bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of the cooperative effects of transforming growth factor α and c‐myc overexpression in rat liver epithelial cells
Authors: Presnell Sharon Collins , Thompson Melissa T. , Strom Stephen C. 
Published: February 2007

AbstractOverexpression of both transforming growth factor (TGF)‐α and c‐myc is consistently reported in hepatic tumors. We transfected rat liver epithelial cells (RLECs) with expression vectors for TGF‐α, c‐myc, or both and analyzed the morphology, biological properties, and tumorigenicity of clones that overexpressed these genes. The transfectants were morphologically indistinguishable from the parental RLECs, but the overexpression of TGF‐α resulted in changes in growth properties and an enhanced response to the mitogenic effects of hepatocyte growth factor. The concomitant overexpression of c‐myc decreased growth factor requirements of the TGF‐α/c‐myc clones compared with RLEC and TGF‐α clones. The TGF‐α and TGF‐α/c‐myc clones were tumorigenic in nude mice at frequencies of 27% and 53%, respectively, indicating that the genes cooperate in malignant transformation. However, the untransformed nature and low tumorigenicity of the transfectants suggest that transformation depends on other cellular events in addition to the overexpression of TGF‐α or c‐myc. Characterization of tumor cell lines showed that in contrast to the transfectants, the tumor clones were morphologically transformed, capable of autonomous growth and anchorage‐independent growth, and aggressively tumorigenic with a frequency of 100%. Clearly, the tumor cells differed from the transfectants and had undergone biological or genetic alterations (or both) as a consequence of the overexpression of TGF‐α or c‐myc. Our data suggest that the overexpression of TGF‐α leads to enhanced responsiveness to hepatocyte growth factor, whereas the concomitant overexpression of c‐myc confers growth‐factor independence, providing a potential explanation of the mechanisms by which the overexpression of these genes results in transformation. © 1995 Wiley‐Liss, Inc.
Allelic loss at the tuberous sclerosis 2 locus in spontaneous tumors in the Eker rat
Authors: Yeung Raymond S. , Xiao Guang‐Hui , Everitt Jeffery I. , Jin Fang , Walker Cheryl L 
Published: February 2007

AbstractSomatic events leading to the inactivation of tumor suppressor genes often involve chromosomal alterations that can be detected as loss of heterozygosity(a). In the Eker rat, spontaneous tumors of the kidney, uterus, and spleen develop as a result of a germline mutation of the tuberous sclerosis 2(Tsc2) gene. We examined the pattern and frequency of LOH at the predisposing locus in 77 primary tumors and cell lines to gain an understanding of the role of Tsc2 allelic loss in the pathogenesis of Eker‐derived tumors. Although most renal and uterine tumors(primary and cell lines) displayed LOH, splenic hemangiosarcomas did not. Although the presence of normal tissue may account for some of this difference, the possibility exists that an alternative mechanism, such as subtle mutation or gene dosage effects, may be involved during splenic tumorigenesis. Northern analysis confirmed that LOH resulted in loss of the wild‐type transcripts for the Tsc2 gene. Thus, the inactivation of both alleles plays an important role in renal and uterine tumor development, in keeping with Knudson's two‐hit hypothesis. In addition, renal tumors that retained the wild‐type allele also did not express the normal transcript, suggesting that the remaining Tsc2alleles had acquired subtle mutations resulting in loss of gene function.© 1995 Wiley‐Liss, Inc
Genetic mapping and expression analysis of the murine DNA ligase I gene
Authors: Gariboldi Manuela , Montecucco Alessandra , Columbano Amedeo , Ledda‐Columbano Giovanna M. , Savini Elena , Manenti Giacomo , Pierotti Marco A. , Dragani Tommaso A. 
Published: February 2007

AbstractWe mapped the murine DNA ligase I gene (Lig1) in the mouse genome by using a mapping panel from an interspecific cross. Lig1 mapped to a centromeric part of chromosome 7, a region homologous to human chromosome 19q, where the human homologue LIG1 was localized. In addition, Lig1 expression was analyzed during the course of mouse liver‐cell regeneration induced by partial hepatectomy, necrogenic doses of carbon tetrachloride, or the mitogen 1,4–bis[2–(3,5—dichloropyridyloxy)]benzene. The results demonstrate that Lig1 is expressed in the liver during active cell proliferation. ©1995 Wiley‐Liss, Inc.
LAR‐PTPase cDNA transfection suppression of tumor growth of neu oncogene‐transformed human breast carcinoma cells
Authors: Zhai Yifan , Wirth Julia , Kang Sanmao , Welsch Clifford W. , Esselman Walter J. 
Published: February 2007

AbstractThe incidence of amplification of neu oncogene‐encoded protein tyrosine kinase in human breast cancer strongly supports the concept that protein tyrosine phosphorylation and dephosphorylation are key regulatory mechanisms in the proliferation, differentiation, and neoplastic transformation of breast epithelial cells. We examined the potential regulatory role of protein tyrosine phosphatases (a) in the maintenance of cellular tyrosine phosphorylation by the introduction of leukocyte common‐antigen‐related PTPase (LAR‐PTPase) cDNA into a tumorigenic human breast carcinoma cell line that overexpressed p185neu protein tyrosine kinase. The transfected human breast carcinoma cells expressed elevated levels of LAR‐PTPase as assessed by reverse transcription‐polymerase chain reaction and by analysis of LAR‐PTPase protein. The LAR‐PTPase‐transfected human breast carcinoma cells had a significantly (P<0.01) slower proliferation rate in vitro than control‐trans‐fected cells. When LAR‐PTPase‐transfected cells were inoculated into athymic nude mice, a consistent and significant (P<0.05) suppression of tumor growth was observed. These results provide evidence that a specific PTPase, LAR‐PTPase, can play a suppressive regulatory role in the tumor growth of human breast carcinoma cells that overexpress p185neu protein tyrosine kinase. ©1995 Wiley‐Liss, Inc.
Cytochrome P450 2a of nasal epithelium: Regulation and role in carcinogen metabolism
Authors: Béréziat Jean‐Claude , Raffalli Francoise , Schmezer Peter , Frei Eva , Geneste Olivier , Lang Matti A. 
Published: February 2007

AbstractIn this study, we found that rat nasal coumarin‐7–hydroxylase (a) activity was two orders of magnitude higher than rat hepatic COH activity and could be induced by adding coumarin to the rats' drinking water. In western blot analysis, an anti‐cytochrome P450 (a) 2a‐5 (mouse liver COH) antibody recognized a sharp band in the microsomal fraction of rat nasal epithelium but not of the liver; the band comigrated with Cyp2a‐5. The intensity of the band was increased by the coumarin treatment. Similarly, in northern blot analysis, a cDNA probe specific for Cyp2a‐5 recognized an mRNA in the nasal epithelium having the same size as mouse liver Cyp2a‐5 mRNA; however, no hybridizable mRNA was recognized in liver preparations. Unlike the protein level, the level of the mRNA was not increased by coumarin. When northern blot analyses were performed with two oligoprobes specific for rat lung CYP2A3, an mRNA of similar size to Cyp2a‐5 mRNA was recognized. In immunoinhibition analysis, anti‐Cyp2a‐5 antibody inhibited rat nasal COH activity and aflatoxin B1 (AFB1) metabolism completely. It inhibited N‐nitrosodiethylamine (a) and 4‐ (a) ‐1‐(3‐pyridyl)‐1‐butanone (a) metabolism by 80–90%. In contrast, the hepatic metabolism of the four compounds was not affected by the antibody. When coumarin instead of anti‐Cyp2a‐5 antibody was used, a strong but variable inhibition of the nasal metabolism of AFB1, NDEA, and NNK was seen. The results suggest that an enzyme or enzymes similar to mouse liver Cyp2a‐5, one of which may be CYP2A3, is expressed at high levels in rat nasal epithelium but not in the liver and that its expression is increased by coumarin, an odorant and a substrate of Cyp2a‐5. The increase probably occurs by protein stabilization or stimulation of translation. The results also show that the enzyme has a key role in the nasal metabolism of three well‐known carcinogens, AFB1, NDEA, and NNK and may therefore be an important contributing factor in nasal carcinogenesis.©1995 Wiley‐Liss, Inc.
Identification of protein kinase C ζ isozyme in hamster pancreas and pancreatic carcinoma cell lines
Authors: Nair Satish C. , Pour Parvis M. , Lawson Terence , Kolar Carol , Vaughn Rick , Birt Diane F. 
Published: February 2007

AbstractCellular differentiation and proliferation are dependent upon phosphorylation by endogenous protein kinase C (a) isozymes in many cell types. Western blotting with a C‐terminally directed rabbit polyclonal anti‐PKC ζ antibody detected a doublet of approximately 81 kDa in normal hamster pancreatic tissue and hamster pancreatic carcinoma (PC‐1) and human pancreatic carcinoma (PANC‐1) cells, Preabsorption of the antibody with the specific peptide blocked the appearance of the 81–kDa band, indicating that the band was specifically recognized by the PKC ζ antibody. In contrast, antibodies for PKC α, β, γ, δ, and ϵ failed to show specific immunoreactivity for normal pancreatic tissue or PANC‐1 or PC‐1 cells. Immunocytochemical analysis identified PKC ζ in the cytoplasm of ductules and large ducts, to a lesser extent in the islets of the hamster pancreas, and in the normal cultured pancreatic duct epithelial cells and pancreatic carcinoma (PANC‐1 and PC‐1) cell lines. Specific reactivity was seen by electron microscopy in the ductal cells of the normal pancreatic tissue. In normal pancreatic ductal tissue and primary pancreatic ductal hyperplasia and carcinoma, the proportional labeling of PKC ζ in nuclei and cytoplasm was similar. Our results demonstrating the presence of PKC ζ isozyme in the normal pancreas, cultured normal pancreatic duct epithelial cells, and pancreatic carcinoma cells or carcinoma tissue suggests a role for this isozyme in the normal physiology of the pancreas and perhaps in pancreatic carcinoma. © 1995 Wiley‐ Liss, Inc.
A unique spectrum of p53 mutations in B‐cell chronic lymphocytic leukemia distinct from that of other lymphoid malignancies
Authors: Newcomb Elizabeth W. , Rouby Soumaya El , Thomas Anju 
Published: February 2007

AbstractThe spectrum and pattern of p53 mutations detected in 42 cases of B‐cell chronic lymphocytic leukemia (B‐CLL) were analyzed, and several interesting features were noted. Codon 209 in the p53 gene may be a new hot‐spot for p53 mutation in B‐CLL disease. Four of the 42 (10%) reported B‐CLL p53 mutations occurred at codon 209 versus none in 214 cases of other lymphoid malignancies screened for p53 mutations (P = 0.0006). Transversion mutations predominated at codon 273 rather than the transition mutations that are known to occur at this CpG site. Four of six (67%) B‐CLL cases had transversions at codon 273 compared with two of 17 (12%) of all other lymphoid tumors examined (P = 0.02). In addition, over 65% of the p53 mutations detected in B‐CLL showed a strand bias for p53 mutations on the untranscribed DNA strand. This feature of DNA strand bias is notable in cancers of the lung, esophagus, and head and neck, which may result from high exposure to carcinogens. This spectrum of p53 mutations in B‐CLL together with the high frequency of transversion mutations and DNA strand bias may implicate environmental carcinogens associated with p53 gene damage in some B‐CLL patients. © 1995 Wiley‐ Liss, Inc.
Mutational specificity of 1‐(2‐chloroethyl)‐3‐cyclohexyl‐1‐nitrosourea in the Escherichia coli lacl gene of O6‐alkylguanine‐DNA alkyltransferase‐proficient and ‐deficient strains
Authors: Jurado Juan , Ferrezuelo Francisco , Pueyo Carmen 
Published: February 2007

AbstractForward mutations induced by 1‐(2‐chloroethyl)‐3‐cyclohexyl‐1‐nitrosourea (a) in the lacl gene of Escherichia coli were recovered from bacteria proficient (Ogt+ Ada+) and deficient (Ogt− Ada−) in O6‐alkylguanine‐DNA alkyltransferase activity. A CCNU dose of 1 mM was selected for DNA sequence analysis. A total of 245 induced mutations were characterized. The mutations were almost exclusively (95%) GC→AT transitions, indicating that CCNU‐induced mutations arose in bacteria primarily from misreplication of O6‐chloroethylguanine, in total agreement with results obtained for monofunctional alkylating agents. The distribution of CCNU‐induced GC→AT mutations was significantly altered by the presence of DNA alkyltransferase activity (P = 0.01). In the Ogt+ Ada+ mutational spectrum, guanines flanked on both sides by A:T base‐pairs were on average 2.8 times more likely to mutate than those flanked by G:C base‐pairs on at least one side. This bias disappeared in the Ogt− Ada− genetic background, thereby providing evidence that O6‐chloroethylated guanines adjacent to G:C base‐pairs are better targets for bacterial alkyltransferase than those not adjacent to G:C base‐pairs. We recently reported a similar bias for ethyl methanesulfonate, strengthening the idea that CCNU is acting as a simple ethylating compound. In summary, this paper presents for the first time evidence that DNA repair by O6‐alkylguanine‐DNA alkyltransferases plays a major role in removing lesions responsible for GC→AT transitions induced by CCNU, influencing their ultimate distribution with respect to sequence Context. © 1995 Wiley‐ Liss, Inc.
Use of wild‐type p53 to achieve complete treatment sensitization of tumor cells expressing endogenous mutant p53
Authors: Gjerset Ruth A. , Turla Sally T. , Sobol Robert E. , Scalise Jason J. , Mercola Dan , Collins Heli , Hopkins Penelope J. 
Published: February 2007

AbstractIt is known that transfer of the wild‐type p53 gene into p53‐negative cells from transgenic mice increases their sensitivity to drug and radiation‐induced apoptosis. However, unlike many human tumors, these transgenic cells do not express mutant p53, and it is not known from these earlier studies whether wild‐type p53 dominates the effects of mutant p53 with respect to drug and radiation sensitivity. We addressed this question in glioblastoma, a disease characterized by an unusually high level of intrinsic resistance to therapy and poor prognosis: mean survival time from diagnosis is only about 1 yr. We introduced the gene for wild‐type p53 into human T98G glioblastoma cells, which express endogenous mutant p53 but not wild‐type p53. Stable transfectants that co‐expressed mutant and wild‐type p53 had enhanced sensitivity to cisplatin and gamma radiation, compared with parental cells, control vector‐transduced cells, and transduced cells that had lost expression of wild‐type p53. Transient wild‐type p53 expression after high‐efficiency gene transfer by a p53 adenovirus also sensitized the cells to cisplatin and correlated with the induction of apoptosis. The sensitization effect was also observed in p53 adenovirus‐infected H23 small cell lung carcinoma cells, which express endogenous mutant p53. Therefore, wild‐type p53 gene transfer has dominant effects over mutant p53 in sensitizing tumor cells to therapy, which supports the potential of p53 gene therapy to enhance the efficacy of traditional therapy. © 1995 Wiley‐ Liss, Inc.
High frequency of ki‐ras amplification and p53 gene mutations in adenocarcinomas of the human esophagus
Authors: Galiana Corinne , Lozano Jean‐Claude , Bancel Brigitte , Nakazawa Hisayoshi , Yamasaki Hiroshi 
Published: February 2007

AbstractMutated ras genes have been found to be conspicuously absent from primary tumors of the esophagus, although high expression of ras p21 oncoprotein in some esophageal squamous cell carcinomas and mutations of the Ki‐ and Ha‐ras genes in esophageal carcinoma cell lines have been reported. In this study, we found amplification of the Ki‐ras gene in four of 10 esophageal adenocarcinomas (40%). No such amplification was observed among 61 squamous cell carcinomas, one pseudosarcomatous carcinoma, and eight esophageal cell lines, nor in six adenocarcinomas of the stomach. In two samples on which immunohistochemical analysis could be performed, we found overexpression of Ki‐ras proteins when compared with normal samples. This Ki‐ras amplification in esophageal tumors did not correlate with any pathological feature of the tumors, with the survival of the patients, or with the presence of other genetic alterations. These findings provide the first evidence for amplification of the Ki‐ras gene in human esophageal cancer, which is restricted to adenocarcinomas. We also found that six of eight adenocarcinomas had point mutations in the p53 gene; this is a considerably higher prevalence than that reported for esophageal squamous cell carcinomas. These results strongly suggest that esophageal adenocarcinomas differ from squamous cell carcinomas in their molecular genetic characteristics. © 1995 Wiley‐ Liss, Inc.
Induction of karyotype instability in a murine tumor cell line by quercetin, 2‐amino‐1‐methyl‐6 phenylimidazo[4,5‐ b]pyridine, and okadaic acid, as revealed by transmission distortion of the inactive X chromosome
Authors: Kuwabara Katsuhiro , Odani Sumiko , Takahashi Yoshiaki , Arakawa Masaaki , Takagi Nobuo , Nagao Minako , Kominami Ryo 
Published: February 2007

AbstractQuercetin, 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (a), and okadaic acid are found in various foods and have been shown to have mutagenic or promoter‐like activity. The effects of these three compounds on the transmission of the inactive × chromosome were examined in MST‐C6 murine tumor cells, which were derived from hybrid F1 mice from matings between C57BL/6 and MSM mice. Polymerase chain reaction analysis using polymorphic markers on the × chromosome detected transmission distortion of the inactive × chromosome due to nondisjunction as a copy‐number imbalance in allelic bands. The cells exposed to all three chemicals (but not untreated cells) exhibited such imbalances at high frequencies under exposure conditions similar to those in previous experiments in which tumor progression and recombination were observed. The cells also showed increased frequencies of tumor formation when subcutaneously injected. These results suggest that the three chemicals are capable of inducing transmission distortion of the inactive × chromosome and that such activity may be a causative factor in promoting the tumorigenicity of MST‐C6 cells. © 1995 Wiley‐ Liss, Inc.
Reference urodynamic values for stress incontinent women
Authors: Nager C.W. , Albo M.E. , FitzGerald M.P. , McDermott S. , Wruck L. , Kraus S. , Howden N. , Norton P. , Sirls L. , Varner E. , Zimmern P. ,   for the Urinary Incontinence Treatment Network
Published: February 2007

AbstractObjectiveTo determine reference urodynamic values for preoperative urodynamic studies in women undergoing surgery for pure or predominant stress urinary incontinence (SUI).Materials and MethodsSix hundred fifty‐five women with pure or predominant SUI were enrolled in a multicenter surgical trial and were randomized to undergo a Burch or autologous fascia sling procedure as part of the Urinary Incontinence Treatment Network (UITN) Stress Incontinence Surgical Treatment Efficacy Trial (SISTEr). Preoperative free uroflowmetry, filling cystometry, and pressure flow studies were performed in all women using a standardized research protocol and standardized urodynamic interpretation guidelines. We define the normal range of urodynamic values in this population as the values that encompass 95% of the results.ResultsIn 655 women undergoing filling cystometry in the standing position, baseline vesical and abdominal pressures were between 12 and 60 cm H2O. The upper limit of detrusor pressure increase during bladder filling to maximum cystometric capacity was 16 cm H2O. Ten percent of women who qualified for stress incontinence surgery with a positive cough stress test on physical exam did not demonstrate urodynamic stress incontinence (USI) and less than 10% of subjects in this study demonstrated detrusor overactivity.ConclusionsResults from a large cohort of women with SUI are now available for quantitative plausibility assessments or as reference values when interpreting urodynamic studies. Neurourol. Urodynam. 26:333–340, 2007. © 2007 Wiley‐Liss, Inc.
Current status of functional MRI on small animals: application to physiology, pathophysiology, and cognition
Authors: Van der Linden Annemie , Van Camp Nadja , Ramos‐Cabrer Pedro , Hoehn Mathias 
Published: February 2007

AbstractThis review aims to make the reader aware of the potential of functional MRI (fMRI) in brain activation studies in small animal models. As small animals generally require anaesthesia for immobilization during MRI protocols, this is believed to be a serious limitation to the type of question that can be addressed with fMRI. We intend to introduce a fresh view with an in‐depth overview of the surprising number of fMRI applications in a wide range of important research domains in neuroscience. These include the pathophysiology of brain functioning, the basic science of activity, and functional connectivity of different sensory circuits, including sensory brain mapping, the challenges when studying the hypothalamus as the major control centre in the central nervous system, and the limbic system as neural substrate for emotions and reward. Finally the contribution of small animal fMRI research to cognitive neuroscience is outlined. This review avoids focusing exclusively on traditional small laboratory animals such as rodents, but rather aims to broaden the scope by introducing alternative lissencephalic animal models such as songbirds and fish, as these are not yet well recognized as neuroimaging study subjects. These models are well established in many other neuroscience disciplines, and this review will show that their investigation with in vivo imaging tools will open new doors to cognitive neuroscience and the study of the autonomous nervous system in experimental animals. Copyright © 2007 John Wiley & Sons, Ltd.
Scapular development from the neonatal period to skeletal maturity: A preliminary study
Authors: Rissech C. , Black S. 
Published: February 2007

AbstractAn understanding of the basic growth rates and patterns of development for each element of the human skeleton is important for a thorough understanding and interpretation of data in all areas of skeletal research. Yet surprisingly little is known about the detailed ontogenetic development of many bones, including the scapula. With the intention of describing the changes that accompany postnatal ontogeny in the scapula and algorithms to predict sub‐adult age at death, this communication examines the development of the scapula through nine measurements (3 from the glenoidal area, 4 from the body and 2 related to the spinous process) by polynomial regression. Data were collected from 31 of the individuals that comprise the Scheuer Collection, which is housed at the University of Dundee (Scotland).Four of the derived mathematical curves (scapular length, infra‐ and suprascapular height and spine length) displayed linear growth, whilst three (maximum length of the glenoid mass, acromial width and scapular width) were best expressed by a second‐degree polynomial and two (maximum and middle diameter of the glenoidal surface) by a third‐degree polynomial. All single measurements proved useful in the prediction of age at death, although derived indices proved to be of limited value. In particular, scapular width, suprascapular height and acromial width showed reliable levels of age prediction until late adolescent years. Copyright © 2007 John Wiley & Sons, Ltd.