bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dexamethasone Destabilizes Nmyc to Inhibit the Growth of Hedgehog-Associated Medulloblastoma
Authors: Heine Vivi M. , Priller Markus , Ling Jason , Rowitch David H. , Schüller Ulrich 
Published: June 2010

Abstract
Mouse studies indicate that the synthetic glucocorticoid dexamethasone (Dex) impairs the proliferation of granule neuron precursors in the cerebellum, which are transformed to medulloblastoma by activation of Sonic hedgehog (Shh) signaling. Here, we show that Dex treatment also inhibits Shh-induced tumor growth, enhancing the survival of tumor-prone transgenic mice. We found that Nmyc was specifically required in granule cells for Shh-induced tumorigenesis and that Dex acted to reduce Nmyc protein levels. Moreover, we found that Dex-induced destabilization of Nmyc is mediated by activation of glycogen synthase kinase 3β, which targets Nmyc for proteasomal degradation. Together, our findings show that Dex antagonizes Shh signaling downstream of Smoothened in medulloblastoma. Cancer Res; 70(13); 5220–5. ©2010 AACR.
Serum Signature of Hypoxia-Regulated Factors Is Associated with Progression after Induction Therapy in Head and Neck Squamous Cell Cancer
Authors: Byers Lauren Averett , Holsinger F. Christopher , Kies Merrill S. , William William N. , El-Naggar Adel K. , Lee J. Jack , Hu Jianhua , Lopez Adriana , Tran Hai T. , Yan Shaoyu , Du Zhiqiang , Ang K. Kian , Glisson Bonnie S. , Raso Maria Gabriela , Wistuba Ignacio I. , Myers Jeffrey N. , Hong Waun-Ki , Papadimitrakopoulou Vali , Lippman Scott M. , Heymach John V. 
Published: June 2010

Abstract
Tumor hypoxia regulates many cytokines and angiogenic factors (CAF) and is associated with worse prognosis in head and neck squamous cell cancer (HNSCC). Serum CAF profiling may provide information regarding the biology of the host and tumor, prognosis, and response to therapy. We investigated 38 CAFs in HNSCC patients receiving induction therapy on a phase II trial of carboplatin, paclitaxel, and cetuximab. CAFs were measured by multiplex bead assay and enzyme-linked immunosorbent assay in 32 patients. Baseline and postinduction CAF levels were correlated with disease progression (PD) and human papilloma virus (HPV) status by Wilcoxon rank sum test. Baseline levels of eight hypoxia-regulated CAFs (the “high-risk signature” including vascular endothelial growth factor, interleukins 4 and 8, osteopontin, growth-related oncogene-α, eotaxin, granulocyte-colony stimulating factor, and stromal cell–derived factor-1α) were associated with subsequent PD. Elevation in ≥6 of 8 factors was strongly associated with shorter time to progression (P = 0.001) and was 73% specific and 100% sensitive for PD. Increasing growth-related oncogene-α from baseline to week 6 was also associated with PD. Progression-free and overall survival were shorter in patients with HPV-negative tumors (P = 0.012 and 0.046, respectively), but no individual CAF was associated with HPV status. However, among 14 HPV-negative patients, the high-risk CAF signature was seen in all 6 patients with PD, but only 2 of 14 without PD. In conclusion, serum CAF profiling, particularly in HPV-negative patients, may be useful for identifying those at highest risk for recurrence. Mol Cancer Ther; 9(6); 1755–63. ©2010 AACR.
High-Content Phenotypic Profiling of Drug Response Signatures across Distinct Cancer Cells
Authors: Caie Peter D. , Walls Rebecca E. , Ingleston-Orme Alexandra , Daya Sandeep , Houslay Tom , Eagle Rob , Roberts Mark E. , Carragher Neil O. 
Published: June 2010

Abstract
The application of high-content imaging in conjunction with multivariate clustering techniques has recently shown value in the confirmation of cellular activity and further characterization of drug mode of action following pharmacologic perturbation. However, such practical examples of phenotypic profiling of drug response published to date have largely been restricted to cell lines and phenotypic response markers that are amenable to basic cellular imaging. As such, these approaches preclude the analysis of both complex heterogeneous phenotypic responses and subtle changes in cell morphology across physiologically relevant cell panels. Here, we describe the application of a cell-based assay and custom designed image analysis algorithms designed to monitor morphologic phenotypic response in detail across distinct cancer cell types. We further describe the integration of these methods with automated data analysis workflows incorporating principal component analysis, Kohonen neural networking, and kNN classification to enable rapid and robust interrogation of such data sets. We show the utility of these approaches by providing novel insight into pharmacologic response across four cancer cell types, Ovcar3, MiaPaCa2, and MCF7 cells wild-type and mutant for p53. These methods have the potential to drive the development of a new generation of novel therapeutic classes encompassing pharmacologic compositions or polypharmacology in appropriate disease context. Mol Cancer Ther; 9(6); 1913–26. ©2010 AACR.
Enhanced Expression of PCAF Endows Apoptosis Resistance in Cisplatin-Resistant Cells
Authors: Hirano Gen , Izumi Hiroto , Kidani Akihiko , Yasuniwa Yoshihiro , Han Bin , Kusaba Hitoshi , Akashi Koichi , Kuwano Michihiko , Kohno Kimitoshi 
Published: June 2010

Abstract
Histone acetyltransferase (HAT) regulates transcription. We have previously shown that two HAT genes, Clock and Tip60, are overexpressed, and upregulate glutathione biosynthesis and the expression of DNA repair genes in cisplatin-resistant cells. To better understand the mechanism of HAT-related drug resistance, we investigated the role of another HAT gene, p300/CBP-associated factor (PCAF), and found that PCAF was also overexpressed in cisplatin-resistant cells and endowed an antiapoptotic phenotype through enhanced E2F1 expression. PCAF-overexpressing cells showed enhanced expression of E2F1 and conferred cell resistance to chemotherapeutic agents. Downregulation of PCAF decreased E2F1 expression and sensitized cells to chemotherapeutic agents. Moreover, knockdown of PCAF induced G1 arrest and apoptosis. These results suggest that PCAF is one of pleiotropic factors for drug resistance and seems to be critical for cancer cell growth. Mol Cancer Res; 8(6); 864–72. ©2010 AACR.
The Kingdoms of Nanzhong China's Southwest Border Region Prior to the Eighth Century
Authors: Herman John 
Published: June 2010

AbstractThis article utilizes recent ethno-historical scholarship and archaeological discoveries in southwest China to examine the accuracy of the earliest Chinese historical sources dealing with the peoples and cultures in Nanzhong, the most common name for the southwest region (Yunnan, Guizhou, and southern Sichuan) prior to the Tang dynasty. Archaeology makes clear that Nanzhong was a settled border region with several highly sophisticated and divergent cultures. Early Chinese incursions into Nanzhong left an indelible mark on the peoples living there, but these brief and generally unsuccessful forays also influenced the views of China's elites regarding China's relations with this region. Since at least the Qin and Han, China's scholar-officials considered Nanzhong not only as an inhospitable frontier populated with uncivilized barbarians (manyi), but also as a peripheral part of China where intrepid commanders such as Tang Meng in the second century BCE and Zhuge Liang at the beginning of the third century CE had staked China's claim. This article casts doubt on the historical fiction of a staked claim. Cet article s'appuie sur les recherches ethno-historiques et des découvertes archéologiques récentes pour vérifier l'exactitude des sources chinoises les plus anciennes concernant les peuples et les cultures du Nanzhong, comme était communément appelé le Sud-Ouest (le Yunnan, le Guizhou et le sud du Sichuan) avant la dynastie des Tang. L'archéologie montre à l'évidence que le Nanzhong était une région frontière habitée, siège de plusieurs cultures hautement sophistiquées et différenciées. Si les premières incursions chinoises dans le Nanzhong ont laissé une empreinte indélébile sur les populations locales, ces campagnes brèves et en général infructueuses ont également influencé l'opinion des élites chinoises concernant les relations de la Chine avec le Sud-Ouest. Depuis au moins les Qin et les Han les lettrés-fonctionnaires chinois considéraient le Nanzhong non seulement comme une frontière inhospitalière peuplée de barbares dénués de civilisation (manyi), mais aussi comme un territoire périphérique de la Chine où des généraux intrépides comme Tang Meng au iie siècle avant notre ère et Zhuge Liang au début du iiie siècle de notre ère avaient établi des droits pour la Chine. L'article met en doute cette fiction historique d'un droit établi.
Language Shift in Northern Pakistan: The Case of Domaakí and Pashto
Authors: Weinreich Matthias 
Published: June 2010

AbstractThe paper is devoted to the phenomenon of mother tongue change, which is known as the most common course of language death. The languages under consideration are Domaakí, with ca. 350 speakers in the Nager and Hunza Valleys, and Pashto, as spoken by permanent migrants in ca. 150 households scattered all over the Northern Areas. By analysing and comparing the social environment of both speech communities the author attempts to illustrate the importance of the speakers' attitude towards their own mother tongue in the process of language shift.
LFA-1 activity state on dendritic cells regulates contact duration with T cells and promotes T-cell priming
Authors: Balkow Sandra , Heinz Stefanie , Schmidbauer Patricia , Kolanus Waldemar , Holzmann Bernhard , Grabbe Stephan , Laschinger Melanie 
Published: June 2010

AbstractA key event in the successful induction of adaptive immune responses is the antigen-specific activation of T cells by dendritic cells (DCs). Although LFA-1 (lymphocyte function–associated antigen 1) on T cells is considered to be important for antigen-specific T-cell activation, the role for LFA-1 on DCs remains elusive. Using 2 different approaches to activate LFA-1 on DCs, either by deletion of the αL-integrin cytoplasmic GFFKR sequence or by silencing cytohesin-1–interacting protein, we now provide evidence that DCs are able to make use of active LFA-1 and can thereby control the contact duration with naive T cells. Enhanced duration of DC/T-cell interaction correlates inversely with antigen-specific T-cell proliferation, generation of T-helper 1 cells, and immune responses leading to delayed-type hypersensitivity. We could revert normal interaction time and T-cell proliferation to wild-type levels by inhibition of active LFA-1 on DCs. Our data further suggest that cytohesin-1–interacting protein might be responsible for controlling LFA-1 deactivation on mature DCs. In summary, our findings indicate that LFA-1 on DCs needs to be in an inactive state to ensure optimal T-cell activation and suggest that regulation of LFA-1 activity allows DCs to actively control antigen-driven T-cell proliferation and effective immune responses.
Identifying drugs that cause acute thrombocytopenia: an analysis using 3 distinct methods
Authors: Reese Jessica A. , Li Xiaoning , Hauben Manfred , Aster Richard H. , Bougie Daniel W. , Curtis Brian R. , George James N. , Vesely Sara K. 
Published: June 2010

AbstractDrug-induced immune thrombocytopenia (DITP) is often suspected in patients with acute thrombocytopenia unexplained by other causes, but documenting that a drug is the cause of thrombocytopenia can be challenging. To provide a resource for diagnosis of DITP and for drug safety surveillance, we analyzed 3 distinct methods for identifying drugs that may cause thrombocytopenia. (1) Published case reports of DITP have described 253 drugs suspected of causing thrombocytopenia; using defined clinical criteria, 87 (34%) were identified with evidence that the drug caused thrombocytopenia. (2) Serum samples from patients with suspected DITP were tested for 202 drugs; drug-dependent, platelet-reactive antibodies were identified for 67 drugs (33%). (3) The Food and Drug Administration's Adverse Event Reporting System database was searched for drugs associated with thrombocytopenia by use of data mining algorithms; 1444 drugs had at least 1 report associated with thrombocytopenia, and 573 (40%) drugs demonstrated a statistically distinctive reporting association with thrombocytopenia. Among 1468 drugs suspected of causing thrombocytopenia, 102 were evaluated by all 3 methods, and 23 of these 102 drugs had evidence for an association with thrombocytopenia by all 3 methods. Multiple methods, each with a distinct perspective, can contribute to the identification of drugs that can cause thrombocytopenia.
Matrix metalloproteinase-9gene polymorphisms in nasal polyposis
Authors: Wang Ling-Feng , Chien Chen-Yu , Tai Chih-Feng , Kuo Wen-Rei , Hsi Edward , Juo Suh-Hang Hank 
Published: June 2010

Abstract

Background
Matrix metalloproteinase (MMP) is involved in the upper airway remodeling process. We hypothesized that genetic variants of the MMP-9 gene are associated with cases of chronic rhinosinusitis with nasal polyposis.

Methods
We conducted a case-control study where 203 cases of chronic rhinosinusitis with nasal polyposis and 730 controls were enrolled. Three tagging single nucleotide polymorphisms (SNPs) and one promoter functional SNP rs3918242 were selected. Hardy-Weinberg equilibrium (HWE) was tested for each SNP, and genetic effects were evaluated according to three inheritance modes. Haplotype analysis was also performed. Permutation was used to adjust for multiple testing.

Results
All four SNPs were in HWE. The T allele of promoter SNP rs3918242 was associated with chronic rhinosinusitis with nasal polyposis under the dominant (nominal p = 0.023, empirical p = 0.022, OR = 1.62) and additive models (nominal p= 0.012, empirical p = 0.011, OR = 1.60). The A allele of rs2274756 has a nominal p value of 0.034 under the dominant model and 0.020 under the additive model. Haplotype analysis including the four SNPs showed a global p value of 0.015 and the most significant haplotype had a p value of 0.0045. We did not see any SNP that was more significant in the recurrent cases.

Conclusions
We concluded that MMP-9 gene polymorphisms may influence susceptibility to the development of chronic rhinosinusitis with nasal polyposis in Chinese population.
Differential expression of centrosomal proteins at different stages of human glioma
Authors: Loh Joon-Khim , Lieu Ann-Shung , Chou Chia-Hua , Lin Fang-Yi , Wu Chia-Hung , Howng Sheng-Long , Chio Chung-Ching , Hong Yi-Ren 
Published: June 2010

Abstract

Background
High-grade gliomas have poor prognosis, requiring aggressive treatment. The aim of this study is to explore mitotic and centrosomal dysregulation in gliomas, which may provide novel targets for treatment.

Methods
A case-control study was performed using 34 resected gliomas, which were separated into low- and high-grade groups. Normal human brain tissue was used as a control. Using immunohistochemical analysis, immunofluorescent microscopy, and RT-PCR, detection of centrins 1 and 2, γ-tubulin, hNinein, Aurora A, and Aurora B, expression was performed. Analysis of the GBM8401 glioma cell line was also undertaken to complement the in vivo studies.

Results
In high-grade gliomas, the cells had greater than two very brightly staining centrioles within large, atypical nuclei, and moderate-to-strong Aurora A staining. Comparing with normal human brain tissue, most of the mRNAs expression in gliomas for centrosomal structural proteins, including centrin 3, γ-tubulin, and hNinein isoforms 1, 2, 5 and 6, Aurora A and Aurora B were elevated. The significant different expression was observed between high- and low-grade glioma in both γ-tubulin and Aurora A mRNA s. In the high-grade glioma group, 78.6% of the samples had higher than normal expression of γ-tubulin mRNA, which was significantly higher than in the low-grade glioma group (18.2%, p < 0.05).

Conclusions
Markers for mitotic dysregulation, such as supernumerary centrosomes and altered expression of centrosome-related mRNA and proteins were more frequently detected in higher grade gliomas. Therefore, these results are clinically useful for glioma staging as well as the development of novel treatments strategies.
Isothiocyanates induce oxidative stress and suppress the metastasis potential of human non-small cell lung cancer cells
Authors: Wu Xiang , Zhu Yu , Yan Huiqin , Liu Boning , Li Ying , Zhou Qinghua , Xu Ke 
Published: June 2010

Abstract

Background
Isothiocyanates are natural compounds found in consumable cruciferous vegetables. They have been shown to inhibit chemical carcinogenesis by a wide variety of chemical carcinogens in animal models. Recent studies have also shown that isothiocyanates have antitumor activity, inhibiting the growth of several types of cultured human cancer cells. Our previous study showed that PEITC inhibited human leukemia cells growth by inducing apoptosis. However, the effect of isothiocyanates on lung cancer cell metastasis has not been studied. In the present study, we investigated the inhibitory effects of BITC and PEITC on metastatic potential of highly metastatic human lung cancer L9981 cells.

Methods
Cell migration and invasion were measured by wound healing assay and transwell chemotaxis assay. Expression of metastasis-related genes was assessed by quantitative RT-PCR and Western blotting. The mechanisms of action were evaluated by flow cytometry, reporter assay and Western blotting.

Results
Our data showed that both BITC and PEITC inhibited L9981 cell growth in a dose-dependent manner, the IC50 values were 5.0 and 9.7 μM, respectively. Cell migrations were reduced to 8.1% and 16.5% of control, respectively; and cell invasions were reduced to 2.7% and 7.3% of control, respectively. Metastasis-related genes MMP-2, Twist and β-catenin were also modulated. BITC and PEITC inhibited cell survival signaling molecules Akt and NFκB activation. Moreover, BITC and PEITC increased ROS generation and caused GSH depletion. Pretreatment with NAC blocked BITC and PEITC induced ROS elevation and NFκB inhibition.

Conclusion
Our results indicated that BITC and PEITC suppress lung cancer cell metastasis potential by modulation of metastasis-related gene expression, inhibition of Akt/NFκB pathway. Induction of oxidative stress may play an important role.
Targeting melanoma growth and viability reveals dualistic functionality of the phosphonothionate analogue of carba cyclic phosphatidic acid
Authors: Altman Molly K , Gopal Vashisht , Jia Wei , Yu Shuangxing , Hall Hassan , Mills Gordon B , McGinnis A Cary , Bartlett Michael G , Jiang Guowei , Madan Damian , Prestwich Glenn D , Xu Yong , Davies Michael A , Murph Mandi M 
Published: June 2010

Abstract

Background
Although the incidence of melanoma in the U.S. is rising faster than any other cancer, the FDA-approved chemotherapies lack efficacy for advanced disease, which results in poor overall survival. Lysophosphatidic acid (LPA), autotaxin (ATX), the enzyme that produces LPA, and the LPA receptors represent an emerging group of therapeutic targets in cancer, although it is not known which of these is most effective.

Results
Herein we demonstrate that thio-ccPA 18:1, a stabilized phosphonothionate analogue of carba cyclic phosphatidic acid, ATX inhibitor and LPA1/3 receptor antagonist, induced a marked reduction in the viability of B16F10 metastatic melanoma cells compared with PBS-treated control by 80-100%. Exogenous LPA 18:1 or D-sn-1-O-oleoyl-2-O-methylglyceryl-3-phosphothioate did not reverse the effect of thio-ccPA 18:1. The reduction in viability mediated by thio-ccPA 18:1 was also observed in A375 and MeWo melanoma cell lines, suggesting that the effects are generalizable. Interestingly, siRNA to LPA3 (siLPA3) but not other LPA receptors recapitulated the effects of thio-ccPA 18:1 on viability, suggesting that inhibition of the LPA3 receptor is an important dualistic function of the compound. In addition, siLPA3 reduced proliferation, plasma membrane integrity and altered morphology of A375 cells. Another experimental compound designed to antagonize the LPA1/3 receptors significantly reduced viability in MeWo cells, which predominantly express the LPA3 receptor.

Conclusions
Thus the ability of thio-ccPA 18:1 to inhibit the LPA3 receptor and ATX are key to its molecular mechanism, particularly in melanoma cells that predominantly express the LPA3 receptor. These observations necessitate further exploration and exploitation of these targets in melanoma.
Enzymatic digestibility and ethanol fermentability of AFEX-treated starch-rich lignocellulosics such as corn silage and whole corn plant
Authors: Shao Qianjun , Chundawat Shishir PS , Krishnan Chandraraj , Bals Bryan , da Costa Sousa Leonardo , Thelen Kurt D , Dale Bruce E , Balan Venkatesh 
Published: June 2010

Abstract

Background
Corn grain is an important renewable source for bioethanol production in the USA. Corn ethanol is currently produced by steam liquefaction of starch-rich grains followed by enzymatic saccharification and fermentation. Corn stover (the non-grain parts of the plant) is a potential feedstock to produce cellulosic ethanol in second-generation biorefineries. At present, corn grain is harvested by removing the grain from the living plant while leaving the stover behind on the field. Alternatively, whole corn plants can be harvested to cohydrolyze both starch and cellulose after a suitable thermochemical pretreatment to produce fermentable monomeric sugars. In this study, we used physiologically immature corn silage (CS) and matured whole corn plants (WCP) as feedstocks to produce ethanol using ammonia fiber expansion (AFEX) pretreatment followed by enzymatic hydrolysis (at low enzyme loadings) and cofermentation (for both glucose and xylose) using a cellulase-amylase-based cocktail and a recombinant Saccharomyces cerevisiae 424A (LNH-ST) strain, respectively. The effect on hydrolysis yields of AFEX pretreatment conditions and a starch/cellulose-degrading enzyme addition sequence for both substrates was also studied.

Results
AFEX-pretreated starch-rich substrates (for example, corn grain, soluble starch) had a 1.5-3-fold higher enzymatic hydrolysis yield compared with the untreated substrates. Sequential addition of cellulases after hydrolysis of starch within WCP resulted in 15-20% higher hydrolysis yield compared with simultaneous addition of hydrolytic enzymes. AFEX-pretreated CS gave 70% glucan conversion after 72 h of hydrolysis for 6% glucan loading (at 8 mg total enzyme loading per gram glucan). Microbial inoculation of CS before ensilation yielded a 10-15% lower glucose hydrolysis yield for the pretreated substrate, due to loss in starch content. Ethanol fermentation of AFEX-treated (at 6% w/w glucan loading) CS hydrolyzate (resulting in 28 g/L ethanol at 93% metabolic yield) and WCP (resulting in 30 g/L ethanol at 89% metabolic yield) is reported in this work.

Conclusions
The current results indicate the feasibility of co-utilization of whole plants (that is, starchy grains plus cellulosic residues) using an ammonia-based (AFEX) pretreatment to increase bioethanol yield and reduce overall production cost.