bluuebunny/crossref_metadata_2025 huggingface dataset:
The geochemical characterization and correlation of Late Holocene tephra layers at Ambra Crater and Kuk Swamp, Papua New Guinea
Authors: Coulter Sarah E. , Denham Tim P. , Turney Chris S. M. , Hall Valerie A.
Published: June 2009

Major element geochemical analyses of volcanic glass shards from visible, macroscopic tephra layers in Papua New Guinea were used to test field‐based correlations between local Late Holocene sequences. Previously, synchronization of sediment records at archaeological and palaeoecological sites across the Papua New Guinea highlands had been based largely on the physical properties and stratigraphic relationships of visible volcanic layers. The geochemical analysis of tephra‐derived glass demonstrates miscorrelations and enables more robust tephrostratigraphic links to be made between a globally significant archaeological site, Kuk Swamp, and a nearby volcanic cone, Ambra Crater. The results indicate that field‐based correlations of tephras can be problematic, especially given variable post‐depositional changes in colour and texture of relatively thin tephra layers in different depositional environments. Additionally, the findings call into question some previous tephrochronological associations at archaeological and palaeoecological sites in the Papua New Guinea highlands, and demonstrate the necessity of grain‐discrete geochemical analysis of glass shards as a basis for future tephrochronological studies in this region. Copyright © 2009 John Wiley & Sons, Ltd.
Functional and anatomical connectivity abnormalities in left inferior frontal gyrus in schizophrenia
Authors: Jeong Bumseok , Wible Cynthia G. , Hashimoto Ryu‐Ichiro , Kubicki Marek
Published: June 2009

Functional studies in schizophrenia demonstrate prominent abnormalities within the left inferior frontal gyrus (IFG) and also suggest the functional connectivity abnormalities in language network including left IFG and superior temporal gyrus during semantic processing. White matter connections between regions involved in the semantic network have also been indicated in schizophrenia. However, an association between functional and anatomical connectivity disruptions within the semantic network in schizophrenia has not been established. Functional (using levels of processing paradigm) as well as diffusion tensor imaging data from 10 controls and 10 chronic schizophrenics were acquired and analyzed. First, semantic encoding specific activation was estimated, showing decreased activation within the left IFG in schizophrenia. Second, functional time series were extracted from this area, and left IFG specific functional connectivity maps were produced for each subject. In an independent analysis, tract‐based spatial statistics (TBSS) was used to compare fractional anisotropy (FA) values between groups, and to correlate these values with functional connectivity maps. Schizophrenia patients showed weaker functional connectivity within the language network that includes left IFG and left superior temporal sulcus/middle temporal gyrus. FA was reduced in several white matter regions including left inferior frontal and left internal capsule. Finally, left inferior frontal white matter FA was positively correlated with connectivity measures of the semantic network in schizophrenics, but not in controls. Our results indicate an association between anatomical and functional connectivity abnormalities within the semantic network in schizophrenia, suggesting further that the functional abnormalities observed in this disorder might be directly related to white matter disruptions. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
Mapping the pathways of information processing from sensation to action in four distinct sensorimotor tasks
Authors: Ivanoff Jason , Branning Philip , Marois René
Published: June 2009

Two sensorimotor tasks that share neither sensory nor motor modality can interfere with one another when they are performed simultaneously. A possible cause for this interference is the recruitment of common brain regions by these two tasks, thereby creating a bottleneck of information processing. This hypothesis predicts that such “bottleneck” regions would be activated by each task even when they are performed separately. To test this prediction, we sought to identify, with fMRI, brain regions commonly activated by sensorimotor tasks that share neither sensory input nor motor output. One group of subjects was scanned while they performed in separate runs an auditory‐vocal (AVo) task and a visuo‐manual (ViM) task, while a second group of subjects performed the reversed sensorimotor mapping tasks (AM and ViVo). The results revealed strong activation preferences in specific sensory and motor cortical areas for each sensory and motor modality. By contrast, the posterior portion of the lateral prefrontal cortex (pLPFC), anterior insula, and, less consistently, the anterior cingulate, presupplementary and supplementary motor areas, and subcortical areas were commonly activated across all four sensorimotor tasks. These results were observed in both blocked and event‐related fMRI designs, in both 3D‐group averaged and 2D‐individual subject analyses, and were replicated within individuals across scanning sessions. These findings not only suggest that these brain regions serve a common amodal function in sensorimotor tasks, they also point to these regions—particularly, the pLPFC and anterior insula—as candidate neural substrates underlying a central hub of information processing in the human brain. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.
Neither one‐time negative screening tests nor negative colposcopy provides absolute reassurance against cervical cancer
Authors: Castle Philip E. , Rodríguez Ana C. , Burk Robert D. , Herrero Rolando , Hildesheim Allan , Solomon Diane , Sherman Mark E. , Jeronimo Jose , Alfaro Mario , Morales Jorge , Guillén Diego , Hutchinson Martha L. , Wacholder Sholom , Schiffman Mark
Published: June 2009

A population sample of 10,049 women living in Guanacaste, Costa Rica, was recruited into a natural history of human papillomavirus (HPV) and cervical neoplasia study in 1993–1994. At the enrollment visit, we applied multiple state‐of‐the‐art cervical cancer screening methods to detect prevalent cervical cancer and to prevent subsequent cervical cancers by the timely detection and treatment of precancerous lesions. Women were screened at enrollment with 3 kinds of cytology (often reviewed by more than one pathologist), visual inspection and cervicography. Any positive screening test led to colposcopic referral and biopsy and/or excisional treatment of CIN2 or worse. We retrospectively tested stored specimens with an early HPV test (hybrid capture tube test) and for >40 HPV genotypes using a research PCR assay. We followed women typically 5–7 years and some up to 11 years. Nonetheless, 16 cases of invasive cervical cancer were diagnosed during follow‐up. Six cancer cases were failures at enrollment to detect abnormalities by cytology screening; 3 of the 6 were also negative at enrollment by sensitive HPV DNA testing. Seven cancers represent failures of colposcopy to diagnose cancer or a precancerous lesion in screen‐positive women. Finally, 3 cases arose despite attempted excisional treatment of precancerous lesions. Based on this evidence, we suggest that no current secondary cervical cancer prevention technologies applied once in a previously under‐screened population is likely to be 100% efficacious in preventing incident diagnoses of invasive cervical cancer. © 2009 UICC
Temporal trends in the incidence and survival of cancers of the upper aerodigestive tract in Ontario and the United States
Authors: Gupta Shlok , Kong Weidong , Peng Yingwei , Miao Qun , Mackillop William J.
Published: June 2009

The Ontario Cancer Registry (OCR) and the Surveillance, Epidemiology and End Results (SEER) databases were used to describe temporal trends in the incidence and survival of squamous cancers of the upper aerodigestive tract (UADT) in Ontario and the US between 1984 and 2001. Between the 1984–86 and 1999–01 periods, the age‐adjusted incidence rate of all first primary cancers of the UADT decreased from 11.6 (11.2–12.0) to 8.8 (8.5–9.1) in Ontario and 13.0 (12.7–13.3) to 10.2 (10.0–10.4) in the US. Significant decreases in incidence were observed in many UADT sites but there was no significant change in the incidence of cancer of the oropharynx in either the US or Canada. Over the same period, the 5‐year relative survival for all UADT cancers increased from 49.2% (47.2–51.2%) to 57.1%(55.0–59.1%) in Ontario and from 48.1% (46.9–49.3%) to 52.4% (51.2–53.6%) in the US. This significant improvement in the outcome of UADT cancer was largely due to a dramatic increase in the 5‐year relative survival for cancers of the oropharynx from 31.1% (27.1–35.1%) to 53.6% (49.3–57.9%) in Ontario and from 35.3% (32.9–37.8%) to 51.0% (48.7–53.3%) in the US. Smaller increases in survival were observed in cancers of the oral cavity, nasopharynx, and hypopharynx, but there was no evidence of any increase in survival for cancer of the larynx. These results are consistent with the hypothesis that there has been a major change in the etiology of cancer of the oropharynx in Canada and the US and a concomitant change in its response to therapy. © 2009 UICC
GLUT‐1 expression and response to chemoradiotherapy in rectal cancer
Authors: Brophy Sarah , Sheehan Katherine M. , McNamara Deborah A. , Deasy Joseph , Bouchier‐Hayes David J. , Kay Elaine W.
Published: June 2009

Preoperative chemoradiotherapy is used in locally advanced rectal cancer to reduce local recurrence and improve operability, however a proportion of tumors do not undergo significant regression. Identification of predictive markers of response to chemoradiotherapy would improve patient selection and may allow response modification by targeting of specific pathways. The aim of this study was to determine whether expression of glucose transporter‐1 (GLUT‐1) and p53 in pretreatment rectal cancer biopsies was predictive of tumor response to chemoradiotherapy. Immunohistochemical staining for GLUT‐1 and p53 was performed on 69 pretreatment biopsies and compared to tumor response in the resected specimen as determined by the tumor regression grade (TRG) scoring system. GLUT‐1 expression was significantly associated with reduced response to chemoradiotherapy and increasing GLUT expression correlated with poorer response (p = 0.02). GLUT‐1 negative tumors had a 70% probability of good response (TRG3/4) compared to a 31% probability of good response in GLUT‐1 positive tumors. GLUT‐1 may be a useful predictive marker of response to chemoradiotherapy in rectal cancer. © 2009 UICC
EP300—A miRNA‐regulated metastasis suppressor gene in ductal adenocarcinomas of the pancreas
Authors: Mees Soeren Torge , Mardin Wolf Arif , Wendel Claudia , Baeumer Nicole , Willscher Edith , Senninger Norbert , Schleicher Christina , Colombo‐Benkmann Mario , Haier Joerg
Published: June 2009

Genetic and epigenetic alterations during development of pancreatic ductal adenocarcinomas (PDACs) are well known. This study investigates genetic and epigenetic data together with tumor biology to find specific alterations responsible for metastasis formation. Using 16 human PDAC cell lines in a murine orthotopic PDAC model, local infiltration and metastatic spread were assessed by standardized dissemination scores. The cell lines were further classified into 3 hierarchical groups according to their metastatic potential. Their mRNA and microRNA (miRNA) expression was profiledviamRNA‐microarray as well as Taqman Low Density Array, and validated by single quantitative RT‐PCR and Western blotting. In the highly metastatic group, a significant induction of EP300 targeting miRNAs miR‐194 (fold change: 26.88), miR‐200b (fold change: 61.65), miR‐200c (fold change: 19.44) and miR‐429 (fold change: 21.67) (p< 0.05) was detected. Corresponding to this, decreased expression of EP300 mRNA (p< 0.0001) and protein (p< 0.05) were detected in the highly metastatic PDAC cell lines with liver metastases compared to the nonmetastatic or marginally metastatic cell lines, while no correlation with local tumor growth was found. In conclusion, epigenetic alterations with upregulated EP300 targeting miRNAs miR‐194, miR‐200b, miR‐200c and miR‐429 are related to reduced EP300 mRNA and protein in PDAC. These results demonstrate that miRNAs might be able to modulate the expression of metastasis‐specific suppressor genes and metastatic behavior in PDAC, suggesting diagnostic and therapeutic opportunities for EP300 and its targeting miRNAs in PDAC.
Estrogen‐induced interaction between KLF5 and estrogen receptor (ER) suppresses the function of ER in ER‐positive breast cancer cells
Authors: Guo Peng , Dong Xue‐Yuan , Zhao Ke‐Wen , Sun Xiaodong , Li Qunna , Dong Jin‐Tang
Published: June 2009

Kruppel‐like factor 5 (KLF5) is implicated in human breast cancer by frequent genomic deletion and expressional deregulation, but the molecular mechanisms by which KLF5 affects breast tumorigenesis are still unknown. This study was conducted to examine whether and how KLF5 affects the function of estrogen receptor (ER) in breast cancer cells. Using different cell lines, we found that restored expression of KLF5 inhibited estrogen‐promoted cell proliferation in ER‐positive MCF‐7 and T‐47D cell lines but had no effect on ER‐negative SK‐BR‐3 cells. Transcriptional activity of ER was also suppressed by KLF5, as detected by using estrogen‐stimulated ER responsive element‐mediated reporter assay and expression analysis of ER target genes including c‐MYC and Cathepsin D (CSTD). Chromatin immunoprecipitation assays showed that KLF5 inhibited ERα binding to the promoter of c‐myc and CSTD. Furthermore, estrogen induced an interaction between KLF5 and ERα. These results suggest that KLF5 inhibits the function of ERα in gene regulation and cell proliferation through protein interaction that interrupts the binding of ERα to target gene promoters to prevent target gene induction.
The influence of cosmetic breast augmentation on the stage distribution and prognosis of women subsequently diagnosed with breast cancer
Authors: Xie Lin , Brisson Jacques , Holowaty Eric J. , Villeneuve Paul J. , Mao Yang
Published: June 2009

This study aimed to determine whether cosmetic breast implants impair the early detection of breast cancer, and adversely influence survival. This analysis derives from a cohort of 24,558 women who received bilateral cosmetic breast implants, and 15,893 women who underwent other plastic surgery procedures at the same practices in Ontario and Quebec, Canada, between 1974 and 1989. Incident cancers and vital status through 1997 were determined by record linkage to the Canadian Cancer Registry and Canadian Mortality Database. Analyses are based on a total of 182 and 202 incident cases of breast cancer identified among the implant and control groups, respectively. Contingency table analyses were performed to test for differences in the stage distribution of breast cancers between the 2 groups. Potential differences in survival were evaluated using the Kaplan–Meier estimates and Cox proportional hazards models. Women who received breast implants were more likely to have advanced stage breast carcinoma relative to the other plastic surgery patients (crude and adjusted ps ≤ 0.01). No statistically significant differences in distributions between the implant and control patients were found for age at diagnosis, tumor size, histological type, period of diagnosis or length of follow‐up. The delayed diagnosis in augmented women did not appear to influence the overall prognosis. Breast cancer‐specific survival was similar in both groups (hazard ratio = 1.06; 95% confidence interval = 0.65–1.74). In conclusion, this study suggests that breast implants delay the detection of breast cancer, but there was no statistically significant difference in survival between the breast implant and other plastic surgery groups.
HDAC inhibitor valproic acid enhances tumor cell kill in adenovirus‐HSVtk mediated suicide gene therapy in HNSCC xenograft mouse model
Authors: Kothari Vishal , Joshi Ganesh , Nama Srikanth , Somasundaram Kumaravel , Mulherkar Rita
Published: June 2009

Safety, efficacy and enhanced transgene expression are the primary concerns while using any vector for gene therapy. One of the widely used vectors in clinical trials is adenovirus which provides a safe way to deliver the therapeutic gene. However, adenovirus has poor transduction efficiency in vivo since most tumor cells express low coxsackie and adenovirus receptors. Similarly transgene expression remains low, possibly because of the chromatization of adenoviral genome upon infection in eukaryotic cells, an effect mediated by histone deacetylases (HDACs). Using a recombinant adenovirus (Ad‐HSVtk) carrying the herpes simplex thymidine kinase (HSVtk) and GFP genes we demonstrate that HDAC inhibitor valproic acid can bring about an increase in CAR expression on host cells and thereby enhanced Ad‐HSVtk infectivity. It also resulted in an increase in transgene (HSVtk and GFP) expression. This, in turn, resulted in increased cell kill of HNSCC cells, following ganciclovir treatment in vitro as well as in vivo in a xenograft nude mouse model.
Forced cytochrome B gene mutation expression induces mitochondrial proliferation and prevents apoptosis in human uroepithelial SV‐HUC‐1 cells
Authors: Dasgupta Santanu , Hoque Mohammad Obaidul , Upadhyay Sunil , Sidransky David
Published: June 2009

Mitochondria encoded Cytochrome B (CYTB) gene mutations were reported in tumors of different anatomic origin but the functional significance of these mutations are not well studied. Earlier, we found a 7‐amino acid deletion mutation in the CYTB gene in a primary bladder cancer patient. In the present study, we overexpressed this 7‐amino acid deletion mutation of CYTB gene in SV‐40 transformed human uroepithelial HUC‐1 cells. The nuclear transcribed mitochondrial CYTB (mtCYTB) was targeted into the mitochondria and generated increased copies of mitochondria and mitochondrial COX‐I protein in the transfected HUC‐1 cells. The proapoptotic protein Bax largely remained confined to the cytoplasm of the mtCYTB transfected HUC‐1 cells without release of Cytochrome C. The downstream apoptotic proteins PARP also remained uncleaved along with increased Lamin B1 in the mtCYTB transfected cells. Our results demonstrate that forced overexpression of mtCYTB in transformed human uroepithelial HUC‐1 cells triggered mitochondrial proliferation and induction of an antiapoptotic signaling cascade favoring sustained cellular growth. Coding mitochondrial DNA mutations appear to have significant functional contribution in tumor progression. Published 2009 UICC.
Identification of cisplatin‐resistance related genes in head and neck squamous cell carcinoma
Authors: Yamano Yukio , Uzawa Katsuhiro , Saito Kengo , Nakashima Dai , Kasamatsu Atsushi , Koike Hirofumi , Kouzu Yukinao , Shinozuka Keiji , Nakatani Ken , Negoro Kenji , Fujita Shigeyuki , Tanzawa Hideki
Published: June 2009

Resistance to cisplatin is a major obstacle to successful treatment of head and neck squamous cell carcinoma (HNSCC). To investigate the molecular mechanism of this resistance, we compared the gene expression profiles between the cisplatin‐sensitive SCC cell lines (Sa‐3, H‐1 and KB) and the cisplatin‐resistant cell lines established from them (Sa‐3R, H‐1R and KB‐R) using Affymetrix U133 Plus 2.0 microarray. We identified 199 genes differentially expressed in each group. To identify important functional networks and ontologies to cisplatin resistance, the 199 genes were analyzed using the Ingenuity Pathway Analysis Tool. Fifty‐one of these genes were mapped to genetic networks, and we validated the top‐10 upregulated genes by real‐time reverse transcriptase‐polymerase chain reaction. Five novel genes, LUM, PDE3B, PDGF‐C, NRG1 and PKD2, showed excellent concordance with the microarray data. In 48 patients with oral SCC (OSCC), positive immunohistochemical staining for the five genes correlated with chemoresistance to cisplatin‐based combination chemotherapy. In addition, the expression of the five genes predicted the patient outcomes with chemotherapy. Furthermore, siRNA‐directed suppressed expression of the five genes resulted in enhanced susceptibility to cisplatin‐mediated apoptosis. These results suggested that these five novel genes have great potential for predicting the efficacy of cisplatin‐based chemotherapy against OSCC. Global gene analysis of cisplatin‐resistant cell lines may provide new insights into the mechanisms underlying clinical cisplatin resistance and improve the efficacy of chemotherapy for human HNSCC.
Precise detection of lymph node metastases in mouse rectal cancer by using 5‐aminolevulinic acid
Authors: Murayama Yasutoshi , Harada Yoshinori , Imaizumi Katsuichi , Dai Ping , Nakano Keimei , Okamoto Kazuma , Otsuji Eigo , Takamatsu Tetsuro
Published: June 2009

Accurate diagnosis of metastatic lymph nodes (LNs) is essential in choosing appropriate treatment for gastrointestinal carcinoma. Our aim was to evaluate the diagnostic power of 5‐aminolevulinic acid (5‐ALA) for LN metastasis in mouse rectal cancer. Colorectal cancer cell lines, isolated cells from normal LNs, and orthotopic mouse model incorporating enhanced green fluorescent protein‐tagged and untagged human rectal cancer cells were studied after 5‐ALA administration by using confocal microscopy, fluorescence stereomicroscopy, fluorescence lifetime imaging microscopy (FLIM), multichannel spectrophotometry and macroconfocal imaging system to precisely detect LN metastases. In vitro confocal microscopic analyses showed that all colorectal cancer cell lines tested were positive for 5‐ALA‐induced fluorescence, whereas isolated normal LN cells were negative. 5‐ALA‐induced protoporphyrin IX (PPIX) fluorescence, verified by FLIM and multichannel spectrophotometry, revealed LN metastases in mice‐bearing human rectal cancer cells. Occult LN metastases, unrecognized on white‐light imaging and simplified hematoxylin‐eosin analyses, were readily detectable on 5‐ALA‐induced PPIX fluorescence imaging. In vivo macroconfocal images clearly revealed PPIX‐fluorescence‐positive cancer cells in draining lymph vessels and nodes. Together with specific speckled patterns of PPIX‐fluorescence in metastatic lesions, the PPIX‐fluorescence intensity ratio of metastatic and nonmetastatic lesions discriminated metastasis with 100% sensitivity and 100% specificity in excised whole LN samples. These results show that fluorescence diagnosis with 5‐ALA is very accurate in the detection of LN micrometastases of mouse rectal cancer, suggesting that this feasible diagnostic approach is applicable to target sectioning of metastases of resected fresh whole node samples in pathology laboratories. © 2009 UICC
The association of plasma androgen levels with breast, ovarian and endometrial cancer risk factors among postmenopausal women
Authors: Danforth Kim N. , Eliassen A. Heather , Tworoger Shelley S. , Missmer Stacey A. , Barbieri Robert L. , Rosner Bernard A. , Colditz Graham A. , Hankinson Susan E.
Published: June 2009

Although androgens may play an etiologic role in breast, ovarian and endometrial cancers, little is known about factors that influence circulating androgen levels. We conducted a cross‐sectional analysis among 646 postmenopausal women in the Nurses' Health Study to examine associations between adult risk factors for cancer, including the Rosner/Colditz breast cancer risk score, and plasma levels of testosterone, free testosterone, androstenedione, dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS). All analyses were adjusted for age, laboratory batch and other cancer risk factors. Free testosterone levels were 79% higher among women with a body mass index of ≥30 vs. <22 kg/m2 (p‐trend <0.01) and 25% higher among women with a waist circumference of >89 vs. ≤74 cm (p‐trend = 0.02). Consuming >30 g of alcohol a day vs. none was associated with a 31% increase in DHEA and 59% increase in DHEAS levels (p‐trend = 0.01 and <0.01, respectively). Smokers of ≥25 cigarettes per day had 35% higher androstenedione and 44% higher testosterone levels than never smokers (p‐value, F‐test = 0.03 and 0.01, respectively). No significant associations were observed for height or time since menopause with any androgen. Testosterone and free testosterone levels were ∼30% lower among women with a hysterectomy vs. without (both p‐values < 0.01). Overall breast cancer risk was not associated with any of the androgens. Thus, several risk factors, including body size, alcohol intake, smoking and hysterectomy, were related to androgen levels among postmenopausal women, while others, including height and time since menopause, were not. Future studies are needed to clarify further which lifestyle factors modulate androgen levels.
Bisphosphonates suppress insulin‐like growth factor 1‐induced angiogenesis via the HIF‐1α/VEGF signaling pathways in human breast cancer cells
Authors: Tang Xudong , Zhang Qunzhou , Shi Shihong , Yen Yun , Li Xiangyong , Zhang Yuefei , Zhou Keyuan , Le Anh D.
Published: June 2009

Adjunctive chemotherapy with bisphosphonates has been reported to delay bone metastasis and improve overall survival in breast cancer. Aside from its antiresorptive effect, bisphosphonates exhibit antitumor activities, in vitro and in vivo, via several mechanisms, including antiangiogenesis. In this study, we investigated the potential molecular mechanisms underlying the antiangiogenic effect of non–nitrogen‐containing and nitrogen‐containing bisphosphonates, clodronate and pamidronate, respectively, in insulin‐like growth factor (IGF)‐1 responsive human breast cancer cells. We tested whether bisphosphonates had any effects on hypoxia‐inducible factor (HIF)‐1α/vascular endothelial growth factor (VEGF) axis that plays a pivotal role in tumor angiogenesis, and our results showed that both pamidronate and clodronate significantly suppressed IGF‐1‐induced HIF‐1α protein accumulation and VEGF expression in MCF‐7 cells. Mechanistically, we found that either pamidronate or clodronate did not affect mRNA expression of HIF‐1α, but they apparently promoted the degradation of IGF‐1‐induced HIF‐1α protein. Meanwhile, we found that the presence of pamidronate and clodronate led to a dose‐dependent decease in the newly‐synthesized HIF‐1α protein induced by IGF‐1 in breast cancer cells after proteasomal inhibition, thus, indirectly reflecting the inhibition of protein synthesis. In addition, our results indicated that the inhibitory effects of bisphosphonates on the HIF‐1α/VEGF axis are associated with the inhibition of the phosphoinositide 3‐kinase/AKT/mammalian target of rapamycin signaling pathways. Consistently, we demonstrated that pamidronate and clodronate functionally abrogated both in vitro and in vivo tumor angiogenesis induced by IGF‐1‐stimulated MCF‐7 cells. These findings have highlighted an important mechanism of the pharmacological action of bisphosphonates in the inhibition of tumor angiogenesis in breast cancer cells.
Evolution of pleural cancers and malignant pleural mesothelioma incidence in France between 1980 and 2005
Authors: Le Stang N. , Belot A. , Gilg Soit Ilg A. , Rolland P. , Astoul P. , Bara S. , Brochard P. , Danzon A. , Delafosse P. , Grosclaude P. , Guizard A.‐V. , Imbernon E. , Lapôtre‐Ledoux B. , Ligier K. , Molinié F. , Pairon J.‐C. , Sauleau E.‐A. , Trétarre B. , Velten M. , Bossard N. , Goldberg M. , Launoy G. , Galateau‐Sallé F.
Published: June 2009

The evolution of pleural cancers and malignant pleural mesothelioma incidence in France between 1980 and 2005 was analysed using data derived from the French network of cancer registries (FRANCIM) and the French National Mesothelioma Surveillance Program (PNSM). Mesothelioma proportions in pleural cancers were calculated by diagnosis year in the 1980–2000 period. Our results suggest that the incidences of pleural cancer and mesothelioma levelled off in French men since 2000 and continued to increase in French women. A decrease of the annual pleural cancer incidence average in men was noticed (−3.4% of annual rate of change) between 2000 and 2005. The proportion of pleural cancers that were mesothelioma was unchanged between 1980 and 2003 with an average of 86%. The age standardised incidence rate of pleural mesothelioma remained relatively stable between 1998 and 2005 with a slight falling trend. For women, the age standardised incidence rate of pleural cancers and mesothelioma increased during the period 1998–2005. Additionally, the proportion of pleural cancers that were mesothelioma increased during the same period of time. Finally, the increased trend observed in the incidence of pleural mesothelioma and cancers in women is credibly due to their under diagnosis in the 1980–1997 period. The comparison between the French incidence and the American and British ones shows that the decreasing trend in incidence of mesothelioma and pleural cancers in French men since 2000 is potentially associated with a lower amphibole consumption and by the implementation of safety regulations at work from 1977.
Attitudes to HPV vaccination among parents of children aged 12‐15 years—A population‐based survey in Sweden
Authors: Dahlström Lisen A. , Tran Trung N. , Lundholm Cecilia , Young Cecilia , Sundström Karin , Sparén Pär
Published: June 2009

In this population‐based survey undertaken in Sweden in 2007, we investigated correlates of attitudes to human papillomavirus (HPV) vaccination among parents of children aged 12–15 years. We invited 16,000 parents of girls and 4,000 parents of boys, randomly selected from the Swedish population. Response rates were 70 and 69%, respectively. Multinomial logistic regression models were applied to investigate correlates of acceptability to HPV vaccination. Among studied parents, 76% were willing to vaccinate their child if the vaccine is for free and 63% were willing to vaccinate even if the vaccine comes with a cost. Having heard of HPV was associated with both willingness to vaccinate if the vaccine is free (odds ratio [OR]: 1.42; 95% confidence interval [CI]: 1.21–1.66) and willingness to vaccinate even if the vaccine is not free (OR: 1.96; 95% CI: 1.75–2.20) compared with those who never heard of HPV. Beliefs about vaccine safety and efficacy were also strong correlates of willingness to vaccinate. Parents born outside Europe and those with higher education were less willing to vaccinate if the vaccine is not free. In conclusion, the willingness to vaccinate was reasonably high and cost did not appear to be a major barrier. Information about vaccine safety and efficacy is important and parents need information about HPV and the HPV vaccine.
Optical coherence tomography and Raman spectroscopy of the ex‐vivo retina
Authors: Evans Julia W. , Zawadzki Robert J. , Liu Rui , Chan James W. , Lane Stephen M. , Werner John S.
Published: June 2009

Imaging the structure and correlating it with the biochemical content of the retina holds promise for fundamental research and for clinical applications. Optical coherence tomography (OCT) is commonly used to image the 3D structure of the retina and while the added functionality of biochemical analysis afforded by Raman scattering could provide critical molecular signatures for clinicians and researchers, there are many technical challenges to combine these imaging modalities. We describe an OCT microscope for ex‐vivo imaging combined with Raman spectroscopy capable of collecting morphological and molecular information about a sample simultaneously. We present our first results and discuss the challenges to further development of this dual‐mode instrument and limitations for future in‐vivo retinal imaging. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Reconstruction of peri‐implant bone defects using impacted bone allograft and BMP‐2 gene‐modified bone marrow stromal cells
Authors: Yan Meng‐Ning , Dai Ke‐Rong , Tang Ting‐Ting , Zhu Zhen‐An , Lou Jue‐Ren
Published: June 2009

Impaction bone allografting represents an attractive procedure for bone defects reconstruction in joint replacement. And it was found that bone morphogenetic protein‐2(BMP‐2) gene therapy can enhance bone healing. The purpose of this study was to determine if combined adenovirus mediated human BMP‐2(Adv‐hBMP‐2) gene‐modified bone marrow stromal cells(BMSCs) with allograft enhanced the defects healing and improved the strength of implant fixation in 3‐mm bone defect around a titanium alloy implant. Using the impaction grafting technique, the defects were reconstructed using freeze‐dried allograft, freeze‐dried allografts loaded with autogenous BMSCs, or freeze‐dried allografts loaded with autogenous BMSCs modified with the human bone morphogenetic protein‐2 (hBMP‐2) gene. At 6 and 12 weeks, the Bone‐implant Contact rate and strength of the interface in the group with BMP‐2 gene medication were significantly higher than those of the non‐cell or cell groups. BMP‐2 gene medication also showed significant effects on allograft healing and replacement compared with those of two other groups, as evidenced by increased new bone formation and reduced graft remnants. The results suggest that BMP‐2 gene medication can enhance allograft healing and osseointegration of the bone‐implant interface. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res 2010
In vitro macrophage response to polyethylene and polycarbonate‐urethane particles
Authors: Smith Richard A. , Hallab Nadim James
Published: June 2009

This study was undertaken to compare macrophage response to polycarbonate‐urethane (PCU), a proposed alternative material to polyethylene in acetabular components of total hip arthroplasty to cross‐linked ultra‐high molecular weight polyethylene (xUHMWPE) in the presence or absence of endotoxin. Polyethylene wear debris that is generated by total hip and knee replacements has been linked to osteolysis and limiting the lifespan of the implant. We added both lipopolysaccharide (LPS)‐free and endotoxin‐associated xUHMWPE and PCU particles to a human monocyte cell line (TH1) in culture and measured cell viability and tumor necrosis factor (TNF)α, interleukin (IL)‐1β, and prostaglandin E2 (PGE2) in the medium after 24 h. Results indicate that particles (both xUHMWPE and PCU) free of endotoxin did not significantly induce secretion of TNFα, IL‐1β, or PGE2 above basal levels. However, endotoxin‐exposed PCU particles induced significantly less TNFα and IL‐1β than endotoxin‐exposed xUHMWPE particles. This indicates that if endotoxin is available for binding to particles in vivo, then xUHMWPE may be more inflammatory to periprosthetic tissue and bone in part because of its affinity/reactivity with endotoxin when compared with PCU. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res 2010
In vitro cytotoxicity evaluation of biomedical nanoparticles and their extracts
Authors: Das Gautom Kumar , Chan Peggy P. Y. , Teo Ailing , Loo Joachim Say Chye , Anderson James M. , Tan Timothy Thatt Yang
Published: June 2009

The present study presents a new approach for evaluating in vitro cytotoxicity of nanoparticles. The approach is based on American National Standard ISO 10993‐5. Hepatoma HepG2 and fibroblast NIH3T3 cell lines were incubated with nanoparticles, and their associated extracts were derived at 70 and 121°C. Nanoparticles proposed as potential biomedical imaging probes were evaluated on the basis of the detection of metabolic activities and cell‐morphology changes. In general, nanoparticles incubated directly with cells showed higher cytotoxicity than their associated extracts. CdSe and core‐shell CdSe@ZnS quantum dots resulted in low cell viability for both cell lines. The cytotoxicity of the quantum dots was attributed to the Cd ion and the presence of the nanoparticle itself. A statistically significant (p < 0.05) decrease in cell viability was found in higher dosage concentrations. Rare earth nanoparticles and their extracts appear to affect NIH3T3 cells only, with cell viability as low as 71.4% ± 4.8%. Magnetic nanoparticles have no observable effects on the cell viabilities for both cell lines. In summary, we found the following: (1) both direct incubation and extracts of nanoparticles are required for complete assessment of nanoparticle cytotoxicity, (2) the rare earth oxide nanoparticles are less cytotoxic than the Cd‐based quantum dots, and (3) the extent of cytotoxicity is dependent upon the cell line. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Proliferation, behavior, and cytokine gene expression of human umbilical vascular endothelial cells in response to different titanium surfaces
Authors: An Na , Schedle Andreas , Wieland Marco , Andrukhov Oleh , Matejka Michael , Rausch‐Fan Xiaohui
Published: June 2009

Success of dental implantation is initially affected by wound healing of both, hard and soft tissues. Endothelial cells (ECs) are involved as crucial cells in the angiogenesis and inflammation process of wound healing. In the present study, proliferation, mobility, cluster formation, and gene expression of angiogenesis‐related molecules of human umbilical vascular endothelial cells (HUVECs) were investigated on titanium surfaces with different roughnesses: acid‐etched (A), coarse‐grit‐blasted and acid‐etched (SLA) surfaces, as well as on hydrophilic modified modA and modSLA surfaces. Cell behaviors were analyzed by proliferation assay and time‐lapse microscopy, gene expression was analyzed by real time PCR. Results showed that cell proliferation, mobility, and cluster formation were highest on modA surfaces compared with all other surfaces. HUVECs moved slowly and exhibited seldom cell aggregation on SLA and modSLA surfaces during the whole observing period of 120 h. The gene expressions of the angiogenesis‐related factors von Willebrand factor, thrombomodulin, endothelial cell protein C receptor, and adhesion molecules intercellular adhesion molecule‐1 and E‐selectin were most enhanced on modSLA surfaces. These results suggest that modA surface is optimal for proliferation and angiogenic behavior of ECs. However, modSLA surface seems to promote ECs to express angiogenesis‐related factor genes, which play essential roles in controlling inflammation and revascularization of wound healing. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res 2010
A role for decorin in controlling proliferation, adhesion, and migration of murine embryonic fibroblasts
Authors: Ferdous Z. , Peterson S. B. , Tseng H. , Anderson D. K. , Iozzo R. V. , Grande‐Allen K. J.
Published: June 2009

The proteoglycan decorin putatively inhibits cell adhesion and cell migration on various extracellular matrix substrates through interactions with β1 integrins. This study, therefore, examined the adhesive, migration, and proliferative characteristics of decorin knockout (Dcn−/−) murine embryonic fibroblasts compared to wild‐type controls on collagen‐coated, fibronectin‐coated, and uncoated tissue culture plates. The Dcn−/− cells showed significantly greater proliferation than wild‐type controls on all substrates. The Dcn−/− cells also showed significantly greater adhesion to both collagen and fibronectin; both cell types showed greater adhesion to collagen. The addition of exogenous decorin had a differential effect on adhesion to collagen between cell types, but not on fibronectin. For collagen, blocking either α2 or β1 integrin subunits significantly reduced adhesion for Dcn−/− cells; whereas for fibronectin, blocking either the α5 or β1 integrin subunits reduced adhesion for both cell types. Decorin and the α5β1 integrin may have lesser roles in adhesion to fibronectin than previously presumed. Finally, compared to wild‐type cells, Dcn−/− cells showed greater migration on both uncoated and collagen substrates. This study demonstrates that decorin affects the biology of various integrins that participate in cell proliferation, adhesion, and migration on various substrates. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Effect of implant surface microtopography on proliferation, neurotrophin secretion, and gene expression of Schwann cells
Authors: Yuan Quan , Liao Dapeng , Yang Xingmei , Li Xiaoyu , Wei Na , Tan Zhen , Gong Ping
Published: June 2009

The purpose of this study was to evaluate the effect of different implant surface properties on the morphology, proliferation, neurotrophin secretion, and gene expression of Schwann cells. Four types of implant surfaces, including ground (smooth surface), sandblasted and acid‐etched (SLA), hydroxyapatite‐coated (HA), and titanium plasma spray (TPS) surfaces were fabricated and photographed by a scanning electron microscopy (SEM). Schwann cells derived from neonatal rats were cultured on the implant surfaces and assessed via SEM observation and methylthiazol tetrazolium (MTT) colorimetric assay. The secretions and mRNA levels of brain‐derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were measured by enzyme‐linked immunosorbent assay (ELISA) and quantitative real time RT‐PCR, respectively, on days 3 and 7. Tissue culture plastic was used as a control. The results demonstrated that Schwann cells exhibited typical bipolar spindle morphology on various surfaces, and proliferated faster than the control. Neurotrophin secretion and gene expression of both BDNF and NGF were also increased by implant surfaces. This study suggests that the function of Schwann cells can be enhanced by implant implants. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res 2010
Characterization of dextrin‐based hydrogels: Rheology, biocompatibility, and degradation
Authors: Carvalho Joana , Moreira Susana , Maia João , Gama Francisco M.
Published: June 2009

A new class of degradable dextrin‐based hydrogels (dextrin‐HEMA) was developed. The hydroxyethyl methacrylate ester (HEMA) hydroxyl groups were activated with N,N′‐carbonyldiimidazole (CDI), followed by their coupling to dextrin, yielding a derivatized material that can be polymerized in aqueous solution to form hydrogels. A comparative study of the stability of the dextrin‐HEMA hydrogels and dextrin‐vinyl acrylate (dextrin‐VA, produced in previous work) revealed that only the firsts are effectively hydrolyzed under physiological conditions. A severe mass loss of dextrin‐HEMA gels occurs over time, culminating in the complete dissolution of the gels. Rheologic analysis confirmed that physical structuring is less pronounced when dextrin is modified with methacrylate side groups. The biocompatibility results revealed that the dextrin hydrogels have negligible cell toxicity, irrespective of the hydrogel type (HEMA and VA), allowing cell adhesion and proliferation. Gathering the biocompatibility and the ability to tailor the release profiles, we consider dextrin a promising biomaterial for biomedical applications, namely for controlled release. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res 2010
A systematic SPR study of human plasma protein adsorption behavior on the controlled surface packing of self‐assembled poly(ethylene oxide) triblock copolymer surfaces
Authors: Chang Yung , Chu Wan‐Ling , Chen Wen‐Yih , Zheng Jie , Liu Lingyun , Ruaan Ruoh‐Chyu , Higuchi Akon
Published: June 2009

A well‐controlled biocompatible nonfouling surface is significant for biomedical requirements, especially for the improvement of biocompatibility. We demonstrate the low or nonbiofouling surfaces by coating hydrophobic–hydrophilic triblock copolymers of poly(ethylene oxide)‐poly(propylene oxide)‐poly(ethylene oxide) (PEO‐PPO‐PEO) on the CH3‐terminated self‐assembled monolayer (SAM). Two types of copolymers are used to modify the surface, one with different PEO/PPO ratios (∼20/80, 40/60, and 80/20, w/w) but the same PPO molecular weight (∼2 k), the other with different copolymer MWs (∼9, 11, and 15 k) but the same PEO/PPO ratio (80/20, w/w). In situ surface plasmon resonance (SPR) sensor is used to evaluate polymer adsorption on the SAMs and subsequent protein adsorption on the copolymer‐treated surface. The effects of PEO‐PPO‐PEO molecular weight, PPO‐to‐PEO ratio, and ionic strength on protein adsorption from single protein solutions of fibrinogen, BSA, and complex mixed proteins are systematically investigated. A Pluronic™ F108 treated surface is highly resistant to nonspecific protein adsorption under the optimized conditions (MW of 15 k and PEO/PPO ratio of 80/20). This work demonstrates that the PEO‐PPO‐PEO polymer is able to achieve ultra low fouling surface via surface modification by controlling surface packing density of polymers (molecular weight, hydrophobic/hydrophilic ratio, and hydrophilic group coverage). © 2009 Wiley Periodicals, Inc. J Biomed Mater Res 2010
Ligand and structure‐based models for the prediction of ligand‐receptor affinities and virtual screenings: Development and application to the β2‐adrenergic receptor
Authors: Vilar Santiago , Karpiak Joel , Costanzi Stefano
Published: June 2009

In this study, we evaluated the applicability of ligand‐based and structure‐based models to quantitative affinity predictions and virtual screenings for ligands of the β2‐adrenergic receptor, a G protein‐coupled receptor (GPCR). We also devised and evaluated a number of consensus models obtained through partial least square regressions, to combine the strengths of the individual components. In all cases, the bioactive conformation of each ligand was derived from molecular docking at the crystal structure of the receptor. We identified the most effective models applicable to the different scenarios, in the presence or in the absence of a training set. For ranking the affinity of closely related analogs when a training set is available, a ligand‐based consensus model (LI‐CM) seems to be the best choice, while the structure‐based MM‐GBSA score seems the best alternative in the absence of a training set. For virtual screening purposes, the structure‐based MM‐GBSA score was found to be the method of choice. Consensus models consistently had performances superior or close to those of the best individual components, and were endowed with a significantly increased robustness. Given multiple models with no a priori knowledge of their predictive capabilities, constructing a consensus model ensures results very close to those that the best model alone would have yielded. © 2009 Wiley Periodicals, Inc. J Comput Chem 2010