bluuebunny/crossref_metadata_2025_split huggingface dataset:
The proto‐oncogene/translation factor eIF4E: A survey of its expression in breast carcinomas
Authors: Kerekatte Vaishali , Smiley Kyle , Hu Bei , Smith Albert , Gelder Frank , De Benedetti Arrigo 
Published: February 2007

AbstractThe eukaryotic translation initiation factor elF‐4E binds to the cap structure of mRNAs as one component of the elF‐4 translation initiation complex, which mediates the recruitment of mRNA to the ribosomes. Overexpression of elF‐4E can result in oncogenic transformation and uncontrolled growth of mammalian cells, presumably by facilitating the expression of growth‐control gene products which are normally translationally repressed. Whereas the mechanism of elF‐4E‐mediated transformation is being actively pursued, clinical investigations into the expression of elF‐4E in prevalent human cancers are lacking. We have recently initiated a screen of breast carcinomas by probing with elF‐4E antiserum. Using Western blots, we have analyzed the level of elF‐4E in 38 carcinomas, 7 normal samples and 3 fibroadenomas. We found that elF‐4E was elevated 3‐ to 10‐fold in virtually all the carcinomas we analyzed, but not in fibroadenomas. This analysis was also confirmed by immunohistological staining in situ, showing that overexpression of elF‐4E can be readily identified at the single‐cell level. Our results suggest that an elevation of elF‐4E may be an essential component in the development of breast cancer. © 1995 Wiley‐Liss, Inc.
The mutational status of p53 protein in gastric and esophageal adenocarcinoma cell lines predicts sensitivity to chemotherapeutic agents
Authors: Nabeya Yoshihiro , Loganzo Frank , Maslak Peter , Lai Lawrence , De Oliveira Alice R. , Schwartz Gary K. , Blundell Maude L. , Altorki Nasser K. , Kelsen David P. , Albino Anthony P. 
Published: February 2007

AbstractResistance to chemotherapy remains a serious problem in the successful treatment of gastric and esophageal cancers. DNA‐damaging agents alter levels of p53 protein in several cell types and it has been speculated that regulation of p53 can be involved in the resistance or sensitivity of cancer cells to some chemotherapeutic drugs, depending on whether cells have mutant or wild‐type p53; however, little is known about the relationship of p53 to drug sensitivity in gastric/esophageal cancers. Here we have examined human gastric/esophageal adenocarcinoma cell lines for p53 mutational status, chemorensitivity to 5‐fluorouracil, mitomycin C, and cis‐dichlorodiammin‐eplatinum(II), alteration in p53 levels following exposure of cells to these drugs, and the mechanisms involved in regulating p53 levels. Our results indicate that wild‐type p53 protein levels increase after treatment with each of these drugs via either post‐translational and/or translational mechanisms and that this increase in wild‐type p53 appears to be required for effective chemotherapeutic growth control of gastric/esophageal adenocarcinoma cells. In contrast, gastric/esophageal cancer cells expressing either mutated p53 protein or no p53 protein are more resistant to the growth‐inhibitory effects of these drugs, despite the fact that drug exposure can also increase mutant p53 levels by a translational mechanism. Thus, these data indicate that the mutational status of p53 is predictive of chemosensitivity of gastric and esophageal adenocarcinomas, and suggest a mechanism in which p53 protein contributes to the cellular response to chemotherapy. © 1995 Wiley‐Liss, Inc.
p53 gene mutations in early colorectal carcinoma. de novo vs. adenoma‐carcinoma sequence
Authors: Hasegawa Hirotoshi , Ueda Masakazu , Furukawa Kazuo , Watanabe Masahiko , Teramoto Tatsuo , Mukai Makio , Kitajima Masaki 
Published: February 2007

Abstractp53 gene mutations in early and advanced colorectal cancer were detected by PCR‐SSCP analysis. Early colorectal cancer was classified intode novo cancer and polyp‐forming cancer, respectively, according to morphology and presence of adenomatous components. A total of 94 paraffin‐embedded tissue specimens from patients with colorectal cancer were analysed.p53 gene mutations were detected in 40.0% (12/30) of de novo cancer, 36.7% (11/30) of polyp‐forming cancer, and 44% (15/34) of advanced cancer. p53 mutations were detected at a high frequency in both types of early colorectal cancer as well as in advanced cancer. No correlations were found between p53 mutations and clinicopathological data. Our data suggest that the p53 gene mutations occurred in the early colorectal cancer stage of carcinogenesis regardless of the pathway. © 1995 Wiley‐Liss, Inc.
Significance of tenascin serum level as tumor marker in primary colorectal carcinoma
Authors: Riedl Stefan , Bodenmüller Heinz , Hinz Ulf , Holle Rolf , Möller Peter , Schlag Peter , Herfarth Christian , Faissner Andreas 
Published: February 2007

AbstractTenascin serum levels were evaluated in 118 patients with primary colorectal carcinoma and in a control group of 51 healthy persons in a double‐sided sandwich ELISA. The data were correlated with post‐operative TNM‐staging. Patients with colorectal carcinomas had significantly higher serum levels of tenascin than the control group. At the 95% level of specificity, sensitivity was 25%. Tumor grading obviously had no influence on the level of tenascin in serum. With increasing pT‐category, tenascin levels increased as well. In patients with distant metastatic disease, serum tenascin levels were significantly higher than in patients without distant metastases. These data suggest that, in colorectal carcinoma, the preoperative level of serum tenascin reflects the total tumor burden and correlates with metastatic disease. Our observation warrants a prospective study of the relevance of tenascin serum levels with regard to prognosis and as an indicator of relapse. © 1995 Wiley‐Liss, Inc.
Neoplastic progression of human colorectal cancer is associated with overexpression of the stromelysin‐3 and BM‐40/SPARC genes
Authors: Porte Henri , Chastre Eric , Prevot Sophie , Nordlinger Bernard , Empereur Sylvie , Basset Paul , Chambon Pierre , Gespach Christian 
Published: February 2007

AbstractThe interaction of neoplastic cells with the extracellular matrix is a critical event for the initiation of cancer invasion and metastasis. This study was designed to evaluate the potential implication of stromelysin‐3 (ST3), a newly identified member of the matrix‐degrading metalloproteinase family, and of BM‐40/SPARC, a glycoprotein associated with the extracellular matrix, during the progression of human colorectal cancers. We analyzed the relative abundance of ST3 and BM‐40/SPARC transcripts by Northern blot, and their distribution by in situ hybridization, in normal mucosa, benign adenomas, and primary colorectal adenocarcinomas and their liver metastases. The ST3 and BM‐40/SPARC transcripts were overexpressed in primary colorectal cancers and their liver metastases compared to non‐neoplastic mucosa. These transcripts were localized in stromal fibroblasts adjacent to the neoplastic foci. Overexpression of ST3 correlated with the progression of human colorectal tumors toward local invasion and liver metastasis. Induction of these genes also occurred in diverticulitis and digestive neoplasms such as gastric and esophageal carcinomas. © 1995 Wiley‐Liss, Inc.
Detection of tumour cells in peripheral blood and bone marrow from ewing tumour patients by rt‐pcr
Authors: Pfleiderer Christa , Zoubek Andreas , Gruber Bernadette , Kronberger Martina , Ambros Peter F. , Lion Thomas , Fink Franz‐Martin , Gadner Helmut , Kovar Heinrich 
Published: February 2007

AbstractThe Ewing family of tumours (et) is characterised at the cytogenetic level by unique chromosome 22 rearrangements. The breakpoints have been cloned and were shown to fuse the EWS gene on chromosome 22 to one of two closely related ETS proto‐oncogenes, FLI‐L or EFG, which reside on chromosomes 11 and 21, respectively. The rearrangement results in the expression of chimaeric transcripts, which can be identified by means of reverse transcriptase‐polymerase chain reaction (RT‐PCR). We applied this method for the monitoring of Et cells circulating in the peripheral blood or infiltrating the bone marrow. The presence of tumour cells could be detected with a sensitivity of I in I × 106 nucleated cells. When samples were kept at 4c, tumour cells could still be identified after 48 hr of storage. Positive RT‐PCR signals originated from intact ET cells rather than from free RNA released by ruptured tumour cells. We analysed peripheral blood, bone marrow samples and peripheral blood stem cell collections from 16 ET patients. At diagnosis, bone marrow specimens collected from 6 patients and 1 peripheral blood specimen tested positive for EWS chimaeric RNA. During therapy tumour cells were detected in bone marrow aspirations obtained from 2 patients. Our results show that ET cells infiltrating the bone marrow or circulating in peripheral blood can be identified by RT‐PCR. The clinical implications for the presence of ET cells in samples detected by RT‐PCR at diagnosis and during therapy requires further evaluation. © 1995 Wiley‐Liss, Inc.
Association between rb‐1 gene alterations and factors of favourable prognosis in human breast cancer, without effect on survival
Authors: Berns Els M. J. J. , De Klein Annelies , Van Putten Wim L. J. , Van Staveren Iris L. , Bootsma Aart , Klijn Jan G. M. , Foekens John A. 
Published: February 2007

AbstractThe retinoblastoma (RB) tumour suppressor gene has been associated not only with retinoblastoma but also with several other tumours like osteosarcoma, small cell lung carcinoma and prostate and breast cancer. We have studied the incidence of RB gene alterations in 96 primary breast tumours using Southern blotting techniques. The outcome has been related with patient and tumour characteristics, oncogene amplifications, p53 mutations and prognosis. RB gene alterations were found to occur more frequently in estrogen receptor (ER)‐positive than in ER‐negative tumours and less frequently in tumours with oncogene amplification than in tumours without oncogene amplification of HHR2/neu, c‐myc or 11q13. RB gene alteration was observed in tumours both with and without a p53 gene mutation. Data on 87 patients (mean age, 59.6 years; median follow‐up, 108 months) and RB gene alterations revealed a significant association between the frequency of RB gene alterations and node‐negative patients (p < 0.01) or smaller (<2 cm) tumours (p < 0.01), but no relation with age, differentiation grade or (relapse‐free) survival. Patients with and without RB gene alterations showed the same relapse‐free and overall survival. © 1995 Wiley‐Liss, Inc.
Microsatellite instability in primary and metastatic colorectal cancers
Authors: Ishimaru Gosei , Adachi Jun‐Ichi , Shiseki Masayuki , Yamaguchi Naohito , Muto Tetsuichiro , Yokota Jun 
Published: February 2007

AbstractMicrosatellite instability characterizes a sub‐set of sporadic colorectal cancers (CRCs) as well as CRCs from patients with hereditary non‐polyposis colorectal cancer (HNPCC). In order to clarify when the cells acquire a replication‐error phenotype (RER) during colorectal‐tumor progression, we examined the incidence of RER in 80 primary tumors and 36 liver metastases at 8 microsatellite loci; I mono‐, 5 di‐, I tetra‐ and I penta‐nucleotide. RER were detected in 20.1% (17/80) of primary tumors, including 5 tumors showing RER at 2 or more loci (RER2), while the incidence of RER in liver metastases (22.2%, 8/36) was almost the same as that in primary tumors, and there was only one RER2 case in metastases. There were 3 cases in which both primary tumors and liver metastases had the same type of RER at the same locus, and there were 2 cases that showed RER in primary tumors but not in liver metastases. In contrast, there was no case in which RER was detected in a metastasis but not in the corresponding primary tumor. The RER phenotype did not show correlation with any clinicopatho‐logical parameters of cancer‐cell aggressiveness, such as clinical staging, histological grade and survival. These results indicate that a sub‐set of CRCs acquire the RER phenotype in the relatively early stages of colorectal carcinogenesis, and that the RER phenotype is not associated with aggressiveness of CRCs. © 1995 Wiley‐Liss, Inc.
Expression of cd44 splice variants in human cutaneous melanoma and melanoma cell lines is related to tumor progression and metastatic potential
Authors: Manten‐Horst Eveliene , Danen Erik H. J. , Smit Lia , Snoek Margriet , Caroline Poole I. Le , Van Muijen Goos N. P. , Pals Steven T. , Ruiter Dirk J. 
Published: February 2007

AbstractExpression of CD44, particularly of certain splice variants, has been linked to tumor progression and metastasis formation in a number of different animal and human cancers. Because human cutaneous melanoma is among the most aggressive human cancers, we explored expression of CD44 isoforms (CD44v) in lesions of melanocytic tumor progression. In addition, by RT‐PCR and FACS analysis we assessed CD44v RNA species and cell surface expression of CD44v in cultured melanocytes isolated from human foreskin and in a panel of 2 non‐, 2 sporadically and 2 highly metastatic human melanoma cell lines. We observed that all melanocytic lesions examined showed strong uniform expression of standard CD44 (CD44s) epitopes. We did not detect CD44v6 expression in the melanocytic lesions. However, CD44 isoforms containing v5 or v10 were differentially expressed. V5 was expressed in 16%, 0%, 20%, 67% and 58% of common nevi, atypical nevi, early primary melanomas (± 1.5 mm), advanced primary melanomas (> 1.5 mm) and metastases, respectively, and hence was related to tumor progression. In contrast, CD44vl0 was expressed in all common nevi, whereas part of the atypical nevi and most primary melanomas and metastases lacked v10. CD44v RNA patterns were closely similar in cultured melanocytes and all melanoma cell lines. Melanocytes expressed high levels of CD44s but no CD44v, whereas all melanoma cell lines expressed CD44v at the surface. Interestingly, expression of v5 was strongly increased in the highly metastatic cell lines. Our results suggest a role for CD44 variant domains, particularly v5 and v10, in human melanocytic tumor progression. © 1995 Wiley‐Liss, Inc.
Increased expression of the nme1 gene is associated with metastasis in epithelial ovarian cancer
Authors: Leary Jennifer A. , Kerr Judith , Chenevix‐Trench Georgia , Doris Claire P. , Hurst Terry , Houghton C. Roger S. , Friedlanders Michael L. 
Published: February 2007

AbstractThe genetic events involved in the development of metastases of epithelial ovarian cancer are largely unknown. One gene postulated to play a role in tumour metastasis suppression is NMEI (nm23‐HI), and an inverse relationship between NMEI expression and metastatic potential has been observed for some solid tumours. In this study we have investigated the levels of mRNA expression of the 2 isoforms of the NME gene, NMEI and NME2. A maximum of 45 tumour samples from 33 patients were available for Northern blot analysis. We observed variable levels of expression of NMEI and NME2 mRNA. The average level of NMEI, but not NME2, mRNA expression was statistically higher in metastatic biopsies when compared with primary tumour biopsies. To examine the possible tumour suppressor gene role of NMEI in ovarian tumours, 76 patients were investigated by Southern blot analysis to determine the rate of allelic deletion. Allele loss at 5 other chromosome 17 loci (D17S5, TP53, NF1, D17S74, D17S4) was also evaluated for many of these 76 patients. Allele loss was observed in 22/30 (73%) informative patients at the NME1 locus. We also observed high rates of allele loss at the other loci evaluated. No correlations with clinical stage, histological subtype or patient survival were observed in either mRNA or DNA analyses. We have established that tumour progression in ovarian cancer is accompanied by over‐expression of the NME1 gene; however, despite high rates of allele loss at the NME1 locus, the concept that NME1 may be a candidate tumour suppressor gene in ovarian cancer cannot be confirmed by this study. © 1995 Wiley‐Liss, Inc.
TP53 and RAS mutations in metachronous tumors from patients with cancer of the upper aerodigestive tract
Authors: Yang Han‐Kwang , Ilona Linnoila R. , Conrad Nicholas K. , Krasna Mark J. , Aisner Seena C. , Johnson Bruce E. , Kelley Michael J. 
Published: February 2007

AbstractPatients who initially develop an upper aerodigestive tract cancer have an increased risk of second primary cancers. We examined TP53 and RAS mutations and p53 protein in 21 tumors from 10 patients with upper aerodigestive tract cancer who developed a metachronous tumor, to assess the genetic changes that occur in multiple primary tumors from the same individual. Thirteen of 21 (62%) tumors were found to have mis‐sense mutations of either TP53 or RAS. Six tumors had TP53 mutations in codons 5 to 8 and 10 tumors from 7 patients had mutations of codons 12 or 13 of K‐RAS. Only one patient had concordance of a mutation in 2 tumors; this mutation occurred in K‐RAS and was accompanied by discordance of TP53 mutation. Three patients had tumors discordant for both T53 and RAS mutations. Smoking‐related tumors had TP53 and RAS mutations which were transversions in 11 (9 G:C to T:A and 2 G:C to C:G) and transitions in 3 (2 G:C to A:T and 1 A:T to G:C). Tumors not associated with smoking contained only transitions (both G:C to A:T). p53 protein was detected by immunohisto‐chemistry in 7 of 13 (54%) tumors and was concordant in the multiple tumors of 3 patients. Three of the 7 tumors staining for p53 also had TP53 mutations. Thus, genetic alterations are discordant in multiple primary cancers and the pattern of mutations is similar to that found in patients with a single primary tumor, supporting the concept that these cancers arise independently. © 1995 Wiley‐Liss, Inc.
Exon scanning for mutations of the nf2 gene in pediatric ependymomas, rhabdoid tumors and meningiomas
Authors: Slavc Irene , Maccollin Mia M. , Dunn Michael , Jones Susan , Sutton Leslie , Gusella James F. , Biegel Jaclyn A. 
Published: February 2007

AbstractDeletions of chromosome 22 have been identified in 3 types of childhood primary brain tumor: meningiomas, rhabdoid or atypical teratoid tumors (ATT) and ependymomas. This implicates the involvement of tumor suppressor genes on chromosome 22 in the genesis of these rare tumors. One such candidate tumor suppressor gene is the recently cloned neurofibromatosis 2 (NF2) locus. The purpose of our study was to determine the frequency of germ‐line and somatic NF2 mutations in a selected group of brain tumors in children. Using single‐strand conformation polymorphism (SSCP) assays we screened 17 exons of the NF2 gene in 13 pediatric brain tumors and 9 matched normal blood DNA samples. Tumors included 3 meningiomas, 2 rhabdoid or ATTs, 7 ependymomas and 1 malignant tumor of glial lineage. In addition, lymphoblastoid cell lines from 3 patients with rhabdoid/ATT in whom no tumor tissue was available were analyzed for germ‐line mutations. Migration shifts were not detected in any of the normal DNA samples analyzed. Of the 13 tumors screened by SSCP, 1 meningioma with monosomy 22 produced a migration shift in exon 13. DNA sequencing of exon 13 revealed a deletion of a single guanine nucleotide (base 1397) in codon 466, causing a frame shift. While not all mutations might have been picked up by this technique, the data suggest that, similar to adult sporadic meningiomas, some pediatric meningiomas may result from somatic mutations in the NF2 gene. For rhabdoid tumors and ependymomas it appears that a locus distinct from NF2 might be responsible for tumorigenesis. © 1995 Wiley‐Liss, Inc.
Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas
Authors: Bellacosa Alfonso , De Feo Daniela , Godwin Andrew K. , Bell Daphne W. , Cheng Jin Quan , Altomare Deborah A. , Wan Minghong , Dubeau Louis , Scambia Giovanni , Masciullo Valeria , Ferrandina Gabriella , Panici Pierluigi Benedetti , Mancuso Salvatore , Neri Giovanni , Testa Joseph R. 
Published: February 2007

AbstractThe AKT2 gene is one of the human homologues of v‐akt, the transduced oncogene of the AKT8 virus, which induces lymphomas in mice. In previous studies, AKT2, which codes for a serine‐threonine protein kinase, was shown to be amplified and overexpressed in some human ovarian carcinoma cell lines and amplified in primary tumors of the ovary. To confirm and extend these findings, we conducted a large‐scale, multicenter study of AKT2 alterations in ovarian and breast cancer. Southern‐blot analysis demonstrated AKT2 amplification in 16 of 132 (12.1%) ovarian carcinomas and in 3 of 106 (2.8%) breast carcinomas. No AKT2 alteration was detected in 24 benign or borderline tumors. Northern‐blot analysis revealed overexpression of AKT2 in 3 of 25 fresh ovarian carcinomas which were negative for AKT2 amplification. The difference in the incidence of AKT2 alterations in ovarian and breast cancer suggests a specific role for this gene in ovarian oncogenesis. No significant association was found between AKT2 amplification and amplification of the proto‐oncogenes MYC and ERBB2, suggesting that amplification of AKT2 defines an independent subset of breast and ovarian cancers. Ovarian cancer patients with AKT2 alterations appear to have a poor prognosis. Amplification of AKT2 was especially frequent in undifferentiated tumors (4 of 8, p = 0.019), suggesting that AKT2 alterations may be associated with tumor aggressiveness. © 1995 Wiley‐Liss, Inc.
p53 and human papillomavirus dna in renal pelvic and ureteral carcinoma including dysplastic lesions
Authors: Furihata Mutsuo , Yamasaki Ichiro , Ohtsuki Yuji , Sonobe Hiroshi , Morioka Masaaki , Yamamoto Akihiro , Terao Naotami , Kuwahara Morimasa , Fujisaki Nobuta 
Published: February 2007

AbstractNinety‐eight cases of transitional‐cell carcinoma (TCC) of the renal pelvis and ureter, including dysplastic lesions, were studied for tumor incorporation of human papillomavirus (HPV) type‐16 and type‐18 DNA by in situ hybridization (ISH) with DNA probes for each HPV viral type. Immunohistochemical analysis of p53 expression was also performed. Fresh tumor tissues from 26 patients were also studied for p53 mutations in exons 4 through 9 by direct sequencing and for HPV infection by polymerase chain reaction (PCR). Thirty‐two tumors were positive for HPV DNAs, including 6 double‐positive cases. Among these tumors, adjacent dysplastic lesions in 21 cases (66%) also revealed identical reactivity. Overexpressed p53 was detected in 26 cases. Expression of p53 was also detected in dysplastic lesions in 19 out of these 26 cases (73%). Three cases were positive for both HPV DNA and p53 antibody. p53 point mutation was detected in 7 of 26 cases, 6 of which were also positive for p53. HPV type‐16 DNA was detected in 6 cases by PCR, 4 of which were also ISH‐positive. Overexpressed p53 was frequently detected in invasive and non‐papillary tumors (p < 0.01) and in high‐grade tumors (p < 0.05). HPV infection was more common in non‐invasive and papillary tumors (p < 0.05). These findings suggest that HPV infection or overex‐pression (mutation) of p53 may be an early event and be related to phenotypes of tumor‐cell growth patterns and progression. © 1995 Wiley‐Liss, Inc.