bluuebunny/crossref_metadata_2025_split huggingface dataset:
High frequency of allelic imbalance at chromosome region 16q22‐23 in human breast cancer: Correlation with high pgr and low s phase
Authors: Skirnisdottir Sigurlaug , Eiriksdottir Gudny , Baldursson Trausti , Barkardottir Rosa B. , Egilsson Valgardur , Ingvarsson Sigurdur 
Published: February 2007

AbstractThe loss of genetic material from a specific chromosome region in tumors suggests the presence of tumor‐suppressor genes. Loss of heterozygosity (LOH) or allelic imbalance (AI) on the long arm of chromosome 16 is a known event in sporadic breast cancer. To locate the commonly deleted regions, and therefore (a) candidate tumor‐suppressor gene(s), a deletion map of chromosome 16 was made, using 10 microsatellite markers on 150 sporadic breast tumors. The 3 smallest regions of overlap (SRO) were detected on the long arm of chromosome 16. Allelic imbalance was observed with at least one marker in 67% of the tumors. One marker, D16S421, at the 16q22‐23 region, showed the highest allelic imbalance, 58%. Tumors with and without AI on 16q were tested for correlation with clinico‐pathological features of the tumors such as estrogen‐ and progesterone‐receptor content (ER and PgR), age at diagnosis, tumor size, node status, histological type, S‐phase fraction, AI on chromosome 3p, and ploidy. A correlation was found between AI on 16q and high PgR content, also low S‐phase fraction (99% confidence limits). A comparison of tumors with and without AI at the D16S421 marker locus revealed a slight correlation with high PgR content. The survival data showed no difference between patients with AI on 16q and those with a normal allele pattern on the long arm of chromosome 16. © 1995 Wiley‐Liss, Inc.
ras, p53 and hpv status in benign and malignant prostate tumors
Authors: Moyret‐Lalle Caroline , Marcais Christophe , Jacquemier Jocelyne , Moles Jean‐Pierre , Daver Alain , Soret Jean‐Yves , Jeanteur Philippe , Ozturk Mehmet , Theillet Charles 
Published: February 2007

AbstractTo study the role of ras, p53 genes and HPV virus (16 and 18) in the development of prostate cancer, we analyzed tissue sections from 27 patients affected with carcinomas (stages A to D) and from 24 patients with adenomas. Mutations of H, K and N‐ras and p53 (exons 2‐9) were studied by SSCP and DNA sequencing. Accumulation of p53 protein was studied by immu‐nohistochemistry on tissue sections. Tumors were also analyzed for the presence of HPV 16 and ‐18 sequences by PCR and DNA hybridization with sequence‐specific oligonucleotides. No mutation was found in the three ras genes studied, either in carcinomas or adenomas. By SSCP analysis we identified p53 mutations in only 2 of 19 carcinomas studied, both in exon 7. Immunohistochemical results strongly correlate with the SSCP results: p53 protein was positive in tumors with p53 mutation but not in others; 32% of studied adenomas had detectable HPV16 DNA, while 53% of carcinomas were HPV16+. Among these I presented a p53 mutation. No HPV 18 E6 sequence could be detected. Our data show that in prostate tumors from France, mutations of p53 and ras are rare events but that these tumors display detectable HPV 16 DNA at a high frequency. The low incidence of p53 mutation, associated to a significant proportion of tumors showing HPV16 DNA, could suggest that in prostate cancer HPV 16 infection could participate in p53 inactivation by E6. © 1995 Wiley‐Liss, Inc.
Detection of mage‐4 protein in lung cancers
Authors: Shichijo Shigeki , Hayashi Akihiro , Takamori Shinzo , Tsunosue Rika , Hoshino Tomoaki , Sakata Motoko , Kuramoto Terukazu , Oizumi Kotaro , Itoh Kyogo 
Published: February 2007

AbstractExpression of genes of the MAGE family, which encode tumor‐rejection antigens recognized on HLA‐AI and ‐Cw1601 by cytotoxic T lymphocytes (CTL), was investigated in lung cancers at the mRNA [MAGE‐1, ‐2, ‐3/‐6, and ‐4 (4a and/or 4b)] and protein (MAGE‐4) levels. MAGE‐1, ‐2, ‐3/‐6 and ‐4 genes were expressed, respectively, at the mRNA level in 6, 7, 20 and 7 of 53 lung cancers (50 non‐small‐cell lung cancers and 3 small‐cell lung cancers) by the reverse transcription‐polymer‐ase chain reaction (RT‐PCR) method. Polyclonal antibody (Ab) and monoclonal antibody (MAb) against recombinant MAGE‐4b protein were developed to detect MAGE‐4 protein. Both the polyclonal Ab and the R5 MAb recognized a 45‐kDa protein in extracts of MAGE‐4 mRNA‐positive lung cancers, and showed no apparent cross‐reactivity with the other MAGE gene products except with MAGE‐4a by immunoblot analyses and transfec‐tion experiments. MAGE‐4 protein was detected on 13 of 44 (30%) lung cancers (18 to 55,989 pg/mg) by ELISA with the polyclonal Ab and R5 MAb. These 13 lung cancers consisted of 6 of 6 MAGE‐4 mRNA‐detectable and 7 of 38 MAGE‐4 MRNA‐undetectable lung cancers. Histologically, these comprised 7 of 10 squamous‐cell carcinomas, 4 of 30 adenocarcinomas and 2 of 3 small‐cell lung cancers. The proportions of MAGE gene‐positive samples, at both the mRNA and protein levels, correlated with the size of the primary tumors and with regional node involvement. These results should provide important information on specific immunotherapy of lung cancers using MAGE gene products. © 1995 Wiley‐Liss, Inc.
Predictive value of statin, a g‐associated cell cycle protein, in childhood acute lymphoblastic leukemia
Authors: Volmu Manfred , Hecker Stefanie , Sauerbrey Axel , Mattern Jurgen 
Published: February 2007

AbstractBlast cells of 71 children with newly diagnosed acute lympho‐blastic leukemia (ALL) were examined with a novel monoclonal antibody (MAb), S‐44, immunoreactive to statin, a nuclear protein specifically expressed in non‐proliferating cells. The statin labeling index (LI) varied greatly from case to case and ranged from 0.3% to 86%, with a mean value of 10%. The degree of statin LI correlated inversely with the expression of Ki‐67. When patients were subdivided according to whether the statin LI was higher or lower than the mean value, patients with higher statin LI did not respond to chemotherapy and survived for a shorter period of time. Our results suggest that labeling of statin with the S‐44 MAb is a useful prognostic marker of the cytotoxic effects of anti‐cancer drugs in patients with ALL. © 1995 Wiley‐Liss, Inc.
c‐erbb growth‐factor‐receptor proteins in ovarian tumours
Authors: Simpson Barbara J. B. , Phillips Hamish A. , Lessells Alastair M. , Langdon Simon P. , Miller William R. 
Published: February 2007

AbstractImmunohistochemical expression of EGF‐R, c‐erbB‐2 and c‐erbB‐3, members of the type‐l family of receptor tyrosine kinases, were investigated in 67 primary ovarian‐tumour samples (46 malignant, 8 borderline and 13 benign), and related to tumour clinicopathological features. The incidence of all 3 receptor proteins was highest in overtly malignant tumours. No significant correlations were observed between either EGF‐R or c‐erbB‐3 and clinical parameters such as tumour stage, differentiation or extent of debulking surgery, but c‐erbB‐2 was significantly associated with several indicators of prognosis, including early stage and good/moderate differentiation in optimally debulked tumours. Multiple expression of c‐erbB receptor proteins was also significantly higher in malignant tumours compared with borderline and benign tumours. Early‐stage tumours were also more likely to express multiple c‐erbB‐receptor proteins than were late‐stage tumours. Co‐expression of EGF‐R with c‐erbB‐2, and c‐erbB‐2 with c‐erbB‐3 was significantly greater in malignant tumours than in borderline or benign tumours, and within the malignant tumour group, positive associations were observed between EGF‐R and c‐erbB‐3, also between c‐erbB‐2 and c‐erbB‐3. Because of the evidence of increased expression of individual c‐erbB proteins as well as multiple expression of this family of growth‐factor receptors in malignant ovarian tumours, we hypothesize that stimulation by the appropriate ligands may confer a selective advantage to cells expressing more than one receptor. Increased expression of c‐erbB growth‐factor receptors in malignancy may mediate increased propensity for tumour development. © 1995 Wiley‐Liss, Inc.
Expression of the mage gene family in primary and metastatic human breast cancer: Implications for tumor antigen‐specific immunotherapy
Authors: Russo Vincenzo , Traversari Catia , Verrecchia Alessandro , Mottolese Marcella , Natali Pier Giorgio , Bordignon Claudio 
Published: February 2007

AbstractSome human tumors express known antigens that can be utilized as targets for specific immunotherapy. An absolute requirement for the efficacy of this therapeutic strategy is an adequate expression of the candidate antigen by all cells of the primary and metastatic tumor. To examine the presence and distribution of tumor‐associated antigens in metastatic breast cancer, we used PCR analysis and ethidium bromide staining to test the expression of genes of the MAGE family in 28 primary tumors and related metastatic samples. Overall, samples obtained from 7 of 28 patients revealed positive. However, 2 of 3 primary tumors positive for MAGE‐1 and/or MAGE‐3 had corresponding negative metastatic lesions. On the contrary, 4 of the 25 MAGE‐negative primary tumors gave rise to positive metastatic nodes. Our results confirm in vivo, at the molecular level, the tumor‐antigen heterogeneity previously observed at the cellular level by in vitro analysis. Our data strongly suggest that, at least in patients with breast cancer, multiple different antigens would be required to optimize the recognition of neoplastic cells in immunotherapeutic protocols using MAGE products as target antigens. © 1995 Wiley‐Liss, Inc.
Immunocytochemical localization of fos protein in human breast cancers and its relationship to a series of prognostic markers and response to endocrine therapy
Authors: Gee Julia M. W. , Ellis Ian O. , Robertson John F. R. , Willsher Peter , McClelland Richard A. , Hewitt Katherine N. , Blamey Roger W. , Nicholson Robert I. 
Published: February 2007

AbstractThe nuclear transcription factor Fos is inducible by both steroid hormones and peptide growth factors. It thus forms a potential point of interaction between steroid hormone‐ and growth factor‐directed pathways and may be critical in the subversion of steroid hormone control in breast cancer. In this light, the present study has used immunocytochemistry to demonstrate in clinical primary breast cancer that Fos expression is indeed significantly associated with a failure to respond to endocrine therapy, with preliminary analysis revealing a survival advantage for those patients whose tumours lacked Fos. Sustained elevated levels of Fos expression were significantly associated with further factors, notably peptide growth factors and their receptors (e.g., EGFR, TGFα), as well as with the proliferation marker Ki‐67, which have been linked previously to endocrine insensitivity in breast cancer. In contrast, there appeared to be a trend for Fos to be absent in those tumours expressing markers of endocrine responsiveness (e.g., oestrogen receptor [ER], and also ER‐mediated markers i.e., PR, pS2 or bcl‐2). Interestingly, many of these trends were maintained in ER+ patients, suggesting that Fos may be of importance in directing loss of endocrine sensitivity in ER+ disease. © 1995 Wiley‐Liss, Inc.
Peptide‐specific ctl in tumor‐infiltrating lymphocytes from metastatic melanomas expressing mart‐1/melan‐a, gp100 and tyrosinase genes: A study in an unselected group of hla‐a2.1‐positive patients
Authors: Spagnoli Giulio C. , Schaefer Christoph , Willimann Thomas E. , Kocher Thomas , Amoroso Antonio , Juretic Antonio , Zuber Markus , Luscher Urs , Harder Felix , Heberer Michael 
Published: February 2007

AbstractPeptide specificity of cultured tumor‐infiltrating lymphocytes (TIL) was systematically investigated in a group of HLA‐A2.1+ metastatic melanoma patients consecutively referred to our department for surgical treatment. Seven samples from 6 patients were studied. All surgical specimens showed evidence of gp100, MART‐1/Melan‐A and Tyrosinose gene expression as detectable by reverse PCR (rPCR). Cultured TIL from 2 patients displayed cytotoxic activity against autologous or HLA‐matched EBV‐transformed cells previously pulsed with MART‐1/Melan‐A27‐35 peptide. In contrast, no CTL activity against gp 100280‐288 or tyrosinase1‐9 peptides could be observed. TIL were then repeatedly stimulated in vitro with the same peptides. After 6 restimulation courses at weekly intervals, specific recognition of gp100280‐288 and MART‐1/Melan‐A27‐35 peptides was detectable in 3 and 5 TIL populations, respectively. In one case Tyrosinase1‐9‐specific CTL could be demonstrated. Two TIL populations from metastases resected from a melanoma patient at 6 months' distance showed a different peptide specificity pattern, and no specific CTL could be generated from simultaneously sampled peripheral blood mononuclear cells (PBMC). All peptide‐specific CTL populations also displayed significant cytotoxic activity against HLA‐A2.1 matched melanoma cell lines expressing the antigens under investigation. Our data indicate that CTL specific for MART‐Melan‐A27‐35, gp100280‐288 or Tyrosinase1‐9 peptides could be expanded with varying frequency from TIL derived from 4 out of 6 HLA‐A2.1+ patients whose tumors expressed the genes encoding these tumor‐associated antigens (TAA). © 1995 Wiley‐Liss, Inc.
Preferential expression of the multidurg‐resistance‐associated protein (MRP) in adenocarcinoma of the lung
Authors: Sugawara Isamu , Yamada Hiroyuki , Nakamura Hisayoshi , Sumizawa Tomoyuki , Akiyama Shinichi , Masunaga Atsuko , Itoyama Shinji 
Published: February 2007

AbstractThe expression of multidrug‐resistance‐associated protein (MRP) was assessed in various types of untreated lung cancer using an immunohistochemical technique. MRP was abundantly expressed in 28 of 59 adenocarcinoma specimens (47%) and its expression was associated with the degree of glandular differentiation of the tumor. MRP expression in well‐differentiated adenocarcinomas (56%) was higher than in poorly differentiated adenocarcinomas (22%) (p < 0.01).In contrast, MRP expression in other cancer types was lower—20% in squamous‐cell carcinomas, 20% in large‐cell carcinomas and 0% in small‐cell carcinomas and carcinoids. RT‐PCR showed that the MRP‐positive adenocarcinomas and squamous‐cell carcinomas expressed mrp mRNA significantly. Immunoelectron microscopically, MRP was localized in the plasma membrane and rough endoplasmic reticulum. It is thus important to take MRP into account when considering chemotherapy for lung cancers because levels of mdr 1 gene product, another multidrugresistance gene family, are low in untreated lung cancers. © 1995 Wiley‐Liss, Inc.
MDM2 gene amplification in bone and soft‐tissue tumors: Association with tumor progression in differentiated adipose‐tissue tumors
Authors: Nakayama Tomitaka , Toguchida Junya , Wadayama Bun‐Ichiro , Kanoe Hiroshi , Kotoura Yoshihiko , Sasaki Masao S. 
Published: February 2007

AbstractWe have studied 107 bone and soft‐tissue sarcomas and 8 lipomas for amplification of the MDM2 gene. This gene was amplified in 3 out of 67 osteosarcomas, 3 out of 20 malignant fibrous histiocytomas, 4 out of 20 liposarcomas, and 4 out of 8 lipomas. The amplification was associated with overexpression of mRNA. In osteosarcomas, contrary to previous findings, all amplifications were observed in primary lesions. In liposarcomas, the amplification was seen exclusively in well‐differentiated tumors with high frequency (4/5) but not in other subtypes (0/15). In addition, MDM2 amplification was also frequently found in deep‐seated intra‐ or intermuscular lipomas (4/5). Hence, it is suggested that MDM2 amplification plays a significant role in the development of differentiated adipose‐tissue tumors. Three well‐differentiated liposarcomas with MDM2 amplification coexisted with high‐grade dedifferentiated sarcomas, in which MDM2 amplification was also observed. Interestingly, in 2 of these cases, the grades of amplification correlated with the histological grades, indicating an important role of MDM2 overexpression in tumor progression. © 1995 Wiley‐Liss, Inc.
Incidence of germ‐line p53 mutations in patients with gliomas
Authors: Li You‐Jun , Sanson Marc , Hoang‐Xaun Khê , Delattre Jean‐Yves , Poisson Michel , Thomas Gilles , Hamelin Richard 
Published: February 2007

AbstractEpidemiological studies on intracranial tumors have suggested that the observed familial aggregation of a proportion of gliomas may be due to inherited predisposition to their development. In the Li‐Fraumeni syndrome (LFS) associated with germ‐line mutations of the p53 gene, nervous‐system tumors are observed with increased frequency. However, the contribution of germ‐line p53 mutation to the incidence of brain tumors has not been investigated. In order to address this point, we have performed 2 independent investigations. First, we have examined an unselected series of brain tumors. Whenever the presence of a p53 mutation in the tumor was observed, the possible germ‐line origin of the mutation was investigated. Germ‐line p53 mutations were also analyzed in constitutional DNA of patients with gliomas that had been selected for an unusual personal or familial history of cancer. Germ‐line p53 mutations were detected in 1 out of 80 unselected cases and in 3 out of 15 selected cases (20%). We conclude that germ‐line p53 mutation may contribute to a small fraction of gliomas that develop in the general population. The presence of a personal or familial history of cancer in a patient with glioma should prompt the search for a germ‐line p53 mutation. However, the low frequency of p53 germ‐line mutation suggests that alterations of this gene may not account for most familial cases of gliomas. © 1995 Wiley‐Liss, Inc.
Risk modifiers in carriers of brca1 mutations
Authors: Narod Steven A. , Goldgar David , Cannon‐Albright Lisa , Weber Barbara , Moslehi Roxanna , Ives Elizabeth , Lenoir Gilbert , Lynch Henry 
Published: February 2007

AbstractThe majority of, but not all, women with mutations in the BRCAI gene will be affected with breast or ovarian cancer by the age of 70. To establish whether known risk factors modify susceptibility to cancer in these women, we have studied the reproductive histories of 333 North American women who were found by haplotype analysis to carry BRCAI mutations. An increased risk for breast cancer was associated with low parity and with recent birth cohort. The risk of ovarian cancer decreased with increasing age at last childbirth; however, in contrast to the case for sporadic cancer, the risk of ovarian cancer in BRCAI carriers was found to increase significantly with increasing parity. © 1995 Wiley‐Liss, Inc.
Expression of leukocyte cell adhesion molecules on gastric carcinomas: Possible involvement of lfa‐3 expression in the development of distant metastases
Authors: Mayer Barbara , Lorenz Claudia , Babic Rudolf , Jauch Karl W. , Schildberg Friedrich W. , Funke Ilona , Johnson Judith P. 
Published: February 2007

AbstractExpression of the cell adhesion molecules ICAM‐1 (CD54) and LFA‐3 (CD58) was examined on primary gastric carcinomas, autologous benign mucosa and metastatic lesions. Although ICAM‐1 was never observed on benign gastric epithelium, even in the presence of chronic inflammation and a strong leukocyte infiltrate, 38% (26/69) of the primary tumors expressed this molecule. ICAM‐1 was restricted to differentiated tumors and correlated with the presence of leukocytes and the absence of vessel invasion. The ICAM‐1 expression pattern of metastatic lesions reflected that of the primary tumor, suggesting that most tumors retain the non‐inducible phenotype seen in normal mucosa while some become cytokine‐sensitive. ICAM‐1 expression showed no correlation with tumor relapse or survival. LFA‐3 was absent from 8% (4/49) of the primary tumors and reduced (e.g., ± 50% positive cells) in 33% (16/49). Expression of LFA‐3 by more than 50% of the tumor cells correlated with cellular dedifferentiation (G3, G4), histologically detectable vessel invasion, tumor recurrence and decreased survival time. Primary tumors and metastases in draining lymph nodes demonstrated a broad range of LFA‐3 expression. In contrast, distant metastases (liver and peritoneum) had uniformly high frequencies of LFA‐3‐positive cells, suggesting a selective advantage for these cells in the establishment of distant metastases. © 1995 Wiley‐Liss, Inc.
p53 protein accumulation and the presence of human papillomavirus dna in bronchiolo‐alveolar carcinoma correlate with poor prognosis
Authors: Nuorva Kyösti , Soini Ylermi , Kamel Dia , Pöllänen Raimo , Bloigu Risto , Vähäkangas Kirsi , Pääkkö Paavo 
Published: February 2007

AbstractAccumulation of the tumour suppressor gene p53 product due to a gene mutation is frequently seen in human carcinomas, including lung carcinoma. Another indirect mechanism involving p53 in malignant growth relates to the E6 protein of the human papillomavirus (HPV), which is able to bind and degrade wild‐type p53 protein, thus eliminating its tumour suppressor activities. Bronchiolo‐alveolar carcinoma (BAC) is a rare type of lung carcinoma. The aim of our study was to examine the occurrence of p53 accumulation and the presence of HPV DNA in BAC. Sections of 22 BACs were immunohistochemically stained using a p53 antibody, CM‐1. The presence of HPV DNA in BACs was verified by in situ hybridisation for HPV types 6, 11, 16, 18, 31 and 33 and confirmed by PCR. Thirty‐six percent of the tumours showed abnormal p53 nuclear accumulation, and HPV DNA, revealed by in situ hybridisation, was found in 36%. Unexpectedly, only 13% of the type 1 BACs were positive for p53, whereas 45% of the type 2 BACs were positive. During a follow‐up of 12‐176 months, only 10% of the patients with BACs negative for both p53 and HPV died of the disease, compared with 42% of the patients with either p53 or HPV positivity. No inverse relationship between abnormal p53 protein accumulation and the presence of HPV DNA was found. © 1995 Wiley‐Liss, Inc.
Genetic alterations distinguish different types of ovarian tumors
Authors: Pieretti Maura , Cavalieri Cristina , Conway Pamela S. , Gallion Holly H. , Powell Deborah E. , Turker Mitchell S. 
Published: February 2007

AbstractSeventy‐four sporadic ovarian tumors were studied for loss of heterozygosity (LOH) and microsatellite instability (MI) with 20 polymorphic markers on chromosome 17 and at least I marker on every other chromosome. Additionally, activation of the K‐ras oncogene was examined through mutation analysis of codon 12. A majority of the tumors analyzed were low grade and/or of the mucinous histologic type. A negative correlation between LOH on chromosome 17 and K‐ras activation was observed, with the former alteration present in the majority of high grade serous and endometrioid tumors and the latter most commonly found in the mucinous and low malignant potential (LMP) tumors. In 60% of cases where LOH on chromosome 17 was present, it was observed at all informative markers, indicating chromosome loss. In these cases, frequent events of LOH were observed on the other chromosomes. When confined events of LOH were observed on chromosome 17, fewer events of LOH were observed on the other chromosomes. In the absence of LOH on chromosome 17, LOH on other chromosomes was rare. K‐ras activation was most commonly observed in tumors with no LOH events. Two endometrioid tumors and 2 mucinous tumors demonstrated MI. Our data support the involvement of different molecular pathways in the development of different types of ovarian tumors. © 1995 Wiley‐Liss, Inc.