bluuebunny/crossref_metadata_2025 huggingface dataset:
Suppressor cell activity of lymphocytes infiltrating human lung and breast tumours
Authors: Vose B. M. , Moore M.
Published: February 2007

Tumour‐infiltrating lymphocytes (TIL) can be isolated from human lung and breast tumours by the stepwise application of velocity and density sedimentations on discontinuous Ficoll‐Triosil or bovine serum gradients. The populations obtained showed variable composition with respect to lymphocyte subsets but generally corresponded to that of peripheral blood lymphocytes (PBL) containing primarily T cells (mean, 49% E rosettes; 15% EA rosettes). Comparison of reactivity to PHA in 15 individuals revealed a significant deficit in reactivity in the TIL population compared with blood and lymph‐node lymphocytes. TIL showed no natural killer (NK) activity, no response to autologous tumour in mixed lymphocyte target interaction tests (MLTI) and no cytotoxicity against autologous tumour, in agreement with previous findings. In order to investigate this depressed reactivity, we measured the effect of admixture of mitomycin‐treated TIL to PBL on PHA and MLTI responsiveness in nine individuals. Eight of these nine showed reduced reactivity to PHA (mean depression of responsiveness, 49%) and five subjects who were responsive to autologous tumour, showed markedly reduced reactivity in the presence of TIL (mean reduction, 65%). In a case of medullary carcinoma of breast it was possible to revover sufficient TIL to allow fractionation on nylon wool columns. Passage through these columns resulted in a higher level of inhibition of PBL reactivity than that seen in unpassed or column‐attached lymphocytes. These data show that TIL have suppressive activity which may account for their poor performance in other assays of effector and memory function.
Rauscher leukemia virus‐induced tumor antigens: Complete separation from gp70, p30 and H‐2
Authors: Alaba Olusola , Rogers M. J. , Law L. W.
Published: February 2007

The possibility that some or all of the viral proteins, gp 70, p 30, and the histocompatibility antigen, H‐2, function as the tumor‐specific transplantation antigen (TSTA) of the R‐MuLV‐induced leukemia, RBL‐5, and also in the secondary in vitro induction of cytotoxic T lymphocytes (CTL), was investigated. The antigen was obtained by isolating the plasma membranes of RBL‐5 cells and solubilizing with sodium deoxycholate (DOC) followed by gel filtration chromatography. A fraction containing excellent tumor‐rejection activity but low amounts of gp 70, p 30 and H‐2 was chromatographed on goat anti‐gp 70 goat anti‐p 30 and sheep anti‐H‐2b immunoaffinity columns. The data obtained indicate that gp 70, p 30 or H‐2 do not function as TSTA of RBL‐5 leukemia, individually or as a complex. Similarly, the antigen responsible for the specific secondary induction of CTL in vitro is distinct from these three proteins.
Clonal analysis of the action of GM‐CSF on the proliferation and differentiation of myelomonocytic leukemic cells
Authors: Metcalf D.
Published: February 2007

With 214 subclones of the BALB/c myelomonocytic leukemia WEHI‐3B, the granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) in impure or purified form, consistently increased the proportion of colonies exhibiting partial or complete differentiation in agar cultures. GM‐CSF also increased colony size and content of daughter colony‐forming cells. Serial recloning of WEHI‐3B colonies in the presence of GM‐CSF showed that when colonies differentiated completely, self‐replication of the colony‐forming cell was suppressed (clonal extinction). However, WEHI‐3B cells exhibited clonal instability and even in the continuous presence of GM‐CSF many colony‐forming cells still generated cells able to form undifferentiated colonies. It appears unlikely that GM‐CSF can completely suppress the progressive proliferation of a myeloid leukemic population of the WEHI‐3B type.
Active, specific immunotherapy of murine leukemia. I. Irradiated tumor cell vaccine
Authors: Bartlett Gerald L. , Kreider John W. , Purnell Dallas M.
Published: February 2007

This report describes a new animal model for active, specific, systemic immunotherapy of leukemia. Mice were challenged (day 0) with 103 viable LSTRA cells and treated later with a vaccine containing 107 irradiated LSTRA cells. Four intraperitoneal or intravenous vaccine injections, on days 2, 9, 16 and 23, caused significant prolongation of survival; single injections by the same routes had inconsistent effects. Vaccine was not effective against a higher initial challenge dose, when given later in the course of tumor growth, when given intradermally or when used in weanling mice. The therapeutic effect was specific since a vaccine composed of an antigenically unrelated leukemia was ineffective. These results suggest that LSTRA is suitable for studying active, systemic, specific immunotherapy.
Augmentation of natural killer activity by pyran copolymer in mice
Authors: Santoni Angela , Puccetti Paolo , Riccardi Carlo , Herberman Ronald B. , Bonmassar Enzo
Published: February 2007

Treatment of older mice with pyran copolymer, a known interferon‐inducer, was found to result in a rapid boosting of cell‐mediated cytolytic activity against YAC‐1 tumor target cells. The effector cells were characterized as being non‐adherent and were presumed to be natural killer (NK) cells. Augmentation occurred in various lymphoid organs and was detectable 2–3 days after drug treatment. Differences in the levels of boosted activity among the lymphoid organs resulted when the route of administration was varied. The degree of augmentation was largely independent of the dose of pyran, but did vary among different strains of mice. Augmentation, moreover, was followed by a rapid decline by 5–7 days.
Characteristics and genetic control of NK‐cell‐mediated cytotoxicity activated by naturally acquired infection in the mouse
Authors: Clark Edward A. , Russell Peter H. , Egghart Margrit , Horton Michael A.
Published: February 2007

Most and perhaps all natural‐cell‐mediated cytotoxicity (NCMC) may be activated by a response to exogenous infections. Specific‐pathogen‐free (SPF) mice have little or no natural killer (NK) cell activity, but when they are relocated in conventional conditions, they develop strong NCMC within 2 to 3 days. Unlike other SPF animals, hypothymic nude mice display good NCMC which is further augmented upon their entry into a pathogenic environment. The ontogeny, genetic control and other features of pathogen‐activated NCMC resemble those previously described for NK cells. An H2‐D region NCMC regulatory gene is active in either a homozygous or heterozygous state, but to be operative seems to require the presence of an additional complementing locus, which maps outside the H‐2 complex. It is proposed that H‐2 influences NCMC levels by affecting the expression or immunogenicity of NK cell‐activating determinants. Recently activated NK cells were non‐adherent and lacked la and Thy‐1 determinants. NCMC was not affected by treatment with monoclonal high‐titer Thy‐1.2 antisera and complement. However, an Ly‐6.2 antiserum did contain anti‐NK cytotoxic activity, which was shown by absorption analysis to be distinct from anti‐Ly‐6.2 activity. The NK antigen has a strain distribution pattern distinct from Ly‐5 and other Ly markers, but may be related or identical to NK‐1.
Enhancement of feline leukemia virus‐induced leukemogenesis in cats exposed to methylnitrosourea
Authors: Schaller J. P. , Mathes L. E. , Hoover E. A. , Olsen R. G.
Published: February 2007

The effect of methylnitrosourea (MNU), a potent resorptive carcinogen, was evaluated for its influence on the susceptibility of adult cats to infection and induction of oncornavirus disease by feline leukemia virus (FeLV). Young adult cats at an age previously demonstrated to be highly resistant to FeLV, were injected intravenously with moderately toxic doses (15–20 mg/kg) of MNU alone or with infectious FeLV (Rickard strain). Following exposure to virus and chemical, cats were monitored for antibody to the feline oncornavirus‐associated cell membrane antigen (FOCMA), viremia by direct infectivity and the presence of gsa in peripheral blood leukocytes, and for toxic effects of MNU by hemogram analyses on peripheral blood. Of 8 cats injected with MNU+FeLV, 6 developed persistent viremia, 5 of which became debilitated from thymic lymphoma. Only 1 of 6 non‐MNU‐treated and infected cats of the same age became transiently viremic. FOCMA antibody development was markedly depressed in MNU+FeLV inoculated cats compared with cats inoculated with FeLV alone. Results show that MNU was apparently responsible for the obliteration of age‐related susceptibility in cats to FeLV infection and induction of FeLV‐related disease, and suggest that in nature exposure to toxic chemical carcinogens may act as factors which determine susceptibility to feline oncornaviruses in the cat.
Content and distribution of macrophages and lymphocytes in solid malignant human tumours
Authors: Svennevig Jan‐L. , Svaar Helge
Published: February 2007

The relative content of lymphocytes and macrophages was studied in 20 solid malignant human tumours. Mechanically prepared tumour‐cell suspensions contained both lymphocytes (0.2–4.0%) and macrophages (0.2–7.0%). Macrophages were characterized as esterase‐positive, phagocytosing cells. The distribution of the cells within the tumours was studied on cryostat sections. A modified esterase method, using α‐naphthyl butyrate as substrate, always gave an intensive staining of tissue‐infiltrating macrophages, even in malignant tissues where some neoplastic cells exhibited a weak to moderate esterase activity. Tumour‐infiltrating lymphocytes were studied in HE‐stained tissue sections. The study demonstrates that both cell types were usually more numerous in the stroma surrounding the tumour tissue and in the stromal septa between the cords of malignant cells (peripheral infiltration) than in the central areas of the tumours. No signs of cell necrosis were seen near the lymphocyte zones or the stromal macrophages; however, some central necrotic areas contained aggregates of macrophages, lymphocytes and PMN.
Is SP1 (pregnancy specific β1 glycoprotein) elevated in cancer patients?
Authors: Engvall E. , Yonemoto R. H.
Published: February 2007

Pregnancy‐specific β1‐glycoprotein, SP1, was measured in serum by competitive double antibody radioimmunoassay. Very low levels of SP1 or SP1‐like activity were found in only 2 out of 85 sera from patients with cancer of the digestive tract, breast cancer, melanoma, and sarcoma, in 2 out of 11 sera from patients with infectious diseases, and in none out of 15 sera from non‐pregnant healthy individuals. SP1 thus does not seem to be ectopically produced in vivo by the types of cancer studied, but is probably highly specific for the normal and malignant trophoblast.
Comparative tumor‐inhibitory and anti‐bacterial activity of soluble and particulate glucan
Authors: di Luzio N. R. , Williams D. L. , McNamee R. B. , Edwards B. F. , Kitahama Akio
Published: February 2007

A soluble fraction of particulate glucan was prepared and evaluated for its anti‐tumor and anti‐bacterial activity. Thin‐layer chromatographic analysis indicated that the soluble preparation was composed of a variety of polyglucoses. Intravenous administration of soluble or particulate glucan resulted in significant reductions in the growth of a syngeneic anaplastic mammary carcinoma and melanoma B16. Survival data demonstrated that intravenous administration of soluble or particulate glucan prolonged survival of A/J and C57BL/6J mice with subcutaneous tumor implants. As regards to bacterial infections, soluble and particulate glucan decreased renal necrosis in S. aureus challenged mice as compared to control mice. Although the exact nature of the active soluble fraction(s) of glucan remains to be delineated, these studies demonstrate that a soluble glucan preparation exhibits significant anti‐tumor and anti‐staphylococcal activity. The active soluble fraction of particulate glucan may be preferable to particulate glucan in view of the inherent ease of parenteral administration.
Immunotherapy of an ascitic rat hepatoma with cord factor (trehalose‐6, 6′‐dimycolate) and synthetic analogues
Authors: Pimm Malcolm V. , Baldwin Robert W. , Polonsky Judith , Lederer Edgar
Published: February 2007

The ability of cord factor (trehalose‐6, 6′‐dimycolate) and a range of shorter carbon chain fatty acid trehalose diesters to suppress growth of an ascitic rat hepatoma has been examined and compared with that of whole, living BCG organisms. Aqueous suspensions of BCG, and cord factor in 0.4% arachis oil:Triton emulsion, injected intra‐peritoneally, retarded growth of up to 105 ascites tumour cells. Trehalose‐6, 6′‐dibehenate was also tumour‐suppressive, but only against lower challenge inocula (104 cells). Trehalose‐6, 6′‐dipalmitate and 6,6′‐di‐0–2‐tetradecyl ‐3‐hydroxyoctadecanoyl β,β trehalose (designated C76) were virtually ineffective and 6,6′ ‐di‐0–2‐eicosyl‐3‐hydroxy‐tetracosanoyl β, β trehalose (designated C100) gave small and variable effects only against low challenge inocula. However, improved responses were seen with light mineral oil in place of arachis oil in the emulsions.
Immunological basis for differences in susceptibility to hydrocarbon oncogenesis among mice of a single genotype
Authors: Prehn Richmond T.
Published: February 2007

The tendency for tumor induction to occur preferentially in certain individual mice of an inbred strain vanished when the putative immune response was reduced either by radiation plus thymectomy or by reduction of the concentration of the chemical oncogen.
Membrane dynamic alteration associated with the tumorigenicity of polyoma‐transformed and revertant hamster cells
Authors: Parola A. H. , Souroujon M.
Published: February 2007

Steady state fluorescence polarization studies were carried out on membranes of polyoma‐virus‐transformed, revertants, re‐revertants, and normal golden hamster cells. Four clones of revertant cells which exhibit different levels of reversion were isolated. The degree of reversion in these revertant clones was characterized in vitro by their contact inhibition behavior and in vivo by their tumorigenicity to hamsters. A good correlation between these two criteria was observed. Re‐revertant cells were obtained from that revertant clone which exhibited the highest degree of reversion (similar to normal cells) and which could still produce tumors in hamsters. Re‐revertants resembled the polyoma‐virus‐transformed cells in both contact inhibition and tumorigenicity. Fluorescence polarization values of 1,6‐diphenyl‐1,3,5‐hexatriene‐labelled cells correlated well with cell tumorigenicity: normal and revertant cells which were not malignant exhibited distinctly lower fluorescence polarization values than those of the tumorigenic transformed and re‐revertant cells. Intermediary revertant clones exhibited fluorescence polarization values in between those of normal and transformed cells, yet indistinguishable within experimental uncertainty.
Activation of mouse macrophages by pyran copolymer and role in augmentation of natural killer activity
Authors: Puccetti Paolo , Santoni Angela , Riccardi Carlo , Holden Howard T. , Herberman Ronald B.
Published: February 2007

Inoculation of mice with pyran copolymer resulted in activation of natural killer (NK) cells as well as macrophages. Conditions optimal for the boosting of NK activity seemed to differ from those optimal for macrophage activation as assessed by cytostasis of tumor target cells. Peak levels of macrophage cytostatic reactivity were found at about 7 days after drug injection and were only achieved by the highest doses of pyran tested. Macrophage activation was consistently higher in the peritoneal cavity than in the spleen, regardless of route of administration, in contrast to the failure of i.v. pyran to induce high NK reactivity in peritoneal exudate cells. At 2–3 days after pyran treatment of older mice, NK augmentation reached peak levels, but only minimal macrophage activation was found. Despite these differences, macrophages played a role in regulating NK activity in pyran‐treated mice. Functional macrophages appeared to be required for augmentation of NK activity by pyran, since boosting was impaired by prior in vivo inoculation of silica. Macrophages also appeared able to inhibit NK activity. In younger mice that exhibited high spontaneous levels of NK activity, pyran treatment produced a substantial reduction in NK activity to levels below those of untreated mice. This depression coincided with the time of peak levels of macrophage cytostasis. Furthermore, removal of adherent cells from the spleen cells of these pyran‐treated mice resulted in levels of NK activity almost as high as those of untreated mice. The possibility that the depression of NK activity in young mice by pyran copolymer is due to suppressor cells is discussed.
Cytotoxicity in vitro of blood lymphocytes from bladder cancer patients and controls to allogeneic or autologous tumor cells derived from established cell lines or short‐term cultures
Authors: Troye M. , Vilien M. , Pape G. R. , Perlmann P.
Published: February 2007

Blood lymphocytes from small groups of patients with transitional‐cell carcinoma of the urinary bladder (TCC), clinical controls (CC) or healthy donors (HD) were tested for cytotoxicity in vitro by a 51Cr‐release assay. The target cells were either from TCC or control tissue (long‐term cultures) or were from short‐term TCC cultures, kept in vitro for 10–20 transfer generations. When tested with allogeneic target cells from long‐term cultures, TCC patients' lymphocytes tended to be more cytotoxic to TCC targets than to control targets. For the control lymphocytes this was not seen. A large proportion but not all of the cytotoxicity to these target cells was due to immunoglobulin‐depen‐dent cellular reactions, probably mediated by natural and disease‐related antibodies of the lymphocyte donors, since it was significantly inhibited by Fab‐fragments of rabbit antibodies to human immunoglobulin. Moreover, it was, to a large extent, mediated by lymphocytes with Fc‐receptors for IgG. For seven of the TCC target cell cultures (two long‐term and five short‐term) autologous lymphocytes were also available for testing. While two patients were non‐reactive to their own tumor cells, five reacted strongly in the autologous combinations. These autologous reactions were immunoglobulin‐independent and were mediated by Fc‐receptor‐negative effector cells. In some instances, autologous cytotoxicity was accompanied by similar reactions to some of the allogeneic TCC targets but not to the allogeneic non‐TCC control targets. On the basis of available information on HLA antigens in this material, the pattern of cross‐reactions suggests that the cytotoxicity encountered in the autologous and in some of the allogeneic TCC‐combinations may be the expression of antibody‐independent but specific CTL‐mediated reactions, regulated by HLA. However, at the present stage of the investigation, other mechanisms must also be considered since the target cells from short‐term TCC cultures were sometimes lysed by control lymphocytes in irnmunoglobulin‐independent reactions. Whatever the explanation, the results show that the cytotoxicity observed in the in vitro systems is usually the net result of several different types of reaction. Which effector cell types and which mechanism of recognition will predominate in a given lymphocyte/target cell combination is greatly influenced by the nature and origin of the target cells used.
AG‐4 complement‐fixing antibodies in cervical cancer and herpes‐infected patients using local herpes simplex virus type 2
Authors: Arsenakis M. , Georgiou G. M. , Welsh J. K. , Cauchi M. N. , May J. T.
Published: February 2007

The incidence of anti‐AG‐4 complement‐fixing antibodies in Australian cervical carcinoma (CaCx), herpes simplex virus (HSV) type 1 and 2, and control patients, was investigated using local HSV strains. The local HSV strains (both HSV‐1Ml and HSV‐2Ml) were found, by neutralization experiments, to vary from the American prototype strains. All HSV‐2 strains tested were able to induce AG‐4 in 4‐h infected HEp‐2 cells. Anti‐AG‐4 complement‐fixing antibodies were detected in 40% of dysplasia patients, 60% of carcinoma‐in‐situ patients, 75% of CaCx patients, 65% of CaCx post‐operative patients, 88% of HSV‐2 patients with active lesions, 10% of HSV‐1 patients with active lesions, 10–20% of normal patients and 20% of patients with cancer, other than CaCx. The AG‐4 test is tumour‐specific in that it distinguishes CaCx from other cancer patients tested, but it cannot distinguish HSV‐2 patients from CaCx patients.
Activated T lymphocytes in infiltrates and draining lymph nodes of nasopharyngeal carcinoma
Authors: Galili Uri , Klein Eva , Klein George , Bal Inderjit Singh
Published: February 2007

Lymphocytes isolated from the tumors and draining lymph nodes of nasopharyngeal carcinoma (NPC) patients exhibit the following characteristics of immune activation: (1) stable E rosette formation, (2) natural attachment to various human cells, (3) sensitivity in vitro to the lytic effect of glucocorticoids. Although the NPC T cells attach in vitroto various cells they kill only EBV‐genome‐carrying targets. These findings suggest the occurrence of a local cellular immune response in NPC, possibly directed to EBV‐determined antigens.
Malignant melanoma in Connecticut and Denmark
Authors: Houghton Alan , Flannery John , Viola Michael V.
Published: February 2007

The rising incidence of malignant melanoma of the skin was reviewed using data from the Connecticut Tumor Registry (1935–1974) (Eisenberg et al., 1967) and the Danish Cancer Registry (1943–1972) (Clemmesen, 1965, 1974, 1977). A total of 7,530 cases were analyzed according to age, sex and anatomic site. The total age‐adjusted incidence rates were similar for these two countries, despite geographic and demographic differences. However, the most rapid changes in melanoma incidence were observed in females from Denmark and males from Connecticut. In addition, the largest increases occurred for lower‐extremity lesions in Danish middle‐aged women and trunk‐neck melanomas in Connecticut middle‐aged men. Melanoma of the face was resistant to changing incidence and occurred in an older age group than melanoma of other skin sites. In general, birth cohort analysis confirmed that changing incidence began for persons born around 1900, but the rising incidence for lower‐extremity melanomas in women and trunk‐neck melanomas in males began earlier. In comparing incidence for anatomic sites by correcting for surface area and melanocyte density, higher than expected rates were seen for melanoma of the face in both sexes and trunk‐neck melanomas in males. The data presented support the concept that a cumulative exposure to solar radiation may be important in the etiology of melanoma of the face, but short, intense sun exposure is probably related to melanoma in other sun‐exposed areas, and that melanoma in areas other than the face is responsible for the rising incidence of this disease.
Comparison of cytosol estrogen and progestin receptor status in malignant and benign tumors and tumor‐like lesions of human ovary
Authors: Jánne O. , Kauppila A. , Syrjálá P. , Vihko R.
Published: February 2007

Some human ovarian malignancies respond favorably to hormone therapy. In order to obtain more information about the endocrine properties of these malignancies, we measured estrogen (ER) and progestin (PR) receptors in 21 malignant ovarian tumors, and compared the findings with those in 29 benign tumors and 28 tumor‐like ovarian lesions. There were marked differences in steroid receptor distributions between the three groups. Only 38% of the malignant tumors simultaneously contained measurable amounts of both receptors, whereas the corresponding figure was 76% for the benign tumors. Malignant tumors were more often (29%) receptor‐negative than the benign ones (7%). The major difference in the tumor‐like lesions was the high frequency (43%) of samples containing PR only, as compared with the two other groups. The respective concentrations (fmol/mg cytosol protein, mean ± SEM) of ER and PR were 114 ± 42 and 148 ± 76 (malignant tumors), 71 ± 34 and 132 ± 32 (benign tumors) and 19 ± 16 and 251 ± 88 (tumor‐like lesions). Of the malignant tumors, endometrioid carcinoma was characterized by a relatively high mean PR content (330 ± 262), whereas in undifferentiated carcinoma a high ER content (149 ± 97) was associated with a low PR concentration (26 ± 15). Steroid receptor content was very similar in benign epithelial tumors with different histological properties. The two main groups of tumor‐like lesions, endometriosis and luteal cysts, typically contained little or no ER and a relatively high amount of PR. Hormone dependency of malignant and benign ovarian tumors and tumor‐like lesions does not seem similar. These data support the notion that receptor determinations from malignant ovarian tumors could aid in selection of patients for endocrine therapy in a manner similar to that already established for certain other hormone‐dependent cancers.
Cancer and other causes of death among U.S. veterinarians, 1966–1977
Authors: Blair Aaron , Hayes Howard M.
Published: February 2007

Causes of death among 1,551 white male veterinarians identified from obituary listings in the Journal of the American Veterinary Medical Association were compared to an expected distribution based on the general US population. The proportion of deaths was significantly high for particular neoplasms, especially leukemia and Hodgkin's disease, and cancers of the brain and skin. Although socioeconomic and methodologic factors may be involved, the excesses were primarily among veterinarians in clinical practice, raising the possibility that specific occupational exposures may be carcinogenic. Mortality was also relatively high for motor vehicle accidents, suicides and asthma, but low for lung cancer and other diseases of the respiratory system.
Clonal extinction of myelomonocytic leukemic cells by serum from mice injected with endotoxin
Authors: Metcalf D.
Published: February 2007

Culture of WEHI‐3B myelomonocytic leukemic cells in semi‐solid agar medium containing post‐endotoxin serum led to the development of maturing granulocytes and macrophages in most leukemic colonies. Colony size was consistently increased but the colony content of colony‐forming cells (stem‐cell self‐replication) was markedly reduced. Serial recloning of WEHI‐3B colony cells in the continuous presence of post‐endotoxin serum led to clonal extinction of the leukemic cells in five of seven experiments. These effects of post‐endotoxin serum on WEHI‐3B cells were not seen in clonal cultures of 10 other tumor lines. Serum with the capacity to induce differentiation in WEHI‐3B cells could be induced by the injection of as little as 0.1 μg endotoxin and by purified bacterial cell‐wall preparations. Serum activity reached peak levels 3 – 6 h after endotoxin injection and returned to preinjection levels within 48 h.
Evaluation of the immunocompetence of macrophages and the generation of T‐cell‐mediated cytotoxic response against allogeneic tumor cells in tumor bearers
Authors: Ting Chou‐Chik , Rodrigues Dennis
Published: February 2007

The present study has examined the competence of peritoneal cells (PC) of tumor bearers to reverse the immunosuppressive effect of tumor cells, and the ability of the tumor bearers to generate a T‐cell‐mediated cytotoxic response against allogeneic spleen cells or allogeneic tumor cells. It was found that PC from tumor bearers possess a greater ability to reverse the tumor cell immunosuppression in normal mice. In contrast to normal hosts, the cytotoxic responses of the tumor bearers against allogeneic tumor cells cannot be restored by PC from normal mice or from tumor bearers. The ineffective cytotoxic response in tumor bearers was not due to deficient T responders or T helpers. Rather, it was due to the presence of suppressor cells which were adherent, radioresistant and resistant to anti‐Thy‐1.2 antibody lysis, and thus were likely to be macrophages. The suppressor macrophages were present only in the spleen and were absent from the peritoneal cavity of the tumor bearers. Their suppressive effect can only be exerted in the presence of tumor cells. These results demonstrate the dichotomy of macrophage function, peritoneal macrophages from the tumor bearers showing increased activity of augmentation of T‐cell‐response whereas the splenic macrophages cause suppression of the T‐cell‐response.
Changes in tumor‐specific antigen expression during passage in vitro and in vivo of newly derived methylcholanthrene‐induced sarcomas of BALB/c mice
Authors: Law Lloyd W.
Published: February 2007

The characteristics of tumor antigens of the transplantation type, TATA, were studied in a series of methylcholanthrene‐induced sarcomas in pedigreed BALB/cAN mice. Each of the six sarcomas exhibited unique TATA when assayed for tumor rejection in syngeneic hosts. In three instances, however, in sarcomas CI‐1, CII‐5 and CII‐7, TATA activity was lost during early in vivo passages. This activity was reestablished in vivo from the in vitro‐passaged lines in CI‐1 and CII‐7 and these sarcomas along with CI‐3, CI‐4 and CII‐10 maintained a stable TATA phenotype throughout the 50 transplant passages; TATA was lost permanently, however, in CII‐5. These results indicate a dimorphic nature of early‐passage neoplasms. No crossreacting antigens were detected among these sarcomas, including also Meth A, a sarcoma well characterized as to its membrane antigens; nor was any evidence obtained for the existence of alien (inappropriate) H‐2 antigens employing tumor rejection assays in F1 hybrids of BALB/c with strains bearing several haplotypes and also with studies of H‐2 serology. In three sarcomas, some evidence was obtained for the existence of alloantigens of the non‐H‐2 type since it was found that (BALB/cXDBA/2)F1 hybrids could not be immunized by the respective sarcomas. These findings suggest the existence on these sarcomas of a tumor antigen that is expressed normally in DBA/2 mice, although no definitive evidence has been otained. Assays for MuLV, for the viral structural proteins gp70 and p30 and for reverse transcriptase showed that three sarcomas were positive and three others, as well as Meth A, were negative. MuLV and its antigens had no influence on tumor rejection activity nor could the cross‐reactivity observed in the radioisotopic footpad assay (IFP) be related to MuLV.
Age‐ and tumor‐correlated changes in functional antibody responses to MTV in neonatally infected mice
Authors: Blair Phyllis B. , Lane Mary‐Ann
Published: February 2007

BALB/cfC3H female mice (neonatally infected with MTV) possess several different specific antibody activities measured functionally by reactivity with MTV‐associated antigens expressed on the surface of isologous MTV‐induced mammary tumor target cells. All females when young develop serum antibody which can block specific T‐cell cytotoxic activity of BALB/cfC3H spleen cells; this activity remains detectable throughout life. In addition, recruiting antibody is found in the postweaning stage. This recruiting activity is apparently directed against the same antigenicity as the blocking activity; it can be detected only rarely in whole serum but is revealed in the 19S fraction when the competing blocking antibodies are sequestered into the 7S fraction. In mid‐adult life, 19S recruiting activity is found in only a few of the females; the incidence increases as the females age, and it occurs earlier in those females which subsequently develop mammary tumors. A third antibody activity of serum is blocking factor directed against different MTV‐associated tumor‐cell‐surface antigenicity; this blocks the antibody‐dependent cell‐mediated cytotoxicity characteristic of spleen cells from BALB/c females horizontally exposed to MTV‐associated antigenicity. This blocking activity of serum is not found in young females, and in the older females it is more frequent in those which develop mammary tumors.
Significance of particle size of benzo(a)pyrene for the induction of respiratory tract tumours in hamsters
Authors: Feron V. J. , van den Heuvel P. D. , Koéter H. B. W. M. , Beems R. B.
Published: February 2007

To study the role of particle size of benzo (a) pyrene (BP) in the induction of respiratory tract tumours, goups of hamsters were given 52 weekly intratracheal instillations of fine (77% < 5.2 μm; 3% < 1.3 μan) or coarse (77 y 42 μm; 0% < 10 μm) BP particles suspended in gelatin‐0.9% NaCl solution. Both the fine and coarse particles were given at two different dose levels, viz., 0.5 and 1.0 mg BP/instillation. Another group of hamsters received 52 weekly intratracheal instillations each consisting of 1.0 mg BP particles of a wide size range (90% y 50 μm; 3% < 5.0 μm) suspended in 0.9% NaCl solution without gelatin. The retention of BP in the respiratory tract was studied in separate groups of hamsters receiving a single instillation of BP particles of the different size ranges. Coarse BP particles cleared less rapidly from the lungs and induced a much stronger tumour response in the respiratory tract than did fine BP particles. These findings demonstrated the crucial significance of particle size for the effectiveness of BP as a respiratory tract carcinogen. No appreciable differences in site of tumour formation were observed between treatment with fine and coarse BP particles, which led to the conclusion that the size of the particles did not play an important role in determining the location of the induced respiratory tract tumours. The elimination rate of the BP particles with a wide size range appeared to be in between those of the fine and the coarse particles. The tumour response found after administration of the BP particles of wide size range was very similar to that obtained with the high dose of coarse BP particles.
Epidemiology of pre‐invasive and invasive malignant melanoma in Western Australia
Authors: Holman C. D. J. , Mulroney C. D. , Armstrong B. K.
Published: February 2007

The annual incidence rates of melanoma in Western Australia in 1975 and 1976 were estimated, by reference to hospital and pathology records. They were 4.4/ 100,000 in males and 6.2/100,000 in females for pre‐invasive lesions and 18.6/100,000 and 18.8/100,000 for invasive lesions. Rates specific to particular body sites showed two distinct patterns of change with age ‐ a progressive rise beginning about age 40 years (shown by Hutchinson's melanotic freckle and invasive melanoma of the head and neck) and an early rise beginning about age 20 years with a peak in middle‐life and subsequent stabilization or decline (shown by superficial spreading melanoma, non‐invasive and invasive melanoma of the lower limbs and, less typically, trunk and upper limbs). Incidence rates were highest in native‐born Australians and higher in immigrants of British origin than in other immigrants. The rates in British immigrants were more than double those in the British Isles. The incidence was highest in residents of high social class areas, and in in‐door rather than outdoor workers. Rates were also highest in the capital city, Perth, and the south‐west corner of the State, rather than in the north where exposure of the population to ultra‐violet light might be expected to be highest. In most of these respects the patterns for pre‐invasive and invasive lesions were similar. Aspects of these data are inconsistent with the solar hypothesis of melanoma aetiology. It is suggested, however, that some of these inconsistencies may be explained if intermittent, intense exposure to the sun were more relevant to the aetiology of melanoma than continuous exposure.
Somatic cell hybrids producing antibodies specific to human fibronectin
Authors: Zardi Luciano , Carnemolla Barbara , Siri Annalisa , Santi Leonardo , Accolla Roberto S.
Published: February 2007

We have produced somatic cell hybrids between mouse plasmocytoma cells deficient in hypoxanthine phosphoribosyltransferase (P3 × 63 Ag8) and spleen cells derived from mice immunized with purified human plasma fibronectin. We report herein the properties of monoclonal anti‐fibronectin antibodies released by eight different clones.
Augmentation of cell‐mediated cytotoxicity to a rat lymphoma. III. In vitro stimulation of natural killer cells by a soluble factor
Authors: Shellam G. R. , Winterbourn V. , Dawkins H. J. S.
Published: February 2007

The in vitro cytotoxicity of rat natural killer cells was augmented by the incubation of normal spleen cells with a soluble factor derived from the 24‐h culture of spleen cells and various tumour cells. Cytotoxicity was augmented approximately 4‐, 3‐ or 2‐fold depending on whether the spleen cells were incubated with the factor for 18 or 3 h or during the course of the cytotoxicity assay respectively. The factor was produced in cultures containing syngeneic, allogeneic or xenogeneic tumours and no correlation was observed between the ability of tumour cells to induce the production of the factor and their susceptibility to lysis in the 4‐h cytotoxicity assay. The factor was produced in cultures of spleen cells of several rat strains, and it stimulated the cytotoxicity of syngeneic and allogeneic spleen cells. The cells responsive to stimulation closely resembled NK cells of normal rats. Culture supernatants containing the stimulatory factor possessed anti‐viral activity, and evidence suggested that NK cells were stimulated by a factor resembling a type‐1 interferon. The relevance of these findings to the stimulation of NK cells by tumours in vivo is discussed.
Embryo‐derived teratocarcinoma II. Teratocarcinogenesis depends on the type of embryonic graft
Authors: Solter Davor , Dominis Mara , Damjanov Ivan
Published: February 2007

Early post‐implantation mouse embryos or their embryonic and extraembryonic portions were transplanted under the kidney capsule of adult isogenic recipients in order to test the tumor‐producing potential of various grafts and to establish the optimal conditions for teratocarcinoma production. The highest yield of malignant tumors was obtained from 7‐day embryos transplanted in toto. Severing the extraembryonic portion of 7‐day egg cylinders prior to transplantation of the embryonic part reduced the number of teratocarcinomas to values comparable with those obtained from transplanted 6‐day embryos. The extraembryonic portion of 7‐day embryos produced no tumors. These data suggest that extraembryonic portions of the 7‐day egg cylinder do not have tumorigenic potential alone, but may increase the yield of teratocarcinomas from the embryonic portion of the egg cylinder.
Enrichment of suppressor cell activity by hydrocortisone: Suppression of in vitro activation of splenocytes from mice bearing lewis lung carcinoma
Authors: Clerici Enrico , Schechter Bilha , Feldman Michael
Published: February 2007

Suppressor cells in spleens of mice bearing the Lewis lung carcinoma (3LL) suppressed the anti‐tumor immune response in vivo but not in vitro. The hydrocortisone (HC)‐resistant fraction of spleen cells from tumor‐bearing mice (TBM) was, on the other hand, suppressive in vitro, due to enrichment for HC‐resistant suppressor cells. This cellular fraction suppressed the tumor‐induced differentiation of memory cells as well as the tumor‐independent in vitro activation of TBM spleen cells. The in vitro lymphoproliferative response of TBM spleen cells to mitogens was also subjected to suppression: these cells showed a lower response to a mitogen such as Concanavalin A (Con A) and were capable of suppressing the response of normal spleen cells to this mitogen. HC treatment of TBM 2 days prior to spleen harvest enriched the splenic population for suppressor cells that suppressed Con A‐induced activation.
Selection for virulence and organ‐specific metastasis of herpesvirus‐transformed lymphoma cells
Authors: Shearman P. J. , Longenecker B. M.
Published: February 2007

The Marek's Disease virus‐transformed, non‐producer, lymphoma cell line, MDCC‐RP1, was selected by sequential transplantation to produce a highly malignant variant, MDCC‐AL1. This is evidenced by an 18‐fold decrease in LD50‐. The new cell line has an increased ability to form metastatic lesions in a distribution which mimics the natural disease. Further selections for organ‐specific metastasis were undertaken with the isolation of two cell lines, MDCC‐AL2, selected for liver metastasis, and MDCC‐AL3, selected for ovary metastasis. In vivo studies show that the selection was unsuccessful in the case of the ovary but successful in the case of the liver. Two assays were developed, utilizing the chick embryo and intravenous injection of lymphoma variants. One measures liver‐specific metastasis by the enumeration of tumour foci on the embryonic liver. The second, chorioallantoic membrane (CAM) focus formation, correlates with the virulence of the injected lymphoma cells. The liver‐selected tumour variant cells form more liver foci than any other tumour variant cells. The genetic background of the embryo does not affect formation of liver foci. Resistance to CAM focus formation correlates with major histocompatibility complex associated resistance to MD.
Effect of lentinan on tumor growth in murine allogeneic and syngeneic hosts
Authors: Zákány József , Chihara Goro , Fachet József
Published: February 2007

The effect of lentinan on retardation and regression of transplanted tumors was analysed in allogeneic and syngeneic tumor‐host systems. The effect of lentinan treatment was most variable in random‐bred Swiss albino mice bearing sarcoma 180. With inbred host strains, it was most effective in A/Ph and less, or not at all, in others (A.BY, A.CA, A.SW, DBA/2, BALB/c, C3H/Di, AKR, B10, B10.A, B10. BR, B10.D2). Inorder to eliminate the allogeneic differences, a syngeneic transplantable 3‐methylcholanthrene‐induced sarcoma (A/Ph.MC.SI) has been developed in the A/Ph strain, previously found to be the most responsive to lentinan. The growth of this sarcoma was dramatically inhibited and regression was detected in all lentinan‐treated syngeneic recipients. Both the lentinan‐treated and untreated regressor animals exhibited a high degree of resistance to a secondary challenge. However, the growth of a spontaneous, transplantable syngeneic adenocarcinoma in A/Ph mice was not influenced by lentinan treatment. The results presented substantiate further the conclusion that the effect of lentinan is mediated through host mechanisms, and show that these mechanisms are able to act against a syngeneic tumor.
Quantification of mouse mammary tumor virus structural proteins in hormone‐induced mammary tumors of low mammary tumor mouse strains
Authors: Nüsse R. , Michalides R. , Boot L. M. , Röpcke G.
Published: February 2007

The expression of the mouse mammary tumor virus (MMTV) in hormone‐induced mammary tumors was investigated by means of a radioimmunoassay for two major MMTV proteins, gp52 and p27. MMTV proteins were isolated on lectin affinity‐ and ion‐exchange chromatography columns. The purified viral proteins were electrophoretically homogeneous and retained immunoreactivity after labelling with 125iodine. Standard competition assays showed that group‐specific antigenic determinants were reacting. Mammary tumors were induced in three strains of mice with a low natural incidence of mammary tumors, C57BL, 020 and C3Hf, by a combined hormone treatment, consisting of hypophyseal isografts and administration of progesterone and estrone. Mammary tumors and mammary glands of hormone‐treated animals were extracted and used for competition radioimmunoassays. In general, the tumorigenic hormone treatment resulted in enhanced amounts of MMTV proteins in the mammary glands, compared to the amounts found in lactating mammary glands of untreated animals. The levels of MMTV proteins in the mammary tumors were lower than in the mammary glands.
Surgical adjuvant chemotherapy of metastatic murine osteosarcoma
Authors: Hiramoto R. N. , Ghanta V. K.
Published: February 2007

A C3H murine osteosarcoma was used to investigate the effects of surgical adjuvant chemotherapy and to establish the relationship between primary tumor size and the number of metastatic lung tumor foci. The transplanted primary tumor was allowed to grow for 28 or 33 days and the lungs were monitored for microscopic colonies. Animals whose tumors were left in situ had 6–124 and 32–338 colonies in the lungs at 28 and 33 days, respectively. When the primary tumor was excised on day 10 post implantation, metastatic tumor colonies on day 33 were reduced to 0–24 colonies. The results indicated that the longer the primary tumor was left in the host the greater was the number of tumor cells which seeded to the lungs. Early surgical (day 10) removal of the tumor gave better survival than late (day 20) surgical removal of the tumor. When cyclophosphamide chemotherapy was used with surgery, better survival (80 %) was seen. Cyclophosphamide alone did not improve survival over that seen for tumor‐bearing controls. Late surgery with adjuvant chemotheraphy increased survival time.
Positive correlation between in vitro NK activity and in vivo resistance towards AKR lymphoma cells
Authors: Riesenfeld Inger , Anders Örn  , Gidlund Magnus , Axberg Inger , Alm Gunnar V. , Wigzell Hans
Published: February 2007

The possible in vivo relevance of murine natural killer (NK) cells in resistance towards grafted lymphoma was analyzed. The system comprised two AKR T lymphomas having similar behavior as to growth patterns but significant differences in vitro with regard to susceptibility to NK‐cell‐mediated lysis. These tumor cells were grafted into (AKRxCBA)F1 hybrids which had been lethally irradiated and then protected with bone marrow of CBA or AKR origin. Some adult animals were thymectomized before irradiation. The F1 chimeras could be shown to be repopulated with donor cells at the level of peripheral white blood cells and displayed high or low NK levels if coming from CBA and AKR donors respectively. Thymectomy resulted in a significant increase in the final levels of NK activity in the recipients. The in vivo growth patterns of the two AKR lymphomas were in a strikingly positive manner correlated with the NK activities of the recipients. Thus, high NK activity in the recipients resulted in a significant increase in resistance towards the outgrowth of the NK‐sensitive AKR lymphoma but had only marginal impact on the relatively NK resistant lymphoma. This was true irrespective of whether or not the recipients were thymectomized before marrow reconstitution and in general the T‐deficient mice were thus more resistant towards tumor grafting than their non‐thymectomized counterparts. In all, the results would thus further suggest an important role for NK cells in mediating in vivo resistance towards NK‐susceptible tumors, and they fail to provide any evidence for T lymphocytes in tumor protection in the same system.