld I. J. , Trapman J.
Published: February 2007

The effect of high doses of poly (l)‐poly (C)‐induced mouse L‐cell interfered on the development of Rauscher murine leukemia virus (R‐MuLV)‐induced erythro‐leukemia in BALB/c mice was determined. Female mice, 4 to 5 weeks old, were infected with R‐MuLV and treated with interferon every 24 h starting 6 h after virus inoculation. Under these conditions injection of 3–5 × 104 units of interferon caused a partial inhibition of the leukemic process. Daily application of 3 × 105 units completely or almost completely inhibited the eryth‐roleukemia. After 14 days of treatment with these high doses of interferon, spleen weights of interferon‐treated infected mice were comparable to those of uninfected animals which received only interferon. Also, no Rauscher cells in spleens and livers of R‐MuLV‐infected interferon‐treated animals could be demonstrated and the spleen structure was well preserved in these mice. In interferon‐treated infected animals no virus could be detected in the serum as judged from the absence of reverse transcriptase activity in the serum. Moreover, no virus‐infected cells could be demonstrated in spleen or liver as deduced from negative immunofluorescence data using anti‐p30 and anti‐gp70 sera. No virions budding from spleen cell membranes were seen by electron microscopic studies. However, when interferon treatment was stopped the leukemic process was reactivated and all the mice died. In control experiments interferon caused an inhibition of red blood cell formation and a 50 to 100% enlargement of the spleen. Pharmacokinetic data showed that, after intraperitoneal inoculation, maximum amounts of interferon were present in the peripheral blood after 1–2 h. After 12–24 h almost all interferon activity had disappeared from the blood.
Isolation of two novel envelope recombinant leukemogenic viruses from moloney leukemia virus stocks
Authors: Gisselbrecht Sylvie , Fischinger Peter J. , Elder John H. , Levy Jean Paul
Published: February 2007

Two dual tropic recombinant murine leukemia viruses were isolated from Moloney leukemia virus passed in France for 17 years. These new isolates share most of the biological properties of previously described HIX virus isolated from a line of Moloney virus maintained in the United States. However, they differ from the HIX virus and from other recombinant viruses by the absence of a xenotropic oligopeptide thought to have been characteristic of all xenotropic and recombinant virus envelope glycoprotein.
Solubilization and partial characterization of a tumor‐rejection antigen from an ultraviolet light‐induced murine tumor
Authors: Ransom Janet H. , Schengrund Cara‐Lynne , Bartlett Gerald L.
Published: February 2007

Tumor rejection antigen (TRA) of an ultraviolet‐light‐induced murine skin tumor was solubilized, fractionated and partially characterized. Subcellular fractions were prepared by differential centrifugation of tumor cells that had been ruptured via nitrogen cavitation. Only the 110,000‐g membrane fraction induced significant tumor protection, as determined by in vivo immunization and challenge assays. Extraction of the membrane fraction with 3 M KCI resulted in solubilization of material that could induce in vivo tumor‐rejection immunity. Both the membrane fraction and soluble extract had a limited effective dose range. The KCI extract was separated on a Sepharose, CL‐6B column in the presence of 6 M guanidine‐HCI. Only one of five fraction pools (molecular weight range of 76,000–127,000 daltons) was immunogenic. It contained at least eight protein bands by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE), but no lipid components. This immunogenic Sepharose fraction was chromatographed on a Sephadex G‐150 column. Each of the four Sephadex fraction pools was immunogenic. One protein component was common to each of those fractions. It migrated as a single 76,000‐dalton band on SDS‐PAGE and contained [14C]‐leucine and [3H]‐glucosamine that had been incorporated during cell growth. These results suggest that the TRA of this tumor is a 76,000‐dalton glycoprotein.
Detection of a histone‐2a related polypeptide in differentiated human myeloid cells (hl‐60) and its distribution in human acute leukemia
Authors: Pantazis P. , Sarin P. S. , Gallo R. C.
Published: February 2007

A human myeloid cell line, HL‐60, has been shown to terminally differentiate to mature granulocytes in the presence of dimethylsulfoxide (DMSO) and other compounds. A histone polypeptide (HP) with an apparent molecular weight of 12,500 has been identified among the acid‐extractable chromosomal proteins of DMSO‐treated HL‐60 cells. The detection of HP in total chromatin, total cell proteins or acid extracts of intact HL‐60 cells treated with DMSO indicates that HP is present in intact cells and is not generated during the isolation procedures used for preparation of chromatin or histones. No radiolabelled HP was detected when chromatin was isolated from a mixture of radiolabelled mouse cells and HL‐60 cells treated with DMSO. The relative increase in the amount of HP in DMSO‐treated HL‐60 cells correlates with a concomitant decrease of histone H2A. Fingerprint analysis of tryptic digests shows HP to be related to histone H2A. Generation of HP from endogenous and exogenous H2A is probably due to a proteolytic enzyme associated with the chromatin of the differentiated HL‐60 cells. HP was not observed in chromatin from a number of human or mouse hematopoietic tissues and cell lines but low levels of HP were detected in human lymphocytes and granulocytes prepared from peripheral blood of normal donors. HP was also detected in leukocytes from patients with acute leukemia. Our results suggest that: (1) HP is a proteolytic product of histone H2A and not a product of an independent gene; (2) the observed level of HP in HL‐60 cells is related to the stage of differentiation; and (3) HP is a potential biological marker for human acute leukemia.
The effect of hysterectomies and screening on mortality from cancer of the uterus in canada
Authors: Miller A. B. , Visentin T. , Howe G. R.
Published: February 2007

The trends in mortality from cancer of the uterine cervix, cancer of the endometrium and all uterus in Canada and the ten Canadian Provinces from 1951‐53 to 1974‐76 at ages 30‐64 have been re‐evaluated in relation to screening for cancer of the cervix in 1966 and 1971 and hysterectomies for non‐malignant conditions from 1969 to 1976. By means of a series of mathematical models, the effect of different prior extrapolations of the numbers of hysterectomies performed by age and province has enabled the potential impact of hysterectomies on the trends of mortality from uterine cancer to be evaluated by relating deaths to ‚uteri at risk’︁ rather than ‚women at risk’︁ irrespective of the presence of an intact uterus. It has been found that the numbers of hysterectomies performed have little impact on the fall in mortality certified to cancer of the cervix or to all uterine cancer, but in the decade 1964‐66 to 1974‐66 they convert an apparent fall in mortality from cancer of the endometrium to stability. Re‐evaluation of the fall in mortality from 1960‐62 to 1970‐72 in relation to the intensity of screening shows little impact of the hysterectomies performed on the significant correlation reported previously. However, after extension of the analysis to 1974‐76 the correlation disappears. This finding may indicate a more limited potential for the application of screening, as practised in Canada, to reduce mortality from cancer of the cervix, than has been anticipated previously.
Cytomegalovirus: Detection in human colonic and circulating mononuclear cells in association with gastrointestinal disease
Authors: Roche J. K. , Cheung K ‐S , Huang I. Boldogh , Lang D. J.
Published: February 2007

The specificity and strength of the reported association between cytomegalovirus (CMV) and colonic adenocarcinoma were tested by analysis of a consecutive series of surgically resected colons for: CMV‐DNA by a DNA‐DNA reassociation kinetics (hybridization) procedure; latent virus by co‐cultivation of fresh tissue with indicator fibroblasts; and CMV viral antigens by immunofluorescence. Ten of 13 cancer patients whose colonic tissue was able to be examined by all techniques showed some evidence of active or prior CMV infection. Four cancer specimens were CMV‐DNA (hybridization)‐positive; an additional specimen from a cancerous colon was culture‐positive. In six instances, CMV DNA was detected in mucosal cells adjacent to colon adenocarcinoma. In tissue from one of three patients with ulcerative colitis and two of seven patients with other non‐neoplastic colonic disease, CMV DNA was also detected. No fresh colonic tissues were demonstrated to have CMV surface or nuclear antigens when examined by immunofluorescence. Culture of peripheral lymphocytes was positive for CMV in three of 14 cancer patients. A CMV‐specific defect in humoral immunity could not be documented in that most cancer patients, as well as cancer‐free patients, exhibited circulating specific antibody to CMV and had a normal capacity for CMV‐specific antibody‐dependent cellular cytotoxicity. We conclude that CMV, probably in a latent form, is readily detectable in colonic cells of man, including those derived from malignant, pre‐malignant and non‐malignant tissues. Neither preferential replication in damaged tissue nor carriage of CMV by peripheral lymphocytes homing to gut appear to explain the presence of CMV in colon cells.
Class‐specific antibodies (Igg and Iga) to membrane antigens of herpes simplex type‐2 infected cells in patients with cervical dysplasia and neoplasia
Authors: Mendis Lalitha N. , Best Jennifer M. , Banatvala J. E.
Published: February 2007

Indirect immunofluorescence (IF) techniques were used to measure IgG and IgA antibodies to membrane antigens (anti‐MA) and IgA antibodies to virus capsid antigens (anti‐VCA) of herpes simplex type 2 (HSV‐2)‐infected cells in sera from patients with cervical dysplasia and neoplasia, controls who had been matched for ethnic origin, age and social class, patients with other malignancies and patients with genital herpes. IgA anti‐MA were detected significantly more frequently and at higher titres in patients with cervical dysplasia and neoplasia than among matched controls. A high proportion of patients whose cervical cancer had previously been treated by radiotherapy, patients with other squamous carcinomas and patients with genital herpes also had IgA anti‐MA and at higher titres than matched controls and patients with non‐squamous cancers. In contrast, IgG anti‐MA and IgA anti‐VCA did not distinguish patients from controls. The IgA anti‐MA response was more type‐specific than the IgG anti‐MA response. IgA anti‐MA appeared to persist in sera from patients with genital herpes for at least 17 months after clinical attack, while IgA anti‐VCA were usually detected for only 2‐3 months. The persistence of IgA anti‐MA may suggest a persisting antigenic stimulus among patients with genital herpes as well as patients with cervical dysplasia and neoplasia. HSV‐2‐specific antibodies measured by ELISA were also detected in a significantly higher proportion of patients with cervical neoplasia than in matched controls, although 32–48% of patients did not possess these antibodies. Furthermore, there was no consistent difference in the prevalence of HSV‐2‐specific antibodies when cohorts of patients with cervical neoplasia and controls born at the same time were compared. The possibility is discussed that IgA anti‐MA, which were detected in a high proportion of patients with other squamous carcinomas as well as in patients with squamous carcinoma of the cervix, are reacting with cross‐reacting antigens found both in human squamous carcinoma cells and in HSV‐infected cells.
Detection and characterization of viral genomes and search for tumoral antigens in two hamster cell lines derived from tumors induced by bovine papillomavirus type 1
Authors: Breitburd FrançOise , Favre Michel , Zoorob Rima , Fortin Dominique , Orth Gérard
Published: February 2007

Two cell lines, designated HT2 and HT3, were isolated from two transplanted hamster sarcomas induced by bovine papillomavirus type I (BPV‐I) and studied after 50 to 60 subcultures. Cells are tumorigenic for hamsters and showed no detectable viral capsid protein synthesis by immunofluorescence technique. Cells contained multiple copies of the entire BPV‐I genome, 100 to 500 and 10 to 100 per diploid amount of HT2 and HT3 cell DNA, respectively, as determined by blot hybridization experiments. In unrestricted cell DNA, viral genomes migrated as free single viral DNA molecules and slow migrating species. HT2 cell DNA restricted by single cut enzymes for BPV‐I DNA (Eco RI and Bam HI endonucleases) yielded only one viral genome unit length DNA molecule, indicating that the slow migrating species could correspond to free oligomeric or catenated molecules. Patterns of HT3 cell DNA restricted by Eco RI or Bam HI enzymes showed the presence of additional bands, suggesting that the slow migrating species could correspond to viral DNA sequences integrated in cell DNA. Up to five polypeptides (190 K, 125 K, 59 K, 33 K, 30 K) were reproducibly precipitated from [35S]‐methionine‐ or 32P ‐ labelled HT2 or HT3 cell extracts by sera from hamsters bearing HT2 or HT3 cell‐induced tumors and by sera from pikas bearing BPV‐I induced fibrosarcomas. Polypeptides with similar molecular weights were detected by HT2 sera in a SV40 tumor hamster cell line (TSV5 CI.2) and in a rat cell line transformed in vitro by SV40 DNA form I (VII FI CI. I). The 190 K polypeptide was also detected in a normal hamster embryo cell strain (EH). Conversely, a pool of SV40 tumor hamster sera precipitated the 59 K and the 33 K polypeptides from HT2 cells. The polypeptides thus identified are most probably transformation‐related cell proteins. Whether or not their synthesis is related to the expression of some BPV‐I transforming genes remains to be established.
Control of a human tumour (ewing sarcoma) in mice by a single lethal dose of dimethyl‐myleran and bone marrow
Authors: Floersheim G. L. , Torhorst J.
Published: February 2007

A Ewing sarcoma grown in immunosuppressed mice was eradicated with a single lethal dose of dimethylmy‐leran (DMM) followed by autologous or syngeneic bone marrow. Sarcomas treated 2 weeks after grafting in a phase of rapid proliferation disappeared and large sarcomas treated after 6 or 10 weeks were reduced to necrotic tissue. A human osteosarcoma also regressed distinctly after this therapy while a human colon carcinoma responded poorly. Sub‐lethal DMM treatment induced complete remissions in only 62% of the mice. Tumours which display sensitivity in this model may be treated clinically with lethal doses of DMM and autologous marrow transplantions.
Adoptive transfer of immunity induced by semi‐allogeneic hybrid cells, against a murine fibrosarcoma
Authors: Payelle Béatrice , Poupon Marie‐France , Lespinats Geneviè
Published: February 2007

Semi‐allogeneic somatic hybrid cells derived from the fusion of a C57BL/6 fibrosarcoma (MCB6–1) and A9 cells (C3H origin) were used to immunize C57BL/6 mice against the parental tumor cells. These hybrid cells expressed H‐2 histocompatibility antigens of both parental cells (H‐2b and H‐2k), and failed to produce tumors in normal C57BL/6 mice. A single i.p. injection of hybrid cells induced anti‐tumor immunity which could be transferred to normal C57BL/6 recipient mice by immune spleen or peritoneal cells; the efficient cells were T cells, as this activity was completely abrogated by treatment with anti‐Thy‐1–2 antiserum and complement. Among immune splenic T cells, only the light‐density T cells, obtained after fractionation on Percoll gradient, were effective in the transfer of immunity. Immunity induced by the hybrid cells was specific for MCB6‐1 parental tumor cells. This immunity could be transferred during two brief periods, 7 to 12 days, and 40 to 50 days, after hybrid cell injection; there appeared to be an intermediate period, 12 to 40 days after immunization, during which no immunity could be transferred. These results suggest a suppressive mechanism implicated during hybrid cell immunization and interacting with the anti‐tumor immune response.
Tumorigenesis of mammary gland by 7,12 dimethylbenz(a)anthracene during pregnancy: Relationship with DNA synthesis
Authors: Sinha Dilip K. , Pazik James E.
Published: February 2007

The relationship between mammary cell proliferation during pregnancy and susceptibility to 7,12‐dimethyl‐benz(a)anthracene (DMBA) was examined. DMBA was administered intravenously to Sprague‐Dawley rats on the 5th, 10th or 15th day of pregnancy. [3H]thymidine labelling index (LI) of the mammary cells at the time of treatment with the carcinogen was determined and found to be higher in the pregnant rats than in agematched virgin controls. In spite of the high proliferative index of the mammary cells, significant inhibition of tumorigenesis occurred in the pregnant rats allowed to complete pregnancy and parturition following treatment with DMBA. However, when pregnancy was terminated by cesarian section shortly after treatment with DMBA, there was a significantly higher tumor incidence as compared to the ‘full‐term’ rats. It was observed that the earlier the pregnancy was terminated, the greater was the incidence of mammary tumors. This would indicate that the inhibitory effect of pregnancy is related to changes occurring during the later half of gestation. The differentiation of mammary cells for milk synthesis as pregnancy progresses is postulated to be a major reason for the observed refractoriness of the mammary cells to DMBA at that time.
Lack of induction of murine mammary tumor virus expression in cultured mammary glands treated with chemical carcinogens
Authors: Tonelli Quentin J. , Long Carole A. , Vaidya Akhil B. , Sorof Sam
Published: February 2007

Chemical carcinogens have previously been found to bring about an epithelial transformation of mouse mammary glands in whole‐organ culture, as evidenced by the escape of lobuloalveoli from the normal hormonal controls of mammary development, and by glandular hyperplasia, dysplasia and metaplasia. In order to assess whether a general induction of endogenous murine mammary tumor virus (MuMTV) genes is associated with the chemical transformation process, we assayed steady‐state levels of MuMTV RNA and protein after treatment of the cultured mammary glands with the carcinogens, 7,12‐dimethylbenz[a]anthracene and N‐2‐fluorenylacetamide. Viral RNA was measured by hybridization with a representative MuMTV‐complementary DNA probe, and viral protein was analyzed by a group‐specific radioimmunoassay for the major MuMTV envelope glycoprotein, gp52. In control glands not treated with carcinogen, there were extremely low levels of MuMTV‐specific RNA in the cultured mammary glands originating from BALB/c mice, and between 10‐ and 50‐fold higher levels in glands from C57BL/6 and C3H mice. Among the untreated glands, only those from C3H mice contained a detectable level of gp52. This order of MuMTV gene expression in the cultured glands of the three strains of mice is consistent with that observed in vivo. Treatment of the cultured mammary glands of these three strains of mice with either of the two chemical carcinogens resulted in all cases in no elevation in the level of either MuMTV RNA or protein. Thus, our studies indicate that the transformation of the cultured mammary glands by the two chemical carcinogens occurs by a process that apparently does not involve a general induction of endogenous MuMTV gene expression.
Helper virus‐dependent RSV rescue from two lines of hamster cells transformed in vivo by XC RSV
Authors: Svoboda J.
Published: February 2007

Newborn hamsters were inoculated with chicken sarcoma tissue produced by XC RSV which had been rescued by transfection from XC cells. Tumours with a latency of up to 20 months appeared in all inoculated hamsters. Three tumour cell lines were successfully established for in vitro growth and cloned. The virus was rescued from the PR RSH‐9 cell line by cell fusion with chicken fibroblasts and from the other two lines (PR RSH‐12 and PR RSH‐14) and clones only if chicken fibroblasts used for fusion had been preinfected with a helper virus. The last two cell lines evidently harboured a functional envgene since the synthesis of transforming virus started soon after they were fused with 16Q cells producing defective BH‐RSV(‐) lacking the envelope glycoprotein. Produced viruses acquired subgroup C specificity which is the specificity of XC RSV originally used for transformation of these two cell lines. The nature of provirus alterations in PR RSH‐12 and PR RSH‐14 cells as well as the mechanisms underlying these changes are discussed.
Monoclonal antibodies to epithelium‐specific components of the human milk fat globule membrane: Production and reaction with cells in culture
Authors: Taylor‐Papadimitriou Joyce , Peterson J. A. , Arklie J. , Burchell Joy , Ceriani R. L. , Bodmer W. F.
Published: February 2007

Three hybridomas producing monoclonal antibodies (IgG), reacting with components of the human mammary milk fat globule have been isolated. When tested for binding to a wide range of human cell lines and strains, all three antibodies show negative reactions with fibroblasts, lymphoblastoid cells, and a large number of epithelial cell lines of non‐breast origin. Two of the antibodies (1.10.F3 and 3.14.A3) reacted with seven out of eight breast cancer lines tested, and with epithelial cells cultured from human milk. The other antibody (3.15.C3) reacted with only two of the breast cancer cell lines.
Plasma prolactin levels and breast cancer: Relation to parity, weight and height, and age at first birth
Authors: Kwa H. G. , Cleton F. , Bulbrook R. D. , Wang D. Y. , Hayward J. L.
Published: February 2007

Plasma prolactin has been measured in over 3,500 women volunteers from a normal population. In premenopausal women there was a significant decrease in prolactin levels with increasing parity. However, this effect was transitory since plasma prolactin concentration rose with increasing time after the birth of the last child. There were no significant differences in prolactin levels with respect to height and weight, although overweight compared to underweight women had approximately 15% more plasma prolactin. If prolactin is a carcinogen, then these results are in keeping with the epidemiological findings that multiparity affords protection and that age at last delivery is a risk factor in the development of breast cancer.
Characteristics of membrane and cytosol forms of the mammary tumor glycoprotein molecule mtgp in human breast carcinoma cell cultures and tumors
Authors: Leung Julia P. , Nelson‐Rees Walter A. , Moore George E. , Cailleau Relda , Edgington Thomas S.
Published: February 2007

The presence, concentration and selected molecular characteristics of the human mammary carcinoma glycoprotein molecule set MTGP, a trace and apparently tumor‐specific molecule, were examined in fifteen cell cultures established from mammary carcinomas, tissue from seven mammary carcinomas and control cultures. Both cytosol and membrane‐associated forms of MTGP were analyzed, and each was phenotyped by reference to isoelectric point and buoyant density. All cells or tissues of mammary carcinoma origin contained membrane MTGP, whereas cytosol MTGP was undetectable in cell cultures from half of the mammary carcinomas. Neither membrane nor cytosol MTGP were detectable in cells other than mammary carcinomas. Cytosol MTGP could be assigned to three groups by reference to presence, isoelectric point and buoyant density. Membrane MTGP also exhibited heterogeneity between different tumors and could be assigned to three groups by isoelectric point and buoyant density. Each form of MTGP was homogeneous for a given single tumor or cell culture and retained its phenotypic features with passage and cloning. Four general types of MTGP are proposed, though there may be additional fine heterogeneity that cannot be further resolved at this time. These data provide an initial characterization of the membrane form of MTGP and an integrated characterization that is consistent with the concept that tumor‐specific antigens may possess both constant regions by reference to antigens recognized by the antisera and variable structure by reference to physicochemical characteristics.
Primary hepatocellular carcinoma in alaskan natives, 1969–1979
Authors: Heyward William L. , Lanier Anne P. , Bender Thomas R. , Hardison H. Huntley , Dohan Peter H. , McMahon Brian J. , Francis Donald P.
Published: February 2007

The records of 20 Alaskan Native patients with primary hepatocellular carcinoma (PHC) diagnosed in the II‐year period 1969–1979 were reviewed. The annual incidence of PHC was found to be high among Alaskan Native males and especially high among Alaskan Eskimo males (7.6 and 11.2 per 100,000, respectively) in comparison to Greenland and Canadian Eskimos and US white males. Familial and geographic clustering of PHC patients was noted in areas known to be hyperendemic for hepatitis B virus (HBV) infection. A bimodal age distribution among PHC patients occurred with peaks at 15–25 years and 40–65 years. A high prevalence of hepatitis B surface antigen (HBsAg) in serum of patients in the younger age group suggests that HBV infection might be a factor associated with the development of PHC in young Eskimos. PHC in Alaskan Natives is apparently not closely associated with alcoholic cirrhosis.