bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pelvic congestion syndrome: the role of interventional radiology in the treatment of chronic pelvic pain
Authors: Freedman J , Ganeshan A , Crowe P M 
Published: November 2010

Abstract
Chronic pelvic pain is a common problem for female patients and is defined as pain that has been present for 6 months or more. Chronic pelvic pain with associated ovarian vein varicosities is termed pelvic congestion syndrome (PCS) and is an important but under-diagnosed condition. The aetiology of pelvic varicosities is reflux of blood in the ovarian veins due to the absence of functioning valves, resulting in retrograde blood flow and eventual venous dilatation. The cardinal presenting symptom of PCS is pelvic pain, usually described as a dull ache, without evidence of inflammatory disease. Clinical signs may include vulval varicosities extending on to the medial thigh and long saphenous territory as well as tenderness on deep palpation at the ovarian point; however, such signs are not always present. Non-invasive imaging (ultrasound, CT and magnetic resonance venography) plays a central role in establishing the diagnosis, excluding alternative causes of pelvic pain and providing a road map for novel minimally invasive treatment options that are now available. Day-case percutaneous-directed venous embolisation is now accepted as a valuable treatment option for PCS with promising results from early clinical trials and is fast becoming the first-line treatment option for this condition. This paper aims to raise awareness of PCS among clinicians and reviews the pathogenesis, imaging assessment and minimally invasive treatment options that are now available.
The effect of São Paulo's smoke-free legislation on carbon monoxide concentration in hospitality venues and their workers
Authors: Issa Jaqueline S , Abe Tania M O , Pereira Alexandre C , Megid Maria Cristina , Shimabukuro Cristina E , Valentin Luis Sergio O , Ferreira Marizete M da C , Nobre Moacyr R C , Lancarotte Ines , Barretto Antonio Carlos Pereira 
Published: November 2010

BackgroundStudies have shown that there is no safe level of secondhand smoke (SHS) exposure and there is a close link between SHS and the risk of coronary heart disease and stroke. Carbon monoxide (CO) is one of the most important components present in SHS.ObjectiveTo evaluate the impact of the smoking ban law in the city of Sao Paulo, Brazil, on the CO concentration in restaurants, bars, night clubs and similar venues and in their workers.MethodsIn the present study we measured CO concentration in 585 hospitality venues. CO concentration was measured in different environments (indoor, semi-open and open areas) from visited venues, as well as, in the exhaled air from approximately 627 workers of such venues. Measurements were performed twice, before and 12 weeks after the law implementation. In addition, the quality of the air in the city during the same period of our study was verified.ResultsThe CO concentration pre-ban and pot-ban in hospitality venues was indoor area 4.57 (3.70) ppm vs 1.35 (1.66) ppm (p<0.0001); semi-open 3.79 (2.49) ppm vs 1.16 (1.14) ppm (p<0.0001); open area 3.31(2.2) ppm vs 1.31 (1.39) ppm (p<0.0001); smoking employees 15.78 (9.76) ppm vs 11.50 (7.53) ppm (p<0.0001) and non-smoking employees 6.88 (5.32) ppm vs 3.50 (2.21) ppm (p<0.0001). The average CO concentration measured in the city was lower than 1 ppm during both pre-ban and post-ban periods.ConclusionSão Paulo's smoking-free legislation reduced significantly the CO concentration in hospitality venues and in their workers, whether they smoke or not.
PTAS FOR k-TOUR COVER PROBLEM ON THE PLANE FOR MODERATELY LARGE VALUES OF k
Authors: ADAMASZEK ANNA , CZUMAJ ARTUR , LINGAS ANDRZEJ 
Published: November 2010

Let P be a set of n points in the Euclidean plane and let O be the origin point in the plane. In the k-tour cover problem (called frequently the capacitated vehicle routing problem), the goal is to minimize the total length of tours that cover all points in P, such that each tour starts and ends in O and covers at most k points from P. The k-tour cover problem is known to be [Formula: see text]-hard. It is also known to admit constant factor approximation algorithms for all values of k and even a polynomial-time approximation scheme (PTAS) for small values of k, k = Ø( log n/ log log n). In this paper, we significantly enlarge the set of values of k for which a PTAS is provable. We present a new PTAS for all values of k ≤ 2 log δ n, where δ = δ(ε). The main technical result proved in the paper is a novel reduction of the k-tour cover problem with a set of n points to a small set of instances of the problem, each with Ø((k/ε)Ø(1)) points.
OPTIMAL EXTRACTION OF IRREDUNDANT MOTIF BASES
Authors: APOSTOLICO ALBERTO , TAGLIACOLLO CLAUDIA 
Published: November 2010

The problem of extracting a basis of irredundant motifs from a sequence is considered. In previous work such bases were built incrementally for all suffixes of the input string s in O(n3), where n is the length of s. Faster, non-incremental algorithms have been based on the landmark approach to string searching due to Fischer and Paterson, and exhibit respective time bounds of O(n2log n log |Σ|) and O(|Σ|n2log2n log log n), with Σ denoting the alphabet. The algorithm by Fischer and Paterson makes crucial use of the FFT, which is impractical with long sequences.The present paper describes an off-line algorithm for binary strings that takes O(n2) time. The algorithm does not need to resort to the FFT and yet its performance is optimal for finite Σ.
ON THE HARDNESS OF THE BORDER LENGTH MINIMIZATION PROBLEM ON A RECTANGULAR ARRAY
Authors: KUNDETI VAMSI , RAJASEKARAN SANGUTHEVAR 
Published: November 2010

DNA microarray technology has proven to be an invaluable tool for molecular biologists. Microarrays are used extensively in SNP detection, genomic hybridization, alternative splicing and gene expression profiling. However the manufacturers of the microarrays are often stuck with the problem of minimizing the effects of unwanted illumination (border length minimization (BLM)) which is a hard combinatorial problem. In this paper we prove that the BLM problem on a rectangular grid is NP-hard – this however does not mean the BLM problem on a square grid is NP-hard. We also give the first integer linear programming (ILP) formulation to solve BLM problem optimally. Experimental results indicate that our ILP method produces superior results (both in runtime and cost) compared to the current state of the art algorithms to solve the BLM problem optimally.
Multicenter Study of the Association between Betapapillomavirus Infection and Cutaneous Squamous Cell Carcinoma
Authors: Bavinck Jan Nico Bouwes , Neale Rachel E. , Abeni Damiano , Euvrard Sylvie , Green Adele C. , Harwood Catherine A. , de Koning Maurits N.C. , Naldi Luigi , Nindl Ingo , Pawlita Michael , Pfister Herbert , Proby Charlotte M. , Quint Wim G.V. , ter Schegget Jan , Waterboer Tim , Weissenborn Sönke , Feltkamp Mariet C.W. 
Published: November 2010

AbstractHuman papillomaviruses (betaPV) from the beta genus cannot be classified according to their oncogenicity due to a paucity of information. This study evaluates the association between betaPV infection and cutaneous squamous cell carcinoma in conjunction with measures of UV exposure and susceptibility. We performed case–control studies in the Netherlands, Italy, and Australia, countries with profoundly different UV exposures. The presence of 25 betaPV types in eyebrow hair follicles was determined using a highly sensitive HPV DNA genotyping assay, and antibodies for the 15 most prevalent betaPV types in a total of 689 squamous cell carcinoma cases and 845 controls were detected using multiplex serology. Multivariate logistic regression models were used for case–control comparisons and interaction analyses. BetaPV DNA was detected in eyebrow hairs of more than 90% of all participants. The presence of betaPV DNA was associated with an increased risk of squamous cell carcinoma in the Netherlands (OR = 2.8; 95% CI 1.3–5.8) and Italy (OR = 1.7; 95% CI 0.79–3.6), but not in Australia (OR = 0.91; 95% CI 0.53–1.6). Seropositivity for betaPV in controls ranged between 52% and 67%. A positive antibody response against 4 or more betaPV types was associated with squamous cell carcinoma in Australia (OR = 2.2; 95% CI 1.4–3.3), the Netherlands (OR = 2.0; 95% CI 1.2–3.4) and fair-skinned Italians (OR = 1.6, 95% CI 0.94– 2.7). The association between UV susceptibility and squamous cell carcinoma was stronger in betaPV-seropositive people. These combined data support the hypothesis that betaPV may play a role in the development of cutaneous squamous cell carcinoma. Cancer Res; 70(23); 9777–86. ©2010 AACR.
A Novel Signaling Axis of Matriptase/PDGF-D/β-PDGFR in Human Prostate Cancer
Authors: Ustach Carolyn V. , Huang Wei , Conley-LaComb M. Katie , Lin Chen-Yong , Che Mingxin , Abrams Judith , Kim Hyeong-Reh Choi 
Published: November 2010

Abstract
Increasing evidence indicates the significance of platelet-derived growth factor receptor-β (β-PDGFR) signaling in prostate cancer (PCa). Accordingly, preclinical studies suggest the potential of β-PDGFR as a therapeutic target in metastatic PCa. However, a ligand responsible for β-PDGFR activation in PCa was unknown, and recent clinical trials with imatinib mesylate showed limited success due to normal tissue toxicity. Similarly, in spite of mounting evidence indicating the significance of matriptase in PCa, little is known about its substrates or molecular actions during PCa progression. Here, we identified PDGF-D as a ligand for β-PDGFR in PCa and discovered matriptase as its regulator. Matriptase activates PDGF-D by proteolytic removal of the CUB domain in a 2-step process, creating a hemidimer, followed by growth factor domain dimer (GFD-D) generation. Matriptase can deactivate PDGF-D by further proteolytic cleavage within the GFD, revealing its biphasic regulation. Importantly, PDGF-D/matriptase colocalization is accompanied with β-PDGFR phosphorylation in human PCa tissues. This study unveiled a novel signaling axis of matriptase/PDGF-D/β-PDGFR in PCa, providing new insights into functional interplay between serine protease and growth factor signaling networks. Cancer Res; 70(23); 9631–40. ©2010 AACR.
Integration of Host-Related Signatures with Cancer Cell–Derived Predictors for the Optimal Management of Anticancer Chemotherapy
Authors: Zitvogel Laurence , Kepp Oliver , Aymeric Laetitia , Ma Yuting , Locher Clara , Delahaye Nicolas F. , André Fabrice , Kroemer Guido 
Published: November 2010

Abstract
Current cancer management aims to integrate molecular signatures into the design of personalized therapies. Recent advances in “omics” done on tumor specimens have led to the identification of factors that either recognize cancers of dismal prognosis or pinpoint “druggable” signaling pathways, which can be interrupted by targeted therapies. However, accumulating evidence underscores the biological and clinical significance of immune predictors in several compartments (blood, serum, tumor) in a variety of malignancies. An additional aspect that has been overlooked is the bidirectional, tumor-host interaction during therapeutic intervention, suggesting that dynamic molecular, biochemical, and metabolic signatures should be developed in the future. We review immune parameters of prognostic or predictive value during cancer therapy, and highlight existing “descriptive-prognostic” and “functional-therapeutic” molecular signatures, with the hindsight of designing appropriate compensatory therapies. Cancer Res; 70(23); 9538–43. ©2010 AACR.
Melanoma Cells Express ICOS Ligand to Promote the Activation and Expansion of T-Regulatory Cells
Authors: Martin-Orozco Natalia , Li Yufeng , Wang Yijun , Liu Shijuan , Hwu Patrick , Liu Yong-Jun , Dong Chen , Radvanyi Laszlo 
Published: November 2010

Abstract
CD4+CD25+Foxp3+ T-regulatory cells (Tregs) accumulate in tumors; however, little is known about how the tumor environment influences this process. Here we show that human melanomas express inducible T-cell costimulator ligand (ICOS-L/B7H) that can provide costimulation through ICOS for the expansion of activated Tregs maintaining high Foxp3 and CD25 expression as well as a suppressive function. Thus, ICOS-L expression by melanoma tumor cells may directly drive Treg activation and expansion in the tumor microenvironment as another mechanism of immune evasion. Cancer Res; 70(23); 9581–90. ©2010 AACR.
Cancer Exosomes Trigger Fibroblast to Myofibroblast Differentiation
Authors: Webber Jason , Steadman Robert , Mason Malcolm D. , Tabi Zsuzsanna , Clayton Aled 
Published: November 2010

Abstract
There is a growing interest in the cell–cell communication roles in cancer mediated by secreted vesicles termed exosomes. In this study, we examined whether exosomes produced by cancer cells could transmit information to normal stromal fibroblasts and trigger a cellular response. We found that some cancer-derived exosomes could trigger elevated α-smooth muscle actin expression and other changes consistent with the process of fibroblast differentiation into myofibroblasts. We show that TGF-β is expressed at the exosome surface in association with the transmembrane proteoglycan betaglycan. Although existing in a latent state, this complex was fully functional in eliciting SMAD-dependent signaling. Inhibiting either signaling or betaglycan expression attenuated differentiation. While the kinetics and overall magnitude of the response were similar to that achieved with soluble TGF-β, we identified important qualitative differences unique to the exosomal route of TGF-β delivery, as exemplified by a significant elevation in fibroblast FGF2 production. This hitherto unknown trigger for instigating cellular differentiation in a distinctive manner has major implications for mechanisms underlying cancer-recruited stroma, fibrotic diseases, and wound-healing responses. Cancer Res; 70(23); 9621–30. ©2010 AACR.
Negative Regulation of p53 by the Long Isoform of ErbB3 Binding Protein Ebp1 in Brain Tumors
Authors: Kim Chung Kwon , Nguyen Truong L.X. , Joo Kyeung Min , Nam Do-Hyun , Park Jihye , Lee Kyung-Hoon , Cho Sung-Woo , Ahn Jee-Yin 
Published: November 2010

Abstract
The ErbB3 binding protein Ebp1 has been implicated in a number of human cancers. Ebp1 includes 2 isoforms, p48 and p42, that exhibit different cellular activities. Here we show that the larger p48 isoform is transforming and that it promotes cell growth, clonogenicity, and invasion in human glioblastoma (GBM). P48 overexpression in GBM cells facilitated tumorigenesis and enhanced tumor growth in mouse xenograft models. Human GBM tissues displayed elevated levels of p48 compared with surrounding normal tissues or low-grade tumors. Notably, p48 levels were inversely correlated with poor prognosis in GBM patients. We determined that p48 binds to the p53 E3 ligase HDM2, enhancing HDM2-p53 association and thereby promoting p53 polyubiquitination and degradation to reduce steady-state p53 levels and activity. Together, our findings suggest that p48 functions as an oncogene by promoting glioma tumorigenicity via interactions with HDM2 that contribute to p53 downregulation. Cancer Res; 70(23); 9730–41. ©2010 AACR.
Persistent Activation of the Fyn/ERK Kinase Signaling Axis Mediates Imatinib Resistance in Chronic Myelogenous Leukemia Cells through Upregulation of Intracellular SPARC
Authors: Fenouille Nina , Puissant Alexandre , Dufies Maeva , Robert Guillaume , Jacquel Arnaud , Ohanna Mickaël , Deckert Marcel , Pasquet Jean-Max , Mahon François-Xavier , Cassuto Jill-Patrice , Raynaud Sophie , Tartare-Deckert Sophie , Auberger Patrick 
Published: November 2010

Abstract
SPARC is an extracellular matrix protein that exerts pleiotropic effects on extracellular matrix organization, growth factor availability, cell adhesion, differentiation, and immunity in cancer. Chronic myelogenous leukemia (CML) cells resistant to the BCR-ABL inhibitor imatinib (IM-R cells) were found to overexpress SPARC mRNA. In this study, we show that imatinib triggers SPARC accumulation in a variety of tyrosine kinase inhibitor (TKI)–resistant CML cell lines. SPARC silencing in IM-R cells restored imatinib sensitivity, whereas enforced SPARC expression in imatinib-sensitive cells promoted viability as well as protection against imatinib-mediated apoptosis. Notably, we found that the protective effect of SPARC required intracellular retention inside cells. Accordingly, SPARC was not secreted into the culture medium of IM-R cells. Increased SPARC expression was intimately linked to persistent activation of the Fyn/ERK kinase signaling axis. Pharmacologic inhibition of this pathway or siRNA-mediated knockdown of Fyn kinase resensitized IM-R cells to imatinib. In support of our findings, increased levels of SPARC mRNA were documented in blood cells from CML patients after 1 year of imatinib therapy compared with initial diagnosis. Taken together, our results highlight an important role for the Fyn/ERK signaling pathway in imatinib-resistant cells that is driven by accumulation of intracellular SPARC. Cancer Res; 70(23); 9659–70. ©2010 AACR.
An Ex(o)citing Machinery for Invasive Tumor Growth
Authors: Hendrix An , Westbroek Wendy , Bracke Marc , De Wever Olivier 
Published: November 2010

Abstract
Cancer cells communicate with the environment through delivery of surface proteins, release of soluble factors (growth factors and cytokines), and sophisticated nanovehicles (exosomes) for establishment of invasive tumor growth. This communication occurs in part through constitutive exocytosis, regulated exocytosis, or release of intraluminal vesicles, and is modulated by small Rab GTPases, the master regulators of vesicle traffic. We studied Rab GTPases implicated in regulated exocytosis and showed a unique role for Rab27B in invasive tumor growth. Emerging evidence indicates that various exocytic routes are implemented by cancer cells to relay crucial information for fostering growth, migration, and matrix degradation. Cancer Res; 70(23); 9533–7. ©2010 AACR.
Plectin-1 as a Novel Biomarker for Pancreatic Cancer
Authors: Bausch Dirk , Thomas Stephanie , Mino-Kenudson Mari , Fernández-del Castillo Carlos , Bauer Todd W. , Williams Mark , Warshaw Andrew L. , Thayer Sarah P. , Kelly Kimberly A. 
Published: November 2010

Abstract
Purpose: We are in great need of specific biomarkers to detect pancreatic ductal adenocarcinoma (PDAC) at an early stage, ideally before invasion. Plectin-1 (Plec1) was recently identified as one such biomarker. However, its suitability as a specific biomarker for human pancreatic cancer, and its usability as an imaging target, remain to be assessed.
Experimental Design: Specimens of human PDAC, chronic pancreatitis, and normal pancreata were evaluated by immunohistochemistry and Western blot analysis. To validate Plec1 as an imaging target, Plec1-targeting peptides (tPTP) were used as a contrast agent for single photon emission computed tomography in an orthotopic and liver metastasis murine model of PDAC.
Results: Plec1 expression was noted to be positive in all PDACs but negative in benign tissues. Plec1 expression increases during pancreatic carcinogenesis. It was found to be misexpressed in only 0% to 3.85% of early PDAC precursor lesions (PanIN I/II) but in 60% of PanIN III lesions. Plec1 expression was further noted to be retained in all metastatic foci assayed and clearly highlighted these metastatic deposits in lymph nodes, liver, and peritoneum. In vivo imaging using tPTP specifically highlighted the primary and metastatic tumors. Biodistribution studies performed after imaging show that the primary pancreatic tumors and liver metastases retained 1.9- to 2.9-fold of tPTP over normal pancreas and 1.7-fold over normal liver.
Conclusions: Plec1 is the first biomarker to identify primary and metastatic PDAC by imaging and may also detect preinvasive PanIN III lesions. Strategies designed to image Plec1 could therefore improve detection and staging. Clin Cancer Res; 17(2); 302–9. ©2010 AACR.
Caveolin-1 Modulates the Ability of Ewing's Sarcoma to Metastasize
Authors: Sáinz-Jaspeado Miguel , Lagares-Tena Laura , Lasheras Jaime , Navid Fariba , Rodriguez-Galindo Carlos , Mateo-Lozano Silvia , Notario Vicente , Sanjuan Xavier , Garcia del Muro Xavier , Fabra Àngels , Tirado Oscar M. 
Published: November 2010

Abstract
Metastasis is the final stage of tumor progression and is thought to be responsible for up to 90% of deaths associated with solid tumors. Caveolin-1 (CAV1) regulates multiple cancer-associated processes related to malignant tumor progression. In the present study, we tested the hypothesis that CAV1 modulates the metastatic ability of cells from the Ewing's sarcoma family of tumors (ESFT). First, we analyzed the expression of CAV1 by immunostaining a tissue microarray containing 43 paraffin-embedded ESFT tumors with known EWS translocations. Even though no evidence was found for a significant association between CAV1 expression and stage, size or tumor site, all metastatic samples (10 of 10) had significantly high CAV1 expression, suggesting that high CAV1 content could positively contribute to enhance ESFT metastasis. To determine the effect of CAV1 on the migratory and invasive capabilities of ESFT cells, we knocked down CAV1 expression in TC252 and A673 cells by stably transfecting a previously validated shRNA construct. In vitro, migration and invasion assays showed that for both cell lines, CAV1 knocked-down cells migrated and invaded significantly less (P ≤ 0.01) than control cells. Moreover, control A673 cells introduced into BALB/c nude mice by tail vein injection strongly colonized the lungs. In contrast, animals injected with CAV1 knocked-down cells showed either no incidence of metastasis or developed lung metastases after a significant delay (P &lt; 0.0001). Finally, we show that the molecular mechanisms by which CAV1 carries out its key role in regulating ESFT metastasis involve matrix metalloproteinase production and activation as well as the control of the expression of SPARC, a known determinant of lung colonization. Mol Cancer Res; 8(11); 1489–500. ©2010 AACR.