bluuebunny/crossref_metadata_2025 huggingface dataset:
Moloney virus (M‐MuLV) leukemogenesis: Virus spread, antibody production and antigenic expression in neonatally virus‐inoculated young mice
Authors: Åsjö Birgitta , Fenyö Eva Maria , Klein George
Published: February 2007

(A × C57BL) and (A × C57L)F1, hybrid mice were inoculated neonatally with M‐MuLV. Virus spread, antigenic expression and antibody production were followed during the preleukemic period. M‐MuLV was first detectable in the spleen and later in the thymus. Virus spread was faster and the level of viremia higher in A × C57L than in A × C57BL mice. Also, A × C57L mice had no or only low titers of virus neutralizing antibodies, whereas A × C57BL mice had high titers. Anti‐MCSA antibodies, reacting with the surface of syngeneic M‐MuLV‐induced lymphoma cells, were present in a minority of the mice, but disappeared ultimately in all mice. The two groups of mice differed with regard to the length of the preleukemic latency period. High virus load and a low level of virus neutralizing and anti‐MCSA antibodies were correlated with an earlier onset of leukemia.
Relationship of carcinogen‐induced sister chromatid exchange and neoplastic cell transformation
Authors: Popescu N. C. , Amsbaugh S. C. , Dipaolo J. A.
Published: February 2007

Sister chromatid exhanges (SCE) and morphological transformation induced by five chemical carcinogens, N‐acetoxy‐2‐fluorenyl‐acetamide (AcAAF), N‐methyl‐N‐nitro‐N‐nitrosoguanidine (MNNG), methyl methanesulfonate (MMS), benzo[a]‐pyrene (BP), and cis‐platinum(II) diamine dichloride (PT) as well as by X‐irradiation were quantified in parallel experiments with cultures of Syrian hamster embryo cells (HEC). Incubation of HEC with 5‐bromodeoxyuridine (10−5M) for two rounds of replication (24 h) required for SCE visualization neither caused morphological transformation nor altered the transformation frequency induced by carcinogen alone. All chemical carcinogens, but not X‐ir‐radiation, produced a dose‐dependent increase in SCE and transformation frequency, demonstrating the sensitivity of both assays to carcinogens. The ratios of induced SCE relative to transformation frequency, however, varied with the carcinogen. BP, MNNG, and AcAAF were similarly efficient in inducing SCE compared to transformation but were considerably less effective than MMS and PT. X‐irradiation at doses of 200, 300, and 500 R did not cause transformation and induced a low frequency of SCE. On a molar basis, MMS and PT were the most effective in SCE induction relative to transformation, MNNG and AcAAF were less effective, and BP was the least effective carcinogen. The positive linear correlation between chemical carcinogen‐induced SCE and transformation suggests a relationship between the two cellular responses.
The dependence of tumor neutralization on bone‐marrow‐derived cells
Authors: Scuderi Philip , Rosse Cornelius
Published: February 2007

Radiosensitive host cells capable of potentiating tumor neutralization by immunocytes in normal recipients are present only in the bone marrow and not in the spleen or thymus. This was shown by selectively eliminating either the bone marrow, spleen or thymus of groups of mice and then subcutaneously injecting these animals with sensitized splenocytes and tumor cells. Bone marrow ablation was accomplished by the administration of the bone‐seeking radioactive isotope 88Sr which did not reduce thymic or splenic cellularity. Sensitized splenocytes completely inhibited the growth of admixed tumor cells in normal, nude, splenectomized, or 88Sr‐treated animals, but the sensitized cells were as ineffective in 89Sr‐treated recipients as in 900‐rad irradiated mice. Bone marrow cells of normal donors admixed with sensitized splenocytes and the sensitizing tumor cells caused a significant inhibition of tumor growth in 900‐rad and 89Sr‐treated mice. Therefore, the radiation‐sensitive host cells that potentiate the tumor‐inhibitory effect of sensitized splenocytes are unique to the marrow and, in the intact animal, apparently emigrate from this organ to interact with sensitized immunocytes at the site of tumor growth.
Induction of epstein‐barr virus by a new tumor promoter, teleocidin, compared to induction by TPA
Authors: Yamamoto Hidehiko , Katsuki Takato , Hinuma Yorio , Hoshino Hiro‐O , Miwa Masanao , Fujiki Hirota , Sugimura Takashi
Published: February 2007

The effect of teleocidin, a new, naturally occurring tumor promoter, on induction of Epstein‐Barr virus (EBV), was compared with that of a known tumor promoter, 12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA). Early antigen (EA) and/or capsid antigen (VCA) of EBV was induced in the EBV genome‐carrying cell lines C‐6 and P3HR‐I cells by teleocidin, its effect being maximal at a concentration of 12.5 ng/ml. The production of infectious EBV from P3HR‐I cells was enhanced by teleocidin maximally at a concentration of 0.5 to 2.5 ng/ml. The outgrowth of EBV‐transformed cells from peripheral lymphocytes of seropositive healthy donors was also enhanced by teleocidin at a concentration of 0.02 to 0.5 ng/ml. TPA tested simultaneously in all experiments exhibited the same activities as teleocidin, and was effective at similar concentrations. Teleocidin enhanced both EA and VCA synthesis in P3HR‐I cells additively with n‐butyrate, but not with TPA. This suggests that teleocidin and TPA have a common mechanism of action, although their chemical structures are different.
Establishment of human cytotoxic T‐cell lines specific for epstein‐barr virus‐transformed autologous cells
Authors: Sugamura Kazuo , Tanaka Yuetsu , Hinuma Yorio
Published: February 2007

EBV‐specific cytotoxic T cells (Tc)1 induced in vitro have continuously proliferated in vitro for over 9 months. The long‐term maintenance of the Tc growth was dependent on periodic supplementation of both irrediated EBV‐transformed autologous lymphoblastoid cell line (LCL) cells and conditioned medium. The latter was derived from supernatants of human spleen‐cell cultures stimulated with phytohemagglutinin. The cultured Tc maintained significant cytotoxic activity to autologous LCL cells but not to EBV‐unrelated target cells, including K‐562, B‐, T‐, null‐cell lines and mitogenstimulated autologous peripheral blood lymphocytes. Thus, established EBV‐specific Tc lines from five different individuals always exhibited highly significant cytotoxicity against autologous LCL cells but not always against allogeneic LCL cells. Furthermore, restriction of the Tc to the autologous LCL was more pronounced after long‐term culture than it was initially. This suggests that certain clones of Tc which are probably restricted to HLA are selectively established during long‐term cultivation.
Smoking and the development of metastases from malignant melanoma
Authors: Shaw Helen M. , Milton Gerald W.
Published: February 2007

Investigations on 2583 malignant melanoma patients indicated that in both men and women, although there did not appear to be a causal relationship between cigarette smoking and melanoma, smoking did facilitate the spread of metastases. Significantly more ex‐smokers or smokers than life‐long non‐smokers first presented for melanoma treatment with established metastases. Also, in patients with localized disease, metastases appeared within 10 years more often in exsmokers than in life‐long non‐smokers.
In vivo anti‐tumor effects of local adoptive transfer of mouse and human cultured lymphoid cells
Authors: Gorelik E. , Kedar E. , Sredni B. , Herberman R.
Published: February 2007

Mouse and human lymphoid cells were cultivated in the presence of T‐cell growth factor (TCGF) and evaluated for their in vivo anti‐tumor effect in mice. Cultured spleen cells of normal BALB/c mice or of mice bearing the M109 tumor had a high level of cytotoxic acitivity in vitro against a variety of tumor target cells and had characteristics of natural killer cells. These cultured cells were evaluated for their in vivo cytotoxic activity by admixture with [125l]dUrd‐labelled M109 tumor cells (2 × 105) at a 30:1 ratio and inoculation of the mixture into the footpads of BALB/c mice. The level of radioactivity remaining in the footpad was determined at various periods following inoculation of radiolabelled tumor cells. The presence of cultured cells in the inocula caused a marked decrease in the footpad radioactivity by 24 h. However, the slope of clearance of the radiolabel then became similar to that in the control mice. The cultured cells delayed, but did not prevent, tumor appearance, and did not influence the subsequent rate of growth of the tumors. The transient effects of the cultured cells contrasted with the more prolonged in vivo effects of alloimmune lymphocytes, and this may be due to their short survival period. Ninety‐nine percent of [125l]dUrd‐labelled cultured mouse lymphoid cells were eliminated within 48 h of i.f.p. inoculation. Cultured human lymphoid cells, initiated from the blood of normal donors, also had a high level of cytotoxic activity in vitro and were evaluated for their in vivo effects by intra‐footpad inoculation into nude mice, together with radiolabelled human tumor cell lines, G‐ll or HT‐29. In vivo cytotoxic activity of the human cultured lymphoid cells correlated with their cytotoxic effect in vitro. These results indicate that cultured mouse and human effector cells have appreciable in vivo cytotoxic effects against tumor cell lines. However, the transient duration of these effects may limit their immunotherapeutic potential.
Natural killing and antibody‐dependent cellular cytotoxicity in specific‐pathogen‐free miniature swine and germ‐free piglets. II. Ontogenic development of NK and ADCC
Authors: Huh Nam Doll , Kim Yoon Berm , Koren Hillel S. , Amos D. Bernard
Published: February 2007

The ontogenic development of natural killing (NK) and antibody‐dependent cellular cytotoxicity (ADCC) in germ‐free and specific‐pathogen‐free (SPF) miniature swine were compared. Activities of NK and ADCC were tested by a short‐term (2.5 to 4 h) 51Cr‐labelled human myeloid cell line K562 and TNP‐conjugated human B‐cell line SB as target cells for NK and ADCC, respectively. Animals obtained by aseptic hysterectomy 3–5 days prior to term showed ADCC activities similar to adult levels but lacked NK activity. Hysterectomy‐derived piglets which were colostrum‐deprived and maintained in germ‐free isolators developed NK activity at 3–4 weeks of age. In comparison, naturally‐farrowed, colostrum‐fed piglets maintained in our SPF facility developed NK activity at 2–3 weeks of age. Thereafter, there was no significant difference in the levels of either NK or ADCC between germ‐free and SPF animals. This suggests that microbial flora and environment do not affect the development of effector cells for ADCC but do play some role in the maturation of NK cells during ontogeny. The differences in ontogeny of NK and ADCC further support our previous suggestion that the effector cells for NK and ADCC in swine are distinct subpopulations.
Comparison of various serological and direct methods for the diagnosis of BLV infection in cattle
Authors: Gupta P. , Ferrer J. F.
Published: February 2007

The sensitivities of several serological and direct methods for the detection of bovine leukemia virus (BLV) infection in cattle have been critically compared. Among the serological methods, the radioimmunoassay (RIA) using the BLV glycoprotein (gp) was found to be more sensitive than the RIA using the internal virion antigen (p25) and the immunodiffusion test using the virion gp antigen. The differences in sensitivity between these tests were particularly evident with sera of cattle in early stages of infection. The sensitivities of the syncytia induction assay and the competitive RIA for the direct demonstration of BLV infection in cattle are comparable. Following natural infection, antibodies to the gp antigen in most cattle were detected by the RIA several months before infectious BLV became detectable by the SIA in the blood lymphocytes. It is concluded that the most accurate, sensitive, and rapid method for the detection of BLV infection in cattle is the RIA using the virion gp antigen. The data presented confirm that BLV infection as well as the antibody responses of naturally infected cattle to the BLV p25 and gp antigens are persistent.
Tumour cells in metastatic deposits with altered sensitivity to natural killer cells
Authors: Brooks Colin G. , Flannery Graham R. , Willmott Neville , Austin Eric B. , Kenwrick Susan , Baldwin Robert W.
Published: February 2007

If natural killer (NK) cells play a role in immunosurveillance it might be expected that, during the metastatic process, selection would occur for tumour cells with reduced NK sensitivity. This hypothesis was tested in the rat by measuring the NK sensitivity of cells freshly isolated from metastases of syngeneic transplanted spontaneous mammary carcinomas. Lysis was measured in a 6‐h chromium release assay using normal syngeneic spleen cells as effectors. Our studies led to the following conclusions. (I) Metastases developing at certain tissue sites (draining lymph node and lung, but not pericardium) were frequently composed of tumour cells with markedly reduced sensitivity to NK cells. (2) This resistance could generally be detected only if freshly isolated tumour cell populations were studied; after a few days in culture, resistant metastasis‐derived tumour cells usually regained normal NK sensitivity. (3) Resistance to NK cells was not always due to the loss of NK target structures; it could also result from an innate resistance to the NK lytic mechanism. (4) The tissue distribution of NK‐resistant metastases suggested that if NK cells exerted an immunoselective pressure they did so at the tissue site rather than in the primary tumour or in the bloodstream.
Mapping of the Fv‐4 mouse gene controlling resistance to murine leukemia viruses
Authors: Ikeda Hidetoshi , Sato Hidetoshi , Odaka Takeshi
Published: February 2007

Fv‐4, a gene controlling susceptibility to ecotropic murine leukemia viruses, was linked to both Pre‐1 (prealbumin) and Igh‐1 (immunoglobulin heavy‐chain constant region) loci on chromosome 12 in mice. The gene order was Fv‐4‐Pre‐1‐Igh‐1, and the estimated frequency of recombination between Fv‐4 and Pre‐1 was about 20%.
Natural killer cell activity in a population of leukemia‐prone wild mice (mus musculus)
Authors: Scott Jonathan L. , Pal Bijay K. , Rasheed Suraiya , Gardner Murray B.
Published: February 2007

Natural cell‐mediated cytotoxicity against YAC‐1 targets was measured in splenocytes from leukemiaprone wild mice trapped near Lake Casitas (LC) in southern California. Cytotoxicity was mediated by cells that were non‐adherent to nylon wool, non‐phagocytic and resistant to thy‐1.2 antiserum plus complement. Natural MuLV viremia in LC mice did not impair splenic cytotoxicity against YAC‐1 target cells. Cells infected with amphotropic and ecotropic MuLV of wild mouse origin were not appreciably lysed by LC splenic effectors. Although variable levels of cytotoxicity were detected against YAC‐1 by normal LC spleen cells, consistently low levels of cytotoxicity against allogenic LC lymphoma, sarcoma and carcinoma targets were found using the same splenocytes. These results indicate that LC mice possess splenocytes with the characteristics of natural killer (NK) cells as defined in inbred mice. The resistance of LC‐derived targets to lysis by LC NK cells suggests that NK cells may not be involved in natural tumor immunosurveillance or that the development of spontaneous tumors may involve escape from NK‐mediated effector mechanisms.
Staphylococcal protein a enhances natural killing activity against lymphoid tumor cell lines
Authors: Patel Pravin C. , Stefanescu‐Soare Irina , Menezes José
Published: February 2007

Protein A (pA), was found to augment the natural killing (NK) activity of peripheral blood lymphocytes against Burkitt's lymphoma‐derived Raji and Daudi cells. This pA‐enhanced NK activity was determined using the 51Chromium release microcytotoxicity assay. It was found that the increased NK activitiy was dependent on the concentration of pA used. In addition, the pA‐enhanced NK activity was dependent on the time of incubation of pA with the effector and target cell mixture. Pretreatment of effectors for 16 h or more dramatically increased the NK activity against a wide range of tumor targets of different origin and possessing either B, T or null cell surface characteristics. The presence of the Epstein‐Barr virus (EBV)‐genome in the target cells did not influence the pA‐enhanced NK activity. Nylon‐wool column‐fractionated, non‐adherant lymphocytes (enriched in NK cells) showed an increased NK activity in the presence of pA than unfractionated lymphocytes. Pretreatment of certain targets with pA rendered them more sensitive to NK lysis. Interferon production was readily detected in supernatants from cultures of pA‐treated effectors or effector‐target mixtures, but not in supernatants from pA‐treated target cultures tested. Results of different physicochemical treatments indicate that the pA‐induced interferon is of γ type (type II). Thus, the data presented suggest that the pA‐induced enhancement of NK activity is most likely mediated by the pA‐induced interferon.
Distribution and molecular characterization of a cell‐surface and a cytoplasmic antigen detectable in human melanoma cells with monoclonal antibodies
Authors: Wilson Barry S. , Imai Kohzoh , Natali Pier G. , Ferrone Soldano
Published: February 2007

The monoclonal antibodies 225.28S and 465.12 to human melanoma‐associated antigens have been tested with a large variety of surgically removed skin lesions and malignant tumors as well as with a panel of cultured cell lines in serological and immunochemical assays. The antibody 225.28S reacts with a plasma membrane antigen while the antibody 465.12 detects a cytoplasmic antigen. Both antibodies fail to react with melanocytes from normal skin as well as benign skin lesions but react with nevi, melanoma cells and some skin carcinomas. Analysis with surgically removed tumors and cultured human cell lines indicated that the plasma membrane antigen is restricted to skin lesions whereas the cytoplasmic antigen is synthesized by tumor cells of various histologcal origins. The plasma membrane antigen is composed of two glyco‐polypeptides of 280,000 and > 440,000 daltons, while the cytoplasmic antigen consists of 4 glycopolypeptides of 94,000, 75,000, 70,000 and 25,000 daltons. None of these components are bridged by disulfide bonds. The cytoplasmic antigen was readily detected in the spent culture medium of melanoma cell lines in the form of a major 94,000 dalton and a minor 72,000 dalton structure, while the plasma membrane antigen was detectable only after vastly increasing the sensitivity of the assay system.
Association of Epstein‐Barr virus with nasopharyngeal carcinoma in alaskan native patients: Serum antibodies and tissue EBNA and DNA
Authors: Lanier Anne P. , Bornkamm Georg W. , Henle Werner , Henle Gertrude , Bender Thomas R. , Talbot Marion L. , Dohan Peter H.
Published: February 2007

Biopsy specimens from Alaskan Native patients with nasopharyngeal carcinoma (NPC) and from other patients seen on the otolaryngology service were tested for Epstein‐Barr virus‐specific DNA and nuclear antigen (EBNA). Serum samples from both groups were tested for various EBV‐related antibodies. EBV DNA and EBNA results were in agreement in 29 of 31 tissue specimens tested by the two methods. Ten of 11 biopsies containing NPC cells were positive for EBV DNA. Two NPC patients had biopsies that showed only atypical epithelium but were also positive for EBV DNA or EBNA. The other tissue specimens were negative except for biopsies from two patients: one with a parotid gland lymphoepithelial lesion; another with undifferentiated carcinoma of salivary gland origin.
In vivo inhibition of the development of myeloid leukemia by injection of macrophage‐and granulocyte‐inducing protein
Authors: Lotem Joseph , Sachs Leo
Published: February 2007

It is shown that injection of macrophage‐ and granulocyte‐inducing protein (MGI) can inhibit the development of myeloid leukemia in vivo and stimulate normal myelopoiesis. The MGI injected contained MGI‐1 activity that induces colony formation with normal myeloblasts, and MGI‐2 activity that induces differentiation of normal and MGI+D+ leukemic myeloblasts to mature macrophages or granulocytes. The MGI preparations injected did not contain interferon and it was shown that the results obtained were not due to minute amounts of contaminating lipopolysaccharide (LPS). Intraperitoneal injection of MGI stimulated myelopoisesis in normal adult mice. Markedly higher levels of serum MGI activity could be obtained by injecting MGI than by injecting LPS, a compound that stimulates the in vivo production of MGI. Injection of MGI into mice that had been inoculated intravenously with MGI+D+ or MGI+D− myeloid leukemic cells showed that, 3 weeks after the beginning of treatment, there was a 3‐ to 5‐fold decrease in the number of leukemic colony‐forming cells and an increase in mature granulocytes in the bone marrow, together with a 2‐ to 5‐fold decrease in the percentage of morphologically identified myeloid blast cells in the bone marrow and peripheral blood. The remaining leukemic colony‐forming cells in the MGI‐treated mice inoculated with MGI+D+ cells were not resistant to the induction of differentiation by MGI‐2. Injection of LPS to mice inoculated with LPS‐resistant MGI+D− leukemic cells also inhibited the development of leukemia, but this inhibition was less effective than with MGI and was presumably indirect. Injection of MGI reduced the tumor volume in mice subcutaneously inoculated with leukemic cells at least 50‐fold. The median survival time of MGI‐treated mice inoculated intravenously with MGI+D+ cells or subcutaneously with MGI+D− cells was increased by about 40%, and 50% of the MGI‐treated mice inoculated subcutaneously with MGI+D+ cells did not develop tumors. MGI also increased the anti‐tumor effect of cyclophosphamide. The leukemia‐inhibiting activity in the injected MGI preparations was associated with the peak of MGI activity separated on a hydroxylapatite column and was destroyed by treatment at the temperature which destroys MGI‐2 activity. This indicates that the inhibition of leukemia development was mediated by MGI‐2. It is suggested that improved schedules of MGI treatment, with or without compounds used in the cytotoxic types of therapy, should be able to give an even better inhibition of leukemia development and that these results should also be applicable to the therapy of human myeloid leukemia.
The formation and persistence of benzo(a)pyrene metabolite‐deoxyribonucleoside adducts in rat skin in vivo
Authors: Ashurst Stephen W. , Cohen Gerald M.
Published: February 2007

The extent of reaction of benzo(a)pyrene with DNA and the formation of benzo(a)pyrene‐deoxyribonucleoside adducts in the skins of male Wistar rats were investigated. Following topical application of benzo(a)pyrene (200 nmoles), binding reached a maximum of 0,74 pmoles/mg DNA, 12 h after treatment, and remained high up to 48 h after treatment. Hydrolysis of the DNA and analysis of the deoxyribonucleoside adducts by HPLC revealed several products. The major adduct, C, (27‐40% of the total adducts), co‐chromatographed with deoxyribonucleoside adducts formed by reaction of (±)7β, 8α‐dihyroxy‐9α, 10α‐epoxy‐7,8,9,10‐tetrahydrobenzo(a)pyrene (anti BPDE) with DNA, whilst product B, (19–23% of the total adducts), also formed in significant amounts, co‐chromatographed with a further metabolite of 9‐hydroxybenzo(a)pyrene bound to an as yet undertermined base in the DNA. Smaller amounts of other deoxyribonucleoside adducts, D and I, were also observed and co‐chromatographed with marker compounds derived from reaction of anti BPDE with deoxyadenosine and (±)7β, 8α‐dihydroxy‐9β, 10β‐epoxy‐7,8,9,10‐tetrahydrobenzo(a)pyrene (Syn BPDE) with DNA respectively. There was no evidence for preferential removal of any of the four adducts (B, C, D and I) during the 48 h after treatment with benzo(a)pyrene. The relative resistance of rat skin, compared with mouse skin, to benzo(a)pyrene‐induced skin carcinogenesis may be due in part to a lower extent of binding of benzo(a)pyrene to DNA, and a smaller percentage of both methanol‐soluble hydrocarbon‐deoxyribonucleoside adducts and of adducts derived from the putative ultimate carcinogen, BPDE.
Development of resistance to vincristine in a childhood rhabdomyosarcoma growing in immune‐deprived mice
Authors: Houghton Janet A. , Houghton Peter J. , Brodeur Garrett M. , Green Alexander A.
Published: February 2007

A cell line of childhood rhabdomyosarcoma (RD) has been grown as a xenograft in immune‐deprived mice. The tumor responded to vincristine (VCR), but not to vinblastine, doxorubicin or actinomycin D. The rate and frequency at which resistance developed from administration of VCR once weekly was investigated. Tumor growth could be inhibited for 6 weeks, after which time 11 of 16 xenografts grew progressively despite continued treatment. That this was a tumor‐acquired resistance was confirmed by growing both parent and “resistant” lines in the same host. Under these conditions VCR completely inhibited growth of the parent tumor, but not growth of the resistant line. Continued passage of the resistant line for 10 months in mice either treated with VCR (1.5 mg/kg/wk) or untreated, demonstrated that resistance to VCR was stable in the absence of selection pressure. In addition, the VCR‐resistant line acquired a stable change in karyotype with the addition of a number 9 chromosome and an additional, unknown marker.
EBV‐positive Burkitt's lymphoma from algeria, with a three‐way rearrangement involving chromosomes 2, 8 and 9
Authors: Philip T. , Lenoir G. M. , Fraisse J. , Philip I. , Bertoglio J. , Ladjaj S. , Bertrand S. , Brunat‐Mentigny M.
Published: February 2007

Burkitt's lymphoma was diagnosed in a male Algerian child presenting with abdominal and jaw tumours. Viral studies revealed that this non‐endemic case was associated with the Epstein‐Barr virus. Cytogenetic examination of tumour cells showed a complex three‐way rearrangement involving chromosomes 2, 8 and 9. Our report indicates that, in Burkitt's lymphoma, not only simple but also complex translocations involving chromosome 8 may arise. This finding in a North African case emphasizes the need for more detailed study of the clinical, virological and cytogenetic features of Burkitt's lymphoma throughout the world.
A note on the role of dietary retinol and carotene in human gastro‐intestinal cancer
Authors: Modan B. , Cuckle H. , Lubin F.
Published: February 2007

Dietary data relating to 406 patients with gastrointestinal cancers (cases) and 812 controls have been analysed to test the hypotheses that dietary vitamin A (retinol) and its precursor, carotene, may be protective agents in human carcinogenesis. There was no deficit among cases in the intake of retinol‐containing food items whereas several of the main carotene‐containing fruits and vegetables were eaten less often among cases than among controls. However, when total daily intake was estimated, there was no protective effect of carotene, perhaps implying that some other constituent of the fruits and vegetables is protective.
Combined effects of natural resistance and chemotherapy against a murine lymphoma in lethally‐irradiated mice
Authors: Iorio Anna M. , Neri Mariella , Enrico Paola , Goldin Abraham , Bonmassar Enzo
Published: February 2007

Lymphoma EL‐4 of B6 origin was inoculated into lethally‐irradiated syngeneic B6 or resistant BD2F1 hybrid recipients. Marked impairment of lymphoma cell proliferation (i.e. hybrid resistance, HR) occurred in the spleen but not in the liver or lung of BD2F1 hosts. Treatment with DTIC at the optimal dose of 80 mg/kg i.p. produced inhibitory effects in spleen, liver and lung of young BD2F, mice, that were much greater than those observed in syngeneic B6 hosts. Increased anti‐lymphoma effects for HR and DTIC chemotherapy were not detectable in the liver or lung of old BD2F1 mice or in the spleen, liver or lung of young hybrid recipients depressed for HR by pretreatment with cyclophosphamide. This is the first report on combined antileukemic effects of the host's anti‐tumor natural resistance and chemotherapy.
Steroids inhibit tumor promoting agent induced Epstein‐Barr virus early antigens in raji cells
Authors: Sundar Syam K. , Ablashi Dharam V. , Armstrong Gary R. , Zipkin Mitchell , Faggioni Alberto , Levine Paul H.
Published: February 2007

Four steroids and one protease inhibitor were evaluated for their effects on 12‐O‐tetradecanoyl phorbol 13‐acetate (TPA)‐induced and Epstein‐Barr virus‐induced early antigens (EBV‐EA) in Raji cells. Continuous treatment with dexamethasone, prednisolone, hydrocortisone and cortisone inhibited TPA‐induced EBV‐EA to varying degrees, but the protease inhibitor N‐α‐p‐tosyl L‐lysine chloromethyl ketone‐HCI (TLCK) had no significant effect. None of the agents tested inhibited EBV‐induced EA. In addition, the effect of the steroids was reversible since the removal of these agents resulted in recovery of the percentage of EBV‐EA‐positive cells in TPA‐treated cultures. These results were in agreement with the in vivo experiments of other investigators, who demonstrated inhibition of tumor promotion with steroids. Since TLCK failed to inhibit TPA‐induced EA, it is unlikely that induction of EA by TPA is the result of production of proteases.
A geographical study of antibodies to membrane antigens of HSV‐2‐infected cells and HSV‐2‐specific antibodies in patients with cervical cancer
Authors: Mendis Lalitha N. , Best Jennifer M. , Senarath Lorraine , Chiphangwi J. , Vestergaard B. F. , Banatvala J. E.
Published: February 2007

Sera were obtained from patients with squamous carcinoma of the cervix from Great Britain (29), Sri Lanka (32), Malawi (27) and Sudan (27), and from controls from all countries except Sudan. Controls were matched for ethnic origin, age and social class. Sera were tested by indirect immunofluorescence (IF) for IgG and IgA antibodies to membrane antigens (MA) and IgA antibodies to VCA of HSV‐2 infected cells. Compared with controls, IgA antibodies to MA (IgA anti‐MA) were detected more frequently and at higher titres in all groups of patients. However, there was no significant difference in prevalence of these antibodies at titres ≥1:4 between Malawian patients and controls, although a significantly higher proportion of patients had IgA anti‐MA titres of ≥1:16. In contrast, IgA anti‐VCA did not distinguish patients from controls. More than 90% of both patients and controls from all countries had IgG antibodies to MA (IgA anti‐MA). Malawian patients had a significantly higher geometric mean titre (GMT) of IgG anti‐MA than controls and both patients and controls and significantly higher GMTs than their counterparts from other countries. The variation between herpes IgG anti‐MA titres in subjects from different countries did not reflect differences in serum immunoglobulin levels and similar variations in titre were not seen in rubella and measles HAI titres. Among the patients there was a geographical variation in the prevalence of HSV‐2 specific antibodies detected by ELISA, which varied from 52% among British and Sudanese patients to 73% among Malawian patients. Even when adjustment was made for possible false negative results, there were between 10 and 31% patients without HSV‐2‐specific antibodies, although only 2 of 103 (1.9%) patients had neither HSV‐1 nor HSV‐2 antibodies. The association of HSV‐2 with cervical carcinoma appeared to vary with age.
Morphological and microbiological signs of endogenous C‐virus in human oocytes
Authors: Larsson E. , Nilsson B. Ove , Sundström P. , Widéhn Sibylle
Published: February 2007

Human oocytes in different stages of maturation were obtained by follicular aspiration from women given Clomovid and Gonadex. Particles similar to type‐C virus were observed in three out of 16 oocytes. The particles were irregularly distributed along the oocyte membrane. They were seen both in a state of budding and lying free in the perivitelline space. Reverse transcriptase activity was detected in three out of nine samples of follicular fluid obtained from women other than those donating the oocytes. The supernatants from bat lung cells and dog thymus cells cultivated with oocytes or follicular fluids were tested for reverse transcriptase. An increased activity was observed only transiently in one case. It is assumed that these findings indicate the expression of endogenous retroviruses in human oocytes.
Retrovirus p30‐related antigen in human syncytiotrophoblasts and IgG antibodies in cord‐blood sera
Authors: Suni Jukka , Wahlström Torsten , Vaheri Antti
Published: February 2007

Sensitive immunological techniques were used to detect retrovirus markers in human pregnancy. A total of 1,540 human cord‐blood sera were tested for retrovirus‐reactive IgG antibodies using solid‐phase enzyme immunoassay and purified RD114 virus as antigen. Of these, 118 (7.7%) sera were positive. Blocking assays with specific animal anti‐p30 sera, use of control antigen, and electrophoretic protein experiments combined with immunological detection indicated that the human antibodies reacted specifically with the p30 protein. The occurrence of antibodies in cord‐blood serum had a highly significant correlation to complications during pregnancy and also correlated to the number of previous abortions and stillbirths. When goat anti‐RD114 p30 serum was used in the peroxidase‐anti‐peroxidase tissue staining procedure, p30‐related antigen was detected in sections of all placental specimens (early and term pregnancies, blighted ova, hydatidiform moles, destructive moles and choriocarcinomas). However, in each case only syncytiotrophoblastic cells were positive. These findings, supplemented with different types of blocking tests, lead us to conclude that retrovirus p30‐related antigen is selectively expressed in the highly differentiated syncytiotrophoblasts, which in the normal placenta are directly exposed to maternal blood. It is suggested that retrovirus‐reactive antibodies may represent an autoimmune‐like immune response to the p30‐related syncytiotrophoblast antigen escaping during cellular damage.
Synergistic action of two polyamine antimetabolites leads to a rapid therapeutic response in childhood leukemia
Authors: Siimes M. , Seppänen P. , Alhonen‐Hongisto L. , Jänne J.
Published: February 2007

Sequential administration of α‐difluoromethyl ornithine and methylglyoxal bis(guanylhydrazone), two differently acting inhibitors of the biosynthesis of natural polyamines, produced a rapid and distinct therapeutic response in four children with advanced lymphoblastic and in one with myeloblastic leukemia. The synergism between the action of the two compounds was based upon a unique drug interaction; a preceding treatment with difluoromethyl ornithine greatly increased the uptake of subsequently administered methylglyoxal bis‐(guanylhydrazone) as verified by the actual determinations of the latter drug in the circulating leukemia cells. The side‐effects associated with the combined drug regimen were either absent or mild.
Binding of 125I‐labelled human αinterferon to human lymphoid cells
Authors: Mogensen Knud Erik , Bandu Marie‐Thérèse , Vignaux Franloise , Aguet Michel , Gresser Ion
Published: February 2007

To investigate the binding of interferon to human lymphoid cells, we purified human α interferon and radio‐labelled it with iodine −125. Binding at 4°C could be saturated and was inhibited by unlabelled interferon; it was specific for cells of human origin. Dissociation constants for the complex of interferon and receptor site were of the order 10−9–10−11 M. All human cells tested showed such binding. Occupation of these high‐affinity sites, at 37°C, was compared with the inhibition of cellular growth due to interferon. The most sensitive cell line (Daudi) gave a complete biological response with only a fraction of its sites occupied. Evidence of two sites was found for a line (P3HRI) showing intermediate sensitivity. A relatively insensitive line (Raji) showed no response when all its high‐affinity sites were occupied.
Natural antibodies carrying a cross‐reactive idiotype enhance tumor growth in the rat
Authors: Natori T. , Takahashi S. , Nakagawa H. , Aizawa M. , Itaya T.
Published: February 2007

A population of Fab fragments was identified in the papain‐solubilized fraction of membranes of a rat chemically‐induced sarcoma, KMT 17. The Fab fragments were partially purified by gel filtration and column electrophoresis. A rabbit antiserum against the partially purified Fab fragments was raised and shown to be specific for Fab fragments by immunoelectrophoresis. Furthermore, four lines of evidence indicated that the KMT 17 Fab fragments carry a cross‐reactive idiotype: (1) the antiserum could bind only with a restricted population of normal Fab fragments having a pl of 6.3; (2) an unrelated antibody (WKA anti‐SRBC) showed a weak cross‐reactivity (less than 6%); (3) syngeneic antisera against the KMT 17 could bind with the 1251‐KMT 17 Fab preparation that was purified by an immunoabsorbent column with the rabbit anti‐KMT 17 Fab antiserum (anti‐idiotype antibody); (4) the rabbit anti‐KMT 17 Fab antiserum could bind with neither heavy nor light chains of WKA IgG. The natural antibody carrying the idiotype was found in normal serum and in various organs as well, especially in the lung of the conventional rats. In addition, the fractions containing Fab fragments (Frll) were shown to enhance tumor growth when injected into syngeneic animals, whereas Fab‐free fractions that were separated from the Fab fragments by column electrophoresis showed no enhancing activity. These results strongly suggested that a population of Fab fragments carrying a cross‐reactive idiotype was responsible for the enhancement of tumor growth. Mechanisms for the biological function of natural anti‐tumor antibodies carrying a cross‐reactive idiotype are discussed.
Inhibitory action of ASPARAGUS racemosus on DMBA‐induced mammary carcinogenesis in rats
Authors: Rao A. R.
Published: February 2007

The present paper reports the inhibitory effect of Asparagus racemosuson DMBA‐induced mammary tumorigenesis in rats of Holtzman strain. When virgin female rats, normal or primed with 17‐β‐estradiol treatment, are put on diets containing 0.25%, 0.5%, 1% or 2% Asparagus root extract powder prior to their exposure to DMBA, mammary tumor incidence shows a sharp decline.
Production of T‐cell lines with inhibitory or stimulatory activity against syngeneic tumors in vivo. A preliminary report
Authors: Mulé J. J. , Forstrom J. W. , George E. , Hellström I. , Hellström K. E.
Published: February 2007

We obtained Thy‐1‐positive cells directly from growing methylcholanthrene‐induced (MCA‐1510) sarcomas using fluorescence‐activated cell sorting, then cultured these lymphocytes in medium containing Interleukin‐2 and tested their activity in vivo against various MCA‐sarcoma lines with the Winn assay. We found that cultured T cells from small MCA‐1510 tumors (17 days after transplantation) significantly inhibited the growth of that particular sarcoma, but not of three other MCA‐tumor lines tested, while cultured T cells from large MCA‐1510 sarcomas (41 days after transplantation) significantly enhanced the growth of that tumor, but not of an unrelated tumor, MCA‐1460. The former cells were primarily Lyt‐1+, 2+ while the latter were primarily Lyt‐1−, 2+.
Regulation of gene expression by tumor promoters. III. Complementation of the developmental program in myeloid leukemic cells by regulating mRNA production and mRNA translation
Authors: Hoffman‐Liebermann Barbara , Liebermann Dan , Sachs Leo
Published: February 2007

Regulation of gene expression has been analysed in different clones of mouse myeloid leukemic cells treated with the tumor promoter 12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA), the macrophage‐ and granulocyte‐in‐ducing protein MGI, and combined treatment with TPA and MGI. Two‐dimensional gel electrophoresis was used to measure changes in the rate of synthesis of specific proteins and in the amount of corresponding translatable mRNAs assayed in the reticulocyte cell‐free translation system. TPA induced different subsets of differentiation‐associated protein changes in the different clones and the degree of response to TPA was not necessarily related to the degree of response to MGI. It is shown that TPA can induce protein changes either by inducing the synthesis of new mRNA, by increasing or decreasing the amount of pre‐existing mRNA, or by modulating the translation of a constant amount of mRNA. Combined treatment with TPA and MGI resulted in an enhancement of protein changes induced by MGI or TPA alone and induced differentiation‐associated protein changes not induced by either compound separately in differentiation‐defective clones. This complementation of gene expression appeared to be due to each compound inducing functions not induced by the other, so that the combined treatment resulted in new gene expression. Complementation also occurred at the level both of mRNA production and of mRNA translation. It is suggested that the ability of TPA to regulate gene expression at the level of mRNA production and mRNA translation and to complement changes in gene expression induced by other compounds such as MGI are important functions for its role as a tumor promoter.
Enhancing effects of dimethylnitrosamine on aflatoxin B1 hepatocarcinogenesis in rats
Authors: Angsubhakorn Subhkij , Bhamarapravati Natth , Romruen Kanda , Sahaphong Somphong
Published: February 2007

In a study of possible enhancing effects of dimethylnitrosamine (DMN) on aflatoxin B1 (AFB1) hepatocarcinogenesis, male Buffalo strain rats were fed diets containing 1 ppm AFB1, 25 ppm DMN, and a combination of 1 ppm AFB1 and 25 ppm DMN (AFB1 + DMN). The diets were replaced by chow pellets after 6 months, and animals were killed 3,6,9 and 12 months after the onset of the experiment. In the untreated control group animals were free of hepatocellular carcinoma but the treated groups fed AFB1, DMN and AFB1 plus DMN developed hepatic lesions ranging from multiple cysts, altered cell foci and neoplastic nodules to hepatocellular carcinomas. Hepatocellular carcinomas developed in 79%, 45% and 5% of rats fed AFB1 plus DMN, AFB1 and DMN respectively at the end of the experiment. Multiple cysts were also found in all periods in animals fed AFB1 plus DMN, whereas rats fed AFB1 and DMN separately developed a few multiple cysts by the end of the experiment. These findings suggest that DMN potentiates the hepatocarcinogenesis induced by AFB1 in rats.
Natural killer cell activity in reticulum‐cell sarcomas of SJL/J mice. II. Analysis of RCS‐associated NK activity
Authors: Fitzgerald Karen L. , Ponzio Nicholas M.
Published: February 2007

Lymphoid cells taken from the grossly enlarged lymph nodes (LN) and spleens of SJL/J mice bearing transplantable reticulum‐cell sarcomas (RCS), showed increased levels of natural killer (NK) cell activity, when compared to LN and spleen cells taken from normal SJL mice. The NK susceptible target cells used for these studies included RL‐1 and YAC‐1. Target cells that were not susceptible to NK lysis by CBA/J effector cells (high NK strain) were also resistant to lysis by RCS tumor cells. Although significant lysis of target cells was detectable at 4 h, optimal NK cytotoxicity was observed in a 16‐h 51Cr‐release assay. In terms of lytic unts (LU)/107 effector cells, greater NK activity was observed in RCS effectors than was apparent in normal CBA/J lymphoid cells. Depletion of macrophages from RCS cell preparations had no effect on the observed NK activity. Purified Mu‐IFN‐α stimulated a small increase in the NK activity expressed by SJL lymphoid cells; however RCS‐derived supernatants (containing Mu‐IFN‐γ) did not augment NK activity of SJL effector cells, nor were they cytotoxic for NK target cells. Therefore, tumor‐derived soluble factors appear not to be involved in the observed RCS‐associated NK activity. The data presented in this report further define the parameters of the NK activity manifested by RCS tumor cell preparations. The accompanying article characterizes the nature of the NK effector cells present within RCS tumors of SJL mice. Taken together, these data indicate that the RCS tumors represent either neoplastic expansion of conventional NK cells with somewhat modified properties, or else an entirely new class of cytotoxic effector cells.
Estrogen receptor quantitation and staging as complementary prognostic indicators in breast cancer: A study of 583 patients
Authors: Godolphin W. , Elwood J. M. , Spinelli J. J.
Published: February 2007

Estrogen receptor (ER) quantity was measured at the time of primary diagnosis on 583 patients with breast cancer seen at the major treatment centre in British Columbia between 1975 and 1979. Survival rates (overall, recurrence‐free and post‐recurrence) were assessed relative to ER concentration, staging, menopausal status, age, differentiation, and therapy. A linear trend in increased survival was demonstrable through variations in ER concentration from ⩽1 to ⩾260 fmoles/mg cytosol protein. This trend was highly significant and remained after adjustment for stage, menopausal status, and age, and was seen for all groups of patients except those with metastatic disease. The association of high ER concentration with increased recurrence‐free survival was not due to differing responses to adjuvant therapy, but the trend in post‐recurrence survival was only significant in patients who had received hormonal therapy. Survival was as strongly associated with receptor concentration as with staging, and these two factors were almost completely independent. A proportional hazards model was fitted to produce predictions of survival, and showed that TNM stage III patients with high ER concentrations have a better survival than stage I or II patients with lower ER concentrations. This suggests that quantitative assessment of ER status is essential to definition of risk in breast cancer patients and that stratification in clinical trials and consideration for adjuvant therapy ought to be guided, in part, by a standardized ER‐quantitative determination performed on the primary tumor.