bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nucleotide excision repair polymorphisms may modify ionizing radiation‐related breast cancer risk in US radiologic technologists
Authors: Rajaraman Preetha , Bhatti Parveen , Doody Michele Morin , Simon Steven L. , Weinstock Robert M. , Linet Martha S. , Rosenstein Marvin , Stovall Marilyn , Alexander Bruce H. , Preston Dale L. , Sigurdson Alice J. 
Published: September 2008

AbstractExposure to ionizing radiation has been consistently associated with increased risk of female breast cancer. Although the majority of DNA damage caused by ionizing radiation is corrected by the base‐excision repair pathway, certain types of multiple‐base damage can only be repaired through the nucleotide excision repair pathway. In a nested case–control study of breast cancer in US radiologic technologists exposed to low levels of ionizing radiation (858 cases, 1,083 controls), we examined whether risk of breast cancer conferred by radiation was modified by nucleotide excision gene polymorphisms ERCC2 (XPD) rs13181, ERCC4 (XPF) rs1800067 and rs1800124, ERCC5 (XPG) rs1047769 and rs17655; and ERCC6 rs2228526. Of the 6 ERCC variants examined, only ERCC5 rs17655 showed a borderline main effect association with breast cancer risk (ORGC = 1.1, ORCC = 1.3; p‐trend = 0.08), with some indication that individuals carrying the C allele variant were more susceptible to the effects of occupational radiation (EOR/GyGG = 1.0, 95% CI = <0, 6.0; EOR/GyGC/CC = 5.9, 95% CI = 0.9, 14.4; phet = 0.10). ERCC2 rs13181, although not associated with breast cancer risk overall, statistically significantly modified the effect of occupational radiation dose on risk of breast cancer (EOR/GyAA = 9.1, 95% CI = 2.1−21.3; EOR/GyAC/CC = 0.6, 95% CI = <0, 4.6; phet = 0.01). These results suggest that common variants in nucleotide excision repair genes may modify the association between occupational radiation exposure and breast cancer risk. © 2008 Wiley‐Liss, Inc.
No increased risk for cervical cancer after a broader definition of a negative Pap smear
Authors: Rebolj Matejka , van Ballegooijen Marjolein , van Kemenade Folkert , Looman Caspar , Boer Rob , Habbema J. Dik F. 
Published: September 2008

AbstractThe definition of minimal relevant Pap smear abnormality is crucial for balancing the beneficial effects of screening (prevented mortality) with negative side‐effects (the high positivity rate). After inflammation ceased to be defined as a borderline abnormal smear outcome in The Netherlands in 1996, the proportion of these smears dropped from 10% to less than 2%. Because this may have caused a loss in smear sensitivity, we analysed the changes in the incidence of cervical cancer after a negative Pap smear. All negative smears made at ages 30–64 in 1990–1995 (n = 1,546,252) and 1998–2006 (n = 3,552,716), registered in the national registry of histo‐ and cytopathology (PALGA), were followed for up to 9 years. During follow‐up of the 1990–1995 smears, 377 women developed cervical cancer within 5,232,959 woman‐years at risk, while during the follow‐up of the 1998–2006 smears, 619 women developed cervical cancer within 11,210,675 woman‐years at risk. The cumulative incidence after the definition change was not significantly higher than before: e.g. at 6 years, the cumulative incidence for smears made in 1990–1995 was 46 per 100,000 (95% CI: 41–52), and for smears in 1998–2006 was 48 per 100,000 (95% CI: 43–54), p = 0.59. The hazard ratio for 1998–2006 compared to 1990–1995 adjusted for age, number of previous negative smears and history of abnormalities was 0.90 (95% CI: 0.78–1.03). In The Netherlands, a setting with high‐quality cytological screening, treating smears with only signs of inflammation as negative leads to a considerably lower positivity rate without increasing the risk for cervical cancer after a negative smear. © 2008 Wiley‐Liss, Inc.
Prospective evaluation of trans‐fatty acid intake and colorectal cancer risk in the Iowa Women's Health Study
Authors: Limburg Paul J. , Liu‐Mares Wen , Vierkant Robert A. , Wang Alice H. , Harnack Lisa , Flood Andrew P. , Sellers Thomas A. , Cerhan James R. 
Published: September 2008

AbstractConcerns regarding the safety of dietary trans‐fatty acids (tFAs) have generated recent public interest, scientific discussion and legislative action. Although most widely recognized as a risk factor for cardiovascular disease, associations between tFA intake and incident cancer have also been proposed. With respect to colorectal cancer (CRC), existing observational data remain limited and inconclusive. Therefore, we conducted a prospective evaluation of tFA intake and CRC risk, overall and by anatomic subsite, among participants in the Iowa Women's Health Study (IWHS), a population‐based cohort of older women (ages 55–69 years at enrollment). Exposure data were collected at baseline using a semiquantitative food‐frequency questionnaire. Incident CRC cases were identified through annual linkage to the Iowa Cancer Registry. CRC risks were estimated using Cox proportional hazards regression models. In total, 35,216 women met our inclusion criteria and 1,229 CRC cases (631 proximal, 571 distal, 27 site not specified) were observed through 18 years of follow‐up. Adjusting for age and total energy consumption, tFA intake in the 4th versus 1st quartile was not significantly associated with overall CRC risk [relative risk (RR) = 1.12; 95% confidence interval (CI) = 0.96–1.32]. Similarly, risk estimates based on proximal (RR = 1.09; 95% CI = 0.87–1.37) and distal (RR = 1.18; 95% CI = 0.93–1.49) CRC subsites did not differ from unity. Multivariable adjustment yielded slightly attenuated risk estimates, but the observed associations were not meaningfully altered. Given these findings, tFA intake does not appear to be a major CRC risk factor, at least among older women. © 2008 Wiley‐Liss, Inc.
Leptin promotes motility and invasiveness in human colon cancer cells by activating multiple signal‐transduction pathways
Authors: Jaffe Tamara , Schwartz Betty 
Published: September 2008

AbstractLeptin serum levels are about 5 times higher in obese people than in normal individuals. We aimed at investigating the signaling pathways induced by leptin in the human colonic cell lines LS174T and HM7. Both cells expressed the leptin transmembrane Ob‐receptor. Leptin activated the mitogen‐activated protein kinase pathway, induced invasion of colonic cells and concomitantly increased the formation of lamellipodial structures. A direct and novel dose‐ and time‐dependent activation of RhoA, Cdc42 and Rac1 by leptin is demonstrated in these aggressive colon cancer cells. The activation of the Rho family of GTPases was amenable to specific inhibition: Wortmannin inhibited leptin‐induced Rac1 and Cdc42 activation but did not affect RhoA activation, and inhibited the formation of leptin‐induced lamellipodia and cell invasion. The Rac1 inhibitor NSC23766 inhibited only leptin‐induced Rac1 activation and concomitantly, lamellipodium formation and cell invasion. The Src kinase inhibitor II (SrcKI‐II) exerted a positive effect on RhoA activation, inhibited tyrosine phosphorylation of p190RhoGAP and inhibited leptin‐induced Cdc42 activation and leptin‐induced lamellopodium formation and cell invasion. The specific JAK2 inhibitor AG490 exerted a positive effect on Rac1 and Cdc42 activation by leptin and concomitantly inhibited RhoA activation. AG490 did not inhibit leptin‐induced lamellopodium formation or cell invasion. Our findings clearly indicate that leptin activates PI3K and Src kinase pathways in the metastatic colon cancer cells LS174T and HM7. These signaling pathways induce the activation of Rac1 and Cdc42, lamellopodium formation and concomitantly enhanced cell invasion, but leptin activation of RhoA is not associated with enhanced cell locomotion and invasion. Understanding in‐depth the pathways involved in leptin‐associated enhanced cell locomotion and invasion may contribute with the design of novel therapeutics to treat obesity‐associated advanced colorectal cancer. © 2008 Wiley‐Liss, Inc.
The resveratrol analogue 3,5,3′,4′,5′‐pentahydroxy‐trans‐stilbene inhibits cell transformation via MEK
Authors: Lee Ki Won , Kang Nam Joo , Rogozin Evgeny A. , Oh Sang‐Muk , Heo Yong Seok , Pugliese Angelo , Bode Ann M. , Lee Hyong Joo , Dong Zigang 
Published: September 2008

AbstractResveratrol, present in grapes and red wine, is reported to be a natural chemopreventive agent against cancer. However, the concentrations required to exert these effects may be difficult to achieve by drinking only 1 or 2 glasses of red wine a day. Therefore, developing more potent, nontoxic analogues of resveratrol may provide a feasible means of achieving an effective physiologic concentration. Here we report that the resveratrol analogue, 3,5,3′,4′,5′‐pentahydroxy‐trans‐stilbene (RSVL2), inhibits 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐induced neoplastic transformation in JB6 P+ mouse epidermal cells. Further, we identified MEK/ERK signaling as the direct molecular target for the anticancer effects of RSVL2 and demonstrated that RSVL2 inhibited MEK1, but not Raf1 or ERK2 kinase activity. RSVL2 also dose‐dependently suppressed MEK1 kinase activity induced by TPA and the inhibition of H‐Ras‐induced cell transformation was much stronger for RSVL2 than for PD098059 or resveratrol. Both in vitro and ex vivo pull‐down assays indicated that RSVL2, but not resveratrol, directly bound with GST‐MEK1, but did not compete with ATP for binding. Docking data indicated that the low inhibitory activity of resveratrol might be due to the lack of the hydroxyl group at the meta position of the B ring, thereby preventing resveratrol from forming a hydrogen bond with the backbone amide group of Ser212, which is the key interaction for stabilizing the inactive conformation of the activation loop. © 2008 Wiley‐Liss, Inc.
Prognostic value of Her‐2/neu and DNA index for progression, metastasis and prostate cancer‐specific death in men with long‐term follow‐up after radical prostatectomy
Authors: Isharwal Sumit , Miller Michael Craig , Epstein Jonathan I. , Mangold Leslie A. , Humphreys Elizabeth , Partin Alan W. , Veltri Robert W. 
Published: September 2008

AbstractAbnormal DNA content in tumor cells represents large scale chromosomal alterations and reflects later changes of genetic instability. Her‐2/neu oncogene is amplified in 20–30% of breast and ovarian cancer patients and is associated with poor prognosis. Therefore, we evaluated prognostic value of Her‐2/neu expression and DNA content measurements in 252 clinically localized PCa patients with long‐term follow‐up after radical prostatectomy for progression, metastasis and PCa‐specific death. Her‐2/neu expression was determined by immunohistochemistry and DNA content measurements employed Feulgen‐stained cancer nuclei captured using static image cytometry system. Cox proportional hazard regression and Kaplan‐Meir plots were used to identify significant prognostic factors for progression, metastasis and PCa‐specific death. The proportions of Her‐2/neu positive and high %DNA index tumors significantly increased from nonprogressor to progressors without metastasis to progressors with metastasis (p < 0.0001; <0.0001). Further, the proportions of Her‐2/neu positive and high %DNA index tumors significantly increased from patients who died from another cause without progression to those who died from another cause with progression to those died with PCa‐specific death (p = 0.027; <0.0001). Her‐2/neu expression and %DNA index were significant prognosticators for progression (p ≤ 0.001), metastasis (p ≤ 0.01) PCa‐specific death (p ≤ 0.04) in univariate analyses. Multivariately, Her‐2/neu expression and %DNA index were also significant for progression (p = 0.001), metastasis (p = 0.001) and PCa‐specific death (p = 0.02). When all other clinicopathologic information is available, the increment in concordance index by addition of either Her‐2/neu or DNA index was ∼2% and of both biomarkers was ∼3% for progression, metastasis and PCa‐specific death free survival models. Therefore, patients with Her‐2/neu positive and high %DNA index are at a higher risk for disease progression, metastasis and PCa‐specific death. Further, Her‐2/neu expression and %DNA index may be used with clinicopathologic parameters for prediction of long‐term prognosis in PCa. © 2008 Wiley‐Liss, Inc.
An epigenetic marker panel for screening and prognostic prediction of ovarian cancer
Authors: Su Her‐Young , Lai Hung‐Cheng , Lin Ya‐Wen , Chou Yu‐Ching , Liu Chin‐Yu , Yu Mu‐Hsien 
Published: September 2008

AbstractAberrant CpG island hypermethylation is a common finding of cancers, which might be detectable in the tissue or serum of affected patients. We analyzed DNA methylation by methylation‐specific polymerase chain reaction of 7 genes, which included secreted frizzled receptor proteins 1, 2, 4, 5 (SFRP1, 2, 4, 5), SRY‐box 1 (SOX1), paired box gene 1 (PAX1) and LIM homeobox transcription factor 1, alpha (LMX1A) in primary tumor samples from 126 patients with ovarian cancer, 75 with a benign tumor and 14 with borderline malignancy of an ovarian tumor, and in the serum from 26 patients with ovarian cancer and 20 with a benign tumor. Six of 7 genes had higher methylation rates in patients with ovarian cancer than in borderline malignancy or benign tumor (p < 0.001). The methylation of SFRP1, SFRP2, SOX1 and LMX1A genes correlated with recurrence and overall survival of ovarian cancer patients. Combining the data for SFRP1, SFRP2 and SOX1 genes gave a relative risk for recurrence of 3.19 (p = 0.013) in patients with at least one gene methylation, and combining the data for SFRP1, SOX1 and LMX1A gave an RR for cancer‐related death of 6.09 (p = 0.010). Methylation analysis of tissues and serum revealed a significant correlation (kappa values, 0.332–0.598) and a highly sensitivity and specificity rates (73.08 and 75%) as a screening marker. In conclusion, promoter hypermethylation of specific genes in critical pathways is common in ovarian cancer and has potential as a prognostic factor and a promising serum marker for early screening. © 2008 Wiley‐Liss, Inc.
Prevalence and frequency of circulating t(14;18)‐MBR translocation carrying cells in healthy individuals
Authors: Schüler Frank , Dölken Lars , Hirt Carsten , Kiefer Thomas , Berg Tobias , Fusch Gerhard , Weitmann K. , Hoffmann W. , Fusch Christoph , Janz Siegfried , Rabkin Charles S. , Dölken Gottfried 
Published: September 2008

AbstractThe t(14;18) translocation is a common genetic aberration that can be seen as an early step in pathogenesis of follicular lymphoma (FL). The significance of low level circulating t(14;18)‐positive cells in healthy individuals as clonal lymphoma precursors or indicators of risk is still unclear. We determined the age dependent prevalence and frequency of BCL2/IgH rearrangements in 715 healthy individuals ranging from newborns to octo‐ and nonagenarians. These results were compared with number of circulating t(14;18)‐positive cells in 108 FL patients at initial presentation. The overall prevalence of BCL2/IgH junctions in this large sample was 46% (327/715). However, there was a striking dependence upon age. Specifically, among individuals up to 10 years old, none had detectable circulating t(14;18)‐positive cells. In the age groups representing 10–50 years old, we found a steady elevation in the prevalence of BCL2/IgH junctions up to a prevalence of 66%. Further increases of the prevalence in individuals older than 50 years were not seen. The mean frequency of BCL2/IgH junctions in healthy individuals ≥40 years (18–26 × 10−6) was significantly higher than in younger subjects (7–9 × 10−6). Four percent (31/715) of individuals carried more than one t(14;18)‐positive cell per 25,000 peripheral blood mononuclear cells (PBMNCs). In comparison, 108 stage III/IV FL patients had a median number of circulating t(14;18)‐positive malignant FL cells of about 9200/1 million PBMNCs (range 7–1,000,000). These findings will further improve the understanding of the relevance of t(14;18)‐positive cells in healthy individuals as a risk marker toward the development into lymphoma precursors. © 2008 Wiley‐Liss, Inc.
Genomic instability and histone H3 phosphorylation induction by the Ras‐mitogen activated protein kinase pathway in pancreatic cancer cells
Authors: Espino Paula S. , Pritchard Susan , Heng Henry H.Q. , Davie James R. 
Published: September 2008

AbstractActivating mutations in K‐Ras occur in most pancreatic cancers. We investigated whether genetic changes (K‐Ras mutations) in human pancreatic cancer cell lines altered genomic instability and epigenetic events responding to Ras‐mitogen activated protein kinase (MAPK) signaling by characterizing 3 human pancreatic cancer cells lines with and without activating mutations in K‐Ras. Activation of the Ras‐MAPK pathway results in the stimulation of the histone H3 kinase, mitogen and stress activated kinase (MSK) 1, and increased phosphorylation of histone H3 at serine 10 (H3 S10ph). MSK1 and H3 S10ph have roles in neoplastic transformation. We demonstrate that the presence of a K‐Ras mutation did not correlate with elevated chromosomal aberrations or increased genomic instability. Although the levels of the epidermal growth factor receptors and MSK were similar, the Ras‐MAPK pathway was differentially induced by phorbol esters (12‐O tetradecanoylphorbol‐13‐acetate) or epidermal growth factor, with the response of this signaling pathway being cell‐type specific. This response corresponded downstream at the level of chromatin where stimuli‐induced elevation of H3 S10ph typically paralleled the increase in phospho‐extracellular signal regulated kinase 1/2. Our results present evidence that nonclonal chromosomal aberrations and epigenetic programming responding to stimulation of the Ras‐MAPK pathway may be better markers for cancer progression than the upstream mutated oncogenes. © 2008 Wiley‐Liss, Inc.
Promoter hypermethylation correlates with the Hsulf‐1 silencing in human breast and gastric cancer
Authors: Chen Zhao , Fan Jie‐Qing , Li Jie , Li Qiu‐Shi , Yan Zhao , Jia Xue‐Ke , Liu Wei‐Dong , Wei Li‐Jun , Zhang Feng‐Zhi , Gao Hong , Xu Jun‐Pu , Dong Xiao‐Ming , Dai Jie , Zhou Hai‐Meng 
Published: September 2008

AbstractThe HSulf‐1 gene is an important factor that modulates the sulfation status of heparan sulfate proteoglycans (HSPGs) in the extracellular matrix, resulting in disturbance of HSPG‐related signal transduction pathways. Recently, HSulf‐1 has been reported to be down‐regulated in several human cancers. In this study, we first cloned and characterized the 5′ promoter region of the HSulf‐1 gene (around 400 bp) that contained high basal promoter activity. We also found that this functional promoter region was hypermethylated in a number of human cancer cell lines. Furthermore, we found that hypermethylation in this promoter region correlated with the down‐regulation of the HSulf‐1 expression in human breast and gastric cancer cell lines and tissue samples. These results suggest that the promoter hypermethylation may be one of the mechanisms of the HSulf‐1 gene silencing in human breast and gastric cancers. Finally, we demonstrated that the HSulf‐1 promoter was more frequently (p < 0.05) methylated in cell‐free DNA extracted from serum samples of human breast and gastric cancer patients than that of healthy people (76.2%, 55.0% and 19.0%, respectively), indicating that detection of the HSulf‐1 promoter methylation in serum samples may have clinical implications in early detection and diagnosis of human breast and gastric cancers. © 2008 Wiley‐Liss, Inc.
NDRG3 is an androgen regulated and prostate enriched gene that promotes in vitro and in vivo prostate cancer cell growth
Authors: Wang Weiqun , Li Yuhua , Li Yang , Hong Aizhen , Wang Jian , Lin Biaoyang , Li Runsheng 
Published: September 2008

AbstractNDRG3 belongs to the N‐myc down‐regulated gene (NDRG) family that contains 4 paralogs: NDRG1, ‐2, ‐3 and ‐4. The function of NDRG3 and its relationship to cancer has not been studied. We herein report our examination of the expression and biological roles of NDRG3 in prostate cancers. We showed that NDRG3 expression is enriched in testis and prostate using gene expression data derived from massively parallel signature sequencing from 33 different human organs. We further showed that NDRG3 is expressed in both epithelial prostate cancer cells and prostatic stromal cells at both mRNA and proteins levels. We demonstrated that NDRG1 is significantly up‐regulated by androgen in LNCaP cells. Over‐expression of NDRG3 in stably transfected PC‐3 cells increased their growth rates and migration capabilities when compared to parental or mock empty vector transfected PC‐3 cells. In addition, we found that overexpresson of NDRG3 promoted the growth of xenograft tumors in nude mice. Finally, we found that NDRG3 expression was detected in 58.6% (41/70) of prostate cancer specimens compared to 13.2% (5/38) of benign prostatic hyperplasia specimens by immunohistochemistry. We showed by microarray and by RT‐PCR that NDRG3 overexpression up‐regulates the expression of many angiogenic chemokines including CXCL1 (chemokine ligand 1), CXCL3 (chemokine ligand 3) and CXCL5 (chemokine ligand 5), which may increase angiogenesis of tumors. Taken together, these results demonstrate that NDRG3 is a tumor promoter, the overexpression of which may contribute to the malignant phenotype of tumors. © 2008 Wiley‐Liss, Inc.
Reciprocal activating interaction between 6‐sulfo LacNAc+ dendritic cells and NK cells
Authors: Wehner Rebekka , Löbel Bärbel , Bornhäuser Martin , Schäkel Knut , Cartellieri Marc , Bachmann Michael , Rieber Ernst Peter , Schmitz Marc 
Published: September 2008

AbstractDendritic cells (DCs) display an extraordinary capacity to induce T‐cell responses providing the opportunity of DC‐based cancer vaccination strategies. Additional findings indicate that DCs may also play a crucial role for the activation of natural killer (NK) cells, which are important effectors in innate antitumor immunity. However, studies investigating the interaction between native human DCs and NK cells are limited. Recently, we defined 6‐sulfo LacNAc (slan) DCs as a major subpopulation of myeloid human blood DCs, which represent principal producers of the proinflammatory cytokines tumor necrosis factor‐α and interleukin (IL)‐12. Functional data revealed that slanDCs efficiently induce neoantigen‐specific CD4+ T cells and activate tumor‐reactive cytotoxic T cells. When evaluating the crosstalk between slanDCs and NK cells in this study, we found that lipopolysaccharide (LPS)‐activated slanDCs efficiently enhance NK cell CD69 expression and interferon (IFN)‐γ secretion. NK cell‐mediated tumor‐directed cytotoxicity was significantly improved by slanDCs. NK cell activation induced by slanDCs was critically dependent on IL‐12. When investigating the impact of NK cells on the immunostimulatory capacity of slanDCs, we observed that they promote DC maturation. In addition, NK cells strongly enhanced the secretion of immunomodulatory IL‐12 and reduced the release of immunosuppressive IL‐10 by slanDCs. IFN‐γ and cell‐to‐cell contact contributed to these effects. Furthermore, data revealed that DC‐NK cell crosstalk improves slanDC‐mediated differentiation of naïve CD4+ T lymphocytes into IFN‐γ‐producing Th1 cells. In conclusion, we demonstrate a reciprocal activating interaction between slanDCs and NK cells, which may play a pivotal role in the regulation of antitumor immunity. © 2008 Wiley‐Liss, Inc.