bluuebunny/crossref_metadata_2025 huggingface dataset:
In utero tumor induction by murine sarcoma virus (moloney) in the rat. I. Biological characteristics
Authors: Vandeputte M. , Sobis H. , Billiau A. , Van De Maele B. , Leyten R.
Published: February 2007

Female R rats mated with an R male and inoculated in utero, after fetectomy, with murine sarcoma virus (Moloney), developed tumors. These tumors originated in the uterus and were of fetal origin. Intravenous or intraperitoneal injection of the virus induced similar tumors. Infectious virus could not be isolated from the tumor cells kept as transplantable lines or cultured in vitro. However, the presence of the MSV genome could be demonstrated by a direct rescue test. In non‐pregnant rats treated in the same way no neoplasms were recorded. The results are discussed in the light of current theories on the special immunological fetal‐maternal relationship.
Inheritance of susceptibility to friend mouse leukemia virus. X. Separate genetic control of two viruses in friend virus preparation
Authors: Odaka Takeshi
Published: February 2007

Susceptibility of mice to viral components present in Friend leukemia virus (FLV) preparation, lymphatic leukemia virus (LLV) and spleen focus‐forming virus (SFFV), was studied by separately determining end point for infection of each component. Mice with Fv‐1n genotype were much more susceptible to LLV of N‐tropic FLV than those with Fv‐1b genotype. This difference in susceptibility to LLV was shown to be controlled by a single gene locus with the recessive allele for susceptibility. Mouse strains congenic except for Fv locus showed marked differences in susceptibility to SFFV according to their Fv genotypes; mice with Fvs genotype were much more susceptible to SFFV than those with Fvr genotype. These results indicate that the innate susceptibility to FLV in mice is under the simultaneous control of two separate gene loci, one locus (probably Fv‐1) for LLV multiplication and the other (Fv or Fv‐2) for proliferation of infected spleen cells (spleen focus formation and splenomegaly induction) as well as SFFV multiplication. All the data obtained support Lilly's interpretation for two‐gene control. Interaction of these two gene loci with respect to multiplication of the two viruses is discussed.
Antibodies against avian GS antigen in chickens infected naturally and experimentally with avian RNA tumor viruses
Authors: Ruoslahti Erkki , Vaheri Antti , Estola Timo , Sandelin Karin
Published: February 2007

Using a radioimmunoassay (RIA) we detected antibodies against one of the major group specific (gs) antigens of avian RNA tumor viruses in chickens with a naturally acquired leukosis virus infection or bearing Rous sarcoma virus (RSV)‐ induced tumors. The antibodies were absent in leukosis‐free animals, but appeared a few weeks after inoculation with infectious RSV. Out of 11 chickens with a natural or experimental infection, nine had demonstrable anti‐gs antibodies. Titers as high as 1:10,000 were observed in chicken sera, but these titers were lower than those in the sera of tumor‐bearing hamsters and guinea‐pigs. The RIA was about 10,000 times more sensitive in the detection of anti‐gs antibodies than the COFAL test. The chicken antibodies could be inhibited with the purified gs antigen and appeared to be of the IgG type. There would seem to be no complete tolerance in chickens at least to one of the major avian gs antigens. The significance of these results as related to the presence and nature of gs antigens in normal cells is discussed.
In situ hybridization of adenovirus RNA and DNA. II. Detection of adenovirus‐specific DNA in transformed and tumour cells
Authors: Dunn A. R. , Gallimore P. H. , Jones K. W. , McDougall J. K.
Published: February 2007

The method of in situ molecular hybridization has been used to detect adenovirus DNA in permissively and non‐permissively infected cells. Onset of viral DNA synthesis can be detected by this method in individual cells by 12 h after infection. Viral nucleic acid hybrids have been detected at the cytological level in adenovirus‐transformed and tumour cells.
Influence of age and 3‐methylcholanthrene on azo‐dye carcinogenesis and metabolism of p‐dimethylaminoazobenzene in rat liver
Authors: Decloitre Françoise , Chauveau Jean , Martin Michelle
Published: February 2007

Two groups of male Sprague‐Dawley rats of different ages received a carcinogenic diet containing 0.06% dimethylaminoazobenzene (DAB). Out of a group of 4‐ to 6‐ week‐old rats, 20% developed hepatomas 31/2 months after the beginning of the diet, and after 10 months the percentage of tumors reached 56%. Rats aged 10–11 weeks old did not present hepatomas before 6 months of DAB feeding; the yield was only 28% after 10 months of carcinogen ingestion. In control rats, in vitro DAB metabolites binding to DNA and proteins proceeding from microsomal activation of carcinogen decreased by 70% between 4 and 12 weeks; within the same time azoreductase activity remained constant. A single injection of 3‐methylcholanthrene (20 mg/kg) greatly increased binding but not azoreductase activity. Time‐effect was similar in treated and control rats. Results were discussed looking for age and methylcholanthrene effect on carcinogenesis‐DAB metabolism relationship.
Ultraviolet inactivation of murine leukemia virus and its assay in permissive and non‐permissive cells
Authors: Yoshikura H.
Published: February 2007

This study confirms the different titration patterns of murine leukemia viruses (MuLV) in permissive and non‐permissive cells reported by Hartley et al. (Lilly and Pincus, in press); the titration kinetics was one‐hit in the permissive host and two‐hit in the restrictive host. The following phenomena were also observed: (1) UV‐inactivation curves were nearly the same, regardless of whether the virus was titrated in permissive or restrictive cells. (2) Infection by MuLV of its restrictive host was enhanced by the UV‐inactivated homologous MuLV. (3) UV‐inactivated NB‐tropic virus propagated in N‐type cells enhanced plaque formation of N‐tropic virus in B‐type cells and not that of B‐tropic virus in N‐type cells. UV‐inactivated NB‐tropic virus propagated in B‐type cells enhanced plaque formation of B‐tropic virus in N‐type cells, but not that of N‐tropic virus in B‐type cells.
The effects of long‐term feeding of DDT to BALB/c mice
Authors: Terracini B. , Testa Maria Cristina , Cabral J. R. , Day N.
Published: February 2007

A multigenerational study on the long‐term effects of three dose levels of DDT (2, 20 and 250 ppm in the diet) and one dose level of N‐nitrosodimethylamine (DMN) (0.0003% in the drinking water) was started in 1968. Each treatment was administered to two separate colonies of BALB/c mice. Treatment of parent mice started at 4‐5 weeks of age. The results observed in the first two generations are presented in this report. Survival in males was poor because of fighting. In females, the highest dose level of DDT produced liver‐cell tumours in 44% of the parent mice and 74% of the first generation mice, whereas no liver‐cell tumours were found in mice given the control diet, or lower dietary concentrations of DDT. Liver cell tumours did not give metastases, but grew after transplantation to syngeneic mice. The ability of DDT to induce liver‐cell tumours was identical in both colonies of mice given 250ppm DDT. Malignant lymphomas occurred in about 50% of the mice in all colonies given 0, 2 or 20 ppm DDT. In one of the two colonies given 250ppm DDT, the incidence of malignant lymphomas was 14%, whereas in the other it was 36%. The incidence of lung adenomas was not affected by DDT treatment. Tumours at sites other than liver, lymphatic system and lungs were highest in control mice and lowest in mice given 250 ppm DDT. However, no linear dose‐response was found, and the decrease was more obvious in the parental than in the first generation. A study on the combinations of tumours in mice with more than one tumour and an analysis of litter distribution of liver‐cell tumour‐bearing mice did not reveal any particular trend in the distribution of liver‐cell tumours. The quantitative aspects of tumour induction by DDT in BALB/c mice are compared with data from previous studies in mice. DMN consistently produced lung adenomas, liver blood cysts and haemangioendotheliomas.
Genetic control of MuLV‐gs expression in crosses between high and low leukemia incidence strains
Authors: Hilgers Jo , Galesloot Jan
Published: February 2007

A newly developed test for MuLV‐gs antigen, based on disappearance rate (DR) of injected rat anti‐MuLV antibody in mice, has been used in combination with a previously described quantitative immunofluorescence adsorption (IFA) technique for the antigen in spleens, in order to classify inbred strains of mice of European and American origin. The following groups could be distinguished: (1) low leukemia incidence strains, mice which were MuLV‐gs negative in their spleens and sera; (2) low leukemia incidence strains, of which young adult mice were generally MuLV‐gs negative, whereas old mice were occasionally positive, levels of the antigen being invariably low in the spleens of positive animals; (3) one low leukemia strain (NZB, a mouse strain with auto‐immune disease), of which young adult mice were generally MuLV‐gs negative, whereas all older mice were highly positive, levels in spleens reaching those in spleens of high leukemia strain mice; and (4) high leukemia strains, mice of which were always MuLV‐gs positive, levels of the antigen in spleens and sera being invariably high, even in young adult mice. Spleens and sera of adult animals of the F1 hybrid between a high (AKR) and a low (C57BL) leukemia incidence strain contain intermediate amounts of MuLV‐gs. In this heterozygote, the antigen was generally found at an earlier age than in all low leukemia incidence strains, but at a later age than in the high leukemia incidence strain. Typing for MuLV‐gs in spleens and sera of normal segregants between mice of high and low leukemia strains revealed that: (1) one semidominant host gene, presumably Fv‐1, controls MuLV‐gs levels as shown in back‐crosses to the high incidence strain, and (2) two additional dominant genes are involved in all‐or‐none expression of MuLV‐gs as shown in backcrosses to the low incidence strain and in F2 generations.
The predictive value of mouse liver tumour induction in carcinogenicity testing—a literature survey
Authors: Tomatis L. , Partensky C. , Montesano R.
Published: February 2007

A survey of the available data in the literature was carried out in an attempt to verify the possible correlation between the capacity of a number of chemicals to induce parenchymal liver tumours in the mouse and their capacity to induce tumours in the liver and/or other organs in the rat and hamster. Data on 58 chemicals were collected. A positive correlation appears to exist between the capacity of a chemical to induce liver tumours in the mouse and its capacity to induce tumours at any site in the rat or the hamster. The strongest correlation is found when the chemical, given to adult mice, induces tumours of the liver and other sites in both sexes. The induction of liver tumours in the mouse by a chemical does not signify that the liver would be the target organ in the rat or the hamster. Among the 58 chemicals considered, seven are recognized or suspected human carcinogens. All were hepatocarcinogenic in the mouse and six were carcinogenic in the liver and/or other organs in the rat. Four were tested in the hamster and found to be carcinogenic.
Cancer of respiratory organs among workers at a nickel refinery in Norway
Authors: Pedersen Einar , Høgetveit Arne Chr. , Andersen Aage
Published: February 2007

A follow‐up study has revealed a clearly increased incidence of cancer of respiratory organs among men employed at a nickel refinery in Norway. During the period 1953–71 there were 48 cases of lung cancer, 14 cases of cancer of nasal sinuses and 5 cases of laryngeal cancer. The highest risk was among men involved in roasting, smelting and electrolysis. For these men the ratio of observed to expected number of cases was 7:1 for lung cancer and 40:1 for cancer of nasal sinuses. Still higher relative risks were found for workers of these categories whose employment had started before 1940. The refinery, established in 1910, practically discontinued production when the war hit Norway in 1940. Production was resumed in 1945, and subsequently the processes have undergone major changes. Of the 14 cases of cancer of nasal sinuses only one has occurred among men whose first employment started after 1945, but as the induction time for this form of cancer was found to be very long in this material, it is still uncertain whether a reduction of the risk has been achieved. As regards lung cancer, it is clear that the hazard of exposure still persisted around 1950. Although it has not been practicable in this study to obtain information on smoking habits and on possible exposure in other occupations, it is concluded that the increased risk among the men is largely ascribable to exposure at the refinery. Deaths and cases of cancer among the men were identified by computer linkage of past and current employees against all deaths in Norway and against all cases of cancer reported to the Cancer Registry of Norway during the follow‐up period.
Carcinoembryonic antigen (CEA): Comparison of the farr and solid‐phase methods for detection of CEA
Authors: McPherson T. A. , Band P. R. , Grace M. , Hyde H. A. , Patwardhan V. C.
Published: February 2007

Carcinoembryonic antigen (CEA) was detected in 180 preoperative malignant serum samples, or from the first benign serum sample if more than one sample was taken by the Farr assay using reagents provided by the Montreal laboratory of Gold and Freedman and in 148 plasma and 178 serum samples by a solid‐phase assay using reagents provided by the Cancer Diagnostic Laboratory of Hoffmann‐La Roche, Inc. Disposable, polystyrene tubes were coated with anti‐CEAγG in the solid‐phase assay. These were then used along with 125I‐CEA to construct an antibody dilution curve, standard inhibition curve and to test plasma or serum samples directly for CEA. In general, levels of CEA were higher for all diagnostic categories by the Farr assay than by the solid‐phase assay. For CEA levels greater than 10 ng/ml, samples from colorectal cancer patients were clearly separable from other samples by both techniques. Thus, levels greater than 10 ng/ml were found by the Farr and solid‐phase assays done on serum and by the solid‐phase assay done on plasma respectively in 39%, 23% and 13% of patients with colorectal cancer, and in 14%, 4.5% and 1% of patients with other diseases. Aliquots from 123 blood samples were tested by both the Farr and the solid‐phase assays. Serum was studied in all 123 by the Farr assay. Fifty‐seven of the solid‐phase assays were done on serum and the remaining 66 were done on plasma. The results showed good agreement (77% overall) for the two assays when serum results were considered, but lesser agreement (59% overall) when serum results by the Farr assay were compared with plasma results by solid‐phase. The serum/plasma disagreement noted between the Farr and solid‐phase assays was largely found in samples from patients with colorectal cancer (45% agreement), and appeared to be due mainly to samples from patients with Duke's A or B colonic cancer. Antibody dilution and standard inhibition curves done using reagents from the two laboratories in both the Farr and solid‐phase assays indicated that the CEA from Montreal detects antibody sites on both anti‐CEA preparations which are not available to the CEA from Roche. Further, the unlabelled CEA from Roche appears to be more similar antigenically to the Montreal 125I‐CEA than unlabelled Montreal CEA itself. This suggests that iodination of CEA may have altered the anti‐genie character of the molecule. It is suggested that this alteration, as well as the use of CEA preparations of higher specific activity than those used initially, might account, at least in part, for the apparent loss of specificity of recent “CEA tests” for colorectal cancer as compared to the earlier report from Thomson and colleagues.
Low‐leukemogenic variants of rauscher leukemia virus obtained in long‐term cultures at supra‐optimal temperature
Authors: Barski Georges , Barbieri Dominique , Youn Jung Koo , Hue Gilbert
Published: February 2007

Taking as a starting point the previously demonstrated genetic variability of in vitro cultivated murine leukemia viruses (MuLV), with particular regard to their leukemogenic potential, an attempt was made to accumulate and study Rauscher leukemia virus (RLV) variants selected by long‐term cultivation at a supra‐optimal temperature of 40.5°C (± 0.5°C). The most significant results were obtained with cells of the CL91 line originating from normal C57BL lung tissue, initially virus‐free and infected with a highly leukemogenic RLV prepared from leukemic spleens. After 184 days of cultivation, the infected cells were divided into two parallel series: (I) the CL91RR which was continued at 37°C, (2) the CL91RRHT series which was transferred, after a transitory adaptation period at 39°C, for permanent culture at 40.5°C. Supernatants from the parallel series were checked periodically for their leukemogenic capacity as related to the number of virions found in the supernatant aliquots inoculated into sensitive weanling or new‐born BALB/c mice. The number of virions present in the CL91RRHT supernatants was regularly at least equal but usually significantly higher than in parallel CL91RR cultures. However, the leukemia‐producing capacity of the first was very low: only 11% of leukemias were obtained after an average of 98 days' latency with the CL91RRHT supernatants, when checked after 201 or more days of culture at 40.5°C, as compared with an average of 89% rapidly evolving leukemias (within an average of 23 days) obtained with material from CL91RR cultures. These differences were seen repeatedly in 19 independent assays performed on a total of 132 and 111 animals, respectively, and extending over an experimental period of 586 days following the in vitro infection. These results were discussed in the light of other data concerning temperature‐dependent selection of variants of pathogenic viruses.
Inhibition of lymphocyte cytotoxicity for human colon carcinoma by treatment with solubilized tumour membrane fractions
Authors: Baldwin R. W. , Embleton M. J. , Price M. R.
Published: February 2007

The in vitro cytotoxic action of patients' lymphocytes against colon carcinoma cells was evaluated following incubation of the lymphocytes with papain‐solubilized tumour‐membrane preparations. Soluble extracts of pooled colon carcinomas inhibited cytotoxicity by sensitized lymphocytes, but similar extracts of normal colon or melanoma had no inhibitory effect. The results suggest that soluble tumour antigen may play a role in abolishing lymphocyte reactivity, and this is interpreted as supporting the concept that cellular immunity against tumours in vivo may be inhibited by circulating antigen.
Difference in the mobility of lectin sites on the surface membrane of normal lymphocytes and malignant lymphoma cells
Authors: Inbar Michael , Ben‐Bassat Hannah , Sachs Leo
Published: February 2007

Binding sites for Concanavalin A (Con A) can move on the surface membrane. This induction of movement resulted in the formation of caps of Con A membrane‐site complexes in normal lymph‐node or spleen lymphocytes, but not in a line of malignant lymphoma cells. This indicates a difference in the mobility of Con A sites on the surface membrane of normal lymphocytes and lymphoma cells. Binding sites for the lectin from wheat germ (WGA) did not form caps either on normal lymphocytes or on lymphoma cells. Normal lymphocytes with caps induced by Con A still showed binding of WGA to the rest of the membrane. The mobility of Con A sites was, therefore, independent of WGA sites. The difference in the mobility of binding sites for Con A on the surface membrane of normal lymphocytes and lymphoma cells suggests that changes in the fluid state of the carbohydrate‐containing structures on the surface where the Con A sites are located, are associated with malignant cell transformation.
Multihormonal activities of normal and neoplastic pituitary cells as indicated by immunohistochemical staining
Authors: Ueda G. , Moy P. , Furth J.
Published: February 2007

The hormonal changes during the course of induction and subsequent growth of mouse thyrotropic tumors and rat mammotropic tumors were studied by means of immunohistochemical staining in consecutive sections cut at 3γ. Multihormonal activities were detected in the primary tumors, but were more conspicuous in the transplanted neoplasms. Labelled anti‐thyrotropic hormone stained slightly normal gonadotropes. This is due to the presence of a common antigenic subunit between the two hormones and may explain the earlier finding of biologic gonadotropic activity in thyrotropic tumor‐bearing mice with high serum thyrotropic hormone levels. Antiserum to the β subunit of thyrotropic hormone stained the thyrotropes almost as intensely as did antiserum to the complete hormone. Neoplastic thyrotropes often had somatotropic activities. Neoplastic mammotropes usually had somatotropic, and less often, adrenotropic activities. Derangement of the hormonal spectrum of pituitary tumors is best related to the derepression of the cytogenetic code of differentiated normal cells. The rare findings of multihormonal activities in normal pituitary cells and the possible existence of a stem cell remain to be fully investigated.
Radioimmunoassay of mammalian type‐c polypeptides. IV. Characterization of woolly monkey and gibbon viral antigens
Authors: Parks Wade P. , Scolnick Edward M. , Noon Marian C. , Watson Cynthia J. , Kawakami Thomas G.
Published: February 2007

The ˜30,000 dalton woolly and gibbon type‐C viral polypeptides have been isolated and characterized immunologically. By radioimmunoassay, antibody prepared in rabbits to the woolly and gibbon “gs” protein show only low‐level cross‐reactions with other mammalian type‐C viral gs antigens and their antisera. The woolly and gibbon ˜30,000 dalton polypeptides are highly related on the basis of both serum and antigen titrations, confirming previous studies with the viral reverse transcriptases. The woolly gs assay using a double antibody radioimmunoassay can detect less than one nanogram of purified woolly or gibbon viral protein, and the same protein also reacts in the interspecies of gs‐3 radioimmunoassay indicating that the primate “gs” proteins also contain both species‐specific and interspecies reactivities on the same polypeptide. To establish that the woolly and gibbon type‐C viruses represented distinct isolates with a close immunological relationship and to eliminate the possibility of laboratory contamination, original woolly and gibbon material was studied for antigen. Both the original woolly monkey fibrosarcoma and two separate gibbon lymphoid tumors contained high levels of type‐C interspecies and woolly viral antigen by radioimmunoassay, indicating that natural tumors from distinct species of primates contain immunologically related viral antigen.
The horizontal development of cell‐mediated tumor‐specific immunity in rous sarcoma virus tumorigenesis in rats
Authors: Jonsson Nils
Published: February 2007

The horizontal development of lymphoid cell‐mediated specific antitumor immunity was studied in R/F rats, inoculated with the Schmidt‐Ruppin strain of Rous sarcoma virus (SR‐RSV) during the neonatal period. Lymph‐node cells (LNC) were harvested from individual animals on consecutive occasions and used in colony inhibition tests for the detection of LNC‐mediated immunity to the Rous‐specific tumor‐associated transplantation antigen (s). None of the rats tested, which had been SR‐RSV inoculated within 6 days after birth, had any demonstrable LNC‐mediated immunity when tested within 4 weeks after virus inoculation. At the same time 68% of the rats SR‐RSV‐inoculated at a higher age disclosed a clear‐cut immunity. In the former group sarcomas appeared after short latency periods (average 5 weeks), while the latter group developed sarcomas with long latency periods (average 11 weeks) or remained tumor‐free. Also in tests performed later after SR‐RSV‐inoculation rats remaining tumor‐free or developing very late tumors tended to develop an LNC‐mediated immunity more rapidly than rats with tumors appearing earlier. The majority of both tumor‐positive and tumor‐negative animals developed at some time an LNC‐mediated immunity, which often persisted for several months in negative animals but sometimes disappeared in rats with a large tumor burden. The results indicate that the kinetics of the LNC‐mediated antitumor immune response can be of importance for the development of primary Rous sarcomas.
Cell‐mediated immune reaction against tumors induced by oncornaviruses. III. Studies by mixed lymphocyte—tumor reaction
Authors: Senik A. , Gomard E. , Plata F. , Levy J. P.
Published: February 2007

A one way mixed lymphocyte—tumor‐cell reaction (MLTR)‐was applied to the study of anti‐tumor cell‐mediated immunity in MSV‐infected mice. No stimulation of normal, non‐immune lymphocytes by tumor cells was observed. Lymphoid cells which can be stimulated in vitro by various tumor cells of the same antigenic specificity as MSV‐induced tumor cells were detected in the spleen and lymph nodes of MSV‐infected mice. These “responder cells” were only found before the appearance of the tumor, and at a time (3 to 7 days after MSV inoculation) when no cytotoxic cells can be detected in the chromium‐51 release test (CRT). The reactivity of responder cells declines rapidly and remains undetectable thereafter, both when palpable tumors and cytotoxic cells are present and after tumor rejection, when none or very few CRT‐killer cells are active. An inverse relationship between responder cells in MLTR and killer cells in CRT was also detected after allogeneic immunization; its significance is briefly discussed.
Effect of BCG on delayed hypersensitivity responses of patients with neoplastic disease
Authors: Sokal Joseph E. , Aungst C. William , Han Tin
Published: February 2007

BCG is a potent immunologic stimulant which can increase cellular immune responses generally, as well as induce sensitivity to tuberculin. A single BCG vaccination induced significant increases in delayed hypersensitivity responses of patients whose neoplastic disease was under good control. Repeated vaccinations exerted cumulative effects, and very substantial increases in delayed skin test responses to a battery of antigens were seen in some groups of patients. The major determinant of responsiveness to these effects of BCG was the status of the neoplastic disease. Patients with uncontrolled, actively progressing disease showed little immunologic response to BCG vaccination.
Ultrastructural effects of N‐methyl‐N‐nitrosourea on the tracheobronchial epithelium of the Syrian Golden hamster
Authors: Harris Curtis C. , Kaufman David G. , Sporn Michael B. , Smith Joseph M. , Jackson Frank , Saffiotti Umberto
Published: February 2007

Ten intratracheal instillations of N‐methyl‐N‐nitrosourea (NMU) caused squamous metaplastic and neoplastic changes in the tracheobronchial epithelium. Abnormal squamous metaplastic cells contained enlarged nuclei deeply indented by cytoplasmic invaginations, pleomorphic nucleoli, filamentous granules and many cytoplasmic fibrils. Prior to the appearance of tumors, autoradiograms revealed cells preparing for division, first in basal and then in all layers of the abnormal squamous metaplastic epithelium. Defects in the basement lamina were found in squamous metaplastic lesions. The ultrastructural changes in the tracheobronchial epithelium were similar to those described in hamsters exposed to benzo[a]pyrene‐ferric oxide as well as to those described in smoking dogs and in human bronchogenic carcinoma. The squamous metaplastic changes induced by NMU were clearly distinguishable from squamous metaplasia found in vitamin‐A deficiency.
An evaluation of the TNM classification in cancer of the breast
Authors: Phillips A. J.
Published: February 2007

A prospective 5‐year clinical trial was conducted by the National Cancer Institute of Canada to assess the TNM classification for breast cancer proposed by the International Union Against Cancer (UICC). The study period was 1960–1964 with a 5‐year follow‐up on all cases. Excluding those with distant metastases (59), lost to follow‐up (14), and incomplete data (97) there are 1,347 cases in the study. The clinical data recorded covered the size of the primary tumour and involvement of skin and underlying structures. Tumours less than 5 cm in diameter but with varying degrees of nodal involvement accounted for 66.1% of the total while 56.6% had no palpable axillary nodes. Only 1.4% of all cases had clinical evidence of involvement of supraclavicular or infra‐clavicular nodes. These proportions are significantly different from those reported for retrospective studies. This study shows that the survived of patients is related to the size of the tumour, the presence of skin fixation and the degree of nodal involvement. There does not appear to be a relationship with involvement of the pectoral muscle. The determination of whether or not involved axillary nodes contain growth is difficult— the study shows that 39.1% of cases with no palpable nodes had positive histology. The survival rate for certain categories of cases did not fit the stage groupings proposed by the UICC and possible explanations for these variations are presented. No relationship could be found between involvement of the pectoral muscle, based on clinical assessment, and prognosis.
Pilot experiments with EB virus in owl monkeys (aotus trivirgatus). I. Reticuloproliferative disease in an inoculated animal
Authors: Epstein M. A. , Hunt R. D. , Rabin H.
Published: February 2007

A pilot experiment is described in which EB virus‐containing cultured lymphoblasts were inoculated into a group of three adult owl monkeys. Virion‐free cells were inoculated into three other monkeys, and four further animals were kept as uninoculated controls. One of the animals receiving the virus died after 14 weeks with a striking reticulopro‐liferative disease very compatible with certain forms of malignant lymphoma. The findings are described and their significance considered in relation to a possible onocgenic capacity for EB virus.
Pilot experiments with EB virus in owl monkeys (aotus trivirgatus). II. EB virus in a cell line from an animal with reticuloproliferative disease
Authors: Epstein M. A. , Rabin H. , Ball G. , Rlckinson A. B. , Jarvis J. , Meléndez L. V.
Published: February 2007

A continuous cell line has been established in culture from a pathological lymph node of an owl monkey with reticuloproliferative disease after inoculation with EB virus. The cells grow in suspension in clumps or as single individuals and show the characteristic features of lymphoblasts with some differentiation to reticulum cells; their karyotype is typical of one sub‐species of owl monkey. A herpes virus has been found in the cells and has been identified as EB virus in two types of immunofluorescence test using two different specific antisera; this identification was confirmed by the ability of the virus to transform normal human cord‐blood lymphocytes and make them grow as a continuous cell line. Infection by a carcinogenic simian virus, herpesvirus saimiri, has been excluded by tests for neutralizing antibodies and virus growth in susceptible cells. The continuous growth of the monkey cells, the presence in them of EB virus, and the possible relationship of the virus to the original reticuloproliferative disease of the inoculated monkey, are considered and discussed.
Primary immunodeficiency diseases and cancer: The immunodeficiency‐cancer registry
Authors: Kersey John H. , Spector Beatrice D. , Good Robert A.
Published: February 2007

Data from the newly established Immunodeficiency‐Cancer Registry show 151 tumors in 145 patients with primary immunodeficiency syndromes, including: sex‐linked (Bruton's) agammaglobulinemia, 6 patients; severe combined system immunodeficiency, 9 patients; Wiskott‐Aldrich syndrome, 24 patients; ataxia‐telangiectasia, 52 patients; common variable (late onset) immunodeficiency, 41 patients; isolated IgA deficiency, 7 patients; and isolated IgM deficiency, 6 patients. The risk of development of malignancy is from 2–10%, indicating that these individuals have a far greater than chance risk of developing malignancies, in spite of their short life‐spans. Tumors are divided into major histologic types: lymphoreticular, 58% of total; leukemias, 17% of total; epithelial. 18% of total; mesenchymal, 3% of total; and nervous system, 4% of total. Data are reported on 14 families in which 12 siblings had the same tumors and identical primary immunodeficiency diseases. The majority of tumors are lymphoreticular or leukemias: these findings are consistent with the hypothesis that individuals with primary immunodeficiency syndromes have intrinsic abnormalities of the lymphoid system which result in increased frequency of malignant transformation and inability to eliminate transformed cells. Further reporting of tumors is urged.
Increase of lymphocyte‐mediated tumor‐cell destruction by certain patient sera
Authors: Hellström Ingegerd , Hellström Karl Erik , Warner Glenn A.
Published: February 2007

Sera from one patient with an ovarian carcinoma, one with sarcoma, one with a breast carcinoma, and four patients with melanoma were found to “potentiate” (i.e. increase) the cytotoxic effect of blood lymphocytes reactive to the respective type of tumor target cells. This effect was specific. Furthermore, sera from the breast cancer and sarcoma patients and from one of the melanoma patients “armed” (i.e. made cytotoxic) lymphocytes from non‐reactive donors, not having (had) the respective tumor studied. The possible relevance, in vivo, of these findings, and the frequency with which they occur, need further clarification.
Spontaneous breakdown of immunological tolerance to gross‐virus‐induced cell‐surface antigens in the rat
Authors: Kuzumaki Noboru , Takeichi Noritoshi , Kodama Takao , Kobayashi Hiroshi
Published: February 2007

WKA/Mk rats injected with undiluted Gross virus at birth demonstrated loss of resistance to transplanted Gross lymphoma (WGT‐4), and also during later life did not contain detectable cytotoxic antibody to Gross virus‐specific cell‐surface antigen. These rats were considered to be immunologically tolerant to the Gross‐virus‐induced cell‐surface antigens, and all of them developed primary Gross lymphoma about 3 months after birth. Some rats injected with diluted virus at birth or undiluted virus at the age of 1 or 2 weeks also continued to be immunologically tolerant to Gross‐virus‐induced cell‐surface antigens for a certain period in proportion to the amount of virus administered, or age at the time of exposure to the virus. Thereafter, this tolerant state was spontaneously broken down and the rats developed transplantation resistance to WGT‐4, and produced cytotoxic antibody to Gross antigens for a considerable period. These rats did not develop Gross lymphoma. These facts suggest that susceptibility to leukemogenesis by the Gross virus in WKA/Mk rats might be ascribed to the immunologically tolerant state to the Gross‐virus‐induced cell‐surface antigens.
Cutaneous delayed hypersensitivity responses to tumor‐associated and other antigens in acute leukemia
Authors: Char Devron H. , Lepourhiet Annick , Leventhal Brigid G. , Herberman Ronald B.
Published: February 2007

Fifty‐three patients with ALL (acute lymphocytic leukemia), twenty‐five patients with AML (acute myelogenous leukemia), and thirty‐eight healthy persons were tested for cutaneous delayed hypersensitivity with a standard battery of recall antigens and membrane extracts of normal white cells. The leukemic patients were also tested with membrane extracts of autologous and allogeneic blast and remission cells. There was not a significant difference between normals and leukemics in their response to PPD, mumps or SKSD. Positive results were elicited in the leukemia patients by blast cell extracts and not by extracts of remission or normal cells. In both AML and ALL patients, there was a statistically significant difference in the percentage of positive responses to autologous (and in ALL, allogeneic) blast extracts in remission and relapse. Serial responses of patients to autologous blast material were usually related to clinical status, being positive in remission and negative when a patient relapsed. There was a slight increase in remission length for patients who had positive responses to autologous material. A small group of ALL patients on an immunotherapy protocol, receiving BCG and allogeneic blast cells, was studied. There was no increase in incidence of positive reactions to the immunizing or other allogeneic blast cells after being on this protocol as compared with the reactions prior to receiving the cells. On different ALL treatment protocols there were different percentages of positive responses to autologous blast material. The pattern of responses seen in leukemia patients to autologous and allogeneic blast cells as compared with their responses to normal cells, remission cells, and other leukemia type cells provides evidence for cell‐mediated immunity to tumor‐associated antigens on human acute leukemia cells.
Detection by immunofluorescence of intracytoplasmic antigens in cell lines derived from human sarcomas
Authors: Moore M. , Witherow P. J. , Price C. H. G. , Clough Sylvia A.
Published: February 2007

Fourteen cell lines originating from a variety of tumours of human connective tissue including osteosarcoma (6), fibrosarcoma (3), chondrosarcoma (2), rhabdomyosarcoma (1), Ewing's tumour (1) and chordoma (1) were maintained in tissue culture for variable periods ranging from 2 to 48 weeks. During their term in culture, acetone‐fixed monolayers of cells were serially subjected to indirect immunofluorescence (IF) tests using serum from cancer patients and individuals without malignancy, in an attempt to detect intracytoplasmic sarcoma‐associated antigens. Antigen‐positive cells were demonstrated in 10/14 cell lines, although their expression in tissue culture was variable, and cells exhibiting their IF features could not be unequivocally detected in the original tumour specimens. Such cells were present in cultures derived from sarcomas of different type (osteosarcoma, chondrosarcoma, fibrosarcoma, etc.) indicating the cross‐reactive nature of the antigens associated with them. The overall incidence of antibodies reactive with the cell lines in sarcoma patients in various phases of disease was 13/34 (38%) but antibodies were only occasionally detected in the sera of individuals without malignancy or with histologically unrelated neoplasms. Similar antigen‐positive cells could not be identified in 15 tissue cultures of comparable age in vitro originating from normal adult, carcinoma, or embryonic tissue or in seven long‐established cell lines, thereby implying a degree of specificity for sarcoma‐derived cell lines. The nature of the IF+ cells and of the antigen (s) expressed by them is discussed.
Study by the isotopic antiglobulin technique of a cross‐reacting murine antibody produced by immunization with a syngeneic SV40 tumor
Authors: Burdick James F. , Stemple Dale , Wells Samuel A.
Published: February 2007

Tumor line SV‐AL/N, derived from SV40 transformation of an embryonic cell line, was employed to immunize syngeneic mice, and the resultant antisera were investigated with the modified isotopic antiglobulin assay. A single specificity was detected in the antiserum, which reacted strongly with an antigen present on SV40‐transformed lines. However, the antigen was also present on cells derived from the same embryonic line as SV‐AL/N but transformed instead either spontaneously or by polyoma virus. The antigen was present on one non‐transformed syngeneic embryonic line and may have been present in low concentration in a non‐transformed syngeneic fibroblast line; it was not detected in several methylcholanthrene‐induced lines. Antiserum derived from multiple immunizations with irradiated syngeneic fetuses reacted weakly in a similar pattern. The results suggest that the antigen detected is present in the host genome in occult form, and is derepressed by several processes, perhaps including embryogenesis.
Analysis of minimal functions of simian virus 40. I. Oncogenic transformation of Syrian Hamster kidney cells in vitro by photodynamically inactivated SV40
Authors: Seemayer N. H. , Hirai K. , Defendi V.
Published: February 2007

SV40 was photodynamically inactivated in the presence of Toluidine blue 0 by irradiation with white light for different periods of time. Different functions of SV40 were inactivated at different rates. The most sensitive function was the capacity of the virus to replicate followed by the capacity to induce T antigen and cell DNA synthesis. The transformation capacity was the most resistant. No evidence was obtained that the survival of transformation activity after large decrease in infectivity was due to multiplicity reactivation. Syrian hamster kidney cells transformed in vitro by photodynamically inactivated SV40 had the same properties as those transformed by control virus. They showed identical morphology, were T‐antigen positive, contained the same number of SV40 DNA genome equivalents integrated in their DNA and were oncogenic when inoculated into adult hamsters.
A comparison of DNA binding proteins from normal and virus‐transformed mouse cells
Authors: Rubio Victor , Tsai Wen‐Po , Rand Kenneth , Long Cedric
Published: February 2007

Proteins from normal and virally transformed mouse cells, capable of binding to calf thymus DNA, were isolated and compared by DNA cellulose chromatography and sodium dodecyl sulfate polyacrylamide gel electrophoresis. In accordance with previous studies (Salas and Green, 1971; Tsai and Green, 1973), two major proteins, P6 and P8, and two minor proteins, P3 and PS, were found in normal fibroblasts. Extracts prepared from log phase 3T6‐MSV (RLV) synthesized increased amounts of P3, P5, and P6, while SV‐3T3 cells grown under identical conditions showed an increased level of P3 protein. Non‐producer 3T3 cells carrying a defective murine sarcoma virus genome grown under conditions of serum deprivation produced normal levels of P5, P6, and P8 proteins whereas these proteins were present in low amounts in 3T3 cells grown in a similar fashion.
Induction of type C virus‐related functions in normal rat embryo fibroblasts by treatment with 5‐iododeoxyuridine
Authors: Verwoerd Daniel W. , Sarma Padman S.
Published: February 2007

Secondary cultures of rat embryo fibroblasts, derived from six different strains of normal laboratory and wild rats, were treated with 5‐iododeoxyuridine in an attempt to establish the presence of endogenous type C viruses in rat cells. All the cell lines tested responded with a transient appearance of RNA‐dependent DNA polymerase (RDP) activity which reached a peak 3 days after the beginning of treatment. However, no viral particles or rat gs‐antigen could be detected at this stage. In the cells derived from two highly inbred strains, a spontaneous second burst of RDP activity was observed after 10–12 days, and on subculturing these cells a 20‐ to 40‐fold increase of enzyme activity could be obtained. During this peak of activity both gs‐antigen and viral particles capable of incorporating labelled uridine were detected. Electron microscopic examination revealed the presence of complete or immature virions in one cell strain. The virus induced was non‐infective for monolayer cultures of 10 different animal species. Attempts to rescue infective virus by complementation with murine leukemia or sarcoma viruses failed. Prolonged cultivation of treated cultures did yield cells with trasformed morphology, but no oncogenicity could be demonstrated for these cells.
Characterization of guinea‐pig embryo cells transformed by Kirsten mouse sarcoma virus
Authors: Rhim Johng S. , Duh Fuw G. , Cho Han Y. , Huebner R. G.
Published: February 2007

Guinea‐pig embryo cells were transformed in vitro by the Kirsten strain of mouse sarcoma virus (Ki‐MSV). The transformed cells were found to release infectious virus continuously and produced high titers of group‐specific, complement‐fixing antigen characteristic of the murine leukemia—sarcoma virus complex. Foci of transformed cells were similar in appearance to those obtained with Ki‐MSV in mouse and rat cells. The transformed cells produced RNA‐dependent DNA polymerase and type‐C virus particles with a density of approximately 1.15 g/ml in sucrose gradients by 3H‐uridine labelling. The transformed cells from one line produced tumors when transplanted into newborn guinea‐pigs. A number of focus‐derived clonal lines and “normal cells” derived from infected cells were isolated and characterized. All the focus‐derived lines were found to be MSV producers. The Ki‐MSV grown in guinea‐pig cells replicated efficiently in guineapig and NRK cells but very poorly in mouse cells. A non‐cytopathic type‐C virus‐producing line (clone No. 2) was isolated. A non‐focus‐forming virus grown in guinea‐pig embryo cells (clone No. 2) rescued infectious MSV by direct cocultivation with Ki‐MSK non‐producer NRK cells. The rescued MSV virus was neutralized by Ki‐MSV antiserum and produced foci readily in mouse, rat and guinea‐pig cells.
Differentiation of neuroblastoma cells induced in culture by 6‐thioguanine
Authors: Prasad Kedar N.
Published: February 2007

In addition to cell death, 6‐thioguanine (TG) and 6‐mercaptopurine induced neurite formation in mouse neuroblastoma cell culture, whereas 2‐aminopurine had no effect on growth or morphology. 6‐TG was much more potent in causing morphological differentiation than any other agents used in this study. It increased the levels of catechol‐o‐methyltransferase and choline acetyltransferase, but had no significant effect on the tyrosine hydroxylase (TH) activity. 5‐bromodeoxyuridine increased the levels of all three enzymes. 6‐TG produced cell death with very little neurite formation in human neuroblastoma cell culture.
The humoral antibody response to a primary viral neoplasm (MSV) through its entire course in BALB/c mice
Authors: Lamon E. W. , Klein E. , Andersson B. , Fenyö E. M. , Skurzak H. M.
Published: February 2007

BALB/c mice injected with Moloney sarcoma virus developed within 5–12 days tumors at the site of inoculation which usually completely regressed by day 20–25. Maximal tumor size was reached around day 15. Sera from these animals were examined for complement‐dependent cytotoxic activity against Moloney lymphoma cells. The cytotoxic antibody response was biphasic. The first peak was reached at day 10 and extended to day 15 (peak tumor size). Twenty days after virus infection in the early regressor sera, antibody titres fell to normal serum values, followed by a progressive rise which persisted in the long‐term regressors during the entire observation period of 3 to 6 months. Active sera from days 10, 15, 30 and long‐term regressors were pooled separately and fractionated on Sephadex G‐200 into 19S and 7S fractions, and reconcentrated to the original volume. The fractions were then tested for cytotoxic activity. Both 19S and 7S fractions of all pools contained cytotoxic activity. Immunofluorescence analysis of these fractions showed the 7S fractions to be detectable by membrane immunofluorescence but not the 19S. Virus neutralizing activity was found in both 19S and 7S fractions with higher activity in the sera from regressor animals.