bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of ‘h‐2k, d‐like structures’ on mm2 × mouse l cell hybrids. i. ‘h‐2k, d‐like’ alloantigen encoded by the d region and/or to the right of the d region of the h‐2 gene complex
Authors: Kubota Koichi , Manson Lionel A.
Published: February 2007

It was found that anti‐MM2 serum, which had been prepared by immunizing C3H/He mice with syngeneic MM2 mouse mammary ascites tumor, detected molecules of 44–46,000 and 12,000 daltons on EL4 leukemic cells and on C57BL/6 lymph node cells, as well as on somatic cell hybrids between the MM2 and mouse L cells. Experiments with a known rabbit anti‐mouse β2‐microglobulin serum showed that the two molecules detected by anti‐MM2 serum were hydrophobically associated with each other in membrane extracts; thus, the antigen detected by anti‐MM2 serum was structurally similar to H‐2K and D antigens. Preclearing of lysates from C57BL/6 lymph node cells with a mixture of anti‐H‐2.2, anti‐H‐2.33, and anti‐H‐2.28 sera did not remove the ‘H‐2‐like’ antigen, indicating that the antigen was distinct from the H‐2Kb and Db molecules. Neither C3H/He nor B10. BR lymph node cells expressed the ‘H‐2‐like’ antigen, but B10. A(4R) and B10. AM lymph node cells did possess the antigen. Absorption of anti‐MM2 serum with EL4 cells abolished the capacity of the absorbed serum to precipitate the ‘H‐2‐like’ antigen activity on C57BL/6 lymph node cell extracts and reduced the ‘H‐2‐like’ radioactive peaks of the hybrid cells. These results indicate that there are at least two components being recognized by the anti‐MM2 serum in hybrid cells between MM2 tumor and mouse L cells, both of which had originated in the C3H/He mouse (H‐2k). One is the same as or cross‐reactive with an ‘H‐2‐like’ alloantigen of normal C57BL/6 lymph node cells (H‐2d) and the other is another ‘H‐2‐like’ antigen. Experiments with recombinant mice show that the ‘H‐2‐like’ alloantigen on lymph node cells is coded for by the D region and/or to the right of the D region of the major histocompatibility complex (MHC).
Report on international comparative evaluation of possible value of assays for immune complexes for diagnosis of human breast cancer
Authors: Herberman Ronald B. , Bordes M. , Lambert P. H. , Luthra Harvinder S. , Robins R. A. , Sizaret Philippe , Theofilopoulos Argyrios
Published: February 2007

There have been several reports on the possible value of measurement of circulating immune complexes for the diagnosis of human breast cancer. To begin to evaluate this possibility and the comparability of results among laboratories, a cooperative study was organized under the auspices of the International Agency for Research on Cancer and the National Cancer Institute (NCI) of the United States. Investigators from four laboratories performing assays for immune complexes were sent coded aliquots of serum specimens from the NCI‐Mayo Clinic Serum Bank. The serum panel consisted of specimens from 30 patients with breast cancer (including 20 from untreated patients with resectable tumors), 30 preoperative patients with benign breast disease, and 30 normal women. Although some significant differences in levels of immune complexes between cancer patients and controls were seen, none of the assays had sufficient discriminatory capacity to support optimism about the diagnostic value of this approach. To relate the results with immune complexes to those with a widely used cancer marker, the same sera were also tested for levels of carcinoembryonic antigen (CEA). The CEA assay provided significant discrimination between cancer patients and normal donors but did not significantly discriminate between malignant and benign breast diseases.
Induction of differentiation in murine myelomonocytic leukemia cells by the serum of patients with acute myeloid leukemia and other diseases
Authors: Metcalf Donald
Published: February 2007

Sera from patients with leukemia, lymphomas or other diseases were tested for their capacity to induce differentiation in colonies produced in semi‐solid agar by the mouse myelomonocytic leukemia, WEHI‐3B. Of 949 samples tested, higher than normal differentiating activity was detected in patients with infections (31% of sera tested) and with acute myeloid leukemia in relapse (35% of sera tested). The higher activity of the latter sera was correlated with the concurrent presence of infections in the relapse leukemic patients. Elevated differentiating activity was also observed in sera from patients with neutrophil levels below 1,000/μl even if infections were not present. The study indicates that patients with acute myeloid leukemia are able to elevate serum differentiating activity in response to infections or neutropenia and that the serum differentiating factors could play a role in suppressing myeloid leukemic populations by enforcing differentiation in the leukemic cells.
Studies on the role of cellular immunity and genetics in the etiology of rapidly progressing breast cancer in tunisia
Authors: Levine P. H. , Mourali N. , Tabbane F. , Loon J. , Terasaki P. , Tsang P. , Bekesi J. G.
Published: February 2007

It has been suggested that poussée évolutive (PEV) or rapidly progressing breast cancer (RPBC) represents a failure in the host immune system to control the proliferation of breast cancer cells. To evaluate this possibility, we have performed in vivo and in vitro assays of cellular immunity in Tunisian patients with breast cancer. Studies of delayed hypersensitivity using microbial antigens and in vitro studies including lymphocyte transformation tests and measurements of B and T cells indicated that RPBC patients had an immune response comparable to that of breast cancer patients without evidence of rapid progression. Normal Tunisians were more immunocompetent, however, and appeared to have a higher level of immune activity than normal individuals in the United States. In a second, independent series, an increased frequency of blood group A was found in RPBC patients, suggesting a genetic predisposition to this form of breast cancer. However HLA typing for A, B and DRW antigens revealed no specific RPBC‐associated HLA antigen. Our studies clearly demonstrate that RPBC, or PEV, is not a reflection of immunodeficiency.
Mechanism of enhancement of epstein‐barr virus‐induced transformation of peripheral blood lymphocytes by a tumor promoter, tpa, with special reference to lowering of cytotoxicity of t cells
Authors: Harada Shinji , Katsuki Takato , Yamamoto Hidehiko , Hinuma Yorio
Published: February 2007

The mechanism of the previously observed enhancement of Epstein‐Barr virus (EBV)‐induced cell transformation of human lymphocytes by 12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA) was studied. A concentration of TPA (0.5 ng/ml) was used. In cultures of human cord blood lymphocytes infected with EBV in the presence of TPA, a larger number of EBV‐associated nuclear antigen (EBNA)‐positive and/or DNA synthesizing cells was observed than in the absence of TPA. In the virus‐infected lymphocyte cultures of EBV‐seropositive adult donors, in vitro regression of transformation, which is known to be caused by T lymphocytes, was suppressed by TPA. EBV‐specific and ‐non‐specific cytotoxicity of T cells generated in mixed cultures of peripheral blood lymphocytes (PBL) of seropositive adults and autologous lymphoblastoid cell line (LCL) cells was markedly lowered by the presence of TPA in the cultures. However, TPA had little effect on proliferation of T cells in stimulated cultures, and addition of TPA to the reaction mixture for the cytotoxicity test did not lower the cytotoxicity. These results suggest that TPA has an inhibitory effect on T cells which suppress EBV‐transformation. The effect on T cells, together with the direct promoting effect on proliferation of EBV‐transformed cells, may explain the outcome of enhancement of EBV‐induced LCL establishment from PBL of seropositive donors by TPA previously observed.
Characterization of a human papillomavirus from epidermodysplasia verruciformis lesions of a patient from upper‐volta
Authors: Pfister Herbert , Nürnberger Friedrich , Gissmann Lutz , Hausen Harald Zur
Published: February 2007

A case of epidermodysplasia verruciformis in a patient from Upper‐Volta is described. Slightly elevated, flat warts were observed on hands, feet, arms and legs, and pityriasis versicolor‐like lesions were found mainly on the trunk. The patient showed no malignant tumors. Histological examination revealed hyperkeratosis, granulosis and moderate acanthosis with large, foamy, basophilic keratinocytes in stratum granulosum and stratum spinosum. Papillomavirus particles could be prepared from these lesions and were differentiated from known papillomavirus types by immune electron microscopy with monospecific antisera and by DNA‐DNA hybridization. The viral DNA was characterized by cleavage with several restriction endonucleases and a physical map of the resulting fragments was established. The virus is designated as HPV 8. Preliminary seroepidemiologic studies with human sera indicate a rather wide distribution of HPV 8. Blot hybridization of DNA from human carcinomas with 32P‐labelled virus DNA detected no HPV 8‐specific sequences.
Clonal analysis of the ability of tumor cells to form colonies in semi‐solid medium
Authors: Brodskaya R. M. , Stavrovskaya A. A. , Stromskaya T. P. , Vasiliev J. M.
Published: February 2007

Near‐diploid mouse tumor cells CAK‐25 AGr are characterized by low cloning efficiency in semi‐solid medium: about 10−5 per cell plated in methylcellulose. The properties of cells that have formed colonies in methylcellulose were compared with those of the parental population. Nine of 12 subclones of CAK‐25 AGr picked from methylcellulose retained parental cloning efficiency when retested for growth in semi‐solid medium. Thus most colonies in methylcellulose were not formed by variant cells different from the parental cell population. Cloning efficiency of CAK‐25 AGR and of its subclones on the solid substratum was high. All six sub‐subclones randomly isolated from the solid substratum had the ability to form colonies in methylcellulose at a frequency no lower than that of the parental clone. Thus, most cells of the population had not lost the ability to form colonies in methylcellulose. The results suggest that the probability of a cell's initiating a colony in semi‐solid medium is heritable and identical for most cells of the line under investigation.
Radioisotope assay for evaluation of in vivo natural cell‐mediated resistance of mice to local transplantation of tumor cells
Authors: Gorelik E. , Herberman R. B.
Published: February 2007

A radioisotopic assay based on the rate of elimination of [125I]dUrd‐labelled tumor cells from the local site of inoculation was used to study anti‐tumor natural cellmediated immunity in vivo. [125I]dUrd‐labelled YAC‐I, RL♂ I, and M109 tumor cells were inoculated into the footpads of mice and the radioactivity remaining at the site was measured at various times. This method allowed quantitation, in individual mice, of the actual number of tumor cells inoculated and their local clearance. It was found that 90–99% of inoculated YAC‐I or RL♂ I cells were eliminated in the first 24–48 h following transplantation. Participation of NK cells in the local elimination of the transplanted tumor cells was supported by the following findings: (1) The rate of elimination of NK‐sensitive tumor cells was higher than that of the NK‐resistant M 109 tumor cells. (2) There was a positive correlation between the level of in vitro spleen‐cell NK activity of the different strains of mice and the rate of in vivo elimination of YAC‐I. (3) Inoculation of poly I:C or cyclophosphamide increased or decreased, respectively, the clearance of tumor cells in vivo. (4) Local adoptive transfer of normal spleen cells accelerated the rate of tumor cell elimination in vivo. (5) This adoptive transfer of the cytotoxicity was mediated by non‐adherent, non‐T cells that expressed asialo GMI. Despite these correlations between NK activity and the in vivo assay, two major discrepancies were found: YAC‐I cells were eliminated at the same rate in young and old mice, and beige mice were as effective for in vivo clearance of tumor cells as were normal C57BL/6 mice. These data suggested that other natural effector cells may participate in the in vivo destruction of the transplanted tumor cells or that different regulatory processes may operate in vivo. Our findings provide further evidence that natural cell‐mediated immunity can play an important role in the in vivo elimination of the transplanted tumor cells and indicate that this can occur at the local site of tumor inoculation as well as in the lungs or other organs.
Block of a glioma cell line in S by interferon
Authors: Lundblad D. , Lundgren E.
Published: February 2007

The human glioma cell line U‐251 MG, with a well‐characterized defect in growth control, was sensitive to the antiproliferative effects of human (fibroblast) interferon (IFN). IFN inhibited exponentially growing cells by increasing the number of cells in the S stage of the cell cycle. At the same time the number of cells in G0/G1 diminished. The rate of thymidine incorporation was decreased during the first cell cycle, with no prolongation of S. However, in synchronized cultures, the wave of cells with a S‐phase content did not decrease over a time period several hours longer than the length of S measured by pulse labelling. Thus we conclude that, at a sufficient dose, the cells were unable to accomplish cell division as they prematurely stopped synthesizing DNA.
Two human tumor‐associated antigens, p155 and p210, detected by monoclonal antibodies
Authors: Loop S. M. , Nishiyama K. , Hellströ I. , Woodbury R. G. , Brown J. P. , Hellströ K. E.
Published: February 2007

BALB/c mice were immunized with human melanoma cells and their spleen cells hybridized with NS‐I myeloma cells. The hybrids were screened for the production of antibodies that bound to melanoma cells. Two hybridomas of interesting specificity were identified and cloned. Hybridoma 5.1 produces an IgG1 antibody that binds to about half of the melanomas and carcinomas tested. The target is a polypeptide with an apparent molecular weight of 210 kilodaltons on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE). The antigen, denoted p210, is also expressed in normal adult brain and in certain fetal tissues. Hybridoma 6.1 produces an IgM antibody that binds to about 50% of the melanomas, and 80% of the kidney carcinomas tested. The antigen defined by this antibody in melanomas has an apparent molecular weight of 155 kilodaltons and is denoted p155. It has not been observed on any normal adult or fetal tissues. The antigen present in the kidney carcinomas was not p155, but rather consisted of two proteins of approximately 60,000 and 250,000–300,000 daltons. This observation suggests the possibility that the antigenic deteminant recognized by antibody 6.1 may be present on several distinct protein molecules.
Some immunogenic and biochemical properties of tumor‐associated transplantation antigens (TATA) obtained in soluble form or solubilized from two methylcholanthrene‐induced sarcomas, meth A and CI‐4
Authors: Rogers Michael J. , Law Lloyd W.
Published: February 2007

The subcellular distribution of the tumor‐associated transplantation antigens (TATAs) of two highly immunogenic methylcholanthrene‐induced sarcomas, Meth A and CI‐4, were compared. Most of the TATA of CI‐4 was found in the soluble fraction (cytosol) of the cell while the TATA from Meth A was variably distributed between the membrane and cytosol. The soluble fraction TATAs from both tumors were very immunogenic and their strong immunity could not be influenced by administering antigen in a variety of protocols that altered the immune response in other systems. The soluble fraction and membrane‐associated TATAs from both tumors could be specifically bound to liposomes in re‐constitution experiments and the antigenicity of all of the TATAs was significantly enhanced when they were incorporated into these artificial membranes.
Liposomally activated macrophages; subsequent interaction with L1210 leukemic cells
Authors: Luckenbach G. Albrecht , Layton Derek
Published: February 2007

The coincubation of liposomes with mouse leukemia cells or fibroblasts can cause a wide range of effects on their viability. These effects are not particularly specific in terms of destroying the leukemic cells. However, it was observed that the combination of phosphoryl‐choline‐cholesterol (PC‐CHOL)1‐liposomes, which are not toxic by themselves, with alkyl‐lysophospholipids as components of the liposome, can produce the desired specific cytotoxicity for leukemic cells. In this report we show that the cytotoxic effect of vinca alkaloid entrapped in PC‐CHOL‐liposomes was enhanced by syngeneic mouse bone marrow macrophages. In addition, alkyl‐lysophospholipids, which are known to be potent macrophage activators, augment the cytotoxicity. Thus, the macrophage could act as a carrier for liposome‐entrapped drug and, on the other hand, the liposomes partly composed of macrophage activating alkyl‐lysophos‐pholipid and loaded with chemotherapeutic drug seem to be ideal carriers of two effector mechanisms for attacking leukemic cells.
On the mechanism of tumor ‘concomitant immunity’
Authors: Gorelik Eliezer , Segal Shraga , Feldman Michael
Published: February 2007

Experiments were carried out relevant to the mechanisms involved in tumor ‘concomitant immunity’. Mice bearing 3LL, B16, EL4 or the methylcholanthrene‐induced T‐10 tumors were capable of completely suppressing the growth of a subsequent intra footpad graft of tumor cells. The observed inhibitory activity exerted by the primary tumor increased with the increase in size of the tumor and reached its maximum at the latest period of tumor growth when the immune response of the tumor‐bearing host was largely suppressed. In T‐cell‐depleted animals (B mice or nude mice), the inhibitory effect exerted by the first tumor on the subsequently implanted tumor graft was as effective as in normal mice. Hence it appears that concomitant immunity is not mediated via a T‐cell‐dependent immune reaction. The observed inhibitory effect was tumor‐nonspecific. Mice bearing a 3LL tumor manifested resistance to the reinoculation of 3LL, B16 or EL4 tumor cells. Similarly, mice bearing B16, EL4 or T‐10 tumors arrested the growth of reinoculated 3LL tumor cells. Hence, concomitant immunity is not a result of specific immune response. Metastases can be considered as ‘naturally’ occurring secondary grafts. Indeed, we found that the local tumors exert a strong inhibitory effect on their lung metastases. Thus, the surgical removal of the local 3LL tumor led to an acceleration of metastatic growth in the lungs. Such acceleration took place even when the local tumor grew in immune‐suppressed mice. It appears, therefore, that ‘concomitant immunity’ and the suppression of metastatic growth exerted by the local tumor, are based on similar mechanisms.
Suppressor cell activity in melanoma patients. I. Relation to tumor growth and immunoglobulin levels in vivo
Authors: Werkmeister J. , McCarthy W. , Hersey P.
Published: February 2007

The effect of tumor growth on the suppressor cell activity of melanoma patients was examined by measurement of immunoglobulin produced in vitro in pokeweed mitogen (PWM)‐stimulated cultures of B and T lymphocytes. B and T cells were separated by sheep red blood cell resetting and suppressor cell activity was assessed by comparison of immunoglobulins produced in cultures with irradiated T cells (2,000 rads) to that with unirradiated T cells. In the majority of patients with localized melanoma, radiosensitive suppressor T cells were detected and appeared to be an augmentation of a normal physiological state. In patients with Stage I and II melanoma, removal of the tumor resulted in a significant decrease in suppressor activity against IgA and IgM but not against IgG production. Similar sequential changes in suppressor cell activity were not generally detected in patients who had surgery for skin graft after previous removal of the primary melanoma or in patients undergoing surgery for non‐malignant conditions. Sequential studies on the levels of serum immunoglobulins showed an apparent trend for immunoglobulins to increase after surgery. Of particular importance, the decrease in in vitro suppressor cell activity against IgM and IgG production after tumor removal in individual patients was significantly associated with an increase in immunoglobulin levels in the serum of these patients. It is suggested that these findings may account in part for the absence of detectable antibody responses to melanoma antigens in many patients and for the generalized immunodeficiency in patients with disseminated melanoma.
Differentiation antigens expressed by epithelial cells in the lactating breast are also detectable in breast cancers
Authors: Arklie J. , Taylor‐Papadimitriou J. , Bodmer W. , Egan M. , Millis R.
Published: February 2007

Two monoclonal antibodies, 3.14.A3 and 1.10.F3, raised against a delipidated preparation of the human milk fat globule and characterized as epithelium‐specific (Taylor‐Papadimitriou et al., 1981) were assayed histologically, by an indirect immunoperoxidase technique, against formalin‐fixed, paraffin‐embedded, normal and tumour tissue sections, in order to establish their in vivo specificity. Both antibodies bound to less than 10% of the alveoli and ducts in the resting breast, but bound to all areas of alveoli, ducts and secretion in the lactating breast. Binding was to the luminal surface of the alveolar and ductal epithelium. Antibody 3.14.A3 showed positive reactions with each of 20 primary breast carcinomas tested, and with metastatic lesions in lymph nodes from six of these. Antibody 1.10.F3 also reacted with most of the primary carcinomas but not with those of the mucoid type nor with metastatic lesions in lymph nodes. When tested against a variety of normal tissues, 1.10.F3 bound only to the luminal epithelial surface of classically defined exocrine glands, to their associated ducts and to the collecting tubules of kidney and bronchioles of the lung. 3.14.A3 showed a similar pattern of binding to 1.10.F3 but also bound to sweat glands, the alveolar epithelium of lung and the luminal epithelium of the ductuli efferentes of the epididymis. The only tumours, other than breast, showing a positive reaction with the antibodies were adenocarcinomas of the lung, uterus and ovary.
Plasma prolactin levels and age in a female population: Relation to breast cancer
Authors: Bulbrook R. D. , Wang D. Y. , Hayward J. L. , Kwa H. G. , Cleton F.
Published: February 2007

Plasma prolactin levels have been measured in over 4,000 normal women. The relation between hormone levels and age fits a cubic equation. It is suggested that a curve of this nature would generate the observed ageincidence curve for breast cancer, if prolactin were a carcinogen or promoter.
Characterization of clones of tumorigenic feline cells transformed by a chemical carcinogen
Authors: Rhim J. S. , Koh K. S. , Chen A. , Essex M.
Published: February 2007

Tumorigenic clonal lines derived from soft agar colonies induced by DMBA‐transformed feline embryo cells were isolated and characterized, the morphologically altered clonal cells formed large aggregates, growing in this aggregate form when suspended in liquid growth medium above an agar base and forming colonies in soft agar with high efficiency. When inoculated into athymic nude mice, chemically altered clonal cells produced progressively growing sarcomas. Cells established from the tumors morphologically resembled the DMBA‐transformed feline embryo cells and were characterized as cat cells by karyological analysis. The tumorigenic lines were negative for feline oncornavirusassociated cell membrane antigen (FOCMA), and for “gag‐X” the transformation‐related polyprotein which is encoded by the replication defective feline sarcoma virus.
Carcinogenic activity in rats of combined treatment with cyclophosphamide, methotrexate and 5‐fluorouracil
Authors: Habs Michael , Schmähl Dietrich , Lin P. Z.
Published: February 2007

A total of 240 outbred Sprague‐Dawley rats were treated with 3 different doses of the cyclophosphamide‐methotrexate‐5‐fluorouracil (CMF) regimen adopted from clinical chemotherapy studies in breast cancer patients. Eighty untreated rats served as controls. Individual and total doses of the drugs applied were lower than corresponding doses used in human adjuvant therapy protocols compared on a mg/m2 basis. Lifelong observation of the animals demonstrated a strong doserelated carcinogenic response to the tested scheme. Main target organs of treatment‐related neoplasms were the nervous system, the hematopoietic and lymphatic tissue, the urinary bladder, and the suprarenal gland. It is concluded that the CMF drug combination evokes carcinogenic responses in several organ systems in the rat and should be regarded as representing a carcinogenic risk to humans. Uncritical clinical use of the three‐drug protocol should be avoided.
Phosphorylation of chromosomal proteins from mammary cell lines
Authors: Lai David Y. , Bustos Sergio E. , Howard Eugene F.
Published: February 2007

Phosphorylation of histone and non‐histone chromosomal proteins in two clonal mouse mammary cell lines having low (V‐14) ande high (T‐19) tumorigenicity was investigated. Logarithmic phase cells were incubated in medium containing 125 μCi/ml[32P]‐orthophosphate. Cell nuclei were isolated, chromosomal proteins (histones and non‐histones) extracted and their amino acid composition, protein/DNA mass ratios, 32P‐uptake and gel electrophoretic patterns examined. Significant differences in the histone and NHC‐protein phosphorylation of these two cell lines were found. Comparison of radioactivity profiles of electrophoretically separated T‐19 and V‐14 NHC‐proteins showed that 60 % of the T‐19 bands in the mol. wt range of 160,000 to 15,000 daltons had increased [32P]‐orthophosphate uptake. Differences in histone radiolabelling between V‐14 and T‐19 were confined to the HI, H3 and H4 classes. [32P]‐ATP‐pool measurements of V‐14 and T‐19 at 30,60 and 120 min of incubation were similar, hence the difference in 32P‐uptake was not due to ATP‐pool fluctuations. Results of studies on growth rate, growth potential and the possibility that comparisons were made between cells at different stages of the growth cycle indicated that these variables did not account for the higher phosphorylation of T‐19 chromosomal proteins. The increased [32P]‐phosphate uptake into T‐19 cell protein was correlated with an elevated content of NHC and histone proteins and pointed towards a correlation between the degree of phosphorylation and the high tumorigenicity of this cell line.
Activation of the epstein‐barr virus genome by 5‐aza‐cytidine in latently infected human lymphoid lines
Authors: Ben‐Ssson Shmuel A. , Klein George
Published: February 2007

Recent studies indicate that gene expression in higher eukaryotes is accompanied by a decrease in the frequency of 5‐methyl cytosine residues around the activated site (Razin and Riggs, 1980). 5‐aza‐cytidine (5‐aza‐C) is an analogue that reduces cytidine methylation in DNA (Jones and Taylor, 1980) and has been reported to change the differentiation pattern of cultured mouse embryo cells (Taylor and Jones, 1979). We have tested its ability to activate the Epstein‐Barr virus cycle in latently EBV‐infected human lymphoid lines. After an incubation period of 6 to 8 h with the drug, early antigens (EA) were induced in a substantial fraction of the cells in all six lines tested that had a low rate of spontaneous viral antigen production. Optimal conditions for EA induction were defined. The efficiency of 5‐aza‐C was comparable to the inducing effect of iododeoxyuridine. EBV‐DNA and EBNA positive virus‐non‐producer lines did not respond to 5‐aza‐C treatment. The findings are discussed in relation to the possibility that changes in EBV‐gene expression may be related to the state of DNA methylation.
Reversibility of the transformed and neoplastic phenotype. I. Progressive reversion of the phenotype of X‐ray‐transformed C3H/10T1/2 cells under prolonged treatment with interferon
Authors: Brouty‐Boyé Danièle , Gresser Ion
Published: February 2007

X‐ray transtormed mouse C3H/10T1/2 cells were cultivated and passaged in the continuous presence of partially purified mouse interferon. This prolonged interferon treatment resulted in a stepwise progressive reversion of the transformed phenotype to the non‐transformed phenotype. Thus interferon‐treated cells displayed an epithelioid morphology, grew to a lower cell density, and were no longer tumorigenic. Reversion to the non‐transformed phenotype was, however, stable only as long as interferon was continuously present in the culture medium. When interferon was removed, the cells “back reverted” to the transformed phenotype. Our results suggest that interferon induced a reversion of the transformed phenotype in the entire cell population rather than a selection of an interferon resistant cell population. C‐type viral particles and significant levels of reverse transcriptase were present in transformed cells, but neither present in the parental 10T1/2 cells nor in interferon‐treated cells. When interferon was removed from the culture medium, viral particles and reverse transcriptase activity were again detected. It is possible, therefore, that interferon induces reversion through it; antiviral activity, or that it induces reversion by its effects on cell function and structure, independently of any antiviral effect. Inhibition of cell multiplication per se does not appear to be sufficient to induce reversion, since cycloheximide inhibited cell multiplication; however, even after ten passages, it did not affect tumorigenicity. Our results suggest the possibility that interferon may act in vivo not only by inhibiting tumor cell multiplication but also by inducing a reversion. Patients with some tumors may therefore benefit from long‐term interferon treatment.
Feline leukemia ‐ unique and cross‐reacting antigens on individual virus‐producing tumors identified by complement‐dependent antibody
Authors: Grant Chris K. , Michalek Michael T.
Published: February 2007

Following exposure to feline leukemia virus (FeLV), cats that resist leukemia produce complement dependent antibodies (CDA) which lyse leukemia cells in the presence of cat complement. The CDA activity has been shown to be directed to feline oncornavirus‐associated cell membrane antigen (FOCMA) found on the surface of most feline leukemias. Despite the retrovirus etiology of feline leukemia, and the ubiquity of FOCMA expression by individual tumors, we found that CDA activity did not cross‐react when five feline leukemia lines were compared (FL74, F422, 3272, 3281, and 79–14940). Profiles for CDA mediated lysis of the leukemia target lines were determined for sera from 149 FeLV exposed cats, and animals were identified whose sera would selectively lyse almost any possible combination of tumors from one to five lines tested. Cross absorption and cold target inhibition studies were performed on selected sera, and a spectrum of different antigens was identified which included both individual determinants and antigens shared by some of the tumor lines. Leukemias FL74 and F422 carried a cross‐reactive determinant which was distinct from a second antigen shared by 3272 and 3281; lines F422, 3272 and 3281 each also carried a unique antigen. Leukemia 79–14940 did not cross‐react with other target tumor lines. Targets of CDA mediated lysis on leukemia cells maybe associated with normal feline cell surface antigens, because CDA titers were sometimes reduced after serum absorption with normal cat spleen cells. The relevance of multiple FOCMA determinants is discussed in terms of tumor escape from immunity.
Modulation of the expression of alkaline phosphatase genes in a human malignant cell line passaged through nude mice
Authors: Benham Frances J. , Balaban Gloria , Boccelli Denise , Harris Harry
Published: February 2007

Hep 2/5 cells, a clone of HeLa which expresses both placental‐type alkaline phosphatase and fetal intestinal alkaline phosphatase (ALP), were grown as solid tumors in nude mice. Analysis of ALP isozymes present in tumor specimens excised at intervals over a 52‐day period showed that levels of placental‐type ALP had dropped markedly, while levels of the intestinal ALP remained fairly constant. Cells re‐cultured from two two separate tumors regained most of the original placental ALP levels. However, levels of the fetal intenstinal ALP in cells returned to culture rapidly increased to more than six times the levels in the original cultured cells, and these increased levels persisted. Passage through nude mice thus induced at least semi‐permanent changes in the level of expression of fetal intestinal ALP in Hep 2/5 cells, and the nature of these changes may relate to the role of the isozyme locus in malignant cells.
Characterization of a rabbit anti‐human malignant glioma antiserum
Authors: Schnegg Jean‐Franlois , de Tribolet Nicolas , Diserens Annie‐Claire , Martin‐Achard Alec , Carrel Stefan
Published: February 2007

An antiglioma antiserum was produced by immunization of a rabbit with membrane‐enriched preparations of a human malignant glioma cell line, LN‐18. After extensive absorption, this antiserum reacted exclusively with antigenic determinants present on seven out of 16 malignant glioma cell lines tested, as shown by complement‐dependent cytotoxicity in a 51Cr‐release assay. This glioma specificity could be further confirmed by quantitative absorption experiments where cells from a glioma line, LN‐135, abolished the cytolytic reactivity of the antiserum against four other glioma lines. The step‐wise absorption of the crude antiserum consisted of: step 1, absorption with normal peripheral blood lymphocytes from 10 individual donors; step 2, absorption with a pool of cells from four different lymphoblastoid cell lines and one endometrial carcinoma; step 3, absorption with cells from a colon carcinoma; and step 4, absorption with cells from two different melanoma lines. After each absorption step the antiserum was tested by complement‐dependent cytotoxicity against a large panel of malignant glioma lines and control non‐glioma cell lines. After the absorptions from step 1 and 2 the antiserum reacted with all cell lines tested, while after step 3 absorption, it reacted only with cells from malignant glioma, melanomas and fetal brain. Quantitative absorption experiments performed at this stage with fetal brain cells showed that the reactivity for fetal brain and melanoma cells could be abolished, while the antiserum was still cytolytic for malignant gliomas. After the absorption from step 4, the antiserum reacted exclusively with seven malignant gliomas. After a further absorption with normal adult brain homogenate, the antiserum still reacted with four of the seven malignant glioma cell lines. Thus, the antiserum described here recognized three types of antigens: antigens common to cells of neuroectodermal origin, antigens shared by malignant gliomas and adult brain, and antigens expressed only on some gliomas.
Cholesterol metabolism in cancer cells in monolayer culture. III. Low‐density lipoprotein metabolism
Authors: Gal David , Macdonald Paul C. , Porter John C. , Simpson Evan R.
Published: February 2007

The metabolism of low‐density lipoprotein (LDL) was studied in neoplastic and non‐neoplastic cells of human gynecological origin, in monolayer cultures. The neoplastic cells were derived from epidermoid vaginal carcinoma, epidermoid cervical carcinoma and endometrial adenocarcinoma, in various degrees of differentiation. The non‐neoplastic cells were cervical fibroblasts and epithelial cells from proliferative endometrial glands. Both neoplastic and non‐neoplastic cells assimilated and degraded LDL in a similar fashion to other human cells (e.g. skin fibroblasts). However, the neoplastic cells metabolized LDL at a higher rate than the non‐neoplastic cells (e.g. epidermoid cervical cancer cells metabolized LDL at a 20 times higher rate than did cervical fibroblasts). Such a high rate of LDL metabolism probably enables continuously replicating cancer cells to obtain the large amounts of cholesterol required for cell membrane synthesis. If a high rate of LDL metabolism proves to be a general property of cancer cells, such a property could prove useful for tumor chemotherapy, providing cytotoxic chemicals could be incorporated within the LDL molecule.
Epstein‐Barr virus strain‐ and group‐specific antigenic determinants detected by monoclonal antibodies
Authors: Mueller‐Lantzsch Nikolaus , Georg‐Fries Brigitte , Herbst Hermann , Hausen Harald Zur , Braun Dietmar G.
Published: February 2007

In order to differentiate Epstein‐Barr virus (EBV) strains by serological markers we prepared hybridomas producing monoclonal antibodies against polypeptides of the QIMR‐WIL EBV strain. These monoclonal antibodies were screened by indirect immunofluorescence techniques. Immunoprecipitation, using EBV‐positive monoclonal antibodies and the protein A method, of 125I‐labelled polypeptides from purified QIMR‐WIL EBV particles, revealed that a series of monoclonal antibodies against the four main surface and envelope polypeptides precipitating p340, p340/p240, p140, and p80 were obtained. When 125I‐labelled polypeptides from purified P3HR‐I and B95‐8 EBV particles were immunoprecipitated, it could be demonstrated that several anti‐p340 (QIMR‐WIL) antibodies recognized strainspecific antigenic determinants, while anti‐p340/p240 (QIMR‐WIL) as well as anti‐p140 (QIMR‐WIL) antibody clones reacted with antigenic sites which are in common wither among B95‐8 or in addition to P3HR‐I polypeptides. Thus, monoclonal antibodies now provide a serological basis for EBV typing.
Cultivation of human melanomas in soft agar. Factors influencing plating efficiency and chemosensitivity
Authors: Tveit Kjell Magne , Fodstad Øystein , Pihl Alexander
Published: February 2007

As part of a programme to study the predictive clinical value of a soft agar assay for measuring chemosensitivity of human melanomas in vitro, we have observed the effect of three disaggregation methods on the yield of tumor cells, plating efficiency in soft agar and chemosensitivity. The yields and plating efficiencies obtained, as well as sensitivity to DTIC, CCNU, vinblastine and abrin, were about the same whether collagenase/pronase/DNase‐treatment, trypsin/EDTA‐treatment or mechanical treatment was used. When melanoma xenografts of different sizes were studied, an inverse relationship between tumor size and plating efficiency was found, whereas chemosensitivity was unaffected by tumor size. The highest plating efficiencies of melanoma cells, both from patient biopsies and from xenografts, were obtained when red blood cells were present and a low oxygen concentration (5%) was used. The results demonstrate that, in the case of melanomas, the fraction of tumor cells that are clonogenic in vitro depends on the size of the tumors, and even more so on the culture conditions used. An important finding was that chemosensitivity in vitro appears to be unaffected by the disaggregation method and by tumor size.
Sequential changes in peripheral blood leukocyte adherence inhibition (LAI) reactivity during progressive growth and spontaneous regression of canine transmissible venereal sarcoma
Authors: Harding Matthew W. , Yang Tsu‐Ju (Thomas)
Published: February 2007

Sequential changes in canine transmissible venereal sarcoma (CTVS) extract‐induced leukocyte adherence inhibition (LAI) reactivity of peripheral blood leukocytes (PBL) were monitored in dogs from the time of tumor inoculation through progressive growth and spontaneous regression or surgical excision of CTVS. The time‐course profiles of LAI reactivity of tumor dog PBL correlated with the clinical stage of tumor growth, substantiating our previous findings in a cross‐sectional study. The kinetics of the time‐course appearance of LAI reactivity observed and the demonstration of a rapid anamnestic response following tumor challenge indicate further that LAI is a reliable in vitro measure of in vivo tumor immunity. A significant increase in CTVS antigen extract‐induced LAI reactivity observed in the PBL during tumor regression suggests that LAI reflects a functional effector cell mechanism associated with spontaneous regression of CTVS. By contrast, absence of significant LAI reactivity of PBL during progressive tumor growth suggests the presence of serum blocking factors. In addition, a substantial rebound in LAI reactivity observed in the PBL of dogs 3 to 7 days following surgical excision of progressively growing CTVS provides further evidence that tumor‐cell components are associated with progressive tumor growth and diminished LAI reactivity.
Hodgkin and sternberg‐reed cell antigen(S) detected by an antiserum to a cell line (L428) derived from Hodgkin's disease
Authors: Stein Harald , Gerdes Johannes , Kirchner Hartmut , Schaadt Michael , Diehl Volker
Published: February 2007

Antisera to the cell line L428, derived from Hodgkin's disease, were raised in rabbits by injecting L428 cells intravenously and subcutaneously. The anti‐L428 cell serum that did not react with HLA‐DR was absorbed with tonsil cells plus acute myeloid leukemia cells or tonsil cells plus neutrophils, monocytes, and blood lymphocytes. Then it was tested for its ability to discriminate between L428 cells, Hodgkin and Sternberg‐Reed cells, and various other cells. It was found that the anti‐L428 cell serum absorbed with tonsil cells plus acute myeloid leukemia cells stained only L428 cells, Hodgkin and Sternberg‐Reed cells, and neutrophils. The anti‐L428 cell serum absorbed with tonsil cells plus neutrophils, monocytes, and blood lymphocytes reacted with L428 cells and Hodgkin and Sternberg‐Reed cells from 13 cases of Hodgkin's disease. It did not react with any other cell type present in the blood or in lymphoid tissue or with cells from five cases of non‐Hodgkin's lymphoma. The absorbed anti‐L428 cell serum also failed to stain Daudi and HRIK cell line cells. We conclude that the anti‐L428 cell serum defines an antigen that is apparently restricted in expression to L428 cells and Hodgkin and Sternberg‐Reed cells. This is a strong indication that the L428 cell line cells are derived from Hodgkin and Sternberg‐Reed cells.
Chromosomal banding patterns in human large bowel cancer
Authors: Reichmann Amelia , Martin Paulette , Levin Bernard
Published: February 2007

Cytogenetic banding studies were performed on direct preparations from 31 large bowel tumors. Twenty‐eight of these were from primary sites and three from metastases. Some distinctive patterns were observed. The 31 tumors were separable into four groups: (1) Tumors with normal karyotypes (three cases); (2) tumors with simple gains of chromosomes (three cases); (3) tumors with gains, losses and structural aberrations (ten cases). Groups 1, 2 and 3 were all in the diploid range; and (4) tumors with hypotriploid‐hypotetraploid karyotypes (15 cases). Non‐random gains of several chromosomes, especially No. 8 and non‐random losses of No. 17 were seen in this series. Thirteen cases had sex chromosome abnormalities. The most prominent structural abnormalities involved chomosomes No. 1 and No. 5. Marker chromosomes were sometimes absent, but when present ranged from simple translocations to the most complex rearrangements. Doubling of chromosome and/or marker chromosomes were prominent in Group 4. Double minutes were seen in all three metastatic tumors and three primary cancers. Premature chromosome condensation was observed in three cases in the hypotriploid‐hypotetraploid group.
Kaposi's sarcoma. IV. Detection of CMV DNA, CMV RNA and CMNA in tumor biopsies
Authors: Boldogh I. , Beth E. , Huang E.‐S. , Kyalwazi S. K. , Giraldo G.
Published: February 2007

In order to determine whether human cytomegalovirus‐ (CMV) DNA homologous sequences as well as CMV‐specific RNA(s) and antigen(s) exist in tumor biopsies of Kaposi's sarcoma (KS) DNA‐DNA reassociation, RNA‐DNA in situ cytohybridization and anticomplement immunofluorescence test (ACIF) tests were applied. Three of 10 DNAs extracted from Kaposi sarcoma biopsies contained DNA sequences homologous to radioactively labelled human CMV DNA probe. The amount of CMV DNA in these sarcoma tissues was calculated to range from 0.7 to 1 genome equivalent per diploid cell. The presence of virus‐specific RNA was also demonstrated in sections from five of 10 tumor biopsies. CMV‐determined nuclear antigen(s) (CMNA) present in variable degrees were also demonstrated. In contrast, we could not detect any herpes simple virus type II (HSV‐2) or Epstein‐Barr virus (EBV) DNA sequences in DNA of these tumor biopsies. Furthermore, there were no detectable HSV‐2 or EBV‐specific RNA or virus‐specific antigens in sections of these biopsies. These results provide new lines of evidence for the relationship between CMV and Kaposi's sarcoma.
Increased cancer incidence in the progeny of male rats exposed to ethylnitrosourea before mating
Authors: Tomatis L. , Cabral J. R. P. , Likhachev A. J. , Ponomarkov V.
Published: February 2007

Results from previous experiments have indicated the persistence of an increased cancer risk in subsequent generations following prenatal exposure to a chemical carcinogen. In the present experiment, the possible role of prezygotic events in determining cancer risk was investigated in the progeny of male rats treated with ethylnitrosourea (ENU) before mating with untreated females. Eight BDVI male rats were given a single i.p. dose of 80 mg/kg bw ENU and each rat was then caged at weeks 1, 2, 3 and 4 after treatment with three untreated females. Fertility was lower and preweaning mortality higher in the experimental group, as compared to controls, particularly at the 4th‐week mating. Survival rates after weaning were similar in the progeny of treated males and controls, as was the total incidence of tumours. However, analysis of tumour incidence at the various organ sites showed an increased incidence of neurogenic tumours in the progeny of ENU‐treated males, as compared to that of controls.
Embryo‐derived teratocarcinoma. III. Development of tumors from teratocarcinoma‐permissive and non‐permissive strain embryos transplanted to F1 hybrids
Authors: Solter Davor , Dominis Mara , Damjanov Ivan
Published: February 2007

Seven‐day‐old mouse embryos of two teratocarcinoma‐permissive (C3H and BALB/c) and two teratocarcinoma‐non‐permissive (C57BL/6 and AKR) strains were transplanted to their F1 hybrids to determine the role of the genetic background of the recipient animals in controlling embryo‐derived teratocarcinogenesis. The yield of teratocarcinomas in F1 hybrid recipients of embryonic grafts was either identical with the yield in syngeneic recipients or increased or decreased, depending on the strain of the embryo and the F1 hybrid combination. In certain hybrids, the yield of malignant tumors remained the same as in the syngeneic recipients but the F1 hybrids exerted a stimulatory effect on tumor growth and the tumors weighed more than those in syngeneic recipients. A matroclinous effect was also seen in certain hybrids. These data indicate that embryo‐derived teratocarcinogenesis in histocompatible F1 mice depends on the genetic background of adult recipients. The teratocarcinogenic potential of non‐permissive and permissive strain mouse embryos can be modified by choosing appropriate F1 hybrids for embryonic transplantations.