bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lysis of human pancreatic adenocarcinoma cells by autologous hla‐class I‐restricted cytolytic T‐lymphocyte (CTL) clones
Authors: Wölfel Thomas , Herr Wolfgang , Couue Pierre , Schmitt Ute , Zum Büschenfelde Karl‐Hermann Meyer , Knuth Alexander 
Published: February 2007

AbstractFrom the primary site of a pancreatic adenocarcinoma (patient BE) a permanent cell line (MZ‐PC‐2) was established in tissue culture. In the course of mixed lymphocyte‐tumor‐cell cultures (MLTC) with autologous blood‐derived lymphocytes, we isolated CTL clones that lysed autologous tumor cells but not autologous EBV‐transformed B cells (EBV‐B) and not K562. Pre‐treatment of MZ‐PC‐2 cells with IFN‐γ was required to obtain significant lysis in 4‐hr cytotoxicity assays. IFN‐γ was superior to IFN‐α in that respect. Among MLTC responder lymphocytes, tumor‐reactive CTL proliferated more strongly in response to MZ‐PC‐2 cells treated with IFN‐γ than to untreated tumor cells. Three CTL clones derived from MLTC were chosen for further analysis. They were CD3+, CD8+, TCR‐α/β+ and behaved identically in all functional aspects tested. They all expressed the same TCR‐β chain, indicating that they descended from a common precursor lymphocyte and were directed against the same antigen. According to antibody‐inhibition experiments, BE‐CTL recognized their targets via an HLA‐B molecule carrying the Bw6 supertypic determinant. Irrespective of pre‐incubation with IFN‐γ, low levels of tumor‐cell lysis, or none, were seen when MZ‐PC‐2 cells were kept in medium supplemented with autologous serum or serum pooled from healthy volunteers instead of FCS. Lysability was restored when TNF‐α was added to human serum. Serum‐free medium was found to enhance the susceptibility of MZ‐PC‐2 cells to lysis by autologous CTL.
Role of plasminogen activators, metalloproteinases and the tissue inhibitor of metalloproteinase‐1 in the metastatic process of human salivary‐gland adenocarcinoma cells
Authors: Azuma Masayuki , Tamatani Tetsuya , Fukui Kazuhiro , Yoshida Hideo , Kamogashira Takashi , Ogino Koichi , Suzuki Toshimitsu , Sato Mitsunobu 
Published: February 2007

AbstractAn in vitro system has been established in which conversion from non‐metastasizing to metastasizing adenocarcinoma cells can be induced, and subsequently subjected to analysis of the expression of proteases and tissue inhibitor of metalloprotein‐ases‐l (TIMP‐I). A human salivary‐gland adenocarcinoma cell clone HSGc, with no metastatic ability, was exposed to N‐meth‐yl‐N‐nitrosourea (MNU). Following exposure to MNU, cells with altered morphology were cloned. Upon s.c. inoculation into nude mice, MNU‐treated HSGc clones formed metastatic foci in various organs, and then 5 metastasizing clones were isolated. Evaluation of expression of tissue‐type plasminogen activator (tPA), urokinase‐type plasminogen activator (uPA), metalloproteinases and TIMP‐I was performed by means of enzyme immunoassay, zymogram, or immunoblot. MNU‐treated HSGc and metastasizing clones were found to secrete high levels of tPA, while HSGc produced undetectable levels of this enzyme. Expression of uPA was not observed in any of the cell clones. When the secretion of gelatinolytic enzymes was examined, metastasizing clones produced higher levels of 57–and 32–kDa, but not of 92– or 72–kDa gelatinases, as compared to HSGc cells. Although TIMP‐I was detected in all cell clones, metastasizing clones secreted less TIMP‐I than HSGc cells; in addition, one metastasizing clone produced TIMP‐I with a molecular weight distinct from that of 28–kDa TIMP‐I. Our results suggest that the acquisition of metastatic ability by human salivary‐gland tumor cells is closely associated with increased secretion of several metalloproteinases as well as decreased or altered TIMP‐1 expression.
Identification of colon‐tumor‐associated antigens by T‐cell lines derived from tumor‐infiltrating lymphocytes and peripheral‐blood lymphocytes from patients immunized with an autologous tumor‐cell/bacillus calmette‐Guérin vaccine
Authors: Ransom Janet H. , Pelle Barbara A. , Hubers Henk , Keynton Linette M. , Hanna Michael G. , Pomato Nicholas 
Published: February 2007

AbstractTumor immunity developing as a response to an autologous colon‐tumor/bacillus Calmette‐Guerin (BCG) vaccine appears to be associated with induction of CD4 helper T cells, implied by the observation that vaccine efficacy is associated with major histocompatibility complex class‐ll molecule expression on the vaccine tumor cells. Therefore, in an attempt to identify colon‐tumor‐associated antigens responsible for conferring immunity, we examined and compared the proliferative responses of peripheral‐blood lymphocytes (PBL) from patients immunized with the autologous tumor/BCG vaccine to T‐cell lines cloned expanded from colon‐tumor‐infiltrating lymphocytes to 5 antigens isolated on the basis of their reactivity by colon‐tumor‐reactive human monoclonal antibodies. Enzymatically dissociated colon tumors provided a source for establishment of cloned T‐cell lines, tumor cell lines propagated in vitro or in vivo as nude‐mouse xenografts and EBV‐transformed B‐cell lines used as antigen‐presenting cells. Of 104 different T‐cell lines tested, only 3 proliferated in response to CTAA 28A32‐46K, and I to the CTAA28A32‐32K antigen. In contrast, PBL from 64% of patients immunized with the autologous colon‐tumor/BCG vaccine responded to the CTAA 28A32‐32K antigen. This antigen is related to a family of calcium‐ and phospholipid‐binding placental proteins termed annexins. Since proliferative responses developed to this antigen after vaccination in 64% of individuals, this antigen may be an important common colon‐tumor‐associated rejection antigen.
Influence of interleukin‐2 administration on the expression of T‐cell receptor V gene segments in patients with renal‐cell carcinoma
Authors: Farace Françoise , Angevin Eric , Escudier Bernard , Caignard Anne , Dietrich Pierre‐Yves , Genevee Catherine , Hercend Thierry , Triebel Frédéric 
Published: February 2007

AbstractTumor regression induced by IL‐2 in a fraction of patients with metastatic renal‐cell carcinoma (MRCC) could not be predicted by immunological monitoring. In addition, the general mechanisms leading to tumor regression or even the distinct cell subsets (e.g., T vs. NK cells) involved are poorly identified. To evaluate the influence of IL‐2 administration on circulating T‐cell subpopulations, TCR Vα and Vβ gene segment usage was analysed by PCR in 7 MRCC patients using a panel of V gene segment subfamily‐specific oligonucleotide primers (Vα‐w29/ VβI‐w24). Three samples were examined in each patient: (i) peripheral blood cells (PBMCs) before therapy (day I); (ii) PBMC 2 days after the interruption of IL‐2, at day 36 (i.e., at the lymphocytic rebound), (iii) the CD25‐enriched cell fraction at day 36. Virtually all Vα and Vβ subfamily specificities were found in pre‐ as well as in post‐treatment PBMCs and CD25+ cell fractions. These results support the view that circulating T‐cell subpopulations are highly polyclonal after IL‐2 therapy without any major alteration in the TCR Vα and Vβ repertoire. In addition, the results of quantificative densitometric analysis of Vα and Vβ amplified products suggest that a unique Vβ‐expressing T‐cell subpopulation may be expanded in the CD25+ cell fraction after IL‐2 therapy. Further characterization of these T cells may contribute to a better understanding of in vivo effects of IL‐2 on renal‐cell carcinoma metastases.
Deletions of the shorlt arm of chromosome 9, including the interferon ‐ α / β genes, in acute lympocytic leukemia. Stuides on loss of heterozygosity, parental origin of deleted genes and prognosis
Authors: Heyman Mats , Grai Dan , Bröndum‐Nielsen Karen , Lir Yie , Söderhäll Stefen , Einhorn Stefen 
Published: February 2007

AbstractA restriction fragment length polymorphism (RFLP) analysis of the α‐ and β‐interferon (IFN) genes was performed in malignant cells from 52 patients with acute lymphocytic leukemia (ALL). Normal cell DNA was available for comparison in 23 of the patients. Ten patients were found to have gross alterations of their α‐ and β‐IFN genes. Leukemic cells from 2 ALL patients showed a complete loss of α‐ and β‐IFN genes. Seven patients had a hemizygous loss of one of the α‐ and β‐IFN alleles, as shown by RFLP analysis and/or loss of signal intensity. In one other patient the malignant clone was reduced to homozygosity with regard to the α‐ and β‐IFN genes, without loss of signal intensity. In patients without hemizygous deletions, the overall incidence of complete homozygosity for the α‐ and β polymorphisms was higher than expected. Analysis of the data indicates that the total frequency of ALL clones with gross alterations of the IFN‐loci is around 30%. A 9p24 probe detected hemizygous deletions in 2 cases of IFN gene deletions. In the other tested cases the deletions were interstitial. No deletions of 9p24 were detected in patients without allelic losses of IFN genes. In 5 cases of allelic IFN gene deletions, DNA from parents was available for comparison. In 4 cases the deleted allele was derived from the mother, whereas in the fifth it originated from the father. Pediatric ALL patients with IFN‐gene deletions or homozygosity for all polymorphisms in the IFN‐loci had a significantly worse prognosis than heterozygotes. We conclude that deletion of α‐ and β‐IFN genes is a relatively common event in ALL and that RFLP analysis of the IFN genes may provide additional prognostic information in childhood ALL. Whether or not the IFNs act as tumor‐suppressor genes in this disease is not yet known. (c) 1993 Wiley‐Liss, Inc.
Acidic fgf and egf are involved in the autocrine growth stimulation of a human nasopharyngeal carcinoma cell line and sub‐line cells
Authors: Chao Hsiou‐Hsien , Yang Vivian C. , Chen Jan‐Kan 
Published: February 2007

AbstractThe growth of a recently established human nasopharyngeal carcinoma cell line, CG‐1, and 5 randomly selected, single‐cell‐derived sub‐lines in serum‐free medium and in fetal‐bovine‐serum (FBS)‐containing medium was investigated. In basal medium supplemented with insulin, transferrin, fibronectin and high‐density lipoprotein, cell growth was moderately stimulated by aFGF and EGF in a dose‐dependent manner. In contrast, in medium containing as little as 0.5% FBS, most of the stimulatory effect of the aforementioned growth factors observed was masked. Western blotting analysis of the cell lysates and conditioned media showed that CG‐1 and sub‐line cells were all capable of synthesizing and releasing aFGF‐ and EGF‐immunoreactive proteins. The amounts of these 2 growth factors synthesized and released appeared to vary among the parental cell line and sub‐line cells. Moreover, the rate of basal proliferation of these cells appeared to be positively correlated with the amounts of aFGF‐ and EGF‐immunoreactive proteins produced. Addition of the neutralizing antibodies to aFGF and EGF exerted a dose‐dependent suppression on cell growth in medium containing 0.5% FBS. The results suggest a role of aFGF and EGF in autocrine growth stimulation of CG‐1 and sub‐line cells, and may explain the moderate response of these cells to exogenously added aFGF and EGF.
Differential metabolism and trafficking of sphingolipids in differentiated versus undifferentiated HT29 cells
Authors: Babia Teresa , Kok Jan Willem , Hulstaert Caesar , De Weerd Henk , Hoekstra Dick 
Published: February 2007

AbstractTrafficking and metabolism of sphingolipids were examined in undifferentiated (G+) and differentiated (G+ reversed) HT29 human colon adenocarcinoma cell lines. Metabolic experiments employing a fluorescently labeled sphingolipid precursor, 6‐[N‐(7‐nitro‐2,1,3‐benzoxadiazol‐4‐yl)amino]hexanoylceramide (C6‐NBD‐ceramide) revealed that both qualitative and quantitative differences exist in sphingolipid synthesis between the 2 cell lines. One of the C6‐NBD‐sphingolipids synthesized in G+ cells is not found in the G+ reversed cells. Furthermore, the ratio of the 2 main products, C6‐NBD‐glucosyiceramide and C6‐NBD‐sphingomyelin, differs: in G+ cells glucosylceramide is by far the main product, whereas G+ reversed cells synthesize C6‐NBD‐sphingomyelin in slight excess. Once established, these ratios of sphingolipids are quickly restored metabolically when distortion of the ratio is caused by experimental manipulation. This indicates that they represent a true metabolic equilibrium situation of the 2 sphingolipids in these cells, while the distinct ratios are mainly determined by the NBD‐lipid pool in the plasma membrane. Preferential synthesis and transfer of glucosylceramide from its site of synthesis to the cell surface do not occur when the plasma membrane pool of glucosylceramide is selectively removed. This suggests that instantaneous replenishment via specific signalling is probably not involved as a mechanism in re‐establishing perturbed lipid pools. In conjunction with observations on distinct lipid trafficking pathways of glucosylceramide in G+ and G+ reversed cells, the present metabolic studies emphasize a relation between the expression of this glycolipid and the state of differentiation of HT29 cells.
A novel monoclonal antibody specifically reactive with human T‐lymphotropic virus type‐II (HTLV‐II) envelope protein
Authors: Ohara Nobuya , Hayashi Kazuhiko , Takahashi Kiyoshi , Miyamoto Kanji , Akagi Tadaatsu 
Published: February 2007

AbstractA novel monoclonal antibody (MAb), N5.4.4, specifically reactive with human T‐lymphotropic virus type‐ll (HTLV‐II) envelope glycoprotein (gp) has been developed through immunization with a synthetic peptide corresponding to the amino acid sequence 171–196 of the HTLV‐II envelope protein (ll‐env 171–196). This MAb, which belonged to the IgG1 kappa subclass, reacted with the cytosmears of HTLV‐ll‐infected cell lines (Si‐IIA, CR‐MA‐I and AS‐IIA), but not with those of HTLV‐1‐infected cell lines (MT‐1 and MT‐2) or other HTLV‐uninfected cell lines. On Western blot analysis, this MAb reacted with gp46 of HTLV‐II lysates but not with HTLV‐1 lysates. Moreover, flow‐cytometric analysis revealed that this MAb recognized the native surface of only the HTLV‐ll‐producing cells. Through application to immunohistochemical or serological method, this MAb may be of value in elucidating the pathogenesis of HTLV‐II infection in comparison with HTLV‐1.
Induction of mouse tenascin expression by a human sarcomatoid wilms' tumor cell line growing in nude mice
Authors: Talts Jan Fredrik , Aufderheide Enno , Sorokin Lydia , Ocklind Göran , Mattsson Ragnar , Ekblom Peter 
Published: February 2007

AbstractA new cell line from a sporadic Wilms' tumor was established and extensively characterized. In nude mice, the tumor cells rapidly formed tumors which, in histological characteristics and extracellular‐matrix (ECM) composition resembled sarcomatoid Wilms' tumor. The tumor cells produced B chains of laminin, but no A chain, and laminin was deposited into the ECM in a punctate pattern typical of sarcomatoid tumors. Strong expression of tenascin was detected within the stromal ECM of the tumors. Species‐specific antibodies reacting either with human or with mouse tenascin showed that tenascin was exclusively derived from mouse host cells. The human Wilms' cell line thus induced a strong stromal response with increased deposition of tenascin. The cell line may be useful for studying the behavior of sarcomatoid Wilms' tumor cells and for identifying factors that stimulate synthesis of tenascin.
Cancer incidence in the native peoples of far eastern siberia
Authors: Zaridze David G. , Marochko Andrej , Basieva Tamara , Duffy Stephen W. 
Published: February 2007

AbstractCancer incidence rates were examined in the native peoples of the far north‐east of Siberia for the years 1977–1988. Particularly high rates of cancers of the stomach, lung, oesophagus and cervix were observed. For stomach cancer, the male and female age‐standardized (to the world population) rates were 103.9 per 100,000 and 50.0 per 100,000 respectively. The corresponding lung cancer rates were 109.4 and 45.7, and for oesophageal cancer 83.9 and 35.0. The age‐standardized cervical cancer rate was 38.5 per 100,000. Rates of these cancers were considerably higher than in native Alaskan peoples, although the latter had higher rates of breast and colorectal cancers. The rates were also much higher than those of the migrant peoples from Russia and elsewhere who have settled in the far north‐east over the past 3 centuries, particularly at younger ages. Male rates of stomach and lung cancer were highest in the paleo‐Asiatic peoples of the north, whereas male oesophageal rates were highest in the Taiga people. In females, rates of stomach and oesophageal cancers were highest in the paleo‐Asiatic peoples, and rates of lung cancer were highest in the Taiga nationalities. Cervical cancer rates were highest in the Amuro‐Sakhalin nationalities of the south. Further research is needed at individual levels to explain the very high risks and the differences among the ethnic groups.
Parity and cancers of the gall bladder and the extrahepatic bile ducts
Authors: Lambe Mats , Trichopoulos Dimitrios , Hsieh Chung‐Cheng , Ekbom Anders , Adami Hans‐Olov , Pavia Maria 
Published: February 2007

AbstractThe relation of parity and age at first birth to cancers of the gall bladder and extrahepatic bile ducts in women was studied using a database generated by linking 2 Swedish national registries; the Fertility Registry and the Cancer Registry. Among women born between 1925 and 1960, 257 cases of gall‐bladder cancer recorded in the Cancer Registry between 1958 and 1984 were compared with 1,285 controls, age‐matched to cases in a 5:1 ratio. In addition, 60 cases of extrahepatic‐bile‐duct cancer were matched with 300 controls. There was a positive association between number of live births and risk of gall‐bladder cancer (p 0.06), but simultaneous consideration of parity and age at first birth revealed a more complex picture. Parity increases the risk for cancer of the gall bladder when the first birth occurs before the age of about 25 years, whereas parity associated with first birth after the age of about 30 years is associated with reduced risk for the disease. Thus, among parous women there is a highly significant inverse association of age at first birth with risk for gall‐bladder cancer after adjustment for number of live births. Variable levels of pregnancy estrogens according to maternal age and variable effects of parity on non‐pregnancy estrogens by age, may explain the observed pattern. The results on extrahepatic‐bile‐duct cancer, parity and age at first birth did not indicate the existence of an association in either direction.
Modulating the metastatic potential of murine raw117 large‐cell lymphoma cells by selection for resistance to interferon‐γ
Authors: Labiche Ronald A. , Nicolson Garth L. 
Published: February 2007

AbstractHighly metastatic, in vivo‐selected cells of RAW117‐H10 large‐cell lymphoma have been shown to be more resistant than poorly metastatic parental RAW117‐P cells to the cytolytic and cytostatic activities of activated macrophages in co‐culture experiments. Activated macrophages are known to produce soluble, cytostatic respiration‐inhibiting factors, and such activities can be duplicated by interferon‐gamma (IFN‐γ) or by combinations of IFN‐γ and Escherichia coli lipopolysaccharide (LPS). Highly metastatic RAW117‐H10 cells are more resistant to the cytostatic effects of IFN‐γ and LPS than poorly metastatic RAW117‐P cells, and short‐term (up to 72 hr) treatment with IFN‐γ and LPS does not change the metastatic potentials of RAW117 cells. We have studied the effects of sequential selection of RAW117‐P cells for increased resistance to IFN‐γ and LPS. After 7 to 13 sequential selections, the resulting variant lines were completely refractory to the growth‐inhibitory effects of IFN‐γ and LPS and cross‐tolerant to inacro‐phage‐conditioned medium. The selected variants also completely lost their experimental metastatic potentials and their tumorigenicities after s.c. or i.m. injection. Cytofluorographic analysis indicated reduced cell‐surface expression of H‐2Kd antigen and fibronectin receptor on the variant cells but no change in surface μ heavy‐chain immunoglobulin. The IFN‐γ‐selected lines were less adhesive to liver microvascular endothe‐lial cells than the unselected RAW117 cell lines, but were equally sensitive to NK cytolysis by spleen cells. Our results suggest that exposure to certain cytokines can affect the growth and metastatic potential of RAW117 cells and result in the selection of resistant variants with altered biologic properties.
Role and regulation of expression of 92‐kDa type‐IV collagenase (MMP‐9) in 2 invasive squamous‐cell‐carcinoma cell lines of the oral cavity
Authors: Juarez Jose , Clayman Gary , Nakajima Motowo , Tanabe Kenneth K. , Saya Hideyuki , Nicolson Garth L. , Boyd Douglas 
Published: February 2007

AbstractThe present study was undertaken to determine the role of the metalloproteinase MMP‐9 in the invasive phenotype of squamous‐cell carcinoma of the oral cavity and the regulation of its expression. Zymographic analysis of conditioned medium from 2 highly invasive squamous‐cell‐carcinoma cell lines indicated large amounts of an enzyme which was indistinguishable, in size (92 kDa) from the MMP‐9 pro‐enzyme. Conversion of the 92‐kDa gelatinase into a lower‐molecular‐weight species (84 kDa), identical in size to the activated gelatinase, was evident when both cell lines, which are avid secretors of urokinase, were cultured in the presence of plasminogen. Penetration of an extracellular‐matrix‐coated filter was dramatically reduced in the presence of the collagenase inhibitor, tissue inhibitor of metalloproteinase‐2, suggesting a critical role for MMP‐9 in the invasive process. Immunohistochemical studies demonstrating the presence of MMP‐9 in tumor cells of resected squamous‐cell cancers suggested that secretion of this collagenase by cells in vitro was reflective of the in vivo setting. Since several phorbol‐ester response elements are present in the MMP‐9 promoter, we determined the role of protein‐kinase‐C pathways in the regulation of MMP‐9 expression in cultured SCC. Treatment of cells with PMA resulted in a more‐than‐20‐fold increase in the level of protein and mRNA. Conversely, culturing of cells in the presence of the protein‐kinase‐C inhibitor, calphostin‐C, led to a dose‐dependent decrease in the amount of MMP‐9 mRNA and protein, suggesting that the constitutive expression of this collagenase reflects activation of this signal transduction pathway. In summary, our data suggest that, for a sub‐population of squamous‐cell carcinomas, secreted MMP‐9 is an important determinant of the invasive phenotype, and that the expression of this metalloproteinase is regulated by protein‐kinase‐C pathways. © 1993 Wiley‐Liss, Inc.