bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ornithine decarboxylase inhibitor attenuates bombesin enhancement of intestinal carcinogenesis and metastasis induced by azoxymethane
Authors: Iishi Hiroyasu , Tatsuta Masaharu , Baba Miyako , Uehara Hiroyuki , Nakaizumi Akihiko 
Published: February 2007

AbstractThe effects of combined administration of bombesin (40 μ/kg body weight) and the ornithine decarboxylase (ODC) inhibitor, 1,3‐diaminopropane (DAP), on the development of large and small intestinal tumors and the incidence of their metastasis to the peritoneum induced by azoxymethane (AOM, 7.4 mg/kg body weight), the ODC activity of the intestinal wall, and the labeling index of the intestinal mucosa and tumor were investigated in inbred Wistar rats. Rats received weekly s.c. injections of AOM for 10 weeks, s.c. injections of bombesin every other day, and drinking water containing DAP (2.5 g/l) until the end of the experiment at week 40. Administration of bombesin significantly increased the incidence of intestinal tumors at week 40. It had no influence on the location, size, histological features or depth of involvement of intestinal adenocarcinomas, but significantly increased the incidence of their metastasis to the peritoneum. It also resulted in a significant increase in the intestinal ODC activity and labeling index. Administration of DAP with bombesin significantly reduced the enhancement of intestinal carcinogenesis by bombesin. Although the combined use of DAP with bombesin had little or no influence on the location, size, histological features, or depth of involvement of intestinal cancers, the incidence of their metastasis was significantly reduced. DAP significantly attenuated bombesin enhancement of the intestinal ODC activity and labeling index. These findings indicate that ODC inhibition attenuated the enhancement of intestinal carcinogenesis and metastasis to the peritoneum.
Modulation of Mr 72,000 and Mr 92,000 type‐IV collagenase (gelatinase A and B) gene expression by interferons alpha and gamma in human melanoma
Authors: Hujanen Erkki S. , Väisänen Anne , Zheng Aiping , Trygdvason Karl , Turpeenniemi‐Hujanen Taina 
Published: February 2007

AbstractThe purpose of this study was to determine how interferons α and γ influence the expression of Mr 72,000 type‐IV collagenase (gelatinase A) and Mr 92,000 type‐VI collagenase (gelatinase B) genes and whether there are differences in their gene expression. Special emphasis was focused on the treatment time. Total cellular RNA from A2058 human melanoma cells treated for various time periods with IFN‐α or γ was analyzed by Northern‐and slot‐blot hybridization. Both Mr 72,000 and Mr 92,000 type‐IV collagenase mRNAs were detectable in A2058 cells and mRNA levels for both gelatinases were significantly up‐regulated in the cells treated for a short time period with either IFN‐α or γ. In contrast, a long‐term treatment (7 days) with these drugs markedly down‐regulated the genes for both gelatinase A and B. Zymographic analysis showed that human melanoma primarily secretes the gelatinase‐A activity, which showed changes similar to those seen in the corresponding mRNA after the treatments with interferons. The expression of gelatinase‐B activity was, however, detectable only transiently during the stimulating phase with IFN‐α. Western immunoblot analysis showed that alterations in the levels of immunoreactive protein of gelatinase A in the cells correlated with the mRNA levels after the treatments. These findings suggest that IFN‐α and IFN‐γ are potent regulators of both Mr 72,000 and Mr 92,000 type‐IV collagenase/gelatinase A and B genes in human melanoma showing biphasic and parallel effects on mRNA levels of both enzymes, depending on the treatment time, and that the Mr 72,000 metalloproteinase/gelatinase A is the predominant basement‐membrane‐degrading type‐IV collagenase in human melanoma.
Establishment of hormone‐dependent and hormone‐indhpendent carcinoma cell lines with different metastatic potentials from spontaneous mammary tumors in aged wistar rats
Authors: Nakanishi Hayao , Taylor Robert M. , Hawkins Anita L. , Griffin Constance A. , Martin George R. , Passaniti Antonino 
Published: February 2007

AbstractThree stable carcinoma cell lines, designated RM22‐F5, RM17 5R, and RM 1‐4, were established from spontaneously occurring mammary carcinomas in old, outbred, female Wistar rats. The RM22‐F5 and RM 17‐SR cells were keratin‐positive and formed epithelial monolayers, whereas RMI‐4 cells exhibited a spindle‐like morphology and intense vimentin staining. When injected into nude mice, RM22‐F5, RM17‐5R and RM1‐4 cells formed well‐differentiated, poorly differentiated and undifferentiated carcinomas, respectively. The relative growth rates of the tumor cells in vitro were RM1‐4 > RM22‐F5 > RM17‐5R. The growth of RM22‐F5, but not of RM17‐5R and RM1‐4 cells, was significantly stimulated by insulin, epidermal growth factor, dexamethasone, 17β‐estradiol and progesterone in vitro. Ovariectomy reduced the growth of RM22‐F5 cells in vivo and these cells (but not RM1‐4 or RM17‐5R) were estrogen‐receptor (ER)‐positive. None of the lines were positive for the progesterone receptor (PR). Spontaneous lung and lymph‐node metastases were observed in nude mice injected with RM22‐F5 or RM17‐5R cells, respectively. In contrast, RM1‐4 cells were non‐metastatic but invasive. Karyotype analysis revealed that RM22‐FS cells were hyperdiploid, RM 17‐SR were hypotetraploid, and RM1‐4 were diploid with a sizeable insertion in chromosome I. A point mutation in codon 12 (G to A transition) and loss of the normal aliele of the H‐ras‐1 gene was detected in the DNA from RM22‐FS cells. No p53 mutations were apparent in any of the cell lines. The results indicate that RM22‐F5 cells are hormone‐dependent with an ER+/PR− phenotype, while the RM 17‐SR and RM1‐4 lines are hormone‐independent and ER−/PR. These cell lines exhibit the spectrum of biological properties and genetic alterations observed in human breast cancers and may, therefore, be novel and useful models for understanding sporadic breast cancer in post‐menopausal women.
Hox gene expression in human small‐cell lung cancers xenografted into nude mice
Authors: Tiberio Claudia , Barba Pasquale , Magli Maria Cristina , Arvelo Francisco , Chevalier Thierry Le , Poupon Marie France , Cillo Clemente 
Published: February 2007

AbstractTranscription factors are crucial to an understanding of the molecular basis of neoplasia. Horneobox‐containing genes are a family of transcriptional regulators encoding DNA‐binding ho‐meodomains, involved in the control of normal development. Class‐1 human homeobox‐containing genes (HOX genes) display a peculiar chromosomal organization, perhaps directly related to their function. Aberrant expression of homeobox‐genes has been associated with both morphological abnormalities and oncogenesis. We have recently observed that alterations in HOX gene expression are detectable in kidney and colon cancer when compared to the corresponding normal organs. Here we have analyzed the expression of HOX genes in primary and metastatic human small‐cell lung cancer (SCLC) xenografted in nude mice, in order to investigate whether HOX gene expression correlates with the histology and stage of SCLC progression. The results show that different SCLCs display differential patterns of HOX gene expression. Furthermore, in SCLC, the number of actively expressed HOX genes might be substantially lower in metastatic cancers than in primary tumors. The alteration in HOX gene expression in SCLCs mainly concerns the HOX B and C loci. This finding suggests that downregulation of HOX genes may play a role in small‐cell lung cancer progression, possibly through their implication in tumor suppression.
Association of c‐erbB2‐gene amplification with poor prognosis in non‐inflammatory breast carcinomas but not in carcinomas of the inflammatory type
Authors: Lě Monique G. , Douc‐Rasy Sétha , Ahomadegbe Jean Charles , Spielmann Marc , Guérin Martine , Riou Guy 
Published: February 2007

AbstractIt is now accepted that c‐crbB2‐gene amplification is correlated with poor clinical outcome for patients, mainly when axillary nodes are invaded. We have confirmed this result by multivariate analysis in 178 patients with non‐inflammatory breast cancer followed up for a mean period of 6.8 years (SD, 1.6 years). In addition, we have shown that c‐erbB2 amplification, found in 30 (17%) specimens, was associated with a high risk of multiple metastases developing simultaneously. In contrast, for the 67 patients with inflammatory breast carcinoma, the most aggressive type of breast carcinoma, the c‐erbB2 amplification detected in 24 (36%) specimens was not found to be associated with a higher risk of death, suggesting that the oerbB2 gene plays a different role in the progression of these 2 types of breast cancer. Furthermore, our data stress the importance of the methodological approach used to determine gene amplification. Although Southern blot hybridization is a tumour‐ and time‐consuming method not easy to adopt in routine clinical practice, this method remains a reference quantitative method.
Effect of recombinant human interferon‐alpha/2b on epidermal‐growth‐factor‐, estrogen‐ and progesterone‐receptor expression in primary cervical cancer
Authors: Scambia Giovanni , Panici Pierluigi Benedetti , Ferrandina Gabriella , Battaglia Francesco , Sica Gigliola , Coronetta Ferdinando , Rumi Carlo , Mancuso Salvatore 
Published: February 2007

AbstractThe effects of a short period of in vivo systemic rh‐IFN‐alpha/2b treatment on epidermal‐growth‐factor(EGFR)‐, estrogen(ER)‐ and progesterone (PR)‐receptor content in 11 primary human cervical tumors was investigated by the radioreceptorial technique. EGFR levels were found to be significantly higher in cervical tumors after rh‐IFN‐alpha/2b treatment with respect to basal levels. In 2 cases, immunohistochemical and cytofluorimetric analysis showed that rh‐IFN‐alpha/2b treatment induces an increase in EGFR immunoreactivity and in the fraction of EGFR‐positive cells. No difference in ER and PR levels in cervical tumors before and after rh‐IFN‐alpha/2b treatment was observed. Our results suggest that rh‐IFN‐alpha/2b up‐regulates EGFR in primary human cervical tumors in vivo.
Expression of neuronal src mRNA as a favorable marker and inverse correlation to N‐myc gene amplification in human neuroblastomas
Authors: Matsunaga Tadashi , Shirasawa Hiroshi , Tanabe Masahiro , Ohnuma Naomi , Kawamura Kenji , Etoh Takao , Takahashi Hideyo , Simizu Bunsiti 
Published: February 2007

AbstractNeuron‐specific sre mRNA, which is expressed in human brain tissue by alternative splicing, is associated with neural differentiation. Neuronal c‐srcN I expression may be associated with the ability of neu roblastomas to mature; furthermore, c‐srcN2 mRNA is induced in chemically differentiated neuroblastoma cells in vitro. The prognosis of a patient with a neuroblastoma is strongly affected by the ability of the tumor to differentiate in vivo. In order to clarify the relationship between neuronat src mRNA expression and the clinical outcome of a neuroblastoma, we analyzed the expression of src mRNA in neuroblastoma tissues from 28 patients by SI‐nuc I ease‐protection assay. N‐myc gene amplification was also examined by Southern blot hybridization. The clinical significance of neuronal src mRNA expression and its relevance to N‐myc gene amplification was also investigated. A high ratio (more than 10%) of c‐srcN2 mRNA expression was observed in all early‐stage tumors and in advanced neuroblastomas with a favorable prognosis. In contrast, in advanced neuroblastomas with an aggressive clinical phenotype, c‐srcN2 mRNA expression was found at a low ratio (below 10%). Genomic amplification of the N‐myc gene and expression of c‐srcN2 mRNAs were inversely correlated. When combined with other prognostic markers such as N‐myc gene amplification, the expression of c‐srcN2 mRNA may be a new biological marker to predict the prognosis of patients with neuroblastomas.
Prevalence of deletions of YY1‐binding sites in episomal HPV 16 DNA from cervical cancers
Authors: Dong Xiao‐Ping , Stubenrauch Frank , Beyer‐Finkler Elke , Pfister Herbert 
Published: February 2007

AbstractExpression of the oncogenes E6 and E7 of human papillomavirus 16 (HPV 16) appears enhanced in pre‐malignant and malignant genital tumors. We recently identified a transcriptional silencer upstream of the oncogene promoter P97, comprising 4 binding sites for the cellular YYI protein. The analysis of the long transcriptional control regions (LCR) of episomal HPV 16 DNAs from primary tumors and lymph‐rode metastases of 6 patients with cervical cancer revealed deletions and point mutations of YYI binding sites in 4 cases. To test for the activity of the P97 promoter, the mutated LCRs were cloned in a tuciferase reporter gene vector. A point mutation in YYI‐recognition site 4, which prevents DNA‐protein interaction, did not affect promoter activity, probably due to compensation by the overlapping YYI‐binding site 3. However, 5.S‐ to 6.5‐fold increased luciferase expression was obtained under the control of 3 shortened LCRs lacking 2 to A YYI‐binding sites. A point mutation in YYI‐recognition site 2, which was previously shown to stimulate P97 3.5‐fold, could be detected in the HPV 16 LCRs from both primary tumor and metastasis, indicating that the mutation is a stable characteristic of HPV 16 DNA associated with the individual cancer. These findings suggest that deletions or mutations of YYI‐binding sites play a significant role in over‐expression of viral oncogenes and tumor progression.
Differentiation ability and oncogenic potential of HPV‐33‐and HPV‐33+ras‐transfected keratinocytes
Authors: Gilles Christine , Piette Jacques , Peter Wolfgang , Fusenig Norbert E. , Foidart Jean‐Michel 
Published: February 2007

AbstractFive HPV‐33‐immortalized and 5 HPV‐33+ras‐transfected cell lines were characterized in terms of growth in soft agar, tumorigenic potential in nude mice, p2l expression, morphology and expression of differentiation markers in organotypic cultures. No striking differences were observed between the HPV‐33‐immortalized cell lines and their corresponding ras‐transfected counterparts as regards their tumorigenicity in nude mice (only one cell line was able to develop tumors in nude mice) or their behavior on lifted collagen gels. However, all the ros‐transfected cell lines gave rise to colonies in soft agar while only 2 HPV‐33‐transfected lines (CK1 and CK4) displayed this property. The 10 cell lines could be divided into 2 groups with respect to their phenotype in monolayer and in organotypic cultures. Lines from group 1 (CK1,3, 5 and their ras‐transfected homologous lines) shared a typical epithelial phenotype in monolayer and the ability (a) to form an epithelium similar to a CIN‐III lesion and (b) to strongly express keratins KI‐KIO and involucrin in organotypic cultures. On the other hand, for the lines from group II (CKI, CK4, CKI EJ7 and CK4EJ5), there was a correlation between an elongated phenotype in monolayer and the property (a) to form a structure similar to a microinvasive carcinoma and (b) to express vimentin and keratins K‐KI8. These cell lines, exhibiting various transformation‐associated alterations, can be considered as an in vitro model representing various stages of HPV‐33‐associated cervical carcinogenesis.
The human zinc‐finger protein‐7 gene is located 90 kb 3′ of MYC and is not expressed in Burkitt lymphoma cell lines
Authors: Gallego Marta I. , Lazo Pedro A. 
Published: February 2007

AbstractThe zinc‐finger gene‐7 (ZNFT) was located 90 kb 3′ of MYC on human chromosome 8 band q24 by pulsed‐field gel electropho‐resis (PFGE). This position lies between the MLV14 and BVRI loci, 2 variant translocation breakpoints in Burkrtt tymphomas. The structure of the ZNF7 gene was not altered by translocations in Burkitt‐lymphoma cell lines as shown by its germline‐restriction map configuration. The chromosomal region surrounding the ZNF7 gene was extensively methylated. The ZNF7 gene was not expressed in 19 BL cell lines. Expression was detected only in the BL41 and BL47 cell lines and in the SW756 cervical‐carcinoma cell line. The UNA in each was of a different size. We postulate that the lack of ZNF7 expression in Burkitt lymphomas might contribute to the tumor phenotype.
A cleaved form of the receptor for urokinase‐type plasminogen activator in invasive transplanted human and murine tumors
Authors: Solberg Helene , Rømer John , Brünner Nils , Holm Arne , Sidenius Nicolai , Danø Keld , Høyer‐Hansen Gunilla 
Published: February 2007

AbstractIt was recently found that urokinase‐type plasminogen activator (uPA) is involved in the cleavage of its receptor (uPAR) on cultured cells, thereby releasing one of the receptor's 3 domains (the ligand binding domain I) and leaving the 2 others [uPAR(2 + 3)] anchored to the cell surface. With monoclonal antibodies (MAbs) we have now identified human uPAR(2 + 3) in lysates of invasive human MDA‐MB‐231 mammary carcinomas xenografted into nude mice. The production of peptide antibodies recognizing different domains of murine uPAR made it possible to identify a similar cleaved form of uPAR, murine uPAR(2 + 3), in extracts of primary Lewis lung carcinomas. Cleavage of uPAR also occurs in cultured MDA‐MB‐231 cells and Lewis lung carcinoma cells. This cleavage is inhibited by anticatalytic antibodies to either human or murine uPA, respectively, indicating that it is catalyzed by either uPA or plasmin generated by uPA. The amount of uPAR(2 + 3) may therefore be directly related to the activity of the uPA system and it is possible that the level of uPAR(2 + 3) in cancer tissue may prove to be a stronger prognostic parameter than the levels of either full‐length uPAR or UPA.
bcl‐2 expression in normal breast tissue during the menstrual cycle
Authors: Sabourin J. C. , Martin A. , Baruch J. , Truc J. B. , Gompel A. , Poitout P. 
Published: February 2007

Abstractbcl‐2 is a proto‐oncogene discovered through the t(14; 18) translocation occurring in most human follicular lymphomas. The function so far attributed to bcl‐2 is to counteract the occurrence of apoptosis and to prolong cell survival without affecting the cycling cells. Apoptosis has been described in normal breast tissue epithelial cells, and it peaks at the end of the luteal phase. We have studied bcl‐2 expression by an immunohistochemical method in 50 samples of normal breast tissue distributed throughout the menstrual cycle. bcl‐2 staining predominated in the lobular epithelial cells. It displayed a striking cyclic variation, with maximal expression at the midcycle period and a sharp decrease at the end of the cycle. These results strongly suggest that the regulation of bcl‐2 expression in breast tissue is hormone‐dependent. This could be of significance in tumorigenesis.
Phenotypic heterogeneity in breast fibroblasts: Functional anomaly in fibroblasts from histologically normal tissue adjacent to carcinoma
Authors: Schor Ana M. , Rushton Graham , Ferguson Janice E. , Howell Anthony , Redford Judy , Schor Seth L. 
Published: February 2007

AbstractHistologically normal breast tissue was obtained from women undergoing surgery for benign breast lesions (n = 12) and mammary carcinomas (n = 15). Four fibroblast subpopulations (FI, FII, FIII and FIV) were isolated from these specimens by differential digestion and centrifugation. FI cells were the first to be released from the tissue digest and consequently assumed to be derived from the interlobular stroma; FIV fibroblasts were tightly associated with the epithelial organoids and are therefore believed to be of intralobular origin. These cells were characterised in terms of their migratory phenotype (classified as either foetal‐ or adult‐like) and the production of motility factors according to previously described techniques. FI fibroblasts obtained from patients with benign breast lesions displayed a foetal migratory phenotype (10/11) and secreted detectable quantities of motility factors (11/11). In contrast, none of the FIV fibroblasts (0/10) obtained from these same patients displayed a foetal‐like migratory phenotype or secreted motility factors. In the case of fibroblasts obtained from cancer patients, both FI (13/13) and FIV (13/13) fibroblasts displayed a foetal‐like migratory phenotype and secreted motility factors. Fibroblasts were also derived from skin (n = 12) and breast fat tissue (n = 4) of certain patients. In agreement with our previously published observations, skin fibroblasts obtained from non‐cancer and cancer patients also differed in terms of their migratory behaviour: none of the skin fibroblast lines (0/5) obtained from non‐cancer patients were foetal‐like, compared to 3/7 lines from cancer patients. All fat‐derived fibroblasts (I non‐cancer and 3 cancer patients) were also foetal‐like. Our results indicate (i) functional heterogeneity between FI and FIV fibroblasts of normal breast, and (ii) the presence of functionally aberrant (i.e., foetal‐like) FIV fibroblasts in histologically normal breast tissue adjacent to a carcinoma.
Evaluation of epstein‐barr virus antibody patterns and detection of viral markers in the biopsies of patients with Hodgkin's disease
Authors: Levine Paul H. , Pallesen Gorm , Ebbesen Peter , Harris Nancy , Evans Alfred S. , Müeller Nancy 
Published: February 2007

AbstractWe assessed the relationship of Epstein‐Barr virus (EBV) serology to the presence or absence of EBV genome in 39 cases of Hodgkin's disease (HD). Biopsies from patients included in 2 previous published studies, I involving patients from the United States (eastern Massachusetts) and I from Denmark, were evaluated for EBV RNA (EBER‐1) and latent membrane protein (LMP‐I). The presence of EBV in Reed‐Sternberg cells in the biopsies correlated with the histologic subtype of HD (mixed cellularity and lymphocyte depletion) but not with IgG antibody titers against the viral capsid antigen (VCA). These data suggest that, unlike Burkitt's lymphoma, the IgG antibody against VCA is not predictive of the presence or absence of EBV in Reed‐Sternberg cells in HD. The predictive value of other antibodies should be evaluated.
Expression of the WT1 Wilms' tumor gene by normal and malignant human melanocytes
Authors: Rodeck Ulrich , Bossler Anna , Kari Csaba , Humphreys Christopher W. , Györfi Tibor , Maurer Jürgen , Thiel Eckhard , Menssen Hans D. 
Published: February 2007

AbstractWe report expression of the wt I (Wilms' tumor) gene by cultured human melanoma cells. Using RNA polymerase chain reaction analysis, wt I transcripts were detected in 7 of 9 melanoma cell lines but not in 5 normal melanocyte strains. In Northern blot analysis, steady‐state wt I mRNA levels were found in 2 of 4 melanoma lines but not in normal melanocytes. Sequence analysis of the wt I cDNA expressed by melanoma cell line WM 902‐B revealed the presence of 4 previously published splice variants but no evidence for mutations in the coding region. Previous work has shown that WT I modulates transcription after binding to the early growth response (EGR)‐I sites present in the platelet‐derived growth factor (PDGF)‐A chain promoter; the PDGF‐A chain gene is known to be expressed by various melanoma cell lines. Based on these findings, we studied the relationship of wt I and PDGF‐A chain gene expression in melanoma cell lines. Co‐expression of the wt I and the PDGF‐A chain genes was observed in 2 melanoma cell lines with mutated p53 but not in 2 melanoma cell lines with wild‐type p53; this result is consistent with a previous report showing that, in the context of absent or mutated p53, WTI acts as a transcriptional activator, whereas in the presence of wild‐type p53 it acts as a repressor.