Serum factors modifying cell mediated immunity to rat hepatoma D23 correlated with tumour growth

Bowen, J G; Robins, R. A.; Baldwin, Robert

doi:10.1002/ijc.2910150413

Cited by 46 publications

(17 citation statements)

References 27 publications

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“…Sjogren et al (1971) provided evidence that suggested that the blocking factors were antigen-antibody complexes. Bowen, Robins and Baldwin (1975) also demonstrated the presence of blocking antigenantibody complexes in serum obtained from rats bearing the rat hepatoma D23.…”

Section: Discussionmentioning

confidence: 85%

Increased resistance in splenectomized mice to a methylcholanthrene-induced tumour

Chang¹,

Turk²

1977

Br J Cancer

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Summary.-Prior splenectomy increased the resistance of BALB/c mice to a syngeneic methylcholanthrene-induced ascitic tumour inoculated i.p. The survival rate of splenectomized mice was 81-60/ while those of normal and sham-operated controls were 11.5%O and 20% respectively. The effect of splenectomy, however, was seen only within the dose range of 103 to 104 tumour cells. This effect of splenectomy was abolished by the transfer to mice of serum from tumour-bearing mice, and of spleen cells from normal donors, immediately after the inoculation of tumour cells. Cellfree ascitic fluid did not abolish the effect of splenectomy. The findings suggest that there is a subpopulation of spleen cells which produces a tumour growth enhancing factor which is found in the serum of tumour-bearing mice. IN recent years, various investigatorshave shown a renewed interest in the role of the spleen in the immune response to tumours, as the spleen is a relatively rare site for metastases when compared to the rest of the reticulo-endothelial system (Willis, 1973). In vivo experiments to examine the effect of splenectomy on the behaviour of tumours used several different criteria. Thus various workers have examined the effect of splenectomy on (a) the incidence of spontaneously arising tumours (Whitmore, Salerno and Rabstein, 1972; Check et al., 1974); (b) the induction of tumours by chemical carcinogens (Cohen, Headley and Bryan, 1973;Akamatsu, 1975); (c) the incidence of spontaneouis regression of tumours (Pollack, 1971;Ferrer and Mihich, 1968); and (d) the behaviour of transplanted tumours (Moller, 1965; Sjogren, 1973, 1974). The results of these investigations suggest that although splenectomy has no effect on the incidence of spointaneous tumours, or oni the induction of tumours by chemical carcinogens, it reduces the rate of growth of transplanted tumours, and may increase the incidence of spontaneous regression of tumours. However, several criticisms may be made of these reports. The behaviour of transplanted tumours has been followed by measurement of the size of the tumour nodule, a parameter whose significance is difficult to interpret. Furthermore, the effect of splenectomy on the survival of animals with transplanted tumours has not been reported, or has found to be negligible.Using survival as the criterion, we present evidence here that prior splenectomy increases the host resistance to a transplanted tumour. We have also followed the behaviour of the transplanted tumour, by determining the rate of ascites formation and also bv tumour cell counts.

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Section: Discussionmentioning

confidence: 85%

Increased resistance in splenectomized mice to a methylcholanthrene-induced tumour

Chang¹,

Turk²

1977

Br J Cancer

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“…'~J~~~~~~~ High AFP and/or ferritin serum levels of patients with teratomas indicate a poor prognosis.26 Increased levels of circulating antigen or antigen-antibody complexes have been shown to accompany increased tumor progression in animal systems. 2 Synthesis and release of fetal substances comprise one aspect of the inappropriate function of tumor cells compared to normal cells. The recognition of fetal antigens and the study of factors controlling their production and release are of importance in defining the biology both of the fetus and of tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Cea and nca in amniotic fluid of normal and abnormal pregnancies

Gadler¹,

Bremme²,

Wahrén³

et al. 1978

Cancer

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Carcinoembryonic antigen and cross-reacting NCA were demonstrated in 413 amniotic fluid samples representing different stages of pregnancy. Radioimmunoassay of CEA showed a decrease from a mean of 79 ng/ml at 19 weeks to 50 ng/ml near term. NCA, on the other hand, increased slightly from 184 ng/ml at 19 weeks to 219 ng/ml in the terminal part of pregnancy. There was a considerable interindividual variation of both substances at each time period. The NCNCEA quotient increased from 2.5 at 19 weeks to 4.9 at the end of gestation, but the variation precluded its use as a maturation index. The correlations between CEA, NCA, NCNCEA and alpha-fetoprotein levels and the lecithin/ sphingomyelin ratio were studied. The best correlations were found between CEA and NCA levels (r, = 0.52) and between CEA and AFP levels (r, = 0.46). CEA values deviating from the mean 2 2 SD were found in 3 out of 12 samples from fetuses with chromosomal aberrations, and in 3 out of 15 samples from pregnancies with fetuses considered small for date. Two patients with missed abortions both had NCA values outside the normal range. The quotient NCN CEA was lower than expected in two out of four patients with diabetes. Raised AFP levels were found in all ten pregnancies with neural tube defects and in two out of seven patients with chromosomal aberrations.Cancer 42:1579-1584, 1978.ARCINOEMBRYONIC ANTIGEN (CEA), which C is found in and has been characterized from tumors of the gastrointestinal tra~t.~,*,l" has been described to occur in endodermal fetal tissue7 and in amniotic fluid."14 Since a high CEA content can be found in meconiumg and raised values are found in discolored amniotic fluids,5 amniotic CEA may derive mainly from the gut of the fetus. CEA is found in low amounts in the adult gut1' and has been thought to be replaced with nonspecific crossreacting antigen (NCA).13,15 A radioimmunoassay of NCA was therefore used to assess the possible presence of NCA and any variations in this during pregnancy. Alpha-fetoprotein (AFP) has been demonstrated in human fetal liver and yolk sac and is presumably filtered to the amniotic fluid. Raised amniotic AFP is encountered in certain Accepted for publication September 8, 1977. fetal malformations.1~3~21.23.24 In nonpregnant subjects, raised serum values can be seen in tumors of hepatic or germ cell origin.' Fetal proteins are of interest as differentiation products and might therefore be useful as markers of maturity. It was accordingly decided to study the relation between known fetal substances during ontogenesis. Normal values of CEA, NCA and AFP in amniotic fluid at different gestational ages were determined, using specific antisera. Amniotic fluids from abnormal pregnancies were then studied for possible deviations from normal. MATERIALS A N D METHODS Clinical MaterialThe total material consisted of 413 samples collected at the Department of Obstetrics and Gynaecology at the Karolinska Hospital, Stockholm. Of these, 24 were serial samples from 11 patients. Pregnancies were classified as nor...

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“…Under these conditions, significant blocking was found in all animals which developed growing tumours, including both intact and splenectomized animals. Serum from rats bearing D23 tumour has previously been shown to contain factors which can block cytotoxicity when applied to the target cells (Baldwin et al, 1973a;Bowen, Robins and Baldwin, 1975) or to the effector cells (Baldwin et al, 1973b;Bowen et al, 1975). In both situations the blocking effect has been attributed to complexes of tumour antigen and tumour-specific antibody, and inhibition at the effector cell level can also be accomplished by treatment with tumour antigen alone.…”

Section: Discussionmentioning

confidence: 99%

Effect of BCG on cell-mediated cytotoxicity and serum blocking factor during growth of rat hepatoma

Embleton¹

1976

Br J Cancer

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Summary.-Inbred rats were injected s.c. with cells of syngeneic hepatoma D23, D23 cells + BCG as a mixed inoculum, mixed inoculum one side and D23 alone contralaterally, or BCG alone. Their blood mononuclear cells were tested weekly for cytotoxicity against D23 target cells using a microcytotoxicity method and their serum was tested for blocking activity against cytotoxicity by lymph node cells from immunized rats.Tumour growth was suppressed when BCG was in contact with tumour cells but tumours grew unhindered if the BCG was given contralaterally. All rats receiving tumour cells, either alone or mixed with BCG, developed cell-mediated cytotoxicity which remained until termination at 35 days. Rats receiving BCG alone showed slight initial cytotoxicity which disappeared after 7 days. Blocking factors appeared in the serum of rats which developed growing tumours but not in rats whose tumours were suppressed by contact with BCG. Splenectomized rats did not differ markedly from intact rats in the in vitro studies or in vivo.It is concluded that development of cell-mediated immunity and blocking factors depends more upon treatment with tumour cells and the subsequent behaviour of the tumour than upon treatment with BCG per se.

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Serum factors modifying cell mediated immunity to rat hepatoma D23 correlated with tumour growth

Cited by 46 publications

References 27 publications

Increased resistance in splenectomized mice to a methylcholanthrene-induced tumour

Increased resistance in splenectomized mice to a methylcholanthrene-induced tumour

Cea and nca in amniotic fluid of normal and abnormal pregnancies

Effect of BCG on cell-mediated cytotoxicity and serum blocking factor during growth of rat hepatoma

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