bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors for renal‐cell cancer in Shanghai, China
Authors: McLaughlin Joseph K. , Gao Yu‐Tang , Gao Ru‐Nie , Zheng Wei , Ji Bu‐Tian , Blot William J. , Fraumeni Joseph F.
Published: February 2007

A population‐based case‐control study of 154 histologically verified renal‐cell cancer patients and 157 controls was per formed in Shanghai, China, an area with low rates for this tumor. Elevated risks were observed for cigarette smoking (odds ratio (OR) = 2.3; 95% confidence interval (CI): 1.1 to 4.9), and for increasing categories of body weight and meat consumption, while reduced risks were seen for increasing categories of fruit and vegetable intake. An increased risk was also observed for regular use of phenacetin‐containing analgesics (OR = 2.3; 95% CI:0.7 to 7.0). These findings are consistent with earlier studies in Western countries, and indicate that many of the same etiologic factors for renal‐cell cancer operate in low‐and high‐risk societies. © 1992 Wiley‐Liss, Inc.
Frequent loss of heterozygosity on chromosomes Xp and 13q in human ovarian cancer
Authors: Yang‐Feng Teresa L. , Li Shibo , Han Hong , Schwartz Peter E.
Published: February 2007

Loss of heterozygosity (LOH) was examined at 27 loci on chromosomes 3p, 6q, 11p, 13q, 17 and X in 42 human ovarian tumors. LOH was detected in 12 of 26 (46%) and 5 of 12 (42%) informative cases at 2 chromosome 13q loci, D13S32 and D13S34 respectively. On chromosome Xp, tumor‐specific allele loss was observed in 9 out of 15 informative cases (60%) at the ornithine transcarbamylase (OTC) gene locus. Examination of 12 additional Xp and 13q loci has mapped the common deletion regions to Xp21.1 → p11.4 and 13q33 → q34. The observation of significant LOH on Xp represents a strong indication of genetic changes in the X chromosome in a human malignancy. The allele losses on 13q which have been reported for other cancers suggest that chromosome 13, in addition to the retino blastoma gene, may contain other growth‐regulating gene(s) important in the development of several tumor types, including ovarian malignancies. © 1992 Wiley‐Liss, Inc.
Immunohistochemical determination of androgen receptors in relation to oestrogen and progesterone receptors in female breast cancer
Authors: Kuenen‐Boumeester V. , van der Kwast Th. H. , van Putten W. L. J. , Claassen C. , van Ooijen B. , Henzen‐Logmans S. C.
Published: February 2007

The expression of oestrogen (ER), progesterone (PR) and androgen (AR) receptors in female breast cancer was investigated by immunohistochemistry on snap‐frozen tissue specimens of a series of 100 breast cancers. For detection of the AR we used a recently developed mouse monoclonal antibody specific for the N‐terminal domain of the human AR. Expression of AR was compared with that of ER and PR as well as with tumour grade and age. Of the breast cancers investigated, 76% were AR‐positive. This high percentage corresponds well with previous data on AR expression in breast cancer determined with ligand‐binding assays. In 53% of the tumours AR, ER and PR were present, while 9% of the tumours were positive for AR and negative for ER and PR. In 13% of the tumours no ER, PR or AR expression was seen; these were all grade‐III tumours. A positive correlation was found between age and ER expression, but no correlation was seen between age and PR or AR. Future studies should establish the prognostic value of the combination ER, PR and AR determinations on female breast cancer with regard to biological behaviour and response rate to hormonal therapy. © 1992 Wiley‐Liss, Inc.
Involvement of histo‐blood‐group antigens in the susceptibility of colon carcinoma cells to natural killer‐mediated cytotoxicity
Authors: Blottiére Hervé M. , Burg Cédric , Zennadi Rahima , Perrin Pascale , Blanchardie Philippe , Bara Jacques , Meflah Khaled , Le Pendu Jacques
Published: February 2007

The susceptibility to natural‐killer‐cell lysis and expression of histo‐blood‐group antigens of 2 clones from a rat colon adeno‐carcinoma, of variants derived from them and of 17 human colon carcinoma cell lines were assessed in an attempt to determine if the major glycosidic tissue antigens of epithelial cells could influence the NK susceptibility of tumor target cells of epithelial origin. The rat REGb clone, which is relatively NK‐sensitive, expressed higher levels of precursor structures T and Tn and lower levels of H antigenic determinants than the PROb clone, which displays higher resistance to NK‐cell lysis. Cell variants were obtained from these 2 clones; it appeared that whether the cell variants were selected on the basis of expression of a blood‐group antigenic determinant or on the basis of altered susceptibility to NK‐cell lysis, there was a link between increased resistance and higher expression of cell‐surface A and H histo‐blood‐group antigens, or conversely, between increased sensitivity and higher expression of precursor structures. Similar conclusions were obtained upon study of the human cell lines, since a significant correlation was found between the level of expression of T or Tn antigens and sensitivity to NK‐cell lysis. A significant relationship was found between the expression of Lewis antigens and increased resistance to NK‐cell‐mediated cytotoxicity. © 1992 Wiley‐Liss, Inc.
Cytotoxicity of a transferrin‐adriamycin conjugate to anthracycline‐resistant cells
Authors: Fritzer Monika , Barabas Klara , Szüts Viktoria , Berczi Alajos , Szekeres Thomas , Faulk W Page , Goldenberg Hans
Published: February 2007

Conjugates of adriamycin coupled to transferrin by glutaraldehyde are cytotoxic to human promyelocytic (HL‐60) and erythroleukemic (K562) cells. Growth inhibition of adriamycin‐sensitive cells, as evaluated by thymidine incorporation and the MTT‐assay, was higher for conjugates than for free adriamycin. The cytotoxicity toward adriamycin‐resistant K562 and HL‐60 cells was 3‐fold and more than 10‐fold higher, respectively, for the transferrin‐adriamycin conjugate than for the free drug. The effect of the conjugate was dependent on its adriamycin content, i.e., on its coniugation number. © 1992 Wiley‐Liss, Inc.
Cystatin C and cathepsin B in human colon carcinoma: Expression by cell lines and matrix degradation
Authors: Coriicchiato Olivier , Cajot Jean‐Franqois , Abrahamson Magnus , Chan Shu Jin , Keppler Daniel , Sordat Bernard
Published: February 2007

Expression of the cysteine proteinase cathepsin B and its physiological inhibitor cystatin C was analyzed in vitro in I human fibrosarcoma and 4 human colon carcinoma cell lines. Cystatin C antigen as well as cathepsin B activity were detected in the conditioned media of the 5 cell lines. The corresponding cell extracts expressed high levels of cathepsin B activity, whereas only trace amounts of cystatin C antigen could be found. Northern‐blot analysis revealed the presence in the 5 cell lines of a 0.8‐kb cystatin C mRNA transcript and 2 cathepsin B transcripts of 2.3 and 4.3 kb. Pepsin treatment of tumor‐cell‐released cathepsin B induced an average 7.3‐fold increase in activity, indicating that the enzyme was mainly present as a latent form in conditioned medium. The pepsin‐activated cathepsin B from one colon carcinoma cell line was further characterized using the cysteine proteinase inhibitors E‐64, recombinant cystatin C, a cystatin‐C‐derived peptidyl inhibitor (Z‐LVG‐CHN2), and cathepsin‐B‐specific diazomethyl ketone inhibitors (Z‐FT(OBzl)‐CHN2, Z‐FS(OBzl)‐CHN2). This activity was totally neutralized by recombinant cystatin C, suggesting a potential for interaction between released extracellular cathepsin B and cystatin C. In vitro assays of degradation of extracellular matrix showed that cyrteine proteinase inhibitors could decrease matrix degradation induced by pepsin‐activated conditioned media. With colon cells, this inhibition was not observed, indicating a requirement for an extracellular activation of latent cathepsin B. Our data provide evidence that cystatin C and latent cathepsin B are both released extracellularly by colon carcinoma cells in vitro. They suggest that cystatin C and cathepsin B interactions may participate, in an as yet unelucidated way, in the modulation of the invasive phenotype of human colonic tumors. © 1992 Wiley‐Liss, Inc.
Phosphoprotein B23 translocation and modulation of actinomycin D and doxorubicin cytotoxicity by dipyridamole in hela cells
Authors: Bor Amy Meei‐Shuu , Chang Fu‐Jung , Yunc Benjamin Yat‐Ming
Published: February 2007

During continuous exposure, cells were more responsive to doxorubicin (DOX) in the presence of dipyridamole (DPM). Translocation of nucleolar phosphoprotein 823 and inhibition cell growth occurred with a lower dose of DOX and in a shorter incubation time in the presence of DPM. DPM did not change translocation induced by actinomycin D (Act‐D). Short exposure of HeLa cells to Act‐D induced “reversible” translocation of protein 823 as well as “reversible” inhibition of cell growth. DPM included in the cell culture after removal of Act‐Dinhibited the recovery of cell growth as well as the corresponding relocalization of protein 823 from the nucleoplasm to nucleoli. DPM administered in the fresh medium after 30 min exposure to DOX had little effect on the potentiation of the induced translocation of protein 823 and inhibition of cell growth. Our results indicated that “B23 translocation” closely associated with states of cell growth. The potentiation the inhibition of cell growth by DPM is associated with the extent of enhanced protein 823 translocation. “B23 translocation” may therefore be a simple and rapid method for assessing the inhibition of cell growth and for determining the efficacy of combination cancer chemotherapy. © 1992 Wiley‐Liss, Inc.
Differences in expression of SPan‐1 and CA15‐3 antigens in blood and tissues
Authors: Ho Jenny J. L. , Chung Yong‐Suk , Yuan Mei , Henslee Jerry G. , Kim Young S.
Published: February 2007

Pancreatic and mammary cancer cells are reported to have different oligosaccharides on the same apomucin, the MUCI gene product. A better understanding of the tissue specificity of these sugar structures may help in identifying the source of mucins when they are found in the sera. Serum levels of 3 pancreatic‐cancer‐associated carbohydrate epitopes identified by monoclonal antibodies (MAbs) SPan‐1, 19‐9 and DU‐PAN‐2, were compared to those of CA15‐3 in a variety of malignant conditions. CA15‐3 identifies both carbohydrate and peptide determinants associated with the MUCI apomucin in breast tissues. SPan‐1 antigen was elevated in a high percentage of patients with pancreatic, gastric and colorectal cancer but in only a few of the patients with malignancies of non‐G1 origin such as breast, ovary and lung. The 19‐9 and DU‐PAN‐2 antigens had a similar pattern of much greater sensitivity for pancreatic cancer than for these non‐gastrointestinal cancers. The levels of these 3 markers showed significant correlations in pancreatic cancer. In contrast, CA15‐3 was elevated in a large number of patients with breast, lung, ovarian and pancreatic cancers. There was no correlation of CA15‐3 with the 3 other markers in pancreatic cancer. SPan‐1 and DF3/115D8 antigens in blood have different mobilities in SDS‐PAGE and buoyant densities. Moreover, SPan‐1 and DF3 antigenic determinants are localized in different regions of the same normal and malignant pancreas and breast tissues. Thus the SPan‐1 determinant can be dissociated from the breast peptide and/or carbohydrate determinants. © 1992 Wiley‐Liss, Inc.
Breast cancer and timing of surgery during menstrual cycle. A 5‐year analysis of 385 pre‐menopausal women
Authors: Gnant Michael F. X. , Seifert Michael , Jakesz Raimund , Adler Arthur , Mittlboeck Martina , Sevelda Paul
Published: February 2007

It has been proposed that the timing of breast‐cancer surgery in relation to menstrual phase has a prognostic impact on outcome. We carefully evaluated a combined 2‐center series of 385 pre‐menopausal women operated on for stage‐I and stage‐II breast cancer with a median follow‐up of 5 years for a possible impact on outcome of the date of their last menstrual period (LMP) before surgery. The distribution of risk factors of the study cohort as well as prognostic indicators corresponded to previously published results. Nodal status, grading, and (in part) hormone‐receptor status differentiate well between patient subgroups with high and low risk of relapse and death after breast‐cancer surgery. In neither univariate nor multivariate analysis was any impact of the so‐called “unopposed” estrogen secretion detected. We did not observe any effect of LMP on long‐term survival in any of several prognostic subgroups, in particular in hormone‐receptor‐positive patients. From our results and from the literature, we conclude that LMP does not provide any prognostic information for outcome after breast‐ cancer surgery and therefore the proposed modification of scheduling of breast‐cancer operations is not justified. © 1992 Wiley‐Liss, Inc.
Breast cancer is associated with loss of the c‐kit oncogene product
Authors: Natali P. G. , Nicotra M. R. , Sures I. , Mottolese M. , Botti C. , Ullrich A.
Published: February 2007

The proto‐oncogene c‐kit encodes a tyrosine kinase receptor related to the PDGF/CSF‐I receptors. Mutations of this gene result in impairment of hematopoiesis, melanogenesis and gametogenesis. Using monoclonal antibodies to the c‐kit gene product, we have analyzed its expression in normal and transformed human tissues. Unexpectedly, the receptor was found to be expressed in normal mammary epithelium. While in benign breast lesions, the c‐kit gene product was detected at variable levels in 82% of the instances, in primary tumors, no product could be identified in 87% of the cases. This phenotype is maintained in metastatic foci. These findings were confirmed by paired Northern blot analysis of RNA preparations from normal and tumor tissues. These results demonstrate that the c‐kit receptor may also be involved in the growth control of mammary epithelium and that this function may be impaired following malignant transformation and de‐differentiation. © 1992 Wiley‐Liss, Inc.
Expression of carcinoembryonic antigen and related genes in lung and gastrointestinal cancers
Authors: Kim Joohang , Kaye Frederic J. , Henslee Jerry G. , Shively John E. , Park Jae‐Gahb , Lai Shinn‐Liang , Linnoila R. Ilona , Mulshine James L. , Gazdar Adi F.
Published: February 2007

Carcinoembryonic antigen (CEA), a tumor marker for lung cancers of small cell (SCLC) and non‐small cell (NSCLC) types, belongs in a multigene family which includes non‐specific cross‐reacting antigen (NCA) and biliary glycoprotein 1 (BGP). We used specific cDNA probes and a CEA immunoassay to determine the pattern of expression in normal and malignant lung and gastrointestinal (GI) tissues. Normal lung contained high amounts of NCA and a low concentration of CEA. All 3 genes were expressed discordantly in lung tumors and cell lines. In contrast, all three genes were expressed in most GI tumor cell lines. In both king and colorectal cell lines expression of NCA RNA was relatively high, while BGP RNA was relatively low, and the median concentrations of CEA were greater than in corresponding non‐malignant tissues. While CEA protein concentrations in lung cell lines were similar to those present in GI cell lines, the ratio Of NCA:CEA RNA was significantly higher in lung cancer lines than in colorectal lines. Thus, NCA constitutes most of the “CEA‐like” immunoreactivity previously described in lung cancers. There was excellent concordance between expression of CEA RNA and CEA protein, as well as between concentrations of CEA protein in cell line pellets and supernatant fluids. Of interest, significantly higher rates of CEA expression were present in lung cancers expressing neuroendocrine (NE) markers. The association between CEA expression and NE cell properties is intriguing and may prove to be of clinical interest. © 1992 Wiley‐Liss, Inc.
Specific cytogenetic abnormalities and k‐ras mutation in two new human colorectal‐adenoma‐derived cell lines
Authors: Williams Ann C. , Harper Sara J. , Marshall Christopher J. , Gill Robert W. , Mountford Richard A. , Paraskeva Christos
Published: February 2007

Two new human epithelial cell lines from sporadic colorectal adenomas designated S/RR and S/BR are reported. Both cell lines have extended growth capacities in vitro, reaching passages 38 and 40 respectively and show no sign of senescence. S/RR and S/BR cell lines have retained the ability to differentiate in vitro, as shown by mucin production from goblet‐like cells. S/BR was derived from a large colonic tubular villous adenoma (3 to 4 cm), whereas S/RR was derived from a small rectal adenoma (< 1 cm), and may represent a relatively early‐stage adenoma. The parent S/RR cell line has given rise to a clonogenic variant, designated S/RR/Cl, which also has shown no sign of senescence and has currently reached passage 43. Both the S/BR and the S/RR cell lines had mutations in codon 12 of the K‐ras gene, while retaining one normal allele. The presence of this mutation, particularly in the cell line S/RR derived from a small adenoma, is consistent with ras mutation being a relatively early event in colorectal carcinogenesis and is perhaps involved in the ability of the adenoma cells to progress and to give rise to an immortal cell line in vitro. The clonal derivatives of the S/RR cells have an isochromosome Iq and abnormalities Of chromosome 13 which include an isochromosome 13q. The S/BR cells have a deletion on the short arm of chromosome 1 and trisomy 7. The common abnormality for S/RR and S/BR cells involves chromosome 1. The involvement of different chromosomes in the 2 cell lines also suggests different pathways for malignant progression of the premalignant adenoma cells. © 1992 Wiley‐Liss, Inc.
Enhancement of cisplatin activity by lonidamine in human ovarian cancer cells
Authors: Silvestrini Rosella , Zaffaroni Nadia , Villa Raffaella , Orlandi Linda , Costa Aurora
Published: February 2007

The ability of lonidamine, an energolytic derivative of indazole‐carboxylic acid, to modulate the cytotoxicity of cisplatin was investigated in human ovarian‐cancer cell lines sensitive (A2780) or with experimentally induced resistance (A2780/cp8) to the alkylating agent. A 24‐hr post‐incubation with 300 μM lonidamine significantly potentiated the activity of a 1‐hr cisplatin treatment in both cell lines. In particular, the cisplatin IC50 value was reduced 4‐fold in the sensitive line and 5‐fold in the resistant line. Flow cytometric analysis showed that, in the resistant cell line, lonidamine alone did not affect cell kinetics, but when given after cisplatin it was able to transform the temporary G2 + M cell accumulation induced by the alkylating agent to a persistent block in S/G2 + M. In the A2780/cp8 cell line, lonidamine was also able to significantly enhance the accumulation of cisplatin‐induced DNA interstrand cross‐links. Our results suggest that lonidamine can positively modulate the anti‐tumor activity of cisplatin in ovarian cancer cells and also indicate that the drug is potentially useful in combination therapy including the alkylating agent for ovarian cancer patients. © 1992 Wiley‐Liss, Inc.
Secretion of cell‐adhesion‐promoting factors, fibronectin, fibronectin fragments and A 53‐kDa protein, by human rectal adenocarcinoma cells
Authors: Suzukl Katsuo , Ono Tetsuo , Umeda Makoto , Itoh Hajime
Published: February 2007

Production of cell‐adhesion proteins was examined in 10 cell lines and 5 cultured human cancer cells at an early passage. Two‐thirds of the tested cells produced and secreted into their culture medium variable amounts of material active in promoting cell attachment. One of the rectal carcinoma cell lines, CaR‐1, grew well in serum‐free medium and secreted a large amount of the active principle. The active principles produced by CaR‐1 cells were characterized after partial purification, and were found to be fibronectin and its fragments. The presence of fibronectin and its fragments was proved by the following facts: (I) reactivity to the monoclonal antibodies which recognize different epitopes of fibronectin, and (2) reactivity to RGD peptide which is the attachment sequence of fibronectin. In addition to fibronectin and its fragments, CaR‐1 cells were also shown to produce a 53‐kDa attachment factor. Unexpectedly, the protein was proved to be most probably the p53 suppressor gene product. © 1992 Wiley‐Liss, Inc.
Decreased expression of E‐cadherin and increased invasive capacity in EBV‐LMP‐transfected human epithelial and murine adenocarcinoma cells
Authors: Fahraeus Robin , Chen Welching , Trivedi Pankaj , Klein George , Obrink Björn
Published: February 2007

The EBV‐encoded membrane protein LMP is one of 9 viral proteins regularly expressed in virally immortalized B lymphocytes. It is expressed in EBV‐carrying lymphoblastoid cell lines of normal origin and in the majority of the poorly differentiated nasopharyngeal carcinomas, but not in Burkitt lymphomas. LMP has been reported to transform rodent fibroblasts, to inhibit epithelial differentiation and to alter morphology and cytokeratin expression in an in vitro immortalized human keratinocyte cell‐line, RHEK‐1. We now report that an LMP‐transfected mouse mammary carcinoma line, SHG, exhibits a similar morphological change to that previously described in the LMP‐transfected RHEK‐1. In the LMP‐transfected RHEK‐1 and SHG cells, we observed a decreased expression of the calcium‐dependent adhesion molecule E‐cadherin. The LMP‐transfected RHEK‐1 cells were capable of invading type‐1 collagen gels while the control cells were not. The LMP‐transfected SHG cells showed a significantly higher invasive capacity than the original cell line. © 1992 Wiley‐Liss, Inc.
Smoking‐related dna adducts in human gastric cancers
Authors: Dyke G. W. , Craven J. L. , Hall R. , Garner R. C.
Published: February 2007

DNA was extracted from the tumour tissue of 26 patients (18 smokers, 8 non‐smokers) undergoing surgery for gastric cancer, and analyzed for the presence of DNA adducts by the 32P‐post‐labelling method. Adducts were detected in all samples tested, and adduct levels ranged from 2 adducts/108 nucleotides to 60 adducts/108 nucleotides. In male subjects, adduct levels were significantly greater in the DNA of smokers than in that of non‐smokers. These results support epidemiological data suggesting that smoking is a risk factor for gastric cancer. © 1992 Wiley‐Liss, Inc.
Quantitation of biological tumor markers (p53, c‐myc, Ki‐67 and DNA ploidy) by multiparameter flow cytometry in non‐small‐cell lung cancer
Authors: Mørkve Odd , Halvorsen Ole Johan , Stangeland Lodve , Gulsvik Amund , Laerum Ole Didrik
Published: February 2007

Fifteen primary non‐small‐cell lung carcinomas (8 adenocarcinomas and 7 squamous‐cell carcinomas) were analyzed by multiparameter flow cytometry for their expression of p53 and c‐myc proteins. In addition, the fraction of cells staining with the proliferation‐associated antibody Ki‐67 and DNA ploidy was determined. These 4 biological markers were analyzed in parallel samples from a single‐cell suspension made from fresh, frozen biopsies. Thus, the internal relationship between these markers within each tumor‐cell population was established. Three different anti‐pS3 antibodies were used: PAb 421, PAb 1801 and PAb 240. All 15 tumors were p53‐positive with the antibodies PAb 1801 and PAb 240, whereas only 9 were positive as judged by the antibody PAb 421. This indicates that the choice of p53 antibody is not irrelevant. Ten tumors were c‐myc‐positive; 7 of these were adenocarcinomas. The c‐myc‐positive tumors had a significantly higher level of p53 expression, judged by PAb 1801 and PAb 240, than c‐myc‐negative tumors. For PAb 421, there was no difference. We did not find any correlation between Ki‐67 staining and expression of p53 and c‐myc proteins, either with DNA ploidy, S‐phase fraction or histological type. Our study indicates that there might be an association between accumulation of p53 protein and c‐myc over‐expression in non‐small‐cell lung cancer, and that this in particular might apply to adenocarcinomas. Furthermore, we show that multiparameter flow cytometry is a powerful tool in the study of the relationship between different markers in a cell population. © 1992 Wiley‐Liss, Inc.
EGF receptor expression in primary laryngeal cancer: Correlation with clinico‐pathological features and prognostic significance
Authors: Maurizi Maurizio , Scambia Giovanni , Panici Pierluigi Benedetti , Ferrandina Gabriella , Almadori Giovanni , Paludetti Gaetano , De Vincenzo Rosa , Distefano Mariagrazia , Brinchi Domenico , Cadoni Gabriella , Mancuso Salvatore
Published: February 2007

Epidermal‐growth‐factor‐receptor (EGFR) expression was evaluated in 103 primary laryngeal tumors and in 42 normal laryngeal tissue specimens. Significantly higher EGFR levels were found in cancer specimens than in normal mucosa (p = 0.0053). EGFR expression did not correlate with age, tumor localization, T classification, cervical‐lymph‐node involvement or type of surgery, whereas it was higher in poorly differentiated tumors (G3) than in well/moderately differentiated (G1‐G2) tumors (p < 0.05). Follow‐up data were available for 74 patients. When EGFR status and the most important clinico‐pathological characteristics were submitted to univariate analysis, tumor localization, type of surgery and EGFR status were found to be significantly correlated with disease‐free survival. The 24‐month disease‐free survival rate was 58% for EGFR+ cancer patients and 82% for EGFR‐ ones. With multivariate analysis, only EGFR status and tumor localization were identified as significant independent prognostic parameters. Data reported here suggest that high EGFR levels may identify a sub‐set of laryngeal‐cancer patients with a particularly unfavorable prognosis. © 1992 Wiley‐Liss, Inc.
Prognostic relevance of serum hyaluronan levels in patients with breast cancer
Authors: Ponting J. , Howell A. , Pye D. , Kumar S.
Published: February 2007

The serum hyaluronan (HA) level of 238 women with breast cancer was measured by means of a specific radiometric assay. The results show no significant increase in serum HA when compared to levels in 120 control sera. A number of prognostic factors were evaluated including stage of disease, lymph‐node involvement, tumour size, histology and presence of oestrogen and progesterone receptors in the tumour. No correlation was found with serum HA concentration and we conclude that serum HA level is of no prognostic significance in breast cancer. © 1992 Wiley‐Liss, Inc.
Growth of hodgkin cell lines in severely combined immunodeficient mice
Authors: von Kalle Christof , Wolf Jürgen , Becker Andreas , Sckaer Andrea , Munck Martina , Engert Andreas , Kapp Ursula , Fonatsch Christa , Komitowski Dymitr , de Lacroix Wolfgang Féaux , Diehl Volker
Published: February 2007

No animal model exists for the in vivo growth of Hodgkin's‐lymphoma‐derived cells. Neither unmanipulated Hodgkin's‐disease(HD)‐derived cell lines nor primary biopsy tissue could be grown in nude mice. Since the severe combined immunodeficient (SCID) mouse has been reported to be a better recipient for transplanted human lymphatic tissue than the nude mouse, we tested whether SCID mice provide suitable conditions for the in vivo growth of HD cell lines. Tumorigenicity of HD cells was tested in untreated and pre‐treated SCID mice and in another combined immunodeficient mouse strain, beige/nude/X‐linked immunodeficient (BNX) mouse. SCID mice supported in vivo growth of the 6 HD cell lines tested (L428, L540, L591, DEV, HD‐LM2, KM‐H2). Only one of the 6 lines (DEV) was tumorigenic in BNX mice. No HD cell line proliferated in T‐cell‐deficient nude mice. Thus, in vivo growth of HD cell lines appeared to be related to the degree of host immunodeficiency. Additional growth supportive treatments such as fibrosarcoma co‐transplantation, intraperitoneal mineral oil injection or immunosuppressive pre‐treatment (anti‐asialo‐GMI ‐antibody injection) permitted growth of 3 additional HD cell lines in BNX mice. The immunophenotype and karyotype of explanted graft cells were identical to the original cell lines. Our experiments describe an effective and reproducible xenograft model for growth of Hodgkin's‐disease‐derived cell lines. This may be of value for elucidating the growth characteristics of Hodgkin's‐lymphoma‐derived cells as well as for testing new therapeutic regimens. © 1992 Wiley‐Liss, Inc.
DOK, a cell line established from human dysplastic oral mucosa, shows a partially transformed non‐malignant phenotype
Authors: Chang Sidney E. , Foster Sharon , Betts David , Marnock Wendy E.
Published: February 2007

There are many reports of cell lines being established from human oral squamous‐cell carcinomas but apparently none of cell lines from dysplastic or “pre‐malignant” oral mucosa. We describe here the isolation and characterization of a cell line, DOK (dysplastic oral keratinocyte), from a piece of dorsal tongue showing epithelial dysplasia. The tissue was obtained from a 57‐year‐old man who was a heavy smoker prior to the appearance of a white patch on his tongue. Eleven years later a squamous‐cell carcinoma developed at the site and was excised. Subsequently the remaining dysplasia was removed, and it was from a piece of this that the primary cell cultures which eventually gave rise to DOK were initiated. The DOK line has been single‐cell cloned and is apparently immortal. It grows in the absence of 3T3 feeder cells, is anchorage‐dependent for growth and is non‐tumorigenic in nude mice. The keratin profile of the cells shows a striking similarity to that of the original tongue dysplasia. The karyotype of DOK is aneuploid and complex. By PCR and oligonucleotide hybridization on dot blots, codons 12, 13 and 61 of Ha‐ras, Ki‐ras and N‐ras in DNA extracted from DOK cells were shown to be normal. Immunohistochemistry showed no abnormal, i.e., elevated expression of the onco‐suppressor protein p53. Because of its origin and partially transformed phenotype, DOK presents an opportunity to study whether specific carcinogens associated with tobacco and areca nut can cause malignant transformation of oral keratinocytes in vitro. © 1992 Wiley‐Liss, Inc.
Des‐(1–3)‐IGF‐I, an insulin‐like growth factor analog used to mimic a potential IGF‐II autocrine loop, promotes the differentiation of human colon‐carcinoma cells
Authors: Remacle‐Bonnet Maryse , Garrouste Francoise , Atiq Fatima El , Roccabianca Monique , Marvaldi Jacques , Pommier Gilbert
Published: February 2007

HT29‐D4 human colon‐carcinoma cells have been shown to secrete insulin‐like growth factor (IGF)‐II and to simultaneously express type‐I IGF receptors. However, the sequestration of IGF‐II by several molecular forms of IGF‐binding proteins (IGFBP) in the culture medium prevents the establishment of an operative IGF‐II autocrine loop. IGFBPs secreted by HT29‐D4 cells (HT29‐D4 IGFBP) comprise isoforms of IGFBP‐4 (25, 27 and 30 kDa) and 2 unidentified forms (34.5 and 32‐34 kDa). This latter does not bind 125I‐IGF‐I. The net affinity of HT29‐D4 IGFBP is about 12 times stronger for IGF‐II (KD approx. 10−10 M) than for IGF‐I. All the HT29‐D4 IGFBP molecular forms are unable to bind the N‐terminally truncated IGF‐I analog, des‐(1–3)‐IGF‐1. In contrast, HT29‐D4 cell‐surface type‐l IGF receptors bind IGF‐I and des‐(1–3)‐IGF‐l identically (KD approx. 5 × 10−10M). We have taken advantage of these particular binding properties to use des‐(1–3)‐IGF‐1 to mimic a potential IGF autocrine loop and to observe its biological consequences. Nanomolar concentrations of des‐(1–3)‐IGF‐1 induce HT29‐D4 cells to develop into a differentiated phenotype, as judged by a substantial carcinoembryonic antigen release and the induction of numerous intercellular cysts with well‐organized microvilli. In the same way, des‐(1–3)‐IGF‐1 early induces a slight inhibition of HT29‐D4 cell proliferation. Based on these findings, we conclude that the type‐l IGF receptor primarily controls the differentiation of these colonic cells, and that HT29‐D4 cancer cells remain in an undifferentiated state because of their inability to use endogenous IGF‐II as an autocrine regulatory factor. © 1992 Wiley‐Liss, Inc.
Human prolactin regulates transfected MMTV LTR‐directed gene expression in a human breast‐carcinoma cell line through synergistic interaction with steroid hormones
Authors: Haraguchi Soichi , Good Robert A. , Engelman Robert W. , Day Noorbibi K.
Published: February 2007

Prolactin plays a key role in the regulation and growth of mammary cells, and influences tumor promotion. We have shown that chronic energy restriction intake depresses prolactin levels, inhibits production of MMTV proviral DNA and proto‐oncogene expression in mammary glands and prevents development of mammary tumors. Since the expression and proto‐oncogene activation of MMTV are regulated by promoter/enhancer elements within its long terminal repeat (LTR), in the present study we used a chloramphenicol acetyl transferase (CAT) reporter gene system and gene transfection methods to study the effect of prolactin on MMTV LTR using a human ductal carcinoma cell line T47D stably or transiently transfected with a plasmid consisting of the LTR upstream of CAT gene. Human prolactin or dexamethasone induced, respectively, a 2‐fold or 6‐fold increase in CAT activity compared with background CAT activity in the absence of hormones. However, the combination of human prolactin and dexamethasone strongly enhanced (20‐fold) induction of the LTR compared with the control. Human prolactin also showed a synergistic effect with progesterone on LTR induction. Both LTR and CAT genes needed to be linked for induction of CAT activity by prolactin and dexamethasone. Our results indicate that human prolactin can act synergistically with steroid hormones to regulate MMTV LTR‐directed gene expression in transfected T47D cells. © 1992 Wiley‐Liss, Inc.
Functions of estrogens and anti‐estrogens in the rat endometrial adenocarcinoma cell lines RUCA‐I and RUCA‐II
Authors: Schütze Norbert , Kraft Volker , Deerberg Friedrich , Winking Heinz , Meitinger Daniela , Ebert Kirsten , Knuppen Rudolf , Vollmer Günter
Published: February 2007

Inbred rats of the DA/Han and BDII/Han strains have been proposed as suitable model systems for studying hormonal carcinogenesis, because they die mainly from hormone‐dependent endometrial adenocarcinoma. Here we characterize the RUCA‐I cell line derived from an endometrial adenocarcinoma of an inbred DA/ Han rat and the RUCA‐II cell line derived from an endometrial adenocarcinoma of an inbred BDII/Han rat. The RUCA‐I cell line, if transplanted to the neck of female DA/ Han rats, gives rise to endometrial adenocarcinomas at the ectopic site. The morphology of these ectopically grown tumors is predominantly of the moderately differentiated sub‐class. In contrast, ectopic tumor growth of the RUCA‐II cell line can be observed only if cells are transplanted to athymic nude mice. Biochemically, both cell lines are characterized by the stable expression of estrogen receptors. However, no statistically significant mitotic response of RUCA‐I and RUCA‐II cells to estradiol was measurable, and no induction of expression of the progesterone receptor by estradiol was detectable, although estradiol transformed the estrogen receptor into its stable DNA‐binding state. In contrast, the rate of proliferation of RUCA‐I but not of RUCA‐II cells was reduced in the presence of 10−6 M tamoxifen. From these results we conclude that (i) both cell lines, RUCA‐I and RUCA‐II, represent a new and promising endometrial tumor model; (ii) the mechanism of the hormone‐ dependent growth regulation of RUCA‐I and RUCA‐II cells is obviously impaired; (iii) the RUCA‐I cell line appears to be a suitable model system for the study of molecular aspects of estrogen‐ and tamoxifen‐dependent gene expression. © 1992 Wiley‐Liss, Inc.
Analysis of two human monoclonal antibodies against melanoma
Authors: Yeilding Newman M. , Gerstner Carolyn , Kirkwood John M.
Published: February 2007

B cells derived from peripheral‐blood lymphocytes (PBL) and tumor‐infiltrating lymphocytes (TIL) from a patient with a high serum antibody titer to autologous melanoma were transformed with Epstein‐Barr virus (EBV) and evaluated for reactivity against autologous tumor. B cells producing antibody reactive with autologous tumor and unreactive with normal fibroblasts were detected both in TIL and in PBL. One cell line derived from PBL and another derived from TIL sustained production of tumor‐reactive antibody for 10 weeks and over 15 months respectively. The cell line derived from PBL, 2D11, produced an antibody reactive with a trypsin‐resistant antigen expressed on the cell membrane of autologous and allogeneic melanoma cell lines. The cell line derived from TIL, IF6, produced an antibody reactive with a cell‐surface glycoprotein expressed by 5 autologous melanoma cell lines derived from 5 different metastases and 16/19 allogeneic melanoma cell lines. IF6 also showed reactivity with cell lines derived from a blue nevus, a congenital nevus, an astrocytoma, and 1/4 renal‐cell carcinomas; but it was not reactive with 5 foreskin melanocyte cell lines, 2 normal fibroblast lines, 5 leukemia/lymphoma lines, 8 lung‐cancer lines, 8 glioblastoma lines, or lines derived from 1 ovarian carcinoma, f colon carcinoma, 1 vulvar carcinoma, 1 fibrosarcoma, 1 murine melanoma, or 4 murine leukemia/lymphomas. We describe here an antibody that detects a new melanoma specificity obtained by EBV transformation of tumor‐infiltrating B cells. © 1992 Wiley‐Liss, Inc.
Proliferation of human colon cancer cells: Role of epidermal growth factor and transforming growth factorα
Authors: Huang Shuang , Trujillo Jose M. , Chakrabarty Subhas
Published: February 2007

Human colon cancer cells produce and secrete a variety of polypeptide growth factors. The functional role of these growth factors, however, is poorly understood. Though the secretion of epidermal growth factor (EGF)‐like activity and EGF‐related molecules by human colon cancer cells in culture has been reported, it is not known whether colon cancer cells produce and secrete EGF, and the functional role of EGF in the growth control of these cells is also unknown. We have shown that EGF acts as a potent growth stimulator on the moderately differentiated Moser colon cancer cell line and as an inhibitor on the highly metastatic KM12SM cell line. In the present study, we show that EGF is produced by human colon cancer cells and characterize the levels of EGF mRNA expression and EGF protein secretion from 8 human colon cancer cell lines. The cell‐surface EGF receptors on these cell lines were also characterized by radiolabeled ligand binding and Scatchard analyses. All the cell lines expressed EGF mRNA and secreted EGF. Both high‐ and low‐affinity subtypes of EGF receptor were detected on 7 of the cell lines. These lines also secreted transforming growth factor (TGF)α. Some cell lines exhibited a proliferative response to treatment with either exogenous EGF or TGFα, while others did not respond to treatment with these growth factors. Antibody‐blocking experiments, using anti‐EGF or anti‐EGF receptor antibody, suggested that these cell lines could be broadly classified into 2 groups in terms of their autocrine or paracrine growth regulation via the cell‐surface EGF receptor: (1) cells that utilized EGF and/or TGFα; and (2) cells that did not utilize EGF or TGFα (via the cell‐surface receptor), even though they secreted abundant amounts of these growth factors. © 1992 Wiley‐Liss, Inc.
Loss of heterozygosity at chromosome 17p is associated with HER‐2 amplification and lack of nodal involvement in breast cancer
Authors: Imyanitov Evgeny N. , Chernitsa Oleg I. , Nikiforova Irina F.
Published: February 2007

Sixty DNA samples from breast carcinoma (BC) patients were analyzed by Southern blot to examine certain oncogene and anti‐oncogene alterations. Amplification of the HER‐2 oncogene was detected in 15 tumours (25%), c‐myc in 2 (3%) only and HER‐1 in none. Distribution of Hras‐1 oncogene alleles in BC did not significantly differ from that seen in healthy donors. Not a single case of RB‐1 anti‐oncogene alteration and only one of p53 suppressor gene abnormality was found when appropriate cDNA copies were used as probes. With the use of DNA polymorphic markers, loss of heterozygosity (LOH) was revealed at chromosome 17p (probe YNZ‐22) in 18 of 39 (46%) informative cases, at 17q (probe THH‐59) in 10 of 34 (29%) and at 11p (probe Hras‐1) in 8 of 30 (27%). The only significant correlation between these genetic alterations and the clinical characteristics of the tumours studied was the association of LOH at 17p with node‐negative BC (p < 0.02). Also, the tendency for correlation (p < 0.2) between HER‐2 amplification and loss of 17p sequences was revealed: 7 of 10 amplification‐positive, but only 11 of 29 amplification‐negative BC possessed o LOH of YNZ‐22 IOCUS.
Visualization of the plasmin receptor on sections of human mammary carcinoma cells
Authors: Burtin P. , Zhang S. , Schauffler J. , Komano O. , Sastre X. , Mathieu M. C.
Published: February 2007

In previous studies we observed the presence of an antigen reacting with anti‐plasminogen serum on tumor cells found in sections of human colorectal and mammary carcinomas, using immunofluorescence. This antigen could be plasminogen, or plasmin or both. These results led us to surmise that carcinoma cells, and not normal epithelial cells, had a receptor for plasmin and plasminogen. We demonstrated the existence of such a receptor on cells of established tumor cell lines of colonic and mammary origin. We observed that binding of plasmin(ogen) to its receptor was inhibited by lysin and its analogs. We undertook to characterize the plasmin receptor on sections of human mammary Carcinomas (18 series of sections, originating from 15 infiltrating ductal carcinomas). In our immunofluorescence studies, we observed that the fluorescence induced by anti‐plasminogen serum was suppressed by pre‐treatment of the sections with tranexamic acid, a lysin analog. Furthermore, when parallel sections were incubated with tranexamic acid, then with solutions of plasminogen, tumor cells were made fluorescent again. Another important finding was the strong increase of labelling observed when sections were incubated with plasminogen or plasmin before reaction with antiplasminogen serum. This labelling disappeared when tranexamic was added to plasminogen. As a whole, these results confirm the existence of plasmin receptors on tumor cells in mammary carcinoma sections. They also show that these receptors are not saturated in vivo and may bind,in vitro, additional amounts of ligand.
Increased expression of p34cdc2 and its kinase activity in human gastric and colonic carcinomas
Authors: Yasui Wataru , Ayhan Ayse , Kitadai Yasuhiko , Nishimura Kenji , Yokozaki Hiroshi , And Hisao Ito , Tahara Eiichi
Published: February 2007

We examined the expression of p34cdc2 and its kinase activity in human gastric and colonic carcinoma cell lines and carcinoma tissues and studied its relation with a tumor‐suppressor gene product, p53. All the gastric and colonic cancer cell lines expressed p34cdC2 and showed its kinase activity at various levels. When the cells were arrested in mitotic metaphase by the use of nocodazole, p34cdC2 kinase activity was induced and p53 was apparently phosphorylated. Of 12 gastric carcinoma cases, 11 (91.7%) showed higher p34cdC2 kinase activity in tumor tissues than in corresponding non‐neoplastic mucosa. The protein kinase activities in the individual cases were well correlated with the levels of p34cdc2 protein expression. A good correlation was also found between the expression of p34cdc2 and proliferating cell nuclear antigen (PCNA). Almost all the colonic carcinomas showed higher cdc2 kinase activity and increased p34 expression when compared with non‐neoplastic mucosa. Interestingly, most of the gastric and colonic carcinomas having high cdc2 kinase activity expressed high levels of p53. These findings suggest that the increased p34cdc2 kinase activity might cause the development and proliferation of gastric and colonic carcinomas, partly through abnormal p53 accumulation.
Non‐hodgkin lymphoma in gabon and its relation to HTLV‐I
Authors: Delaporte Eric , Klotz Francis , Peeters Martine , Martin‐Prevel Yves , Bedjabaga Léonard , Larouzé Bernard , Nguembi‐Mbina Celestin , Walter Andpaul , Piot Peter
Published: February 2007

A case‐control study was performed in Libreville, Gabon, to determine whether a relationship can be established between the relatively high proportion of non‐Hodgkin lymphoma (NHL) among all cancer cases and the high seroprevalence rate of HTLV‐I observed, and to discover whether cases of adult T‐leukemia/lymphoma (ATLL) related to HTLV‐I exist in Gabon. From November 1987 to April 1989, a total of 32 patients with NHL were recruited; 6 were infants with Burkitt's lymphoma and 26 were adults with NHL. Each patient was matched with 2 asymptomatic controls for age, sex and ethnic group. HTLV‐I serology was done by ELISA and Western blot. Comparison of the groups was done by chi‐square analysis. None of the 6 infants with Burkitt's lymphoma and none of their controls had antibodies to HTLV‐I. Of the 26 patients with NHL, 7 (26.9%) had HTLV‐I antibodies. Among the 52 controls, the HTLV‐I rate was 13.4% (n = 7). There was no difference between cases and controls (Fisher's exact test, p = 0.16). Among the 26 NHL, 4 cases fitted the criteria of ATLL and were HTLV‐I‐positive; 3 others who were positive for HTLV‐I were a woman with lymphoblastic gastric NHL and 2 old men with an unclassified lymphoma. From the results of this limited series it is not possible to state that there is an association between NHL and HTLV‐I infection. Nevertheless, cases of ATLL related to HTLV‐I are reported from this area. Based on the HTLV‐I seroprevalence rates reported in Gabon, the estimated incidence rate of ATL among seropositive people in Gabon appears much lower than in Japan. Different explanations can be proposed, but under‐diagnosis of ATLL is probably one of the main factors.
Desmoplasia and its relevance to colorectal tumour invasion
Authors: Hewitt Robert E. , Powe Desmond G. , Ian Carter G. , Turner David R.
Published: February 2007

Some invasive tumours characteristically have an abundant stroma rich in collagen, the production of which is termed the desmoplastic response. It has been suggested that this response may have a protective effect, and act to limit the process of tumour invasion. To investigate this possibility, we have examined various colorectal tumours for inter‐ and intra‐tumoural variations in the desmoplastic response. As markers of this response, the distributions of collagen‐I protein and myofibroblasts have been demonstrated by immunocytochemistry, while collagen‐I messenger RNA has been demonstrated by in situ hybridization (ISH). Evidence of a desmoplastic response was obvious in carcinomas, but not in non‐invasive adenomas. In carcinomas, we found that the response was marked in the tumour centre, where morphological features of active invasion have been reported to be absent. By contrast, we found little evidence of a desmoplastic response at the invasive edge of these carcinomas, where features suggestive of active invasion are prominent: in this location, collagen‐I immunostaining was limited and myofibroblasts were sparsely distributed or absent. While our ISH results suggested active collagen‐I synthesis in the tumour centre, there was little evidence of collagen‐I synthesis in host tissues ahead of the invasion front. On the basis of these and other reported findings, we suggest that, while the desmoplastic response may reduce the invasive activity of neoplastic cells in the tumour centre, it fails to prevent the spread of colorectal cancer because of its deficiency at the invasive edge.