bluuebunny/crossref_metadata_2025_split huggingface dataset:
A New Diagnostic Marker for Secreted Epstein-Barr Virus–Encoded LMP1 and BARF1 Oncoproteins in the Serum and Saliva of Patients with Nasopharyngeal Carcinoma
Authors: Houali Karim , Wang Xiaohui , Shimizu Yuko , Djennaoui Djamel , Nicholls John , Fiorini Sylvie , Bouguermouh Abdelmadjid , Ooka Tadamasa 
Published: September 2007

Abstract
Purpose: EBV has been associated with nasopharyngeal carcinomas (NPC). In North Africa, the incidence is bimodal—the first peak occurring at ∼20 years of age and the second peak occurring at ∼50 years. Standard diagnostic tests based on immunofluorescence using anti-IgA EBV have shown that young North African patients have a negative serology compared with older patients. We are interested in two EBV-encoded oncoproteins, LMP1 and BARF1, which have thus far not been studied in terms of their potential as diagnostic markers for NPC. These two viral oncoproteins have been detected in cell culture media, so we tested whether they could be detected in the serum and saliva of patients with NPC.
Experimental Design: LMP1 and BARF1 proteins were analyzed in the sera and saliva of young patients and adult patients with NPC from North Africa and China. We then examined whether the secreted proteins had biological activity by analyzing their mitogenic activity.
Results: Both LMP1 and BARF1 were present in the serum and saliva from North African and Chinese patients with NPC. All young North African patients secreted both proteins, whereas 62% and 100% of adult patients secreted LMP1 and BARF1, respectively. From animal studies, the secreted LMP1 was associated with exosome-like vesicles. These secreted EBV oncoproteins showed a powerful mitogenic activity in B cells.
Conclusion: Both proteins will be a good diagnostic marker for NPC whereas BARF1 is a particularly promising marker for all ages of patients with NPC. Their mitogenic activity suggests their implication in the oncogenic development of NPC.
Nelfinavir, A Lead HIV Protease Inhibitor, Is a Broad-Spectrum, Anticancer Agent that Induces Endoplasmic Reticulum Stress, Autophagy, and Apoptosis In vitro and In vivo
Authors: Gills Joell J. , LoPiccolo Jaclyn , Tsurutani Junji , Shoemaker Robert H. , Best Carolyn J.M. , Abu-Asab Mones S. , Borojerdi Jennifer , Warfel Noel A. , Gardner Erin R. , Danish Matthew , Hollander M. Christine , Kawabata Shigeru , Tsokos Maria , Figg William D. , Steeg Patricia S. , Dennis Phillip A. 
Published: September 2007

Abstract
Purpose: The development of new cancer drugs is slow and costly. HIV protease inhibitors are Food and Drug Administration approved for HIV patients. Because these drugs cause toxicities that can be associated with inhibition of Akt, an emerging target in cancer, we assessed the potential of HIV protease inhibitors as anticancer agents.
Experimental Design: HIV protease inhibitors were screened in vitro using assays that measure cellular proliferation, apoptotic and nonapoptotic cell death, endoplasmic reticulum (ER) stress, autophagy, and activation of Akt. Nelfinavir was tested in non–small cell lung carcinoma (NSCLC) xenografts with biomarker assessment.
Results: Three of six HIV protease inhibitors, nelfinavir, ritonavir, and saquinavir, inhibited proliferation of NSCLC cells, as well as every cell line in the NCI60 cell line panel. Nelfinavir was most potent with a mean 50% growth inhibition of 5.2 μmol/L, a concentration achievable in HIV patients. Nelfinavir caused two types of cell death, caspase-dependent apoptosis and caspase-independent death that was characterized by induction of ER stress and autophagy. Autophagy was protective because an inhibitor of autophagy increased nelfinavir-induced death. Akt was variably inhibited by HIV protease inhibitors, but nelfinavir caused the greatest inhibition of endogenous and growth factor–induced Akt activation. Nelfinavir decreased the viability of a panel of drug-resistant breast cancer cell lines and inhibited the growth of NSCLC xenografts that was associated with induction of ER stress, autophagy, and apoptosis.
Conclusions: Nelfinavir is a lead HIV protease inhibitor with pleiotropic effects in cancer cells. Given its wide spectrum of activity, oral availability, and familiarity of administration, nelfinavir is a Food and Drug Administration–approved drug that could be repositioned as a cancer therapeutic.
Long-term Evaluation of Three Multiple-Case Waldenström Macroglobulinemia Families
Authors: McMaster Mary L. , Csako Gyorgy , Giambarresi Therese R. , Vasquez Linda , Berg Melissa , Saddlemire Stephanie , Hulley Benjamin , Tucker Margaret A. 
Published: September 2007

Abstract
Purpose: Because the clinical significance of immunoglobulin abnormalities reported in relatives of familial Waldenström macroglobulinemia (WM) patients is unknown, we initiated a follow-up study of three WM families originally evaluated 27 years previously.
Experimental Design: Of 29 eligible first-degree relatives of WM patients, 27 (93%) had originally participated in clinical and electrophoretic evaluations. We re-contacted all participants for prospective follow-up electrophoretic analysis and other studies.
Results: Initially, five relatives had IgM monoclonal gammopathy (IgM MG), and four had IgM polyclonal gammopathy (PG). Twenty-two relatives (81%) were re-evaluated. Median follow-up was 17 years (range, 7-27). At re-contact, all IgM MG persisted or progressed, including three that evolved to WM. Among the four with PG, two new IgM MG cases developed. Overall, seven relatives (26%) had IgM MG, and five (18%) had IgM PG.
Conclusions: Although based on small numbers, this study provides the longest comprehensive follow-up of WM families to date. IgM MG seems to be a phenotypic marker of WM susceptibility in some families and may have a high risk of progression to WM. IgM PG may also be important in WM families. These observations require validation in larger studies and, if confirmed, may be used to identify a cohort (relatives with IgM MG) for future prevention strategies.
Epigenetic Inactivation of IκB Kinase-α in Oral Carcinomas and Tumor Progression
Authors: Maeda Genta , Chiba Tadashige , Kawashiri Shuichi , Satoh Tazuko , Imai Kazushi 
Published: September 2007

AbstractPurpose: The loss of epithelial phenotypes in the process of carcinoma progression correlates with clinical outcome, and genetic/epigenetic changes accumulate aggressive clones toward uncurable disease. IκB kinase-α (IKKα) has a decisive role in the development of the skin and establishes keratinocyte phenotypes. We assessed clinical implications of IKKα expression in oral carcinomas and epigenetic aberrations for the loss of expression.Experimental Design: We examined IKKα expression in oral carcinomas by immunostaining (n = 64) and genetic instability by microsatellite PCR (n = 46). Promoter methylation status was analyzed by bisulfite-modified sequence (n = 11).Results: IKKα was expressed in the nucleus of basal cells of normal oral epithelium, but not or marginally detected in 32.8% of carcinomas. The immunoreactivity was significantly decreased in less differentiated carcinomas (P &lt; 0.05) and correlated to long-term survival of patients (P &lt; 0.01) with an independent prognostic value (P &lt; 0.05). Although allelic/biallelic loss of the gene was limited to four cases, we detected microsatellite instability in 63.0% cases in which the immunoreactivities were decreased and the promoter was hypermethylated.Conclusion: These results showed that oral carcinomas exhibiting genetic instability and promoter hypermethylation down-regulate expression of IKK and suggest that the epigenetic loss of the expression closely associates with disease progression toward unfavorable prognosis.
Rapid Detection of Epidermal Growth Factor Receptor Mutations in Lung Cancer by the SMart-Amplification Process
Authors: Hoshi Kanako , Takakura Hideki , Mitani Yasumasa , Tatsumi Kenji , Momiyama Nobuyoshi , Ichikawa Yasushi , Togo Shinji , Miyagi Toru , Kawai Yuki , Kogo Yasushi , Kikuchi Takeshi , Kato Chiaki , Arakawa Takahiro , Uno Syuji , Cizdziel Paul E. , Lezhava Alexander , Ogawa Noburou , Hayashizaki Yoshihide , Shimada Hiroshi 
Published: September 2007

Abstract
Purpose: A positive response to gefitinib in non–small cell lung cancer (NSCLC) has been correlated to mutations in epidermal growth factor receptor (EGFR) gene. Previous reports have been based mainly on diagnostic screening by sequencing. However, sequencing is a time-consuming and complicated procedure, not suitable for routine clinical use.
Experimental Design: We have developed rapid, simple, and sensitive mutation detection assays based on the SMart Amplification Process (SMAP) and applied it for analyzing EGFR gene mutations in clinical samples. By using SMAP, we can detect mutations within 30 min including sample preparation. To validate the assay system for potential use in clinical diagnostics, we examined 45 NSCLC patients for EGFR mutations using sequencing and SMAP.
Results: The outcomes of the SMAP assay perfectly matched the sequencing results, except in one case where SMAP was able to identify a mutation that was not detected by sequencing. We also evaluated the sensitivity and specificity of SMAP in mutation detection for EGFR. In a serial dilution study, SMAP was able to find a mutation in a sample containing only 0.1% of the mutant allele in a mixture of wild-type genomic DNA. We also could show amplification of mutated DNA with only 30 copies per reaction.
Conclusions: The SMAP method offers higher sensitivity and specificity than alternative technologies, while eliminating the need for sequencing to identify mutations in the EGFR gene of NSCLC. It provides a robust and point-of-care accessible approach for a rapid identification of most patients likely to respond to gefitinib.
Classification Based on the Combination of Molecular and Pathologic Predictors is Superior to Molecular Classification on Prognosis in Colorectal Carcinoma
Authors: Xu Fangying , Wang Fenjuan , Di Meijuan , Huang Qiong , Wang Min , Hu Hu , Jin Yisen , Dong Jiankang , Lai Maode 
Published: September 2007

Abstract
Purpose: Classification based on a combination of molecular and pathologic predictors had never been done using hierarchical cluster analysis. For this purpose, we identified prognostic classification based on molecular predictors, pathologic and molecular predictors, and compared their respective prognostic efficacy together with that of tumor-node-metastasis (TNM) stage. Moreover, we investigated the prognostic significance of molecular classification in different TNM stage.
Experimental Design: Six pathologic predictors (p) and 13 immunohistochemical predictors (m) were investigated in 221 colorectal carcinomas. Unsupervised hierarchical clustering analysis was done to group the data. Survival analysis was done by Kaplan-Meier method and log-rank test, and by multivariate COX proportional hazard model.
Results: Six pathologic predictors and four molecular predictors were of significant prognostic value (P ≤ 0.05). One molecular predictor showed a trend toward significance (P = 0.085). Hierarchical clustering analysis was done based on different combinations (5p, 13m, 5m, 5p13m, and 5p5m), and distinct groups were produced except 5p (the TNM stage was excluded). Groups identified by 5m (P = 0.053) and 5p5m (P = 0.000) showed significant differences in prognosis. Groups identified by 5p5m and TNM stage were confirmed as the independent prognostic factors in a multivariate COX proportional hazard model. Moreover, groups identified by 5m could predict different prognoses in patients with stage II disease.
Conclusions: Classification based on pathologic and immunohistochemical predictors is superior to that based only on molecular predictors on prognosis. Classification based on 5m could identify additional different prognoses in patients with stage II disease.
Overexpression of Apollon, an Antiapoptotic Protein, Is Associated with Poor Prognosis in Childhood De novo Acute Myeloid Leukemia
Authors: Sung Ki Woong , Choi Jaewon , Hwang Yu Kyeong , Lee Sang Jin , Kim Hee-Jin , Lee Soo Hyun , Yoo Keon Hee , Jung Hye Lim , Koo Hong Hoe 
Published: September 2007

Abstract
Purpose: The genes that encode inhibitor of apoptosis proteins are frequently overexpressed in human cancers and can be associated with resistance to therapy. The overexpression of Apollon, a member of inhibitor of apoptosis proteins, is intuitively expected to be associated with unfavorable clinical features in malignant diseases; however, there have been no clinical studies reporting the prognostic relevance of Apollon expression in human malignancies. This study was done to investigate the clinical relevance of the expression of Apollon in childhood de novo acute myeloid leukemia.
Experimental Design: In 55 pediatric patients with de novo acute myeloid leukemia, the level of Apollon expression was determined by using quantitative reverse transcriptase–PCR and was analyzed with respect to the patients' clinical features and treatment outcomes.
Results: Apollon expression was found to be higher in patients with a leukocyte number of ≥10,000/μL, patients with extramedullary disease, and patients with the French-American-British classification subtype M7. In addition, Apollon overexpression (≥median expression) was associated with an unfavorable day 7 response to induction chemotherapy and also associated with a poorer 3-year relapse-free survival rate (48.3 ± 11.2% versus 78.7 ± 8.5%, P = 0.040).
Conclusion: This is the first study demonstrating the prognostic implication of the Apollon expression in human cancers, indicating that Apollon overexpression may be used as a poor prognostic marker in childhood acute myeloid leukemia through validation by further studies.
Detection of TMPRSS2-ERG Fusion Transcripts and Prostate Cancer Antigen 3 in Urinary Sediments May Improve Diagnosis of Prostate Cancer
Authors: Hessels Daphne , Smit Frank P. , Verhaegh Gerald W. , Witjes J. Alfred , Cornel Erik B. , Schalken Jack A. 
Published: September 2007

Abstract
Purpose: Early detection of prostate cancer can increase the curative success rate for prostate cancer. We studied the diagnostic usefulness of TMPRSS2-ERG fusion transcripts as well as the combination of prostate cancer antigen 3 (PCA3) RNA and TMPRSS2-ERG fusion transcripts in urinary sediments after digital rectal examination (DRE).
Experimental Design: A total of 78 men with prostate cancer–positive biopsies and 30 men with prostate cancer–negative biopsies were included in this study. After DRE, the first voided urine was collected, and urinary sediments were obtained. We used semiquantitative reverse transcription-PCR (RT-PCR) analysis followed by Southern blot hybridization with a radiolabeled probe for the detection TMPRSS2-ERG fusion transcripts in these urinary sediments. A quantitative RT-PCR assay for PCA3 was used to determine the PCA3 score in the same sediments.
Results: TMPRSS2-ERG fusion transcripts can be detected in the urine after DRE with a sensitivity of 37%. In this cohort of patients, the PCA3-based assay had a sensitivity of 62%. When both markers were combined, the sensitivity increased to 73%. Especially in the cohort of men with persistently elevated serum prostate-specific antigen levels and history of negative biopsies, the high positive predictive value of 94% of TMPRSS2-ERG fusion transcripts could give a better indication which patients require repeat biopsies.
Conclusion: In this report, we used for the first time the combination of the prostate cancer–specific biomarkers TMPRSS2-ERG and PCA3, which significantly improves the sensitivity for prostate cancer diagnosis.
Decitabine Up-regulates S100A2 Expression and Synergizes with IFN-γ to Kill Uveal Melanoma Cells
Authors: Gollob Jared A. , Sciambi Catherine J. 
Published: September 2007

Abstract
Purpose: Metastatic uveal melanoma is resistant to conventional chemotherapy and immunotherapy. In this study, we investigated the responsiveness of uveal melanoma cell lines to IFNs and the hypomethylating agent decitabine.
Experimental Design: The uveal melanoma cell lines 92-1, UW-1, OCM-1, and MKT-BR were exposed to varying concentrations of IFN-α, IFN-γ, and decitabine, alone and in combination. The effects of decitabine on gene expression were examined using DNA microarray analysis.
Results: We found that IFN-γ and decitabine induced cell death in uveal melanoma. Whereas a high concentration of IFN-γ (1,000 units/mL) was required to induce cell death, we observed a dose-related increase in cell death when decitabine was used at a range of 0.1 to 10 μmol/L. Strikingly, 1 μmol/L decitabine synergized with 10 to 1,000 units/mL IFN-γ to induce massive cell death. In contrast, decitabine had no effect on three cutaneous melanoma cell lines and exhibited no synergy with either IFN. In uveal melanoma, decitabine up-regulated the expression of genes involved in growth control and apoptosis and down-regulated genes that have been implicated in the malignant phenotype of cutaneous melanoma. The gene up-regulated to the greatest degree by decitabine and whose expression showed a dose-effect across the three concentrations of decitabine was S100A2, a putative tumor suppressor. The genes modulated by decitabine in uveal melanoma were largely unaffected in cutaneous melanoma.
Conclusions: These findings form a basis for testing the decitabine/IFN-γ combination in metastatic uveal melanoma and for exploring the role of S100A2 in the susceptibility of uveal melanoma to IFN-mediated cell death.
Targeting Lymphotoxin β Receptor with Tumor-Specific T Lymphocytes for Tumor Regression
Authors: Yang Dafeng , ud Din Najam , Browning Darren D. , Abrams Scott I. , Liu Kebin 
Published: September 2007

AbstractPurpose: One of the impediments of immunotherapy against cancer is the suppression of tumor-specific CTLs in the tumor microenvironment, partly due to the selective inhibition of the perforin pathway and the emergence of Fas-resistant tumors. Therefore, we sought to identify perforin- and Fas-independent cytotoxic pathways and explored the potential of targeting LTβR with tumor-specific CTLs to induce tumor rejection in vivo.Experimental Design: Fas-resistant tumors were examined for their susceptibility to perforin-deficient (pfp) CTLs via CTL adoptive transfer in mouse models of experimental lung metastasis. The specificity of LTβR, a cell surface death receptor, in causing tumor rejection by CTLs was analyzed by LTβR-specific neutralizing monoclonal antibody in vitro. The specificity and efficacy of LTβR in the suppression of established tumors was further investigated by silencing LTβR in tumor cells in vivo.Results: pfp CTLs exhibited significant cytotoxicity against Fas-resistant tumors in vivo. The perforin- and Fas-independent cytotoxicity was directly mediated, at least in part, by the adoptively transferred CTLs. It was observed that LTβR was expressed on the tumor cell surface, and LTα, LTβ, and LIGHT, all of which are ligands for LTβR, were either constitutively expressed or activated in the tumor-specific CTLs and primary CD8+ T cells. Blocking LTβR with LTβR-specific neutralizing monoclonal antibody decreased CTL cytotoxicity in vitro. Silencing LTβR using LTβR-specific short hairpin RNA reduced the ability of pfp CTLs to induce tumor rejection in vivo.Conclusion: LTβR directly mediates CTL-directed tumor rejection in vivo. Targeting LTβR with tumor-specific CTLs is a potential therapeutic approach.
ASMPKS: an analysis system for modular polyketide synthases
Authors: Tae Hongseok , Kong Eun-Bae , Park Kiejung 
Published: September 2007

Abstract

Background
Polyketides are secondary metabolites of microorganisms with diverse biological activities, including pharmacological functions such as antibiotic, antitumor and agrochemical properties. Polyketides are synthesized by serialized reactions of a set of enzymes called polyketide synthase(PKS)s, which coordinate the elongation of carbon skeletons by the stepwise condensation of short carbon precursors. Due to their importance as drugs, the volume of data on polyketides is rapidly increasing and creating a need for computational analysis methods for efficient polyketide research. Moreover, the increasing use of genetic engineering to research new kinds of polyketides requires genome wide analysis.

Results
We describe a system named ASMPKS (Analysis System for Modular Polyketide Synthesis) for computational analysis of PKSs against genome sequences. It also provides overall management of information on modular PKS, including polyketide database construction, new PKS assembly, and chain visualization. ASMPKS operates on a web interface to construct the database and to analyze PKSs, allowing polyketide researchers to add their data to this database and to use it easily. In addition, the ASMPKS can predict functional modules for a protein sequence submitted by users, estimate the chemical composition of a polyketide synthesized from the modules, and display the carbon chain structure on the web interface.

Conclusion
ASMPKS has powerful computation features to aid modular PKS research. As various factors, such as starter units and post-processing, are related to polyketide biosynthesis, ASMPKS will be improved through further development for study of the factors.
Transcriptional profiling of chickpea genes differentially regulated in response to high-salinity, cold and drought
Authors: Mantri Nitin L , Ford Rebecca , Coram Tristan E , Pang Edwin CK 
Published: September 2007

AbstractBackgroundCultivated chickpea (Cicer arietinum) has a narrow genetic base making it difficult for breeders to produce new elite cultivars with durable resistance to major biotic and abiotic stresses. As an alternative to genome mapping, microarrays have recently been applied in crop species to identify and assess the function of putative genes thought to be involved in plant abiotic stress and defence responses. In the present study, a cDNA microarray approach was taken in order to determine if the transcription of genes, from a set of previously identified putative stress-responsive genes from chickpea and its close relativeLathyrus sativus, were altered in chickpea by the three abiotic stresses; drought, cold and high-salinity. For this, chickpea genotypes known to be tolerant and susceptible to each abiotic stress were challenged and gene expression in the leaf, root and/or flower tissues was studied. The transcripts that were differentially expressed among stressed and unstressed plants in response to the particular stress were analysed in the context of tolerant/susceptible genotypes.ResultsThe transcriptional change of more than two fold was observed for 109, 210 and 386 genes after drought, cold and high-salinity treatments, respectively. Among these, two, 15 and 30 genes were consensually differentially expressed (DE) between tolerant and susceptible genotypes studied for drought, cold and high-salinity, respectively. The genes that were DE in tolerant and susceptible genotypes under abiotic stresses code for various functional and regulatory proteins. Significant differences in stress responses were observed within and between tolerant and susceptible genotypes highlighting the multiple gene control and complexity of abiotic stress response mechanism in chickpea.ConclusionThe annotation of these genes suggests that they may have a role in abiotic stress response and are potential candidates for tolerance/susceptibility.