bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lysophosphatidic acid‐regulated mitogenic ERK signaling in androgen‐insensitive prostate cancer PC‐3 cells
Authors: Kue Pao F. , Taub Jason S. , Harrington Liza Barki , Polakiewicz Roberto D. , Ullrich Axel , Daaka Yehia 
Published: November 2002

AbstractAdvanced and recurrent prostate tumors contain elevated levels of activated extracellular signal‐regulated kinases 1 and 2 (ERK) in comparison to early‐stage or benign specimens, and inhibition of ERK activation attenuates growth factor‐dependent proliferation of prostate cells, suggesting a potential regulatory role for ERK in prostate tumorigenesis. Factors responsible for ERK activation in prostate cells are not well defined. Here, we show positive cooperative interaction between the G protein‐coupled lysophosphatidic acid (LPA) and tyrosine kinase epidermal growth factor (EGF) receptors in androgen‐insensitive prostate cancer PC‐3 cells. Pre‐treatment of the PC‐3 cells with LPA decreases the dose of EGF required to elicit maximal activation of EGFR. Furthermore, treatment with LPA alone induces the rapid (maximal signal within 2 min) tyrosine phosphorylation of EGFR, and subsequent (maximal signal after 5 min) activation of ERK, suggesting that EGFR activation precedes ERK phosphorylation and may constitute a required component for signal relay from the LPA receptor to ERK. Accordingly, we show that inhibition of EGFR kinase activity attenuates the LPA‐regulated ERK activation. In addition, we find that the LPA‐regulated tyrosine phosphorylation of EGFR and activation of ERK are attenuated by batimastat, a generic inhibitor of matrix metalloproteinases (MMP). However, unlike the situation in fibroblasts, we find that the LPA‐induced transactivation of EGFR in PC‐3 cells is not mediated by shedding of heparin‐binding EGF. Together, our data show that LPA and EGF cooperate to induce mitogenic signaling in prostate cancer cells in an MMP‐regulated activation of the ERK pathway. © 2002 Wiley‐Liss, Inc.
Elevated expression of p63 protein in human esophageal squamous cell carcinomas
Authors: Hu Hai , Xia Shu‐Hua , Li Ai‐Dong , Xu Xin , Cai Yan , Han Ya‐Ling , Wei Fang , Chen Bao‐Sheng , Huang Xiao‐Ping , Han Yu‐Sheng , Zhang Jian‐Wei , Zhang Xun , Wu Min , Wang Ming‐Rong 
Published: November 2002

Abstractp63 is a recently identified homologue of the tumor suppressor gene TP53, which encodes multiple isotypes with transactivating, death‐inducing and dominant–negative activities. p63 is expressed in basal cells of squamous epithelia and many kinds of tumors. To explore the penetrance of p63 in esophageal cancer, we analyzed p63 expression in squamous cell carcinomas, adjacent dysplasia and histologically normal mucosa of the esophagus by combination of immunohistochemistry and reverse transcriptase‐polymerase chain reaction (RT‐PCR). The results showed that the ΔNp63 mRNA was easily detectable in all malignant and histologically normal tissues, whereas TAp63 presented extremely low or no expression. The p63 protein was highly expressed in 50 of 51 tumor tissues without significant difference in gender, age, stage and grade. Ten of 11 dysplasia exhibited strong p63 staining in all abnormal cells. Interestingly, p63 expression was observed in 96% (45/47) histologically normal epithelia adjacent to the cancerous tissues but only in 47% (14/30) mucosa far from tumors. Most of the epithelia far from tumors showed weaker staining than that adjacent to the cancerous tissues. In all the histologically normal epithelia with p63 expression, irrespective of the distance from the tumors, immunohistochemical reaction was restricted to the basal and suprabasal cell layers. Our data suggested that ΔNp63 is the major isotype expressed in epithelia and tumors of the esophagus. Elevated expression of p63 is probably an early event in esophageal squamous cell carcinomas, which may play a significant role in the development of the disease. © 2002 Wiley‐Liss, Inc.
Progression of microsatellite instability from premalignant lesions to tumors of the head and neck
Authors: Ha Patrick K. , Pilkington Thomas A. , Westra William H. , Sciubba James , Sidransky David , Califano Joseph A. 
Published: November 2002

AbstractThe role of microsatellite alterations other than loss of heterozygosity (LOH) in the progression of benign epithelium to head‐and‐neck squamous cell cancer (HNSCC) has not been previously described. As the severity of the dysplasia increases at the microscopic level, there is an increase in the prevalence of LOH as defined by microsatellite analysis. Other alterations have been detected in the form of microsatellite instability (MSI), represented by insertions or deletions of base pairs. It is unknown, however, whether the prevalence of these alterations likewise increases during these early stages of tumor progression. Using 6 selected markers that demonstrate a high rate of MSI and allelic imbalance in invasive head‐and‐neck cancer, we examined 111 lesions ranging from hyperplasia without atypia to invasive mucosal HNSCC. Two of 34 (5.9%) of the hyperplasias without atypia, 2/12 (16.7%) of the mild dysplasias, 2/21 (9.5%) of the moderate dysplasias, 7/26 (26.9%) of the high‐grade dysplasias/carcinomas in situ and 6/18 (33%) of the HNSCCs demonstrated microsatellite base pair length alterations. Our findings indicate that MSI becomes increasingly more common as early dysplastic lesions progress to fully malignant HNSCC and confirm this as a supplemental detection method in microsatellite analysis. © 2002 Wiley‐Liss, Inc.
Socio‐economic differences in incidence rates of cancers of the male genital organs in Finland, 1971–95
Authors: Pukkala Eero , Weiderpass Elisabete 
Published: November 2002

AbstractWe studied social class variation in the incidence of cancers of the prostate, testis, penis and scrotum among 1.1 million Finnish men (45–69 years of age) during 1971–95. The incidence of prostate cancer (6,972 cases) was increasing during the study period; the highest at all the times occurred in Social Class I (highest social class), 40–50% higher than in Social Class IV (lowest). The social class gradient was strongest in localized disease but there was some variation in incidence of non‐localized prostate cancer. A total of 174 testicular cancer cases were diagnosed during the study period. In the early 1970s, the incidence of testicular cancer in Social Class I was 5‐fold compared to Social Classes III and IV. Thereafter, the incidence rate decreased in Social Class I, but increased in the lower classes. The positive social class gradient was similar for seminomas and non‐seminomas. For penile cancer (n = 128), the incidence decreased over time and social class variation was small. Only 6 cases of scrotum cancer were observed. In testicular cancer the strong positive social class association in the early 1970s is disappearing along with converging incidence trend slopes in different social classes. The difference diminished to less than 2‐fold in the 1990s. Reasons for this observation remain open. © 2002 Wiley‐Liss, Inc.
Carcinogenesis modifier loci in rat tongue are subject to frequent loss of heterozygosity
Authors: Tanuma Jun‐ichi , Hiai Hiroshi , Shisa Hayase , Hirano Masato , Semba Ichiro , Nagaoka Shigetaka , Kitano Motoo 
Published: November 2002

AbstractRats of the DA strain are highly susceptible to 4NQO‐induced TCs, whereas WF rats are barely susceptible. In (DA × WF)F2 rats, 5 QTL, Tscc1–5, are responsible for most of the phenotypic variations, though they do not account for all of the phenotypic differences between WF and DA rats. Analysis of 40 tongue tumors >5 mm in diameter from (DA × WF)F1 rats for LOH at the Tscc loci revealed a high frequency of LOH in chromosomal regions where the Tscc2, ‐3 and ‐4 loci map. In most cases of LOH, the allele of the barely susceptible WF strain was lost, suggesting that these loci in the WF strain encode tumor‐suppressor genes. Analysis of the same tumors for somatic mutations in oncogenes indicated frequent alteration of Ha‐ras, which maps in the Tscc3 region, but rare mutation of the p15INK4B and p16INK4A genes or the p53 and Msh2 genes. Frequent LOH was also found on rat chromosomes 5 (RNO5) and 6 (RNO6). Tumors of large size accumulated LOH at multiple loci, suggesting the involvement of Tscc loci in tumor progression. © 2002 Wiley‐Liss, Inc.
Vascular endothelial growth factor mediated angiogenic potential of pancreatic ductal carcinomas enhanced by hypoxia: An in vitro and in vivo study
Authors: Sipos Bence , Weber Dirk , Ungefroren Hendrik , Kalthoff Holger , Zühlsdorff Andre , Luther Claudia , Török Virag , Klöppel Günter 
Published: November 2002

AbstractAngiogenesis in pancreatic ductal adenocarcinomas depends on the presence of angiogenic factors such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) and is thought to be stimulated by hypoxia. We tested the angiogenic potential of 9 cell lines of pancreatic ductal carcinoma origin by screening mRNA and protein expression of VEGF and bFGF and the release of VEGF into culture medium under normoxic and hypoxic (5% or 0.2% O2) conditions. Angiogenic activity was determined using 2‐ and 3‐D endothelial cell assays. Furthermore, VEGF expression and tumor vascularization were studied in human pancreatic carcinoma tissues from orthotopic xenografts and resection specimens. All cell lines expressed (mRNA, protein) and secreted VEGF, whereas bFGF was only found in 3 cell lines and was secreted into the medium in low concentrations. In addition to the dominant isoforms VEGF121,VEGF165 and VEGF189, 2 isoforms described recently, VEGF145 and VEGF183, were detected. Severe hypoxia (0.2% O2), but not moderate hypoxia (5% O2) raised VEGF mRNA expression and protein secretion in 7/9 and 5/9 cell lines, respectively. Conditioned media from 7/9, 6/9, 8/9 and 7/9 cell lines stimulated endothelial cell proliferation under normoxic (24 and 48 hr) or hypoxic (24 hr, 0.2% and 48 hr 5% O2) conditions, respectively. Conditioned media from 4/9 cell lines also induced capillary‐like sprouting under normoxic conditions and from 6/9 under hypoxic (0.2% O2) conditions. In xenografted carcinoma tissues microvessel density was found not to be increased around areas of ischemic necrosis. In resected ductal carcinomas showing tumor necrosis VEGF expression and microvessel density were only increased in 3/12 and 2/13 cases, respectively. In conclusion, in vitro most pancreatic ductal carcinomas show a distinct VEGF related angiogenic potential, as demonstrated by 2‐ and 3‐D endothelial cell proliferation, which may be promoted by severe hypoxia. Surprisingly, perinecrotic tumor areas, which are supposed to be hypoxic, only rarely showed the expected increase in microvessel density and VEGF expression. © 2002 Wiley‐Liss, Inc.
Oxidative stress has a role in malignant transformation in Barrett's oesophagus
Authors: Sihvo Eero I.T. , Salminen Jukka T. , Rantanen Tuomo K. , Rämö O. Juhani , Ahotupa Markku , Färkkilä Martti , Auvinen Merja I. , Salo Jarmo A. 
Published: November 2002

AbstractMechanisms underlying the development of oesophageal adenocarcinoma are poorly understood. To discover the role of oxidative stress and radical scavenger capacity in the malignant transformation of Barrett's oesophagus, we measured myeloperoxidase activity, superoxide dismutase activity, glutathione content and total aromatic DNA adducts. Mucosal specimens came from 52 patients in 6 groups: symptomatic gastro‐oesophageal reflux disease (GORD) without and with endoscopic oesophagitis, Barrett's epithelium without and with dysplasia, adenocarcinoma in the oesophagus and controls. In the GORD‐oesophagitis‐metaplasia‐dysplasia‐adenocarcinoma sequence, glutathione content was progressively lower and myeloperoxidase activity higher than in controls, plateauing at Barrett's epithelium without dysplasia. Only in Barrett's epithelium with dysplasia was SOD activity significantly increased. In all patient groups, DNA adduct levels were significantly higher than the control level. Though these levels between patient groups did not differ significantly, the level was highest in Barrett's epithelium without dysplasia and progressively lower in Barrett's with dysplasia and adenocarcinoma. Pooled data showed a negative correlation between glutathione content and DNA adducts (−0.28, p = 0.05). Simultaneous formation of DNA adducts, increased myeloperoxidase‐related oxidative stress, decreased antioxidant capacity (glutathione content) and the negative correlation between glutathione content and DNA adducts in the GORD–oesophagitis–metaplasia–dysplasia–adenocarcinoma sequence of Barrett's oesophagus indicate a role in the pathogenesis and malignant transformation related to oxidative stress. © 2002 Wiley‐Liss, Inc.
Oral vaccination with recombinant Listeria monocytogenes expressing human papillomavirus type 16 E7 can cause tumor growth in mice to regress
Authors: Lin Chih‐Wei , Lee Jen‐Yi , Tsao Yeou‐Ping , Shen Che‐Piao , Lai Hung‐Cheng , Chen Show‐Li 
Published: November 2002

AbstractListeria monocytogenes is a Gram‐positive, facultative intracellular bacterium with the ability to present secreted proteins to the major histocompatibility complex class I pathway to stimulate cell‐mediated immune response. In our study, we constructed the recombinant L. monocytogenes encoding human papillomavirus type 16 E7 gene (rLM‐E7). When orally administered to syngeneic mice, rLM‐E7 could induce a cytotoxic T‐lymphocyte (CTL) response. Furthermore, in vitro flow cytometric assay and in vivo immune deficiency assays showed that rLM‐E7 could prevent and eradicate tumor growth via CD8+‐dependent CTLs. Hence, the potency of rLM‐E7 as a therapeutic vaccine for cervical cancer is the result of the induction E7‐specific cell‐mediated immunity by L. monocytogenes. In addition to potency, this vaccine also offers ease of administration and reduced cost of production compared with other vaccines formulated for injection. Thus, L. monocytogenes encoding HPV‐16 E7 may be a useful oral vaccine for cervical cancer treatment. © 2002 Wiley‐Liss, Inc.
Trend of cervical cancer mortality in Belgium (1954–1994): Tentative solution for the certification problem of unspecified uterine cancer
Authors: Arbyn Marc , Geys Helena 
Published: November 2002

AbstractWe investigated the evolution of mortality from cervical cancer in Belgium between 1954 and 1994 in terms of absolute number of deaths, and standardised and age‐specific mortality rates. Changes over generations were summarised using the standardised cohort mortality ratio. Trend studies of cervical cancer mortality were hampered by certification problems. The number of deaths due to cancer of the uterine cervix is not known exactly since a substantial proportion of death causes are coded as cancer of the uterus without specifying the anatomic site: cervix or corpus uteri. This inaccuracy in codification has been corrected using distribution tables derived from countries where this certification problem is minimal. Trends in mortality from certified and corrected cervical cancers were compared. The corrected age‐standardised mortality rate decreased continuously over the last 4 decades, from over 14 to 5 per 100,000 woman‐years (slope −0.26/100,000 woman‐years, 95% CI −0.28 to −0.24). Its slope is 3.1 times (95% CI 2.9–3.5) more important than for the rate of mortality from certified cervical cancer. In addition to the almost linear decrease, substantial nonlinear cohort influences were observed in certified and corrected mortality rates. The tendency of increasing mortality in women born after 1935 required particular attention. Nevertheless, the slope of the corrected recent cohort effect remained limited in Belgium, probably as a consequence of screening. © 2002 Wiley‐Liss, Inc.
Cyclin E and p27 protein content in human renal cell carcinoma: Clinical outcome and associations with cyclin D
Authors: Hedberg Ylva , Davoodi Estela , Ljungberg Börje , Roos Göran , Landberg Göran 
Published: November 2002

AbstractAberrations in the G1‐S transition have been observed in several malignancies, suggesting that cell cycle defects are linked to the activation of oncogenes and inactivation of suppressor genes involved in the transformation process. The frequency of G1/S aberrations in human renal cell carcinoma (RCC) has not been fully clarified. We have therefore analyzed the cyclin E content, using Western blotting, in 79 RCC and 12 corresponding kidney cortex tissues as well as the fraction of p27‐positive cells in 73 RCCs, using immunohistochemistry. Most of the tumors (65%) exhibited higher cyclin E levels than corresponding normal kidney cortex tissues. However, only a small fraction of the tumors (3 of 80) had excessive levels of cyclin E when cyclin E levels were compared with proliferation. Cyclin E levels higher than the median value were associated with aneuploidy (p = 0.025), high stage (p = 0.027), high grade (p = 0.013) and high erythrocyte sedimentation rate (ESR; p = 0.005). Cyclin E was further inversely correlated with cyclin D1 (p = 0.023) and positively correlated with cyclin D3 (p = 0.003). Most tumors (76%) demonstrated a normal fraction of p27‐positive cells. There was an inverse correlation between p27 positivity and tumor size (p = 0.007), despite a lack of correlation between p27 and proliferation. Patients with p27 low tumors had a poor survival (p = 0.002). There was no correlation between p27 and cyclin E levels. In summary, the results suggest that protein expression of cyclin E and/or p27 is linked to tumor behavior. © 2002 Wiley‐Liss, Inc.
MYEOV: A candidate gene for DNA amplification events occurring centromeric to CCND1 in breast cancer
Authors: Janssen Johannes W.G. , Cuny Marguerite , Orsetti Béatrice , Rodriguez Carmen , Vallés Hélène , Bartram Claus R. , Schuuring Ed , Theillet Charles 
Published: November 2002

AbstractRearrangements of chromosome 11q13 are frequently observed in human cancer. The 11q13 region harbors several chromosomal breakpoint clusters found in hematologic malignancies and exhibits frequent DNA amplification in carcinomas. DNA amplification patterns in breast tumors are consistent with the existence of at least 4 individual amplification units, suggesting the activation of more than 1 gene in this region. Two candidate oncogenes have been identified, CCND1 and EMS1/CORTACTIN, representing centrally localized amplification units. Genes involved in the proximal and distal amplicons remain to be identified. Recently we reported on a putative transforming gene, MYEOV, mapping 360 kb centromeric to CCND1. This gene was found to be rearranged and activated concomitantly with CCND1 in a subset of t(11;14)(q13;q32)‐positive multiple myeloma (MM) cell lines. To evaluate the role of the MYEOV gene in the proximal amplification core, we tested 946 breast tumors for copy number increase of MYEOV relative to neighboring genes or markers. RNA expression levels were studied in a subset of 72 tumors for which both RNA and DNA were available. Data presented here show that the MYEOV gene is amplified in 9.5% (90/946) and abnormally expressed in 16.6% (12/72) of breast tumors. Amplification patterns showed that MYEOV was most frequently coamplified with CCND1 (74/90), although independent amplification of MYEOV could also be detected (16/90). Abnormal expression levels correlated only partially with DNA amplification. MYEOV DNA amplification correlated with estrogen and progesterone receptor‐positive cancer, invasive lobular carcinoma type and axillary nodal involvement. In contrast to CCND1 amplification, no association with disease outcome could be found. Our data suggest that MYEOV is a candidate oncogene activated in the amplification core located proximal to CCND1. © 2002 Wiley‐Liss, Inc.
Both u‐PA inhibition and vitronectin binding by plasminogen activator inhibitor 1 regulate HT1080 fibrosarcoma cell metastasis
Authors: Praus Michael , Collen Désiré , Gerard Robert D. 
Published: November 2002

AbstractOverexpression of plasminogen activator inhibitor 1 (PAI‐1) reduces tumor cell migration in vitro and metastasis in mice in vivo by mechanisms involving either inhibition of urokinase plasminogen activator (u‐PA) activity or competition for an integrin binding site on vitronectin. To analyze the effects of PAI‐1 on tumor cell migration in vitro and metastasis in vivo, recombinant adenoviral vectors expressing wild‐type or mutant PAI‐1 proteins were constructed. The mutant PAI‐1 proteins were defective in either vitronectin binding (PAI‐1VN−), plasminogen activator inhibition (PAI‐1INH−) or both (PAI‐1VN−,INH−). In vitro, migration of HT1080 human fibrosarcoma cells through a reconstituted extracellular matrix (ECM) was reduced 73% by overexpression of wild‐type PAI‐1 and 65% by PAI‐1VN− compared with control virus‐infected cells. Migration of cells infected by virus expressing either PAI‐1INH− or PAI‐1VN−,INH− was unaffected, indicating a requirement for plasminogen activator inhibitory activity. In vivo, however, only overexpression of wild‐type PAI‐1 reduced the burden of metastasis by 68% compared with the control group. This indicates that both u‐PA inhibition and PAI‐1 ECM interactions contribute to the mechanism of PAI‐1‐mediated regulation of cell migration. © 2002 Wiley‐Liss, Inc.
Possible transient adaptive response to mitomycin C in peripheral lymphocytes from thyroid cancer patients after iodine‐131 therapy
Authors: Monteiro Gil Octávia , Oliveira Nuno Guerreiro , Rodrigues António Sebastião , Laires António , Ferreira Teresa Cruz , Limbert Edward , Rueff José 
Published: November 2002

AbstractOur study attempted to assess the possible induction and persistence of an adaptive response in lymphocytes of thyroidectomized thyroid cancer patients treated with 131I (2,590 MBq, corresponding to whole body doses in the range of 200–300 mGy), to a testing dose of mitomycin C (MMC) in vitro. The cytogenetic endpoint studied was the induction of micronuclei in cytokinesis‐blocked peripheral blood lymphocytes, immediately before treatment and 1, 6 and 24 months after therapy. One month after therapy, induction of micronucleated cytokinesis‐blocked lymphocytes (‰) by MMC was lower (34.6 ± 7.7) than before therapy (52.1 ± 5.0). In 7 of 11 patients this reduction was significant. However, at 6 months, induction of micronuclei was markedly higher (133.1 ± 13.6). This significant increase was observed regardless of the decrease at 1 month. At 24 months, the frequency of micronucleated cells decreased (84.8 ± 5.5), but remained higher than before treatment. The results obtained 1 month after therapy could reflect adaptation due to radiation, or a higher rate of early apoptosis or cell death, with bone marrow suppression, visible as a lower response in vitro towards MMC. At 6 months, recovery of the lymphocyte population may occur, and higher responses to MMC in vitro could reflect higher chromosomal instability in the previously irradiated stem cells with a concomitant disappearance of adaptation, whereas at 24 months the results show a tendency to return to pretherapy values. © 2002 Wiley‐Liss, Inc.