bluuebunny/crossref_metadata_2025 huggingface dataset:
Histological and combined chemoimmunostimulation therapy studies against a murine leukemia
Authors: Pearson J. W. , Perk K. , Chirigos M. A. , Pryor J. W. , Fuhrman F. S.
Published: February 2007

A Graffi murine leukemia was utilized as a model system to investigate the effect of chemoimmunostimulation therapy. Subcutaneous inoculation of approximately 1.0 × 106 tumor cells resulted in a rapidly growing tumor at the site of inoculation and subsequent development of splenomegaly and lymphoadenopathy. All animals succumbed to the leukemia within 24 to 30 days. Treatment of diseased animals with two courses of cytoxan over a 2‐week period resulted in a remission period of approximately 16 to 18 days before relapse and eventual death of approximately 70% of the drug‐treated animals. A significant number of long‐term survivors (50 to 83%) was obtained in groups of animals that received combined drug plus BCG or C. parvum therapy. In contrast, the administration of MER (a methanol‐extracted residue of BCG) to animals in a drug‐induced remission period was no more effective than drug alone. The protective effect afforded by BCG and C. parvum was dependent on the time interval between drug therapy and the administration of the immunostimulators. Treatment of leukemic animals with BCG, C. parvum, or MEK alone proved ineffective as all mice died at approximately the same time as untreated control animals. No leukemic cells were observed in any of the histologically examined tissues taken from long‐term survivors. The implication of these results for cancer therapy is discussed.
Tumor induction in rats by feeding aminopyrine or oxytetracycline with nitrite
Authors: Taylor H. W. , Lijnsky W.
Published: February 2007

Sprague‐Dawley rats were given combinations of aminopyrine or oxytetracycline and sodium nitrite in drinking water. Of 30 animals receiving 0.1% (1,000 ppm) of aminopyrine and sodium nitrite for 30 weeks, 29 died with hemangioendothelial sarcomas of the liver. The same tumor caused death in 26 of 30 animals that received 0.025% (250 ppm) of both aminopyrine and sodium nitrite for 50 weeks. No animals in a control group of the same size that received 0.1% aminopyrine for 30 weeks developed this tumor, although one‐half of them were still alive 2 years after the experiment was begun. After feeding a comparable dose (0.1%) of oxytetracycline and sodium nitrite for 60 weeks, liver tumors were present in 4 of 30 rats (3 hepatocellular tumors and 1 cholangioma). Since aminopyrine has been widely used for medicinal purposes in the human population, it is possible that many people have been exposed to a potent carcinogen (dimethylnitrosamine) by its formation in vivo. It is not certain whether the result of feeding oxytetracycline and sodium nitrite indicates significant carcinogenicity of this combination.
Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic tumors. I. Distribution of reactivity and specificity
Authors: Herberman Ronald B. , Nunn Myrthel E. , Lavrin David H.
Published: February 2007

Lymphoid cells from many normal mice of a variety of inbred strains were found to have reactivity, in a 51Cr release cytotoxicity assay, against several syngeneic and allogeneic tumors. Very high reactivity was seen with effector cells from athymic nude mice, which was consistent with other evidence that the reactivity was not T‐cell dependent. Target cells susceptible to lysis included tumors induced by oncogenic type‐C viruses but also tumors induced by other means and expressing endogenous type‐C viruses. The levels of natural reactivity were influenced by age, with highest cytotoxicity produced by cells from 5‐ to 8‐week‐old mice. Lymph‐node cells, spleen cells, peritoneal exudate cells and peripheral blood lymphocytes all had cytotoxic reactivity. The specificity of the reactions was analyzed in detail by an inhibition assay. Evidence was obtained for natural reactivity against several different antigens, each apparently associated with expression of murine endogenous type‐C viruses.
Identification of an antigen associated with malignant melanoma
Authors: Viza D. , Phillips J.
Published: February 2007

Xeno‐antisera, prepared by immunization with soluble membrane material obtained from melanoma tumours and partially purified by column chromatography, were found to detect an antigenic specificity common to some tumour extracts and sera of melanoma patients. The presence of this antigen in patients' sera allows speculation for its possible use for early diagnosis of metastases and its role in the blocking of the immunological defences of the melanoma patients. Preparation of monospecific antisera by immunization with insoluble serum‐antigen/antibody complexes has been successfully undertaken.
Antibodies to Epstein‐Barr virus‐associated nuclear antigen and to other viral and non‐vical antigens in Hodgkin's Disease
Authors: Rocchi G. , Tosato G. , Papa G. , Ragona G.
Published: February 2007

Antibody reactivity to Epstein‐Barr virus (EBV)‐associated nuclear antigen (EBNA) was investigated by means of the anticomplement immunofluorescence technique on sera from patients with Hodgkin's disease (HD) and from appropriate controls. Antibody levels to other EBV‐determined antigens, i.e. viral capsid (VCA) and early antigens (EA), and to measles and rubella viruses, to cytomegalovirus (CMV), and to toxoplasma gondii were also measured. The results of anti‐EBV antibody titrations demonstrated that anti‐VCA, anti‐EA and anti‐EBNA reactivity was significantly higher in HD patients than in healthy subjects. There was no significant difference between the distribution of high rubella and measles antibody titers in HD and control sera. The GMT and the incidence of high titer anti‐CMV and toxoplasma antibodies were greater in HD patients than in controls. The analysis of the data, according to histological subtypes, showed that the condition of lymphocyte depletion was associated in HD patients with the highest anti‐EBNA antibody levels and the lymphocyte predominance with the lowest. This pattern seemed to be peculiar for anti‐EBV reactivity, since anti‐CMV and anti‐toxoplasmn antibody levels in the lymphocytedepleted group of patients did not significantly differ from those of controls. No correlation was found between anti‐VCA and anti‐EBNA in individual sera of HD patients. This observation suggests that different mechanisms are probably responsible in HD for the release of EBV‐related antigens from infected cells.
Increased thymidine uptake by methylcholanthrene‐treated C3H/10T1/2 cells
Authors: Bairstow Fred , Heidelberger Charles
Published: February 2007

The uptake of 3H‐thymidine in post‐confluent cultures of methylcholanthrene‐transformed C3H/10T1/2 mouse embryo cells was markedly higher than in their non‐transformed counterparts. In a reconstruction experiment as few as 2% transformed cells could be detected by increased thymidine uptake. Measurements made at various times up to 110 days in multi‐chambered plates revealed that after 25 days methyl‐cholanthrene‐treated cultures incorporated significantly more thymidine than the acetone‐treated controls. This increased uptake correlated with the appearance of Type III transformed foci.
Temperature‐dependent properties of cells transformed by a thermosensitive mutant (TS‐121) of polyoma virus. II. Characterization of 121‐6 cells
Authors: Okada Yasuhiro S. , Hakura Akira
Published: February 2007

The properties of 121‐6 cells were characterized. This cell line is transformed by ts‐121, a temperature‐sensitive mutant of polyoma virus. Both the morphology and saturation density of the 121‐6 cells were affected by temperature; i.e. at 39° C, the cells grew to monolayer sheets and remained contact inhibited for a long time (at least 25 days), while at 35° C, they grew beyond the monolayer density, like cells transformed by wild‐type polyoma virus. These phenotypic changes were reversible, but increased agglutinability by Concanavalin A, which was another phenotype of these transformed cells, was not temperature‐sensitive, and even at high temperature, 121‐6 cells, like transformed cells, showed high agglutinability.
Non‐organ‐specific and tumour‐specific antibodies in children with Wilms' tumour
Authors: Kumar Shant , Taylor Geoffrey
Published: February 2007

Sera from groups of children with Wilms' tumour, with non‐renal solid tumours, and from control children were studied by immunofluorescence and by absorption techniques. A high proportion of sera from both tumour groups contained non‐organ‐specific auto‐antibodies. Three of the 45 sera in the Wilms' group and one of the 27 sera in the “other” solid tumour group contained antibody reacting with normal kidney cells. Only one of 45 sera in the Wilms' tumour group contained tumour‐specific antibody.
Evidence that blocking factors in the sera of multiparous mice are associated with immunoglobulins
Authors: Tamerius J. , Hellström I. , Hellström K. E.
Published: February 2007

Previous work has shown that lymph‐node cells from pregnant BALB/c mice can kill syngeneic tumor cells in a microcytotoxicity assay, and that sera from pregnant BALB/c mice can block (inhibit) that effect. The present study shows that passage of such sera through immunoadsorbents charged with anti‐mouse IgG2a or IgG2b removed the blocking activity, and that this could be recovered in the eluates; passage through an anti‐IgG1 immunoadsorbent was less effective in decreasing blocking serum activity and adsorption to immunoadsorbent charged with anti‐IgM or anti‐IgA did not remove it at all. Passage of blocking serum through an immunoadsorbent coupled with antibodies from a rabbit anti‐mouse embryo antiserum removed all of its blocking activity, and this could be recovered in the eluates. The findings are compatible with the hypothesis that the blocking factors operating in this system are largely complexes between embryonic antigens and IgG2a and IgG2b.
Therapeutic effect of intratumoral injection of BCG and other substances in rats and mice
Authors: Chassoux D. , Salomon J‐C.
Published: February 2007

The experimental treatment of a rat sarcoma (McFiFi 2) by intratumoral injection of BCG

The abbreviations used are: BCG, Bacillus Calmette‐Guérin; C. parvum, Corynebacterium parvum; MC, 3‐methylcholanthrene; MER, methanol extract residue of Mycobacterium tuberculosis; PHA, phyto‐hemagglutinin; Con A, concanavalin A; IT, intratumoral; SC, subcutaneous; IP, intraperitoneal; IV, intravenous; TSTA. tumor‐specific transplantation antigen.

is described. Tumors which have a mean diameter of less than 10 mm at the beginning of treatment are fully susceptible to BCG, although spontaneous regression is not observed at this stage. The effective dose of living BCG ranges from two injections of 0.1 mg to two injections of 1 mg, given IT at an interval of 7 days. The permanent cure of a proportion of the tumors may also be induced by IT injection of a similar dose of heat‐killed BCG or of MER, or of 109 heat‐killed C. parvum, according to the same schedule. Preimmunization of the rats with living BCG does not improve the efficiency of heat‐killed BCG. Direct contact between the therapeutic material and the tumor cells is critical. If rats are grafted with two pieces of the same tumor in widely separated sites, the intratumoral treatment of only one of these tumors with living BCG is sufficient to induce regression of both tumors in 50% of the animals. The effect of BCG is counteracted by injection of silica or by ingestion of polaramine. The same intratumoral treatment with living BCG was applied to different rat and mouse tumors. Only McFiFi 2 tumors were cured by intralesional BCG. C3H mouse plasmocytoma 5563 was not cured by intratumoral BCG but its growth could be prevented by mixing BCG and tumor cells at the time of grafting; this tumor was considered to be of medium susceptibility. However, until there is definite proof that the two mechanisms are identical, one should consider the regression and cure of a growing tumor, and the prevention of tumor growth, as two different phenomena. The clinical treatment of human tumors resembles the first experimental procedure more closely than the second.
Cellular immune reactivity in vitro and tumor rejection provided by tumor‐associated antigens of friend‐virus‐induced leukemia
Authors: Dean J. H. , McCoy J. L. , Law L. W. , Maurer B. A. , Appella E.
Published: February 2007

Cell‐mediated immunity (CMI) and tumor rejection were studied in the Friend virus leukemia system of C57BI/6 mice. Mice were immunized with Friend leukemia virus (FLV) or X‐irradiated FBL‐3 leukemic cells and studied temporally for the development of CMI reactivity by assays of 51Cr release lymphocyte cytotoxicity, lymphocyte transformation, migration inhibition, Winn tumor cell neutralization and transplantation rejection. High levels of specific lymphocyte cytotoxicity were observed by day 7 following FLV infection; this reactivity reached a peak between 17 and 21 days, and returned to background levels by day 36. Further, positive Winn assays were obtained with spleen cells from mice immunized with FLV at times when the mice resisted live FBL‐3 tumor challenge. Positive lymphocyte transformation was obtained with spleen cells from mice immunized with FLV or FBL‐3, but not with cells from normal mice or mice immune to a syngeneic methycholanthrene‐induced tumor, when cultured with papain‐soluble FBL‐3 or RBL‐5 tumor‐cell extracts or mitomycin‐C (MMC)‐treated FBL‐3 or RBL‐5 cells. Positive reactivity in the lymphocyte transformation assay occurred after reactivity had peaked in the lymphocyte cytotoxicity test. Similar positive macrophage migration inhibition patterns were also obtained with peritoneal exudate cells (PEC) from FLV‐immunized mice using papain‐solubilized tumor‐associated antigen (TAA) from FBL‐3 cells. These data suggest that sequential development and modulation of CMI reactivity occurs as observed in different assays following immunization in this system.
Combination of C. parvum and specific immunization against artificial pulmonary metastases in mice
Authors: Milas Luka , Kogelnik H. Dieter , Bašic Ivan , Mason Kathy , Hunter Nancy , Withers H. Rodney
Published: February 2007

We have studied whether specific immunization administered intraperitoneally can augment the activity ofC. parvum (0.25 mg intraperitoneally or intravenously) against intravenously injected cells of a syngeneic fibrosarcoma in C3Hf/Bu mice as expressed by the reduction of pulmonary metastases (nodules, colonies) and/or by the prolongation of the survival of recipients. Combination of specific immunization and C. parvum, applied either before or after IV inoculation of viable tumor cells, was more effective than the single treatments. IV injection of a mixture of heavily irradiated and viable tumor cells gave more tumor nodules in the lungs of normal mice than injection of viable cells alone. The metastasis‐enhancing effect of admixed irradiated cells was not found in mice previously treated with C. parvum, and was abolished if the immunostimulant was injected after tumor cells. Generation of lung metastases by IV inoculation of fibrosarcoma cells was reduced in mice already having this tumor in the leg. This concomitant immunity to metastases was increased by treating the recipients with C. parvum, but not with irradiated cells: also, the injection of irradiated cells together with C. parvum did not augment the efficiency of the latter. C. parvum was not as effective in T‐cell deprived as in control mice, which suggests that in this system, T‐cells are required for optimal anti‐tumor activity of this immunostimulant. Specific immunization was not effective in T‐cell‐deprived mice and did not augment the efficiency of C. parvum.
Increased lymphocyte‐mediated destruction of tumor cells in microcytotoxicity assays seen after addition of inhibitors of protein synthesis
Authors: Hellström I. , Hellström K. E. , Nepom J. T.
Published: February 2007

Two methylcholanthrene (MCA)‐induced sarcomas were used as targets in a criss‐cross pattern to study lymph‐node‐cell (LNC)‐mediated cytotoxic reactions to tumor‐specific antigens in a 26 h microcytotoxicity assay. Destruction of plated tumor cells by syngeneic LNC from specifically tumor‐immune or multiparous mice significantly increased when cycloheximide was added during the whole duration of the test. A similar increase was also seen if either cycloheximide or puromycin was added during the last 6 h of the 24 h assay. A slight increase of cytotoxicity was seen if, instead, the mixture of fetal calf serum and LNC was simply replaced by serum‐free medium during the last 6 h of the test. The findings suggest that a repair process may occur in target cells contacted by immune LNC or that target cells damaged by contact with immune LNC are more sensitive to further damage by the exposure to certain inhibitors of protein synthesis. Additional mechanisms may contribute to the increased LNC‐mediated cytotoxicity seen when cycloheximide is added for the whole duration of the test.
Antibody‐dependent cell‐mediated cytotoxic activity in syngeneic mouse ascites tumors
Authors: Tracey Daniel E. , Pross Hugh F. , Jondal Mikael , Witz Isaac P.
Published: February 2007

Eight different syngeneic murine ascites tumor preparations were tested for their ability to lyse antibody‐coated chicken erythrocytes in an assay for antibody‐dependent cell‐mediated cytotoxicity (ADCC)

Abbreviations used in this paper: ADCC ‐ antibody‐dependent cell‐mediated cytotoxicity; CRBC ‐ chicken red blood cells; C3 ‐ the third component of complement; FCS ‐ fetal calf serum; PEC ‐ peritoneal exudate cells; NMS ‐ normal mouse serum; MaCRBC ‐ mouse anti‐CRBC antiserum; SRBC ‐ sheep red blood cells; EA ‐ SRBC sensitized with antibody; EAC = SRBC sensitized with antibody and complement; PBS ‐ phosphate‐buffered saline.

. All of the tumor preparations demonstrated significant ADCC effector activity, even at effector‐cell:target‐cell ratios of less than 1:1. In contrast, none of eight in vitro murine tumor‐cell lines showed any consistent ability to function as ADCC effector cells. Several cell fractionation experiments were performed to ascertain the nature of the effector cells in the ascites tumors. Adherent cells were removed from tumor preparations by passage of cells over columns of Degalan plastic beads and 19S Fc‐receptor‐bearing cells were removed by sedimentation of EA rosette‐forming cells. Although each of these procedures depleted only a minority of the total cells, all the ADCC activity was simultaneously removed in each case. Depletion of phagocytic cells by treatment of tumor preparations with carbonyl iron and magnetism only slightly diminished the ADCC activity. These results indicate that the ADCC activity associated with ascites tumors is due to effector cells most probably of host origin, but possibly representing an atypical sub‐population of tumor cells. The characteristics of the effector cell closely parallel those defined for the major nonphagocytic ADCC effector cell in normal mouse spleen and peritoneal exudate.
Tyrosine aminotransferase induction in normal and tumor‐bearing chickens
Authors: Horváth I. , Arányi P. , Náray Anikó , Földes I. , Gyuris Ágnes
Published: February 2007

Tyrosine aminotransferase (TAT) induction by glucagon and dexamethasone in the liver of tumor‐bearing chickens was studied and compared with induction in healthy animals. The transplantable tumor was caused by inoculation of cells from a cell line induced by MC29 avian leukosis virus. TAT was hardly detectable in tumor tissue of control and dexamethasone‐treated chickens, but it was induced by glucagon to levels which were significant although very low when compared to those in host liver or the liver of non‐tumor‐bearing controls after glucagon treatment. Dexamethasone failed to induce TAT in host liver at 8 A.M. while it significantly induced TAT in the normal liver at the same time of the day. Similar failure of TAT induction was not detectable when glucagon was used instead of dexamethasone. Furthermore, it was found that diurnal variations in basal and dexamethasone or glucagon‐induced TAT levels are considerably mitigated in host liver as compared to those observed in the liver of healthy animals. The possible reasons for these findings are discussed.
Inhibition of sensitization of T‐cells by alpha‐fetoprotein
Authors: Dattwyler Raymond J. , Tomasi Thomas B.
Published: February 2007

A two‐phase model of allograft immunity was studied. In the first phase, specific immune T‐cells were generated by incubation of responder cells with mitomycin‐C treated allogeneic stimulator cells of the same H‐2 type as mouse mastocytoma tumor cells. In the second step, the ability of the sensitized cells to kill Cr51‐labelled P‐815 mastocytoma cells was assayed. Alpha‐fetoprotein (AFP) was shown to inhibit the generation of immune cytotoxic T‐cells at low concentrations (1‐100 ng/ml) when added at the beginning of the first phase. When added at the end of the first phase or in the second (killing) phase, AFP was found to have no significant effect on cytotoxicity, indicating that it did not inhibit the killer T‐cell once it was generated.
Antibodies and antigen expression in human melanoma detected by the immune adherence test
Authors: Cornain Santoso , De Vries Jan E. , Collard John , Vennegoor Claudia , Van Wingerden Ineke , Rümke Philip
Published: February 2007

By means of a modified immune adherence (IA) technique, sera from melanoma patients were tested for the presence of antimelanoma antibodies. In total 13/73 sera tested showed a positive IA reaction of which 4/6 sera showed a positive reaction in the autologous situation. Sera from 33 patients with other tumors, 7 patients with non‐neoplastic diseases and 50 healthy individuals did not show any IA reactivity towards melanoma cells. The reaction seemed to be selectively directed against tumor‐associated antigens (TAA) on melanoma cells. No correlation with the stage of the disease could be found. Longitudinal studies indicated that conversions in antibody activity did not correlate with the clinical state of the patients. There was also no correlation with the corresponding in vitro data obtained in cell‐mediated immunity tests. Cell lines and short‐term cultures originating from tumors from different melanoma patients shared a common antigenicity. The expression of TAA on cells from a melanoma cell line fluctuated significantly during prolonged culture. The expression of TAA was influenced by the culture conditions and the growth state of the cells. A relation between TAA‐expression and cell cycle phase was demonstrated.
Increase in the proportion of cells with the C'3 receptor in Balb/c mice bearing mammary tumors
Authors: Dorizzi Mireille , Ortiz‐Muniz Gabriel , Lopez Diana M. , Sigel M. Michael , Epstein Robert S.
Published: February 2007

Transplantation of mammary tumors originally induced by dimethylbenzanthracene caused splenomegaly and an increase in the total population of spleen cells paralleling the increase in tumor size. At least part of the hypercellularity was due to in situ proliferation as evidenced by the increased number of blast forms and mitotic figures. The cells were characterized with respect to parameters generally associated with B‐cells; surface immunoglobulins as detected by immunofluorescence and C'3 receptors as determined by rosette formation with sheep red blood cells (SRBC) coated with rabbit anti‐SRBC and mouse complement. There was no change in the percentage of B‐cells with surface immunoglobulin in tumor‐bearing mice compared with the control animals. However, there was a profound change in the representation of cells bearing C'3 receptors. The percentage of the cells increased dramatically with tumor growth. Various possibilities regarding the nature and function of these cells are considered.
Sensitive method to detect non‐complement‐fixing antibodies to Epstein‐Barr virus nuclear antigen
Authors: Schmitz H. , Kampa D. , Heidenreich W.
Published: February 2007

The anti‐complement immunofluorescence (ACIF) test was modified to detect non‐complement‐fixing antibodies to Epstein‐Barr (EB) virus nuclear antigen (EBNA). These EBNA antibodies belong to the immunoglobulin classes IgA and IgG. In our method anti‐human γ‐globulin (AHG) was bound to the EBNA antibodies before the complement was added. If only non‐complement‐fixing antibodies are present the complement can be fixed to the AHG. Within only a few weeks of the onset of infectious mononucleosis (IM) the non‐complement‐fixing EBNA antibodies reach high titers while the complement‐fixing antibodies (detected by the ACIF test) are not yet present. Anti‐EBNA‐IgM antibodies were not found in the IgM fractions of sera taken at different stages of IM.
Epstein‐barr virus‐specific IgA serum antibodies as an outstanding feature of nasopharyngeal carcinoma
Authors: Henle Gertrude , Henle Werner
Published: February 2007

Stimulated by a report on elevated IgA levels in nasopharyngeal carcinoma (NPC), we tested a total of 372 sera from patients with NPC, other carcinomas of head and neck or elsewhere, Burkitt's lymphoma (BL), infectious mononucleosis (IM) or healthy controls. The sera were titrated in indirect immunofluorescence tests for IgA antibodies to Epstein‐Barr virus (EBV) capsid antigen (VCA) and to the diffuse (D) or restricted (R) components of the EBV‐induced early antigen (EA) complex. The results proved NPC to be outstanding in that prior to therapy 93% of the patients tested revealed IgA antibodies to VCA and 73% to D, often at high titers which occasionally matched the corresponding IgG antibody levels. The EBV‐specific IgA titers increased from stages I or II to stages III or IV; i.e. with the total tumor burden. Conversely, many of the NPC patients examined 2–6 years after initial therapy had only low levels of EBV‐specific IgA or none at all, and the majority of those with high titers were known to have residual or recurrent disease. In contrast to untreated NPC patients, less than 5% of 73 patients with other carcinomas or of 76 healthy donors revealed VCA‐specific IgA and even fewer EA‐specific IgA; only 28% and 4% of 54 BL patients tested at admission had IgA antibodies to VCA and R, respectively, and 38% and 3% of 37 IM patients showed transient VCA‐or D‐specific IgA responses, all at generally low titers. While sera from untreated NPC patients often contained IgA antibodies also to herpes simplex type 1 virus, their incidence and range of low titers were similar to those obtained with sera from patients with other carcinomas or from healthy donors. It thus appears that the elevated IgA levels in NPC might be due to EBV‐specific antibodies. Possible reasons for this unique response in NPC have been discussed.
Immunity to antigens associated with a cell line derived from nasopharyngeal cancer (NPC) in non‐Chinese NPC patients
Authors: Levine P. H. , Herberman R. B. , Ambrosioni J. C. , De‐Thé G. B. , Brugere J. , Schwaab G. , Mourali N. , Revol P.
Published: February 2007

Delayed hypersensibility to antigens derived from four lymphoid cell lines was measured in 27 non‐Chinese patients with nasopharyngeal cancer (NPC) and 63 non‐NPC cancer patients. Of the NPC patients, 17/27 (63%) had a positive skin test response to antigens derived from HKLY‐28, a lymphoid cell line which was developed from an NPC biopsy. Only 10/51 (20%) and 1/13 (8%) patients with solid tumors and hematopoietic malignancies, respectively, had positive skin test responses to HKLY‐28. Positive skin tests were found less frequently when extracts from cell lines derived from normal individuals or lymphoma patients were utilized, although NPC patients were more reactive to two of the non‐NPC derived cell lines than the controls. The NPC patients in this study also had significantly elevated antibody titers to the Epstein‐Barr virus (EBV), capsid antigen (VCA) and early antigen (EA). Titers were highest in the patients with more anaplastic nasopharyngeal carcinomas. The skin test and serologic data are consistent with studies in Chinese patients, indicating that NPC in non‐Chinese and Chinese patients is biologically similar.
Cellular immunity in mammary cancer patients as measured by the Leukocyte Migration Test (LMT). A follow‐up study
Authors: Rieche K. , Arndt A. , Pasternak G.
Published: February 2007

In 58 cases of mammary cancer treated by surgery the leukocyte migration test (LMT) has been applied to the study of cellular immunity using homogenate from autochthonous and homologous tumors as antigens. A positive test, i.e. inhibition of migration by antigen, was observed in 52 patients from 1 day up to 40 days after surgery. Six patients were negative. There was extensive immunological cross‐reactivity among mammary cancer in that a positive test was also obtained with homogenate from homologous mammary tumors. Generally, antigens from other tumors did not react. The test was also negative when the leukocytes were derived from healthy persons. Sera from mammary cancer patients abrogated the inhibitory effect of tumor antigen. The disappearance of positivity about 40 days after surgery and its reappearance during the metastatic process indicates that the positive LMT is associated with progressive disease.
Incomplete viral synthesis in friend leukemia virusinduced reticulum cell sarcomas
Authors: Black Douglas R. , Fieldsteel A. Howard
Published: February 2007

Tissue‐culture‐passaged, Friend leukemia virus (FV)‐induced reticulum cell sarcomas from BALB/c mice (FVTCT‐BALB) did not produce infectious FV, although retrieval of infectious FV occurred when these cells were co‐cultivated with cell lines replicating non‐defective murine leukemia viruses (MLVs). The level of FV expression in the FVTCT‐BALB cell line was studied to understand better the process of FV retrieval. 3H‐uridine labelling techniques and reverse transcriptase assays showed that FVTCT‐BALB cells did not release C‐type virus particles. Nucleic acid hybridization techniques demonstrated that the level of viral RNA synthesis in the FVTCT‐BALB non‐producer cell line was indistinguishable from that in cell lines productively infected with MLVs. These data suggest that in the FVTCT‐BALB cell line the synthesis of FV is blocked in some late stage of virus assembly.
Serum factor levels during the growth of rat hepatoma nodules in the lungs
Authors: Bowen J. Gareth , Baldwin Robert W.
Published: February 2007

The levels of tumour‐specific antigen, antibody and specific immune complexes in the sera of rats bearing lung nodules of a chemically induced rat hepatoma, produced by intravenous inoculation of viable tumour cells, have been examined and compared with the levels of serum factors in animals actively immunized by intravenous inoculation of mixed tumour cells and BCG. Animals inoculated with cells alone developed multiple lung nodules which slowly grew, until on day 24 the remaining animals had to be killed due to respiratory distress. In contrast, the animals receiving a mixed inoculum of BCG and tumour cells developed no visible lung nodules and were capable of rejecting a further challenge of tumour cells. Tumour‐specific antigen could be detected in the sera of both groups of rats at different times. In actively immunized animals free antigen could be detected from day 3 to day 10 after inoculation of cells plus BCG whereas in animals receiving cells alone, free antigen could not be detected until day 14 and persisted until the termination of the experiment. Free tumour‐specific antibody, however, was found in the sera of rats actively immunized with tumour cells and BCG from day 10 onwards, although in the other group of animals it could not be detected. Conversely, immune complexes of tumour‐specific antigen and antibody could be detected from day 10 in rats receiving cells alone and only at day 10 in actively immunized rats. The relevance of these findings in relation to what is known about serum factor levels during tumour growth and regression is discussed.
Fibroblast surface antigen (SF): THE external glycoprotein lost in proteolytic stimulation and malignant transformation
Authors: Keski‐Oja Jorma , Vaheri Antti , Ruoslahti Erkki
Published: February 2007

It was previously shown that the fibroblast surface antigen (SF antigen, SFA) is composed of polypeptides of high molecular weight 210,000 (SF210) and 145,000 (SF145) and that both of these decrease in quantity after transformation of the fibroblasts by Rous sarcoma virus (RSV). The present experiments show that SF210 is a glycoprotein. It is accessible to surface labelling by lacto‐peroxidase catalyzed iodination. The SF210 molecule is highly susceptible to trypsin on cell surface. Anti‐SFA antibodies specifically precipitated the surface labelled polypeptide. The lactoperoxidase iodinated SF210 polypeptide was greatly reduced in cells transformed by RSV. It is concluded from these studies that the large external transformation sensitive (LETS) protein detected by other workers is the same molecule as SF210. Part of the label of surface iodinated fibroblasts did not enter the polyacrylamide gels. This high molecular weight material is also susceptible to trypsin treatment and decreases in quantity after transformation by RSV. The data suggest that it may be antigenically related to SF protein. Treatment of surface or 35S‐methionine‐labelled cultures with trypsin in concentrations able to initiate proliferation of density‐inhibited cells rapidly released SF210 from fibroblast surface. A single high molecular weight polypeptide (mol. wt about 200,000, SF200) was detected in the culture medium. SF210 may thus be a major target molecule of trypsin action. Treatment of cultures with insulin that also stimulated the fibroblasts to initiate proliferation did not result in any detectable alteration in the external glycoprotein SF210. It is concluded that although release of SF210 may be a sufficient trigger to stimulate proliferation in stationary cells, this molecule appears not to be directly involved in initiation of fibroblast proliferation from the G1 (or G0) phase of the cell cycle.
Rat liver microsome‐mediated binding of benzo(A)pyrene metabolites to DNA
Authors: Thompson M. H. , King H. W. S. , Osborne M. R. , Brookes P.
Published: February 2007

Individual metabolites of benzo (a)pyrene were isolated from rat liver microsomal incubation of the parent hydrocarbon, and subsequently bound to DNA in separate incubations with microsomes. Of the metabolites examined, by far the greatest binding resulted with 7,8‐dihydro‐7,8‐dihydroxy‐benzo (a)pyrene (BP‐7,8‐diol); the binding of the benzo (a)pyrene phenols (BP‐OH) was about 50% that of the 7,8‐diol. Analysis of the hydrocarbon‐deoxyribonucleoside derivatives obtained by enzymic degradation of these DNA samples revealed that the binding of BP‐7,8‐diol was accounted for mainly by a single product identical to one of the products obtained from DNA with bound benzo (a)pyrene. Furthermore, the microsome‐induced binding of BPOH to DNA yielded mainly a single product identical in chromatographic behaviour to the major product derived from benzo (a)pyrene when bound to DNA during incubation with microsomes.
Non‐T‐cell resistance against a mouse moloney lymphoma
Authors: Kiessling Rolf , Petrányi Gyözö , Klein George , Wigzell Hans
Published: February 2007

We have previously shown that spleen cells from normal mice contain lymphocytes that kill certain in vitro‐grown Moloney lymphoma lines in a 51Cr release test. The killing activity shows a marked dependence on the genotype of the donor mouse. In vivo rejection studies with a Moloney lymphoma line in various normal semisyngeneic F1 hybrids showed a clear positive correlation between in vitro natural cytotoxicity and in vivo rejection. Thus mice can be grouped as high‐ or low‐reactive according to their in vitro cytolytic behavior as well as their in vivo rejection potential. A lymphoid cell without detectable T‐ or B‐cell markers is responsible for the in vitro killing effect. The present study also shows that the in vivo growth inhibitory function is T‐cell‐independent. Lymphoid cells depleted of T‐and B‐cells and transferred together with Moloney lymphoma cells into an irradiated syngeneic recipient were highly efficient in delaying tumor growth. Furthermore, syngeneic or semisyngeneic thymectomized, irradiated, fetal‐liver‐reconstituted mice showed if anything an increased in vivo resistance to a Moloney lymphoma compared to control mice. In contrast, tumor cells histoincompatible with regard to the H‐2 locus showed the expected preferential growth in the thymectomized animals. We thus conclude that the major in vivo resistance against transplantation of the syngeneic or semisyngeneic Moloney lymphoma used in this study is T‐independent.
Incidence rates of specific histological types of lung cancer in Singapore Chinese dialect groups, and their aetiological significance
Authors: Law C. H. , Shanmugaratnam K. , Day N. E.
Published: February 2007

Significant differences in the incidence levels of lung cancer have been observed among major Chinese dialect groups or communities (Hokkien, Teochew and Cantonese) in Singapore. Among males, the incidence rate is highest in the Hokkiens (agestandardized incidence rate per 100,000 persons per year in Hokkien 67.8, Teochew 55.3, Cantonese 54.0) and among females, it is highest in the Cantonese (Hokkien 12.4, Teochew 12.8, Cantonese 27.2). The present investigation was undertaken to determine the incidence rates of each of the main histological types of lung cancer in the Chinese population and to determine whether there are any correlations between histological patterns and the dialect group differentials that may be of aetiological significance. During the period 1968‐1972, a total of 1,747 cases of lung cancer (1,285 males and 462 females) were reported to the Singapore Cancer Registry. It proved possible to type the neoplasms histologically in 476 males (37.0%) and 154 females (33.3%). Age‐standardized rates by histological type were computed on the assumption that those histologically typed were a representative sample of all lung cancers. This study shows that Hokkien males have a significantly higher incidence rate of epidermoid carcinoma than the other dialect groups (Hokkien 36.1, Teochew 21.1, Cantonese 17.3). The Cantonese females have significantly higher incidence rates of both epidermoid carcinoma (Hokkien 3.7, Teochew 2.3, Cantonese 5.9) and adenocarcinoma (Hokkien 4.6, Teochew 3.6, Cantonese 11.9). Various sources of bias in studies of this type were examined; it is concluded that the differences in the histologic‐specific incidence rates of lung cancer among the various Chinese dialect groups in Singapore are real and not artefactual. The significance of these findings in relation to possible aetiological factors is discussed.
Long‐term follow‐up studies on herpes simplex antibodies in the course of cervical cancer. II. Antibodies to surface antigen of herpes simplex virus infected cells
Authors: Christenson Brith , Espmark Åke
Published: February 2007

In a serological follow‐up of 88 women with active invasive cervical carcinoma, antibodies to membrane antigen of Herpes simplex virus (HSV)‐ infected cells were measured by the use of the mixed hemadsorption method. Sera were collected at the time of initial treatment and then at regular intervals. As controls, 85 healthy age‐matched women and 70 patients suffering from other types of cancer were tested similarly. During the 6‐ to 60‐month observation period 16 patients in the cervix carcinoma group died. The reactivity with membrane antigen of HSV‐infected cells was positive in 71% of the cervical carcinoma patients, whereas the figure for the other cancer group was 27% and for the age‐matched control group 27%. In the group of 16 patients who died, only 3 demonstrated antibodies against surface antigens of HSV‐infected cells. In most cases radiation treatment of the tumor did not significantly alter the mixed hemadsorption titer but in 10 surviving patients there was a significant increase in reactivity as the tumor was treated; 1 patient who had recurrence of her cancer lost reactivity in later sera. Among the 11 cervix carcinoma patients in stage I (by clinical definition carcinoma strictly confined to the cervix) all but one showed positive reaction against the surface antigen of HSV‐infected cells; the patient locking reactivity was the only one out of the 11 patients in stage I who had a recurrence of her cancer. The results confirm that low or missing antibody titers to membrane antigen of HSV‐infected cells are of prognostic significance, and decreasing antibody titers to membrane antigens run parallel to the severity of the lesions. There was poor correlation between antibody titers against membrane antigens and neutralizing antibody titers.
Capillary tube leukocyte adherence inhibition: An assay for cell‐mediated immunity in cancer patients
Authors: Urist Marshall M. , Boddie Arthur W. , Holmes E. Carmack , Morton Donald L.
Published: February 2007

The leukocyte adherence inhibition (LAI) assay has been modified and automated in order to facilitate its clinical application. This new assay‐the capillary tube LAI test‐correlated with delayed cutaneous hypersensitivity using streptokinase‐streptodornase antigen in 83% of the cases. When tested with a 3 m KCI lung carcinoma antigen, lung carcinoma patients' leukocytes were more frequently inhibited (55%) than those of controls (normals 6%, other tumors 20%).
The influence of vitamin a on the susceptibility of the rat lung to 3‐methylcholanthrene
Authors: Nettesheim P. , Williams M. L.
Published: February 2007

The susceptibility of rats to pulmonary carcinogens is increased in the absence of vitamin A intake even when considerable amounts (0.4 nmole/mg) of vitamin A are stored in the liver and deficiency symptoms are absent. This was demonstrated in studies on the induction of metaplastic lung nodules by intratracheally administered 3‐methylcholanthrene. Only moderate amounts of all‐trans‐retinyl acetate in the diet (7.6 nmole/g of diet) were required to prevent the development of this state of enhanced susceptibility. A further increase in intake of retinoids (by intragastric administration of either all‐trans‐retinyl acetate or 13‐cis‐retinoic acid) provided no additional protection against the effects of carcinogen.
Alteration of the cell membrane architecture during suspension and monolayer culturing
Authors: Springer E. Louise , Hackett Adeline J. , Nelson‐Rees Walter A.
Published: February 2007

Using suspension‐growth‐adapted HeLa (S3) cells, we followed the alterations in cell morphology during attachment and spreading on a glass surface in vitro by scanning electron microscopy. Suspension cultivation obviated the need for trypsinization or EDTA treatment of the cells before seeding, thus the cell surface was not chemically altered. The suspension‐grown cells were spherical and covered with microvilli. Three hours after seeding into stationary culture, attached cells had surface blebs and large processes, but no microvilli. During the following 9 h, the surface topography altered stepwise producing a complex lamelloplasm. The paper discusses how these membrane events are related to the cell cycle and metastasis.
Differential induction of Epstein‐barr virus‐related antigens in human lymphoblastoid cells by virus‐mediated cell‐to‐cell contact
Authors: Matsuo T. , Yamamoto K. , Osato T.
Published: February 2007

Differential induction of Epstein‐Barr virus (EBV)‐related antigens was observed after Sendai virusmediated fusion of producer and non‐producer cells with various human and mouse cells. The EBV‐determined early nuclear antigen (ENA), early antigen (EA) and viral capsid antigen (VCA) could be induced at a high rate in producer cells (P3HR‐1 and B95–8), normally expressing these antigens at very low frequency, as early as 12–24 h after fusion with each other or with human amnion FL cells. In contrast, only one antigen, ENA, was induced in producer cells following fusion with non‐producer cells. This limited induction occurred also in non‐producer cells fused with FL cells, but not after fusion with each other. EBV induction did not result from fusion of either producer or non‐producer cells with mouse cells (L‐M (TK‐) Cl1D and MCB‐6). The differential induction was not the result of heterokaryon formation as determined by autoradiography. The implications of these findings are discussed.
Relapse in Burkitt's lymphoma
Authors: Nkrumah F. K. , Perkins I. V.
Published: February 2007

Of 109 patients with histologically confirmed Burkitt's lymphoma who completed a course of chemotherapy, 86 (79%) achieved complete remission. Forty‐five (52%) of patients with initial complete remission relapsed with tumour over an observation period ranging from 2 years to over 5 years. Relapse was more common in patients who initially presented with abdominal or central nervous system (CNS) involvement than in patients who presented with localized facial tumours (p<0.01). Anatomical distribution of tumour on relapse differed from that at presentation. Facial bones were much less frequently involved on relapse; on the other hand, the CNS, cranial nerves, orbits and skin were frequent sites of disease on relapse. CNS involvement occurred in 42% (19/45) of patients at the first relapse and in 73% (11/15) of patients with multiple relapses. Prognosis in these patients was poor. Two relapse types were clinically identifiable. Early relapse (remission duration<12 weeks) was associated with frequent involvement of the CNS, drug resistance and a generally unfavourable outcome. Patients with late relapse (remission duration >12 weeks) responded much better to secondary treatment. Possible pathogenic mechanisms underlying these two relapse types are discussed.
Effect of age at inoculation of asbestos on occurrence of mesotheliomas in rats
Authors: Berry G. , Wagner J. C.
Published: February 2007

An experiment in which rats were injected intrapleurally with asbestos, the injection taking place at an age of either 2 or 10 months, is reported. In the former group 19 out of 48 rats developed a mesothelioma compared with 17 out of 90 in the latter group. However, by considering the two groups at equal times after injection, eliminating the effects of natural mortality and also taking into account that not all of the mesotheliomas were the cause of death, it was shown that the incidence rate of mesotheliomas was significantly higher (p<0.01) in the rats injected at age 10 months and the relative rate was estimated as about 4, with 95% confidence limits of 1.5 and 12. An alternative explanation that the mesotheliomas occurred in the two groups at similar rates, except that in the group injected at age 10 months they occurred on average 4 months sooner after injection, is discussed. Two other groups were also injected, one at age 17 months and the other at 22 months. In the former group two early mesotheliomas were observed, 10 and 74 days after injection, but the next was not observed until over a year later. No explanation of this finding could be suggested other than the possibility that these two tumours were not associated with the asbestos treatment.