bluuebunny/crossref_metadata_2025_split huggingface dataset:
An approach to recurrent aneurysms following endovascular coiling
Authors: Raymond Jean , Darsaut Tim E 
Published: February 2011

BackgroundEvidence regarding the most appropriate management of aneurysm recurrences following coiling consists only of uncontrolled case series and the resulting expert opinions, which range from not following coiled patients at all to performing invasive angiography at regular intervals.MethodsWe discuss several current attitudes toward how to manage post-coiling recurrences and outline an approach to finding concrete, practical answers to common clinical questions.ResultsAlthough some maxims and general statements can be reluctantly offered, in the absence of evidence the best approach is to emphasize proper methods in order to one day find reliable answers. These can only come from randomized clinical trials. The multitude of research questions is an added difficulty. A program of necessary trials is proposed and centers are encouraged to work in a collaborative fashion in order to offer best possible care as well as progress.ConclusionCommon clinical questions, including how to follow coiled aneurysm patients, if and when to re-treat, and with which treatment modality, are best addressed with the sound scientific methodology of clinical trials.
Pneumoconiosis and emphysema in construction workers: results of HRCT and lung function findings
Authors: Meijer E , Tjoe Nij E , Kraus T , van der Zee J S , van Delden O , van Leeuwen M , Lammers J W , Heederik D 
Published: February 2011

ObjectivesTo evaluate the prevalence of HRCT findings in construction workers previously surveyed by chest radiographs classified according to ILO guidelines. To examine the association between HRCT findings and exposure to quartz containing dust, and lung function.MethodsThe study comprised a questionnaire, dynamic and static lung function measurements, single-breath CO diffusion capacity, chest radiographs and HRCT in 79 individuals. Certified ‘B’ readers coded radiographs according to the ILO classification. HRCT scans were read according to an international classification system. A qualitative exposure index for cumulative respiratory quartz on a 10-point scale was used.ResultsAgreement between HRCT readers was good (κ>0.60), except for irregular opacities (κ=0.23). In ILO category 0/0, 8% HRCT round, 22% irregular and/or linear opacities and 41% HRCT emphysema was found. HRCT round opacities was associated with high cumulative quartz exposure (OR 7.1; 95% CI 1.3 to 37.8). Emphysema was associated with smoking (OR 10.1; 95% CI 1.2 to 84.2) and showed a reduction in TL,CO,sb. HRCT round opacities was not associated with lung function. Current smoking was negatively associated with FEV1/FVC ratio and positively with RV/TLC ratio, and showed a reduction in TL,CO,sb(13.4%), adjusted for different HRCT findings.ConclusionsLow grade silicosis cannot be excluded in workers with normal chest radiographs (ILO 0/0). In relatively highly exposed construction workers, a sevenfold increased risk of simple (nodular) silicosis was found. Emphysema on HRCT was associated with current or former smokers, but not with exposure, and contributed to reduced diffusion capacity. Airflow limitation was mainly determined by current smoking and was not associated with simple (nodular) silicosis.
Osteochondrosis lesions of the lateral trochlear ridge of the distal femur in four ponies
Authors: Voute L. C. , Henson F. M. D. , Platt D. , Jeffcott L. B. 
Published: February 2011

Lesions of the lateral trochlear ridge (LTR) of the distal femur were investigated in four pony or pony cross horses. The animals were all geldings and were six to 15 months of age. Lesions were bilateral in three ponies and unilateral in one. Femoropatellar joint effusion and lameness were present in two ponies; clinical signs were absent in the others. The proximal LTR was affected in all four animals. The radiographic appearance of the lesions was a subchondral defect containing mineralised bodies. Arthroscopic and postmortem examination findings included an osteochondral flap, a fissured or irregular articular surface and a smooth surface overlying focally thickened cartilage that extended into subchondral bone. Thickened articular cartilage was a histological feature of all the lesions. Among the other histological features, the most common were chondronecrosis, chondrocyte clusters, phenotypically abnormal chondrocytes, horizontal fissures at the osteochondral junction and retained blood vessels. The signalment of the four ponies, their clinical signs and the pathological features of their lesions were consistent with osteochondrosis of the LTR in horses. The use of multiple criteria was considered to be important in making a specific diagnosis.
Identification of a Soluble Form of B7-H1 That Retains Immunosuppressive Activity and Is Associated with Aggressive Renal Cell Carcinoma
Authors: Frigola Xavier , Inman Brant A. , Lohse Christine M. , Krco Christopher J. , Cheville John C. , Thompson R. Houston , Leibovich Bradley , Blute Michael L. , Dong Haidong , Kwon Eugene D. 
Published: February 2011

Abstract
Purpose: Release of inhibitory coregulatory proteins into the circulation may represent one mechanism by which tumors thwart immune responses. Our objective was to determine whether soluble B7-H1 (sB7-H1) levels in patients with clear cell renal cell carcinoma (ccRCC) are associated with pathologic features and patient outcome.
Experimental Design: We developed an ELISA for quantification of sB7-H1 in biological fluids. Biochemical confirmation of the measured analyte as sB7-H1 was done by protein microsequencing using supernates from tumor cell lines. Biological activity of sB7-H1 was assessed in vitro utilizing T-cell apoptosis assays. We tested sB7-H1 levels in the sera from 172 ccRCC patients and correlated sB7-H1 levels with pathologic features and patient outcome.
Results: sB7-H1 was detected in the cell supernatants of some B7-H1–positive tumor cell lines. Protein sequencing established that the measured sB7-H1 retained its receptor-binding domain and could deliver proapoptotic signals to T cells. Higher preoperative sB7-H1 levels were associated with larger tumors (P &lt; 0.001), tumors of advanced stage (P = 0.017) and grade (P = 0.044), and tumors with necrosis (P = 0.003). A doubling of sB7-H1 levels was associated with a 41% increased risk of death (P = 0.010).
Conclusion: Our observations suggest that sB7-H1 may be detected in the sera of ccRCC patients and that sB7-H1 may systemically impair host immunity, thereby fostering cancer progression and subsequent poor clinical outcome. Clin Cancer Res; 17(7); 1915–23. ©2011 AACR.
Comparative Prognostic Value of Epidermal Growth Factor Quantitative Protein Expression Compared with FISH for Head and Neck Squamous Cell Carcinoma
Authors: Pectasides Eirini , Rampias Theodore , Kountourakis Panteleimon , Sasaki Clarence , Kowalski Diane , Fountzilas George , Zaramboukas Thomas , Rimm David , Burtness Barbara , Psyrri Amanda 
Published: February 2011

AbstractPurpose: Epidermal growth factor receptor (EGFR) overexpression correlates with recurrence and with treatment resistance in head and neck squamous cell carcinoma (HNSCC). The aim of this study was to evaluate the relationship of EGFR gene copy number utilizing FISH and protein expression with automated quantitative analysis (AQUA) and to correlate those with patient outcome.Experimental Design: A tissue microarray composed of 102 HNSCC treated with (chemo)radiation was constructed and analyzed for EGFR copy number by FISH (Vysis; Abbott Laboratories) and EGFR protein expression using AQUA analysis of EGFR staining scored on a scale of 0 to 255. We evaluated associations of EGFR FISH status and AQUA score with clinicopathologic parameters and survival prognosis.Results: Eleven (17.2%) of 64 tumors with FISH results showed EGFR high polysomy and/or gene amplification (FISH positive). Protein levels assessed by AQUA in FISH-positive cases were significantly higher (P = 0.04) than in FISH-negative cases. Using the continuous AQUA scores for EGFR expression, AQUA and FISH showed significant agreement (Pearson's ρ = 0.353, P = 0.04). Patients with high tumor EGFR protein expression had inferior 5-year overall survival (27.7%) compared with those with low tumor EGFR expression (54%; P = 0.029). There was no significant association between EGFR FISH status and overall survival (P = 0.201). In the multivariate model, high tumor EGFR protein expression status remained an independent prognostic factor for overall survival (P = 0.047).Conclusions: EGFR protein content correlates with gene copy number if protein content is quantitated and automatically analyzed, as with AQUA. EGFR protein levels assessed by AQUA strongly predict for patient outcome in HNSCC, whereas EGFR FISH status does not provide prognostic information. Clin Cancer Res; 17(9); 2947–54. ©2011 AACR.
Carfilzomib-Dependent Selective Inhibition of the Chymotrypsin-like Activity of the Proteasome Leads to Antitumor Activity in Waldenstrom's Macroglobulinemia
Authors: Sacco Antonio , Aujay Monette , Morgan Brittany , Azab Abdel Kareem , Maiso Patricia , Liu Yang , Zhang Yong , Azab Feda , Ngo Hai T. , Issa Ghayas C. , Quang Phong , Roccaro Aldo M. , Ghobrial Irene M. 
Published: February 2011

AbstractPurpose: Primary Waldenstrom's Macroglobulinemia (WM) cells present with a significantly higher level of the immunoproteasome compared with the constitutive proteasome. It has been demonstrated that selective inhibition of the chymotrypsin-like (CT-L) activity of constitutive-(c20S) and immuno-(i20S) proteasome represents a valid strategy to induce antineoplastic effect in hematologic tumors. We therefore evaluated carfilzomib, a potent selective, irreversible inhibitor of the CT-L activity of the i20S and c20S in WM cells.Experimental Design: We tested the effect of carfilzomib on survival and proliferation of primary WM cells, as well as of other IgM-secreting lymphoma cell lines. Carfilzomib-dependent mechanisms of induced apoptosis in WM cells, and its effect on WM cells in the context of bone marrow (BM) microenvironment have been also evaluated. Moreover, the combinatory effect of carfilzomib and bortezomib has been investigated. In vivo studies have been performed.Results: We demonstrated that carfilzomib targeted the CT-L activity of both i20S and c20S, which led to the induction of toxicity in primary WM cells, as well as in other IgM-secreting lymphoma cells. Importantly, carfilzomib targeted WM cells even in the context of BM milieu. In addition, carfilzomib induced apoptosis through c-jun-N-terminal-kinase activation, caspase cleavage, and initiation of unfolded protein response. Importantly, the combination of carfilzomib and bortezomib synergistically inhibited CT-L activity, as well as caspase-, PARP-cleavage and GRP94 expression. Antitumor activity of carfilzomib has been validated in vivo.Conclusions: These findings suggest that targeting i20S and c20S CT-L activity by carfilzomib represents a valid antitumor strategy in WM and other IgM-secreting lymphomas. Clin Cancer Res; 17(7); 1753–64. ©2011 AACR.
Human Prostate Cancer Harbors the Stem Cell Properties of Bone Marrow Mesenchymal Stem Cells
Authors: Zhau Haiyen E. , He Hui , Wang Christopher Y. , Zayzafoon Majd , Morrissey Colm , Vessella Robert L. , Marshall Fray F. , Chung Leland W. K. , Wang Ruoxiang 
Published: February 2011

AbstractPurpose: Prostate tumor cells frequently show the features of osteoblasts, which are differentiated from bone marrow mesenchymal stem cells. We examined human prostate cancer cell lines and clinical prostate cancer specimens for additional bone marrow mesenchymal stem cell properties.Experimental Design: Prostate cancer cell lines were induced for osteoblastogenic and adipogenic differentiation, detected by standard staining methods and confirmed by lineage-specific marker expression. Abnormal expression of the markers was then assessed in clinical prostate cancer specimens.Results: After osteoblastogenic induction, cells of the LNCaP lineage, PC-3 lineage, and DU145 displayed osteoblastic features. Upon adipogenic induction, PC-3 lineage and DU145 cells differentiated into adipocyte-like cells. The adipocyte-like cancer cells expressed brown adipocyte-specific markers, suggesting differentiation along the brown adipocyte lineage. The adipogenic differentiation was accompanied by growth inhibition, and most of the adipocyte-like cancer cells were committed to apoptotic death. During cyclic treatments with adipogenic differentiation medium and then with control medium, the cancer cells could commit to repeated adipogenic differentiation and retrodifferentiation. In clinical prostate cancer specimens, the expression of uncoupling protein 1 (UCP1), a brown fat-specific marker, was enhanced with the level of expression correlated to disease progression from primary to bone metastatic cancers.Conclusions: This study thus revealed that prostate cancer cells harbor the stem cell properties of bone marrow mesenchymal stem cells. The abnormally expressed adipogenic UCP1 protein may serve as a unique marker, while adipogenic induction can be explored as a differentiation therapy for prostate cancer progression and bone metastasis. Clin Cancer Res; 17(8); 2159–69. ©2011 AACR.
Targeting Aberrant PI3K/Akt Activation by PI103 Restores Sensitivity to TRAIL-Induced Apoptosis in Neuroblastoma
Authors: Opel Daniela , Naumann Ivonne , Schneider Maxi , Bertele Daniela , Debatin Klaus-Michael , Fulda Simone 
Published: February 2011

Abstract
Purpose: Because we recently identified Akt activation as a novel poor prognostic indicator in neuroblastoma, we investigated whether phosphoinositide 3′-kinase (PI3K) inhibition sensitizes neuroblastoma cells for TRAIL-induced apoptosis.
Experimental Design: The effect of pharmacological or genetic inhibition of PI3K or mTOR was analyzed on apoptosis induction, clonogenic survival, and activation of apoptosis signaling pathways in vitro and in a neuroblastoma in vivo model. The functional relevance of individual Bcl-2 family proteins was examined by knockdown or overexpression experiments.
Results: The PI3K inhibitor PI103 cooperates with TRAIL to synergistically induce apoptosis (combination index &lt; 0.1), to suppress clonogenic survival, and to reduce tumor growth in a neuroblastoma in vivo model. Similarly, genetic silencing of PI3K significantly increases TRAIL-mediated apoptosis, whereas genetic or pharmacological blockage of mTOR fails to potentiate TRAIL-induced apoptosis. Combined treatment with PI103 and TRAIL enhances cleavage of Bid and the insertion of tBid into mitochondrial membranes, and reduces phosphorylation of BimEL. Additionally, PI103 decreases expression of Mcl-1, XIAP, and cFLIP, thereby promoting Bax/Bak activation, mitochondrial perturbations, and caspase-dependent apoptosis. Knockdown of Bid or Noxa or overexpression of Bcl-2 rescues cells from PI103- and TRAIL-induced apoptosis, whereas Mcl-1 silencing potentiates apoptosis. Bcl-2 overexpression also inhibits cleavage of caspase-3, caspase-8, and Bid pointing to a mitochondria-driven feedback amplification loop.
Conclusions: PI103 primes neuroblastoma cells for TRAIL-induced apoptosis by shifting the balance toward proapoptotic Bcl-2 family members and increased mitochondrial apoptosis. Thus, PI3K inhibitors represent a novel promising approach to enhance the efficacy of TRAIL-based treatment protocols in neuroblastoma. Clin Cancer Res; 17(10); 3233–47. ©2011 AACR.
DNA Damage Persistence as Determinant of Tumor Sensitivity to the Combination of Topo I Inhibitors and Telomere-Targeting Agents
Authors: Biroccio Annamaria , Porru Manuela , Rizzo Angela , Salvati Erica , D'Angelo Carmen , Orlandi Augusto , Passeri Daniela , Franceschin Marco , Stevens Malcolm F.G. , Gilson Eric , Beretta Giovanni , Zupi Gabriella , Pisano Claudio , Zunino Franco , Leonetti Carlo 
Published: February 2011

Abstract
Purpose: We previously reported that the G-quadruplex (G4) ligand RHPS4 potentiates the antitumor activity of camptothecins both in vitro and in tumor xenografts. The present study aims at investigating the mechanisms involved in this specific drug interaction.
Experimental Design: Combination index test was used to evaluate the interaction between G4 ligands and standard or novel Topo I inhibitors. Chromatin immunoprecipitation was performed to study the presence at telomeres of various types of topisomerase, while immunolabeling experiments were performed to measure the activation of DNA damage both in vitro and in tumor xenografts.
Results: We report that integration of the Topo I inhibitor SN-38, but not the Topo II poison doxorubicin with telomere-based therapy is strongly effective and the sequence of drug administration is critical in determining the synergistic interaction, impairing the cell ability to recover from drug-induced cytotoxicity. The synergistic effect of this combination was also observed by using novel camptothecins and, more interestingly, mice treated with ST1481/RHPS4 combination showed an inhibition and delay of tumor growth as well as an increased survival. The study of the mechanism(s) revealed that treatment with G4 ligands increased Topo I at the telomeres and the functional relevance of this observation was directly assessed by showing that standard and novel camptothecins stabilized DNA damage both in vitro and in xenografts.
Conclusions: Our results demonstrate an outstanding efficacy of Topo I inhibitors/G4 ligands combination, which likely reflects an enhanced and persistent activation of DNA damage response as a critical determinant of the therapeutic improvement. Clin Cancer Res; 17(8); 2227–36. ©2011 AACR.
Intraoperative qRT-PCR for Detection of Lymph Node Metastasis in Head and Neck Cancer
Authors: Ferris Robert L. , Xi Liqiang , Seethala Raja R. , Chan Jon , Desai Shaun , Hoch Benjamin , Gooding William , Godfrey Tony E. 
Published: February 2011

Abstract
Purpose: Sentinel node biopsy (SNB) has been shown to accurately stage the regional lymphatics in oral carcinoma. However, intraoperative pathology is only moderately sensitive and final pathology takes several days to complete. The purpose of this study was to develop a rapid, automated, and quantitative real-time PCR (qRT-PCR) assay that can match final pathology in an intraoperative time frame.
Experimental Design: Four hundred forty-eight grossly tumor-negative lymph nodes were evaluated for expression of 3 markers [PVA (pemphigus vulgaris antigen), PTHrP (parathyroid hormone-related protein), and TACSTD1 (tumor-associated calcium signal transducer 1)]. Conformity of metastasis detection by qRT-PCR was determined using hematoxylin and eosin and immunohistochemistry staining as the gold standard. PVA and TACSTD1 were then multiplexed with β-glucuronidase to develop a rapid, automated single-tube qRT-PCR assay using the Cepheid GeneXpert system. This assay was used to analyze 103 lymph nodes in an intraoperative time frame.
Results: Four hundred forty-two nodes produced an informative result for both qRT-PCR and pathologic examination. Concordance of qRT-PCR for individual markers with final pathology ranged from 93% to 98%. The best marker combination was TACSTD1 and PVA. A rapid, multiplex assay for TACSTD1 and PVA was developed on the Cepheid GeneXpert and demonstrated an excellent reproducibility and linearity. Analysis of 103 lymph nodes demonstrated 94.2% accuracy of this assay for identifying positive and negative nodes. The average time for each assay to yield results was 35 minutes.
Conclusions: A rapid, automated qRT-PCR assay can detect lymph node metastasis in head and neck cancer with high accuracy compared to pathologic analysis and may be more accurate than intraoperative pathology. Combined, SNB and rapid qRT-PCR could more appropriately guide surgical treatment of patients with head and neck cancer. Clin Cancer Res; 17(7); 1858–66. ©2011 AACR.
Peptide-Loaded Langerhans Cells, Despite Increased IL15 Secretion and T-Cell ActivationIn Vitro, Elicit Antitumor T-Cell Responses Comparable to Peptide-Loaded Monocyte-Derived Dendritic CellsIn Vivo
Authors: Romano Emanuela , Rossi Marco , Ratzinger Gudrun , de Cos Maria-Angeles , Chung David J. , Panageas Katherine S. , Wolchock Jedd D. , Houghton Alan N. , Chapman Paul B. , Heller Glenn , Yuan Jianda , Young James W. 
Published: February 2011

AbstractPurpose: We compared the efficacy of human Langerhans cells (LC) as tumor immunogens in vivo with monocyte-derived dendritic cells (moDC) and investigated how interleukin 15 (IL15) supports optimal DC-stimulated antitumor immunity.Experimental Design: American Joint Committee on Cancer stage III/IV melanoma patients participated in this first clinical trial comparing melanoma peptide-pulsed LC with moDC vaccines (NCT00700167, www.ClinicalTrials.gov). Correlative studies evaluated mechanisms mediating IL15 support of DC-stimulated antitumor immunity.Results: Both DC vaccines were safe and immunogenic for melanoma antigens. LC-based vaccines stimulated significantly greater tyrosinase–HLA-A*0201 tetramer reactivity than the moDC-based vaccines. The two DC subtypes were otherwise statistically comparable, in contrast to extensive prior data in vitro showing LC superiority. LCs synthesize much more IL15 than moDCs and stimulate significantly more antigen-specific lymphocytes with a cytolytic IFN-γ profile even without exogenous IL15. When supplemented by low-dose IL15, instead of IL2, moDCs stimulate 5 to 6 logs more tumor antigen–specific effector memory T cells (TEMRA) over 3 to 4 weeks in vitro. IL2 and IL15 can be synergistic in moDC stimulation of cytolytic T cells. IL15 promotes T-cell expression of the antiapoptotic bcl-2 and inhibits candidate regulatory T-cell (Treg) expansion after DC stimulation, countering two effects of IL2 that do not foster tumor immunity.Conclusions: MoDC-based vaccines will require exogenous IL15 to achieve clinical efficacy. Alternatively, LCs can couple the endogenous production of IL15 with potent T-cell stimulatory activity. Optimization of full-length tumor antigen expression for processing into multiple immunogenic peptides for presentation by both class I and II MHC therefore merits emphasis to support more effective antitumor immunity stimulated by LCs. Clin Cancer Res; 17(7); 1984–97. ©2011 AACR.
Identification of CD44 as a Surface Biomarker for Drug Resistance by Surface Proteome Signature Technology
Authors: Cain Jason W. , Hauptschein Robert S. , Stewart Jean K. , Bagci Tugba , Sahagian Gary G. , Jay Daniel G. 
Published: February 2011

Abstract
We developed surface proteome signatures (SPS) for identification of new biomarkers playing a role in cancer drug resistance. SPS compares surface antigen expression of different cell lines by immunocytochemistry of a phage display antibody library directed to surface antigens of HT1080 fibrosarcoma cells. We applied SPS to compare the surface proteomes of two epithelial derived cancer cell lines, MCF7 and NCI/ADR-RES, which is drug resistant because of overexpression of the P-glycoprotein (P-gp) drug efflux pump. Surface proteomic profiling identified CD44 as an additional biomarker that distinguishes between these two cell lines. CD44 immunohistochemistry can distinguish between tumors derived from these lines and predict tumor response to doxorubicin in vivo. We further show that CD44 plays a role in drug resistance, independently of P-gp, in NCI/ADR-RES cells and increases expression of the antiapoptotic protein Bcl-xL. Our findings illustrate the utility of SPS to distinguish between cancer cell lines and their derived tumors and identify novel biomarkers involved in drug resistance. Mol Cancer Res; 9(5); 637–47. ©2011 AACR.