bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microarray analysis of the differential transformation mediated by Kirsten and Harvey Ras oncogenes in a human colorectal adenocarcinoma cell line
Authors: Roberts Michael L. , Drosopoulos Konstantinos G. , Vasileiou Ioannis , Stricker Mona , Taoufik Era , Maercker Christian , Guialis Apostolia , Alexis Michael N. , Pintzas Alexander 
Published: September 2005

AbstractColorectal cancer arises after a series of mutational events in the colon epithelia and is often used as a model of the multistep progression of tumorigenesis. Mutations in Ki‐Ras have been detected in some 50% of cases and are thought to occur at an early stage. Almost never do mutations arise in the loci of other Ras isoforms (Ha‐ and N‐), leading to the assumption that Ki‐Ras plays a unique role in tumorigenesis. In order to examine the distinctive function that Ki‐Ras plays in cancer development in the colon, we introduced constitutively active mutant Ki‐ and Ha‐Ras genes into an intermediate‐stage colon adenoma cell line (Caco‐2). We found that mutant active Ha‐RasV12 was more efficient at transforming these colon epithelial cells as assessed by anchorage‐independent growth, tumor formation in SCID mice and the development of mesenchymal morphology compared to transformation by Ki‐RasV12. We conducted microarray analysis in an attempt to reveal the genes whose aberrant expression is a direct result of overexpression of either Ki‐RasV12 or Ha‐RasV12. We used Clontech's Atlas cancer cDNA (588 genes) and RZPD's Onco Set 1 (1,544 genes) arrays. We identified fewer genes that were commonly regulated than were differentially expressed between Ki‐ and Ha‐RasV12 isoforms. Specifically, we found that Ki‐RasV12 regulated genes involved in cytokine signaling, cell adhesion and colon development, whereas Ha‐RasV12 mainly regulated genes involved in controlling cell morphology, correlating to an epithelial‐mesenchymal transition only observed in these cells. Our results demonstrate how 2 Ras isoforms regulate disparate biologic processes, revealing a number of genes whose deregulated expression may influence colon carcinogenesis (supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020‐7136/suppmat/index.html). © 2005 Wiley‐Liss, Inc.
Loss of p63 and cytokeratin 5/6 expression is associated with more aggressive tumors in endometrial carcinoma patients
Authors: Stefansson Ingunn M. , Salvesen Helga B. , Akslen Lars A. 
Published: September 2005

Abstractp63 and cytokeratin (CK) 5/6 are markers of basal and squamous differentiation in several normal epithelia and human tumors and are also suggested to be markers of progenitor or stem cells in certain stratified epithelia. In endometrial carcinoma, there is very limited information about the expression pattern of p63 or CK5/6 and no prognostic information. The aim of our study was to examine whether the expression of these markers was associated with a certain tumor phenotype in terms of other biomarkers, clinicopathologic characteristics and patient prognosis. Immunohistochemical expression of p63 and CK5/6 was examined using tissue microarrays (TMAs) in a large population‐based series of 276 endometrial carcinomas with long and complete follow‐up. Selected cases of normal and hyperplastic endometrium were examined for comparison (n = 15). Absence of p63 expression (70%) was significantly associated with nonendometrioid carcinomas, high histologic grade (FIGO), higher mitotic count and tumor cell proliferation by Ki‐67, microsatellite instability (MSI) and loss of hMSH6 expression. A tendency toward reduced patient survival was also seen (p = 0.098). Presence of CK5/6 expression was more frequent in endometrioid tumors with squamous differentiation, while loss of CK5/6 expression (54%) was significantly associated with high FIGO stage, reduced β‐catenin expression, MSI and reduced patient survival (p = 0.0001); the latter was also found within the endometrioid subgroup (p = 0.0004). Multivariate survival analysis revealed that loss of CK5/6 expression had an independent prognostic impact in addition to well‐known prognostic variables. Expression of both markers was increased in simple hyperplasia compared with normal endometrium. In complex hyperplasia, p63 expression was also increased, whereas CK5/6 was positive in areas with squamous differentiation only. Thus, loss of p63 or CK5/6 was associated with features of aggressive tumors, and lack of CK5/6 was significantly associated with reduced survival in multivariate analysis. © 2005 Wiley‐Liss, Inc.
Indole‐3‐carbinol activates the ATM signaling pathway independent of DNA damage to stabilize p53 and induce G1 arrest of human mammary epithelial cells
Authors: Brew Christine T. , Aronchik Ida , Hsu Jocelyn C. , Sheen Joon‐Ho , Dickson Robert B. , Bjeldanes Leonard F. , Firestone Gary L. 
Published: September 2005

AbstractThe phytochemical indole‐3‐carbinol (I3C), from cruciferous vegetables such as broccoli, has been shown to elicit a potent anti‐proliferative response in human breast cancer cell lines. Treatment of the immortalized human mammary epithelial cell line MCF10A with I3C induced a G1 cell cycle arrest, elevated p53 tumor suppressor protein levels and stimulated expression of downstream transcriptional target, p21. I3C treatment also elevated p53 levels in several breast cancer cell lines that express mutant p53. I3C did not arrest MCF10A cells stably transfected with dominant‐negative p53, establishing a functional requirement for p53. Cell fractionation and immunolocalization studies revealed a large fraction of stabilized p53 protein in the nucleus of I3C‐treated MCF10A cells. With I3C treatment, phosphatidyl‐inositol‐3‐kinase family member ataxia telangiectasia‐mutated (ATM) was phosphorylated, as were its substrates p53, CHK2 and BRCA1. Phosphorylation of p53 at the N‐terminus has previously been shown to disrupt the interaction between p53 and its ubiquitin ligase, MDM2, and therefore stabilizing p53. Coimmunoprecipitation analysis revealed that I3C reduced by 4‐fold the level of MDM2 protein that associated with p53. The p53–MDM2 interaction and absence of p21 production were restored in cells treated with I3C and the ATM inhibitor wortmannin. Significantly, I3C does not increase the number of 53BP1 foci or H2AX phosphorylation, indicating that ATM is activated independent of DNA double‐strand breaks. Taken together, our results demonstrate that I3C activates ATM signaling through a novel pathway to stimulate p53 phosphorylation and disruption of the p53–MDM2 interaction, which releases p53 to induce the p21 CDK inhibitor and a G1 cell cycle arrest. © 2005 Wiley‐Liss, Inc.
Tetracycline analogues (doxycycline and COL‐3) induce caspase‐dependent and ‐independent apoptosis in human colon cancer cells
Authors: Onoda Toshinao , Ono Takashi , Dhar Dipok Kumar , Yamanoi Akira , Nagasue Naofumi 
Published: September 2005

AbstractTetracycline analogues (TCNAs) possess cytotoxic activities as well as matrix metalloproteinase (MMP) inhibitory properties. Previously, we demonstrated that doxycycline (DOXY) could induce apoptosis in human HT29 colon cancer cells. In present study, the molecular apoptotic mechanisms induced by two kinds of TCNAs, designated as DOXY and COL‐3 (chemically modified tetracycline‐3; 6‐demethyl, 6‐deoxy, 4‐dedimethylamino tetracycline), were evaluated in cultured HT29 cells. Both TCNAs inhibited the proliferation of 6 different colorectal cancer cell lines in a dose‐dependent manner. Especially, COL‐3 had a stronger effect on cancer cells than DOXY. Apoptotic changes were actually observed by 10 μg/ml COL‐3 and 20 μg/ml DOXY in a time‐dependent manner. COL‐3 produced the increase in cytosolic cytochrome c and the loss of mitochondrial membrane potential after 3 hr treatment, and thereafter activated caspases. In case of DOXY, these changes were observed after 24 hr. Bax translocation was not a prerequisite for cytochrome c releasing in COL‐3 treatment. Pretreated pancaspase inhibitor (Z‐VAD‐FMK) reduced COL‐3 and DOXY mediated apoptosis up to 81.3 and 35.3%, as compared with nontreated cells, respectively. These data indicated that TCNAs could induce mitochondria‐mediated apoptosis through both caspase‐dependent and ‐independent pathway. In fact, endonuclease G and apoptosis‐inducing factor were released into cytosol after the treatment of TCNAs, which indicated that caspase‐independent apoptotic pathway is also one of the key mechanisms for the treatment of TCNAs. Taken together, we believe that TCNAs could have strong potentials for clinical application in treating colorectal cancers and improve cancer chemotherapy. © 2005 Wiley‐Liss, Inc.
Detection of human papillomavirus type 18 E6 and E7‐specific CD4+ T‐helper 1 immunity in relation to health versus disease
Authors: Welters Marij J.P. , van der Logt Pauline , van den Eeden Susan J.F. , Kwappenberg Kitty M.C. , Drijfhout Jan Wouter , Fleuren Gert Jan , Kenter Gemma G. , Melief Cornelis J.M. , van der Burg Sjoerd H. , Offringa Rienk 
Published: September 2005

AbstractThe most common high‐risk human papillomavirus types, HPV16 and 18, differ markedly with respect to their interaction with the host. Clearance of HPV18 infections generally takes longer and HPV18‐positive cancers have a poorer prognosis. We therefore evaluated Th1‐type immunity against the E6 and E7 oncoproteins of HPV18 in healthy subjects and in patients with HPV18‐positive genital cancer, and compared the results to our previously obtained data for HPV16. Approximately 20% of the healthy individuals displayed immunity against HPV18 E6. In contrast, none of the patients showed such responses, despite the presence of HPV18‐positive lesions. Several of the patients did respond to HPV18 E7, whereas this immunity is rarely found in healthy subjects. This pattern of immune reactivity is essentially similar to that previously found for HPV16. It is unlikely that this similarity is the result of immunological cross‐reactivity between the E6 and E7 antigens of HPV types 16 and 18. Our data confirm the relation between failure of E6‐specific Th1 immunity and high‐risk HPV‐induced cervical neoplasia and argue that parameters other than these determine the differences in pathological impact between HPV types 16 and 18. © 2005 Wiley‐Liss, Inc.
Genetic and epigenetic inactivation of LTF gene at 3p21.3 in lung cancers
Authors: Iijima Hironobu , Tomizawa Yoshio , Iwasaki Yasuki , Sato Koji , Sunaga Noriaki , Dobashi Kunio , Saito Ryusei , Nakajima Takashi , Minna John D. , Mori Masatomo 
Published: September 2005

AbstractAllelic loss on the short arm of chromosome 3 is one of the most common events in the pathogenesis of lung cancer. The lactotransferrin gene (LTF, also referred to as the lactoferrin gene, LF) is located at 3p21.3 common eliminated region 1, which is frequently deleted in lung and other cancers. The expression of the LTF gene was absent in 16 (59%) of 27 small cell lung cancer cell lines, 33 (77%) of 43 nonsmall‐cell lung cancer (NSCLC) cell lines and 7 (54%) of 13 primary NSCLC, while LTF mRNA was overexpressed in 3 (7%) of 43 NSCLC cell lines. Its expression was restored by treatment with 5‐aza‐2′‐deoxycytidine (5‐aza‐dC), trichostatin A (TSA) or a combination of both in a subset of lung cancer cell lines without LTF expression. In addition, we found 8 different types of nucleotide substitutions and one frameshift mutation. These results indicate that the LTF gene is inactivated by genetic and epigenetic mechanisms in lung cancer. © 2005 Wiley‐Liss, Inc.
Genetic variants in the MDM2 promoter and lung cancer risk in a Chinese population
Authors: Hu Zhibin , Ma Hongxia , Lu Daru , Qian Ji , Zhou Jiannong , Chen Yijiang , Xu Lin , Wang Xinru , Wei Qingyi , Shen Hongbing 
Published: September 2005

AbstractOverexpression of MDM2 may attenuate the P53 stress response pathway through direct blocking of P53 transcriptional activity and mediating P53 degradation. Two promoter polymorphisms (one is a T to G substitution at the intronic P53‐response promoter, and the other is a 40‐bp insertion/deletion polymorphism in the constitutive promoter) were identified, and recently the T/G substitution (SNP309) has been demonstrated to alter the levels of MDM2 gene products. In this molecular epidemiological study with 717 incident lung cancer cases and 1,083 cancer‐free controls, we genotyped these 2 promoter polymorphisms of MDM2 and evaluated their associations with risk of lung cancer. We found that there were no significant associations between MDM2 SNP309 variant genotypes and lung cancer risk (adjusted OR = 1.20, 95% CI = 0.95–1.53 for TG and adjusted OR = 1.12, 95% CI = 0.85–1.48 for GG, respectively). Similarly, we did not find evidence for any association between risk of lung cancer and MDM2 insertion/deletion polymorphism. The findings suggest that these two MDM2 promoter polymorphisms may not play a major role in lung cancer susceptibility in this Chinese population. © 2005 Wiley‐Liss, Inc.
ADAMTS8 and ADAMTS15 expression predicts survival in human breast carcinoma
Authors: Porter Sarah , Span Paul N. , Sweep Fred C.G.J. , Tjan‐Heijnen Vivianne C.G. , Pennington Caroline J. , Pedersen Tanja X. , Johnsen Morten , Lund Leif R. , Rømer John , Edwards Dylan R. 
Published: September 2005

AbstractWe recently undertook expression profiling of all 19 human ADAMTS metalloproteinases (a disintegrin and metalloproteinase with thrombospondin motifs) in malignant and non‐neoplastic breast tissue and showed that 11 of the ADAMTS genes are dysregulated in breast carcinoma. We identified a subgroup of ADAMTSs, based on functional and amino acid sequence similarity (ADAMTS1, 4, 5, 8 and 15), to be the focus of further study in breast carcinoma. Further RNA expression analysis by real‐time PCR on a different cohort of 229 patients with breast cancer has identified ADAMTS8 as a predictor of poor overall survival (OS) (hazard ratio (HR) = 2.20, 95% C.I. = 1.29–3.74, p = 0.004) and confirmed ADAMTS15 as a predictor of prolonged relapse‐free survival (RFS) (HR = 0.54, 95% C.I. = 0.32–0.89, p = 0.016). We explored the differences in survival of the 4 groups that could be categorized based on the expression levels of ADAMTS8 and ADAMTS15. For both RFS and OS, the group with high ADAMTS8 and low ADAMTS15 expression had a particularly poor prognosis. This group had a 3‐fold higher chance of recurrence (HR = 3.03, 95% C.I. = 1.49–6.15, p = 0.001) and a greater than 5‐fold higher chance of death (HR = 5.40, 95% C.I. = 2.16–13.5, p < 0.001) than the most favorable prognostic group. This prediction of poor prognosis by ADAMTS8 and ADAMTS15 expression was found to be independent of other classical clinicopathological factors. Results observed in FVB‐PyMT mice, a robust transgenic model of highly metastatic breast carcinoma, fitted the expectation that relatively high expression levels of ADAMTS8 together with low expression levels of ADAMTS15 seen in human breast carcinoma are associated with a poor clinical outcome. In summary, ADAMTS8 and ADAMTS15 have emerged as novel predictors of survival in patients with breast carcinoma. © 2005 Wiley‐Liss, Inc.
Hydrothermal treatments of two cowpea (Vigna unguiculata L. Walp) varieties: effect of micronisation on physicochemical and structural characteristics
Authors: Mwangwela Agnes M , Waniska Ralph D , Minnaar Amanda 
Published: September 2005

AbstractThe effects of a hydrothermal treatment consisting of tempering (to 41% moisture) and heating to 153 °C (micronisation) on the structural and physicochemical characteristics of two cowpea varieties were studied. The untreated varieties had similar cooking times, although cooked Bechuana white cowpeas were significantly (P ≤ 0.05) softer and had a higher incidence of splitting than Var. 462 cowpeas. This may be due in part to differences in cotyledon structure affecting water uptake during cooking. The hydrothermal treatment changed the physical structure and chemical properties of the cowpea seeds. This led to significant (P ≤ 0.05) reductions in the cooking time of micronised Bechuana white and Var. 462 cowpeas, by 47 and 36% respectively, as compared with control samples. Micronisation caused physical fissuring of the seed coat and cotyledon and significantly (P ≤ 0.05) reduced the bulk density of treated seeds. These changes in the physical structure significantly (P ≤ 0.05) improved the initial water uptake during soaking and cooking, increased the enzyme‐susceptible starch and reduced the protein solubility and hydration capacity of the cowpea seeds. Cooked (60 min) micronised cowpeas also had significantly (P ≤ 0.05) more splits and a significantly (P ≤ 0.05) softer texture than control samples. Copyright © 2005 Society of Chemical Industry
Chemical constituents, antimicrobial investigations and antioxidative potential of volatile oil and acetone extract of star anise fruits
Authors: Singh Gurdip , Maurya Sumitra , deLampasona MP , Catalan Cesar 
Published: September 2005

AbstractGC and GC‐MS analysis of fruit volatile oil of star anise (Illicium verum Hook) showed the presence of 25 components which account for the 99.9% of the total amount. The major components were trans‐anethole (94.37%), methyl chevicol (1.82%) and cis‐anethole (1.59%). 15 Components were identified from its acetone extract accounting for 80.27% of the total amount. trans‐Anethole (51.81%) was found as a major component along with linoleic acid (11.6%), 1‐(4‐methoxyphenyl)‐prop‐2‐one (6.71%), foeniculin (5.29%) and palmitic acid (1.47%). Using an inverted petriplate method, the volatile oil completely inhibited the growth of Fusarium moniliforme at 6 µl dose. In case of extract, 50% mycelial zone inhibition was obtained for Penicillium citrinum and Penicillium viridicatum. Moreover, using food poison technique, the volatile oil was found to be effective for controlling the growth of F. moniliforme and Aspergillus niger whereas the extract has been found to be highly effective for Aspergillus flavus. In antibacterial investigations, using agar well diffusion method, the extract has shown better activity for Staphylococcus aureus and Bacillus cereus in comparison with volatile oil and commercial bactericide, ie Ampicillin. However, volatile oil has shown better activity for Salmonella aeruginosa and Bacillus subtilis. Moreover, the extract has shown excellent activity for the inhibition of primary and secondary oxidation products in rapeseed oil which were evaluated using peroxide, thiobarbituric acid, p‐anisidine and carbonyl values. The activity of extract was further confirmed using other antioxidant properties such as ferric thiocyanate method in linoleic acid system, reducing power and scavenging effect (%) on 1,1‐diphenyl‐2‐picrylhydrazyl radical (DPPH) radical. Hence, the extract could be considered as natural antioxidant which may be used for chemoprevention of diseases occurring due to oxidative deterioration. Copyright © 2005 Society of Chemical Industry
Physiological properties of fresh‐cut watermelon (Citrullus lanatus) in response to 1‐methylcyclopropene and post‐processing calcium application
Authors: Mao Linchun , Jeong Jiwon , Que Fei , Huber Donald J 
Published: September 2005

AbstractSeedless watermelon (Citrullus lanatus Thunb. Mansfeld, cv. Millionaire) fruit were exposed to 10 µL L−1 1‐methylcyclopropene (1‐MCP) or air for 18 h. Afterward, the fruit were processed into placental‐tissue pieces, treated with calcium dips (20 g kg−1 CaCl2) or deionized water, and stored in vented containers for 7 days at 10 °C. At intervals during storage, fresh‐cut placental tissue was monitored for respiration, ethylene production, firmness, electrolyte leakage, total soluble solids, titratable acidity and microbial growth. Ethylene production was below detection in fresh‐cut placental tissue, consistent with the low ethylene production in intact watermelon fruit. Respiration rates were significantly enhanced in response to tissue processing, and continued to increase throughout the 7 days of storage. Tissue derived from 1‐MCP‐treated fruit showed enhanced 1‐aminocyclopropane‐1‐carboxylate synthase (ACS, EC 4.4.1.14) activity, suppressed respiratory rates and undetectable levels of 1‐aminocyclopropane‐1‐carboxylate oxidase (ACO) activity during storage. Post‐processing calcium dips (CaCl2) had little influence on ACS activity relative to tissue not receiving calcium, but significantly enhanced ACO activity and maintained firmness of fresh‐cut tissue throughout storage. The data collectively support the conclusion that 1‐methylcyclopropene treatment of intact watermelon fruit is alone unlikely to benefit the storage duration of fresh‐cut watermelon. Copyright © 2005 Society of Chemical Industry
Erucic acid content in some rapeseed/mustard cultivars developed in Bangladesh
Authors: Mortuza Md Golam , Dutta Paresh C , Das Manik L 
Published: September 2005

AbstractSeed samples of 21 indigenous and developed rapeseed/mustard cultivars (Brassica campestris, B. juncea and B. napus) were characterized for their fatty acid composition. Erucic acid was one of the main fatty acids, in proportions ranging from 21.59 to 51.57% followed by oleic acid ranging from 7.03 to 25.21%. The other major monounsaturated fatty acid was gadoleic acid, which accounted for 4.12–12.06%. The major polyunsaturated fatty acids were linoleic and linolenic acid, ranging from 11.79 to 16.89% and 6.29 to 11.15%, respectively. Among the saturated fatty acids, palmitic acid accounted for 1.20–3.36%. Erucic acid content was negatively correlated with all other major fatty acids. The cultivars Binasarisha‐3, Binasarisha‐4, Binasarisha‐5, MM 22‐12‐98, MM 2‐16‐98, MM 36‐6‐98, MM 49‐3‐98, MM 34‐7‐98 and Barisarisha‐8 of B. napus had significantly (P < 0.001) low levels of erucic acid and high levels of oleic, linoleic and linolenic acids among all the cultivars. These four cultivars and five advanced generation mutant lines may be exploited in breeding programmes for the development of nutritionally better‐quality locally adaptive cultivars. Copyright © 2005 Society of Chemical Industry
Extraction and determination by liquid chromatography and spectrophotometry of naloxone in microparticles for drug‐addiction treatment
Authors: Gil‐Alegre Maria Esther , Barone Monica Lareo , Torres‐Suárez Ana Isabel 
Published: September 2005

AbstractThis paper discusses the development and validation of two analytical methods for the assay of naloxone in microparticles, as used in the therapy of opioid drug addiction (weaning). A UV‐Vis spectrophotometric method is proposed to study drug loading and drug release, due to its ease and simplicity of performance, while a high performance liquid chromatographic method is developed as a means of stability‐indication. Both analytical procedures were validated according to the International Committee for Harmonization (ICH) guidelines. Although the ranges and wavelengths were different for the two analytical methods, they were both found to be specific, linear, precise, and accurate under the determined conditions.