bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pregnancy‐associated β1‐macroglobulin: Detection on the surface of ovarian cancer cell lines
Authors: Stimson W. H. , McAdam A. , Lang G. , Dodd J. 
Published: February 2007

AbstractPregnancy‐associated β1‐macroglobulin (β1‐PAM) is a serum protein which can be detected at elevated levels in the blood of many ovarian cancer patients. The presence of the antigen was investigated on the surface of 4 human ovarian cancer lines and 32 other human and rodent cell types and lines by means of immunofluorescent staining and anti‐β1‐PAM‐enzyme conjugate. The antigen was detected only on the ovarian lines but no secretion of β1‐PAM into the culture supernatants was observed. The ovarian cancer cells appeared to display the β1‐PAM constantly during culture, and enzymic treatment of the cells indicated that detection of the cell‐bound antigen with antiserum could be, at least partially, eliminated with proteases but not glycosidases or neuraminidase. The results serve to confirm the association of β1‐PAM with ovarian cancer.
Modulatory effects of 5‐azacytidine, phorbol ester, and retinoic acid on the malignant phenotype of human lung cancer cells
Authors: Olsson Lennart , Behnke Olav , Sørensen Hans Rahbek 
Published: February 2007

AbstractCloned human cell lines of squamous‐cell lung carcinoma and small‐cell lung carcinoma were treated with 5‐azacytidine (5‐azaC), 12‐0‐tetradecanoyl‐phorbol‐13 acetate (TPA), retinoic acid (RA), or a combination of these drugs, and the effects on cellular morphology, in vitro growth properties, antigenicity, tumorigenicity and metastatic activity in nude mice were studied. Antigenicity was measured by the expression of major histocompatibility antigens (MHC) and of lung‐tumor‐associated antigens.5‐AzaC treatment resulted in subclones with shorter population doubling times (from 40–50 hr down to 14–20 hr) and increased cloning efficiencies (from < 1% to 5–50%). TPA and RA induced loss of proliferative activity in vitro and tumorigenicity in vivo of both lines. This was morphologically associated with the appearance of an abundance of large vacuolated cells which by DNA‐analysis were all found to be in G0‐G1 phase. However, 2 of the 5‐azaC‐treated subclones were insensitive to both TPA and RA, whereas the remaining subclones (20) all responded like untreated lines to TPA and RA. One of the sublines insensitive to TPA and RA formed metastases in nude mice in contrast to all the other lines used. The density of lung‐tumor‐associated antigens was significantly reduced by TPA‐RA treatment, whereas the expression of MHC antigens was unaffected. In contrast, 5‐azaC resulted in some cases in increased density of MHC antigens. The effects of 5‐azaC on cellular phenotypes were not directly correlated to the total genomic content of 5‐methylcytosine. The data suggest that this experimental system is suitable for studies of phenotypic features of malignant cells as related to cellular differentiation.
Infiltrating mononuclear cells in human breast carcinoma: Predominance of T4+ monocytic cells in the tumor stroma
Authors: Göttlinger Heinrich G. , Rieber Peter , Gokel Josef M. , Lohe Klaus J. , Riethmüller Gert 
Published: February 2007

AbstractFrozen sections of 52 breast carcinomas were examined for the presence and nature of a leukocytic infiltrate. The number of “common leukocyte (T200‐) antigen”‐bearing cells was remarkably high in the stromal compartment of the carcinomas, whereas the tumor foci themselves were usually infiltrated only sparsely. Approximately 80% of these T200+ stromal cells carried the myelomonocyte lineage‐associated antigens M‐M522 and 63D3 and exhibited “non‐specific esterase” activity. More than 2/3 of the stromal monocytic cells expressed the T4 antigen as verified by monoclonal antibodies (MAbs) directed against different T4‐associated epitopes. A T‐cell analysis showed that T4+ cells clearly outweighed the total number of T cells as defined by anti‐T3 and anti‐TII antibodies. In addition, a correlation became apparent between the HLA‐DR phenotype and the T lymphocyte content of tumor cell areas in the sense that densely infiltrated tumor areas were invariably HLA‐DR+.
Prevalence of human papillomavirus type 16 DNA in cervical carcinoma samples in East Anglia
Authors: Scholl S. M. , Pillers E. M. Kingsley , Robinson R. E. , Farrell P. J. 
Published: February 2007

AbstractA substantial increase in the incidence of severely dysplastic cervical lesions (CIN 3) has been observed during the period 1975–1982 in the East Anglian region of England. Since patients with severe dysplasia have an enhanced risk of developing cervical carcinoma, it seems possible that a substantial increase in the rate of cervical carcinoma is likely to occur in the near future. Evidence of a relationship between human papillomavirus (HPV) infection and cervical carcinoma has accumulated recently. We have studied the incidence of HPV 16 DNA in cervial tissue samples from patients with cervical carcinoma, severe dysplasias and normal controls. Five out of II invasive squamous carcinomas of the cervix, 3/4 dysplasias and 0/12 normal samples were positive in Southern blot assays for HPV 16 DNA. Some of the tissue samples had as many as 500 copies of HPV 16 DNA per cell. The amount of HPV 16 DNA present correlated with the aggressiveness of tumour growth.
Changes in fibronectin synthesis and binding distribution in SV40‐transformed human keratinocytes
Authors: Edelman B. , Steinberg M. L. , Defendi V. 
Published: February 2007

AbstractWe have studied the synthesis and distribution of fibronectin in human epidermal keratinocytes infected by SV40, a system in which the acquisition of transformed properties occurs in a sequential and progressive manner. Immunofluorescence studies showed that cultured unifected keratinocytes do not exhibit fibronectin on the superficial cell surface, but that virus‐infected cells come to display superficial fibronectin‐containing cables in a density‐dependent manner after a certain point in the transformation process. In contrast, organized arrays of fibronectin‐containing fibrils associated with the cell‐substrate attachment complex were seen in uninfected keratinocytes and in virus‐infected cells at all stages of the transformation process. Studies of fibronectin synthesis using metabolic labelling of cell proteins with 35S methionine showed that viral infection caused a striking increase in overall fibronectin synthesis, although with a much higher proportion of newly synthesized fibronectin being secreted into the cell culture medium than in the case of the uninfected cells.
Expression of ki‐ras oncogene in tumor cell variants exhibiting different metastatic capabilities
Authors: Kris R. M. , Avivi A. , Bar‐Eli M. , Alon Y. , Carmi P. , Schlessinger J. , Raz A. 
Published: February 2007

AbstractThe expression of oncogenes in well‐characterized 616 melanoma and UV‐2237 fibrosarcoma cell variants that exhibit distinct metastatic properties was explored. The search for the expression of II different oncogenes revealed that the major oncogene in those two tumor systems is the Kirsten‐ras (ki‐ras). The results indicate that the amounts of specific ki‐ras mRNA and the p21 protein are similar in both low‐ and highmetastatic counterparts. These results suggest that in these systems there is no apparent direct correlation between the amount and expression of the major cellular oncogene so far identified and the metastatic potential of these tumor cells.
Identification of Marek's disease virus‐specific antigens in Marek's disease lymphoblastoid cell lines using monoclonal antibody against virus‐specific phosphorylated polypeptides
Authors: Ikuta Kazuyoshi , Nakajima Kazuhiro , Naito Matao , Ann Soo H. , Ueda Shigeharu , Kato Shiro , Hirai Kanji 
Published: February 2007

AbstractFor identification of the antigens specific to Marek's disease virus (MDV) in virus‐non‐producer lymphoblastoid cell lines established from a tumor of Marek's disease (MD), hybridomas producing monoclonal antibodies (MABs) against the antigens were isolated. Immunogens for preparation of the hybridomas were purified from the lysate of an MD‐lymphoblastoid cell line, MSB I, by affinity chromatography coupled with chicken anti‐MDV serum immunoglobulin G. Three of the MAbs obtained, MB1, MB2 and MB3, were specific to MDV by immunofluorexence test. An immunofluorexence test using MB2 antibody showed that immunofluorexence‐positive cells in non‐producer MD‐lymphoblastoid line cells became detectable when the culture temperature was shifted from 41° C to 33° C or when treatment with 5‐iodo‐2‐deoxyuridine (IUdR) was performed, indicating that the antigen reactive with MB2 antibody is an MDV‐specific early antigen. This temperature shift of IUdR‐treatment did not induce other MDV‐specific antigens, such as late gene products of MDV, detected with MAbs. MB1 and MB2 antibodies immunoprecipitated 4 MDV‐specific phosphorylated polypeptides with molecular weights (MWs) of 43,000 (43kd), 39kd, 36kd and 24kd from chick embryo fibroblasts productively infected with virulent MDV. In the place of 43kd, phosphorylated 44kd polypeptide was precipitated from avirulent MDV‐infected fibroblasts. However, MB3 antibody did not precipitate any MDV‐specific polypeptides from infected fibroblasts. These results suggest that the phosphorylated polypeptides are MDV‐specific polypeptides predominantly expressed in non‐producer MD‐lymphoblastoid cell lines.
Studies on clonal heterogeneity in two spontaneously metastasizing mammary carcinomas of recent origin
Authors: Brodt P. , Parhar R. , Sankar P. , Lala P. K. 
Published: February 2007

AbstractWe have studied the clonal heterogeneity of 2 spontaneously metastasizing mammary carcinomas which recently arose spontaneously in C3H/He female retired breeders. Cells of early (2nd to 5th) transplant generations of these tumors were cloned by a combination of semi‐solid agarose colony formation and limiting dilution techniques.Growth characteristics of the various clones in vitro and their tumorigenicity in vivo were evaluated. Subsequently, the role of host immunity and of interclonal interactions in regulating growth of the different clones in vivo were analyzed. We found that, whereas all 16 clones isolated from one tumor (T‐58) grew rapidly in vivo and in vitro, 10 clones isolated from the second tumor (MT‐2) showed a wide disparity in their growth rates in vivo. Taken together, these clones could generally be divided into 3 categories: (I) rapidly growing lines which grew in vivo at rates similar to or higher than those of the parental line; (2) slow‐growing lines which grew more slowly than the parental line; and (3) non‐growers which failed to produce tumors in vivo with doses of up to 5 × 106 cells injected either s. c. or i. v. but grew in vitro at rates comparable to the parental line. No correlation could be established between the various growth potentials exhibited by these tumor lines and tumor cell morphology in vitro and in vivo, as determined by light and electron microscopy. Sublethal irradiation (550‐650 R) of young animals prior to tumor inoculation, or before inoculation of tumor cells into old, low NK syngeneic mice, failed to modify the growth of slow or non‐growing lines in vivo, indicating that host cellular defense mechanisms against the clones, if existent, were not mediated by NK or radiosensitive B or T cells. When clonal interactions were studied by the simultaneous injection of different clones in vivo at different s. c. sites, we found that a slow‐growing line failed to modify the growth rate of a rapidly growing line, but accelerated the growth of a second slowgrowing line injected simultaneously on the contralateral side, and that this enhancement of tumor growth was radioresistant. A mixture of these 2 lines also grew more rapidly than the individual lines alone. Our findings suggest that phenotypic variations in tumorigenicity can be found in clonal lines derived from spontaneous primary tumors and that these variations are not related to cell cycle properties as measured in vitro. Furthermore, it appears that growth properties of these tumor lines in vivo are not easily modifiable by manipulation of the host immune reactivity but may be subject to interclonal growth regulation.
Neoplastic transformation of human diploid fibroblasts (KMST‐6) by treatment with 60Co gamma rays
Authors: Namba Masayoshi , Nishitani Koji , Hyodoh Fuminori , Fukushima Fujiko , Kimoto Tetsuo 
Published: February 2007

AbstractNormal fibroblasts (KMS‐6) derived from a human embryo were transformed in culture into neoplastic cells (KMST‐6) by repeated treatment with 60Co gamma ray irradiation. Repeated treatment was necessary to obtain transformation. Control normal cells exhibited normal karyotype (46, XX) and stopped dividing due to cellular ageing at the 40th passage. The transformed cells are presently growing indefinitely (140th passage) and exhibit prominent karyologic aberrations, both numerical and structural. These 2 characteristics, indefinite growth and abnormal karyotype, are thought to be the most important parameters for neoplastic transformation of human fibroblasts. Other indispensable parameters are the presence of active mitotic figures on confluent cell sheets and colony‐type morphology. Transformed cells grow into colonies with relatively smooth edges, while normal fibroblasts form colonies with jagged edges, due to the protrusion of growing fibroblasts. Other parameters, such as elevated plating efficiency, enhanced colony formation in soft agar, low serum requirement for growth, high saturation density, and acquisition of transplantability, are not reliable in the early stages of transformation. These parameters probably appear at rather later stages of transformation following several cell divisions. Among other characteristics, the transformed KMST‐6 cells exhibit a B‐type isozyme pattern of glucose‐6‐phosphate dehydrogenase, lactate‐dehydrogenase isozyme pattern of human origin, no evidence of viral infection and no production of C‐type virus particles.
Behaviour of dendritic reticulum cells possessing immunoreactive acid cysteine‐proteinase inhibitor in human lymphoid secondary follicles and in follicular‐centre cell lymphomas
Authors: Alavaikko M. , Aine R. , Rinne A. , Järvinen M. , Blanco G. , Apaja‐Sarkkinen M. , Hopsu‐Havu V. K. 
Published: February 2007

AbstractIn our previous studies acid cysteine‐proteinase inhibitor (ACPI) was shown to be a common characteristic of human squamous epithelia and dendritic reticulum cells (DRC) in lymphoid secondary follicles. In the present study, the behaviour of ACPI‐immunoreactive DRC in reactive lymphoid secondary follicles and neoplastic follicles of follicular‐centre cell (FCC) lymphomas was compared by the peroxidase‐antiperoxidase method. The secondary follicles in reactive lymphoid tissues revealed a staining pattern characteristic of DRC comparable with the results of other studies. Contrary to this, the number of ACPI‐positive DRC in the neoplastic lymphoid follicles was greatly reduced. This was occasionally accompanied by a weak reaction and in many cases the DRC were totally abolished. Moreover, morphological aberrations were observed in ACPI‐positive DRC, especially diminution and shortening of dendritic processes. On occasion, ACPI‐positive cell types were observed, which may represent intermediate forms between DRC and fibroblastic reticulum cells. Only one case‐with a rather favourable clinical outcome (out of 41 follicular FCC lymphomas) exhibited an ACPI‐positive DRC pattern comparable with that of reactive lymphoid follicles. Thus it seems that the ACPI‐immunohistochemistry of DRC provides an additional tool for discerning the difference between reactive and neoplastic lymphoid follicles. This method is of particular value since it can be used with formalin‐fixed, paraffinembedded tissues. There was a tendency among the follicular FCC lymphoma patients towards a better survival rate for those with ACPI‐positive DRC than for those lacking this cell type, although no statistically significant differences emerged from this limited material.
Generation of Epstein‐Barr virus antigen‐specific suppressor T cells in vitro
Authors: Sundar Syam K. , Menezes José 
Published: February 2007

AbstractImmunosuppression is a commonly observed phenomenon in Epstein‐Barr virus (EBV)‐associated disorders and malignancies. The purpose of this study was to determine whether EBV antigens could generate suppressor cell activity in vitro. Pepripheral blood lymphocytes (PBL) were first treated with various concentrations of EBV antigens or culture medium for 5 days and then with mitomycin C. The cells were then washed and tested for their ability to abrogate the blastogenic response of fresh, autologous PBL to previously determined optimal concentrations of EBV antigens. It was found that excess of both EBV antigens tested (soluble antigen and virus particles) induced suppressor cells, while optimal antigen concentrations failed to do so. In addition, PBL incubated with excess of EBV antigens for 10 days, without mitomycin treatment, inhibited the response of fresh autologous lymphocytes to EBV antigens. The generated suppressor cells were found to be antigen‐specific since they inhibited the response of sensitized lymphocytes to the inducing antigen only. Moreover, experiments performed using purified lymphocyte subpopulations indicated that the suppressor activity was associated with T‐cell populations. Using T‐cell specific monoclonal antibodies, we further determined that the inhibitory activity was due to suppressor (OKT 8+) T‐lymphocytes; treatment of T‐lymphocyte populations (exhibiting suppressor activity) with OKT 8 antibody and complement abrogated the inhibitory effect of these populations on the response of sensitized lymphocytes to EBV antigens. Taken together, these observations suggest that similar supressor cells may be at least partly responsible for the immunosuppression observed in patients with an antigenic overload, particularly during persistently active virus infection or malignancy.
Alterations in the phosphoprotein composition of tumor cell clones induced by cell culture techniques used routinely in assessing metastatic behavior in vivo
Authors: Greig Russell G. , Caltabiano Lyn , Feild John , Reid Robert , Poste George 
Published: February 2007

AbstractTo investigate whether the cell dispersion techniques commonly employed to harvest monolayer cultures of tumor cells for injection into experimental animals might induce alterations in cellular biochemistry, we compared the phosphoprotein profiles of 6 B16 melanoma clones of distinct metastatic potential using 2‐D gel electrophoresis after growth in monolayer culture, after suspension by treatment with trypsin/EDTA and after injection of suspended cells into syngeneic mouse plasma. Trypsin/EDTA treatment and subsequent exposure to syngeneic mouse plasma induced significant alterations in phosphoprotein composition in all clones. Most alterations were quantitative, involving either enhanced or diminished expression of specific phosphoproteins, but qualitative changes involving expression of novel phosphoproteins were also observed. None of the changes in phosphoprotein composition correlated with metastatic potential. The principle alteration induced in all clones by trypsin/EDTA involved enhanced phosphorylation of an NP‐40‐soluble component with a molecular weight of 79,000 and an isoelectric point of 6.3 [pp 79 (6.3)]. This determinant was detected in extracts of BI6 monolayer cultures but its level of phosphorylation was enhanced significantly by trypsin/EDTA treatment and by exposure of the harvested cells to syngeneic mouse plasma. These data indicate that procedures commonly employed to harvest tumor cells for assay of tumorigenic and metastatic potential may provoke extensive alterations in phosphoprotein composition and that biochemical investigations of tumor cells grown in monolayer culture may not accurately reflect the metabolic status of the same cells immediately prior to and following i.v. injection into experimental animals.
Characterization of tumor progression from threshold tumor inocula: Evidence for natural resistance
Authors: Brown Garth W. , Chow Donna A. 
Published: February 2007

AbstractAn examination of the variant generation and selection hypothesis of tumor progression was undertaken using the NK‐sensitive, NAb‐sensitive SL2‐5 lymphoma in the threshold inoculum model of tumor progression. Tumor cells obtained from the i.p. injection site expressed increased heterogeneity for sensitivity to syngeneic NAb and to NR measured in the 131 IUdR‐labelled tumor elimination assay. Cells retrieved from the s.c. injection site exhibited reductions in sensitivity to NR which correlated with decreases in sensitivity to syngeneic NAb and NK cells in vitro. These data confirm and extend our previousobservations with the NK‐resistant L5178Y‐F9 lymphoma and further substantiate the evidence for the participation of NAb and NK cells in host‐mediated anti‐tumor resistance. Characterization of the model revealed that the selection for reduced sensitivity to NR in thymus‐depleted AT × BM mice and normal animals could not be distinguished, suggesting that thymus‐independent mechanisms may be major contributors to the surveillance of nascent tumors. The decreases in susceptibility to NR occurred in a stepwise and time‐dependent manner in accord with the sequential multistage concept of progression. Furthermore, the selection for tumor cells which exhibited reductions in sensitivity to NR correlated with selection for increased tumorigenicity, in keeping with the idea that progression is associated with development towards an increasingly autonomous tumor.
Effects of diazoxide‐induced reversible diabetes on chemically induced autochthonous mammary carcinomas in sprague‐dawley rats
Authors: Berger M. R. , Fink M. , Feichter G. E. , Janetschek P. 
Published: February 2007

AbstractThe effect of oral administration of diazoxide on rats bearing mammary carcinomas induced by dimethylbenzanthracene (7,12‐DMBA) or methylnitro sourea (MNU) was investigated. Administration of 300 mg/kg diazoxide caused mild reversible diabetes with maximum glucose levels of 305 ± 74 (control: 119 ± 12) mg/dl and related insulin levels of 15 ± 5 (control: 24 ± II) μ U/ml after 4 hr in tumor‐bearing animals. Following the same dose of diazoxide a more than 90% inhibition of tumor growth was observed in 7, 12‐DMBA‐ and MNU‐induced autochthonous rat mammary carcinomas as well as remission of the median total tumor volume per group in 7, 12‐DMBA‐induced lesions. Frequency, onset of remissions and median remission duration proved to be dose‐dependent in 7,12‐DMBA‐induced mammary carcinoma and, with the exception of the median remission duration, in MNU‐induced tumors too. After cessation of diazoxide application, 30% rebound responses were observed in 7, 12‐DMBA‐induced tumors of animals that had had a first remission due to diazoxide. Application of insulin (2 IU per rat) together with diazoxide (300 mg/kg) reversed the tumor‐inhibiting effect of diazoxide in MNU‐induced tumors. The diazoxide effect might in part be due to a decrease in the percentage of proliferating cells caused by insulin depletion as indicated by a lower amount of cells in S‐phase, as measured by DNA‐flow cytometry. Marked toxicity was observed after effective doses of diazoxide; the experiments indicate that induction of reversible diabetes might be a useful tool in the treatment of hormone‐dependent mammary carcinoma.