bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adoptive immune therapy in mice bearing poorly immunogenic metastases, using T lymphocytes stimulated in vitro against highly immunogenic mutant sublines
Authors: Dennis J. W. , Laferté S. , Man M. S. , Elliott B. E. , Kerbel R. S. 
Published: February 2007

AbstractMDW3, a highly immunogenic and non‐tumorigenic (tum−) mutant of the poorly immunogenic metastatic murine tumor called MDAY‐D2, has been employed in an immune therapy scheme for the treatment of widespread established visceral MDAY‐D2 metastases in syngeneic mice. MDW3 was selected from a mutagenized population of MDAY‐D2 cells for the ability to grow in the presence of toxic concentrations of wheat‐germ agglutinin (WGA) in vitro. The mutant expresses a common tumor‐associated antigen (TAA) present on MDAY‐D2 as well as a new antigen whose presence enhances the anti‐TAA cell‐mediated immune response in vivo and in mixed lymphocyte tumor cultures (MLTC) in vitro. For immune therapy, spleen cells from DBA/2 mice which had rejected an inoculum of MDW3 cells were restimulated in MLTC and injected i.v. into MDAY‐D2 tumor‐bearing mice. Two protocols were used. In the first, mice were given an i.v. injection of 10 MDAY‐D2 cells (“artificial metastasis”) and subsequently treated with 400 R whole‐body irradiation and MDW3‐stimulated T cells. Such mice had a 75% long‐term survival rate, whereas 400 R alone, or no treatment, resulted in 25% and 0% long‐term survivors, respectively. In the second protocol, treatment of mice bearing a 12‐day‐old subcutaneous MDAY‐D2 tumor by surgical removal of the solid tumor, 400 R whole‐body irradiation, and systemic administration of MDW3‐stimulated spleen cells, resulted in a 75‐100% survival rate, whereas omitting any part of the treatment resulted in 0‐50% survival rates. The treatment increased splenic anti‐TAA CTL activity, and the mice acquired immunity against the new antigen on MDW3, suggesting that the injected lymphocytes were proliferating in the host. The optimal combination of resection, whole‐body irradiation and passive infusion of MDW3‐stimulated spleen cells was ineffective when used on mice bearing a tumor‐antigen‐loss variant of MDAY‐D2, suggesting that success of our immune therapy protocol required specific recognition of the tumor‐associated antigen of MDAY‐D2.
Mouse lewis lung carcinoma and hepatoma ascites treatment by combination of liposome chemotherapy and non‐specific immunotherapy
Authors: Patel Kanaiyalal R. , Baldeschwieler John D. 
Published: February 2007

AbstractLiposomes have been used as biological carriers of anti‐tumor drugs, and their potential use has been tested in mouse Lewis lung carcinoma and hepatoma ascites tumor models. Ara‐C3 given by the intraperitoneal i.p. route either at 35 mg/kg in a single dose or at 2.5 mg/kg/dose with 5 doses/day for 3 days had no effect on the average survival time of i.v. implanted LLC. However, the same single dose of Ara‐C encapsulated in positively charged MLV significantly improved the average survival time of LLC‐bearing mice. MTX was chosen as a test drug for the treatment of hepatoma ascites. Non‐encapsulated MTX given at either 3 or 30 mg/kg by the i.p. route had little effect on the average survival of i.p.‐implanted hepatoma ascites. However, MTX encapsulated in SUV at a 3 mg/kg dose by the i.p. route significantly improved the average survival time of tumor‐bearing mice. A combination of chemotherapy and non‐specific immunotherapy has also been tested with these 2 tumor models. Two non‐specific microbial immune stimulators, Bacillus Calmette Guérin (BCG) and Corynebacterium parvum (CP) were tested by both the i.v. and i.p. routes. A combination of BCG therapy with non‐encapsulated anti‐tumor drugs was not effective for either of the tumor models. A combination of BCG therapy with liposome therapy appeared to improve the average survival time of LLC‐bearing mice. In particular, BCG treatment by the i.p. route in combination with liposome therapy resulted in a 20% long‐term survival rate among treated mice. However, BCG therapy by either route in combination with SUV encapsulated MTX therapy had no effect on the average survival time of hepatoma ascites‐bearing mice. Immunostimulation with CP at a given dose appears to be superior to BCG therapy for both tumor models. In the treatment of LLC, injection of CP by either the i.v. or i.p. route appears to be equally effective in combination with liposome therapy. However, for the treatment of hepatoma ascites, CP was only effective by the i.p. route, in combination with liposome therapy.
Generation of invasive and metastatic variants of a non‐metastatic T‐cell lymphoma by in vivo fusion with normal host cells
Authors: De Baetselier Patrick , Roos Ed , Brys Lea , Remels Linda , Feldman Michael 
Published: February 2007

AbstractIntravenous inoculation of the AKR mouse‐strain‐derived BW lymphoma into CBA recipients resulted in a case of liver metastasis; cells derived from this metastatic nodule were termed BW‐Li cells. BW‐Li cells, upon reinoculation, generated metastases in the spleen, liver, kidney and ovaries in 100% of CBA recipients. Furthermore, BW‐Li cells, in contrast to BW cells, were found to infiltrate in vitro monolayers of hepatocytes, thus confirming their inherent invasive potential. Analysis of the alloantigenic phenotype of BW‐Li cells revealed that such cells were Thy 1.1+, Thy 1.2+, Lyt 1.2+, Lyt 1.1−, Lyt 2− and H‐2Dk+, as compared to BW cells which exhibited the membrane phenotype Thy 1.1+, Thy 1.2−, Lyt 1.2−, Lyt 1.1k−, Lyt 2−, H‐2Dk−. BW‐Li cells also differed functionally from BW cells since these cells secreted IL‐2 upon stimulation with Concanavalin A. BW tumor transplantation experiments were repeated in a semi‐allogeneic F1 strain combination, i.e. (AKR × CBA)F1, and again a case of massive liver metastasis was observed. Cells derived from these liver metastases (termed BW‐O‐Li) manifested an invasive and metastatic potential similar to that of BW‐Li cells. Furthermore, BW‐O‐Li cells secreted IL‐2 upon stimulation with Con A and manifested the following alloantigenic phenotype: Thy 1.1+, Thy 1.2+ Lyt 1.2+, Lyt 1.1−, Lyt 2−, H‐2Dk+ and H‐2Kk+. These results indicate that BW‐Li and BW‐O‐Li cells are functional T‐cell hybrids which express T‐cell markers derived from BW cells and Thy 1.2+ CBA host cells. The acquisition of host‐derived T‐cell properties may have led to the expression of metastatic and invasive capabilities. From these results we conclude that the acquisition of metastatic properties following somatic cell fusion with normal lymphoreticular cells may represent a mechanism for tumor progression in vivo.
Possible association between HLA‐DR5 and superficial spreading melanoma (SSM)
Authors: Mueller‐Eckhardt G. , Schendel D. J. , Hundeiker M. , Riedel T. , O'Neill G. J. , Riethmüller G. , Mueller‐Eckhardt C. 
Published: February 2007

AbstractPrevious analyses of possible associations between MHC determinants and cutaneous malignant melanoma (MM) have been inconclusive. We have investigated 98 patients with special emphasis on histologically determined subtypes of MM, and 5 multiple‐case families. In addition to HLA‐ABC and DR typing, complement allotypes of C2, C4A, C4B, BF were determined. Among the unrelated patients HLA‐DR5 and, secondarily, B49 were observed to be associated with superficial spreading (SSM) but not with nodular (NM) or lentigo maligna melanoma (LMM). In families with MM, no definite segregation of the disease according to HLA and complement haplotypes was discernible. Moreover, no coincidence of haplotypes occurred in patients of the different families. HLA region recombinations including B/DR and/or DR/GLO were found in all the families investigated.
Neoplastic x and λ cells in a B‐PLL with chromosome translocations of both light chain gene regions
Authors: Brito‐Babapulle V. , Melo J. V. , Foroni L. , Robinson D. , Parreira L. , Brozovic M. , Catovsky D. 
Published: February 2007

AbstractWe describe a chromosome translocation t(2;13) (p11‐12;p11) involving the kappa (x) light chain gene region (2p11‐12), and a subsequent translocation t(11;22) (q23;11) involving the lambda (λ) light chain gene region (22qll) within the same clone, in a patient with B‐cell prolym‐phocytic leukaemia (B‐PLL), of whose peripheral mono‐nuclear cells 82% expressed (x) chains and 8% expressed (λ) chains. Electron microscope (EM) studies using the immunogold method showed that both x− and λ‐producing cells were prolymphocytes. Immunoglobulin (Ig) gene analysis by Southern blotting demonstrated rearrangement of both Ig heavy (H) chain genes and one x gene. Although a λ gene rearrangement corresponding to the minor λ‐positive population was not detected, a small monoclonal (M) band of IgM‐λ was present in the serum. The chromosome translocations and the pattern of light chain expression, particularly the λ‐producing cells, are discussed in the light of the restricted light chain expression observed in Burkitt's lymphomas with variant translocations involving the light chain genes.
Follow‐up study of hbs ag‐positive blood donors with special reference to effect of drinking and smoking on development of liver cancer
Authors: Oshima Akira , Tsukuma Hideaki , Hiyama Tomohiko , Fujimoto Isaburo , Yamano Hajime , Tanaka Masayoshi 
Published: February 2007

AbstractIn order to confirm the close association between chronic hepatitis B virus (HBV) infection and primary hepatocellular carcinoma (PHC) in Japan, 8,646 male hepatitis B surface antigen (HBs Ag)‐positive blood donors (GPT ± 35 Karmen units) were followed up. Twenty liver cancer cases were observed during the follow‐up period (average 6.2 years), the expected number calculated on the basis of age‐specific incidence rates among the general population being 3.03. Therefore, the observed to expected ratio of liver cancer was 6.60, that is significantly higher than 1.0. During the same follow‐up period, a total of 76 deaths were observed, of which 20 were due to liver cancers and 9 to liver cirrhoses, meaning that nearly 40% of deaths among the study subjects due to chronic liver diseases. Drinking and smoking habits in the liver cancer cases were compared with those observed in healthy male HBV carriers. A strong positive association between drinking habits and liver cancer was observed and there was a significant dose‐response relationship after adjustment for cigarette smoking habits. A high risk of liver cancer was also observed among heavy smokers, but a significant dose‐response relationship could not be found between smoking habits and liver cancer, partly because of the limited number of the study subjects. These findings suggest that HBV is a major etiologic agent of PHC in Japan where the HBs Ag prevalence rate is about 2%, and alcohol drinking and cigarette smoking may promote the process of HB viral hepato‐carcinogenesis.
Epitopes immunologically related to glycophorin a on human malignant and non‐malignant cells in culture
Authors: Barsoum A. L. , Czuczman M. S. , Bhavanandan V. P. , Davidson E. A. 
Published: February 2007

AbstractNine monoclonal antibodies specific to different antigenic determinants on the cyanogen bromide fragments CNBr3 (1‐8) and CNBrl (9‐8l) of glycophorin A, the major sialoglycoprotein of human red blood cells, were used for the detection of similar or cross‐reactive epitope(s) on nucleated somatic cells. A panel of human malignant and non‐malignant cells consisting of erythroleukemia, melanoma and carcinomas of breast, cervix, larynx, nasopharynx and colon, as well as human fibroblasts and mammary cells, were tested using a sensitive enzyme‐linked immunoassay. The presence of glycophorin‐like epitopes were demonstrated, in varying concentrations, on all cells tested. These epitropes were found to be localized on the cell membranes by indirect immunofluorescence.
The inhibition of lymphocyte stimulation by autologous human metastatic melanoma cells correlates with the expression of HLA‐DR antigens on the tumor cells
Authors: Taramelli Donatella , Fossati Giuseppe , Balsari Andrea , Marolda Raffaele , Parmiani Giorgio 
Published: February 2007

AbstractPrevious studies indicated that peripheral blood lymphocytes from patients (Pt‐PBL) with lymph node metastatic melanomas proliferated in vitro and developed into tumor‐restricted cytotoxic lymphocytes in response to alloantigens or interleukin 2 (IL‐2). However, Pt‐PBL were not stimulated by irradiated autologous metastatic melanoma (Auto‐Me) cells. In the present study we report that the lack of stimulatory activity of Auto‐Me cells may be due to a suppressive effect exerted by Auto‐Me cells on the responder lymphocytes. In fact, we found that in 62% of cases examined, the addition of 5‐10% Auto‐Me cells to Pt‐PBL cultures strongly inhibited both proliferation and the generation of tumor cytotoxic lymphocytes induced by alloantigens or IL‐2. The inhibition was dose‐dependent and tumor‐restricted, and was not due either to toxicity, medium depletion or IL‐2 absorption by Auto‐Me cells. Normal fibroblasts, K562 cells and autologous E‐ lymphocytes were not suppressive. Auto‐Me cells were able to inhibit Pt‐PBL responses only when added during the first 24 h of culture and not later. Phenotypic analysis of Auto‐Me cells using monoclonal antibodies directed against HLA‐A,B,C, HLA‐DR and melanoma‐associated antigens revealed that the expression of high levels of DR antigens on Auto‐Me cells was associated with an elevated suppressive activity. Conversely, Auto‐Me cells with low or undetectable levels of DR antigens were not inhibitory. Furthermore, the increased expression of DR antigens on Auto‐Me cells obtained by in vitro treatment with human interferon gamma (IFN‐γ) also resulted in an increased suppressive activity. We conclude that HLA‐DR+ metastatic melanoma cells can interfere with the generation of an anti‐tumor immune response, thus potentially favoring the escape of the tumor from the host's control mechanism.
Passive adoptive immunotherapy of low‐immunogenic BALB/C lymphoma by syngeneic alloimmune T lymphocytes
Authors: Colombo Mario P. , Arioli Ivano , Parmiani Giorgio 
Published: February 2007

AbstractThe virus‐induced BALB/c lymphoma YC8 is known to be lysed in vitro by syngeneic lymphoid cells immune to non‐H‐2 antigens of B10.D2 and DBA/2 backgrounds. This tumor is weakly immunogenic in vivo and kills 100% of syngeneic mice with 1 × 103 cells given either intravenously (i.v.) or intraperitoneally (i.p.). We show here that i.v.‐injected YC8 cells grow preferentially in the liver, where colonies become microscopically visible after 7‐10 days, and, less frequently, in the kidneys and spleen but not in the lung. Passive adoptive immunotherapy of this tumor was carried out with alloimmune BALB/c anti‐B10.A, anti‐pool (donors were immunized with lymphocytes from 5 different strains), anti‐A and anti‐DBA/2 splenic and lymph node cells. When administered i.p. 1, 3 or 5 days after tumor cells had been given i.p. and with a schedule of 5 subsequent daily inocula, anti‐DBA/2 lymphocytes cured 100%, 80% and 60% of animals respectively. A weaker effect was obtained with anti‐pool immune cells whereas anti‐B10.A and anti‐A lymphoid cells had not therapeutic effects. When given i.v., the anti‐DBA/2 immune lymphocytes were able to cure both i.v. and i.p. tumor‐injected mice. A significant effect was observed also when the onset of immunotherapy was delayed until 7 or 10 days after tumor injection. By depleting the BALB/c anti‐DBA/2 immune cells with appropriate monoclonal antibodies and complement, it was found that Lyt 1 + 2‐ cells played the major role in eradicating the neoplasm. in vitro phenotypic and functional analysis showed that the immune cell population included 70% of Thy 1 +, 38% of Lyt 1 + and 18‐20% of Lyt 2+ cells. Immune lymphocytes were not cytotoxic in vitro to YC8 or DBA/2 targets whereas they proliferated after restimulation with DBA/2 but only weakly with YC8 cells. This shows that it is possible to cure mice bearing a disseminated lymphoma which expresses non‐immunogenic antigens recognized by BALB/c anti‐DBA/2 immune T lymphocytes. These immune lymphocytes had no cytotoxic activity in vitro and their major effector cell subpopulation displayed the Thy 1+, Lyt 1+ phenotype.
Biochemical characterization of human carcinoma surface antigen associated with protein kinase activity
Authors: Seehafer Jutta , Longenecker B. Michael , Shaw Andrew R. E. 
Published: February 2007

AbstractMAb 50H.19 immunoprecipitates two proteins from lysates of human carcinoma cell lines, and embryonic fibroblasts intrinsically labelled with 3H‐leucine, 35S‐methionine, or a 3H‐amino acid mixture; a major component of M, = 22,000 (22 kd component) and a minor component of M, = 24,000 (24 kd component). Oligomeric forms of the proteins are not observed under reducing or non‐reducing conditions. Both proteins are expressed on the plasma membrane, and are glycoproteins. We investigated the relationship between the proteins in terms of their glycosylation and derivation from precursors. The 22 kd component is O‐glycosylated as demonstrated by 3H‐galactose incorporation, insensitivity to tunicamycin (TM), and its stepwise generation from a 20.5 kd precursor. The 24 kd protein is N‐glycosylated, as shown by 3H‐mannose incorporation, and by the total inhibition of its synthesis in the presence of TM. Further evidence for its N‐glycosylation is provided by the appearance of a 23 kd precursor in lysates from the osteogenic sarcoma cell line SKOSC pulse‐labelled for 5 min, a time preceding O‐glycosylation of the 20.5 kd protein. Furthermore, mild alkali treatment of the immune complex leads to a loss of approximately 1,000 daltons in each glycoprotein confirming the O‐glycosylated nature of the 22 kd component, and suggesting that the 24 kd component is additionally O‐glycosylated. Both glycoproteins undergo an apparent increase of molecular weight of about 500 daltons when run in the non‐reduced form on SDS polyacrylamide gels under standard electrophoretic conditions, suggesting they contain a similar degree of intra‐chain disulphide bonding. Confirmatory evidence that the two components share a common polypeptide backbone is provided by the appearance of only the 20.5 kd component in lysates from SKOSC cells pulse‐labelled for 5 min in the presence of TM.
Subgroup analysis of BL‐cell lines with polyclonal bl‐specific antibodies
Authors: Gazitt Yair , Ehlin‐Henriksson Barbro , Lerner Ana , Klein George 
Published: February 2007

AbstractA Burkitt's lymphoma (BL)‐specific antibody (antiGP70), previously described, was used to analyse 22 different BL‐cell lines. The results indicated specificity of antibodies to lines that contain both surface membrane Ig (Smlg) and cytoplasmic Ig (Cylg). BL‐cell lines derived from more immature B cells that do not have Smlg but rather have only Cylg were negative. A comparative study with antibody to common ALL antigen (CALLA) and to another BL‐specific antigen (BLA) revealed coexpression of GP70 with those two antigens, but no identity between them.
Macrophage oxidative burst and related cytotoxicity. I. Differential activation by tumor‐promoting and non‐tumor‐promoting phorbol esters
Authors: Keisari Yona , Flescher Eliezer , Geva Ita 
Published: February 2007

AbstractMouse peritoneal macrophages elicit an oxidative burst (OB) response upon stimulation with the tumor promoter 12‐O‐tetradecanoyl‐phorbol 13‐acetate (TPA). In this study we compare the OB‐stimulating capacity of phorbol ester derivatives, structurally related to TPA, which differ in their tumor‐promoting activity. Non‐tumor‐promoting derivatives such as phorbol 13‐acetate, phorbol 12‐myristate, TPA‐2‐O‐aldehyde and 4‐O‐methyl TPA were tested. These reagents stimulate macrophages to generate OB products such as O−2 and H2O2, yet the amounts required for stimulation are 1,000 times higher than the amounts of TPA required to elicit a comparable response. It has also been observed that, in the same order of magnitude, the above‐mentioned derivatives are less efficient than TPA in rendering macrophages cytolytic toward erythrocytes. Another strong tumor promoter tested, teleocidin, has been found to be as potent as TPA in the activation of macrophage OB and in related activities.
Non‐random chromosome changes in a herpes‐virus‐transformed syrian hamster cell line and its metastatic derivatives
Authors: Pratt Norman R. , Lowther Gordon W. , Rees Robert C. , Teale David M. , Potter Christopher W. 
Published: February 2007

AbstractA primary subcutaneous tumour of low spontaneous metastatic capacity, produced after inoculation of Herpesvirus hominis type‐2‐transformed hamster fibroblasts (parent line) and two in vivo derived highly metastatic lung deposits (Met A and Met B) were karyotyped and compared after trypsin G‐banding. The parent line was cytogenetically heterogeneous with a modal chromosome number of 74. However, a number of cells were of a higher ploidy level. A large variation in both numerical and structural abnormalities was observed, the chromosome rearrangements were often complex and unstable, but all the cells contained a theme of common marker chromosomes. Met A and Met B were near diploid (mean chromosome numbers 42 and 44 respectively) with a low level of tetraploid cells. They shared many chromosome rearrangements but could be readily distinguished by an additional translocation unique to Met A. Cytogenetic homogeneity within and between metastases suggested that they were of monoclonal origin and had been derived from a karyotypically similar subpopulation within the parent tumour. We were unable to detect such cells in the parent line; thus, their numbers within the parent tumour were likely to be low. Metastasis, therefore, has been highly selective, depending on the particular phenotypic properties of Met A and Met B. All cells of the parent and metastatic lines have homogeneously staining regions (HSR) and abnormalities of chromosomes 15 (C15) which may be important in tumorigenesis. In addition, Met A and Met B cells have a number of chromosome rearrangements [translotions, deletions and a double minute chromosome (DM)] not present in the parent cells. They are retained at a high frequency in the cells of Met A and Met B and thus it seems likely that the metastatic phenotype is associated with one or more of these chromosome aberrations.
Preparation and characterization of antibodies to o‐phosphotyrosine and their use for identification of phosphotyrosine‐containing proteins
Authors: Ohtsuka Masahiro , Ihara Seiji , Ogawa Ryoichi , Watanabe Toshiteru , Watanabe Yasushi 
Published: February 2007

AbstractTo facilitate the identification of phosphotyrosine (Ptyr)‐containing proteins, rabbit polyclonal antibodies and mouse monoclonal antibody specifically reactive to P‐tyr were prepared by hyperimmunizing the animals with P‐tyr‐conjugated bovine serum albumin or poly‐L‐lysine. As determined by a solid‐phase radioimmunoassay and an enzyme‐linked immunosorbent assay, the antibodies reacted with P‐tyr‐conjugated target antigens but not with those conjugated with phosphoserine (P‐ser) or phosphothreonine (P‐thr). This immune reaction was strongly blocked by 2 mM P‐tyr and phenylphosphate but not by P‐ser or P‐thr. The antibodies were capable of isolating, as the major P‐tyr‐containing components, a 170kd protein (most likely the EGF receptor) from EGF‐stimulated, 32P‐labelled A431 cells, and 130kd and 60kd proteins from Rous sarcoma virus (RSV)‐transformed chick cell lysate which had been labelled in vitro, with γ‐32P‐ATP. Immunofluorescent staining of RSV‐transformed cells and A431 cells showed specific localization of P‐tyr‐containing proteins in the cytoplasm, plasma membrane, and nucleoluslike structures. The results demonstrated the usefulness of the antibodies for identification or isolation of P‐tyr‐containing proteins.