bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of aquaporin 5 in antigen‐induced airway inflammation and mucous hyperproduction in mice
Authors: Shen Yao , Wang Yaoli , Chen Zhihong , Wang Diane , Wang Xiangdong , Jin Meiling , Bai Chunxue 
Published: June 2010

AbstractAirway inflammation and mucus hyperproduction play the central role in the development of asthma, although the mechanisms remain unclear. The aquaporin (AQP)‐5 may be involved in the process due to its contribution to the volume of liquid secreted from the airways. The present study firstly found the overexpression of AQP5 in the airway epithelium and submucosal glands of asthmatics. Furthermore, we aimed at evaluating the role of AQP5 in airway inflammation and mucous hyperproductions during chronic allergic responses to house dust mite (HDM). Bronchoalveolar lavage levels of interleukin (IL)‐2, IL‐4, IL‐10, interferon‐γ and Mucin 5AC (MUC5AC), and number of peribronchial and perivascular cells were measured in AQP5 wild‐type and AQP5 knockout (KO) mice. We found that HDM induced airway inflammation, lung Th2 cell accumulation and mucin hypersecretion in C57BL/6 mice rather than AQP5 KO mice. Expression of MUC5AC and MUC5B proteins and genes in the lung tissue was significantly lower in AQP5 KO mice. Thus, our results implicate involvement of AQP5 in the development of airway inflammation and mucous hyperproduction during chronic asthma.
Analysis of TSC Cortical Tubers by Deep Sequencing of TSC1, TSC2 and KRAS Demonstrates that Small Second‐Hit Mutations in these Genes are Rare Events
Authors: Qin Wei , Chan Jennifer A. , Vinters Harry V. , Mathern Gary W. , Franz David N. , Taillon Bruce E. , Bouffard Pascal , Kwiatkowski David J. 
Published: June 2010

AbstractTuberous sclerosis complex (TSC) is an often severe neurocutaneous syndrome. Cortical tubers are the predominant neuropathological finding in TSC, and their number and location has been shown to correlate roughly with the severity of neurologic features in TSC. Past studies have shown that genomic deletion events in TSC1 or TSC2 are very rare in tubers, and suggested the potential involvement of the MAPK pathway in their pathogenesis. We used deep sequencing to assess all coding exons of TSC1 and TSC2, and the activating mutation hot spots within KRAS in 46 tubers from TSC patients. Germline heterozygous mutations were identified in 81% of tubers. The same secondary mutation in TSC2 was identified in six tuber samples from one individual. Further study showed that this second hit mutation was widely distributed in the cortex from one cerebral hemisphere of this individual at frequencies up to 10%. No other secondary mutations were found in the other 40 tubers analyzed. These data indicate that small second hit mutations in any of these three genes are very rare in TSC tubers. However, in one TSC individual, a second hit TSC2 point mutation occurred early during brain development, and likely contributed to tuber formation.
Sonographic evaluation of renal transplant complications
Authors: Sutherland T , Temple F , Chang S , Hennessy O , Lee W‐K 
Published: June 2010

SummaryRenal transplants are the most frequent visceral transplant, and because of the absence of nephrotoxicity and radiation, ultrasound is widely used to monitor grafts and assess for complications. Complications can be categorised as vascular, parenchymal, ureteric and perinephric collections, with many occurring at predictable times post transplant. Awareness of these pathologies and their features is vital for all radiologists to enable early intervention and prolong graft survival.
‘GAP’ in radiotherapy services in Australia and New Zealand in 2009
Authors: Morgan GW , Barton M , Atkinson C , Millar J , Gogna N Kumar , Yeoh E 
Published: June 2010

SummaryAim: In this study we estimated (a) the number of linear accelerators required in Australia and New Zealand to achieve a 52.3% treatment rate; (b) the ‘GAP’ between the actual and required number of linear accelerators; c) the number of persons not treated (PNT), premature deaths (PD) and years of life lost (YLL) as a result of the ‘GAP’; and (d) to review the actions being taken by health jurisdictions in Australia and in New Zealand to address the ‘GAP’ and reach the 52.3% treatment rate.Material and Methods: The actual number of fully staffed and operating linear accelerators (A) in Australian and New Zealand was obtained from a survey of radiotherapy facilities in December 2009. The required number of linear accelerators (R) was calculated from the projected cancer incidence figures for 2009 and was based on 1.6 linear accelerators being required per 1000 new cancer patients. The ‘GAP’ in Radiotherapy services (G) was R minus A. The maximum treatment capacity (MTC) was the ratio of A over R multiplied by 52.3%, assuming that all linear accelerators were operating at 100% capacity. As each linear accelerator can treat 331 new patients each year, the number of new cancer PNT is G × 331. The estimated 5‐year survival benefit from radiotherapy is 16%, and the average survival for all patients receiving radiotherapy (radical and palliative) is 0.76 year. Hence, the number of PD attributed to the ‘GAP’ is PNT × 16%, and the YLL to cancer is PNT × 0.76. A literature search and local knowledge of health department Radiotherapy Plans in all jurisdictions were used to determine the action being taken to achieve a 52.3% treatment rate.Results: In 2009, the ‘GAP’ was 50 linear accelerators in Australia and the MTC was 38%, the same as it was in 1999, but there has been an increase in PNT each year from 7419 in 1999 to 16 550 in 2009, and PD each year increased from 1187 in 1999 to 2649 in 2009, and YLL each year increased from 5638 in 1999 to 12 585 in 2009. In New Zealand in 2009, the ‘GAP’ was nine linear accelerators and the MTC was 38%. An estimated 3310 persons did not receive radiotherapy in 2009 in New Zealand, and as a result, there were 523 PD and 2266 YLL. The review showed that new and replacement machines were being installed in all jurisdictions in Australia and in New Zealand. Only Victoria and Queensland have a Radiotherapy Plan beyond 2010, but both have underestimated the projected cancer incidence.Conclusion: Urgent action is needed by health departments and governments on both sides of the Tasman to improve access and equity to this essential cancer treatment. There is merit in the Baume Report recommendation of establishing a national body to oversee radiotherapy services in all jurisdictions in Australia. A similar central body should also be considered for New Zealand.
Identification of Neotropical felid faeces using RCP‐PCR
Authors: ROQUES S. , ADRADOS B. , CHAVEZ C. , KELLER C. , MAGNUSSON W. E. , PALOMARES F. , GODOY J. A. 
Published: June 2010

AbstractFaeces similarity among sympatric felid species has generally hampered their use in distributional, demographic and dietary studies. Here, we present a new and simple approach based on a set of species‐specific primers, for the unambiguous identification of faeces from sympatric neotropical felids (i.e. puma, jaguar, jaguarundi and ocelot/ margay). This method, referred to as rapid classificatory protocol‐PCR (RCP‐PCR), consists of a single‐tube multiplex PCR yielding species‐specific banding patterns on agarose gel. The method was optimized with samples of known origin (14 blood and 15 fresh faeces) and validated in faecal samples of unknown origin (n = 138), for some of which (n = 40) we also obtained species identification based on mtDNA sequencing. This approach proved reliable and provides high identification success rates from faeces. Its simplicity and cost effectiveness should facilitate its application for routine surveys of presence and abundance of these species.
Correlating Phosphatidylinositol 3-Kinase Inhibitor Efficacy with Signaling Pathway Status: In silico and Biological Evaluations
Authors: Dan Shingo , Okamura Mutsumi , Seki Mariko , Yamazaki Kanami , Sugita Hironobu , Okui Michiyo , Mukai Yumiko , Nishimura Hiroyuki , Asaka Reimi , Nomura Kimie , Ishikawa Yuichi , Yamori Takao 
Published: June 2010

Abstract
The phosphatidylinositol 3-kinase (PI3K) pathway is frequently activated in human cancers, and several agents targeting this pathway including PI3K/Akt/mammalian target of rapamycin inhibitors have recently entered clinical trials. One question is whether the efficacy of a PI3K pathway inhibitor can be predicted based on the activation status of pathway members. In this study, we examined the mutation, expression, and phosphorylation status of PI3K and Ras pathway members in a panel of 39 pharmacologically well-characterized human cancer cell lines (JFCR39). Additionally, we evaluated the in vitro efficacy of 25 PI3K pathway inhibitors in addition to conventional anticancer drugs, combining these data to construct an integrated database of pathway activation status and drug efficacies (JFCR39-DB). In silico analysis of JFCR39-DB enabled us to evaluate correlations between the status of pathway members and the efficacy of PI3K inhibitors. For example, phospho-Akt and KRAS/BRAF mutations prominently correlated with the efficacy and the inefficacy of PI3K inhibitors, respectively, whereas PIK3CA mutation and PTEN loss did not. These correlations were confirmed in human tumor xenografts in vivo, consistent with their ability to serve as predictive biomarkers. Our findings show that JFCR39-DB is a useful tool to identify predictive biomarkers and to study the molecular pharmacology of the PI3K pathway in cancer. Cancer Res; 70(12); 4982–94. ©2010 AACR.
Frequent Attenuation of the WWOX Tumor Suppressor in Osteosarcoma Is Associated with Increased Tumorigenicity and Aberrant RUNX2 Expression
Authors: Kurek Kyle C. , Del Mare Sara , Salah Zaidoun , Abdeen Suhaib , Sadiq Hussain , Lee Suk-hee , Gaudio Eugenio , Zanesi Nicola , Jones Kevin B. , DeYoung Barry , Amir Gail , Gebhardt Mark , Warman Matthew , Stein Gary S. , Stein Janet L. , Lian Jane B. , Aqeilan Rami I. 
Published: June 2010

Abstract
The WW domain-containing oxidoreductase (WWOX) is a tumor suppressor that is deleted or attenuated in most human tumors. Wwox-deficient mice develop osteosarcoma (OS), an aggressive bone tumor with poor prognosis that often metastasizes to lung. On the basis of these observations, we examined the status of WWOX in human OS specimens and cell lines. In human OS clinical samples, WWOX expression was absent or reduced in 58% of tumors examined (P &lt; 0.0001). Compared with the primary tumors, WWOX levels frequently increased in tumors resected following chemotherapy. In contrast, tumor metastases to lung often exhibited reduced WWOX levels relative to the primary tumor. In human OS cell lines having reduced WWOX expression, ectopic expression of WWOX inhibited proliferation and attenuated invasion in vitro, and suppressed tumorigenicity in nude mice. Expression of WWOX was associated with reduced RUNX2 expression in OS cell lines, whereas RUNX2 levels were elevated in femurs of Wwox-deficient mice. Furthermore, WWOX reconstitution in HOS cells was associated with downregulation of RUNX2 levels and RUNX2 target genes, consistent with the ability of WWOX to suppress RUNX2 transactivation activity. In clinical samples, RUNX2 was expressed in the majority of primary tumors and undetectable in most tumors resected following chemotherapy, whereas most metastases were RUNX2 positive. Our results deepen the evidence of a tumor suppressor role for WWOX in OS, furthering its prognostic and therapeutic significance in this disease. Cancer Res; 70(13); 5577–86. ©2010 AACR.
Concurrent Suppression of Integrin α5, Radixin, and RhoA Phenocopies the Effects of miR-31 on Metastasis
Authors: Valastyan Scott , Chang Amelia , Benaich Nathan , Reinhardt Ferenc , Weinberg Robert A. 
Published: June 2010

Abstract
miR-31 inhibits breast cancer metastasis via the pleiotropic suppression of a cohort of prometastatic target genes that include integrin α5 (ITGA5), radixin (RDX), and RhoA. We previously showed that the concomitant overexpression of ITGA5, RDX, and RhoA was capable of overriding the antimetastatic effects of ectopically expressed miR-31 in vivo. However, these prior studies failed to investigate whether the combined suppression of the endogenous mRNAs encoding these three proteins recapitulated the in vivo consequences of miR-31 expression on metastasis. We show here that short hairpin RNA–mediated concurrent downregulation of ITGA5, RDX, and RhoA is sufficient to phenocopy the full spectrum of described influences of miR-31 on metastasis in vivo, including the effects of this microRNA (miRNA) on local invasion, early post-intravasation events, and metastatic colonization. These findings provide mechanistic insights into the metastatic process and have implications about the importance of pleiotropy for the biological actions of miRNAs. Cancer Res; 70(12); 5147–54. ©2010 AACR.
Overexpression of p73 as a Tissue Marker for High-Risk Gastritis
Authors: Carrasco Gonzalo , Diaz Jose , Valbuena Jose R. , Ibanez Paulina , Rodriguez Paz , Araya Gabriela , Rodriguez Carolina , Torres Javiera , Duarte Ignacio , Aravena Edmundo , Mena Fernando , Barrientos Carlos , Corvalan Alejandro H. 
Published: June 2010

Abstract
Purpose: Histologic assessment of high-risk gastritis for the development of gastric cancer is not well defined. The identification of tissue markers together with the integration of histologic features will be required for this assessment.
Experimental Design: Matched tumor/nontumor adjacent mucosa (NTAM) of 91 early gastric cancer and 148 chronic gastritis cases were evaluated for histologic characteristics (atrophy, intestinal metaplasia, chronic inflammation, polymorphonuclear infiltration, and Helicobacter pylori) by the Sydney System. Atrophy risk assessment was also evaluated by the Operative Link on Gastritis Assessment (OLGA) staging system. Eight tissue markers (BRCA1, HSP90, STAT1, FHIT, EGFR, p73, p53, p16INK4a) and EBV were also evaluated by tissue microarray/immunohistochemistry/in situ hybridization platform. Data were analyzed by contingency tables (2 × 2) using Fisher's exact two-tailed test (P &lt; 0.001) and integrated by Significance Analysis of Microarrays (SAM) and clustering analysis.
Results: Histologically, NTAM have severe intestinal metaplasia/chronic inflammation and severe atrophy assessed by Sydney and OLGA staging systems. H. pylori infection was similar in both groups, and EBV was found only in 5.5% of the tumor samples. Overexpression of p73 was higher in NTAM (50.5%) than in chronic gastritis (10.8%; P &lt; 0.0001). Integration of histologic features and tissue markers showed that overexpression of p73, severe atrophy, and OLGA stage 4 were the most relevant features in NTAM. Clustering analysis correctly assigned NTAM and control cases (P &lt; 0.0001).
Conclusions: Overexpression of p73 should be considered for the assessment of high-risk chronic gastritis. SAM allows the integration of histology and tissue markers for this assessment. Clin Cancer Res; 16(12); 3253–9. ©2010 AACR.
Controversies in Cancer Stem Cells: Targeting Embryonic Signaling Pathways
Authors: Takebe Naoko , Ivy S. Percy 
Published: June 2010

Abstract
Selectively targeting cancer stem cells (CSC) or tumor-initiating cells (TIC; from this point onward referred to as CSCs) with novel agents is a rapidly emerging field of oncology. Our knowledge of CSCs and their niche microenvironments remains a nascent field. CSC's critical dependence upon self-renewal makes these regulatory signaling pathways ripe for the development of experimental therapeutic agents. Investigational agents targeting the Notch, Hedgehog, and Wnt pathways are currently in late preclinical development stages, with some early phase 1-2 testing in human subjects. This series of articles will provide an overview and summary of the current state of knowledge of CSCs, their interactive microenvironment, and how they may serve as important targets for antitumor therapies. We also examine the scope and stage of development of early experimental agents that specifically target these highly conserved embryonic signaling pathways. Clin Cancer Res; 16(12); 3106–12. ©2010 AACR.
Phase II Clinical and Pharmacokinetic Study of Plitidepsin 3-Hour Infusion Every Two Weeks Alone or with Dexamethasone in Relapsed and Refractory Multiple Myeloma
Authors: Mateos María Victoria , Cibeira Maria Teresa , Richardson Paul G. , Prosper Felipe , Oriol Albert , de la Rubia Javier , Lahuerta Juan José , García-Sanz Ramón , Extremera Sonia , Szyldergemajn Sergio , Corrado Claudia , Singer Harald , Mitsiades Constantine S. , Anderson Kenneth C. , Bladé Joan , San Miguel Jesús 
Published: June 2010

Abstract
Purpose: This trial evaluated the antitumor activity and safety of the marine-derived cyclodepsipeptide plitidepsin in patients with relapsed/refractory multiple myeloma.
Experimental Design: This was a prospective, multicenter, open-label, single-arm, phase II trial with plitidepsin at 5 mg/m2 as a 3-hour i.v. infusion every two weeks. The protocol was amended to allow patients with suboptimal response to single-agent plitidepsin to add 20 mg/day on days 1 to 4 of oral dexamethasone every two weeks.
Results: Fifty-one patients started treatment with plitidepsin and 47 were evaluable for efficacy. The overall response rate (complete response plus partial response plus minimal response) was 13% with plitidepsin alone and 22% in the cohort of patients with the addition of dexamethasone (n = 19, 18 evaluable). Both plitidepsin alone and with dexamethasone were feasible and well tolerated. Anemia (29%) and thrombocytopenia (18%) were the most frequent grade 3/4 hematologic toxicities. Fatigue (16%), muscular toxicity (6%), and transient alanine aminotransferase/aspartate aminotransferase (27%) and creatine phosphokinase (23%) increases were the most relevant nonhematologic side effects. A prolonged plasma half-life was observed in responding patients as compared with nonresponding patients (P = 0.009).
Conclusions: Single-agent plitidepsin has limited but reproducible activity in relapsed/refractory multiple myeloma patients. Activity observed after dexamethasone addition merits further study. Both regimens were well tolerated in this heavily pretreated population. Clin Cancer Res; 16(12); 3260–9. ©2010 AACR.
Statin Use and Risk of Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders
Authors: Sørensen Henrik Toft , Riis Anders Hammerich , Lash Timothy L. , Pedersen Lars 
Published: June 2010

Background—
Use of statins has been associated with an amyotrophic lateral sclerosis-like syndrome in 2 analyses of overlapping surveillance databases that record adverse events potentially related to prescription drug use. We assessed whether statin use is associated with the occurrence of amyotrophic lateral sclerosis and other motor neuron disorders.

Methods and Results—
We conducted a population-based case-control study in Northern Denmark, with a population of 1.8 million. From the Danish National Registry of Patients, we identified incident cases coded with amyotrophic lateral sclerosis or other motor neuron syndromes during the period from 1999 to 2008. We selected 10 population control subjects matched to cases on sex, birth year, and calendar time. Statin use was ascertained in the prescription database in the region—and so recorded before diagnosis—and associated with disease occurrence by conditional logistic regression adjusting for covariates. We identified 556 cases of amyotrophic lateral sclerosis or other motor neuron syndromes and 5560 population control subjects. The odds ratio associating disease occurrence with statin use was 0.96 (95% confidence interval, 0.73 to 1.28). Recent users of statins, former users, and users of short or long duration had similarly near-null associations.

Conclusions—
Any risk of amyotrophic lateral sclerosis associated with statin use probably is small, so outweighed by the important clinical advantages of statin medications to prevent and treat cardiovascular diseases.
In Defense of the City and the Polity: The Xuanmiao Monastery and the Qing Anti-Taiping Campaigns in Mid-Nineteenth Century Nanyang
Authors: Liu Xun 
Published: June 2010

AbstractThis paper examines the role played by the Quanzhen Daoist Xuanmiao monastery in the defense of Nanyang (Henan) during the Taiping rebellion. It shows that Daoist loyalty to the Qing state and to the local community did not just stem from the abbot's personal hatred of the Taiping; it also mirrored the monastery's established pattern of collaboration with the imperial state since the early Qing and its long history of ritual service to and economic involvement in the local community. Because of its wealth and cultural and political influence the Xuanmiao monastery functioned as a vital and dynamic actor in shaping the history and society of late nineteenth-century Nanyang. Cet article est consacré au rôle joué par un monastère taoïste Quanzhen, le Xuanmiao guan, dans la défense de Nanyang (Henan) pendant la rébellion des Taiping. Il montre que la loyauté des taoïstes envers l'État Qing et la communauté locale n'était pas simplement l'effet de la détestation qu'inspiraient les Taiping au supérieur du monastère; elle reflétait aussi un modèle bien établi de collaboration avec l'État impérial depuis le début des Qing, ainsi qu'une longue histoire de service rituel et d'intervention économique au bénéfice de la communauté. Grâce à sa richesse et à son influence politique et culturelle, le monastère Xuanmiao a été un acteur important et dynamique dans l'histoire et l'évolution sociale de Nanyang à la fin du xixe siècle.
Do Numerical Rating Scales and the Roland-Morris Disability Questionnaire capture changes that are meaningful to patients with persistent back pain?
Authors: Hush Julia M , Refshauge Kathryn M , Sullivan Gerard , De Souza Lorraine , McAuley James H 
Published: June 2010

Objectives: To investigate patients’ views about two common outcome measures used for back pain: Numerical Rating Scales for pain and the Roland-Morris Disability Questionnaire. Subjects: Thirty-six working adults who had previously sought primary care for back pain and who could speak and read English. Method: Eight focus groups were conducted to explore participants’ views about the 11-point Numerical Rating Scales and the 24-item Roland-Morris Disability Questionnaire. Each group was led by a facilitator and an interview topic guide was used. Audio recordings of focus groups were transcribed verbatim. Framework analysis was used to chart participants’ views and an interpretive analysis performed to explain the findings. Results: Participants reported that neither the Roland-Morris nor the Numerical Rating Scales captured the complex personal experience of pain or relevant changes in their condition. The time-frame of assessment was identified as particularly problematic and the Roland-Morris did not capture relevant functional domains. Conclusion: This study provides empirical data that working adults with persistent back pain consider these clinical outcome measures largely inadequate. These measures currently used for back pain may contribute to misleading conclusions about treatment efficacy and patient recovery.