bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of a serum factor stimulating the differentiation of myelomonocytic leukemic cells
Authors: Burgess Antony W. , Metcalf Donald
Published: February 2007

Culture of WEHL‐3B myelomonocytic leukemic cells in semi‐solid agar medium containing serum from mice injected with endotoxin serum (ES) led to the development of maturing granulocytes and macrophages in most leukemic colonies. ES contains high levels of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF), a regulator known to stimulate differentiation of these leukemic cells, but an antiserum which neutralized >85% of the GM‐CSF in ES did not suppress the differentiation‐inducing activity of ES on WEHI‐3B cells. The active factor in endotoxin serum stimulating differentiation in WEHI‐3B leukemic cells (GM‐DF) was separated from most of the GM‐CSF by gel filtration using Ultrogel AcA44. The residual CSF associated with the GM‐DF appeared to stimulate selectively granulocytic colonies. Disproportionation of GM‐DF and GM‐CSF was observed in ES fractions obtained using concanavalin‐A/Sepharose chromatography: none of the GM‐DF bound to this matrix, whereas 40% of the GM‐CSF bound and was eluted with competing α methylglucopy‐ranoside. Although no separation of GM‐CSF and GM‐DF was obtained using DEAE‐Sepharose, non‐isoelectric focusing in amphoteric buffers indicated charge differences between the differentiation factor and several sub‐species of GM‐CSF. Sequential purification of GM‐DF from ES using 40 ‐ 70 % ammonium sulfate precipitation gel filtration and phenyl‐Sepharose chromatography resulted in a 25‐fold purification. In all fractionation procedures used, a sub‐species of GM‐CSF, stimulating granulocyte colony formation, was consistently associated with partially purified GM‐DF, but some subspecies of GM‐CSF clearly lacked any capacity to induce differentiation in the leukemic cells. The observations suggest that the factor in post‐endotoxin serum most efficient in enforcing differentiation in myelomonocytic leukemic cells may be a subset of GM‐CSF molecules with a selective capacity to stimulate granulocyte colony formation by normal cells.
The effect of bursectomy on the adoptive transfer of resistance to Marek's disease
Authors: Powell P. C. , Rennie M. , Ross L. J. N. , Mustill Brenda M.
Published: February 2007

Immunization with inactivated viral antigens protected chickens against Marek's disease. Non‐immunized chickens could be protected by injections of spleen cells but not of serum from immunized, histocompatible donors. Chickens rendered agammaglobulinaemic by bursectomy and irradiation could also be immunized against Marek's disease by inoculation with viral antigens, but spleen cells from these immunized, bursectomized and irradiated donors did not confer protection on the recipients into which they were injected. It was concluded that, although in the bursectomized, immunized donors cell‐mediated immunity alone was able to provide a fair degree of protection against Marek's disease, the protection afforded against the disease by spleen‐cell transfer was at least partly attributable to the transfer of antibody‐producing cells, and that humoral immunity, while not being an absolute requirement for resistance, is normally an important component of the resistance mechanism.
Adhesion of metastatic and non‐metastatic carcinoma cells to glass surfaces
Authors: Cottler‐Fox M. , Ryd W. , Hagmar B. , Fox C. H.
Published: February 2007

Adhesion in vitro is described in cells from a tumor pair originating from a single methylcholanthrene‐induced mouse carcinoma. One member of this tumor pair shows a high incidence of metastases while the other does not metastasize. Cells from the non‐metastasizing carcinoma were found to form close and focal contacts with a glass substrate consecutively, as do normal mouse kidney epithelial cells. Cells from the metastasizing carcinoma, however, had only limited areas of close contact and generally failed to form focal contacts. It is suggested that this alteration in cell‐substrate adhesion contributes to the release and mobility of metastatic cells.
Demographic patterns for nasopharyngeal carcinoma in the united states
Authors: Levine Paul H. , Connelly Roger R. , Easton John M.
Published: February 2007

Demographic and pathologic information on over 1,000 newly diagnosed patients with nasopharyngeal carcinoma was obtained from population‐based registries in the United States. Age‐adjusted incidence rates were similar for whites and blacks and both were significantly lower than for Chinese Americans. Age‐related differences in cell type were observed in white NPC patients, lymphoepithelial carcinomas having a younger age distribution than either squamous‐cell or transitional‐cell carcinomas. Mortality rates for nasopharyngeal cancer were substantially lower than incidence rates for nasopharyngeal carcinoma, but both indices revealed a minor peak in rates among teenaged whites and blacks. The five‐year survival rate for nasopharyngeal carcinoma was less than 25% and has not changed in recent years. Prognosis was better for females and for young patients. Despite the difficulties in obtaining uniform pathologic classification in such a large study, the interrelationship between pathologic subtype of nasopharyngeal carcinoma and demographic features emphasizes the need for adherence to a more uniform histologic classification.
A possible correlation between the degree of karyotype aberrations and the rate of sister chromatid exchanges in lymphoma lines
Authors: Fonatsch Christa , Schaadt Michael , Kirchner Hartmut , Diehl Volker
Published: February 2007

The sister chromatid exchange (SCE) frequencies of six freshly established and two old cell lines derived from patients with lymphatic tumors or leukemia were compared to the SCE rates of lymphoblastoid cell lines of normal controls. All cell lines from malignant tumors displayed significantly higher SCE values than the control lines. In general, the SCE rates seem to be correlated to the number of chromosomal markers and the degree of karyotypic instability of each line.
Malignant bone tumours induced by a local injection of colloidal radioactive 144cerium in rats as a model for human osteosarcomasl
Authors: Allouche Michele , Delbrück Hermann G. , Klein Bernard , Masse Roland , Matar Abdou , Morin Michele , Lafuma Jacques , Jasmin Claude
Published: February 2007

Lung metastases were observed in 80% to 85% of rats bearing advanced malignant bone tumours (osteogenic osteosarcomas and angiosarcomas). These tumours were induced in 2‐month‐old Sprague‐Dawley rats by inoculation of a colloidal suspension of radioactive cerium (144Ce) into the hind leg, in close contact to the bones of the knee joint. Twenty‐eight rats were killed or died spontaneously shortly after detection of palpable tumours at the site of injection: the incidence of lung metastases was 73.3% and 53.8%, respectively, for osteogenic sarcomas and angiosarcomas, showing that most lung metastases are present at the time of diagnosis of the primary tumour. Tumour‐cell kinetic parameters were studied in 49 rats bearing tumours following intraperitoneal injection of [3H]thymidine. The labelling index (LI) of the primary tumours was significantly lower in advanced tumours (7.2% for osteosarcomas and 10.1% for angiosarcomas) than in tumours examined at the time of detection (12.2% and 13.5%, respectively). Mitotic indices (MI) of all tumours were less than 1%. From the curve of the percentage of labelled mitoses (PLM) at different times after [3H]thymidine injection, Ts (6.5 h) and TG2 (1.75 h) were determined. Tc and TG1, were also evaluated (18 h and 9.25 h, respectively). These results show that malignant bone tumours induced in rats with 144Ce may be a good model for human osteosarcomas and may be useful in studying the numerous problems in the therapy of malignant bone tumours in man.
Tumorigenicity of friend murine erythroleukemia cell lines differing in spontaneous differentiation rates
Authors: Axelrod David E. , Majumdar Shyamal K. , Wivell Judith A. , Terry Robert W.
Published: February 2007

The relationship between tumorigenicity and in vitro differentiation was studied in four Friend erythro‐leukemia cell lines. The cell lines were isolated by repeated subcloning of an unmutagenized population (sib selection). The cell lines differed in their ability to form tumors when 103 cells were injected subcutaneously into syngeneic mice (8 to 56% animals with tumors). The ability of cell lines to form tumors was not proportional to their ability to be induced to differentiate by dimethylsulfoxide. The cell lines had indistinguishable chromosome numbers, plating efficiencies, number of cycling cells, population doubling times and spontaneous mutation rates to drug resistance. However, the cell lines had different spontaneous differentiation rates in the absence of dimethylsulfoxide (0.87 to 16.0 × 10−4 per cell per generation). The ability of cell lines to form tumors was inversely proportional to their spontaneous differentiation rate. Apparently cells which are most efficiently blocked in differentiation have the highest probability of forming tumors.
Presensitization of human cells with extrinsic signals to induced chemical carcinogenesis
Authors: Milo G. E. , Dipaolo J. A.
Published: February 2007

Foreskin‐derived low‐passage human cell populations were reproducibly transformed with chemical carcinogens when the cells were blocked in G1, released from the block, and treated with either the carcinogen N‐methyl‐N‐nitro‐N‐nitrosoguanidine (MNNG) or with Aflatoxin BI in the S period of the cell cycle. Arginine‐and glutamine‐deficient medium was required to effectively block the cells in the G1 period. Estradiol, insulin, anthralin or phorbol myristate acetate sensitized the cell population to carcinogen treatment when added 10 h before the carcinogen in early S period. Presensitized cells kept blocked in G1 period for 48 h or longer, released and treated in S period with MNNG or Aflatoxin BI were not transformed; nor did transformation occur in presensitized cell populations treated in G2 (4.5 h), M (1.5 h) or G1 (8.2 h). Cells derived from carcinogen‐treated presensitized cells grew as colonies in soft agar at 16‐20 PDL. When cells derived from colonies isolated from the soft agar were injected subcutaneously into nude mice, tumors developed.
Transplantation resistance of drug‐treated hybrid or allogeneic mice against murine lymphomas. I. Immunopharmacology studies
Authors: Bonmassar Anna , Riccardi Carlo , Rivosecchi‐Merletti Paola , Goldin Abraham , Bonmassar Enzo
Published: February 2007

Sequential treatment of mice with non‐lethal doses of 5(3,3′‐dimethyl‐I‐triazeno)‐imidazole‐4‐carboxamide (DTIC) and cyclophosphamide (Cy) was found to produce long‐term inhibition of endogenous cell proliferation in the spleen and profound impairment of classical allograft responses, similar to that detectable in lethally irradiated mice. Studies were carried out with drug‐treated (i.e. treated with DTIC + Cy) conventional or nude mice inoculated with lymphoma cells homozygous for the H‐2b or H‐2d haplotype. Transplantation resistance in various tumor‐host combinations was studied in terms of survival times after tumor challenge or lymphoma cell proliferation in spleen and liver, measured by the uptake of DNA precursor 125I‐labelled 5‐iodo‐2′‐deoxyuridine ([125I]dUrd). The results of in vivo transplantation immunity tests or in vitro tests of generation of cytotoxic lymphocytes confirmed that classical T‐dependent allograft responses were abrogated by drug treatment of H‐2‐incompatible hosts. However, localized resistance against lymphoma graft, mainly at spleen level, was found in drug‐treated hybrid mice, or conventional and “nude” allogeneic recipients, as judged by [125I]dUrd uptake inhibition. Resistance presumably regulated, at least in part by the Hh (hemopoietic histocompatibility) system, was abrogated by pretreatment with carrageenan, an antimacrophage agent. In addition, treatment with DTIC + Cy did not abrogate NK activity of mice when the in vitro cytotoxicity test was conducted 5h after Cy administration, i.e. at the time used for tumor challenge in vivo. It was concluded that selected immunological functions (i.e., antilymphoma natural resistance insensitive to DTIC + Cy, called drug‐resistant inhibition of tumors, DRIT) possibly of non‐T origin, similar to those detectable in lethally‐irradiated mice, can be retained by hosts subjected to high doses of certain anti‐tumor agents.
Suppression of activity of mouse natural killer (NK) cells by activated macrophages from mice treated with pyran copolymer
Authors: Santoni Angela , Riccardi Carlo , Barlozzari Teresa , Herberman Ronald B.
Published: February 2007

Treatment of young mice with pyran copolmyer caused a substantial decrease in natural killer (NK) cell activity at 7 days. The decrease in cytotoxicity was associated with the presence of splenic suppressor cells, capable of inhibiting in vitro the NK activity of spleen cells from normal mice. The suppressor cells appeared to be macrophages, being plastic‐adherent, phagocytic and radioresistant, and lacking demonstrable Thy 1.2 antigen. Sonicates or culture supernatants of adherent spleen cells from pyran‐treated mice were also able to inhibit NK activity, suggesting that suppressor cells act by release of soluble factors.
Chemotherapy of human colorectal tumor xenografts in athymic mice with clinically active drugs: 5‐fluorouracile and 1‐3‐bis‐(‐2‐chloroethyl)‐1‐nitrosourea (bcnu). Comparison with doxorubicin derivatives: 4′deoxydoxorubicin and 4′‐0‐methyldoxorubicin
Authors: Giuliani Fernando C. , Zirvi Karimullah A. , Kaplan Nathan O. , Goldin Abraham
Published: February 2007

The effects of single‐agent therapy with two clinically useful drugs, 5‐fluorouracil (5‐FU) and 1‐3‐bis‐(2‐chloro‐ethyl)‐1‐nitrosourea (BCNU) against nine human colorectal tumors (rectum T 157 and T 348, lung metastasis T 84, lymph‐node metastasis T 245, colon, T 183, T 219, T 347, T 362 and T 380) transplanted and passed serially in athymic (nude) mice were studied. In addition, chemosensitivity of the tumors to 5‐FU and BCNU was compared with the chemosensitivity of the tumors to two new doxorubicin analogues, 4′‐deoxydoxorubicin and 4′‐O‐methyldoxorubicin. BALB/c nude mice were treated intravenously on a weekly basis for 3–4 weeks, starting when the tumor volume became relatively large (advanced stage of tumor treatment). All the tumors showed a 90–100% take rate and stable growth. In these experiments, 77% (5/9) of the colorectal tumors were biologically sensitive to the treatment with 5‐FU but the percentage of statistically significant sensitive tumors was 22%, which is in good agreement with the clinical data reported in the literature (21%). In patients, BCNU has been reported to give up to 13% response. In contrast, we have found a 33% statistically significant response rate in our panel of colorectal tumors. The difference could be related to the higher tolerance of nude mice to certain drugs, including BCNU. The results suggest that the two new doxorubicin derivatives, 4′‐deoxydoxorubicin and 4′‐O‐methyl‐doxorubicin, should be more active in the patient than both of the clinically used drugs, 5‐FU and BCNU. Furthermore, there is a good correlation between the results obtained in the experimental system (human tumor/nude mouse) and in human patients with the active drugs, 5‐FU and BCNU.
Early changes in the glycopeptides of human B‐lymphocytes after epstein‐barr virus infection in vitro
Authors: Van Beek Wim , Breekveldt Jan , De Bakker Ellen , Hilgers Jo , Hilgers Frans , Nilsson Kenneth
Published: February 2007

Human B lymphocytes obtained from healthy donors were infected with Epstein‐Barr virus in vitro. From the initiation of infection to the final establishment of a permanent lymphoblastoid cell line, fucosyl glycopeptides of the cell surface were investigated. In order of appearance the following events took place: expression of Epstein‐Barr virus‐determined nuclear antigen, mitotic activity of the cells and specific glycopeptide alterations on the cell surface. This specific alteration in glycopeptides, as determined by gel filtration, is manifested by the appearance of fast‐eluting glycopeptides and was similar to that found on Burkitt lymphoma cells. Neither pokeweed‐mitogen‐stimulated B lymphocytes nor exponentially growing normal T lymphocytes exposed fast‐eluting glycopeptides on their surfaces. Therefore, it is concluded that the appearance of these fast‐eluting glycopeptides on the surface of lymphoblastoid cells after EBV infection is not the result of culture conditions or conditions of growth as such. The similarity with glycopeptides derived from Burkitt lymphoma cells, and the observation that a considerable proportion of the B cells becomes immortalized, are discussed.
Chromosome 15 trisomy in spontaneous and carcinogen‐induced murine lymphomas of B‐cell origin
Authors: Wiener F. , Babonits M. , Spira J. , Bregula U. , Klein G. , Merwin R. M. , Asofsky R. , Lynes M. , Haughton G.
Published: February 2007

G‐banding analyses of 14 independently derived B‐cell lymphomas showed the frequent occurrence of chromosome 15 trisomy. It was present in seven of nine spontaneous B‐cell lymphomas, but in company with other trisomies, monosomies and marker chromosomes. In five carcinogen‐induced primary B‐cell leukemias, trisomy 15 was the dominating change. Taken together with the previously demonstrated importance of chromosome 15 trisomy for T‐cell leukemogenesis and of the 12;15 translocation in plasmacytogenesis in the mouse, it appears likely that the distal part of chromosome 15 carries a cluster of genes, perhaps a supergene region, that may play an important role in the differentiation and/or the normal responsiveness of various lymphoreticular cell types to growth control.
Induction of type‐C retrovirus by the tumor promoter TPA
Authors: Hellman Kiki B. , Hellman Alfred
Published: February 2007

The tumor promoter 12‐0‐tetradecanoyl‐phorbol‐13‐acetate (TPA) induced endogenous murine xenotropic type‐C retrovirus from A1‐2 cells, derived from the BALB/c mouse, as determined by infectious center focus‐forming assay on permissive normal rat kidney (NRK) cells. Kinetic dose‐response studies showed that the number of cells induced to release virus was dependent on TPA concentration and the time of assay following TPA exposure. Maximal induction occurred when cells were treated with 80 ng/ml of TPA for 24 h and assayed at 24 or 48 h. A 30‐min pulsed TPA exposure of 200 ng/ml induced virus levels approximating those observed after a continous 24‐h exposure to 80 ng/ml. The combination of TPA at concentrations of 10 and 20 ng/ml and a suboptimal level of 5‐iodo‐2‐deoxyuridine (IdUrd) enhanced retrovirus induction threefold above that seen by the optimum IdUrd concentration alone. The protease inhibitors, antipain and leupeptin, decreased virus induction by TPA, a protease inducer. The capacity of TPA to induce type‐C retrovirus complements results demonstrating the enhancement of Epstein‐Barr virus (EBV) and murine mammary tumor virus (MMTV) synthesis by TPA.
Epstein‐barr virus‐induced malignant lymphoma in a white‐lipped marmoset
Authors: Sundar Syam K. , Levine Paul H. , Ablashi Dharam V. , Leiseca Sergio A. , Armstrong Gary R. , Cicmanec John L. , Parker George A. , Nonoyama Meihan
Published: February 2007

One of six white‐lipped marmosets inoculated with cell‐free B95‐8 virus developed diffuse malignant lymphoma. Epstein‐Barr virus (EBV) DNA was detected in a pathologically enlarged mandibular lymph node by DNA‐DNA hybridization. The affected animal at the time of killing had EBV antibody titers of 1:320 for viral capsid antigen (VCA) and 1:20 for early antigen (EA) while all non‐diseased animals had ≦1:80 VCA antibody and no detectable EA antibody. This is the first report of lymphoma development in a white‐lipped marmoset following EBV inoculation.
Analysis of normal neoplastic human tissues for the tumor‐associated protein p97
Authors: Woodbury Richard G. , Brown Joseph P. , Loop Stephen M. , Hellström Karl Erik , Hellström Ingegerd
Published: February 2007

We have used immunoprecipitation to test tumor biopsies and normal adult and fetal human tissues for p97, a tumor‐associated protein. Five of nine melanoma biopsies contained p97 in low to very high levels. Three of seven non‐melanoma tumors contained p97, but in smaller amounts. No p97 was detected in any of the normal adult tissues examined. The protein was, however, observed in samples of fetal colon and umbilical cord, and in one sample of fetal lung. One of two benign nevi contained high levels of p97, while one benign angiofibroma was negative. We conclude that the presence of p97, in levels detectable by our method, appears to be characteristic of certain neoplastic and fetal tissues.
Capping of peripheral blood lymphocyte C3 receptors in chronic lymphocytic leukemia: Relationship to chemotherapy
Authors: Gormus Bobby J. , Basara Michael L. , Oken Martin M. , Leech Stephen H. , Kaplan Manuel E.
Published: February 2007

The data show that in chronic lymphocytic leukemia (CLL) there are elevated numbers of peripheral blood lymphocytes (PBL) capable of rosette formation (complement‐rosetting lymphocytes, CRL) with bacteria (B)‐antibody‐(A)‐complement (C) (BAC) complexes. In most of the CLL patients studied, large percentages of CRL were impaired in their ability to undergo BAC‐C3R cap formation compared to normal donors. The degree of impairment varied from one patient to the next. A consideration of clinical information suggested that the variation was related to the clinical response of patients to chemotherapy. Four categories of CLL patients could be identified on the basis of clinical data: (1) patients who had never received therapy for CLL; (2) those whose clinical history indicated a failure to respond to ongoing chemotherapy; (3) patients who had received successful prior chemotherapy and who were asymptomatic or stable and were receiving no therapy at the time of study; and (4) those who were undergoing therapy at the time of study and who subsequently became stable or asymptomatic and were removed from therapy. The first two categories of patients failed to show significant BAC‐C3R capping, whereas the last two were able to form C3R caps on significant percentages of CRL No direct relationship could be discerned between C3R capping and currently accepted classifications or stages (Rai) of CLL. These results suggest that monitoring the percentages of BAC‐C3R cap‐forming CRL may be useful in determining the success of chemotherapy of CLL patients. The microtubule‐disrupting agent colchicine enhanced BAC‐C3R capping in all CLL patients to normal levels, whereas the microfilament‐disrupting agent cytochalasin B (CB) had no effect on CLL PBL C3R capping. CB totally abolished C3R capping of CRL from normal donors. These results suggest that abnormalities exist in both cytoskeletal and contractile systems of CRL from CLL peripheral blood.
Enhancement of outgrowth of EB virus‐transformed cells from normal human peripheral blood by a tumor promoter, TPA
Authors: Yamamoto Hidehiko , Katsuki Takato , Harada Shinji , Hinuma Yorio
Published: February 2007

Effect of 12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA) on the establishment of lymphoblastoid cell lines (LCL) following spontaneous transformation of B cells by Epstein‐Barr virus (EBV) from peripheral lymphocytes of healthy EBV‐seropositive adults was examined. In the lymphocyte culture with TPA (0.5 ng/ml), the frequency of establishment of LCL increased and the time required for appearance of transformation decreased. A larger number of EBV‐positive cells in the peripheral blood were detected in the assay by co‐cultures with cord blood lymphocytes in the presence of TPA than in the absence of it. The enhancement of LCL establishment by TPA was largely abolished in the culture with EBV neutralizing antibody‐containing human umbilical cord serum. This suggests that the enhancement by TPA may be caused mostly by transformation of coresident B lymphocytes infected with active virus induced from the EBV genome‐positive cells by TPA.
Acute promyelocytic leukemia: Cytogenetics and bone‐marrow culture
Authors: Fraser Jan , Hollings P. E. , Fitzgerald P. H. , Day A. , Clark Vivienne , Heaton D. C. , Hamer J. W. , Beard M. E. J.
Published: February 2007

Six patients were diagnosed as having acute promyelocytic leukemia (APL) according to FAB criteria. One patient conformed to the M3 variant. Informative cytogenetic results (G‐banding) on five of the patients showed that three of them, including the M3 variant, had the 15;17 translocation in bone‐marrow or blood cells. Cells with the translocation were accompanied by cells with a normal karyotype in all patients and no other chromosomal abnormality was present. This first report of the 15;17 translocation from the South Pacific region is relevant to the uneven geographical distribution of APL patients with the translocation. Five of the six patients, including the M3 variant, showed a distinctive pattern of cell growth in agar culture characterized by a profusion of small, uniform clusters containing 6–20 cells with the appearance of promyelocytes. The remaining patient had a pattern of cell growth more typical of M2 acute leukemia. This cell growth pattern may be useful in diagnosing and monitoring the course of APL.
IgA antibody, antibody‐dependent cellular cytotoxicity and prognosis in patients with nasopharyngeal carcinoma
Authors: Mathew Gregory D. , Qualtiere Louis F. , Neel H. Bryan , Pearson Gary R.
Published: February 2007

Immunoglobulin fractions containing antibodies to the Epstein‐Barr virus (EBV) were isolated from different sera and tested in the antibody‐dependent cellular cytotoxicity (ADCC) assay. All cytotoxic activity resided in the IgG fraction. IgA antibodies were not cytotoxic in this assay against cells expressing the EBV‐induced membrane antigen complex. However, IgA antibodies were able to block the IgG‐mediated ADCC reaction, indicating that the IgA and IgG antibodies recognized the same EBV‐specific antigenic determinants. This was supported by results from radioimmune precipitation experiments. Our findings suggest that low ADCC titers previously identified in the sera of patients with nasopharyngeal carcinoma (NPC) who had a poor prognosis could be due to the blocking acitivity of IgA antibodies. The results further suggest that IgA antibodies are detrimental to the patient with this disease, if one assumes that ADCC functions in vivo in immunity to this tumor.
Interferon production and activation of non‐specific effector cells by stimulation with lymphoblastoid cell lines in vitro
Authors: Biron Christine A. , Hutt‐Fletcher Lindsey M. , Wertz Gail T. , Pagano Joseph S.
Published: February 2007

A population of non‐specific effector lymphocytes is generated in response to stimulation with lymphoblastoid cell lines (LCL). These cytotoxic cells have an activity analogous to that exhibited by natural killer (NK) cells. When lymphoid cell lines established by transformation with Epstein‐Barr virus (EBV) are used to stimulate autochthonous T‐cell‐enriched lymphocytes, the activity against the NK‐sensitive target, K562, is increased up to 14‐fold. The stimulated T lymphocytes produce interferon, and this factor augments the cytotoxic activity of unstimulated cells. The size distribution of cytotoxic lymphocytes after stimulation with the autochthonous EBV line is unlike that of either T‐cells or interferon‐augmented T‐cells. Autochthonous stimulated lymphocytes which kill K562 are of several size classes, and are included in populations containing large blast cells. In contrast, the K562 activity of both unstimulated T‐cells and interferon‐augmented T‐cells is contained in a more discrete population of cells, just slightly larger than the majority of lymphocytes. Thus, the generation of non‐specific effector cells during stimulation with lymphoblastoid cell lines appears to involve the activation of a population of blast‐size cells in addition to those initially responsive to interferon augmentation.
Plasminogen activator content of neoplastic and benign human prostate tissues; fibrin augmentation of an activator activity
Authors: Camiolo S. M. , Markus G. , Evers J. L. , Hobika H. , Depasquale J. L. , Beckley S. , Grimaldi J. P.
Published: February 2007

The plasminogen activator content of the extracts of excised prostate cancers (25 specimens) was determined with an azocasein assay and found to be on the average 1.7 times higher than that of extracts of excised prostate benign hyperplasias (29 specimens). Both groups contained the same average percentage of human urokinase type activator (∼45%) as determined by the inhibition of activity when anti‐human urokinase antibody was included in the assay system. The two types of activators were partially purified and found to have distinctly different properties. The most striking difference was the large augmentation of activity of the non‐urokinase enzyme in fibrinolysis. The implications of an enhanced fibrinolysis relative to azocaseinolysis (or other) is discussed, particularly with respect to its importance in the quantitation and characterization of activators by different investigators. Highly purified urokinase‐like activator was found to be similar to commercial urokinase preparation with respect to molecular weight, isoelectric point, inhibition by the antibody, and inhibition by placenta inhibitor.
Differences in lung cancer risk from smoking among Japanese, Chinese and hawaiian women in Hawaii
Authors: Hinds M. Ward , Stemmermann Grant N. , Yang Hong‐Yi , Kolonel Laurence N. , Lee James , Wegner Eldon
Published: February 2007

The age‐adjusted lung cancer incidence rates among Japanese, Chinese and Hawaiian women in Hawaii do not correlate to their respective cigarette smoking exposures. We conducted a case‐control study to determine the lung cancer risk associated with smoking among these three ethnic groups of women by reviewing the medical records of 176 Japanese, 67 Chinese and 132 Hawaiian lung cancer patients diagnosed from 1968 to 1978. Smoking histories, as well as socioeconomic indexes, for these cases were compared to those of 2,404 sex‐ and race‐matched controls from the general population. Controlling for age and socioeconomic index, we found that lung cancer risk associated with smoking was greatest for Hawaiian (O.R.=10.5), less for Japanese (O.R.=4.9) and least for Chinese women (O.R.=1.8). While smoking was associated with a significant increase in lung cancer risk for all histologies among Japanese and Hawaiian women, the risk was much greater for epidermoid and small‐cell types than for adenocarcinoma. Among Chinese women, epidermoid and small‐cell lung cancer were the only histologies showing a significant association with smoking. There was some suggestion that increased lung cancer risk was associated with a higher socioeconomic index after controlling for age and smoking, at least among Japanese born in Japan and Hawaiians with adenocarcinoma. The population risk for lung cancer attributable to smoking was found to be 79% for Hawaiian women, but only 44% for Japanese and merely 11% for Chinese women. Thus, we concluded that the majority of lung cancer occurring in Japanese and particularly Chinese women in Hawaii is due to factors other than cigarette smoking.
Immunoselection in vitro of a non‐metastatic variant from a highly metastatic tumor
Authors: Frost Philip , Kerbel Robert S.
Published: February 2007

Immunoselection of a non‐metastatic variant of the highly metastatic MDAY‐D2 tumor of DBA/2 mice was achieved by means of an antiserum directed to the LY6.2 surface marker of MDAY‐D2. While the new tumor (MDAY‐D2.L61) expresses no detectable LY6.2, other measurable surface markers including H2d, FcR and TAA remain unchanged. The phenotypic behavior of MDAY‐D2.L61 is that of a non‐metastatic tumor and has remained stable after 1 year of maintenance in vivo and in vitro. Immunoselection can now be used to derive variants with stable phenotypic behavior from heterogeneous parent tumor cell populations.
Surface proteins of simian‐virus‐40‐transformed cells
Authors: Chandrasekaran K. , Winterbourne David J. , Luborsky Samuel W. , Mora Peter T.
Published: February 2007

Mammalian cells transformed in tissue culture by SV40 were shown to contain, in addition to the SV40‐coded 94,000 d large T antigen and the 20, 000 d small t antigen, a ∼ 56,000 d cellular protein, which specifically precipitates with sera of animals bearing SV40‐induced tumor (s) (tumor or T serum). We investigated the presence of these three proteins at the surface of logarithmically growing SV40‐transformed cloned mouse cells, after metabolic labelling with [35S]‐methionine for 3 h. The 56,000 d protein was found to be susceptible to digestion by trypsin under conditions which did not disrupt the cells, while no small t antigen was found to be digested. Both the 56,000 d cellular protein and the SV40 large T antigen were susceptible to lactoperoxi‐dase‐catalyzed iodination from the outside of intact cells. Trypsin treatment removed both the iodinated 56,000 d protein and the iodinated SV40 large T antigen. These experiments indicated that (a certain amount of) the 56,000 d protein and a relatively small amount of the large T antigen (which is present mainly in the nucleus) are present on the cell surface. The results confirm and extend independent experiments using subcellular frac‐tionation techniques (Luborsky and Chandrasekaran, 1980; Soule and Butel, 1979). After heat treatment (at 50°C for 30 min) of the whole‐cell extract the 56,000 d cellular protein was precipitated by the tumor serum in the absence of precipitation of SV40 large T antigen. This result showed that the 56,000 d protein is more (thermostable (in the whole‐cell extract) than the SV40 large T antigen, and also indicated that the tumor serum employed had antibodies against the 56,000 d cellular antigen. The heat‐treated whole‐cell extract of SV40‐transformed mouse cells was able to immunize and fully protect mice against a lethal tumorigenic dose of SV40‐transformed cells. These results suggest the need for further experiments to characterize the chemical and immunologic properties of the 56,000 d protein.
Fibronectin in human solid tumors
Authors: Stenman Svante , Vaheri Antti
Published: February 2007

Fibronectin in human solid tumors was studied by indirect immunofluorescence staining of biopsy material. Altogether 73 tumors were examined, comprising 12 sarcomas, 3 melanomas I reticulum cell sarcoma, 39 carcinomas, 6 benign soft‐tissue tumors and 12 benign epithelial tumors. In all sarcomas the individual tumor cells were surrounded by a network of fibronectin which was continuous with the stroma. The distribution of fibronectin was similar in the benign soft‐tissue tumors. In contrast, no fibronectin was detected in the individual carcinoma cells or in their periphery. However, the reactive connective tissue stroma of carcinomas was strongly positive for fibronectin. This was true also for the stroma of benign epithelial tumors. These results show that, contrary to the situation in cell culture,in vivosarcoma cells and benign soft‐tissue tumor cells contain fibronectin in their pericellular matrix. On the other hand, fibronectin can be used to distinguish carcinomas from sarcomasin vivo.
Intraperitoneal administration of corynebacterium parvum in patients with ascitic ovarian tumors resistant to chemotherapy: Effects on cytotoxicity of tumor‐associated macrophages and NK cells
Authors: Mantovani Alberto , Sessa Cristiana , Peri Giuseppe , Allavena Paola , Introna Martino , Polentarutti Nadia , Mangioni Costantino
Published: February 2007

Eight ovarian cancer patients with ascites resistant to various chemotherapy protocols were treated i.p. with C. parvum in an effort to obtain a palliative reduction of peritoneal effusions. C. parvum(7–14 mg) was given i.p. on days 0, 7, 28 and then at monthly intervals. Three patients showed no clinical evidence of therapeutic benefit from C. parvum administration. Three subjects had a complete disappearance of ascites, and two additional patients showed a marked reduction of their effusions. Solid tumor masses were not affected by i.p. C. parvum. C. parvum injection caused a rapid decrease of the percentage of tumor cells in the ascites as early as 7–15 days after the first treatment. Concomitantly, the percentage of polymorphs and, to a lesser extent, of macrophages in the ascitic tumor increased, whereas tumor‐associated lymphoid cells (TAL) were not altered in a consistent pattern. The tumoricidal activity of peripheral blood monocytes and natural killer (NK) cells was not consistently modified after C. parvum treatment. Pretreatment NK activity of TAL was usually very low and was not appreciably modified by i.p. C. parvum. In one patient, whose TAL had NK activity in the range of normal PBL, C. parvum administration was followed by a profound depression of intratumor NK cytotoxicity. The tumoricidal activity of tumor‐associated macrophages (TAM) was not enhanced following C. parvum administration; 14–21 days after the first C. parvum inoculation, a marked decrease of the cytolytic capacity of TAM was observed, cytotoxicity returning to pretreatment values thereafter. These observations do not elucidate the mechanism of the limited, but significant, anti‐tumor activity of i.p. C. parvum in human ovarian carcinomatous ascites. The lack of enhancement of macrophage cytotoxicity after i.p. C. parvum, predicted on the basis of data in rodents, cautions against the empirical use in humans of agents assumed to affect human neoplasia through activation of host defense mechanisms.
Monoclonal antibody to ganglioside gq discriminates between haemopoietic cells and infiltrating neuroblastoma tumour cells in bone marrow
Authors: Kemshead J. T. , Walsh F. , Pritchard J. , Greaves M.
Published: February 2007

An immunological approach has been sought for the identification of minimal metastatic spread of neuroblastoma to bone marrow. Here we describe the reactivity of the monoclonal antibody A2B5 to human neuroblastoma cell lines and fresh tumour tissue. This reagent, raised against chick retinal cells, reacts with all human neuroblastoma lines assayed although quantitative differences in antigenic expression exist between cultures. Analysis of tumour cells in heavily infiltrated bone marrow aspirates indicated that only 70% of the samples reacted with A2B5, suggesting that the heterogeneity seen in the expression of antigen on cell lines is paralleled in fresh tumour material. A2B5 showed no reactivity to either a panel of human leukaemic cell lines or normal human bone marrow, although reactivity to an occasional leukaemic marrow aspirate was detected. We suggest that A2B5 could form part of a panel of monoclonal reagents necessary for detecting metastatic spread of all neuroblastoma cells to bone marrow. Such a group of reagents may be useful therapeutically in a programme of autologous bone marrow transplantation for the removal of tumour cells prior to reinfusion of haemopoietic cells to patients receiving high‐dose chemotherapy.
Antibodies to epstein‐barr virus‐specific antigens in patients with hairy‐cell leukemia
Authors: Sakamoto Kiyoshi , Aiba Motohiko , Katayama Isao , Sullivan John L. , Humphreys Robert E. , Purtilo David T.
Published: February 2007

Antibody titers to Epstein‐Barr virus (EBV)‐specific antigens of 19 patients with hairy‐cell leukemia (HCL) were markedly elevated. All patients showed high titers of IgG anti‐viral capsid antigen (VCA) reactivity equal to or greater than 320 (reciprocal titer). The anti‐VCA reciprocal geometric mean titer (GTM) was 1106 in contrast to a GMT of 80 for healthy controls (p < 0.001). No IgM anti‐VCA antibody was detected, but three patients had IgA anti‐VCA antibodies. Fourteen patients had elevated anti‐early antigen (EA) titers (GMT = 177) which were indicative of active infections with EBV. Seven of the 14 patients demonstrated the diffuse component antibody of the early antigen (EA) complex at a GMT of 98. Anti‐Epstein‐Barr virus nuclear antigen (EBNA) was detected in sera of 16 patients (GMT = 64, controls GMT = 79). It is noteworthy that three patients with anti‐VCA titers lacked anti‐EBNA titers. These antibody responses suggest that immunodeficiency secondary to HCL allowed reactivation of the virus.
Murine natural anti‐tumor antibodies. II. The contribution of natural antibodies to tumor surveillance
Authors: Chow D. A. , Wolosin L. B. , Greenberg A. H.
Published: February 2007

The objective of this study was to investigate whether natural anti‐tumor antibodies (NAb) contributed to the surveillance of small inocula of syngeneic tumors. Experiments were designed to distinguish between NAb and NK‐mediated host resistance. Four approaches were used: (I) the isolation of tumor variants differing in their tumorigenicity and susceptibility to these mechanisms, and to activated macrophages; (2) a comparison of the effects of adjuvants on the modification of both host resistance and the activity of these effectors; (3) the relationship between the ontogeny of the natural resistance mechanisms and tumorigenicity in aged mice; and (4) the use of a Winn‐type assay. These studies provided support for a role in natural resistance correlated with both the ability of tumors to bind NAb, and the production of NAb in adjuvant‐stimulated mice. Furthermore, the frequency of tumors observed after tumor challenge more closely correlated with the ontogeny of natural antibody than NK cells, and tumors coated with NAb were less tumorigenic than controls. The reduced tumorigenicity of an NK‐sensitive tumor, when compared to an NK‐resistant variant of the same line, provided evidence for NK‐cell‐mediated natural resistance in young adult mice. It was concluded that natural resistance to tumors is a complex phenomenon dependent on the tumor phenotype, as well as the activity of several effector mechanisms, and that natural anti‐tumor antibody must be considered an important component of host resistance.
Cell‐mediated suppression of tumor immunity has a non‐specific component. II. Evidence from cell culture experiments
Authors: Hellstrom Ingegerd , Hellstrom Karl Erik
Published: February 2007

In vitro studies were performed to search for cells in the thymus of BALB/c mice with MCA‐induced sarcomas which could suppress either a secondary immune response to MuLV‐associated tumor antigens present on a Moloney leukemia virus‐induced lymphoma, LSTRA, or a primary cytotoxic response to C57BL/6 alloanti‐gens. They showed that thymocytes from mice with sarcomas were suppressive in both systems, and that suppression was independent of whether or not the sarcomas expressed MuLV antigen gp70. Furthermore, normal thymocytes, when combined with mitomycin‐C‐treated cells from any of several different MCA‐induced sarcomas, suppressed the in vitro generation of a secondary cytolytic response to LSTRA. We postulate that exposure of mice to certain tumor antigens induces cells which, in the presence of the same tumor antigens, can suppress the immune response also to antigens which are not detectably present on the tumor cells inducing the response.
Target cell heterogeneity in murine leukemia virus infection. II. Demonstration of friend leukemia‐virus‐permissive and non‐permissive subsets of splenic T cells
Authors: Isaak Dale D. , Cerny Jan
Published: February 2007

The permissiveness of normal splenic lymphocytes to Friend murine leukemia virus was determined by enumeration of cells producing infectious MuLV following infection with Friend virus in vitro. The infection was enhanced greatly in the presence of mitogens in the culture medium. The number of infected cells in cultures stimulated with bacterial lipopolysaccharide increased progressively between days 1 and 7 whereas in cultures with concanavalin A, the number of infected cells reached a maximum on days 3–4 post infection and then declined to the level observed in unstimulated cultures. The con‐A‐enhanced infection was absent in cultures of splenocytes from nude mice but was present in cultures from nude mice implanted with thymus glands 6 weeks or more before use as donors of spleen cells. The cells permissive to MuLV upon con‐A stimulation segregated in the nylon‐wool‐adherent fraction (together with B cells involved in the LPS‐dependent infection) whereas the nylon‐non‐adherent fraction, containing approximately 90% T cells, was refractory to in vitro infection. The con‐A‐dependent infectious centers were inhibited by cytotoxic treatment with anti‐Thy 1.2 antibody plus complement. These results indicate the existence of two subpopulations of splenic T cells, a major nylon‐non‐adherent and a minor, nylon‐adherent subpopulation, which are, respectively, non‐permissive and permissive to MuLV‐Friend.
Generation in vitro of ebv‐induced specific cytotoxic T cells in autologous serum avoids complications due to self‐preferred foetal calf serum‐specific t‐cell cytotoxicity
Authors: Misko I. S. , Kane R. G. , Pope J. H.
Published: February 2007

A previous report has established that in cultures of human mononuclear leukocytes, foetal calf serum (FCS) is capable of generating high levels of T cells preferentially cytotoxic for the autologous lymphoblastoid cell line (LCL). The present study compared the capacity of Epstein‐Barr virus (EBV) to generate cytotoxic T cells in cultures of mononuclear cells grown in FCS or autologous serum in order to clarify the role of FCS in this system. Five EBV‐seropositive and three seronegative donors were used and cultures were harvested at 14 days. With cultures from seropositive donors, whether grown in FCS or in autologous serum, EBV infection generated T cells cytotoxic for the autologous LCL; the response in uninfected control cultures was markedly lower. With seronegative donor cultures grown in FCS, there was virtually no difference in the capacity of T cells generated in infected or uninfected cultures to lyse the autologous LCL. Moreover, cells from seronegative donors cultured in human serum gave no detectable lysis of autologous LCL in either infected or uninfected cultures, clearly showing the absence of a response to EBV. This evidence shows that it is possible to distinguish the generation of specific cytotoxic T cells by FCS from generation by EBV, and with certain donors the apparently EBV‐induced response may actually include a significant component induced by FCS in the medium. The cytotoxicity patterns of EBV‐induced and FCS‐induced T cells for autologous and allogeneic LCL targets showed a degree of parallelism, stressing the need for caution in interpretation of data obtained from cultures using FCS.