bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear Factor-κB p65 Inhibits Mitogen-Activated Protein Kinase Signaling Pathway in Radioresistant Breast Cancer Cells
Authors: Ahmed Kazi M. , Dong Shaozhong , Fan Ming , Li Jian Jian 
Published: December 2006

Abstract
The molecular mechanism by which tumor cells increase their resistance to therapeutic radiation remains to be elucidated. We have previously reported that activation of nuclear factor-κB (NF-κB) is causally associated with the enhanced cell survival of MCF+FIR cells derived from breast cancer MCF-7 cells after chronic exposure to fractionated ionizing radiation. The aim of the present study was to reveal the context of NF-κB pathways in the adaptive radioresistance. Using cell lines isolated from MCF+FIR populations, we found that the elevated NF-κB activity was correlated with enhanced clonogenic survival, and increased NF-κB subunit p65 levels were associated with a decrease in phosphorylation of mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK in all radioresistant MCF+FIR cell lines. Further irradiation with 30 fractions of radiation also inhibited MEK/ERK phosphorylation in paired cell lines of MCF+FIR and parental MCF-7 cells. Activation of ataxia-telangiectasia mutated (ATM) protein, a sensor to radiation-induced DNA damage, was elevated with increased interaction with NF-κB subunits p65 and p50. The interaction between p65 and MEK was also enhanced in the presence of activated ATM. In contrast, both interaction and nuclear translocation of p65/ERK were reduced. Inhibition of NF-κB by overexpression of mutant IκB increased ERK phosphorylation. In addition, MEK/ERK inhibitor (PD98059) reduced the interaction between p65 and ERK. Taken together, these results suggest that NF-κB inhibits ERK activation to enhance cell survival during the development of tumor adaptive radioresistance. (Mol Cancer Res 2006;4(12):945–55)
Regulation of systemic and local neutrophil responses by G-CSF during pulmonary Pseudomonas aeruginosa infection
Authors: Gregory Alyssa D. , Hogue Lisa A. , Ferkol Thomas W. , Link Daniel C. 
Published: December 2006

AbstractGranulocyte colony-stimulating factor (G-CSF) regulates the production, maturation, and function of neutrophils. Its expression is often induced during infection, resulting in high concentrations of G-CSF in inflammatory exudates and in the blood, suggesting that it may regulate both local and systemic neutrophil responses. Herein, we characterize the neutrophil response in G-CSFR−/− mice following intratracheal injection with Pseudomonas aeruginosa–laden agarose beads, modeling the pulmonary infection observed in many patients with cystic fibrosis. G-CSFR−/− mice are markedly susceptible to bronchopulmonary P aeruginosa infection, exhibiting decreased survival and bacterial clearance as well as extensive damage to lung tissue. The systemic neutrophil response was mediated primarily by enhanced neutrophil release from the bone marrow rather than increased neutrophil production and was attenuated in G-CSFR−/− mice. Despite normal to increased local production of inflammatory chemokines, neutrophil accumulation into the infected lung of G-CSFR−/− mice was markedly reduced. Moreover, the percentage of apoptotic neutrophils in the lung was elevated, suggesting that G-CSF signals may play an important role in regulating neutrophil survival at the inflammatory site. Collectively, these data provide new evidence that G-CSF signals play important but specific roles in the regulation of the systemic and local neutrophil response following infection.
Family history of hematopoietic malignancies and risk of non-Hodgkin lymphoma (NHL): a pooled analysis of 10 211 cases and 11 905 controls from the International Lymphoma Epidemiology Consortium (InterLymph)
Authors: Wang Sophia S. , Slager Susan L. , Brennan Paul , Holly Elizabeth A. , De Sanjose Silvia , Bernstein Leslie , Boffetta Paolo , Cerhan James R. , Maynadie Marc , Spinelli John J. , Chiu Brian C. H. , Cocco Pier Luigi , Mensah Fiona , Zhang Yawei , Nieters Alexandra , Dal Maso Luigino , Bracci Paige M. , Costantini Adele Seniori , Vineis Paolo , Severson Richard K. , Roman Eve , Cozen Wendy , Weisenburger Dennis , Davis Scott , Franceschi Silvia , La Vecchia Carlo , Foretova Lenka , Becker Nikolaus , Staines Anthony , Vornanen Martine , Zheng Tongzhang , Hartge Patricia 
Published: December 2006

AbstractA role for genetic susceptibility in non-Hodgkin lymphoma (NHL) is supported by the accumulating evidence of common genetic variations altering NHL risk. However, the pattern of NHL heritability remains poorly understood. We conducted a pooled analysis of 10 211 NHL cases and 11 905 controls from the International Lymphoma Epidemiology Consortium (InterLymph) to evaluate NHL risk among those with hematopoietic malignancies in first-degree relatives. Odds ratios (ORs) and 95% confidence intervals (CIs) of NHL and its subtypes were estimated from unconditional logistic regression models with adjustment for confounders. NHL risk was elevated for individuals who reported first-degree relatives with NHL (OR = 1.5; 95% CI = 1.2-1.9), Hodgkin lymphoma (OR = 1.6; 95% CI = 1.1-2.3), and leukemia (OR = 1.4; 95% CI = 1.2-2.7). Risk was highest among individuals who reported a brother with NHL (OR = 2.8; 95% CI = 1.6-4.8) and was consistent for all NHL subtypes evaluated. If a first-degree relative had Hodgkin lymphoma, NHL risk was highest if the relative was a parent (OR = 1.7; 95% CI = 1.0-2.9). If a first-degree relative had leukemia, NHL risk was highest among women who reported a sister with leukemia (OR = 3.0; 95% CI = 1.6-5.6). The pattern of NHL heritability appeared to be uniform across NHL subtypes, but risk patterns differed by specific hematopoietic malignancies and the sex of the relative, revealing critical clues to disease etiology.
Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis
Authors: Cortes Jorge , Rousselot Philippe , Kim Dong-Wook , Ritchie Ellen , Hamerschlak Nelson , Coutre Steven , Hochhaus Andreas , Guilhot Francois , Saglio Giuseppe , Apperley Jane , Ottmann Oliver , Shah Neil , Erben Philipp , Branford Susan , Agarwal Prasheen , Gollerkeri Ashwin , Baccarani Michele 
Published: December 2006

AbstractThe prognosis for patients with chronic myeloid leukemia (CML) in myeloid blast crisis (MBC) or lymphoid blast crisis (LBC) remains poor. Although imatinib can induce responses in a subset of these patients, resistance to the drug develops rapidly. Dasatinib is a novel, oral, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases. After promising phase 1 results, we report the results of phase 2 clinical trials of dasatinib in patients with imatinib-resistant or -intolerant blast crisis CML (MBC, n = 74; LBC, n = 42). At the 8-month follow-up, dasatinib induced major hematologic responses (MaHRs) in 34% and 31% of MBC- and LBC-CML patients and major cytogenetic responses (MCyRs) in 31% and 50% of these patients, respectively. Most (86%) of these MCyRs were complete cytogenetic responses (CCyRs). Responses were rapid and durable: 88% and 46%, respectively, of MBC- and LBC-CML patients achieving MaHR had not experienced disease progression at the 8-month follow-up. Response rates were similar in patients with and without BCR-ABL mutations known to confer resistance to imatinib. Dasatinib was well tolerated. Nonhematologic adverse events were mild to moderate. Cytopenias were common and could be managed by dose modification. Dasatinib is highly active and produces hematologic and cytogenetic responses in a significant number of patients with imatinib-resistant or -intolerant MBC- and LBC-CML. These trials were registered at www.clinicaltrials.gov as #CA180006 and #CA180015.
A common genetic factor for Parkinson disease in ethnic Chinese population in Taiwan
Authors: Fung Hon-Chung , Chen Chiung-Mei , Hardy John , Singleton Andrew B , Wu Yih-Ru 
Published: December 2006

Abstract

Background
Parkinson's disease (PD) is the most common neurodegenerative movement disorder, characterized clinically by resting tremor, bradykinesia, postural instability and rigidity. The prevalence of PD is approximately 2% of the population over 65 years of age and 1.7 million PD patients (age ≥ 55 years) live in China. Recently, a common LRRK2 variant Gly2385Arg was reported in ethnic Chinese PD population in Taiwan. We analyzed the frequency of this variant in our independent PD case-control population of Han Chinese from Taiwan.

Methods
305 patients and 176 genetically unrelated healthy controls were examined by neurologists and the diagnosis of PD was based on the published criteria. The region of interest was amplified with standard polymerase chain reaction (PCR). PCR fragments then were directly sequenced in both forward and reverse directions. Differences in genotype frequencies between groups were assessed by the X
2 test, while X
2 analysis was used to test for the Hardy-Weinberg equilibrium.

Results
Of the 305 patients screened we identified 27 (9%) with heterozygous G2385R variant. This mutation was only found in 1 (0.5%) in our healthy control samples (odds ratio = 16.99, 95% CI: 2.29 to 126.21, p = 0.0002). Sequencing of the entire open reading frame of LRRK2 in G2385R carriers revealed no other variants.

Conclusion
These data suggest that the G2385R variant contributes significantly to the etiology of PD in ethnic Han Chinese individuals. With consideration of the enormous and expanding aging Chinese population in mainland China and in Taiwan, this variant is probably the most common known genetic factor for PD worldwide.
Development and validation of vectors containing multiple siRNA expression cassettes for maximizing the efficiency of gene silencing
Authors: Wang Shunqing , Shi Zhenqi , Liu Wei , Jules Joel , Feng Xu 
Published: December 2006

Abstract

Background
RNA interference (RNAi) was originally identified as a biological process in which short double-stranded RNA (dsRNA) suppress the expression of genes complimentary to the dsRNA. This cellular intrinsic gene silencing mechanism has subsequently been developed as a useful tool for studies of gene function. A major strategy for producing small interfering RNA (siRNA) in cultured cells involves the use of siRNA expression vectors in which a RNA polymerase III (Pol III) promoter and transcription stop signal are designed to constitute a functional siRNA expression cassette for production of siRNA. However, most of the available vectors contain only one siRNA expression cassette.

Results
In order to maximize the efficiency and versatility of the vector-based siRNA approach, we have developed vectors containing multiple (up to six) tandem siRNA expression cassettes. Moreover, we demonstrated that these vectors can be used not only to produce different siRNA to simultaneously suppress the expression of multiple genes but also to maximize the silencing of a singe gene.

Conclusion
The vectors containing multiple siRNA expression cassettes can serve as useful tools for maximizing the efficiency of gene silencing.
Identification of ciliary and ciliopathy genes in Caenorhabditis elegansthrough comparative genomics
Authors: Chen Nansheng , Mah Allan , Blacque Oliver E , Chu Jeffrey , Phgora Kiran , Bakhoum Mathieu W , Hunt Newbury C Rebecca , Khattra Jaswinder , Chan Susanna , Go Anne , Efimenko Evgeni , Johnsen Robert , Phirke Prasad , Swoboda Peter , Marra Marco , Moerman Donald G , Leroux Michel R , Baillie David L , Stein Lincoln D 
Published: December 2006

Abstract
Background
The recent availability of genome sequences of multiple related Caenorhabditis species has made it possible to identify, using comparative genomics, similarly transcribed genes in Caenorhabditis elegans and its sister species. Taking this approach, we have identified numerous novel ciliary genes in C. elegans, some of which may be orthologs of unidentified human ciliopathy genes.

Results
By screening for genes possessing canonical X-box sequences in promoters of three Caenorhabditis species, namely C. elegans, C. briggsae and C. remanei, we identified 93 genes (including known X-box regulated genes) that encode putative components of ciliated neurons in C. elegans and are subject to the same regulatory control. For many of these genes, restricted anatomical expression in ciliated cells was confirmed, and control of transcription by the ciliogenic DAF-19 RFX transcription factor was demonstrated by comparative transcriptional profiling of different tissue types and of daf-19(+) and daf-19(-) animals. Finally, we demonstrate that the dye-filling defect of dyf-5(mn400) animals, which is indicative of compromised exposure of cilia to the environment, is caused by a nonsense mutation in the serine/threonine protein kinase gene M04C9.5.

Conclusion
Our comparative genomics-based predictions may be useful for identifying genes involved in human ciliopathies, including Bardet-Biedl Syndrome (BBS), since the C. elegans orthologs of known human BBS genes contain X-box motifs and are required for normal dye filling in C. elegans ciliated neurons.
Comparison of Free and Total Forms of Serum Human Kallikrein 2 and Prostate-Specific Antigen for Prediction of Locally Advanced and Recurrent Prostate Cancer
Authors: Steuber Thomas , Vickers Andrew J , Serio Angel M , Vaisanen Ville , Haese Alexander , Pettersson Kim , Eastham James A , Scardino Peter T , Huland Hartwig , Lilja Hans 
Published: December 2006

Abstract
Background: We evaluated the association of total and free forms of serum human kallikrein 2 (hK2) and prostate-specific antigen (PSA) with prostate cancers of unfavorable prognosis.
Methods: We retrospectively measured total PSA (tPSA), free PSA (fPSA), and total hK2 (thK2) in preoperative serum samples from 867 men [and assessed free hK2 (fhK2) measured in 577 of these men] treated with radical prostatectomy for clinically localized prostate cancer. Associations between biomarker concentrations and extracapsular extension, seminal vesicle invasion, and biochemical recurrence (BCR) were evaluated. A subset of patients with PSA ≤10 μg/L, the group most commonly seen in clinical practice in the US, was analyzed.
Results: thK2 was the strongest predictor of extracapsular extension and seminal vesicle invasion (areas under the ROC curve [AUC], 0.662 and 0.719, respectively), followed by tPSA (AUC, 0.654 and 0.663). All biomarkers were significant predictors of BCR. hK2 forms, but not PSA forms, remained highly significant for predicting BCR in the low-PSA group. Combining tPSA, fPSA, and thK2 in a multivariable model improved prediction compared with any biomarker used individually (AUC, 0.711, 0.755, and 0.752 for this combination predicting extracapsular extension, seminal vesicle invasion, and BCR, respectively; P &lt;0.001 for all).
Conclusions: Increased concentrations of hK2 in the blood are significantly associated with unfavorable features of prostate cancer, and thK2 is predictive of locally advanced and recurrent cancer in patients with PSA ≤10 μg/L. Independent of tPSA and fPSA, hK2 predicts unfavorable prognosis.
Human brain structural change related to acute single exposure to sarin
Authors: Yamasue Hidenori , Abe Osamu , Kasai Kiyoto , Suga Motomu , Iwanami Akira , Yamada Haruyasu , Tochigi Mamoru , Ohtani Toshiyuki , Rogers Mark A. , Sasaki Tsukasa , Aoki Shigeki , Kato Tadafumi , Kato Nobumasa 
Published: December 2006

AbstractObjectiveThis study aimed to identify persistent morphological changes subsequent to an acute single‐time exposure to sarin, a highly poisonous organophosphate, and the neurobiological basis of long‐lasting somatic and cognitive symptoms in victims exposed to sarin.MethodsThirty‐eight victims of the 1995 Tokyo subway sarin attack, all of whom had been treated in an emergency department for sarin intoxication, and 76 matched healthy control subjects underwent T1‐weighted and diffusion tensor magnetic resonance imaging (DTI) in 2000 to 2001. Serum cholinesterase (ChE) levels measured immediately and longitudinally after the exposure and the current severity of chronic reports in the victims were also evaluated.ResultsThe voxel‐based morphometry exhibited smaller than normal regional brain volumes in the insular cortex and neighboring white matter, as well as in the hippocampus in the victims. The reduced regional white matter volume correlated with decreased serum cholinesterase levels and with the severity of chronic somatic complaints related to interoceptive awareness. Voxel‐based analysis of diffusion tensor magnetic resonance imaging further demonstrated an extensively lower than normal fractional anisotropy in the victims. All these findings were statistically significant (corrected p < 0.05).InterpretationSarin intoxication might be associated with structural changes in specific regions of the human brain, including those surrounding the insular cortex, which might be related to elevated subjective awareness of internal bodily status in exposed individuals. Ann Neurol 2006
Neural precursors attenuate autoimmune encephalomyelitis by peripheral immunosuppression
Authors: Einstein Ofira , Fainstein Nina , Vaknin Ilan , Mizrachi‐Kol Rachel , Reihartz Etti , Grigoriadis Nikolaos , Lavon Iris , Baniyash Michal , Lassmann Hans , Ben‐Hur Tamir 
Published: December 2006

AbstractObjectiveIntracerebroventricular or intravenous (IV) injection of neural precursor cells (NPCs) attenuates experimental autoimmune encephalomyelitis (EAE), the animal model of multiple sclerosis. Although stem cell therapy was introduced initially for cell replacement, we examine here whether NPCs possess immunomodulatory effects.MethodsWe examined the effects of systemic administration of NPCs on central nervous system (CNS) inflammation in EAE and the interactions between NPCs and T cells in vitro and in vivo.ResultsIV NPC therapy decreased significantly CNS inflammation and tissue injury and attenuated the clinical severity of EAE. IV‐injected NPCs could not be found in the CNS but were detected in lymphoid organs. Coculture experiments showed that NPCs inhibited the activation and proliferation of lymph node–derived T cells in response to CNS‐derived antigens and to nonspecific polyclonal stimuli. The relevance of NPC/lymph node cell interactions in vivo was further demonstrated when lymph node cells obtained from IV NPC‐treated mice exhibited poor encephalitogenicity on transfer to naive mice and caused a markedly milder EAE compared with those obtained from nontreated mice.InterpretationIV administration of neural precursors inhibits EAE by a peripheral immunosuppressive effect. Our findings suggest a profound bystander inhibitory effect of NPCs on T‐cell activation and proliferation in the lymph nodes, leading to amelioration of EAE. Ann Neurol 2006
First trimester exposure to paroxetine and risk of cardiac malformations in infants: the importance of dosage
Authors: Bérard Anick , Ramos Élodie , Rey Évelyne , Blais Lucie , St.‐André Martin , Oraichi Driss 
Published: December 2006

AbstractBACKGROUND: Conflicting findings with regard to the teratogenic risks of first trimester use of paroxetine have prompted the FDA, Health Canada, and the manufacturer of the drug to issue warnings against its use during pregnancy. Given that untreated depression during pregnancy can lead to deleterious effect on the mother and her unborn fetus, data on the relationship between the dose and the range of malformations is warranted. This study attempts to quantify the association between first trimester exposure to paroxetine and congenital cardiac malformations, adjusting for possible confounders, and to quantify the dose–response relationship between paroxetine use and cardiac defects. METHODS: The Medication and Pregnancy registry was used. This population‐based registry was built by linking three administrative databases (RAMQ, Med‐Écho, and ISQ), and includes all pregnancies in Quebec between 01/01/1997 and 06/30/2003. Date of entry in the registry is the date of the first day of the last menstrual period. To be eligible for this study, women had to: 1) be 15–45 years of age at entry; 2) be covered by the RAMQ drug plan ≥12 months before and during pregnancy; 3) be using only one type of antidepressant during the first trimester; and 4) have a live birth. Two nested case‐control studies were carried out comparing the prevalence of paroxetine use in the first trimester of pregnancy to the prevalence of other antidepressant exposures during the same time period. Cases were defined as: 1) any major malformations; or 2) any cardiac malformations diagnosed in the first year of life; controls were defined as no major or minor malformations. Multivariate logistic regression techniques were used to analyze data. RESULTS: Among the 1,403 women meeting inclusion criteria, 101 infants with major congenital malformations were identified; 24 had cardiac malformations. Adjusting for possible confounders, the use of paroxetine (odds ratio [OR] = 1.38, 95% confidence interval [CI] = 0.49–3.92), and the use of other SSRIs (OR = 0.89, 95% CI = 0.28–2.84) during the first trimester of pregnancy did not increase the risk of congenital cardiac malformations compared with the use of non‐SSRI antidepressants. When considering the dose, however, a dose–response relationship was observed, thus women exposed to >25 mg/day of paroxetine during the first trimester of pregnancy were at increased risk of having an infant with major congenital malformations (adjusted [adj] OR = 2.23, 95% CI = 1.19, 4.17), or major cardiac malformations (adj OR = 3.07, 95% CI = 1.00, 9.42). CONCLUSIONS: Gestational exposure to paroxetine is associated with major congenital malformations and major cardiac malformations for only first trimester exposure above 25 mg/day. Birth Defects Res (Part B). © 2006 Wiley‐Liss, Inc.
Coupled positive and negative feedback circuits form an essential building block of cellular signaling pathways
Authors: Kim Dongsan , Kwon Yung‐Keun , Cho Kwang‐Hyun 
Published: December 2006

AbstractCellular circuits have positive and negative feedback loops that allow them to respond properly to noisy external stimuli. It is intriguing that such feedback loops exist in many cases in a particular form of coupled positive and negative feedback loops with different time delays. As a result of our mathematical simulations and investigations into various experimental evidences, we found that such coupled feedback circuits can rapidly turn on a reaction to a proper stimulus, robustly maintain its status, and immediately turn off the reaction when the stimulus disappears. In other words, coupled feedback loops enable cellular systems to produce perfect responses to noisy stimuli with respect to signal duration and amplitude. This suggests that coupled positive and negative feedback loops form essential signal transduction motifs in cellular signaling systems. BioEssays 29: 85–90, 2007. © 2006 Wiley Periodicals, Inc.