bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis and clinical implications of k‐ras gene mutations and infection with human papillomavirus types 16 and 18 in primary adenocarcinoma of the uterine cervix
Authors: Tenti Patrizia , Romagnoli Solange , Silini Enrico , Pellegata Natalia S. , Zappatore Rita , Spinillo Arsenio , Zara Carlo , Ranzani Guglielmina N. , Carnevali Luciano 
Published: February 2007

AbstractExperimental models indicate that activated ras genes and HPV oncogenic sequences may cooperate in inducing a completely transformed phenotype in epithelial cells. We searched for K‐ras gene mutations and HPV type‐16 and ‐18 sequences in 67 primary adenocarcinomas of the uterine cervix by analyzing DNAs from formalin‐fixed, paraffin‐embedded tissue samples. Target sequences were amplified by PCR and analyzed by denaturing gradient gel electrophoresis (DGGE) and sequencing for the detection of K‐ras gene mutations and by Southern blotting for the detection of HPV infection. We found 16 mutations in 15 cases; 14 were at codon 12 and 2 at codon 13; 11 were base transitions and 5 were transversions. Mutations were more frequent in mucin‐secreting than in non‐mucinous tumors. HPV oncogenic sequences were detected in 58 cases with no significant difference between K‐ras‐mutated and wild‐type tumors. HPV oncogenic sequences were also more frequent in mucin‐secreting than in non‐mucinous tumors. Both molecular events were present simultaneously in 13 out of 58 cases, all of which had histologically grade‐2 and grade‐3 tumors. Clinico‐pathological parameters of the disease and the overall survival, however, were independent of K‐ras mutations and of HPV‐16 and ‐18 infection, as shown by univariate and multivariate analysis. In contrast, stage of disease, lymph‐node metastases, deep infiltration, clear‐cell histology and low grade of differentiation were risk factors for tumor‐related death. © 1995 Wiley‐Liss, Inc.
Interphase cytogenetic analysis of erbB2 and topollα co‐amplification in invasive breast cancer and polysomy of chromosome 17 in ductal carcinoma in situ
Authors: Murphy Dermot S. , McHardy Peter , Coutts Jacqueline , Mallon Elizabeth A. , David George W. , Kaye Stanley B. , Brown Robert , Nicol Keith W. 
Published: February 2007

AbstractBreast cancer is a genetically complex disease. Fluorescence in situ hybridisation can be used to analyse the genetics of breast‐cancer progression by interphase cytogenetics. We have analysed the histological distribution of erbB2 and topollα co‐amplification in paraffin sections of invasive breast cancer and show that the co‐amplified loci share the same histological distribution in the tumour and have a similar nuclear distribution within individual nuclei. Regions of the tumours without amplification are easily recognized and tumours with erbB2 and topollα co‐amplification can be distinguished from those with erbB2 amplification alone. In addition, FISH was used to show polysomy of chromosome 17 in non‐invasive ductal carcinoma in situ of the breast and erbB2 amplification in both the invasive and non‐invasive components of a breast cancer biopsy. This report of an interphase cytogenetic analysis of non‐invasive breast carcinoma in situ demonstrates the usefulness of FISH for the genetic study of breast cancer progression. © 1995 Wiley‐Liss, Inc.
Expression of galectin‐1 in normal human thyroid gland and in differentiated and poorly differentiated thyroid tumors
Authors: Chiariotti Lorenzo , Berlingieri Maria Teresa , Battaglia Caterina , Benvenuto Giovanna , Martelli Maria Luisa , Salvatore Paola , Chiappettaxy Gennaro , Bruni Carmelo Bruno , Fusco Alfredo 
Published: February 2007

AbstractWe previously reported that galectin‐l gene expression increases up to 100‐fold in oncogene‐transformed rat thyroid cells compared with their normal counterparts and that the relative mRNA levels correlate with the degree of malignancy. In the present study we investigated whether galectin‐l is differentially expressed in human thyroid neoplasms, which range from well‐differentiated tumors to undifferentiated ana‐plastic carcinomas. We analyzed 74 human thyroid specimens of neoplastic, hyperproliferative and normal tissues and several tumor cell lines. Galectin‐l mRNA and protein levels were higher in 6 thyroid carcinoma‐derived cell lines than in normal thyroid primary cultures and adenoma cells. Galectin‐l mRNA levels increased in 28/40 papillary carcinomas and in 6/7 anaplastic carcinomas compared with normal or hyperplastic thyroid. Conversely, galectin‐l expression was unaffected in follicular carcinomas and benign adenomas. Immunohistochemi‐cal analysis of normal thyroid and papillary carcinoma sections revealed a higher content of galectin‐l protein in neoplastic follicular cells than in normal cells. © 1995 Wiley‐Liss, Inc.
p53 antibodies in the sera of lung cancer patients: Comparison with p53 mutation in the tumour tissue
Authors: Wild Christopher Paul , Ridanpaa Maaret , Anttila Sisko , Lubin Richard , Soussi Thierry , Husgafvel‐Pursiainen Kirsti , Vainio Harri 
Published: February 2007

AbstractThis study examined the sensitivity and specificity of serum auto‐antibodies to p53 protein as a non‐invasive marker of p53 genetic alterations or protein accumulation in lung cancer cases. A sensitive ELISA to detect serum p53 antibodies was developed and used to examine sera from 186 patients undergoing pulmonary surgery for a suspected lung cancer. Target antigens in ELISA were wild‐type p53 protein and 5 peptides covering the N‐ and C‐terminal parts of the protein. Sixteen sera were positive for serum p53 antibodies in both ELISAs and all were among the 136 patients with confirmed primary lung carcinoma. Of 50 patients with other pulmonary diseases, none had p53 antibodies. In 92 cancer patients exons 5 to 8 of the p53 gene were examined for mutations by denaturing gradient gel electrophoresis and direct sequencing of PCR products. Forty‐seven tumours had a p53 mutation and 7 (15.2%) of these were positive for p53 antibodies. Two patients had serum antibodies but no detectable mutation in exons 5 to 8. Frequencies of p53 mutations and serum antibodies were higher in squamous cell carcinoma patients than in adenocarcinoma. Accumulation of p53 protein in tumour tissue was observed in 32 patients, but only 5 were positive for p53 antibodies. In conclusion, serum p53 antibodies were detected only in a proportion of lung cancer cases, but the majority were specifically associated with a detectable p53 mutation in the tumour. © 1995 Wiley‐Liss, Inc.
Can a test for E6/E7 transcripts of human papillomavirus type 16 serve as a diagnostic tool for the detection of micrometastasis in cervical cancer?
Authors: Czeglédy Judit , Iosif Constantin , Hansson Bengt Göran , Evander Magnus , Gergely Lajos , Wadell Göran 
Published: February 2007

AbstractTissue from 11 cases of cervical cancer positive for human papillomavirus (HPV) type 16 DNA and 69 pelvic lymph nodes from the same patients were examined for HPV 16 DNA and mRNA from the E6/E7 genes. Five of the tumors were squamous, 3 adeno‐ and 3 adenosquamous carcinoma. From the primary tumors and the extirpated lymph nodes DNA and RNA or mRNA was subjected to PCR and RT‐PCR. Three transcription profiles (only E6*1, E6*1 and E6*11 or full‐length E6‐E7 plus both of the spliced transcripts) were found in all of the 11 HPV 16 DNA‐positive primary tumors. From the total of 69 lymph nodes analyzed 28 were positive for mRNA. HPV 16 DNA was found in 7 additional samples. Cytokeratin was found in 19 of these lymph nodes, indicating epithelial origin of tumor cells. Only 1 patient had 2 metastases evidenced by histology. These were both positive for HPV DNA and mRNA. The finding of HPV DNA, mRNA and cytokeratin in lymph nodes of patients with cervical cancer should be an indication of lymphogenically driven micrometastases of the tumor. The HPV mRNA assay should offer higher specificity than the DNA test since mRNA can be found in live cells only, while HPV DNA also can originate from dead cell material sequestered in the lymph nodes. © 1995 Wiley‐Liss, Inc.
Analysis of the gap‐related domain of the neurofibromatosis type 1 (NF1) gene in childhood brain tumors
Authors: Scheurlen Wolfram G. , Senf Leonore 
Published: February 2007

AbstractrasThe neurofibromatosis type‐1 (NF1) gene contains a 360‐bp region with significant homology to the catalytic domain of mammalian GTPase‐activating protein. This particular GAP‐related domain of the NF1 gene (NF1‐GRD) stimulates ras GTPase and inactivates ras protein p21. Therefore, it has been suggested that the NF1 gene represents another tumor‐suppressor gene. In the search for molecular markers of possible diagnostic relevance, childhood brain‐tumor specimens of different histologic diagnoses were tested for mutations of the so‐called FLR‐exon within the NF1 ‐GRD. This part of the NF1‐GRD has been shown to be most crucial for the GAP‐like function. Using a highly sensitive PCR‐SSCP technique, we tested 51 tumor specimens were tested, but found no mutations. We conclude that inactivation of this putative tumor‐suppressor gene by mutations does not play a significant role in tumorigenesis of childhood brain tumors. Next, we compared the splice variants of the NF1‐GRD in 33 brain tumors and 8 extraneural embryonal tumors. Primitive neuroectodermal tumors (PNET) (n = 10) and one intracranial teratoma were the only tumors that predominantly expressed a splice pattern that can be observed in the immature developing brain. In contrast to other embryonal neuronal tumors, this NF1‐GRD splicing pattern could not be modified in a newly established medullo‐blastoma cell line by retinoic acid treatment. Since this particular splice variant suppresses p21ras more effectively than other NF1‐GRD transcripts, its predominant expression may interfere with the physiological signal transduction of p21ras during differentiation of neurons. There may be a neurofibromin‐induced and p21ras‐mediated differentiation pathway of neuronal stem cells that is blocked in PNET. Such an arrest of a p21ras‐dependent differentiation pathway may explain the persistence of primitive pluripotent neuronal cells in PNET. © 1995 Wiley‐Liss, Inc.
Expression of α3β1 integrin receptor and its ligands in human lung tumors
Authors: Bartolazzi Armando , Cerboni Cristina , Flamini Giovanna , Bigotti Aldo , Lauriola Libero , Natali Pier Giorgio 
Published: February 2007

AbstractIncreasing experimental evidence demonstrates that malignant transformation is associated with changes in the repertoire of expression of the integrin family of molecules, which mediate cell‐matrix and cell‐cell interactions. We have analyzed immuno‐histochemically and immunochemically the expression of VLA‐3 integrin and its known ligands, namely, laminin (LM), fibronectin (FN), collagen type IV (Coll IV), nicein (NIC), and entactin/nidogen (ENT), in lung tumors of various histological types. α3β1 was detectable in normal bronchial epithelium and along basement membranes of alveolar walls. In non‐small cell lung carcinomas (NSCLC) the integrin was expressed in 82% of the cases, independently of histological type and degree of differentiation of the tumors. On the other hand, only 13% of the small cell lung carcinomas (SCLC) displayed a weak and heterogeneous distribution of the α3β1 complex. Our findings were confirmed immunochemically using long‐term tumor cell lines. While the expression of both α3β1 and ligands LM, FN, Coll IV, and Ent correlated in NSCLC with the presence of basement membranes, FN was the only ligand detectable in the stroma of SCLCs. A selective loss of nicein in basement membranes was demonstrated in NSCLC indicating an impairment of expression of this glycoprotein following malignant transformation. © 1995 Wiley‐Liss, Inc.
Microsatellite instability and pathological aspects of breast cancer
Authors: Contegiacomo Alma , Palmirotta Raffaele , De Marchis Laura , Pizzi Claudia , Mastranzo Paolo , Delrio Paolo , Petrella Giuseppe , Figliolini Marino , Bianco Angelo Raffaele , Frati Luigi , Cama Alessandro , Mariani‐Costantini Renato 
Published: February 2007

AbstractGenomic instability plays a key role in hereditary non‐polyposis colorectal cancer and in a significant sub‐set of non‐hereditary colorectal tumors. Recent evidence suggests that microsatellite instability also occurs in various sub‐sets of common, non‐hereditary forms of extra‐colorectal carcinoma. To investigate the role of microsatellite instability in breast cancer, and to correlate this type of alteration with clinico‐pathological characteristics, including tumor proliferative activity, we analyzed the status of 8 different microsatellite loci in 28 cases of primary mammary carcinoma. For this purpose, microsatellite banding patterns were compared in paired breast‐cancer/peripheral‐blood DNA samples. Microsatellite instability was observed in 6/28 (21%) of the cases. Four of the 6 tumors had low proliferative activity, one had high proliferative activity, and in one case proliferative activity values were not available. All chromosomal loci investigated demonstrated microsatellite instability in one or more representative tumors of the series. Shifts in length larger than 2 bp were the most frequent change. Microsatellite instability significantly correlated with the lobular histotype, and with lymph‐node involvement. A trend was also observed associating microsatellite instability and large tumor size. © 1995 Wiley‐Liss, Inc.
Microsatellite instability in japanese esophageal carcinoma
Authors: Nakashima Hideaki , Mori Masaki , Mimori Koshi , Inoue Hiroshi , Shibuta Kenji , Baba Kinva , Mafune Ken‐Ichi , Akiyoshi Tsuyoshi 
Published: February 2007

AbstractRecent studies have shown that microsatellite instability (MSI) may play an important role in the development of various types of cancer. However, there have been only 2 reports describing MSI in esophageal carcinoma and the clinicopathologic significance of MSI in this malignancy has not yet been clarified. To better elucidate the role of genetic instability in the development of esophageal carcinoma, we investigated the presence of MSI in 32 cases of esophageal cancer using paired samples of fresh frozen tumor and normal tissue by a method based on the polymerase chain reaction. MSI was defined as occurring in tumors which showed altered banding patterns at one or more microsatellite loci. The incidence of MSI in esophageal carcinoma was 6 out of 32 patients. MSI was observed more frequently in cases with small‐cell carcinoma (2 out of 2) than in cases with squamous‐cell carcinoma (4 out of 29). No cases with adenocarcinoma or Barrett's metaplasia were included in our series. No significant correlations between MSI and other clinicopathologic parameters were observed. The present study suggests that (I) some Japanese esophageal carcinomas certainly correlate with DNA replication error, and (2) MSI may be more frequent in small‐cell carcinoma of the esophagus than in squamous‐cell carcinoma of the esophagus. © 1995 Wiley‐Liss, Inc.
Characterization of monoclonal antibodies against stromelysin‐3 and their use to evaluate stromelysin‐3 levels in breast carcinoma by semi‐quantitative immunohistochemistry
Authors: Santavicca Maria , Noel Agnès , Chenard Marie‐Pierre , Lutz Yves , Stoll Isabelle , Segain Jean‐Pierre , Rouyer Nicolas , Rio Marie‐Christine , Wolf Catherine , Bellocq Jean‐Pierre , Basset Paul 
Published: February 2007

AbstractStromelysin‐3 (ST3) is a matrix metalloproteinase which is expressed in fibroblastic cells of most human invasive carcinomas and represents a potential new prognostic indicator. Expression of recombinant ST3 forms in Escherichia coli from cDNA constructs indicated that high levels of expression were achieved when the ST3 pro‐domain was deleted. The putative mature form of ST3 thus produced and recovered from bacterial inclusion bodies was used to prepare monoclonal antibodies (MAbs) against ST3 by immunization of BALB/C mice. Ten hybridomas producing MAbs against ST3 were obtained and analyzed for their ability to detect endogenous ST3 in breast cancer and in conditioned media from human fibroblasts. One of these MAbs (5ST‐4A9) was found to be suitable for the routine detection of ST3 on breast cancer tissue sections, thus opening the possibility to evaluate ST3 prognostic value in breast cancer using semi‐quantitative immunohistochemistry. © 1995 Wiley‐Liss, Inc.
CD44 expression patterns in breast and colon tumors: A pcr‐based study of splice variants
Authors: Rodriguez Carmen , Monges Geneviéve , Rouanet Philippe , Dutrillaux Bernard , Lefrançois Daniéle , Theillet Charles 
Published: February 2007

AbstractCD44 cell‐surface receptor expresses multiple isoforms, some of which are believed to play a role in tumor growth and metastasis. The CD44 gene is composed of 19 exons, of which 9 (exons 6 to 14) are alternatively spliced to form inclusions in the intervening membrane proximal region. Sequences present in the shortest metastatic variant cloned from a rat metastatic cell line have been shown to correspond to human exons 10 and 11, also called exons v6 and v7. Using RT‐PCR, we have addressed in detail the CD44 isoforms produced in human breast and colon tumors. We analyzed 53 breast‐tumor‐ and 58 colon‐tumor‐related samples as well as I benign mastopathy, I normal breast, 4 non‐invaded lymph nodes and 8 normal colon tissues. All tumors analyzed expressed the hemopoietic CD44 (CD44H) isoform (no alternatively spliced exons added), whereas 81% expressed the CD44E form (addition exons 12, 13 and 14). Furthermore, 85% of tumors presented complex patterns of expression, with an average number of 5 to 6 bands detected. In view of their implication in the metastatic process, we investigated in greater detail the isoforms containing exons 10 and 11 (v6 and v7). Exon 10 was more frequently expressed than exon 11, 80% and 57% of the samples respectively. The great majority of cases showed ladder‐like patterns starting from the shortest forms (exons 5‐10 or 5‐10‐11) and larger‐molecular‐weight bands corresponding predominantly to sequential inclusions of exons from 3' to 5'. Exon‐10 and exon‐11 variants were also found in one benign mastopathy. The majority of normal tissues (1 breast and 6/8 colon) expressed only the CD44H isoform. These data indicate that expression of metastatic variants is common in human breast and colon tumors and can occur early during cancer progression, as testified by their presence in a benign breast tumor. While expression of exon‐10 variants were correlated with presence of distal metastases in colon tumors, exon‐11 variants were not (metastatic events were too rare in our breast‐tumor series to reach significance). This suggest that exon 10 may correspond to the minimal sequences required to favor metastatic events. © 1995 Wiley‐Liss, Inc.
Loss of heterozygosity on chromosome 9 in human breast cancer: Association with clinical variables and genetic changes at other chromosome regions
Authors: Eiriksdottir Gudny , Sigurdsson Asgeir , Jonasson Jon Gunnlaugur , Agnarsson Bjarni A. , Sigurdsson Helgi , Gudmundsson Julius , Bergthorsson Jon Thor , Barkardottir Rosa Björk , Egilsson Valgardur , Ingvarsson Sigurdur 
Published: February 2007

AbstractPrimary breast tumors were tested for loss of heterozygosity (LOH), on chromosome 9p with microsatellite markers restricted to a 28 cM region including the MTS1 gene. LOH was found with at least I marker in 38% of the 201 cases analyzed. A high frequency of deletions was detected at the 9p23‐p21 region, indicating a tumor suppressor gene(s) important for breast cancer tumorigenesis. Tumors with and without LOH on 9p were compared with respect to clinico‐pathological factors using X2 analysis. Tumors with 9p LOH were significantly associated with high S‐phase status and aneuploidy, but not with type, node status, estrogen and progesterone receptor content or age of the patients at diagnosis. Survival analysis showed that LOH at 9p did not significantly affect the survival rate of breast cancer patients. Our results indicate that the aberrations on 9p detected in this study are not of independent prognostic value. A significant association was found between LOH at 9p and LOH at chromosomal arms 3p and 6q, which is an additional contribution toward understanding the genetic events in breast tumor pathogenesis. © 1995 Wiley‐Liss, Inc.
Life‐time risk of different cancers in hereditary non‐polyposis colorectal cancer (hnpcc) syndrome
Authors: Aarnio Markku , Mecklin Jukka‐Pekka , Aaltonen Lauri A. , Nyström‐Lahti Minna , Järvinen Heikki J. 
Published: February 2007

AbstractIdentification of hereditary non‐polyposis colorectal cancer (HNPCC) indicates theoretical life‐time risks of 50% for the descendants of an affected family member and of 100% for the true gene carriers. However, besides colorectal cancer (CRC), many other cancer types and sites are also involved, which gives reason to evaluate the magnitude of risk for various other cancer types. A detailed pedigree analysis of 40 families with HNPCC identified 414 patients affected with cancer. A Kaplan‐Meier life‐table analysis for the cumulative risk of various cancers was performed on the basis of the 293 putative gene carriers who had adequate clinical and histological documentation of their tumors. Cumulative risks were highest for colorectal (78%) and endometrial cancers (43%, women only), followed by gastric, biliary tract, urinary tract and ovarian cancers (19‐9%). For the other probably HNPCC‐related cancer types, such as small bowel carcinoma and brain tumors, the life‐time risk was only 1%. The risk of any metachronous cancer reached 90% after treatment of CRC and 75% after endometrial cancer; the second tumor was most often a new CRC or endometrial cancer. CRC remains the most important cancer type in the HNPCC syndrome but does not develop in all gene carriers. This makes the decision of possible prophylactic colectomy for test‐detected gene carriers difficult. Of the many other cancer types involved, at least endometrial cancer is common enough to necessitate a specific surveillance program. © 1995 Wiley‐Liss, Inc.
Fracture of Ni‐Ti superelastic alloy under sustained tensile load in physiological saline solution containing hydrogen peroxide
Authors: Yokoyama Ken'ichi , Ogawa Toshio , Fujita Atsushi , Asaoka Kenzo , Sakai Jun'ichi 
Published: February 2007

AbstractThe fracture of Ni‐Ti superelastic alloy has been investigated by a sustained tensile‐loading test in physiological saline solution containing hydrogen peroxide (0.15M NaCl + 0.3M H2O2). The fracture always occurs when the applied stress exceeds the critical stress for martensite transformation. In contrast, under a low applied stress, the fracture does not always occur within 1000 h. The fracture is probably mainly caused by localized corrosion associated with the preferential dissolution of nickel ions. In 0.3M H2O2 solution without NaCl, the fracture does not occur even under a high applied stress. The results of the present study imply that one reason for the fracture of the Ni‐Ti superelastic alloy in vivo is localized corrosion due to the synergistic effects of hydrogen peroxide and sodium chloride under applied stress. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res, 2007