bluuebunny/crossref_metadata_2025_split huggingface dataset:
Copy-Neutral Loss of Heterozygosity at the p53 Locus in Carcinogenesis of Esophageal Squamous Cell Carcinomas Associated with p53 Mutations
Authors: Saeki Hiroshi , Kitao Hiroyuki , Yoshinaga Keiji , Nakanoko Tomonori , Kubo Nobuhide , Kakeji Yoshihiro , Morita Masaru , Maehara Yoshihiko 
Published: February 2011

Abstract
Purpose: LOH at the p53 locus has been reported to be associated with esophageal squamous cell carcinogenesis. The aim of this study is to identify potential mechanisms resulting in LOH around the p53 locus in its carcinogenesis.
Experimental Design: We investigated 10 esophageal cancer cell lines and 91 surgically resected specimens, examining them for LOH at the p53 locus on chromosome 17. We examined the p53 gene by using microsatellite analysis, comparative genomic hybridization (CGH), FISH, and single-nucleotide polymorphism–CGH (SNP–CGH).
Results: In an analysis of specimens by microsatellite markers, a close positive correlation was found between p53 mutations and LOH at the p53 locus (P &lt; 0.01). Although four cell lines were found to be homozygous for p53 mutations, LOH at the p53 locus was not detected by CGH. Among two p53 mutant cancer cell lines and five p53 mutant/LOH cancer specimens analyzed by FISH, both the cell lines and four of the specimens exhibited no obvious copy number loss at the p53 locus. SNP–CGH analysis, which allows both determination of DNA copy number and detection of copy-neutral LOH, showed that LOHs without copy number change were caused by whole or large chromosomal alteration.
Conclusions: LOH without copy number change at the p53 locus was observed in p53 mutant esophageal squamous cell carcinomas. Our data suggest that copy-neutral LOH occurring as a result of chromosomal instability might be the major mechanism for inactivation of the intact allele in esophageal squamous cell carcinogenesis associated with p53 mutation. Clin Cancer Res; 17(7); 1731–40. ©2011 AACR.
White Paper on Adoptive Cell Therapy for Cancer with Tumor-Infiltrating Lymphocytes: A Report of the CTEP Subcommittee on Adoptive Cell Therapy
Authors: Weber Jeffrey , Atkins Michael , Hwu Patrick , Radvanyi Laszlo , Sznol Mario , Yee Cassian 
Published: February 2011

AbstractAdoptive T-cell therapy (ACT) using expanded autologous tumor-infiltrating lymphocytes (TIL) and tumor antigen-specific T cell expanded from peripheral blood are complex but powerful immunotherapies directed against metastatic melanoma. A number of nonrandomized clinical trials using TIL combined with high-dose interleukin-2 (IL-2) have consistently found clinical response rates of 50% or more in metastatic melanoma patients accompanied by long progression-free survival. Recent studies have also established practical methods for the expansion of TIL from melanoma tumors with high success rates. These results have set the stage for randomized phase II/III clinical trials to determine whether ACT provides benefit in stage IV melanoma. Here, we provide an overview of the current state-of-the art in T-cell–based therapies for melanoma focusing on ACT using expanded TIL and address some of the key unanswered biological and clinical questions in the field. Different phase II/III randomized clinical trial scenarios comparing the efficacy of TIL therapy to high-dose IL-2 alone are described. Finally, we provide a roadmap describing the critical steps required to test TIL therapy in a randomized multicenter setting. We suggest an approach using centralized cell expansion facilities that will receive specimens and ship expanded TIL infusion products to participating centers to ensure maximal yield and product consistency. If successful, this approach will definitively answer the question of whether ACT can enter mainstream treatment for cancer. Clin Cancer Res; 17(7); 1664–73. ©2011 AACR.
Measurements of Tumor Cell Autophagy Predict Invasiveness, Resistance to Chemotherapy, and Survival in Melanoma
Authors: Ma Xiao-Hong , Piao Shengfu , Wang Dan , Mcafee Quentin W. , Nathanson Katherine L. , Lum Julian J. , Li Lin Z. , Amaravadi Ravi K. 
Published: February 2011

Abstract
Purpose: Autophagy consists of lysosome-dependent degradation of cytoplasmic contents sequestered by autophagic vesicles (AV). The role of autophagy in determining tumor aggressiveness and response to therapy in melanoma was investigated in this study.
Experimental Design: Autophagy was measured in tumor biopsies obtained from metastatic melanoma patients enrolled on a phase II trial of temozolomide and sorafenib and correlated to clinical outcome. These results were compared with autophagy measurements in aggressive and indolent melanoma cells grown in two- and three-dimensional (3D) culture and as xenograft tumors. The effects of autophagy inhibition with either hydroxychloroquine or inducible shRNA (short hairpin RNA) against the autophagy gene ATG5 were assessed in three-dimensional spheroids.
Results: Patients whose tumors had a high autophagic index were less likely to respond to treatment and had a shorter survival compared with those with a low autophagic index. Differences in autophagy were less evident in aggressive and indolent melanoma cells grown in monolayer culture. In contrast, autophagy was increased in aggressive compared with indolent melanoma xenograft tumors. This difference was recapitulated when aggressive and indolent melanoma cells were grown as spheroids. Autophagy inhibition with either hydroxychloroquine or inducible shRNA against ATG5 resulted in cell death in aggressive melanoma spheroids, and significantly augmented temozolomide-induced cell death.
Conclusions: Autophagy is a potential prognostic factor and therapeutic target in melanoma. Three dimensional culture mimics the tumor microenvironment better than monolayer culture and is an appropriate model for studying therapeutic combinations involving autophagy modulators. Autophagy inhibition should be tested clinically in patients with melanoma. Clin Cancer Res; 17(10); 3478–89. ©2011 AACR.
Principles and Current Strategies for Targeting Autophagy for Cancer Treatment
Authors: Amaravadi Ravi K. , Lippincott-Schwartz Jennifer , Yin Xiao-Ming , Weiss William A. , Takebe Naoko , Timmer William , DiPaola Robert S. , Lotze Michael T. , White Eileen 
Published: February 2011

Abstract
Autophagy is an evolutionarily conserved, intracellular self-defense mechanism in which organelles and proteins are sequestered into autophagic vesicles that are subsequently degraded through fusion with lysosomes. Cells, thereby, prevent the toxic accumulation of damaged or unnecessary components, but also recycle these components to sustain metabolic homoeostasis. Heightened autophagy is a mechanism of resistance for cancer cells faced with metabolic and therapeutic stress, revealing opportunities for exploitation as a therapeutic target in cancer. We summarize recent developments in the field of autophagy and cancer and build upon the results presented at the Cancer Therapy Evaluation Program (CTEP) Early Drug Development meeting in March 2010. Herein, we describe our current understanding of the core components of the autophagy machinery and the functional relevance of autophagy within the tumor microenvironment, and we outline how this knowledge has informed preclinical investigations combining the autophagy inhibitor hydroxychloroquine (HCQ) with chemotherapy, targeted therapy, and immunotherapy. Finally, we describe ongoing clinical trials involving HCQ as a first generation autophagy inhibitor, as well as strategies for the development of novel, more potent, and specific inhibitors of autophagy. Clin Cancer Res; 17(4); 654–66. ©2011 AACR.
Spatial-Scale Dependence of Climate Model Performance in the CMIP3 Ensemble
Authors: Masson David , Knutti Reto 
Published: February 2011

Abstract
About 20 global climate models have been run for the Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report (AR4) to predict climate change due to anthropogenic activities. Evaluating these models is an important step to establish confidence in climate projections. Model evaluation, however, is often performed on a gridpoint basis despite the fact that models are known to often be unreliable at such small spatial scales. In this study, the annual mean values of surface air temperature and precipitation are analyzed. Using a spatial smoothing technique with a variable-scale parameter it is shown that the intermodel spread, as well as model errors from observations, is reduced as the characteristic smoothing scale increases. At the same time, the ability to reproduce small-scale features is reduced and the simulated patterns become fuzzy. Depending on the variable of interest, the location, and the way that data are aggregated, different optimal smoothing scales from the gridpoint size to about 2000 km are found to give good agreement with present-day observation yet retain most regional features of the climate signal. Higher model resolution surprisingly does not imply much better agreement with temperature observations, in particular with stronger smoothing, and resolving smaller scales therefore does not necessarily seem to improve the simulation of large-scale climate features. Similarities in mean temperature and precipitation fields for a pair of models in the ensemble persist locally for about a century into the future, providing some justification for subtracting control errors in the models. Large-scale to global errors, however, are not well preserved over time, consistent with a poor constraint of the present-day climate on the simulated global temperature and precipitation response.
New Gravity Wave Treatments for GISS Climate Models
Authors: Geller Marvin A. , Zhou Tiehan , Ruedy Reto , Aleinov Igor , Nazarenko Larissa , Tausnev Nikolai L. , Sun Shan , Kelley Maxwell , Cheng Ye 
Published: February 2011

AbstractPrevious versions of GISS climate models have either used formulations of Rayleigh drag to represent unresolved gravity wave interactions with the model-resolved flow or have included a rather complicated treatment of unresolved gravity waves that, while being climate interactive, involved the specification of a relatively large number of parameters that were not well constrained by observations and also was computationally very expensive. Here, the authors introduce a relatively simple and computationally efficient specification of unresolved orographic and nonorographic gravity waves and their interaction with the resolved flow. Comparisons of the GISS model winds and temperatures with no gravity wave parameterization; with only orographic gravity wave parameterization; and with both orographic and nonorographic gravity wave parameterizations are shown to illustrate how the zonal mean winds and temperatures converge toward observations. The authors also show that the specifications of orographic and nonorographic gravity waves must be different in the Northern and Southern Hemispheres. Then results are presented where the nonorographic gravity wave sources are specified to represent sources from convection in the intertropical convergence zone and spontaneous emission from jet imbalances. Finally, a strategy to include these effects in a climate-dependent manner is suggested.
The Concertación and Homelessness in Chile
Authors: Özler Ş. İlgü 
Published: February 2011

Housing has been a persistent problem in Chile. Concertación governments have sought to address the housing problem through a continuation of the neoliberal policies established by the dictatorship under Pinochet, emphasizing housing as commodity rather than a right. A study of housing policies under the Concertación reveals improvements in the quantitative supply with increased spending. Yet these neoliberal housing programs stratify residents into categories of poverty in which the poorest residents compete against one another to access subsidies and find housing. These programs prevent citizens from acting collectively to demand policy changes; instead housing is treated as a problem of poor families who must seek to resolve their situation on the individual level by enrolling in subsidy programs. As a result, the unequal distribution of housing in Chile continues, and the poor end up in low-quality housing in economically segregated neighborhoods far from jobs and services. La vivienda ha sido un problema constante en Chile. Los gobiernos de Concertación han intentado atender este problema a través de la continuación de una serie de políticas neoliberales establecidas durante la dictadura de Pinochet, las cuales presentan la vivienda como mercancía más que un derecho. Un estudio de las políticas de vivienda bajo la Concertación revela mejoras en la cantidad de oferta a raíz de un gasto mayor. Sin embargo, estos programas neoliberales de vivienda estratifican a los residentes en categorías de pobreza dentro de las cuáles lo más pobres deben competir unos contra otros para tener acceso a los subsidios y encontrar casa. Estos programas evitan que la ciudadanía actúe de manera colectiva y exija cambios en las políticas. En lugar de esto, la vivienda se trata como un problema de las familias pobres, las cuales deben encontrar una solución individual a su situación enrolándose en los programas de subsidio. El resultado es que Chile continúa con una distribución desigual de la vivienda y los pobres acaban en casas de mala calidad en vecindades económicamente marginales lejos de sus trabajos y servicios.
Endurance Athletes and Type 1 Diabetes
Authors: Devadoss Mercy , Kennedy Laura , Herbold Nancie 
Published: February 2011

Objective The purpose of this study was to gain insight into the current diabetes management practices of endurance athletes with type 1 diabetes and to compare these practices with the guidelines for athletes established by the American Diabetes Association (ADA). Methods Participants included in this descriptive study were endurance athletes aged 18 years and older with type 1 diabetes. The survey questions were based on the current clinical recommendations for endurance athletes with type 1 diabetes, as established by the ADA. A link to the questionnaire was posted on the Web site of the Diabetes Exercise and Sports Association (DESA). A total of 38 questions were included in the survey, and 91 usable surveys were received. Analysis of variance was used for several comparisons using SPSS version 17. Results Half of the clinical guidelines were followed by the participants. Among these, about 50% followed many of the guidelines “most of the time” or “almost always” and 40% followed the guidelines “sometimes” or “most of the time.” Results of ANOVA showed several trends (nonsignificant) in the occurrence of low blood glucose when the guidelines were not followed. Conclusion Endurance athletes with type 1 diabetes do not consistently follow the clinical guidelines for blood glucose management as recommended by the ADA. The results of this study reflect a need among athletes for diabetes management education programs that promote a better understanding of the potential negative side effects of suboptimal blood glucose control.
Auditory Changes in Mobile Users
Authors: Panda Naresh K. , Modi Rahul , Munjal Sanjay , Virk Ramandeep S. 
Published: February 2011

ObjectiveGenuine concerns are being raised as to the potential health risks posed by electromagnetic frequency exposure secondary to mobile phone usage. This study was undertaken to assess and compare potential changes in hearing function at the level of the inner ear and central auditory pathway due to chronic exposure to electromagnetic waves from both global system for mobile communications (GSM) and code division multiple access (CDMA) mobile phone usage.DesignCohort study.SettingTertiary referral center.Subjects and MethodsOne hundred twenty‐five subjects who were long‐term mobile phone users (more than 1 year; 63 GSM and 62 CDMA) and 58 controls who had never used mobile phones underwent audiological investigations including pure tone audiometry (250‐12 kHz), tympanometry, distortion product otoacoustic emissions (DPOAE), auditory brain responses (ABR), and middle latency responses (MLRs). The changes in various parameters were studied in mobile‐using and non‐mobile‐using ears of both GSM and CDMA subjects and corresponding ears of the controls to ascertain the effects of electromagnetic exposure.ResultsGSM and CDMA users were found to be at a significantly higher risk of having DPOAE absent as compared with controls (P <. 05). They were found to have higher speech frequency thresholds and lower MLR wave and Na and Pa amplitudes. More than 3 years of mobile phone usage emerged as a risk factor (P <. 05). The damage done was bilateral, with the quantum of damage being the same for both GSM and CDMA.ConclusionLong‐term and intensive GSM and CDMA mobile phone use may cause damage to cochlea as well as the auditory cortex.
The Value of Otolaryngologists’ Services in America
Authors: Frake Paul C. , Domanski Mark , Howell Rebecca J. , Troost Thomas 
Published: February 2011

ObjectiveTo evaluate the perceived monetary value of physician services within the general population and to foster academic discussion about the finances of clinical practice in the setting of recent health care reform.Study Design, Subjects, and MethodsNational survey of 409 members of the general population and review of Centers for Medicare and Medicaid Services data.ResultsThe perceived monetary values of office visits were comparable to the actual physician reimbursements. However, the average perceived value associated with surgical treatments was significantly higher than the true Medicare reimbursement amount. For example, survey participants said that a reasonable price for a doctor to be paid for performing a tonsillectomy is $955.58, whereas the national average Medicare reimbursement is $257.74. Furthermore, 59% of respondents also believe that insurers, Medicare, and Medicaid pay doctors more than the respondent’s perceived value for each service.ConclusionThe current patterns of Centers for Medicare and Medicaid Services reimbursement reveal a trend of declining payments for physician services. A survey of a sample of the general population indicated that most people believe that their doctors are paid far more than they actually are. It is important for otolaryngologists and head and neck surgeons to understand and discuss the economic forces that continue to shape our practices, and it is vital that we all play an active role in the discussions surrounding the evolution of the American health care system.
Impact of pH Monitoring on Laryngopharyngeal Reflux Treatment
Authors: Friedman Michael , Maley Alexander , Kelley Kanwar , Pulver Tanya , Foster Michael , Fisher Michelle , Joseph Ninos 
Published: February 2011

ObjectivesTreatment of laryngopharyngeal reflux (LPR) often suffers from poor patient compliance and hence poor symptom improvement. The aim of this study was to determine whether 24‐hour oropharyngeal pH monitoring was associated with higher rates of treatment compliance and symptom improvement compared with empirical treatment for LPR.Study DesignRetrospective, case‐control study.SettingTertiary care center.Subjects and MethodsCharts were reviewed from 170 consecutive adult patients diagnosed with LPR from January 2008 to March 2010. After clinical diagnosis, all patients were offered the option of empiric treatment with a proton pump inhibitor versus treatment based on a 24‐hour oropharyngeal pH study using the Dx‐pH system (Restech, San Diego, California). Treatment compliance and pretreatment and posttreatment reflux symptom index (RSI) scores were compared for the 2 groups. Only consecutive patients with complete data were included.ResultsOne‐hundred and seventy patients were included in 2 groups. Group I consisted of 73 patients who underwent pH monitoring. Group II consisted of 70 patients treated empirically. Compliance with medication therapy (68.5% vs 50.0%, P =. 019) and lifestyle modification (82.2 vs 25.7%, P =. 0001) were greater among patients in group I. Symptom improvement was greater among patients in group I following treatment compared with patients in group II, with a significantly greater reduction in RSI (36.6% vs 24.4%, P =. 023).ConclusionAmong our patient population, treatment of LPR based on pH monitoring resulted in greater compliance, as well as greater symptom improvement, compared with empirical therapy alone.
A case–control study of risk factors for multiple sclerosis in Iran
Authors: Alonso Alvaro , Cook Stuart D , Maghzi Amir-Hadi , Divani Afshin A 
Published: February 2011

Background: Numerous studies have assessed risk factors for multiple sclerosis (MS), although none have been conducted previously in Iran. Objective: The objective of this study was to study lifestyle and environmental risk factors of MS in the Iranian population. Methods: A case–control study, including 394 MS cases and 394 matched controls, was conducted in MS clinics in different Iranian cities. Information on lifestyles, environmental exposures, and past medical history was obtained from medical charts and phone interviews. Results: In multivariable analysis, sunlight exposure was associated with a lower risk of MS: the odds ratio (OR) and 95% confidence interval (CI) of MS associated with a 1-h increment in daily sunlight was 0.62 (0.53–0.73). Smoking was associated with MS risk in women (OR: 6.48, 95% CI: 1.46–28.78), but not in men (OR: 0.72, 95% CI: 0.31–1.68) ( p = 0.002 for interaction). Finally, past history of common surgical procedures, infectious disorders, or exposure to pets and farm animals was not associated with MS risk. Conclusions: Different modifiable lifestyles, including sunlight exposure and smoking, were associated with lower MS risk in Iran. Interventions aimed at promoting smoking cessation and, more importantly, at increasing exposure to sunlight might contribute to the prevention of MS.
Long-term safety profile of mitoxantrone in a French cohort of 802 multiple sclerosis patients: a 5-year prospective study
Authors: Le Page E , Leray E , Edan G ,   for the French Mitoxantrone Safety Group
Published: February 2011

Background: From 2001, a French multicentre study was conducted prospectively in a large cohort of MS patients and annually updated up to at least 5 years after initiation of MITOX therapy. Objective: To determine long-term safety profile of mitoxantrone (MITOX) in multiple sclerosis (MS). Methods: Eight hundred and two patients from 12 MS centres (308 relapsing–remitting, 352 secondary progressive and 142 primary progressive) received MITOX monthly for 6 months (87%) or every 3 months (13%). Patients underwent clinical and haematologic evaluations before every MITOX infusion and every 6–12 months up to 5 years after MITOX start. Echocardiograms were performed at the start and end of MITOX and up to 5 years after. Results: The cohort was followed for 5354 patient-years (mean). One out of 802 patients (0.1%) presented with acute congestive heart failure and 39 out of 794 patients (4.9%) presented with asymptomatic left ventricular ejection fraction reduction under 50% (persistent in 11 patients (28%), transient in 27 patients (69%), on the last scan at year 5 in 1 patient). Two cases of therapy-related leukaemia (0.25%) were detected 20 months after MITOX start (one death and one with 8 years confirmed remission). Of the 317 women treated before the age of 45, 17.3% developed a persistent age-dependant amenorrhea. Conclusion: This large cohort with at least 5 years of follow-up provided good insights into the long-term safety profile of MITOX in MS.