bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of differentially expressed proteins in oral squamous cell carcinoma by MALDI‐TOF MS
Authors: Thiel Uta J. E. , Feltens Ralph , Adryan Boris , Gieringer Rita , Brochhausen Christoph , Schuon Robert , Fillies Thomas , Grus Franz , Mann Wolf J. , Brieger Juergen 
Published: December 2010

J Oral Pathol Med (2010) 40: 369–379Purpose:  To explore the presence of differentially expressed proteins in OSCC for discrimination of tumour and normal mucosa to establish potential biomarkers and therapeutic targets.Experimental Design:  Paired protein samples of 12 individuals (tongue cancer and non‐cancerous mucosa) were separated by two‐dimensional polyacrylamid gel electrophoresis. The protein patterns were compared pairwise and protein spots were quantified. We identified about 70 regulated proteins which we subsequently identified by MALDI‐TOF mass spectrometry.Results:  Cancerous and non‐cancerous tissues could be most precisely distinguished by a panel of proteins. They include the heat shock proteins (hsp)70 and 90, keratins (ck) 5, 6, 13, 14, 16, 17 and 19, beta globin, alpha‐2‐actin, stratifin, tropomyosin, calreticulin precursor, beta‐2‐tubulin, galectin7, thioredoxin, involucrin, adenylyl‐cyclase‐associated protein, disulfide isomerase‐associated protein, thyrosine 3‐monooxygenase, MYL2 and the s100 calcium binding protein. MYL3, cardiac muscle alpha actin 1 proprotein and transferrin were under‐represented in OSCC. Six biomarkers, ck6 und ck13, beta globin, alpha‐2‐actin, hsp70 and hsp90 discriminated best between cancerous and non‐cancerous oral tissues. All over‐expressed proteins were analysed by STRING‐analysis to highlight experimentally determined and computationally predicted interactions between the proteins. Especially involucrin, hsp70, calreticulin precursor, stratifin, (ck) 5, 6, 14, 19, tyrosine 3‐monooxygenase, beta‐2‐tubulin and disulfide isomerase associated protein showed multiple relations.Conclusion:  We identified six proteins which are differentially expressed in most OSCC compared to healthy tissues. Of those, by string analysis, multiple interaction partners are assumed for hsp70. This protein is supposed to be the most promising candidate as marker molecule and target for OSCC therapy.
MPEG‐hexPLA Micelles as Novel Carriers for Hypericin, a Fluorescent Marker for Use in Cancer Diagnostics
Authors: Mondon Karine , Zeisser‐Labouèbe Magali , Gurny Robert , Möller Michael 
Published: December 2010

AbstractOvarian cancer is the most common gynecological cancer diagnosed in Western countries. Detection of micrometastases at an early stage of the disease could lead to a cure rate of 90% by limiting the spread of the disease outside the ovaries. In this article, hypericin (Hy), a hydrophobic photosensitizer used for the photodynamic diagnosis (PD) of ovarian cancer, was efficiently incorporated into a core of micelles made from methoxy‐poly(ethylene glycol) and hexyl‐substituted poly(lactides) copolymers. The fate of these micelles following intravenous injection was studied in vivo in two ovarian tumor‐bearing animal models. In the chick embryo chorioallantoic membrane model, 17 times more Hy accumulated in tumor nodules when Hy was delivered with micelles than when Hy was delivered as an ethanol solution. Studies of the biodistribution of Hy in Fisher rats revealed escape of these nanosized micelles (<32 nm) from the mononuclear phagocyte system. Hy‐loaded micelles showed maximal accumulation in tumors and demonstrated the best tumor/muscle contrast visible 3 h after injection in the rat model. The rapid and highly selective accumulation of Hy in tumors that we demonstrated in this study suggests that these micelle formulations could be used for the PD of ovarian cancer in the future.
Research Methodology: An Innovative Approach to a Venerable Course
Authors: Morrel‐Samuels Palmer , Zimmerman Marc 
Published: December 2010

AbstractThis paper outlines a number of innovations that we have recently implemented in the Research Methodology Course at the University of Michigan’s School of Public Health. Consistent with the goals of evidence‐based medicine, evidence‐based public health, intrinsic motivation, and phase 4 (T4) translational research, we have placed the emphasis on enhancing the students’ desire to learn—and more specifically on their desire to learn rigorous methods for conducting useful research that delivers practical benefits in a straightforward manner. A dozen innovations, along with some preliminary outcomes, are outlined in detail. Clin Trans Sci 2010; Volume 3: 309–311
Enhancing Participant Safety through Electronically Generated Medication Order Sets in a Clinical Research Environment: A Medical Informatics Initiative
Authors: Formea Christine M. , Picha Andrew F. , Griffin Monica G. , Schaller Jane A. , Lee Mary R. 
Published: December 2010

AbstractWhile clinical medicine is often well supported by health system information technology infrastructure, clinical research may need to create strategies to use clinical‐medicine informational technology tools. The authors describe a medication‐safety initiative that was carried out in a National Institutes of Health Clinical and Translational Science Award (CTSA)‐sponsored clinical research environment. A web based, medical informatics application was designed and implemented that allowed research groups to build protocol specific, electronic medication templates that were subsequently used to create participant‐specific medication order sets for conductance of clinical research activities in the CTSA‐sponsored clinical research environment. The medical informatics initiative eliminated typewritten or handwritten medication orders, created research protocol‐specific templates meeting institutional order‐writing requirements, and formalized a rigorous review and approval process. Enhancing safety in medication ordering and prescribing practices in a clinical research environment provided the background for multidisciplinary cooperation in medical informatics. Clin Trans Sci 2010; Volume 3: 312–315
Pseudoxanthoma Elasticum: A Streamlined, Ethnicity‐based Mutation Detection Strategy
Authors: LaRusso Jennifer , Ringpfeil Franziska , Uitto Jouni 
Published: December 2010

AbstractPseudoxanthoma elasticum (PXE), an autosomal recessive multisystem disorder, is caused by mutations in the ABCC6 gene, and approximately 300 distinct mutations representing >1,000 mutant alleles have been disclosed thus far. Few population‐based studies have reported mutational hotspots in some geographic areas. In this study, we attempted to correlate recurring mutations with the individuals’ ethnic origin. Specifically, we plotted our international database of 70 families from distinct or mixed ethnic backgrounds against their mutations. The frequent p.R1141X mutation was distributed widely across Europe, while deletion of exons 23–29 (del23–29) was encountered in Northern Europe and in Northern Mediterranean countries. p.R1138W may be a marker for French descent, evidenced by its presence also in French Canadians. The splice site transition mutation 3736–1G→A was seen in the neighboring countries Greece and Turkey, whereas 2542 delG occurs only in the Japanese. Two mutations seem to be present worldwide without evidence of a founder effect, p.Q378X and p.R1339C, suggesting the presence of mutational hotspots. Knowledge of this distribution will allow us to streamline mutation screening through a targeted, stepwise approach when the ethnicity of a patient is known. This will facilitate the identification of individuals at risk, improving their care to prevent ophthalmological and vascular disease. Clin Trans Sci 2010; Volume 3: 295–298
Exploring the Functional Advantages of Spatial and Visual Cognition From an Architectural Perspective
Authors: Lathrop Scott D. , Wintermute Samuel , Laird John E. 
Published: December 2010

AbstractWe present a general cognitive architecture that tightly integrates symbolic, spatial, and visual representations. A key means to achieving this integration is allowing cognition to move freely between these modes, using mental imagery. The specific components and their integration are motivated by results from psychology, as well as the need for developing a functional and efficient implementation. We discuss functional benefits that result from the combination of multiple content‐based representations and the specialized processing units associated with them. Instantiating this theory, we then discuss the architectural components and processes, and illustrate the resulting functional advantages in two spatially and visually rich domains. The theory is then compared to other prominent approaches in the area.
Saharan dust and daily mortality in Emilia-Romagna (Italy)
Authors: Zauli Sajani Stefano , Miglio Rossella , Bonasoni Paolo , Cristofanelli Paolo , Marinoni Angela , Sartini Claudio , Goldoni Carlo Alberto , De Girolamo Gianfranco , Lauriola Paolo 
Published: December 2010

ObjectiveTo investigate the association between Saharan dust outbreaks and natural, cardiovascular and respiratory mortality.MethodsA case–crossover design was adopted to assess the effects of Saharan dust days (SDD) on mortality in the Emilia-Romagna region of Italy. The population under study consisted of residents in the six main towns of the central-western part of the region who died between August 2002 and December 2006. The association of Saharan dust outbreaks and PM10concentration with mortality was estimated using conditional logistic regression, adjusted for apparent temperature, holidays, summer population decrease, flu epidemic weeks and heat wave days. The role of the interaction term between PM10and SDD was analysed to test for effect modification induced by SDD on the PM10-mortality concentration–response function. Separate estimates were undertaken for hot and cold seasons.ResultsWe found some evidence of increased respiratory mortality for people aged 75 or older on SDD. Respiratory mortality increased by 22.0% (95% CI 4.0% to 43.1%) on the SDD in the whole year model and by 33.9% (8.4% to 65.4%) in the hot season model. Effects substantially attenuated for natural and cardiovascular mortality with ORs of 1.042 (95% CI 0.992 to 1.095) and 1.043 (95% CI 0.969 to 1.122), respectively.ConclusionsOur findings suggest an association between respiratory mortality in the elderly and Saharan dust outbreaks. We found no evidence of an effect modification of dust events on the concentration–response relationship between PM10and daily deaths. Further work should be carried out to clarify the mechanism of action.
Detection of Coxiella burnetii in placenta and abortion samples from British ruminants using real‐time PCR
Authors: Jones R. M. , Twomey D. F. , Hannon S. , Errington J. , Pritchard G. C. , Sawyer J. 
Published: December 2010

A real‐time PCR was developed to detect Coxiella burnetii (the cause of Q fever) in ruminant placentas and aborted fetuses. Primer and probe sets previously developed for human tissue studies were used to target the insertion sequence IS1111 gene for C burnetii. The assay was highly sensitive, with a limit of detection of 10 copies of template, theoretically equating to a single bacterium, and did not cross‐react with a panel of other bacteria. To determine sensitivity on field samples submitted for the diagnosis of abortion, results using the IS1111 PCR assay were compared with a com 1 PCR assay. When applied to ruminant abortion material, including placental cotyledons and fetal samples, the IS1111 and com 1 assays yielded positive results in 23 (25 per cent) of 93 and 19 (20 per cent) of 93 samples, respectively. One infected goat herd was monitored for 31 months: 57 (92 per cent) of 62 placental cotyledon samples from aborting and non‐aborting goats, and 10 (30 per cent) of 33 fetal samples were positive by the IS1111 PCR assay.
Cancer Causes Cardiac Atrophy and Autophagy in a Sexually Dimorphic Manner
Authors: Cosper Pippa F. , Leinwand Leslie A. 
Published: December 2010

Abstract
Approximately one-third of cancer deaths are caused by cachexia, a severe form of skeletal muscle and adipose tissue wasting that affects men more than women. The heart also undergoes atrophy in cancer patients, but the mechanisms and the basis for apparent sex differences are unclear. In a mouse colon-adenocarcinoma model, cancer causes a loss of cardiac mass due to a decrease in cardiac myocyte size that is associated with reduced levels of all sarcomeric proteins. Unlike skeletal muscle cachexia, atrophic hearts do not upregulate the ubiquitin-proteasome system or its activity but increase autophagy. Thus, cancer causes cardiac atrophy by a mechanism distinct from that in skeletal muscle. Male tumor-bearing mice have a more severe phenotype than females, including greater cardiac mass loss and mortality, a more robust pro-inflammatory response to the tumor, and greater cardiac autophagy. In females, estrogen protects against cancer-induced cardiac atrophy and body weight loss by signaling through its receptor. Sex differences in cardiac atrophy need to be considered during the treatment of patients suffering from chemotherapy-induced cardiomyopathy to prevent exacerbation of cardiac dysfunction. Cancer Res; 71(5); 1710–20. ©2010 AACR.
A Hypoxia- and α-Fetoprotein–Dependent Oncolytic Adenovirus Exhibits Specific Killing of Hepatocellular Carcinomas
Authors: Kwon Oh-Joon , Kim Pyung-Hwan , Huyn Steven , Wu Lily , Kim Minjung , Yun Chae-Ok 
Published: December 2010

Abstract
Purpose: Oncolytic adenoviruses (Ad) constitute a new promising modality of cancer gene therapy that displays improved efficacy over nonreplicating Ads. We have previously shown that an E1B 19-kDa-deleted oncolytic Ad exhibits a strong cell-killing effect but lacks tumor selectivity. To achieve hepatoma-restricted cytotoxicity and enhance replication of Ad within the context of tumor microenvironment, we used a modified human α-fetoprotein (hAFP) promoter to control the replication of Ad with a hypoxia response element (HRE).
Experimental Design: We constructed Ad-HRE6/hAFPΔ19 and Ad-HRE12/hAFPΔ19 that incorporated either 6 or 12 copies of HRE upstream of promoter. The promoter activity and specificity to hepatoma were examined by luciferase assay and fluorescence-activated cell sorting analysis. In addition, the AFP expression- and hypoxia-dependent in vitro cytotoxicity of Ad-HRE6/hAFPΔ19 and Ad-HRE12/hAFPΔ19 was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and cytopathic effect assay. In vivo tumoricidal activity on subcutaneous and liver orthotopic model was monitored by noninvasive molecular imaging.
Results: Ad-HRE12/hAFPΔ19 exhibited enhanced tumor selectivity and cell-killing activity when compared with Ad-hAFPΔ19. The tumoricidal activity of Ad-HRE12/hAFPΔ19 resulted in significant inhibition of tumor growth in both subcutaneous and orthotopic models. Histologic examination of the primary tumor after treatment confirmed accumulation of viral particles near hypoxic areas. Furthermore, Ad-HRE12/hAFPΔ19 did not cause severe inflammatory immune response and toxicity after systemic injection.
Conclusions: The results presented here show the advantages of incorporating HREs into a hAFP promoter–driven oncolytic virus. This system is unique in that it acts in both a tissue-specific and tumor environment–selective manner. The greatly enhanced selectivity and tumoricidal activity of Ad-HRE12/hAFPΔ19 make it a promising therapeutic agent in the treatment of liver cancers. Clin Cancer Res; 16(24); 6071–82. ©2010 AACR.
The 2010 Health Care Reform Act: A Potential Opportunity to Advance Cancer Research by Taking Cancer Personally
Authors: Dalton William S. , Sullivan Daniel M. , Yeatman Timothy J. , Fenstermacher David A. 
Published: December 2010

Abstract
The Patient Protection and Affordable Care Act of 2010 will have a profound influence on health care in the United States, including how we conduct cancer research and cancer care delivery. For this reason, oncologists and researchers must be intimately involved in the implementation and interpretation of this important legislation. A major goal of the Act is to improve access to affordable, quality health care. An important element in achieving this goal will be to learn from patients' experiences and build the foundation for evidence-based personalized medicine. This will require a partnership among researchers, clinicians, policy makers and regulators, and patients to design an integrated information network system that will be the basis for providing the right treatment for the right patient in the right place at the right time. In this review, we will discuss the salient points of the Act that specifically affect cancer research and care, as well as highlight opportunities for oncologists and researchers to play a primary role in developing a health care system that includes personalized medicine approaches that will in turn enhance the likelihood of achieving the goals and objectives of the health care reform act. Clin Cancer Res; 16(24); 5987–96. ©2010 AACR.
Biologically Targeted Cancer Therapy and Marginal Benefits: Are We Making Too Much of Too Little or Are We Achieving Too Little by Giving Too Much?
Authors: Fojo Tito , Parkinson David R. 
Published: December 2010

Abstract
We describe the development and approval of biologically targeted agents in the clinic through examples chosen from the experience with inhibitors of the epidermal growth factor (EGF) and VEGF pathways. Despite extensive biological rationale for the use of these classes of molecules, marginal clinical benefits have been observed in broad patient populations, and the agents have entered into general clinical practice. We discuss why this situation is unsatisfactory because marginal general benefit may often be at the expense of toxicity to nonbenefiting or even harmed patients. Finally, we point out that emerging technologies bring the promise of allowing the identification of patients who might potentially benefit from a therapy. However, development of this technology will not move forward without broader recognition of its need by the range of stakeholders, including patients, advocates, academic and private oncologists, drug sponsors, and those who develop drugs and diagnostic tests. Clin Cancer Res; 16(24); 5972–80. ©2010 AACR.
Translating Clinical Trials into Meaningful Outcomes
Authors: LoRusso Patricia M. , Schnipper Lowell E. , Stewart David J. , Boerner Scott A. , Averbuch Steven D. , Wolf Walter 
Published: December 2010

Abstract
Efforts to unravel the complex biology that is necessary to develop new therapies best suited for an individual with cancer are at a crossroads with a strained health care system and an insufficient clinical trial apparatus. The resulting failures have been described as the “valley of death.” Progress into the future will require new considerations and the engagement of a broad band of stakeholders. To identify novel therapeutics that are likely to succeed in late development and to be meaningful for clinical practice, investigators will need to make a paradigm shift in designing clinical trials and endpoints while adhering to scientific rigor when interpreting results and making informed decisions. Large phase III trials that show a modest incremental benefit will continue to diminish in value for patients, clinicians, payers, and industry. Outcomes that are robust in both magnitude and application to the real world will take on increasing importance. Ensuring active participation by patients, lowering barriers to health care access, and protecting patients through health care reform are requirements for the future success of the cancer clinical research enterprise. The challenge today is to develop new approaches to translate scientific discovery into cost-effective and meaningful improvements in cancer outcomes. Clin Cancer Res; 16(24); 5951–5. ©2010 AACR.
A Five-Gene and Corresponding Protein Signature for Stage-I Lung Adenocarcinoma Prognosis
Authors: Kadara Humam , Behrens Carmen , Yuan Ping , Solis Luisa , Liu Diane , Gu Xuemin , Minna John D. , Lee J. Jack , Kim Edward , Hong Waun-Ki , Wistuba Ignacio I. , Lotan Reuben 
Published: December 2010

Abstract
Purpose: Identification of effective markers for outcome is expected to improve the clinical management of non–small cell lung cancer (NSCLC). Here, we assessed in NSCLC the prognostic efficacy of genes, which we had previously found to be differentially expressed in an in vitro model of human lung carcinogenesis.
Experimental Design: Prediction algorithms and risk-score models were applied to the expression of the genes in publicly available NSCLC expression data sets. The prognostic capacity of the immunohistochemical expression of proteins encoded by these genes was also tested using formalin-fixed paraffin-embedded (FFPE) tissue specimens from 156 lung adenocarcinomas and 79 squamous cell carcinomas (SCCs).
Results: The survival of all-stages (P &lt; 0.001, HR = 2.0) or stage-I (P &lt; 0.001, HR = 2.84) adenocarcinoma patients that expressed the five-gene in vitro lung carcinogenesis model (FILM) signature was significantly poorer than that of patients who did not. No survival differences were observed between SCCs predicted to express or lack FILM signature. Moreover, all stages (P &lt; 0.001, HR = 1.95) or stage-I (P = 0.001, HR = 2.6) adenocarcinoma patients predicted to be at high risk by FILM transcript exhibited significantly worse survival than patients at low risk. Furthermore, the corresponding protein signature was associated with poor survival (all stages, P &lt; 0.001, HR = 3.6; stage-I, P &lt; 0.001, HR = 3.5; stage-IB, P &lt; 0.001, HR = 4.6) and mortality risk (all stages, P = 0.001, HR = 4.0; stage-I, P = 0.01, HR = 3.4; stage-IB, P &lt; 0.001, HR = 7.2) in lung adenocarcinoma patients.
Conclusions: Our findings highlight a gene and corresponding protein signature with effective capacity for identification of stage-I lung adenocarcinoma patients with poor prognosis that are likely to benefit from adjuvant therapy. Clin Cancer Res; 17(6); 1490–501. ©2010 AACR.
One Allele's Loss Is Another's Gain: Alterations of NKX2–8 in Non–Small Cell Lung Cancer
Authors: Neal Joel W. , Shaw Alice T. 
Published: December 2010

Abstract
Large-scale genetic changes such as loss or gain of chromosomes are important drivers of solid tumor carcinogenesis. Recent technological advances in genomic profiling have allowed quantitative detection of gene copy numbers, leading to identification of the 14q13.3 gene locus as functionally important in non–small cell lung cancers.
Prolactin and Venous Thrombosis
Authors: van Zaane Bregje , Squizzato Alessandro , Reuwer Anne Q. , van Zanten Anton P. , Twickler Marcel T.B. , Dekkers Olaf M. , Cannegieter Suzanne C. , Büller Harry R. , Gerdes Victor E.A. , Brandjes Dees P.M. 
Published: December 2010

Objective—
Several acquired risk factors for venous thrombosis (VT) are associated with high prolactin levels. Our goal was to investigate VT risk for different levels of prolactin.

Methods and Results—
We used data of a case-control study on leg vein thrombosis conducted between September 1999 and August 2006 at the Academic Medical Center, Amsterdam, the Netherlands. Prolactin was assessed in 187 cases (mean age, 57 years; range, 19 to 90) and 374 gender-matched controls (mean age, 57 years; range, 18 to 93). Odds ratios and 95% CI for VT risk were estimated based on several cutoff levels derived from prolactin levels in controls. Odds ratios for VT risk clearly increased with higher prolactin levels. For prolactin levels above the 75th percentile (8 μg/L), we found an odds ratio of 1.7 (95% CI 1.0 to 2.7) as compared with levels below the 50th percentile (6 μg/L). This further increased up to an odds ratio of 4.7 (95% CI 1.8 to 11.8) for prolactin levels above the 97.5th percentile (16 μg/L). The risk was most pronounced in premenopausal women.

Conclusion—
Our data suggest that prolactin levels are associated with VT in a dose-dependent fashion. Future studies are needed to evaluate the causality of this relationship.