bluuebunny/crossref_metadata_2025 huggingface dataset:
Cytotoxic action of prostaglandin D2 on mouse neuroblastoma cells
Authors: Higashida Haruhiro , Kano‐Tanaka Kyoko , Natsuume‐Sakai Shunnosuke , Sudo Katsuko , Fukami Hiroko , Nakagawa Yuzo , Miki Naomasa
Published: February 2007

Addition to the culture medium of prostaglandin (PG) D2 resulted in the degeneration in a dose‐ and time‐dependent manner of NI8TG‐2 cells cloned from mouse neuroblastoma. The ED50 for PGD2‐induced cytotoxicity was about 10 μM. The degenerative changes were irreversible when the cells were exposed for more than 10 h. Scanning and transmission electron microscopic examination revealed that treatment with PGD2 resulted in apearance of numerous blebs of various sizes along the cell surface and also in destruction of surface membrane and of cytoplasmic organelles. Tumor weight of NI8TG‐2 neuroblastoma inoculated subcutaneously on the backs of A/J mice was about 35‐70% less than that of controls after 14 days of single daily i.p. or s.c. injections of 0.5‐1 mg/kg of PGD2. The results indicate that PGD2 has growth‐inhibitory effects on mouse neuroblastoma cells in vitro and in vivo.
Detection of different states of immunity to colon cancer in rats by a leukocyte adherence inhibition (LAI) assay assessing the adherence of T lymphocytes and monocytes selectively
Authors: Morizane Toshio , Sjögren Hans Olov
Published: February 2007

Peripheral blood mononuclear cells (MNC) of rats, which had received a subcutaneous inoculation of either viable or X‐irradiated syngeneic DMH‐W49 colon carcinoma cells, were investigated sequentially for sensitization against tumor‐associated antigens by a new micro‐glass‐tube leukocyte adherence inhibition (LAI) assay. The number of adherent cells of MNC subpopulations was estimated by a cellular radioimmunoassay (CRIA), which utilizes anti‐monocyte (MC) antiserum or anti‐T‐cell monoclonal antibody (McAb) and 125I‐labelled protein A. LAI reactivity was demonstrated in rats sensitized with X‐irradiated tumor cells when assessing the adherence of both T lymphocytes and monocytes. It was found that reactivity with the two different types of indicator cells did not usually coincide in time. The same phenomenon was also observed in tumor‐bearing rats although with lower levels of LAI reactivity. In both groups the LAI response detected by anti‐T‐cell reagent mostly appeared earlier after tumor‐cell inoculation than the response demonstrated by anti‐MC serum. The T‐lymphocyte‐associated reactivity also disappeared more rapidly. These results suggest that different states of immune reactivity are reflected in LAI responses involving T lymphocytes and monocytes as indicator cells.
International variations and temporal trends in mortality from multiple myeloma
Authors: Cuzick Jack , Velez Ramon , Doll Richard
Published: February 2007

Mortality statistics for multiple myeloma over the period 1960–1975 have been analysed for 23 countries. Attention has been focused on international variations, secular trends, and the male to female mortality ratio. The greatest percentage increases have been found in countries with low overall rates. The male:female ratio was generally higher in countries with high rates, and the national rates correlated more strongly with GNP per caput than with an index of medical care (hospital beds/10,000). Further analyses have been carried out over the period 1955–79 in Sweden, a country with high but relatively stable rates, and Japan, where the rates are very low but are increasing rapidly. An age, period, and cohort analysis of the trends in these countries is presented and criticized. The contributions made by increased diagnostic capability and by an increase in the true incidence of the disease are discussed.
Expression of Thy‐1 antigen on human melanoma cells
Authors: Hersey P. , Grace Julienne , Murray Elaine , Palmer A. , McCarthy W. H.
Published: February 2007

The expression of Thy‐1 was examined on fresh frozen sections of melanoma and control skin lesions using a monoclonal antibody to Thy‐1 and immunoperoxidase‐labelled second antibodies. Thy‐1 was detected on 12 of 19 primary melanomas but on only 1 of 23 melanoma metastases in lymph nodes, skin or brain. Expression of Thy‐1 did not appear related to other known histological features of primary melanoma. Thy‐1 was also expressed on 2 of 7 naevi but not on normal melanocytes or carcinoma of squamous cells, basal cells and sweat glands of the skin. Some lymphocytes below primary melanomas were Thy‐1 positive. These results suggest that Thy‐1 may be a marker of melanocytes at certain stages of differentiation analogous to its expression on cell lineages in the haemopoietic system. The relative paucity of Thy‐1 on metastases may indicate that its expression on melanoma cells has prognostic significance for behaviour of the tumour in its host.
Among the human antibodies reacting with intracytoplasmic a particles of mouse mammary tumor virus, some react with MMTV p14, the nucleic‐acid‐binding protein, and others with MMTV p28, the main core protein
Authors: Zotter Stefan , Grossmann Heinz , François Camille , Kozma Sara , Hainaut Pierre , Calberg‐Bacq Claire‐Michelle , Osterrieth Paul M.
Published: February 2007

Human IgG antibodies reacting in the indirect immunofluorescence test with clusters of intracytoplasmic A particles in mouse tissues were analyzed by means of both radioimmunoprecipitation and enzyme‐linked immuno‐absorbant assays. Generally, antibody‐containing sera reacted with epitopes of p14, the nucleic‐acid‐binding core protein of mouse mammary tumor virus, corresponding to the protein Ap14 of intracytoplasmic A particles. Comparatively few sera reacted with epitopes of the main core protein p28 corresponding to the protein Ap28 of intracytoplasmic A particles. The two types of reactivity occurred independently of each other.
Correlation of drug sensitivity on human colon adenocarcinoma cells grown in soft agar and in athymic mice
Authors: Zirvi Karimullah A. , Masui Hideo , Giuliani Fernando C. , Kaplan Nathan O.
Published: February 2007

A well‐differentiated colorectal tumor T 219 which grows as a xenograft in athymic mice (human‐tumor‐nude‐mouse system) and forms colonies in culture (soft agar colony‐formation assay) has been used to test the correlation between the above two methods of exposure of human tumor cells to antineoplastic agents. In in vitro studies, two protocols were used: I h drug exposure and continuous drug exposure. In the I h drug exposure experiments six drugs, doxorubicin (DX), 4′‐deoxydoxorubicin (deoDX), 4′epidoxorubicin (epiDX), 4′‐O‐methyldoxorubicin (O‐DX), N‐trifluoroacetyldoxorubicin‐14‐valerate (AD‐32) and 5‐fluorouracil (FUra) were studied, while in continuous drug exposure experiments four of the above drugs (DX, deoDX, epiDX, O‐DX) were studied. The survival of the tumor clonogenic cells (HC219) was determined by counting the number of colonies formed during 13–14 days of incubation and dose‐response curves were obtained. In in vivostudies, the mice were treated with all of the drugs used in in vitro I h drug exposure experiments (DX, deoDX, epiDX, O‐DX, AD‐32 and FUra). To quantitate the chemotherapeutic effectiveness of the drugs, T/C% (relative tumor volume of treated group as percentage of the control group) values were calculated each time the tumors were measured. The experimental data suggest that in vitro I h drug exposure results are in good agreement with the in vivo results, while the continuous drug exposure results do not agree with the in vivo data. The most active drug in in vivo studies, deoDX, was found to be the most active drug in the in vitro I h drug exposure experiments as well. However, in continuous drug exposure experiments, O‐DX, not deoDX, was found to be the most active drug. Activities of the other drugs tested also differed from their respective activities in in vivo studies. Although the relative effectiveness of various drugs can be compared by determining molar concentrations of the drugs producing 50% inhibition of colonies (ID50) the expression, PEI = LD10/ID50 × 1000, which takes into consideration toxicity of the drugs, is probably a better indicator of the in vitro drug activity. The results suggest that soft agar colony‐formation assay (with established cell lines from the same tumor) may be used for the prediction of in vivo activity of potential antineoplastic agents against human tumor xenografts in nude mice.
Differential cytotoxicity of tumour promoter TPA for EBV‐negative human lymphoma cell lines and their EBV‐converted sublines
Authors: Béchet Jean‐Marie , Guétard Denise
Published: February 2007

The tumour‐promoting phorbol diester 12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA) is toxic at nanomolar concentrations for Epstein‐Barr virus (EBV)‐negative human lymphoma cell lines BJAB and Ramos. Sublines that have been converted to Epstein‐Barr nuclear antigen (EBNA)‐positivity by infection with EBV survive and grow in TPA concentrations that are lethal for their non‐converted parental lines. Resistance to the growth‐inhibiting effect of TPA is higher in sublines of BJAB and Ramos that have been converted by the transforming B95‐8 strain of EBV than in those converted by the non‐transforming P3‐HRI strain. The loss of TPA‐sensitivity may reflect a change in the transformation or differentiation state of lymphoma cells as a result of EBV‐conversion.
Plasminogen activator activity of metastatic variants from a murine fibrosarcoma; effect of thrombin in vitro
Authors: Coen Daniele , Bottazzi Barbara , Bini Alessandra , Conforti Maria Grazia , Mantovani Alberto , Mussoni Luciana , Donati Maria Benedetta
Published: February 2007

In order to investigate the possible correlation between plasminogen activator (PA) activity and metastatic potential of tumour cells, we studied cultured cells from the murine fibrosarcoma mFS6 and from its two sublines M4 and M9 which differ markedly in their capacity to cause spontaneous metastases in the lung. PA activity was detected in all the sublines by an amidolytic method and was almost completely inhibited by treatment with anti‐urokinase antiserum. No significant differences were shown between mFS6, M4 and M9. Moreover, molecular analysis of PA by SDS‐PAGE electrophoresis and fibrin overlay revealed in all the cell types a single species having a mol. wt. of approximately 48,000 daltons. Thrombin treatment dramatically inhibited the amidolytic activity of all cells, suggesting a role for this enzyme in the modulation of fibrin formation and dissolution within the primary neoplasm.
Liver‐to‐lung traffic of cancer cells
Authors: Weiss Leonard , Ward Pamela M. , Holmes Janet C.
Published: February 2007

Following the injection of B16 melanoma cells into the portal veins of mice, all animals developed liver tumors, but only 16% developed lung tumors. Portal vein injections of radiolabelled B16 and Walker 256 cancer cells into mice and rats, respectively, revealed that all of the cells were temporarily arrested in the liver and most were then slowly released. Bioassays indicated that of 8 × 104 B16 cells released from the liver over 24 h after portal vein injections of 105 cells, only approximately 1% were delivered to the lungs in a viable state. Experiments made with radiolabelled B16 cells showed that transit through either the liver or lungs following portal vein or tail vein injections, respectively, resulted in massive death of cancer cells. It is suggested that the death of most circulating cancer cells passing through the first organ encountered after leaving their primary tumor, serves to severely limit their further direct spread to other organs. It is therefore expected that metastases to these other organs would, to a large extent, be generated by cancer cells from metastases in the “first organs” as distinct from direct seeding from cancer cells released from the primary tumor. If the results of the present experiments have general application, they serve to emphasize the importance of metastasis of metastases in the natural history of the spread of cancer. In a previous publication (Weiss, 1980), studies of lung‐to‐liver traffic of cancer cells in rats revealed that, after tail vein injections, most Walker 256 cells were temporarily arrested in the pulmonary vasculature and then slowly released. A large proportion of the released cancer cells were dead or lethally injured on release from the lungs, and this “first organ processing” apparently accounted for the comparative rarity of extrapulmonary tumors following tail vein injections. In this communication, the concept of “first organ processing” of circulating cancer cells is further examined with respect to the liver‐to‐lung traffic of B16 melanoma and Walker 256 cells injected into the portal veins of mice or rats respectively. Both of these cell types grow well in the lungs following tail‐vein injection.
Alpha‐fetoprotein synthesis in relation to structural peculiarities in postnatal and regenerating mouse liver
Authors: Gleiberman A. S. , Kuprina‐Khramkova N. I. , Rudinskaya‐Beloshapkina T. D. , Abelev G. I.
Published: February 2007

The localization of alpha‐fetoprotein (AFP) and of antigens of liver‐cell plasma membrane (Ag I, Ag II and Ag III) was studied in adult, postnatal and regenerating (CCI4 or paracetamol‐treated mouse liver). Ag I, Ag II and Ag III were solubilized by Triton X‐100 from ghosts of the mouse liver cells. The purification of antigens was performed by gel filtration on Sephadex G‐200 or Ultrogel ACA‐54 with subsequent treatment of antigenic fractions eluted from the column with 5% HCIO4. Ag I and Ag II are common for liver and some other mouse organs, but Ag III is strictly specific for liver. The Ag I is predominantly found in the region of the bile capillaries. Ag II and Ag III are mainly present on membrane adjoining blood sinusoids. The distribution of these three antigens in newborn mouse liver is quite different from that in adult liver and reflects the specific arrangement of hepatocytes at different stages of development — the acinar structure in newborn liver and the plate structure in the adult organ. During regeneration as well as during postnatal development, AFP has been found in areas of marked tissue rearrangement. In both cases, these areas lose the plasma membrane antigens, especially Ag I — the antigen of bile capillary. The reappearance of Ag I on the surface of liver cells coincides with cessation of AFP synthesis and establishment of definitive plate structure. The possible role of liver plate structure in the regulation of AFP synthesis is discussed.
Lymphotoxin amplification of tumor growth inhibition is specific for natural killer cells but not for macrophages
Authors: Ransom Janet H. , Pintus Cristina , Evans Charles H.
Published: February 2007

Lymphotoxin augments the susceptibility of tumorigenic guinea‐pig cells to natural killer (NK) cell cytolysis in vitro but does not directly stimulate either NK cell or macrophage cytolytic action. The question whether lymphotoxin enhances the susceptibility of tumorigenic guinea‐pig cells to cytolysis or other means of growth inhibition in vivo by syngeneic NK cells or macrophages was, therefore, examined using a modified tumor cell neutralization (Winn) assay. Mineral oil‐, thioglycollateor casein‐induced peritoneal leukocytes, but not the macrophges isolated from the elicited leukocytes obtained from nonimmunized strain 2/N guinea‐pigs, effected enhanced cytolysis of lymphotoxin‐treated guinea‐pig benzo (a)pyrene‐induced 104CI tumor cells in vitro. Neither guinea‐pig splenic NK cells nor oil‐induced peritoneal macrophages alone inhibited the growth of 104CI cells as tumors in vivo when admixed with 104CI cells and injected into guinea‐pigs. However, when the 104CI cells were treated with lymphotoxin before addition of effector cells, NK cells but not macrophages significantly reduced tumor growth in vivo. Therefore, the ability of lymphotoxin to increase the sensitivity of tumor cells to destruction mediated by natural leukocytes is specific for NK cells as compared to macrophages. This form of lymphokine amplification of natural leukocyte cytotoxicity may be one mechanism by which natural and acquired immunity serves or fails to prevent cancer and should be an important consideration in therapeutic approaches to eradicate or control tumor growth.
Coupling of growth and differentiation in normal myeloid precursors and the breakdown of this coupling in leukemia
Authors: Lotem Joseph , Sachs Leo
Published: February 2007

Normal myeloid precursors are dependent on the macrophage and granulocyte growth‐inducing protein MGI‐I for cell viability and multiplication. MGI‐I also induces production of the differentiation‐inducing protein MGI‐2, and this induction of a differentiation‐inducing protein by a growth‐inducing protein provides a mechanism for the normal coupling of growth and differentiation. It is shown that this induction of MGI‐2 by MGI‐I occurs in the myeloid precursors and not in some other cells in the normal bone marrow, that the induced MGI‐2 can be detected 6 h after the addition of MGI‐I, and that MGI‐2 can be induced in these cells by purified MGI‐I. There are clones of myeloid leukemic cells that no longer require MGI‐I for cell viability and multiplication, but in which this requirement for MGI‐I can be restored after induction of differentiation by MGI‐2. A similar concentration of MGI‐I was required for the optimum induction of growth in these differentiating leukemic cells and in normal myeloid precursors. In the presence of MGI‐I these differentiating leukemic cells multiplied and then lost their differentiation‐associated properties. In contrast to normal myeloid cells, MGI‐I did not induce MGI‐2 in the MGI‐I requiring differentiating myeloid leukemic cells. This lack of induction of MGI‐2 by MGI‐I occurred in cells cultured in serum‐containing or serum‐free‐medium, and can explain the loss of differentiation‐associated properties. The results indicate that there has been a genetic breakdown of the normal coupling mechanism between growth and differentiation in these leukemic cells so that MGI‐I can no longer induce MGI‐2.
Establishment of a cell line (HCC‐M) from a human hepatocellular carcinoma
Authors: Watanabe Tetsu , Morizane Toshio , Tsuchimoto Kanji , Inagaki Yasutaka , Munakata Yoshio , Nakamura Tatsuya , Kumagai Naoki , Tsuchiya Masaharu
Published: February 2007

A continuous human cell line was established from a hepatocellular carcinoma of an HBsAg‐positive Japanese male. The cell line, designated HCC‐M, grows as an adhering monolayer with a doubling time of 24 h in medium RPMI‐1640 supplemented with 10% FCS and grows with 30% clonal efficiency in soft agar. The cells have been shown by light and electron microscopy to be of epithelial type. When they were transplanted sub‐cutaneously into the back of athymic nude mice (BALB/c, nu/nu), tumors developed at the sites of inoculation, which were shown to be hepatocellular carcinoma, similar in morphology to the original tumor from which they were derived. HCC‐M had a chromosome mode of 63 with five identifiable marker chromosomes. HCC‐M produced albumin at the 10th passage but this property was lost by the 30th passage. This cell line has not secreted alpha‐fetoprotein. Hepatitis B viral particles or HBsAg have not been demonstrated in the cells from the primary culture nor in several subsequent subcultures tested.
Flow karyotype analysis and fluorescence‐activated sorting of burkitt‐lymphoma‐associated translocation chromosomes
Authors: Wirschubsky Zvi , Perlmann Catharina , Lindsten Jan , Klein George
Published: February 2007

Flow karyotype analysis was performed to assess the feasibility of fluorescence‐activated sorting of Burkitt lymphoma (BL)‐associated translocation chromosomes. The typical 14q+ chromosome in the t(8;14) and the two “variant translations”, the 2q+ in the t(2;8) and the small 22q‐ in the t(8;22), could be identified as single peaks within the flow karyotypes of metaphase chromosomes isolated from several different BL‐lines for each translocation. The translocation chromosomes could be separated with a high degree of purity and in quantities suitable for biochemical analysis. The same analytical and preparative technique was also successfully applied to the identification and sorting of the Philadelphia (Ph1) chromosome in a 9;22 translocation‐carrying CML‐derived line and a familial (11;22) translocation.
Identification by a monoclonal antibody of a glycolipid highly expressed by cells from the human myeloid lineage
Authors: Girardet Christophe , Ladisch Stephan , Heumann Didier , Mach Jean‐Pierre , Carrel Stefan
Published: February 2007

A monoclonal antibody4 (MAb) HL‐C5, which bound selectively to cells of the myeloid lineage tested, was derived from a fusion between P3/NS2/I‐AG8 myeloma cells and splenocytes from a mouse immunized with cells of the promyelocytic leukemia line HL‐60. Among a panel of 29 human cell lines derived from either hematopoietic or solid tumors, MAb HL‐C5 was found to react exclusively with cells from the five differentiated acute myeloid leukemia lines, HL‐60, MLI, ML2, ML3, KG‐IB and not with the less differentiated myeloid lines. Fluorescence‐activated cell sorter analysis of normal bone marrow samples confirmed that the reactivity of MAb HL‐C5 was limited to myeloid cells, from the promyelocytic stage of differentiation to the mature granulocytes. Indirect immunoperoxidase staining of cytocentrifuge preparations of normal bone marrow and peripheral blood leukocytes confirmed these results and showed that MAb HL‐C5 stained neutrophils but not eosinophils or basophils. The antigen recognized by HL‐C5 was recovered in the upper phase of chloroform‐methanol‐water lipid extracts prepared from HL‐60 cells. By competitive binding experiments, it was found that MAb HL‐C5 recognizes the same antigenic determinant as MAb WGHS 29‐1, which has been reported to react with glycolipids containing the sugar sequence lacto‐N‐fucopentaose III. Autoradiographs of thin layer chromatograms of HL‐60 glycolipid extracts which were revealed by incubation with MAb HL‐C5 or WGHS 29‐1 followed by the addition of 125l‐labelled rabbit anti‐mouse immunoglobulin antibody confirmed that the two MAbs reacted with the same or structurally very similar glycolipids.
Differential expression of c‐erbB, c‐myc and c‐myb oncogene loci in human lymphomas and leukemias
Authors: Roy‐Burman Pradip , Devi B. Gayathri , Parker John W.
Published: February 2007

Total cellular polyadenylated RNA from a variety of fresh human lymphoma and leukemia cells, characterized by histopathology and certain cell surface markers, was analyzed for the expression of three distinct cellular oncogenes (c‐oncgenes), c‐erbB, c‐myc and c‐myb by dotblot hybridization assays. Probes used were molecularly cloned DNA containing the respective oncogene sequence of avian erythroblastosis virus, myelocytomatosis virus (MC29) and myeloblastosis virus. All lymphoma‐leukemia cells irrespective of B, T or non‐B/non‐T lymphocyte lineage expressed the c‐erbB locus. This gene was also found to be active in normal peripheral blood lymphocytes and lymphocytes from lymph nodes showing reactive hyperplasia. This observation suggested that c‐erbB might be normally involved in cell growth functions since it was not unique to hematopoietic malignancies. In contrast to c‐erbB, elevated expressions of c‐myc or c‐myb were detected in certain neoplasms of B‐lymphocytes and some other lymphoproliferative disorders as compared to the majority of the samples tested which showed either low or undetectable levels of these transcripts. An examination of B‐cell lymphomas and leukemias in which the majority of the cellular populations expressed either Kappa or lambda surface lg light chain molecules revealed variations in the levels of c‐onc transcripts within a morphologic and immunologic subtype. These findings support the notion that, in general, genetic heterogeneity exists in groups of hematopoietic proliferations defined by conventional histopathologic and immunologic criteria. Although with the majority of the specimens there was no obvious correlation between the morphologic cell type of lymphoma/leukemia and the c‐onc RNA levels, interestingly two of the three samples diagnosed as chronic lymphocytic leukemia, B‐cell type, showed considerably increased transcription of the c‐myc gene relative to the other B‐cell neoplasms. Thus a class of differentiated B‐cell leukemia has been identified in which the molecular mechanisms which affect c‐mycgene expression can now be investigated.
Expression of human placental‐type alkaline phosphatase in primary breast cancer
Authors: McDicken I. W. , Stamp G. H. , McLaughlin P. J. , Johnson P. M.
Published: February 2007

A monoclonal antibody (H317) with specificity for the heat‐stable placental‐type alkaline phosphatase (Pl‐ALP) isoenzyme has been used to investigate the occurrence of Pl‐ALP in patients with primary breast carcinoma. All pre‐operative plasma samples were negtive for Pl‐ALP in a sensitive solid‐phase enzyme immunoassay with a lower limit of detection of 0.1 U/I. In contrast, using a peroxidase‐anti‐peroxidase staining technique on fixed tissue sections, as well as enzyme immunoassay on fresh tissue extracts, Pl‐ALP could be demonstrated in the carcinomatous tissue of all seven patients investigated.
Variance in resistance to natural and antibody‐dependent cellular cytotoxicity and to complement‐mediated lysis among K562 lines
Authors: Kimber Ian , Moore Michael , Roberts Kevan
Published: February 2007

Isolation of sub‐populations of the NK‐sensitive ery‐thro‐leukaemic cell line K562 by limiting dilution techniques has revealed‐marked clonal variation in susceptibility to natural cytotoxicity. Detailed examination of two such lines (E10/P2 and F9/P2) which differed significantly in their susceptibility to both native and activated NK‐cell‐mediated lysis revealed that their differences were stable and independent of culture conditions. The resistant (F9/P2) and sensitive (E10/P2) lines had comparable cold‐inhibitory and effector‐cell adsorption capacities, indicating that differential susceptibility was not attributable to variable expression of NK target structures. F9/P2 was also less susceptible to antibody‐dependent cellular cytotoxicity (ADCC) and complement‐mediated lysis, indicating the existence of variants with a generalized capacity to resist several immunolytic processes.
Genetic control of immune responses to moloney sarcomas in rats: Role of non‐RT‐1 background genes
Authors: Jones Joe M.
Published: February 2007

Bone marrow chimeras, athymic nude rats and a congeneic strain were utilized to verify and further examine non‐RT‐I linked background genes that influence immune responses of BN and LEW rats to Moloney sarcomas. In transplants that did not involve RT‐I incompatibility, infusion of high‐responder bone marrow into a lethally irradiated low‐responder recipient, or low‐responder bone marrow into a high‐responder recipient, would restore a high antibody response to the gp70 antigen of MuLV. Such transplants did not restore a high response to the p30 antigen. Athymic nude rats did not exhibit a significant response to either p30 or gp70 while euthymic littermates exhibited a significant response to both antigens. Growth of Moloney sarcomas as well as antibody and cellular responses to antigens expressed by such tumors were measured in LEW‐IN rats which carry the RT‐I of BN and the background of LEW. For each of these parameters, LEW‐IN resembled LEW more closely than BN.
Noncarcinogenic chemotherapy with a combination of vincristine, methotrexate and 5‐fluorouracil (VMF) in rats
Authors: Berger M. , Habs M. , Schmähl D.
Published: February 2007

The CMF regimen, which is clinically used in adjuvant therapy of breast cancer, is known to be carcinogenic in rats (Habs and Schmähl, 1981). To examine alternative regimens, a long‐term carcinogenicity study was performed, using the VMF regimen as follows: V (i.v.), M (i.p.) and F (p.o.) at 0.8, 20 and 300 mg/m2, respectively. These doses and a half‐dose regimen (0.5 VMF) were administered every 6 weeks to 80 rats (40 males, 40 females) in each of three groups. Group I served as an untreated control. Groups II, III and IV received 6 × VMF, 18 × 0.5 VMF and 18 × VMF, respectively. Unlike treatment with comparable doses of CMF, the present therapy did not result in an increased tumor rate or a change in tumor type over controls. The chemotherapeutic efficacy of VMF was compared with that of CMF by administering the following doses (mg/m2 i.p.) to groups of 20 rats bearing methylni‐trosourea‐induced primary mammary carcinomas: group I: C (420), 2: V (2.1), 3: M (35) and F (350), 4: C (210), M (21) and F (280), 5: V (1.05), M (21) and F (280), 6: as in 4 except that C was given 24 h prior to M and F, 7: as in 5 except that V was given 24 h prior to M and F, 8: ovariectomy on day 1, 9: control group. Animals bearing a tumor volume of ⩾ 0.8 cm3 were randomly allocated to the individual groups (day 1) and subsequently treated on days 1,8, 15 (V only) 22, and 29. After 5 weeks the following T/C values were recorded: group I: 12.6%, 2:80%, 3:49%, 4: 42.8%, 5: 67%, 6: 49.2%, 7: 26.5%, 8: 45.5%. These results indicate a possible superiority of VMF over CMF, since the former exhibits little or no carcinogenicity at comparable therapeutic activity.
Malignant myeloblastic transformation of murine long‐term bone marrow cultures by F‐MuLV: In vitro reproduction of a long‐term leukemogenesis, and investigation of preleukemic events
Authors: Heard Jean Michel , Fichelson Serge , Sola Brigitte , Martial Marie Antoinette , Berger Roland , Varet Bruno , Levy Jean Paul
Published: February 2007

A Friend helper virus I−5(F‐MuLV) which induces my‐eloblastic leukemias in mice after a latency of several months, was used to infect long‐term bone marrow cultures. From 48 to 71 weeks after in vitro infection, 4/14 cultures gave rise to transplantable malignant myeloblas‐tic cells. These cells were shown to genuinely result from an in vitro transformation of virus‐infected normal bone marrow cells. The in vitro transformation reproduced the course of the in vivo disease. It provided unique material for in vitro investigation of the preleukemic stages of long‐term leukemogenesis. Successive cellular events were: (I) freezing of the normal myelomonocytic differentiation process; (2) change from factor‐dependent to an autonomous growth; (3) acquisition of in vivo tumorigenicity.
Incidence and type of tumors induced by DMBA carcinogenesis in H‐2 congenic strains on a B10 background
Authors: Grönberg Alvar , Cochran Alistair J. , Kärre Klas , Klein George , Klein Gunnar O. , Kiessling Rolf
Published: February 2007

Five congenic strains on B10 background (B10, B10.S, B10.G, B10.BR and B10.A) were investigated for their susceptibility to tumor induction by 9,10 dimethyl‐1,2 benzanthracene (DMBA). The DMBA was administered via a stomach tube five times at weekly intervals (total 5 mg). Two types of malignancies predominated: diffuse lymphocytic lymphomas with or without thymic involvejent, and epidermal tumors. B10 (H‐2b) was the most resistant strain when total tumor incidences were compared. B10.S (H‐2s) had the highest incidence of both lymphomas and epithelial tumors and B10.G was significantly more susceptible to thymic lymphomas than B10. In B10.S mice thymic lymphomas were more frequent in males than in females, the reverse being true for tumors of epithelial origin. No correlation between tumor incidence and in vitro NK activity was demonstrated.
Histopathological study on N‐ethyl‐N′‐nitro‐N‐nitrosoguanidine‐induced colon cancer in dogs
Authors: Kamano Toshiki , Kishino Hiroshi , Mizukami Ken , Azuma Noboru , Tamura Junji , Katami Atsuo , Kidokoro Tsutomu
Published: February 2007

We prepared a suppository containing 50 mg of N‐ethyl‐N′‐nitro‐N‐nitrosoguanidine (ENNG), and successfully produced experimental colon cancer with good reproducibility by continuous intrarectal insertion of one or two suppositories per day in dogs. The tumors were very similar to human colon cancers, macroscopically and histologically. In one of three dogs subjected to histopathological study, metastases to the lymph nodes, lung, liver and kidney were observed. This animal model produced by a simple procedure will be helpful in investigating treatment of rectal cancer.
Rat AL2, AL3, AL4 and AL5 monoclonal antibodies bind to the common acute lymphoblastic leukaemia antigen (CALLA gp 100)
Authors: Lebacq‐Verheyden Anne‐Marie , Ravoet Anne‐Marie , Bazin Hervé , Sutherland D. Robert , Tidman Nicholas , Greaves Melvyn F.
Published: February 2007

Four distinct rat monoclonal antibodies against the common ALL antigen (CALLA, gp 100) were obtained in a single fusion. Rat AL2, AL3, AL4, AL5 and the previously reported mouse J5 monoclonal antibodies identified the same subsets of leukaemic cells. AL2 and AL3 reacted weakly with terminal transferase‐positive cells in normal bone marrow and foetal liver, as well as with a minority of mature granulocytes in blood. Immunoprecipitation experiments and competitive binding assays demonstrated that the four rat antibodies and J5 bound to the same glycoprotein of approximately 100, 000 mol. wt This set of rat monoclonal antibodies directed against CALLA has not only a diagnostic usefulness but may also be of therapeutic value.
Adult T‐cell leukemia (ATL) virus‐specific antibodies in atl patients and healthy virus carriers
Authors: Yamamoto N. , Schneider J. , Koyanagi Y. , Hinuma Y. , Hunsmann G.
Published: February 2007

The adult T‐cell leukemia (ATL)‐associated antigen complex (ATLA) is recognized by serum antibodies of carriers of ATL virus (ATLV). ATLA consists mainly of ATLV polypeptides and their precursors. The sera from 22 ATL patients, 21 healthy carriers and 9 healthy individuals were examined quantitatively by immunofluorescence assay (IF) for ATLA and by a newly developed radioimmunoprecipitation test with purified 125I‐gp68, the putative env gene product of ATLV. More qualitative results were obtained by analysis on polyacrylamide gel (PAGE) of immunoprecipitates from lysates of 35‐S‐cysteine‐la‐belled cells producing ATLV, pelleted ATLV and cell‐free culture supernatant. The two quantitative assays gave negative results with sera from all normal subjects and a few patients, but detected ATLA antibodies in all the healthy ATLV carriers. An important finding was that sera of patients that gave negative results in one assay gave positive, results in the other, and vice versa. In contrast, all sera from ATL patients and healthy carriers, but not normal donors, precipitated ATLV‐specific glycopolypeptides, gp68 and gp46 from 35S‐labelled materials. But core polypeptides p28, p24, p19 and p15 were precipitated only by sera with IF titers of over 80. Thus, anti‐ATLA antibodies in seropositive sera are predominantly directed against glycopolypeptides of ATLV, and the antibody reactivity to ATLA antigens does not differentiate between ATL patients at various stages of the disease and healthy ATLV carriers.
Monoclonal antibody (1116 NS 19‐9) defined monosialoganglioside (GICA) in colorectal carcinoma in relation to stage, histopathology and DNA flow cytometry
Authors: Arends J. W. , Wiggers T. , Schutte B. , Thijs C. T. , Verstijnen C. , Hilgers J. , Blijham G. H. , Bosman F. T.
Published: February 2007

Immunoreactivity of 1116 NS 19‐9 monoclonal antibody defined monosialoganglioside (gastrointestinal cancer‐associated antigen, GICA) has been studied in a series of colorectal carcinoma patients of a multicentre prospective controlled trial in order to assess its correlation with parameters such as localization, stage histopathological characteristics and DNA flow cytometry. GICA could be detected in 60% of the carcinomas, but no correlation was observed between its status of immunoreactivity and any of the parameters studied. It is concluded that, though study of the expression of the monosialganglioside may be worth while in relation to fundamental aspects of behaviour of colorectal carcinomas, the significance of its immunohistochemical detection in a diagnostic or prognostic sense is limited.
Epstein‐Barr virus specific T‐cell response in nasopharyngeal carcinoma patients
Authors: Moss D. J. , Chan S. H. , Burrows S. R. , Chew T. S. , Kane R. G. , Staples J. A. , Kunaratnam N.
Published: February 2007

There is a substantial body of evidence suggesting an association between Epstein‐Barr virus (EBV) and undifferentiated nasopharyngeal carcinoma (NPC). The present study has compared a group of NPC patients (newly diagnosed and long‐term survivors) and controls for EBV‐specific T‐cell immunity using the regression of transformation assay. Newly diagnosed patients (17 tested) when compared with either long‐term survivors (20 tested) or controls (30 tested) showed a significant impairment in virus‐specific T‐cell immunity (p = 0.036, p = 0.043 respectively). Furthermore, donors with IgA antibody to EBV showed a significant depression in virus‐specific T‐cell immunity compared with donors without IgA antibody (19 IgA‐positive, 48 IgA‐negative; p = 0.0025). These results may be important in explaining the postulated role of EBV in the aetiology of NPC.
Purification of a protein (60K/58K) associated with the Epstein‐Barr virus‐induced early antigen complex in Raji cells
Authors: Dölken Gottfried , Lange Winand , Weitzmann Ulrike , Hirsch Friedrich W. , Löhr Georg W.
Published: February 2007

A double antibody sandwich ELISA has been established for the detection and quantitation of EBV‐associated early antigens (EA) in IUdR‐induced Raji cells. The EA complex extracted from Raji cells could be separated by ion exchange chromatography and isoelectric focusing into several components. One EA‐associated subspecificity has been purified by DEAE‐, CM‐, and Blue‐Sepharose chromatography followed by isoelectric focusing. The isolated protein has an apparent molecular weight of 240,000 ± 20,000 daltons under non‐dissociating conditions on Sephacryl S‐300, an isoelectric point of 4.5, and seems to be composed of two polypeptides of 60,000 and 58,000 daltons as shown by SDS‐gel electrophoresis and two‐dimensional gel electrophoresis. Preliminary data indicate that the 58,000 polypeptide is generated by limited proteolysis of the 60,000 polypeptide. The EA activity of the isolated protein has been confirmed by the double antibody sandwich ELISA and its reactivity with anti‐EA‐positive sera in an ELISA for the detection of anti‐EA antibodies.
A study of gastrointestinal cancer‐associated antigen (GICA) in human fetal organs
Authors: Raux Hélène , Labbe François , Fondaneche Marie‐Claude , Koprowski Hilary , Burtin Pierre
Published: February 2007

The gastrointestinal cancer‐associated antigen (GICA) characterized by 1116 NS 19‐9 monoclonal antibody was studied in human fetal organs by immunohistology and immunofixation on nitrocellulose sheets. It was found in all the gastrointestinal tracts of fetuses and newborns. Other fetal organs, except biliary and pancreatic ducts, were negative. Immunohistological data and enzymatic studies led us to conclude that GICA is predominantly a mucin‐type glycoprotein in fetal organs.
Detection of serum antibodies to adult T‐cell leukemia virus in non‐human primates and in people from Africa
Authors: Hunsmann Gerhard , Schneider Josef , Schmitt Jakob , Yamamoto Naoki
Published: February 2007

The distribution of serum antibodies to adult T‐cell leukemia virus (ATLV) was examined as a marker for virus infection among non‐human primates as well as people from Africa and Germany. The virus is present in Africa in certain primate species including man. Altogether, 468 sera from 27 monkey species were examined. Only African green monkeys, less frequently also chimpanzees and crab‐eating monkeys, were found to be infected. About 1–2% of people from Kenya have antibodies, while ATLV‐antibodies may be present in well below 0.1% of the German population.
Natural infection in non‐human primates with adult T‐cell leukemia virus or a closely related agent
Authors: Miyoshi I. , Fujishita M. , Taguchi H. , Matsubayashi K. , Miwa N. , Tanioka Y.
Published: February 2007

A total of 703 sera from 10 species of monkeys were examined for the presence of antibodies to adult T‐cell leukemia (ATL)‐associated antigens (ATLA). ATLA represent core protein(s) of ATL virus (ATLV) and ATLV‐determined polypeptides. Anti‐ATLA antibodies were found in all seven macaque species tested but not in three non‐macaque species. The frequencies of seropositive macaques ranged from 10 to 50%. In three macaque species (Japanese monkeys, rhesus monkeys, and crabeating monkeys) in which sufficient numbers of animals were studied, more females than males were anti‐ATLA positive and the antibody‐positive rate increased with age. In Japanese monkeys, over 70% were seropositive after the age of 10 years. A family study of Japanese monkeys suggested maternal transmission of ATLV or a closely related agent. These seroepidemiological features are consistent with those of Japanese in the ATL‐endemic area. Three of 10 rhesus monkeys were found to be anti‐ATLA‐positive 13 days after arrival in Japan, suggesting that they had been infected with ATLV in Indonesia where they were captured. Thus, ATLV appears to be prevalent among several macaque species as well as in man, and its pathogenetic role in these non‐human primates should be explored in relation to ATL in man.
In vitro responses of human prostate tumour cell lines to a range of antitumour agents
Authors: Metcalfe Sylvia A. , Whelan Richard D. H. , Masters John R. W. , Hill Bridget T.
Published: February 2007

Four human prostate tumour continuous cell lines were employed for in vitro drug sensitivity testing of nine cytotoxic drugs, X‐irradiation and two hormonal preparations. Responses were assessed by measuring cell survival as judged by colony formation in agarose. A marked heterogeneity of responses was noted to many of the agents studied, including X‐irradiation. However, in terms of ID70 values for 24‐h drug exposures, comparable responses in all the cell lines tested, with values falling within a 1.4‐ to 2.9‐fold range, were noted with actinomycin D, adriamycin, m‐AMSA4, dibromodulcitol, 5‐fluorouracil, hydroxyurea and ICRF‐159. In contrast, mixed responses to cis‐platinum and methotrexate were particularly marked, with ID70 values differing by factors of 3.8 and 7.5 respectively. In addition, when higher drug concentrations of m‐AMSA, cis‐platinum, dibromodulcitol and ICRF‐159 were employed, significant deviations in the four survival curves became apparent. Continuous exposure to diethylstilboestrol and medroxyprogesterone acetate caused negligible cell kill. Due to these variable responses it was not possible to predict that any agent tested might have specific value in the treatment of prostate cancer. However, preliminary in vitro screening with such a panel of cell lines may complement in vivo studies with models of prostatic cancer and prove useful in investigations of mechanisms of drug resistance.
Effect of coordinated therapeutic assays using C. parvum, interferon and arginine butyrate on spontaneous disease and survival of AKR mice
Authors: Chany Charles , Cerutti Italina , Mace Bertrand
Published: February 2007

AKR mice, known to develop spontaneous leukemia in almost 100% of cases, were studied throughout their lifespan. Different treatments combining a potent immune stimulator, Corynebacterium parvum (CP), with interferon (IFN) and arginine butyrate were initiated at the 15th week of life. In a preliminary series of experiments, CP (200 μg), IFN (20,000 units) and butyrate 50 mM) were employed in a well‐defined chronological order. In controls, the mean survival time (MST) was 35.17±1.67 weeks and the final survival rates was 0/50 mice for all experiments. Only CP associated with arginine butyrate significantly augmented the MST (42.5±3.66 weeks) and final survival rate (9/35 mice). In an adjusted set of experiments, reducing the IFN concentration to 10,000 and 5,000 units and that of butyrate to 6 mM greatly improved the results. The MST was substantially increased with the combinations of CP+IFN+butyrate (41.4±1.86 weeks), CP+IFN (42.73±3.29 weeks) and butyrate+IFN (41±2.34 weeks), as well as the final survival rates (8/15, 10/15 and 6/15 mice respectively). An important finding was that when CP and IFN were used separately, they were ineffective.
Patterns of tumor colony development over time in soft‐agar culture
Authors: Kirkels Wim J. , Pelgrim Olga E. , Hoogenboom Adrie M. M. , Aalders Mathilde W. , Debruyne Frans M. J. , Vooijs G. Peter , Herman Chester J.
Published: February 2007

Human tumors were cultured by the two‐layer soft‐agar technique and the time course of tumor colony development was evaluated during periods of up to 6 weeks in culture. All colony counting was performed with an automated tumor colony counter (Omnicon; Bausch and Lomb, Inc, Rochester, NY, USA). This instrument provided colony counts per culture plate in six size categories from >60 μm diameter colonies to > 149 μm diameter colonies. Six to 24 culture plates were used for each “growth curve”, generally 24. Control (non‐drug‐treated) cultures were obtained from 117 tumors, of which 25 also provided enough cells to allow evaluation of the time course of colony development after exposure to cytostatic agents. The development of colonies in non‐drug‐treated plates usually demonstrated a lag phase, a logarithmic growth phase to maximum colony development and a subsequent deterioration of colonies. In spite of clumps seeded into the agar, real colony growth could be recognized by frequent colony counting of culture dishes, although the temporal patterns of growth were sometimes different if pure single‐cell suspensions were compared with suspensions containing clumps from the same tumor. Drug pre‐incubation caused changes in the temporal pattern of colony growth as well as in the total number of colonies. Some cultures showed drug sensitivity when evaluated at certain time points while evaluation at later time points showed only borderline drug effect or none at all. The potential utility of tumor colony growth curves in the clinical applications of tumor colony cultures is discussed.
Enhancement by TPA of phenotypes associated with transformation in carcinogen‐treated human cells: Evidence for a selective mechanism
Authors: Siegfried Jill M. , Kaufman David G.
Published: February 2007

The tumor promoter 12‐O‐tetradecanoylphorbol 13‐acetate (TPA) was found to increase the incidence of phenotypic alterations induced by the direct‐acting carcinogen N‐methyl‐N‐nitro‐N‐nitrosoguanidine (MNNG) in human endometrial stromal cells. Following carcinogen treatment, changes in saturation density, γ‐glutamyl‐transpeptidase expression, morphology, and growth in selective media were enhanced in cell cultures subjected to continuous TPA exposure as compared to cultures receiving ethanol vehicle. This enhancement may have resulted, at least in part, from selection of cells altered by carcinogen, as evidenced by differences in the colony‐forming abilities of MNNG‐treated and control cultures after prolonged TPA exposure, and by differences in morphologic response to TPA challenge in these two populations.
Human lung tumour cell line adapted to grow in serum‐free medium secretes angiogenesis factor
Authors: Kumar S. , West D. , Daniel Mary , Hancock Anne , Carr T.
Published: February 2007

A human lung tumour cell line has been grown in serum‐free medium for 12 months and during this period cells were subcultured every 4 days. The culture medium contained an angiogenesis factor which has been purified and shown to be similar to that isolated from other sources including solid tumours. This is the first report that demonstrates de novo synthesis and secretion of angiogenesis factor by a cell line adapted to grow in a serum‐free medium.