bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combinational chemotherapy of L1210 and L1210/ARA‐C leukemia with 5‐AZA‐2′‐deoxycytidine and β‐2′‐deoxythioguanosine
Authors: Momparler Richard L. , Momparler Louise F. , Samson Johanne 
Published: February 2007

AbstractThe in vitro and in vivo antineoplastic activity of 5‐AZA‐2'‐deoxycytidine (5‐AZA‐CdR) and β‐2‐deoxythioguanosine (TGdR) on L1210 an L1210/ARA‐C (resistant to cytosine arabinoside) leukemic cells was investigated. 5‐AZA‐CdR was a very potent cytotoxic agent against the L1210 leukemic cells. This analogue was inactive against L1210/ARA‐C leukemic cells because these cells lack deoxycytidine kinase, the enzyme that converts 5‐AZA‐CdR to its active nucleotide form. TGdR was a potent cytotoxic agent to both L1210 and L1210/ARA‐C leukemic cells. In mice which were injected simultaneously with both L1210 and L1210/ARA‐C leukemic cells, the drug combination of 5‐AZA‐CdR plus TGdR had a very potent antineoplastic activity and producet long‐term survivors. Either agent alone did not produce any long‐term survivors in the mice with L1210 and L1210/ARA‐C leukemia. This experimental model indicates that 5‐AZA‐CdR plus TGdR is an interesting drug combination for the treatment of leukemia with drug‐resistant cells.
Neoplastic transformation of rabbit cells by murine sarcoma viruses
Authors: Rhim J. S. , Bedigian H. G. , Fox R. R. 
Published: February 2007

AbstractNeoplastic transformation of rabbit cells by Kirsten murine sarcoma virus (Ki‐MSV), the Ki‐MSV pseudotype of baboon endogenous virus (Ki‐MSV[BaEV]) and the Moloney‐MSV pseudotype of feline leukemia virus (M‐MSV[FeLV]) is reported. Rabbit cells can be readily transformed by Ki‐MSV, Ki‐MSV(BaEV) and M‐MSV(FeLV). Rabbit cells transformed by Ki‐MSV and M‐MSV(FeLV) were found to be virus producers, whereas those transformed by Ki‐MSV(BaEV) were nonproducers (NP). The NP cells were obtained by simply infection rabbit cells with Ki‐MSV(BaEV) and subculturing the infected cells. Although the morphologically altered NP cells did not produce infectious virus or murine leukemia virus antigen, they did contain a rescuable MSV genome. All of the transformed cells formed colonies in soft agar, grew to high saturation densities and produced tumors when transplanted into nude mice. The Ki‐MSV and M‐MSV(FeLV)‐transformed cells produced tumors in newborn WH/J rabbits, thus providing an important tool for studying tumor immunity in the rabbit.
Environmental and genetic factors determine the level of NK activity of nude mice and affect their suitability as models for experimental metastasis
Authors: Hanna N. , Davis T. W. , Fidler I. J. 
Published: February 2007

AbstractIn these studies we have evaluated the effects of age, genetic background, and housing conditions on the NK‐cell activity of nude mice measured in vitro and resistance to tumor metastasis in vivo. BALB/cAnN nude mice exhibited lower levels of NK‐cell‐mediated cytotoxicity than age‐matched N:NIH(S) nude mice maintained under similar housing conditions. The stronger response of N:NIH(S) nude mice was observed also after experimental activation of NK cells by Corynebacterium parvum. Nude mice maintained under barrier conditions have weaker NK‐cell activity than mice maintained under conventional conditions. The incidence of experimental pulmonary metastases of allogeneic tumors injected into nude mice was inversely correlated with the levels of NK‐cell‐mediated cytotoxicity. Thus, 3‐week‐old BALB/cAnN nude mice raised under barrier conditions were more sensitive to development of experimental metastasis than age‐matched N:NIH(S) nude mice maintained under barrier conditions or nude mice of either strain maintained under conventional conditions. In both strains, however, the relative differences in metastatic potential among the tumor cell lines observed in syngeneic recipients were maintained. We conclude that young BALB/cAnN nude mice raised under barrier conditions may provide a valuable in vivo model for studying metastasis of neoplasms.
Epstein‐Barr virus strain‐specific differences in transformed cell lines demonstrated in growth characteristics, induction of viral antigens and ADCC susceptibility
Authors: Sairenji Takeshi , Jones Wendy , Spiro Robert C. , Reisert Patricia S. , Humphreys Robert E. 
Published: February 2007

AbstractPaired lymphoid cell lines were established by transformation with both B95‐8 (B) and QIMR‐WIL (Q) EBV strains, of cells either from cord blood or from peripheral blood or spleens of patients with leukemias or lymphomas. The morphologies of the transformed cell clumps differed consistently between B‐transformed lines (B‐lines) and Q‐transformed lines (Q‐lines) even after 1 year in culture. When the B‐ and Q‐lines were compared for superinfection with P3HR‐1 EBV, B‐lines had a higher frequency of EA induction than did the Q‐lines. The shape of dose‐response curves for superinfection indicated that a much higher multiplicity of infection by P3HR‐1 EBV was required for EA expression in Q‐lines than in B‐lines. This difference in superinfection was independent of the EBV receptor concentration on the two types of lines and reflected apparent control of the level of EA induction by the resident EBV genome of the transformed line. Transforming EBV could be rescued by P3HR‐1 EBV superinfection of both B‐ and Q‐lines originating from cells of patients with Hodgkin's disease and hairy cell leukemia but not from cord blood. The cord blood lines transformed with virus produced spontaneously from these B‐ or Q‐lines, showed that the cell lines contained antigen‐determining information of the resident genome in the original B‐ or Q‐lines, respectively. Superinfected B‐lines were more susceptible to ADCC with anti‐EBV‐positive sera than were superinfected Q‐lines. These experiments demonstrate that distinct biology. differences exist in paired cell lines transformed by different EBV strains.
Human melanoma cells can be killed in vitro by an immunotoxin specific for melanoma‐associated antigen p97
Authors: Casellas P. , Brown J. P. , Gros O. , Gros P. , Hellström I. , Jansen F. K. , Poncelet P. , Roncucci R. , Vidal H. , Hellstrom K. E. 
Published: February 2007

AbstractConjugates (immunotoxins) comprising ricin A‐chain and monoclonal antibody 96.5, which is specific for human melanoma‐associated antigen p97, inhibited protein synthesis and colony formation of cultured human melanoma cells that expressed more than 80,000 molecules of p97 per cell. Cells expressing fewer than 5,000 molecules of p97 were not killed. The presence of 10 mM ammonium chloride significantly increased the efficiency of the immunotoxin, tumor cells expressing high levels of p97 being killed at immunotoxin concentrations as low as 10−10 M.
Natural cytotoxic cells against solid tumors in mice. IV. Natural cytotoxic (NC) cells are not activated natural killer (NK) cells
Authors: Lattime Edmund C. , Pecoraro Gene , Stutman Osias 
Published: February 2007

AbstractNatural cell‐mediated cytotoxicity (NCMC), measured against a variety of tumors, is mediated by at least two sub‐populations of effector cells: natural cytotoxic (NC) and natural killer (NK). The studies described in this report show that target lysis by NC cells requires a prolonged (18‐ to 24 h) assay period, whereas NC‐susceptible targets can be lysed in short‐term (4 h) [3H]‐proline assays using allo‐sensitized CTL or mitogen‐activated cytotoxic populations. NC cells are not “activated” during the long‐term assay as indicated by: (1) demonstrating that lysis of NC‐susceptible targets in long‐term (20 h) 51Cr assays is still the function of a Qa‐5 effector cell (NC) and (2) the fact that preincubation of the NC effector cell with susceptible targets for 18 h did not result in the activation of an NK‐like population (kinetics of target lysis were comparable to those noted with fresh NC cell preparations). We show that NC cell activity is preserved in both the beige mutant and the PL/J mouse strains, both of which exhibit low NK cell activity, even in long‐term assays. These combined studies support the view that NC and NK cell activities are the function of distinct cell types and not the property of a single cell class under different states of activation.
Discordant Epstein‐Barr virus nuclear antigen (EBNA) antibody patterns in nasopharyngeal carcinoma
Authors: Hewetson John F. , Levine Paul H. , Neubauer Russell H. , Rabin Harvey 
Published: February 2007

AbstractEpstein‐Barr virus nuclear antigen (EBNA) preparations from three sources were tested with sera from normal individuals and patients with Hodgkin's disease, breast carcinoma, Burkitt's lymphoma, and American and Chinese nasopharyngeal carcinoma. Individual sera with discordant antibody patterns were noted in all groups. Sera from both NPC groups gave significantly higher anti‐EBNA titers on cell lines converted with P3HR‐1 or B95‐8 virus compared with anti‐EBNA titers on Raji cells. Anti‐EBNA titers of Chinese NPC sera showed no correlation among the three EBNA sources, while all other groups had highly correlated titers. Cross‐absorption experiments present evidence for more than one antigenic determinant on EBNA. These results suggest an additional parameter for distinguishing Chinese NPC from other EBV‐related disorders.
Effect of interleukin 2 on cytotoxic effectors: I. short‐term culture of the cytotoxic effectors and the in vivo anti‐tumor activity of the cultured effectors isolated from tumor site
Authors: Ting Chou‐Chik , Yang Stringner S. 
Published: February 2007

AbstractThe effects of interleukin 2 (IL2) on the in vitro and in vivo activity of cytotoxic T cells have been studied. IL2 was produced by W/Fu rat spleen cells cultured with concanavalin A. The IL2 thus prepared gave an optimal T‐cell growth‐promoting effect at a concentration of 5–20% equivalents of the original preparation. In the primary, syngeneic mixed lymphocyte/tumor cell cultures (MLTC) against FBL‐3 tumor cells, the addition of IL2 failed to generate a cytotoxic response. However, the cytotoxic response could be generated in MLTC by addition of exogenous macrophages. On the other hand, IL2 could maintain the growth of preformed cytotoxic T cells for 3 to 5 weeks. These cytotoxic T cells were generated either by in vitro sensitization (MLC or MLTC) or by in vivo sensitization of B6 mice against a syngeneic tumor FBL‐3. In short‐term cultures, augmentation of the cytotoxic activity was seen after 10 days' culturing with IL2. The antigenic specificity of the cytotoxic reaction was altered after 28–35 days in culture, and the effectors broadly reactive. When growing a nonadherent population of lymphocytes isolated from FBL‐3 ascites tumor, supplementation with IL2 selectively promoted the growth of a T‐cell population, resulting in the elimination of the contaminating tumor cells. These purified T cells were highly cytotoxic for FBL‐3 cells in vitro and also possessed strong in vivo anti‐tumor activity against FBL‐3 cells in the adoptive transfer experiments. The present study demonstrates that short‐term culture (2–3 weeks) in IL2 promotes the growth of T cells and augments their cytotoxic activity with the appropriate antigenic specificity. IL2 also promoted the selective growth of T cells isolated from tumor site and these T cells showed augmented in vitro and in vivo anti‐tumor activity.
Cytogenetic changes during tumor progression towards invasion, metastasis and immune escape in the Eb/ESb model system
Authors: Dzarlieva R. , Schirrmacher V. , Fusenig N. F. 
Published: February 2007

AbstractRelated tumor lines which represent different stages in their progression towards metastatic capacity were investigated and compared at the chromosomal level. The parental low‐metastatic tumor line (L5178Y/Eb) was derived from a long‐term transplanted, chemically induced T‐cell lymphoma of the DBA/2 mouse. The cytogenetic analysis included this Eb line, a spontaneous high metastatic variant thereof which expressed a distinct tumor‐associated transplantation antigen (ESb TATA+), and an immunoresistant TATA‐negative variant of the latter (ESb TATA−). All three cell lines were characterized by a near‐diploid chromosome count and by some common chromosomal markers derived from Nos. 6, 13 and 16 Large‐scale chromosomal rearrangments resulted in the formation of eight marker chromosomes in Eb cells, 16 in ESb TATA+ cells and 18 in ESb TATA− cells. Tumor progression in this system showed a tendency to monosomies, which could bring the corresponding genes to a hemizygous state and possibly to a release from repression. Chromosome 15 was trisomic in Eb cells, monosomic in ESb TATA+ cells and hardly detectable in ESb TATA− cells. The Ig heavy‐chain gene‐carrying region of both chromosomes No. 12 was found in translocation with chromosomes Nos. 5, 13 and 14 (Eb cells) and with Nos. 1 and 17 (ESb cells). ESb TATA− cells differed from ESb TATA+ cells at four different chromosomes (Nos. 5, 8, 14 and 15).
Adenovirus‐12 genes undetectable in human retinoblastoma
Authors: Mak S. , Mak I. , Gallie B. L. , Godbout R. , Phillips R. A. 
Published: February 2007

AbstractRetinoblastoma is a rare eye tumor found predominantly in young children. Intra‐ocular injection of adenovirus‐12 (Ad‐12) into newborn recipients induces in rats and in baboons tumors morphologically similar to human retinoblastoma tumors. In addition, Ad‐12 DNA can transform human embryonic retinal cells and the transformed cells form retinoblastoma‐like tumors in nude mice. These observations have led to the suggestion that Ad‐12 may also be involved in the induction of human retinoblastoma tumors. To test this possibility, DNA and RNA were isolated from six human tumors. Analysis of RNA and DNA by blotting with labelled Ad‐12 failed to reveal viral sequences in human retinoblastoma.
Histologic features of bladder cancer in Boston, USA, Manchester, UK, and Nagoya, Japan
Authors: Morrison Alan S. , Proppe Karl H. , Verhoek Wendy G. , Aoki Kunio , Leck Ian , Ohno Yoshiyuki , Obata Koji 
Published: February 2007

AbstractHistologic characteristics of bladder cancer in Boston, USA, Manchester, UK, and Nagoya, Japan, were evaluated. In each of these areas broadly‐based series of cases were assembled during a collaborative case‐control study. The present analysis was based on 589 cases in Boston, 484 cases in Manchester, and 241 cases in Nagoya. A single pathologist reviewed a slide of the primary tumor without reference to identifying information or other data. The primary histologic type of nearly all tumors was transitional‐cell, and there was little variation in the proportion of transitional‐cell tumors among the study areas. Nor was there much variation in the distribution of histologic grade, the proportion of tumors showing submucosal invasion, or the proportion of tumors with a papillary surface. Age at diagnosis was strongly correlated with histologic grade. The proportion of grade III (most malignant) tumors was about twice as high among patients 80 years of age and over as among those aged less than 50. An apparent association between age and submucosal invasion was explained in large part by the relationships of histologic grade to submucosal invasion and to age. Other histologic features had only weak and inconsistent relations with age. None of the features evaluated showed consistent associations with history of cigarettesmoking or with sex.
Cloning of human solid tumors in soft agar
Authors: Kern David H. , Campbell Mary Ann , Cochran Alistair J. , Burk Martyn W. , Morton Donald L. 
Published: February 2007

AbstractOf 1,014 human solid tumors of various histologic types, 690 (68%) showed evidence of colony formation within 2 to 4 weeks. Tumors which grew particularly well were colon carcinoma (104/175), melanoma (134/155), lung carcinoma (62/85), breast cancer (100/140), ovarian carcinoma (50/67), and sarcoma (72/122). Histologic examination indicated that the colony‐forming cells retained functional and morphologic features similar to those of the original tumor. Plating efficiencies varied between 0.01% and 0.2%, and the numbers of colonies observed formed a direct linear correlation with the number of cells plated. Recovery of viable tumor cells was increased when enzymatic tumor dissociation was used rather than a mechanical method. A simplified, supplemented medium resulted in improved cloning efficiencies when compared to previously reported methods (Hamburger and Salmon, 1977 b).
Effect of epidermal growth factor on clonogenic growth of primary human tumor cells
Authors: Pathak Meera A. , Matrisian Lynn M. , Magun Bruce E. , Salmon Sydney E. 
Published: February 2007

AbstractThe effect of EGF on the soft agar colony‐forming ability of fresh human tumor cells was assessed in 40 specimens obtained from various types of carcinoma including those of the breast, endometrium, ovary, and other sites. Cells from four established human tumor cell lines (three breast and one endometrial) were also included in this study. The results showed that addition of EGF at a concentration of 50 ng/ml resulted in a 50% higher cloning efficiency in soft agar in 40% of the samples of fresh human tumors. When cells from tumor cell lines were plated in semi‐solid medium containing EGF, the number of colonies formed was at least twice as high as controls. Cells from fresh tumor biopsies were assayed for EGF receptors to determine whether the correlation between the proliferative response in EGF‐supplemented semi‐solid medium as compared to control could be related to the number of EGF receptors present on the cells. Specific receptors for EGF were detected by using radioiodinated EGF in early‐passage cell cultures from some of the tumors tested for clonogenicity. The number of receptors ranged from 0.3 to 3.27 × 105 per cell. Cells from two melanoma specimens possessed less than 0.3 × 103 EGF receptors per cell. We found no correlation between the number of EGF receptor on a cell surface and the mitogenic effect of EGF on the same tumor cells grown in semi‐solid medium.
Autoinduction of differentiation in wehi‐3B leukemia cells
Authors: Metcalf Donald , Nicola Nicos A. 
Published: February 2007

AbstractCells of the differentiation‐responsive mouse myelomonocytic leukemia cell line WEHI‐3B D+ form colonies in agar exhibiting a low frequency of spontaneous differentiation mainly in the macrophage pathway. Compared with undifferentiated colonies, spontaneously differentiating colonies have a reduced content of clonogenic cells and surviving clonogenic cells tend themselves to form differentiating colonies, both being characteristics of differentiated colonies induced by the regulator, granulocyte colony‐stimulating factor, G‐CSF. Colony crowding increased the frequency of spontaneously differentiating colonies and WEHI‐3B D+ colony cells were shown to release material able to induce differentiation in WEHI‐3B D+ colonies. Cells from spontaneously differentiating D+ colonies were not hyperresponsive to the induction of differentiation by G‐CSF and did not release larger amounts of differentiation‐inducing material than did cells from undifferentiated colonies. Cells of the differentiation‐unresponsive WEHI‐3B D− line produced similar amounts of differentiation‐inducing material to those produced by D+ cells. Apparently spontaneous differentiation in WEHI‐3B D+ colonies seems most likely to be due to exposure of the colony‐forming cell or its ancestors to a differentiation‐inducing factor of WEHI‐3B origin prior to culture in agar, the genetic program initiating differentiation being inherited by the progeny of the exposed cell.
Characterization and activation of cyclic adenosine 3′:5′‐monophosphate‐dependent protein kinase in C1300 murine neuroblastoma clones growing in vivo
Authors: Nakajima Fumiaki , Imashuku Shinsaku , Green Alexander A. 
Published: February 2007

AbstractCyclic adenosine 3′:5′‐monophosphate (cAMP)‐dependent protein kinases from three clones of C1300 neuroblastoma, established as growing tumors in A/jax mice, were identified and characterized. Mean (± SD) intratumor concentrations of cAMP ranged from 5.0±2.4 to 6.8±1.9 pmol/mg protein; cytosolic protein kinase activity ratios, calculated from the ‐cAMP/+cAMP value, ranged from 0.12±0.02 to 0.18±0.02. The total amount of cytosolic cAMP‐binding activity was highest in the NBA2 clone and nearly equal in N‐18 and NBP2. By DEAE chromatography, two peaks of cAMP‐binding activity eluting at ionic strengths of 0.09 and 0.15 M of NaCl were resolved from each clone. The latter peak was associated with catalytic activity (type II cAMP‐dependent protein kinase), whereas the former was not (free type I cAMP‐binding protein). Photoaffinity labeling with 8‐azido (N3)‐[32P]cAMP, followed by sodium‐dodecyl‐sulfate:polyacrylamide gel electrophoresis, resolved four major cAMP‐binding proteins with molecular weights ranging from 39,000 to 56,000 in each clone. The mol. wt 47,000 protein was judged to be a free regulatory subunit of type I kinase, and the mol. wt 39,000 protein a cleavage product. The mol. wt 54,000 and 56,000 proteins were both endogenously phosphorylated and both had a lower affinity for 8‐N3‐[32P]cAMP, characteristic of type II kinase. Selected properties of the cAMP‐binding proteins (kinetic and autophosphorylating features, response to tryptic hydrolysis, specificity for cAMP and temperature sensitivity) did not differ appreciably among clones. Despite initially low intratumor concentrations of cAMP, it was possible to activate the protein kinase system by simultaneous injection of N6, O‐dibutyryl‐cAMP and papaverine. This indicates that mouse C1300 neuroblastoma can be used profitably to study cAMP‐induced neuroblast differentiation.
Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation
Authors: Gerdes Johannes , Schwab Ulrich , Lemke Hilmar , Stein Harald 
Published: February 2007

AbstractThe production of a mouse monoclonal antibody, Ki‐67, is described. The Ki‐67 antibody recognized a nuclear antigen present in proliferating cells, but absent in resting cells. Immunostainings with Ki‐67 revealed nuclear reactivity in cells of germinal centres of cortical follicles, cortical thymocytes, neck cells of gastrointestinal mucosa, un‐differentiated spermatogonia and cells of a number of human cell lines. The Ki‐67 antibody did not react with cells known to be in a resting stage, such as lymphocytes, monocytes, parietal cells and Paneth's cells of gastrointestinal mucosa, hepatocytes, renal cells, mature sperm cells, brain cells, etc. Expression of the antigen recognized by Ki‐67 could be induced in peripheral blood lymphocytes after stimulation with phytohaemagglutinin, whereas it disappeared from HL‐60 cells stimulated with phorbol esters to differentiate into mature macrophages in a resting stage. These findings suggest that Ki‐67 is directed against a nuclear antigen associated with cell proliferation. A first series of immunostainings of tumour biopsies indicated that Ki‐67 may be a potent tool for easy and quick evaluation of the proportion of proliferating cells in a tumour.
Epstein‐barr virus (EBV)‐induced lymphoproliferative disease in cotton‐topped marmosets
Authors: Johnson Donald R. , Wolfe Lauren G. , Levan Göran , Klein George , Ernberg Ingemar , Åaman Pierre 
Published: February 2007

AbstractSix cotton‐topped marmoset monkeys (Sangiunus oedipus) were inoculated with 105 tranforming units of B95‐8 virus, and two of them developed fatal lymphoproliferative disease. The EBV‐carrying tumor cells from these marmosets had the following characteristics: (I) they were polyclonal by surface immunoglobulin and immunoglobulin production in vitro; (2) they had no specific chromosome abnormalities, and (3) they failed to form colonies in large percentages in agarose. It is proposed that a spectrum of phenotypes of EBV‐induced lympho‐proliferative diseases in the cotton‐topped marmosets may be identified and are more akin to fatal infectious mononucleosis or X‐linked lymphoproliferative syndrome than to Burkitt's lymphoma.