bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidermal‐growth‐factor‐receptor expression is associated with rapid tumor proliferation in bladder cancer
Authors: Sauter G. , Haley J. , Chew K. , Kerschmann R. , Moore D. , Carroll P. , Moch H. , Gudat F. , Mihatsch M. J. , Waldman F. 
Published: February 2007

AbstractEpidermal‐growth‐factor‐receptor (EGF‐r) expression has been proposed as a prognostic marker in bladder cancer and is associated with rapid proliferation in cell lines. Ninety‐three fresh and 74 formal in‐fixed bladder tumors were examined by fluorescence in situ hybridization (FISH) and immunohistochemistry to assess the relationship between EGF‐r expression and proliferation as well at the prevalence of epidermal‐growth‐factor‐receptor (EGF‐r) gene amplification. EGF‐r expression was strongly associated with BUdr labeling index, grade and stage. EGF‐r expression emerged as a stronger predictor of tumor proliferation than grade or stage in analysis of variance. Rapid tumor proliferation might be responsible for bad prognosis reported in EGF‐r positive bladder tumors. Also chromosome 7 copy number was associated with grade and stage. EGF‐r gene amplification was uncommon (5 of 107 tumors). However, FISH analysis allowed characterization of the pattern of amplification, with clustering of signals suggestive of intrachromosomal amplification more common than diffuse distribution consistent with extrachromosomal amplification. © 1994 Wiley‐Liss, Inc.
Molecular mechanisms possibly affecting WT1 function in human ovarian tumors
Authors: Viel Alessandra , Giannini Franca , Capozzi Eugenia , Canzonieri Vincenzo , Scarabelli Carlo , Gloghini Annunziata , Boiocchi Mauro 
Published: February 2007

AbstractThe frequent allelic deletions observed on the short arm of chromosome 11 in ovarian tumors suggest that the WTI gene, a proposed tumor‐suppressor gene located on chromosome 11 p 13 and expressed in the human fetal genitourinary system, may contribute to the development of ovarian neoplasms. Structural and sequence analysis of the entire coding portions of the WTI gene did not reveal any abnormalities in the 20 ovarian tumor specimens (13 of which showed 11p13 allelic deletions) and 5 cell lines which we analyzed. These findings invalidate the hypothesis that the WTI gene functions as a classical tumor‐suppressor gene in ovarian tumorigenesis and suggest that a different recessive oncogene may be “exposed” by the observed 11 p 13 allelic deletions. Expression analysis showed that the WTI gene was transcriptionally active in all the tumors tested, but considerable variations in the mRNA levels were found. This apparent variability, which should be confirmed at the cellular level in the tumor specimens, was also observed in the ovarian tumor‐cell lines. Finally, WTI expression data were evaluated in conjunction with immunohistochemical data on p53. The possible functional effects of altered WTI mRNA expression in ovarian tumors are discussed, taking into account the potential WTI/p53 protein interaction. © 1994 Wiley‐Liss, Inc.
Cellular and karyotypic characterization of two doxorubicin resistant cell lines isolated from the same parental human leukemia cell line
Authors: Zalcberg John R. , Hu Xiu F. , Wall Dominic M. , Mirski Shelagh , Cole Susan , Nadalin Gabrielle , de Luise Mario , Parkin John D. , Vrazas Vickie , Campbell Lynda , Kantharidis Phillip 
Published: February 2007

AbstractSeparate mechanisms underlying the multidrug resistant (MDR) phenotype were identified in 2 independent approaches to select tumour cells resistant to low concentrations of doxorubicin (Dox) from the sensitive T cell leukemia cell line CCRF‐CEM. The CEM/A7 cell line was selected at an initial concentration of 0.005 μg/ml of Dox and maintained at 0.07 μg/ml. In contrast, the CEM/A5 line was selected using an initial concentration of 0.01 μg/ml and maintained in Dox at a concentration of 0.05 μg/ml. P‐glycoprotein expression was demonstrated in the CEM/A7 line but not the CEM/A5 line. Amplification of the mdr1 gene was not observed in the CEM/A7 cell line. Both cell lines showed cross‐resistance to a number of structurally unrelated cytotoxic drugs including anthracyclines and etoposide (VP‐16), although only the CEM/A7 line was cross resistant to Vinca alkaloids. Immunoblots of total cell lysates of the CEM/A5 line have revealed almost undetectable levels of topoisomerase 11 α and β in this line. Cytogenetic analyses of both lines revealed numerous karyotypk abnormalities which were present in the parental cell line as well as both resistant cell lines. The CEM/A7 line also demonstrated a duplication of part of the long arm of chromosome 7 which included the region containing the mdr1 gene, a finding not seen in the parental or CEM/AS line. CEM/AS, however, demonstrated an abnormality of chromosome 7, outside the region of the mdr1 gene, and it also contained a deletion of the short arm of chromosome 2. Abnormalities in this latter region of genome have been associated with non‐P‐glycoprotein‐mediated MDR. © 1994 Wiley‐Liss, Inc.
Inhibition of tumour promotion by various palm‐oil tocotrienols
Authors: Goh S. H. , Hew N. F. , Norhanom A. W. , Yadav M. 
Published: February 2007

AbstractInhibition of tumour promotion by various vitamin E compounds (tocopherols and tocotrienols) and some of their dimers was examined by an in vitro assay utilizing the activation of Epstein‐Barr virus (EBV) early antigen (EA) expression in EBV‐genome‐carrying human lymphoblastoid cells. The results reveal that γ‐ and δ‐tocotrienols derived from palm oil exhibit a strong activity against tumour promotion by inhibiting EBV EA expression in Raji cells induced by 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA). However, α‐ and γ‐tocopherols and dimers of γ‐tocotrienol or γ‐tocopherol lack this activity. © 1994 Wiley‐Liss, Inc.
The pattern of cytokine gene expression in freshly excised human metastatic melanoma suggests a state of reversible anergy of tumor‐infiltrating lymphocytes
Authors: Lüscher Urs , Filgueira Luis , Juretic Antonio , Zuber Markus , Lüscher Nicolas J. , Heberer Michael , Spagnoli Giulio C. 
Published: February 2007

AbstractExpression of an extended panel of cytokine genes was investigated by reverse polymerase chain reaction (PCR) in 10 freshly excised melanoma metastases infiltrated by lymphocytes (TIL). cDNA encoding for CD3‐δ and tyrosinase could be amplified in all samples, confirming the presence of T lymphocytes and melanoma cells. Cytokine genes possibly transcribed by both cell types, such as GM‐CSF, IL‐6 and IL‐10 could be amplified from 5, 2 and 2 samples respectively. In contrast, IL‐β and TNF‐α mRNA were never detectable, IL‐1α, IL‐3 and IL‐7 mRNA could be observed only in one case each. Transcripts encoding for TGF‐β1 were observed in 8 samples, while TGF‐β2 and 3 mRNA were detectable in only 2 specimens. mRNA encoding for cytokine genes typically transcribed by antigen‐stimulated T lymphocytes, such as IL‐2, IL‐4 and IFN‐7 were rarely or never detectable (none, none and 1 of the samples respectively). In one case, where no cytokine gene transcription was detectable at the time of surgery, we addressed the question of the antigenicity of the tumor and of the functional competence of TIL. A primary tumor cell line was generated and cultured TIL were induced to transcribe IL‐2 and IFN‐γ genes by incubation with the autologous irradiated tumor cell line, but not with autologous EBV‐transformed cells. In these conditions, tumor‐specific cytotoxic T lymphocytes (CTL) could be generated only after 3 weekly re‐stimulations. In contrast, if autologous irradiated EBV‐transformed cells were added to the cultures, specific CTL could be detected after one single tumor stimulation. Thus, signs of active responsiveness in terms of lymphokine gene mRNA are seldom detectable in melanoma metastases. Tumor‐specific responses, however, including IL‐2 and IFN‐γ gene expression and generation of CTL can be produced in vitro from specimens in which no cytokine gene mRNA is detectable ex vivo.
Biological‐clinical significance of selective loss of HLA‐class‐I allelic product expression in squamous‐cell carcinoma of the uterine cervix
Authors: Honma Shigeru , Tsukada Seiji , Honda Shuji , Nakamura Minoru , Takakuwa Koichi , Maruhashi Toshihiro , Kodama Shojj , Kanazawa Koji , Takahashi Takeshi , Tanaka Kenichi 
Published: February 2007

AbstractTo determine possible correlations between the selective loss of HLA‐class‐l allelic forms on neoplastic cells and their biological‐clinical characteristics, 89 squamous‐cell carcinomas of the uterine cervix were evaluated immunohistochemically using monomorphic and polymorphic antibodies against HLA‐A, ‐B, and ‐C molecules and analyzed clinico‐pathologically. Four of the carcinomas exhibited a lack of detectable class‐l heavy‐chain expression associated with β2‐microglobulin. In 19 of 42 HLA‐A2‐positive patients, tumor cells revealed loss of the HLA‐A2 allelic product. Loss of HLA‐B7 and/or 40 (B7/40) allelic product(s) on tumor cells was observed in 12 of 2S HLA‐B7/40‐positive cases. These alterations did not correlate with patient age, clinical stage (FIGO) of the disease, histological sub‐type (WHO) or depth of cervical invasion. However, a statistically significant correlation was observed between lymph‐node metastases and selective loss of HLA‐B7/40 allelic produces), but not with HLA‐A2 allelic product on cancer cells of the primary lesion. Our results indicate that selective loss of certain HLA‐class‐l alleles on neoplastic cells can influence the nodal metastatic potential and suggest that these 2 class‐l molecules may have different immune functions as restriction elements in T‐cell‐mediated cytotoxicity.
Tumor‐derived transforming growth factor‐β1 and interleukin‐6 are chemotactic for lymphokine‐activated killer cells
Authors: Delens Nadia , Torreele Els , Savelkool Huub , de Baetselier Patrick , Bouwens Luc 
Published: February 2007

AbstractAdherent lymphokine‐activated killer (A‐LAK) cells are purified IL‐2 activated natural killer (NK) cells with potent anti‐tumor cytotoxic activity. They have been used in the adoptive immunotherapy of metastatic canters. However, it has been shown that intravenously transferred LAK cells have a poor horning capacity to tumor sites. For the present study, the effects of tumor‐derived factors on the in vitro migratory capacity of A‐LAK cells was investigated. In a micropore migration assay the conditioned medium from 3LL Lewis lung carcinoma cell cultures was found to exert a strong chemotactic, but not chemokinetic effect on A‐LAK cells. This effect was partially inhibited by neutralizing antibodies against the cytokines TGF‐β1 and IL‐6. A combination of the 2 antibodies completely suppressed the chemotactic activity of tumor‐cell‐conditioned medium. Purified TGF‐β1 and recombinant IL‐6 were chemotactic for A‐LAK cells. Biological activities of both cytokines were detectable in the tumor‐cell‐conditioned medium. The in vivo relevance of these findings, with respect to tissue infiltration of NK cells and LAK cells in inflammation or cancer, remains to be elucidated.
Mitogenic activity of procathepsin D purified from conditioned medium of breast‐cancer cells by affinity chromatography on pepstatinyl agarose
Authors: Stewart A. J. , Piggott N. H. , May F. E. B. , Westley B. R. 
Published: February 2007

AbstractA simple procedure for the affinity purification of procathepsin D from tissue culture medium conditioned by breast‐cancer cells is described. This procedure yielded 2 μg of procathepsin D/100 ml medium. The procathepsin D was approximately 95% pure as judged by silver staining of polyactylamide gels, the major contaminant being mature cathepsin D. The ability of procathepsin D to stimulate the proliferation of oestrogen‐responsive MCF‐7 breast cancer cells was determined. The purified procathepsin D had no mitogenic effect alone or in combination with oestradiol or other growth factors. These data suggest that procathepsin D does not act as an oestrogen‐regulated autocrine growth factor for malignant breast epithelial calls.
Regulation of fibronectin and laminin receptor expression, fibronectin and laminin secretion in human colon cancer cells by transforming growth factor‐β1
Authors: Huang Shuang , Chakrabarty Subhas 
Published: February 2007

AbstractTransforming growth factor (TGF)‐β1, modulates the expression of extracellular matrix (ECM) glycoproteins, fibronectin and laminin and the adhesion of Moser colon cancer cells to these glycoproteins. Since adhesion can be altered through expression of cell‐surface receptors, binding affinities of adhesion molecules for receptors, or both, we investigated the effect of TGF‐β1, on the binding properties of fibronectin and laminin to their cell‐surface receptors by saturation binding and Scatchard analyses using radiolabeled fibronectin and laminin. Fibronectin bound to its cell‐surface receptor with high affinity (Kd = 1.25 × 10−9 M), Moser cells had approximately 7.1 × 104 fibronectin‐binding sites per cell. TGF‐β1 treatment rapidly up‐modulated the number of cell‐surface fibronectin‐binding sites by 1.9‐fold. The binding affinity of fibronectin for the receptor, however, was not altered. Laminin was found to bind to a higher‐affinity and a lower‐affinity receptor. Moser cells expressed approximately 1.1 × 103 higher‐affinity laminin‐binding sites and approximately 3.1 × 10 lower‐affinity‐binding sites per cell. TGF‐β1 rapidly increased the expression of the higher‐affinity sites 3‐fold and the lower‐affinity sites 5‐fold. The binding affinity of both the higher‐affinity and lower‐affinity laminin receptors increased 3‐fold after 2 and 6 hr of TGF‐β1 treatment respectively. Concurrent with receptor modulation, TGF‐β1 induced the secretion of fibronectin and laminin from Moser cells. Northern hybridization analyses showed a concurrent stimulation of the expression of the mRNAs for ligands (fibronectin and laminin) and the mRNAs for the integrin species of the fibronectin and laminin receptors (α5 and α6 subunits). Thus the production of fibronectin and laminin and the expression of their receptors were tightly co‐regulated by TGF‐β1.
Effect of B‐lymphocyte‐ and NPC‐derived EBV‐1 gene expression on in vitro growth and differentiation of human epithelial cells
Authors: Zheng Xi , Yuan Fang , Hu Lifu , Chen Fu , Klein George , Christensson Birger 
Published: February 2007

AbstractThe effect of expression of the Epstein‐Barr‐virus (EBV) latent membrane protein (LMP1) derived from B‐lymphocytes (B) and nasopharyngeal carcinoma (NPC) (C) on the in vitro growth and differentiation of a human keratinocyte line, Rhek‐1, was analyzed in clonal growth and in in vitro differentiation assays. In contrast to the polygonal parental cells, the B‐LMP1‐expressing sublines were spindle‐shaped while the C‐LMP1‐expressing cells were pleomorphic. Both B‐ and C‐LMP1‐expressing sublines showed increased proliferation as evidenced by: (1) higher colony‐forming efficiency (CFE) and larger colony size at reduced serum levels; (2) an increased number of epithelial cell layers formed in the air‐liquid‐interface culture system and (3) increased expression of proliferative cell nuclear antigen (PCNA). At low serum concentration, the C‐LMP1‐expressing sublines formed larger colonies than those expressing B‐LMP1. In the air‐liquid‐interface culture system, both B‐ and C‐LMP1‐expressing lines showed reduced epithelial differentiation resulting in reduced stratification and reduced involucrin expression similar to those of the cancer cell line, Siha. The results of the present study indicate that the expression of LMP1 in human keratinocytes is associated with morphological transformation and predisposes these cells to a more neoplastic phenotype. The structural difference between the 2 genes responsible for the functional differences and transforming ability will be pinpointed in further experiments.
Mothers' active and passive smoking during pregnancy and risk of brain tumours in children
Authors: Filippini G. , Farinotfi M. , Lovicu G. , Maisonneuve P. , Boyle P. 
Published: February 2007

AbstractAs part of a collaborative study of risk factors for childhood brain tumours, the effects of the mother's smoking and her potential for passive smoking exposure during the pregnancy were assessed in a case‐control study. Parents of 91 cases and 321 population controls from Northern Italy, matched for age, sex and residence, were interviewed about their lifetime smoking habits. Mother's smoking during pregnancy was associated with an odds ratio (OR) of 1.7 (95% CI 0.8, 3.8) of brain tumour in her child although this was not statistically significant. Among non‐smoking mothers, the risk for light and heavy exposure to passive smoking was 1.7(0.8, 3.6) and 2.2 (1.1, 4.5) respectively, and a statistically significant dose‐response relationship was found (p trend = 0.02). These results must be interpreted within the constraints of the relatively small sample size and the likely misclassification produced by the difference between the potential for exposure to passive smoke and the true exposure. However, they add another piece of information to the growing body of evidence available about the health consequences both of active and of passive smoking and highlight the need for more information about this putative association. © 1994 Wiley‐Liss, Inc.
Gastric cancer in Iceland: A retrospective study of resected gastric specimens in a high‐risk country during 30 years (1960–1989)
Authors: Jónasson Lárus , Hallgrímsson Jónas , Sigvaldason Helgi , Ólafsdóttir Gudrídur , Tulinius Hrafn 
Published: February 2007

AbstractThe world‐wide incidence of gastric cancer is decreasing, especially in high‐risk populations such as the Icelanders. We examined retrospectively 1,040 specimens of resected gastric cancers from a 30‐year period, 1960–1989. The decrease in incidence in both sexes involved mainly the largest histological group, the intestinal‐type tumours. In males there was also a decrease in diffuse tumours but in females these remained relatively unchanged. Tumours of the antrum and the corpus decreased in both sexes. In males there was a significant increase in tumours of the cardia and most of these were of the intestinal type. In females there was a minor increase in tumours of the cardia, all of which were of the intestinal type. An increase in incidence of tumours of the cardia concomitant with a decrease in incidence of tumours in other parts of the stomach suggests a difference in aetiological factors. The death risk for patients with tumours of the cardia was 59% higher than that for those with tumours in other parts. The death risk following gastric resection was not significantly different when patients with intestinal‐type tumours and diffuse tumours were compared. © 1994 Wiley‐Liss, Inc.
Metastatic renal‐cell carcinoma patients treated with interleukin 2 or interleukin 2 plus interferon γ: Immunological monitoring
Authors: Farace Françoisc , Pallardy Marc , Angevin Eric , Hercend Thierry , Escudier Bernard , Triebel Frédéric 
Published: February 2007

AbstractWe investigated the biological response of 73 patients with metastatic renal‐cell carcinoma (MRCC) treated by repetitive weekly cycles of high‐dose interleukin 2 (IL‐2) (protocol 1, 40 patients) or IL‐2 plus interferon‐gamma (IFN‐γ) (protocol 2, 33 patients). The objectives of this study were (i) to evaluate the effects of this IL‐2 administration schedule on biological response, (ii) to compare the effects of IL‐2 alone with those of IL‐2 plus IFN‐γ, (iii) to search for any correlation between certain biological marker values and the clinical response to treatment. Mean CD56+ lymphocyte counts (i. e., NK cells) were significantly higher than those of CD3+ cells in the 2 protocols and a subpopulation of CD56bright cells in protocol I was found to be preferentially expanded in vivo. Cytotoxic activity against K562 and Daudi cell lines as well as TNF‐α and sTNF‐αR (but not IL‐6) significantly increased following treatment. Comparison of the data obtained from patients treated with IL‐2 alone vs. IL‐2 plus IFN‐γ did not show any significant changes except for eosinophilia (higher in protocol I). Therefore, addition of IFN‐γ did not affect either lymphocyte distribution or non‐MHC‐restricted cytotoxicity in vivo. No difference in cell subpopulation or cytotoxicity was detected between responders and non‐responders. Pre‐treatment sTNF‐αR concentration, in contrast to IL‐6 and TNF‐α, was significantly higher in progressive than in stable and responder groups, suggesting that this parameter may be predictive of the clinical response. © 1994 Wiley‐Liss, Inc.
Immunohistochemical evaluation of P‐glycoprotein in human malignancies by monoclonal antibody MC57
Authors: Leonardo Eugenio , Valente Guido , Cappia Susanna , Cianfriglia Maurizio , Arancia Giuseppe , Meschini Stefania , Scagliotti Giorgio V. 
Published: February 2007

AbstractP‐glycoprotein expression was analyzed on 137 formalinfixed, paraffin‐embedded human tumours by monoclonal antibody (MAb) MC57. This MAb recognizes an extracellular human specific P‐glycoprotein epitope and defines their multidrug resistance (MDR) phenotype by its binding on cells. Immunohistochemistry indicated that this MAb reacted in human cells and tissues in the same pattern as that found with other MAbs to P‐glycoprotein. However, the present extensive study demonstrated that MAb MC57 is a highly specific reagent for the evaluation of an extracellular P‐glycoprotein epitope preserved after fixation procedures and that this MAb is available to assess P‐glycoprotein expression in routinely processed human tumour specimens. © 1994 Wiley‐Liss, Inc.
Endogenous TGF‐β contributes to the induction of the EBV lytic cycle in two burkitt lymphoma cell lines
Authors: di Renzo Livia , Alttok Aysin , Klein George , Klein Eva 
Published: February 2007

AbstractA low proportion of cells in the BL lines P3HR‐1 and Akata enter spontaneously into the EBV lytic cycle, detectable by the expression of early antigens (EA). We found that both lines produce the active and inactive forms of TGFß. It was shown earlier that a larger number of cells can be induced to enter the lytic cycle by exposing P3HR‐1 to phorbol esters and n‐butyrate and the surface IgG‐positive Akata cells to anti‐IgG. We now show that the same treatments raise the level of active TGFß release. Exposure to anti‐TGFß antibodies reduced EA induction by 75‐85%. Our results indicate that induction of the viral productive cycle by the above‐mentioned reagents is at least partly dependent on the activation of endogenous TGFß production. © 1994 Wiley‐Liss, Inc.