bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mutational analysis of IDH1 codon 132 in glioblastomas and other common cancers
Authors: Kang Mi Ran , Kim Min Sung , Oh Ji Eun , Kim Yoo Ri , Song Sang Yong , Seo Seong Il , Lee Ji Youl , Yoo Nam Jin , Lee Sug Hyung 
Published: February 2009

AbstractMissense somatic mutations in IDH1 gene affecting codon 132 have recently been reported in glioblastoma multiforme (GBM) and other gliomas. The recurrent nature of the IDH1 mutations in the same amino acid strongly suggests that the mutations may play important roles in the pathogenesis of glial tumors. The aim of this study was to see whether the IDH1 codon 132 mutations occur in other human cancers besides glial tumors. We also attempted to confirm the occurrence of the IDH1 mutations in GBM of Korean patients. We have analyzed 1,186 cancer tissues from various origins, including carcinomas from breast, colon, lung, stomach, esophagus, liver, prostate, urinary bladder, ovary, uterine cervix, skin and kidney, and malignant mesotheliomas, primary GBM, malignant meningiomas, multiple myelomas and acute leukemias by single‐strand conformation polymorphism analysis. We found four IDH1 codon 132 mutations in the GBM (4/25; 16.0%), two in the prostate carcinomas (2/75; 2.7%) and one in the B‐acute lymphoblastic leukemias (B‐ALL) (1/60; 1.7%), but none in other cancers. The IDH1 mutations consisted of five p.R132H and two p.R132C mutations. The data indicate that IDH1 codon 132 mutations occur not only in GBM, but also in prostate cancers and B‐ALL. This study suggests that despite the infrequent incidence of the IDH1 mutations in prostate cancers and B‐ALL, mutated IDH1 could be therapeutically targeted in these cancers and in glial tumors with the IDH1 mutations. © 2009 UICC
Combined targeting of interleukin‐6 and vascular endothelial growth factor potently inhibits glioma growth and invasiveness
Authors: Saidi Ahlame , Hagedorn Martin , Allain Nathalie , Verpelli Chiara , Sala Carlo , Bello Lorenzo , Bikfalvi Andreas , Javerzat Sophie 
Published: February 2009

AbstractInterleukin‐6 (IL6) and vascular endothelial growth factor (VEGFA) are abundantly produced by glioma cells and contribute to malignancy by promoting angiogenesis, cell proliferation and resistance to apoptosis. We compared the effect of inhibiting IL6 and VEGF on U87‐derived experimental glioma grown on the chick chorio‐allantoic membrane (CAM) or in the brain of xenografted mice. Tumor growth was monitored by biomicroscopy and immunohistology. In vitro, IL6 knockdown had no effect on proliferation but substantially enhanced invasion. In the CAM experimental glioma, IL6 or VEGF knockdown reduced growth and vascularization of the tumors with a comparable efficiency, but increased invasion of residual tumor cells. In contrast, combined IL6/VEGF knockdown not only showed enhanced reduction of tumor growth and angiogenesis but also significantly prevented invasion of residual tumor cells. In mice, combining IL6 knockdown and Avastin™ treatment completely abrogated tumor development and infiltration. Molecular response of tumor cells to single or combined treatment was studied by transcriptomic profiling. Many cell cycle promoting genes and chromatin components were silenced in the double knockdown. In addition, specific migratory signatures detected in tumors under single IL6 or VEGF knockdown were partially erased in combined IL6/VEGF knockdown tumors. Our results show that treatment with a combination of IL6 and VEGF inhibitors brings synergistic antitumoral benefit and reduces global activity of major pathways of cell survival, proliferation and invasiveness in remaining tumor cells that may be induced by using VEGF or IL6 inhibitors alone. © 2009 UICC
Systemic delivery of siRNA specific to tumor mediated by atelocollagen: Combined therapy using siRNA targeting Bcl‐xL and cisplatin against prostate cancer
Authors: Mu Ping , Nagahara Shunji , Makita Naoki , Tarumi Yuzo , Kadomatsu Kenji , Takei Yoshifumi 
Published: February 2009

AbstractThe largest obstacle to the effective use of short interfering RNA (siRNA) in an animal body is the ability to deliver it to the target tissue. Here we showed a systemic delivery method of siRNA specific to pregrown solid tumors via atelocollagen. Atelocollagen facilitated the selective uptake of siRNA into the tumors when an siRNA/atelocollagen complex was administered intravenously to mice. We chose a Bcl‐xL protein as a model target to prove the therapeutic efficacy of the atelocollagen‐mediated method. Bcl‐xL acts as an anti‐apoptotic factor, which is overexpressed in many cancers, including prostate cancer. One of the four designed siRNAs to human Bcl‐xL potently inhibited the expression of Bcl‐xL by the PC‐3 human prostate cancer cell line in vitro, leading to cell apoptosis. Intravenous injections for3 consecutive days (siRNA, 100 μg/injection per day as a complex with atelocollagen) effectively downregulated Bcl‐xL expression in the PC‐3 xenograft. We administered four series of 3 consecutive days of intravenous injections each, for a total of 12 injections, which significantly inhibited tumor growth when the treatment was combined with cisplatin (2 mg/kg). Local injection of Bcl‐xL siRNA also potently inhibited tumor growth. All of the tumors treated with Bcl‐xL siRNA/atelocollagen complex via both intravenous and intratumoral injection showed terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labeling‐positive apoptosis. There were no severe side effects such as interferon‐α induction and liver or renal damage in mice. Our results indicate that systemic delivery of siRNA via atelocollagen, which specifically targets tumors, is safe and feasible for cancer therapy. © 2009 UICC
Family history of hormonal cancers and colorectal cancer risk: A case‐control study conducted in Ontario
Authors: Jang Ji‐Hyun , Cotterchio Michelle , Gallinger Steven , Knight Julia A. , Daftary Darshana 
Published: February 2009

AbstractAggregation of cancers among families with highly penetrant genetic mutations such as hereditary nonpolyposis colorectal cancer is well‐described. However, there is a paucity of data regarding familial aggregation of hormonal cancers (cancers of the breast, endometrial, ovarian and prostate) and colorectal cancer (CRC) in the general population. We investigated the association between having a first‐degree family history of breast, endometrial, ovarian, or prostate cancer and CRC risk. Population‐based CRC cases and controls were recruited by the Ontario Familial Colorectal Cancer Registry (OFCCR). Logistic regression was conducted to obtain odds ratio (OR) estimates and 95% confidence intervals (95% CIs). First‐degree family history of breast cancer was associated with a modest, borderline statistically significant increased CRC risk (age‐, sex‐adjusted OR = 1.2, 95% CI = 1.0, 1.5). The magnitude of CRC risk was greatest if more than one first‐degree kin had breast cancer (age‐, sex‐adjusted OR = 1.7, 95% CI = 1.0, 2.0), as well as if the kin was diagnosed at >50 years of age (age‐, sex‐adjusted OR = 1.4, 95% CI = 1.1, 1.8). Family history of ovarian cancer was associated with reduced CRC risk (multivariate‐adjusted OR = 0.6, 95% CI = 0.3, 1.0). Although statistically significant increases in CRC risk were observed in the age‐, sex‐adjusted OR estimates for family history of endometrial and prostate cancers, the associations were no longer significant after multivariate‐adjustment. In conclusion, individuals with a first‐degree kin with breast cancer may have a modest increased risk for CRC compared to individuals without. © 2009 UICC
Enhanced invasiveness of drug‐resistant acute myeloid leukemia cells through increased expression of matrix metalloproteinase‐2
Authors: Song Ju Han , Kim Seung Hyun , Cho Daeho , Lee Il‐Kwon , Kim Hyeoung‐Joon , Kim Tae Sung 
Published: February 2009

AbstractThe acquired drug resistance as well as extramedullary tissue infiltration of leukemic cells is a major obstacle in leukemia treatment. Excessive egress of leukemia cell blasts results in invasion into various organs or tissues, which is facilitated by the catalytic activities of matrix metalloproteinases (MMPs). However, the migration of chemoresistant leukemia cells remains unclear. Here, we generated drug‐resistant variants of the human acute myeloid leukemia cell line (AML‐2/WT) by stepwise exposure to anticancer drugs and evaluated the level of MMP‐2 in the drug‐resistant variants, along with their invasiveness. Each of the drug‐resistant cell variants demonstrated predominant increases in the expression and gelatinolytic activity of MMP‐2 as well as in invasiveness, which were significantly suppressed by both a MMP‐2 inhibitor and a blocking antibody. Knockdown experiments using MMP‐2 short hairpin RNA also indicated that its upregulation was strongly associated with the cells' increased invasive properties. Importantly, elevated levels of MMP‐2 activity and invasiveness were observed in ex vivo mononuclear cell of bone marrow from patients with poor responses to chemotherapy. These findings suggest that advanced malignancy due to acquired drug resistance is responsible for the progressive invasiveness of leukemia cells via MMP‐2. © 2009 UICC
Meat and fat intake and pancreatic cancer risk in the Netherlands Cohort Study
Authors: Heinen Mirjam M. , Verhage Bas A.J. , Goldbohm R. Alexandra , van den Brandt Piet A. 
Published: February 2009

AbstractMeat contains numerous carcinogens, such as heterocyclic amines, polycyclic aromatic hydrocarbons, and N‐nitroso compounds, which can be derived either from natural food or during the process of food preparation. These carcinogens may increase pancreatic cancer risk. Furthermore, studies in animals showed that polyunsaturated fatty acids, especially linoleic acid, increase pancreatic cancer risk. We examined prospectively the relation between pancreatic cancer risk and intake of fresh meat, processed meat, fish, eggs, total fat, and different types of fat. The Netherlands Cohort Study consisted of 120,852 men and women who completed a baseline questionnaire in 1986. After 13.3 years of follow‐up, 350 pancreatic cancer cases (66% microscopically confirmed) were available for analysis. A validated 150‐item food‐frequency questionnaire was used to calculate intake of fresh meat, processed meat, fish, eggs, fat and different types of fat. No association was found when examining the association between intake of fresh meat, other types of meat, fish, eggs, dietary intake of total fat and different types of fat and risk of pancreatic cancer. It is important for future studies to investigate the relation between different meat‐cooking methods and pancreatic cancer. © 2009 UICC
Induction of osteopontin expression by nicotine and cigarette smoke in the pancreas and pancreatic ductal adenocarcinoma cells
Authors: Chipitsyna Galina , Gong Qiaoke , Anandanadesan Rathai , Alnajar Amer , Batra Surinder K. , Wittel Uwe A. , Cullen Diane M. , Akhter Mohammed P. , Denhardt David T. , Yeo Charles J. , Arafat Hwyda A. 
Published: February 2009

AbstractPancreatic ductal adenocarcinoma (PDA) is a lethal disease with etiological association with cigarette smoking. Nicotine, an important component of cigarettes, exists at high concentrations in the bloodstream of smokers. Osteopontin (OPN) is a secreted phosphoprotein that confers on cancer cells a migratory phenotype and activates signaling pathways that induce cell survival, proliferation, invasion, and metastasis. Here, we investigated the potential molecular basis of nicotine's role in PDA through studying its effect on OPN. Nicotine significantly (p < 0.02) increased OPN mRNA and protein secretion in PDA cells through activation of the OPN gene promoter. The OPN mRNA induction was inhibited by the nicotinic acetylcholine receptor antagonist, mechamylamine. Further, the tyrosine kinase inhibitor genistein inhibited the nicotine‐mediated induction of OPN, suggesting that mitogen activated protein kinase signaling mechanism is involved. Nicotine activated the phosphorylation of ERK1/2, but not p38 or c‐Jun NH2‐terminal MAP kinases. Inhibition of ERK1/2 activation reduced the nicotine‐induced OPN synthesis. Rats exposed to cigarette smoke showed a dose‐dependent increase in pancreatic OPN that paralleled the rise of pancreatic and plasma nicotine levels. Analysis of cancer tissue from invasive PDA patients, the majority of whom were smokers, showed the presence of significant amounts of OPN in the malignant ducts and the surrounding pancreatic acini. Our data suggest that nicotine may contribute to PDA pathogenesis through upregulation of OPN. They provide the first insight into a nicotine‐initiated signal transduction pathway that regulates OPN as a possible tumorigenic mechanism in PDA. © 2009 UICC
Functional coexpression of Interleukin (IL)‐7 and its receptor (IL‐7R) on Hodgkin and Reed‐Sternberg cells: Involvement of IL‐7 in tumor cell growth and microenvironmental interactions of Hodgkin's lymphoma
Authors: Cattaruzza Lara , Gloghini Annunziata , Olivo Karin , Di Francia Raffaele , Lorenzon Debora , De Filippi Rosaria , Carbone Antonino , Colombatti Alfonso , Pinto Antonio , Aldinucci Donatella 
Published: February 2009

AbstractThe clinical and pathological features of classical Hodgkin lymphoma (cHL) mirror an abnormal tissue and systemic immune response due to the production of a variety of cytokines and chemokines by the malignant Hodgkin‐Reed‐Sternberg (H‐RS) cells and/or surrounding reactive cells. Here, we demonstrate that HL‐derived cell lines (L‐428, KM‐H2, HDLM‐2, L‐1236 and L‐540) and primary H‐RS cells from lymph node tissues of HL patients express the IL‐7(R) receptor. IL‐7 appears to be involved in autocrine circuitries of HL because L‐1236, HDLM‐2 and KM‐H2 cells display the constitutive production of IL‐7 and neutralizing anti‐IL‐7 antibodies induces a statistically significant inhibition of their basal proliferation. In addition, IL‐7, either exogenous or fibroblasts‐derived, promotes the clonogenic growth and reduces apoptosis of cultured H‐RS cells, being also able to partially protect these cells from the cytotoxic effects of doxorubicin. We also provide evidence that IL‐7 stimulates IL‐6 secretion from IL‐7R‐expressing fibroblasts from HL‐involved lymph nodes (HLFs), and that a striking increase in IL‐6 secretion can be observed in cocultures of HLFs with L1236 cells. Finally, we show that L‐1236 cells‐derived IL‐7 represents a costimulator for proliferation of purified CD4+CD25+CD127dim/− regulatory T cells (Tregs). Taken together, our data indicates that the IL‐7/IL‐7R axis constitutes an additional signaling pathway between H‐RS cells and their reactive cellular background, thereby affecting proliferation and survival of tumor cells, acting as a cofactor for Tregs expansion and enhancing the microenviromental production of IL‐6, a cytokine associated with the presence of “B” symptoms and a poor outcome in HL patients. © 2009 UICC
Identification of novel microRNA targets based on microRNA signatures in bladder cancer
Authors: Ichimi Takahiro , Enokida Hideki , Okuno Yasushi , Kunimoto Ryo , Chiyomaru Takeshi , Kawamoto Ken , Kawahara Kazuya , Toki Kazuki , Kawakami Kazumori , Nishiyama Kenryu , Tsujimoto Gozoh , Nakagawa Masayuki , Seki Naohiko 
Published: February 2009

AbstractMicroRNAs (miRNAs) are small noncoding RNAs that negatively regulate protein‐coding genes. To identify miRNAs that have a tumor suppressive function in bladder cancer (BC), 156 miRNAs were screened in 14 BCs, 5 normal bladder epithelium (NBE) samples and 3 BC cell lines. We identified a subset of 7 miRNAs (miR‐145, miR‐30a‐3p, miR‐133a, miR‐133b, miR‐195, miR‐125b and miR‐199a*) that were significantly downregulated in BCs. To confirm these results, 104 BCs and 31 NBEs were subjected to real‐time RT‐PCR‐based experiments, and the expression levels of each miRNA were significantly downregulated in BCs (p < 0.0001 in all). Receiver‐operating characteristic curve analysis revealed that the expression levels of these miRNAs had good sensitivity (>70%) and specificity (>75%) to distinguish BC from NBE. Our target search algorithm and gene‐expression profiling in BCs (Kawakami et al., Oncol Rep 2006;16:521–31) revealed that Keratin7 (KRT7) mRNA was a common target of the downregulated miRNAs, and the mRNA expression levels of KRT7 were significantly higher in BCs than in NBEs (p = 0.0004). Spearman rank correlation analysis revealed significant inverse correlations between KRT7 mRNA expression and each downregulated miRNA (p < 0.0001 in all). Gain‐of‐function analysis revealed that KRT7 mRNA was significantly reduced by transfection of 3 miRNAs (miR‐30‐3p, miR‐133a and miR‐199a*) in the BC cell line (KK47). In addition, significant decreases in cell growth were observed after transfection of 3 miRNAs and si‐KRT7 in KK47, suggesting that miR‐30‐3p, miR‐133a and miR‐199a* may have a tumor suppressive function through the mechanism underlying transcriptional repression of KRT7. © 2009 UICC
Identification of integrins α6 and β7 as c‐Jun‐ and transformation‐relevant genes in highly invasive fibrosarcoma cells
Authors: Kielosto Mari , Nummela Pirjo , Järvinen Kristiina , Yin Miao , Hölttä Erkki 
Published: February 2009

AbstractUnderstanding the mechanisms of tumor cell invasion is essential for our attempts to prevent cancer deaths. We screened by DNAmicroarrays the c‐Jun‐ and transformation‐related gene expression changes inS‐adenosylmethionine decarboxylase (AdoMetDC)‐overexpressing mouse fibroblasts that are highly invasivein vivo, and their derivatives expressing a tetracycline‐inducible dominant‐negative mutant of c‐Jun (TAM67) or c‐Jun shRNA. Among the small set of target genes detected were integrins α6 and β7, cathepsin L and thymosin β4, all upregulated in the AdoMetDC‐transformed cells and downregulated upon reversal of transformation by TAM67 or c‐Jun shRNA. The upregulation of integrin α6 subunit, pairing with integrin β1, endowed the transformed cells with the capability to attach to basement membrane laminin and to spread. Further, inhibition of integrin α6 or β1 function with neutralizing antibodies blocked the invasiveness of AdoMetDC‐transformants and human HT‐1080 fibrosarcoma cells in three‐dimensional Matrigel. Moreover, immunohistochemical analyses showed strong integrin α6 staining in high‐grade human fibrosarcomas. Our data show that c‐Jun can regulate all three key steps of invasion: cell adhesion (integrin α6), basement membrane/extracellular matrix degradation (cathepsin L) and cell migration (thymosin β4). In addition, this is the first study to associate integrin β7, known as a leukocyte‐specific integrin binding to endothelial/epithelial cell adhesion molecules, with the transformed phenotype in cells of nonleukocyte origin. As tumor cell invasion is a prerequisite for metastasis, the observed critical role of integrin α6β1 in fibrosarcoma cell invasion/spreading allures testing antagonists to integrin α6β1, alone or combined with inhibitors of cathepsin L and thymosin β4, as chemotherapeutic agents. © 2009 UICC
Gene expression profiling of alpha‐radiation‐induced rat osteosarcomas: Identification of dysregulated genes involved in radiation‐induced tumorigenesis of bone
Authors: Daino Kazuhiro , Ugolin Nicolas , Altmeyer‐Morel Sandrine , Guilly Marie‐Noëlle , Chevillard Sylvie 
Published: February 2009

AbstractTo better understand the molecular basis of radiation‐induced osteosarcoma (OS), we performed global gene expression profiling of rat OS tumors induced by the bone‐seeking alpha emitter 238Pu, and the expression profiles were compared with those of normal osteoblasts (OB). The expressions of 72 genes were significantly differentially expressed in the tumors related to OB. These included genes involved in the cell adhesion (e.g., Podxl, Col18a1, Cd93, Emcn and Vcl), differentiation, developmental processes (e.g., Hhex, Gata2, P2ry6, P2rx5, Cited2, Osmr and Igsf10), tumor‐suppressor function (e.g., Nme3, Blcap and Rrm1), Src tyrosine kinase signaling (e.g., Hck, Shf, Arhgap29, Cttn and Akap12), and Wnt/β‐catenin signaling (e.g., Fzd6, Lzic, Dkk3 and Ctnna1) pathways. Expression changes of several genes were validated by quantitative real‐time RT‐PCR analysis. Notably, all of the identified genes involved in the Wnt/β‐catenin signaling pathway were known or proposed to be negative regulators of this pathway and were downregulated in the tumors, suggesting the activation of β‐catenin in radiation‐induced OS. By using immunohistochemical and immunoblot analyses, constitutive activation of the Wnt/β‐catenin signaling pathway in the tumors was confirmed by observing nuclear and/or cytoplasmic localization of β‐catenin and a decrease in its inactive (phosphorylated) form. Furthermore, we found a significant reduction in the levels of glycogen synthase kinase 3β (GSK‐3β) protein in the tumors relative to OB. Taken together, these findings provide new insights into the molecular basis of radiation‐induced OS. © 2009 UICC
Methylation of multiple genes as molecular markers for diagnosis of a small, well‐differentiated hepatocellular carcinoma
Authors: Moribe Toyoki , Iizuka Norio , Miura Toshiaki , Kimura Naoki , Tamatsukuri Shigeru , Ishitsuka Hideo , Hamamoto Yoshihiko , Sakamoto Kazuhiko , Tamesa Takao , Oka Masaaki 
Published: February 2009

AbstractThe current study was conducted to identify robust methylation markers and their combinations that may prove useful for the diagnosis of early hepatocellular carcinoma (HCC). To achieve this, we performed in silico CpG mapping, direct sequencing and pyrosequencing after bisulfite treatment, and quantitative methylation‐specific PCR (MSP) in HCC and non‐HCC liver tissues. In the filtering group (25 HCCs), our direct sequencing analysis showed that, among the 12 methylation genes listed by in silico CpG mapping, 7 genes (RASSF1A, CCND2, SPINT2, RUNX3, GSTP1, APC and CFTR) were aberrantly methylated in stages I and II HCCs. In the validation group (20 pairs of HCCs and the corresponding non‐tumor liver tissues), pyrosequencing analysis confirmed that the 7 genes were aberrantly and strongly methylated in early HCCs, but not in any of the corresponding non‐ tumor liver tissues (p < 0.00001). The results obtained using our novel quantitative MSP assay correlated well with those observed using the pyrosequencing analysis. Notably, in MSP assay, RASSF1A showed the most robust performance for the discrimination of HCC and non‐HCC liver tissues. Furthermore, a combination of RASSF1A, CCND2 and SPINT2 showed 89–95% sensitivity, 91–100% specificity and 89–97% accuracy in discriminating between HCC and non‐HCC tissues, and correctly diagnosed all early HCCs. These results indicate that the combination of these 3 genes may aid in the accurate diagnosis of early HCC. © 2009 UICC
On 2‐factorizations of the complete graph: From the k‐pyramidal to the universal property
Authors: Bonvicini Simona , Mazzuoccolo Giuseppe , Rinaldi Gloria 
Published: February 2009

AbstractWe consider 2‐factorizations of complete graphs that possess an automorphism group fixing k⩾0 vertices and acting sharply transitively on the others. We study the structures of such factorizations and consider the cases in which the group is either abelian or dihedral in some more details. Combining results of the first part of the paper with a result of D. Bryant, J Combin Des, 12 (2004), 147–155, we prove that the class of 2‐factorizations of complete graphs is universal. Namely each finite group is the full automorphism group of a 2‐factorization of the class. © 2009 Wiley Periodicals, Inc. J Combin Designs 17: 211‐228, 2009
The Hamilton–Waterloo problem for cycle sizes 3 and 4
Authors: Danziger Peter , Quattrocchi Gaetano , Stevens Brett 
Published: February 2009

AbstractThe Hamilton–Waterloo problem seeks a resolvable decomposition of the complete graph Kn, or the complete graph minus a 1‐factor as appropriate, into cycles such that each resolution class contains only cycles of specified sizes. We completely solve the case in which the resolution classes are either all 3‐cycles or 4‐cycles, with a few possible exceptions when n=24 and 48. © 2009 Wiley Periodicals, Inc. J Combin Designs 17: 342–352, 2009