bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cone penetration test (CPT) methods for end-bearing assessment of open- and closed-ended driven piles in siliceous sand
Authors: Xu Xiangtao , Schneider James A. , Lehane Barry M. 
Published: August 2008

The cone penetration test (CPT) has been used as a means of assessing the end bearing of driven piles in sand for many decades. This paper examines the predictive performance of four new such CPT-based methods recently included in the commentary of the 22nd edition of the American Petroleum Institute’s recommended practice for fixed offshore structures. It is demonstrated that the formulations given by one of these methods, referred to as UWA-05, provides better predictions than the three other CPT methods when tested against (i) an existing database of base-capacity measurements, (ii) results from a new series of load tests on small-diameter piles, and (iii) base capacities measured in two recently conducted load tests on 1.5 m diameter pipe piles. It is shown that the UWA-05 has better predictive performance (and hence reliability) as it accounts explicitly for the effects of partial plugging during pipe–pile installation and for variations in CPT resistance in the vicinity of the pile tip.
Vascular Endothelial Growth Factor Reduces Tamoxifen Efficacy and Promotes Metastatic Colonization and Desmoplasia in Breast Tumors
Authors: Qu Zhican , Van Ginkel Sabrina , Roy Anshu M. , Westbrook Louise , Nasrin Mubina , Maxuitenko Yulia , Frost Andra R. , Carey Delicia , Wang Wenquan , Li Rongbao , Grizzle William E. , Thottassery Jaideep V. , Kern Francis G. 
Published: August 2008

Abstract
Clinical studies have shown that decreased tamoxifen effectiveness correlates with elevated levels of vascular endothelial growth factor (VEGF)-A165 in biopsy samples of breast cancers. To investigate the mechanisms underlying tamoxifen resistance and metastasis, we engineered the estrogen receptor (ER)–positive MCF-7 human breast cancer cell line to express VEGF to clinically relevant levels in a doxycycline-regulated manner. Induction of VEGF expression in orthotopically implanted xenografts that were initially tamoxifen responsive and noninvasive resulted in tamoxifen-resistant tumor growth and metastasis to the lungs. Lung metastases were also observed in a VEGF-dependent manner following tail vein injection of tumor cells. At both primary and metastatic sites, VEGF-overexpressing tumors exhibited extensive fibroblastic stromal content, a clinical feature called desmoplasia. VEGF-induced metastatic colonies were surrounded by densely packed stromal cells before detectable angiogenesis, suggesting that VEGF is involved in the initiation of desmoplasia. Because expression of VEGF receptors R1 and R2 was undetectable in these tumor cells, the observed VEGF effects on reduction of tamoxifen efficacy and metastatic colonization are most likely mediated by paracrine signaling that enhances tumor/stromal cell interactions and increases the level of desmoplasia. This study reveals new roles for VEGF in breast cancer progression and suggests that combination of antiestrogens and VEGF inhibitors may prolong tamoxifen sensitivity and prevent metastasis in patients with ER-positive tumors. [Cancer Res 2008;68(15):6232–40]
Diagnostic and Prognostic MicroRNAs in Stage II Colon Cancer
Authors: Schepeler Troels , Reinert Jørgen T. , Ostenfeld Marie S. , Christensen Lise L. , Silahtaroglu Asli N. , Dyrskjøt Lars , Wiuf Carsten , Sørensen Frank J. , Kruhøffer Mogens , Laurberg Søren , Kauppinen Sakari , Ørntoft Torben F. , Andersen Claus L. 
Published: August 2008

Abstract
MicroRNAs (miRNA) are a class of small noncoding RNAs with important posttranscriptional regulatory functions. Recent data suggest that miRNAs are aberrantly expressed in many human cancers and that they may play significant roles in carcinogenesis. Here, we used microarrays to profile the expression of 315 human miRNAs in 10 normal mucosa samples and 49 stage II colon cancers differing with regard to microsatellite status and recurrence of disease. Several miRNAs were differentially expressed between normal tissue and tumor microsatellite subtypes, with miR-145 showing the lowest expression in cancer relative to normal tissue. Microsatellite status for the majority of cancers could be correctly predicted based on miRNA expression profiles. Furthermore, a biomarker based on miRNA expression profiles could predict recurrence of disease with an overall performance accuracy of 81%, indicating a potential role of miRNAs in determining tumor aggressiveness. The expression levels of miR-320 and miR-498, both included in the predictive biomarker, correlated with the probability of recurrence-free survival by multivariate analysis. We successfully verified the expression of selected miRNAs using real-time reverse transcription-PCR assays for mature miRNAs, whereas in situ hybridization was used to detect the accumulation of miR-145 and miR-320 in normal epithelial cells and adenocarcinoma cells. Functional studies showed that miR-145 potently suppressed growth of three different colon carcinoma cell lines. In conclusion, our results suggest that perturbed expression of numerous miRNAs in colon cancer may have a functional effect on tumor cell behavior, and, furthermore, that some miRNAs with prognostic potential could be of clinical importance. [Cancer Res 2008;68(15):6416–24]
RUNX3 Methylation Reveals that Bladder Tumors Are Older in Patients with a History of Smoking
Authors: Wolff Erika M. , Liang Gangning , Cortez Connie C. , Tsai Yvonne C. , Castelao J. Esteban , Cortessis Victoria K. , Tsao-Wei Denice D. , Groshen Susan , Jones Peter A. 
Published: August 2008

Abstract
Exposure to tobacco smoke is associated with increased DNA methylation at certain genes in both lung and bladder tumors. We sought to identify interactions in bladder cancer between DNA methylation and a history of smoking, along with any possible effect of aging. We measured DNA methylation in 342 transitional cell carcinoma tumors at BCL2, PTGS2 (COX2), DAPK, CDH1 (ECAD), EDNRB, RASSF1A, RUNX3, TERT, and TIMP3. The prevalence of methylation at RUNX3, a polycomb target gene, increased as a function of age at diagnosis (P = 0.031) and a history of smoking (P = 0.015). RUNX3 methylation also preceded methylation at the other eight genes (P &lt; 0.001). It has been proposed that DNA methylation patterns constitute a “molecular clock” and can be used to determine the “age” of normal tissues (i.e., the number of times the cells have divided). Because RUNX3 methylation increases with age, is not present in normal urothelium, and occurs early in tumorigenesis, it can be used for the first time as a molecular clock to determine the age of a bladder tumor. Doing so reveals that tumors from smokers are “older” than tumors from nonsmokers (P = 0.009) due to tumors in smokers either initiating earlier or undergoing more rapid cell divisions. Because RUNX3 methylation is acquired early on in tumorigenesis, then its detection in biopsy or urine specimens could provide a marker to screen cigarette smokers long before any symptoms of bladder cancer are present. [Cancer Res 2008;68(15):6208–14]
An Integrative Genomic and Proteomic Analysis of PIK3CA, PTEN, and AKT Mutations in Breast Cancer
Authors: Stemke-Hale Katherine , Gonzalez-Angulo Ana Maria , Lluch Ana , Neve Richard M. , Kuo Wen-Lin , Davies Michael , Carey Mark , Hu Zhi , Guan Yinghui , Sahin Aysegul , Symmans W. Fraser , Pusztai Lajos , Nolden Laura K. , Horlings Hugo , Berns Katrien , Hung Mien-Chie , van de Vijver Marc J. , Valero Vicente , Gray Joe W. , Bernards René , Mills Gordon B. , Hennessy Bryan T. 
Published: August 2008

Abstract
Phosphatidylinositol 3-kinase (PI3K)/AKT pathway aberrations are common in cancer. By applying mass spectroscopy–based sequencing and reverse-phase protein arrays to 547 human breast cancers and 41 cell lines, we determined the subtype specificity and signaling effects of PIK3CA, AKT, and PTEN mutations and the effects of PIK3CA mutations on responsiveness to PI3K inhibition in vitro and on outcome after adjuvant tamoxifen. PIK3CA mutations were more common in hormone receptor–positive (34.5%) and HER2-positive (22.7%) than in basal-like tumors (8.3%). AKT1 (1.4%) and PTEN (2.3%) mutations were restricted to hormone receptor–positive cancers. Unlike AKT1 mutations that were absent from cell lines, PIK3CA (39%) and PTEN (20%) mutations were more common in cell lines than tumors, suggesting a selection for these but not AKT1 mutations during adaptation to culture. PIK3CA mutations did not have a significant effect on outcome after adjuvant tamoxifen therapy in 157 hormone receptor–positive breast cancer patients. PIK3CA mutations, in comparison with PTEN loss and AKT1 mutations, were associated with significantly less and inconsistent activation of AKT and of downstream PI3K/AKT signaling in tumors and cell lines. PTEN loss and PIK3CA mutation were frequently concordant, suggesting different contributions to pathophysiology. PTEN loss rendered cells significantly more sensitive to growth inhibition by the PI3K inhibitor LY294002 than did PIK3CA mutations. Thus, PI3K pathway aberrations likely play a distinct role in the pathogenesis of different breast cancer subtypes. The specific aberration present may have implications for the selection of PI3K-targeted therapies in hormone receptor–positive breast cancer. [Cancer Res 2008;68(15):6084–91]
RhoA-Dependent Regulation of Cell Migration by the Tumor Suppressor hSNF5/INI1
Authors: Caramel Julie , Quignon Frédérique , Delattre Olivier 
Published: August 2008

Abstract
Malignant rhabdoid tumors (MRT) are extremely aggressive pediatric tumors caused by the inactivation of the hSNF5/INI1 tumor suppressor gene, which encodes a core member of the SWI/SNF chromatin remodeling complex. Roles for hSNF5/INI1 in cell cycle and differentiation have been documented. Based on the observation that MRTs are highly invasive, we investigated a role for hSNF5/INI1 in cell migration. MRT cell lines exhibit high migration properties that are dramatically reduced upon hSNF5/INI1 expression. This effect is associated with the disorganization of the actin stress fiber network and is mediated by the inhibition of the activity of the small GTPase RhoA, through a nuclear, SWI/SNF-dependent transcriptional mechanism. We further show that the knockdown of hSNF5/INI1 in epithelial 293T or MCF7 cells results in increased cell size, loss of cell-cell adhesions, and enhanced migration, associated with an increased RhoA activity. Finally, we show that the SNF5 homology domain is required for hSNF5/INI1-mediated inhibition of migration, and that a missense mutation (S284L) associated with cancer is sufficient to impair hSNF5/INI1 function in migration. We conclude that the inhibition of migration is another crucial tumor suppressor function of hSNF5/INI1, in addition to its previously described functions in proliferation and differentiation, and that its loss-of-function in MRTs may account for the high invasiveness and metastatic potential of these tumors. [Cancer Res 2008;68(15):6154–61]
Variants in Inflammation Genes and the Risk of Biliary Tract Cancers and Stones: A Population-Based Study in China
Authors: Hsing Ann W. , Sakoda Lori C. , Rashid Asif , Andreotti Gabriella , Chen Jinbo , Wang Bin-Shen , Shen Ming-Chang , Chen Bingshu E. , Rosenberg Philip S. , Zhang Mingdong , Niwa Shelley , Chu Lisa , Welch Robert , Yeager Meredith , Fraumeni Joseph F. , Gao Yu-Tang , Chanock Stephen J. 
Published: August 2008

Abstract
To evaluate the role of chronic inflammation in the development of gallstones and biliary tract cancer, we examined the risk associated with 62 single nucleotide polymorphisms (SNPs), in 22 inflammation-related genes, in a population-based case-control study conducted in Shanghai, China, where the incidence of biliary tract cancer has been increasing in recent decades. The study included 411 cases with biliary tract cancer (237 gallbladder, 127 extrahepatic bile duct, and 47 ampulla of Vater), 895 with biliary stones, and 786 controls randomly selected from the population. Unconditional logistic regression was used to calculate odds ratios and 95% confidence intervals for the association of individual SNPs and haplotypes with biliary stones and biliary tract cancer. Of the 62 SNPs examined, 14 were related to the risk of biliary cancer and stones. Specifically, variants in the IL8, IL8RB, RNASEL, and NOS2 genes were associated with biliary stones, whereas VEGF variants were associated with gallbladder cancer. Of the 10 genes with multiple SNPs from which we inferred haplotypes, only one IL8RB haplotype, consisting of 3 SNPs (rs2230054, rs1126579, and rs1126580), was associated with the risk of bile duct cancer (P = 0.003) and biliary stones (P = 0.02), relative to the most frequent haplotype. In summary, common variants in genes that influence inflammatory responses may predispose to gallstones and biliary tract cancer, suggesting the need for future studies into the immunologic and inflammatory pathways that contribute to biliary diseases, including cancer. [Cancer Res 2008;68(15):6442–52]
Effect of Ablation or Inhibition of Stromal Matrix Metalloproteinase-9 on Lung Metastasis in a Breast Cancer Model Is Dependent on Genetic Background
Authors: Martin Michelle D. , Carter Kathy J. , Jean-Philippe Sharon R. , Chang Mayland , Mobashery Shahriar , Thiolloy Sophie , Lynch Conor C. , Matrisian Lynn M. , Fingleton Barbara 
Published: August 2008

Abstract
Matrix metalloproteinases (MMP) are a family of enzymes with a myriad of functions. Lately, we have come to realize that broad-spectrum inhibition of these enzymes, as was tried unsuccessfully in multiple phase III trials in cancer patients, is likely unwise given the protumorigenic and antitumorigenic functions of various family members. Here, we used the multistage mammary tumor model MMTV-PyVT to investigate roles for either MMP7 or MMP9 in tumor progression. We found no effect of genetic ablation of MMP7 or MMP9 on the multifocal tumors that developed in the mammary glands. Lack of MMP7 also had no effect on the development of lung metastases, suggesting that MMP7 is irrelevant in this model. In contrast, MMP9 deficiency was associated with an 80% decrease in lung tumor burden. The predominant cellular source of MMP9 was myeloid cells, with neutrophils being the largest contributor in tumor-bearing lungs. Experimental metastasis assays corroborated the role of host-derived MMP9 in lung metastasis and also facilitated determination of a time frame most relevant for the MMP9-mediated effect. The lung tumors from MMP9-deficient mice showed decreased angiogenesis. Surprisingly, the antimetastatic outcome of MMP9 ablation seemed to be dependent on strain. Only mice that had genetic background derived from C57BL/6 showed reduced metastasis, whereas mice fully of the FVB/N background showed no significant effect. These strain-specific responses were also observed in a study using a highly selective pharmacologic inhibitor of MMP9 and thus suggest that responses to MMP inhibition are controlled by genetic differences. [Cancer Res 2008;68(15):6251–9]
The HER4/4ICD Estrogen Receptor Coactivator and BH3-Only Protein Is an Effector of Tamoxifen-Induced Apoptosis
Authors: Naresh Anjali , Thor Ann D. , Edgerton Susan M. , Torkko Kathleen C. , Kumar Rakesh , Jones Frank E. 
Published: August 2008

Abstract
Greater than 40% of breast cancer patients treated with tamoxifen exhibit de novo or acquired tumor resistance. Recent clinical evidence indicates that loss of expression of HER4 is an independent marker for tamoxifen resistance. In direct corroboration with clinical observations, suppression of HER4 expression in the tamoxifen-sensitive MCF-7 and T47D breast tumor cell lines resulted in resistance to tamoxifen-induced apoptosis. Furthermore, HER4 expression was lost in three independent MCF-7 models of acquired tamoxifen resistance. The HER4 intracellular domain (4ICD) is an independently signaling nuclear protein that functions as a potent ERα coactivator. In addition, mitochondrial 4ICD functions as a proapoptotic BH3-only protein. Tamoxifen disrupts an estrogen-driven interaction between ERα and 4ICD while promoting mitochondrial accumulation of the 4ICD BH3-only protein. BCL-2 inhibition of tamoxifen-induced apoptosis and tamoxifen activation of BAK, independent of BAX, further supports a role for 4ICD during tamoxifen-induced apoptosis. Finally, reintroduction of HER4, but not HER4 with a mutated BH3 domain, restores tamoxifen sensitivity to tamoxifen-resistant TamR cells in a xenograft model. Clinically, breast cancer patients with tumor expression of nuclear 4ICD responded to tamoxifen therapy with no clinical failures reported after 14 years of follow-up, whereas 20% of patients lacking nuclear 4ICD expression succumbed to their disease within 10 years of diagnosis. Our identification of the HER4/4ICD BH3-only protein as a critical mediator of tamoxifen action provides a clinically important role for 4ICD in human cancer and reveals a potential tumor marker to predict patient response to tamoxifen therapy. [Cancer Res 2008;68(15):6387–95]
Down-regulation of Myeloid Cell Leukemia-1 through Inhibiting Erk/Pin 1 Pathway by Sorafenib Facilitates Chemosensitization in Breast Cancer
Authors: Ding Qingqing , Huo Longfei , Yang Jer-Yen , Xia Weiya , Wei Yongkun , Liao Yong , Chang Chun-Ju , Yang Yan , Lai Chien-Chen , Lee Dung-Fang , Yen Chia-Jui , Chen Yun-Ju Rita , Hsu Jung-Mao , Kuo Hsu-Ping , Lin Chun-Yi , Tsai Fuu-Jen , Li Long-Yuan , Tsai Chang-Hai , Hung Mien-Chie 
Published: August 2008

Abstract
Myeloid cell leukemia-1 (Mcl-1), a Bcl-2–like antiapoptotic protein, plays a role in cell immortalization and chemoresistance in a number of human malignancies. A peptidyl-prolyl cis/trans isomerase, Pin1 is involved in many cellular events, such as cell cycle progression, cell proliferation, and differentiation through isomerizing prophosphorylated substrates. It has been reported that down-regulation of Pin1 induces apoptosis, and that Erk phosphorylates and up-regulates Mcl-1; however, the underlying mechanisms for the two phenomena are not clear yet. Here, we showed that Pin 1 stabilizes Mcl-1, which is required for Mcl-1 posphorylation by Erk. First, we found expression of Mcl-1 and Pin1 were positively correlated and associated with poor survival in human breast cancer. We then showed that Erk could phosphorylate Mcl-1 at two consensus residues, Thr 92 and 163, which is required for the association of Mcl-1 and Pin1, resulting in stabilization of Mcl-1. Moreover, Pin1 is also required for the up-regulation of Mcl-1 by Erk activation. Based on this newly identified mechanism of Mcl-1 stabilization, two strategies were used to overcome Mcl-1–mediated chemoresistance: inhibiting Erk by Sorafenib, an approved clinical anticancer drug, or knocking down Pin1 by using a SiRNA technique. In conclusion, the current report not only unravels a novel mechanism to link Erk/Pin1 pathway and Mcl-1–mediated chemoresistance but also provides a plausible combination therapy, Taxol (Paclitaxel) plus Sorafenib, which was shown to be effective in killing breast cancer cells. [Cancer Res 2008;68(15):6109–17]
Targeted Overexpression of Vav3 Oncogene in Prostatic Epithelium Induces Nonbacterial Prostatitis and Prostate Cancer
Authors: Liu Yin , Mo Jun Qin , Hu Qiande , Boivin Gregory , Levin Linda , Lu Shan , Yang Dianer , Dong Zhongyun , Lu Shan 
Published: August 2008

AbstractOur previous study revealed that Vav3 oncogene is overexpressed in human prostate cancer, activates androgen receptor (AR), and stimulates growth in prostate cancer cells. The purpose of this study is to further determine the potential role of Vav3 in prostate cancer development in genetically engineered mouse model. We generated Vav3 transgenic mice by targeted overexpression of a constitutive active Vav3 in the prostatic epithelium. We found that overexpression of Vav3 led to development of mouse prostatic intraepithelial neoplasia and prostate cancer at the age of as early as 3 months. The AR signaling axis and phosphatidylinositol 3-kinase-Akt signaling were elevated in the prostate glands of Vav3 transgenic mice. In addition to prostate cancer, Vav3 transgenic mice developed significant nonbacterial chronic prostatitis in the prostate gland with notable infiltration of lymphomononuclear cells (monocytes, lymphocytes, and plasma cells), which was associated with elevated incidence of prostate cancer. DNA microarray and signaling pathway analysis revealed that the top diseases and disorders were inflammatory diseases and cancer of the prostate gland in Vav3 transgenic mice. In vitro analysis showed that overexpression of Vav3 in prostate cancer cells enhanced nuclear factor-κB (NF-κB) activity, implicating an underlying mechanism of innate inflammatory response induced by elevated Vav3 activity. These data showed that Vav3 overexpression in the prostate epithelium enhanced both the AR signaling axis and NF-κB–mediated pathway, which potentially contributed to the development of nonbacterial prostatitis and prostate cancer. [Cancer Res 2008;68(15):6396–406]
Serum-Soluble B7x Is Elevated in Renal Cell Carcinoma Patients and Is Associated with Advanced Stage
Authors: Thompson R. Houston , Zang Xingxing , Lohse Christine M. , Leibovich Bradley C. , Slovin Susan F. , Reuter Victor E. , Cheville John C. , Blute Michael L. , Russo Paul , Kwon Eugene D. , Allison James P. 
Published: August 2008

Abstract
B7x is the newest member of the B7-CD28 family and is thought to dampen immune responses via negative costimulation. Tumor expression of B7x was recently described in renal cell carcinoma (RCC) and was associated with poor outcome. We developed an assay to detect serum-soluble B7x (sB7x) and investigated 101 patients with clear cell RCC who underwent nephrectomy between 2003 and 2007. For controls, we obtained serum from 101 sex-matched blood donors within the same age range. Following an ELISA for sB7x, detectable levels (&gt;0.1 ng/mL) of sB7x were observed in 53 RCC patients compared with 18 controls (P &lt; 0.001). Median (range) concentrations of sB7x for RCC patients and controls were 14.4 ng/mL (0.1–56.9) and 2.7 ng/mL (0.2–37.1), respectively. For RCC patients with detectable sB7x, median levels were significantly higher for patients with a tumor thrombus (19.2 versus 6.6 ng/mL; P = 0.007), positive lymph nodes (41.3 versus 10.3 ng/mL; P = 0.018), and distant metastases at nephrectomy (43.3 versus 8.5 ng/mL; P = 0.002) and tended to be higher in patients with high-grade tumors (18.8 versus 8.5; P = 0.090). Additionally, median sB7x levels for tumor-node-metastasis stage I to IV RCC were 6.6, 10.3, 14.5, and 43.3 ng/mL, respectively (P = 0.012). In this first evaluation of sB7x in RCC, we show that RCC patients are more likely to have detectable sB7x compared with controls and higher sB7x levels correlate with advanced tumor stage. These early results merit further investigation of this serum marker for potential diagnostic and prognostic purposes. [Cancer Res 2008;68(15):6054–8]