bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Unique MEK-Dependent Genes in GNAQ Mutant Uveal Melanoma Involved in Cell Growth, Tumor Cell Invasion, and MEK Resistance
Authors: Ambrosini Grazia , Pratilas Christine A. , Qin Li-Xuan , Tadi Madhavi , Surriga Oliver , Carvajal Richard D. , Schwartz Gary K. 
Published: May 2012

Abstract
Purpose: Metastatic uveal melanoma represents the most common intraocular malignancy with very poor prognosis and no effective treatments. Oncogenic mutations in the G-protein α-subunit q and 11 have been described in about 85% of uveal melanomas and confer constitutive activation. Multiple signaling pathways are induced as a consequence of GNAQ/11 activation, which include the MEK/ERK kinase cascade. We analyzed the transcriptional profile of cell lines treated with a mitogen-activated protein (MAP)/extracellular signal–regulated (ERK) kinase (MEK) inhibitor to identify gene targets of activated GNAQ and to evaluate the biologic importance of these genes in uveal melanoma.
Experimental Design: We conducted microarray analysis of uveal melanoma cell lines with GNAQ mutations treated with the MEK inhibitor selumetinib. For comparison, we used cells carrying BRAFV600E and cells without either mutation. Changes in the expression of selected genes were then confirmed by quantitative real-time PCR and immunoblotting.
Results: We found that GNAQ mutant cells have a MEK-dependent transcriptional output and identified a unique set of genes that are downregulated by MEK inhibition, including the RNA helicase DDX21 and the cyclin-dependent kinase regulator CDK5R1 whereas Jun was induced. We provide evidence that these genes are involved in cell proliferation, tumor cell invasion, and drug resistance, respectively. Furthermore, we show that selumetinib treatment regulates the expression of these genes in tumor tissues of patients with metastatic GNAQ/11 mutant uveal melanoma.
Conclusions: Our findings define a subset of transcriptionally regulated genes by selumetinib in GNAQ mutant cells and provide new insights into understanding the biologic effect of MEK inhibition in this disease. Clin Cancer Res; 18(13); 3552–61. ©2012 AACR.
Abstract A112: Molecular variants of E7/ HPV58 in women with normal citology from the Colombian cohort. Preliminary results
Authors: Buitrago Oscar , Martin Carolina , Huertas Antonio , Moreno Pablo , Hernandez Gustavo , Martinez Teresa , Molano Monica 
Published: May 2012

Abstract
A112

Introduction
Human papillomavirus type 58 (HPV 58) is the second viral type more prevalent in women with normal cytology from the Colombian population. Also this type is highly prevalent in women with high grade squamous intraepithelial cervical lesions (HGSIL) and in women with invasive cervical cancer worldwide. There are few studies of E7/HPV 58 variants, however some of them have shown an association of variants presence with a higher risk of HGSIL and cervical cancer in Asian populations. In Colombia there are not studies of presence and persistence of E7/HPV58 variants.

Objective
To identify molecular variants of E7/HPV58 in cervical scrapes of women with normal cytology that belongs to the base line of the Bogotá, Colombia Cohort.

Materials and Methods
1845 cervical scrapes of women with normal cytology that belong to the base line of the Bogotá, Colombia cohort were analysed. HPV detection was done using the GP5+/GP6+ primers and 37 different HPV types were typed using a PCR-RLB assay. The E7 region of samples HPV 58 positives was amplified using the E7P1- E7P2 primers that amplify a fragment of 316 bp (561 to 877 nucleotides). E7/HPV 58 variants were detected using automated direct sequencing. The reference sequence of HPV 58 was used to compare sequences.

Results
34 samples were positive for HPV 58 (1.84%). Until this moment 13 samples have been analysed for E7/HPV 58 variants. 12 of these samples have the A694/G744/A761 variant (94.7%), one sample have the A599/A694/G744/A761 variant (5,5%), and none of the samples had the reference sequence of HPV58.

Conclusions
Two variants have been identified in the samples analysed: 1 previously identified in Asian population and 1 new variant (A599/A694/G744/A761). There are few diversity of E7/ HPV58 variants in the analysed samples. The cohort analysis will give important information about the role of these variants in the persistence of HPV 58 infection and in the development of cervical intraepithelial lesions.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A112.
Abstract A113: Association between NSAIDs and PSA, prostate volume, and prostate cancer
Authors: Fowke Jay , Motley Saundra , Byerly Susan , Cookson Michael , Chang Sam , Smith Joseph 
Published: May 2012

Abstract
A113

Purpose
NSAIDs such as aspirin are commonly used to prevent cardiovascular disease, and several prior studies suggest NSAIDs may also reduce prostate inflammation and prostate cancer risk. We investigated the association between NSAID use, PSA, and prostate volume, hypothesizing lower PSA and volume levels with NSAID use.

Methods
The Nashville Men’s Health Study utilizes a multi-centered, rapid-recruitment protocol to collect clinical, biological, behavioral, and body measurement data from 1,277 men over age 40 years and scheduled for diagnostic prostate biopsy. Approximately 95% of eligible men approached for recruitment agree to participate. NSAID use was ascertained by survey and clinical interview, and medical charts were reviewed to ascertain current PSA levels, prostate volume, and clinical diagnoses following biopsy. The distributions of PSA level and prostate volume data were natural log transformed prior to analysis. In a linear model, mean PSA and volume scores across NSAID categories were adjusted for age; race (black/white); family history (yes/no); number of prior PSA tests (1,2, 3 or more); BMI; WHR; height; or treatment for BPH (steroid reductase inhibitors, other), diabetes (Yes/No), CVD (Yes/No), hyperlipidemia (Yes/No); and the diagnosis of PIN, atypical findings suspicious for cancer, low-grade cancer, or high-grade cancer following biopsy. PSA and prostate volume scores were back-transformed and geometric mean values are reported.

Results
Approximately 46% of subjects reported taking an NSAID, primarily aspirin (37% of subjects). After adjusting for age, race, family prostate cancer history, obesity, and treatment for BPH, CVD, hyperlipidemia, and diabetes; aspirin was significantly associated with lower PSA levels (7.3 vs. 8.0 ng/ml, p=0.01). This effect of aspirin on PSA was greatest among men with a prostate volume of 60 mls or more (8.6 vs. 9.7 ng/ml, p=0.06), men diagnosed with prostate cancer (6.1 vs. 7.3 ng/ml, p&lt;0.01), or men with both cancer and prostate enlargement (7.3 vs. 12.7 ng/ml, p&lt;0.01). NSAID use was not significantly associated with prostate volume (47.6 vs. 46.0 mls, p=0.16).

Conclusions
Aspirin use was significantly associated with lower PSA levels. Controlling for BMI, WHR, and the use of medications to treat CVD, hyperlipidemia, BPH, and diabetes had little effect on the association between aspirin use and PSA levels, suggesting aspirin was not simply a proxy for these comorbid conditions or their associated treatments. These results may suggest that aspirin use decreases the ability to detect prostate cancer and may contribute to prior investigations reporting a protective association between NSAID use and prostate cancer risk. Implications for prostate cancer screening recommendations and for clinical decision-making will require further investigation.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A113.
Abstract A117: A meta-analysis of the incidence of non-AIDS cancers in HIV-infected individuals
Authors: Shiels Meredith , Cole Stephen , Poole Charles 
Published: May 2012

Abstract
A117

Objective
To compare the incidence rate of all non-AIDS cancers combined among HIV-infected individuals with the general population rate and to estimate modification of the association by gender and AIDS diagnosis.

Design
A meta-analysis was carried out using data from 11 studies of non-AIDS cancer incidence in HIV-infected individuals.

Methods
Standardized incidence rate ratios (SIR) for non-AIDS cancers in HIV-infected individuals compared to the general population and 95% confidence limits (CL) were abstracted from each study. The results were assessed for between-study heterogeneity and funnel plot asymmetry. Meta-regression was used to estimate modification of the general-population SIR by gender and AIDS.

Results
There was pronounced heterogeneity between studies, thus, an overall pooled estimate was not calculated. The SIR of non-AIDS cancers in HIV-infected individuals, adjusted for AIDS and study design was greater among men (2.3; 95% CL: 1.7, 3.1) than women (1.5; 95% CL: 0.9; 2.3; ratio of SIRs = 1.6; 95% CL: 0.7, 3.2). The SIR also appeared slightly greater among those with an AIDS diagnosis; however, when the analysis was adjusted for gender and study design, the SIRs for those with (1.88; 95% CL: 1.34, 2.66) and without AIDS (1.98; 95% CL: 1.35, 2.88) were similar (ratio of SIRs: 0.95; 95% CL: 0.46, 1.96).

Conclusions
The incidence rate of non-AIDS cancers was elevated among HIV-infected individuals. Additionally, HIV-infected men appeared to have a greater SIR for non-AIDS cancers than HIV-infected women. However, no difference was seen between the SIRs for non-AIDS cancers among those with and without AIDS.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A117.
Abstract A14: The role of Livin in oncogenesis reveals a novel mode of gene regulation
Authors: Itay Lazar , Perlman Riki , Kadouri Luna , Ben-Yehuda Dina 
Published: May 2012

Abstract
A14
Acquired resistance to apoptosis is a hallmark of all types of cancer. The Inhibitor of Apoptosis Protein (IAP) family members is able to inhibit apoptosis induced by a variety of stimuli mainly by binding to and inhibiting caspases.
We and others previously identified the IAP Livin. We further showed that Livin functions as a regulator of apoptosis that can undergo cleavage by effector caspases to produce a truncated form with paradoxical pro-apoptotic activity.
In this study we describe the role of Single Nucleotide Polymorphism (SNP) in the regulation of Livin in normal and malignant cells and demonstrate how the 528 (C/T) SNP regulates Livin protein expression. We show that Livin is expressed in a non-random monoallelic manner as only the 528T allele is expressed in normal blood and in early-stage melanoma. In advanced melanoma, by mechanism of DNA overrepresentation, both 528T and 528C mRNA alleles of Livin are expressed, resulting in expression of the Livin protein.
The variable expression of the Livin protein plays a major role in the survival of melanoma patients: We show that high Livin expression is an independent adverse prognostic marker. Importantly, we show that low-intermediate expression of Livin is associated with favorable prognosis in comparison to no Livin expression.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A14.
Abstract A19: Identification of epigenetic hits can predict breast cancer risk
Authors: Fischer John , Rossetti Stefano , Cheney Richard , Sacchi Nicoletta 
Published: May 2012

Abstract
A19
RARB2 is a master tumor suppressor that mediates the growth-inhibitory action of retinoic acid (RA). Homozygosis for epigenetically silent RARB2 alleles, which results into loss of RARB2 tumor suppressor activity, leads to RA-resistance, and apparently precedes the acquisition of morphological transformation of breast epithelial cells (Bistulfi et al., Cancer Research, 2006). RARB2 epigenetic silencing is marked by chromatin repressive changes, including DNA methylation of the RARB2 CpG island (Sirchia et al., Oncogene, 2000). In a mechanistic study, we demonstrated that methylation arises at a specific epicenter in the RARB2 CpG island, which we call the RARB2 methylation epicenter (RME) (Ren et al., MCB, 2005). Here we show that RME methylation is detectable in both benign and ductal carcinoma in situ within the same patient tissue sample. This finding implies sequential epigenetic silencing of RARB2 alleles. Timely identification of the first epigenetic hit in breast tissue of women at risk of breast cancer could prevent progression to RME methylation homozygosity, the consequent loss of RARB2-mediated tumor suppressor function, RA-resistance, and morphological epithelial cell transformation.
This work was supported by the Roswell Park Alliance Foundation Award (NS), the Breast Cancer Coalition of Rochester (NS), the Susan Komen Foundation (SR).
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A19.
Abstract A22: HIF-1 mediates up-regulation of urokinase-type activator receptor (uPAR) in cervical cancer cells
Authors: Nishi Hirotaka , Isaka Keiichi 
Published: May 2012

Abstract
A22
Hypoxia occurs during development of cervical cancer and is considered to correlate with its invasion. Hypoxia induces cancer cells to have more invasive property through the urokinase plasminogen activator receptor (uPAR) expression. We sought to determine the regulator(s) of uPAR expression during hypoxia. According to the invasion assays, cervical cancer cell lines, CaSki and CA, under hypoxic condotion (1% O2) showed more invasive property than those under normoxia. By western blot analysis, hypoxia enhanced the endogenous hypoxia inducible factor (HIF)-1alpha and uPAR protein expression. uPAR mRNA level was also up-regulated by hypoxia using realtime RT-PCR. Overexpression of HIF-1alpha which is induced by hypoxia activated the transcriptional activity of the uPAR promoter by luciferase assays. HIF-1 protein bound the putative HIF-1 response element on the uPAR promoter using the NoShift Transcription Factor Assay kit, and additional luciferase assays show that this is essential for uPAR transactivation by HIF-1. HIF-1 overexpression enhanced the endogenous uPAR expression and introduction of siRNA for HIF-1alpha diminishes uPAR expression during hypoxia. These results indicate the up-regulation of uPAR by hypoxia in cervical cancer cells is mediated through HIF-1. Using cervical cancer cell tissues, we also demonstrated that the level of uPAR mRNA in normal cervix is significantly lower than cervical cancer. Our results provide evidence that regulation of uPAR expression by HIF-1 represents a mechanism for cervical cancer invasion during hypoxia.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A22.
Abstract A5: Inhibition of tumor cell migration and angiogenesis by sulphated polysaccharides from Sargassum wightii (Greville)
Authors: Delma Caroline , Ramalingam Karthikeyan , Pandian Vijayabaskar , Baskar Albert , Savarimuthu Ignacimuthu , Thangavelu Balasubramanian , Somasundaram Somasundaram 
Published: May 2012

Abstract
A5
Seaweeds are potential renewable resources of the marine environment. They are low in fats but contain vitamins and bioactive compounds like terpenoids and sulphated polysaccharides. Sulphated polysaccharides from brown algae are found to exhibit diverse biological activities like anticoagulant, antihyperlipidemic, antiviral, antioxidant, antitumor, antimetastatic and antiangiogenic activities. In this study, the antiproliferative, antiinvasive and antiangiogenic properties of sulphated polysaccharides from brown seaweed, Sargassum wightii (Greville) against colon carcinoma cell line COLO 320DM were investigated. Crude sulphated polysaccharide was extracted from S. wightii collected from Mandapam coast, South east coast of India. The antiproliferative activity of the seaweed polysaccahrides on COLO 320DM was evaluated by MTT assay and DNA fragmentation studies. The inhibitory potential on the migration of this invasive cell line was assessed by wound healing assay. The effect of sulphated polysaccharides against angiogenesis was investigated by chorio allantoic membrane (CAM) assay in chick embryo. Sulphated polysaccharides from S. wightii exhibited moderate growth inhibitory activity against COLO 320DM at a concentration of 1mg/ml at 24 hours. DNA fragmentation studies revealed characteristic ladder formation which indicates that seaweed polysaccharides have effected the induction of apoptosis. The seaweed extract was found to inhibit the migration of the colon carcinoma cell line. The antiinvasive property increased with increasing concentrations. However, the activity was more or less similar at 24 and 48 hours. The CAM assay showed that sulphated polysaccharides from the brown seaweed exhibited promising activities against neoangiogenesis. These results clearly indicate that sulphated polysaccharides from brown algae are potential molecular leads for antimetastatic drug development.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A5.
Abstract A52: Vitamin K1 enhances sorafenib effects on HCC and induces apoptosis: A nontoxic prevention strategy
Authors: Carr Brian , Wei Gang , Wang Meifung 
Published: May 2012

Abstract
A52
HCC is usually multifocal and non surgical at presentation in the US and arises on a cirrhotic liver which tolerates chemotherapy poorly. A defect in vitamin K metabolism in HCC results in secretion of the useful tumor marker DCP, or des gamma carboxy prothrombin. We previously showed that natural vitamin K, which has no known toxicities in adult humans, is a weak HCC growth inhibitor. The FDA recently approved the multikinase inhibitor sorafenib for HCC treatment. We now show that at doses of each agent (vitamin K1 12.5 μg/ml and sorafenib 2.5 μg/ml) that do not independently alter HCC growth, the combination inhibits growth of Hep3B, PLC/PRF/5 and JM1 HCC cell lines at 24-72 hr and induces apoptosis, as supported by FACS analysis (without G1 or S phase arrest), TUNEL stain, cleavage of caspase 3 and PARP and reduced expression of survivin, Bcl-2 and Mcl-1 at 6-24 hr. At later times, a profound decrease in phospho-ERK and cyclin D1 was found (36-48 hr). The results show that the non-toxic vitamin K1 can decrease the concentrations at which sorafenib works and provides a possible approach to cancer prevention in patients with cirrhosis, who are at risk for HCC development.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A52.
Abstract A54: Epigenetic changes in colon cancer cell lines treated with the tea polyphenolic, EGCG
Authors: Brown Vondina , Lane Hannah , Wargovich Michael 
Published: May 2012

Abstract
A54
Retinoids are known for their role in regulating cell growth and proliferation and for activating tumor suppressor genes. We have previously shown that Retinoid X Receptor alpha (RXR alpha) is silenced in tumors of the colon cancer AOM-APCmin+ mouse model. Upon treatment with green tea, RXR alpha expression was restored and intestinal tumorigenesis was inhibited. We hypothesize that tea polyphenols, especially epigallocatechin gallate (EGCG), induce modification of gene expression through effects of DNA methyltransferases (DNMTs). We first determined the optimal range of EGCG concentration with which to treat the cells by performing cytotoxcity assays. We treated HT-29 and HCT116 colon cancer cells with EGCG concentrations of 0, 50, 100 or 150µM for 24 and 48 hours. The cell lines were chosen based on their methylation status. HCT116 cells are sensitive to methylation while HT-29 cells are not. Using nuclear fractions of the cell lysates, we probed for presence of the most common DNMTs using western blotting. We found that expression of DNMT1, DNMT3a and DNMT3b was inhibited in a dose dependent manner following treatment with EGCG at both 24 and 48 hour time points. We also used the DNMT inhibitor 5-aza-2dC as a positive control to recover DNMT expression in the cells treated with EGCG. We can conclude that the silencing of RXR alpha may be due in part to by repressing effects of EGCG on DNMT activity.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A54.
Abstract A68: Molecular response of pediatric chronic myeloid leukemia (CML) with imatinib mesylate therapy
Authors: Basak Jayasri , Mukhopadhyay Soma , Konar Sukanta , Mukhopadhyay Ashis 
Published: May 2012

Abstract
A68

Background
Childhood cases (&lt;18yrs of age) represent approximately 2% of all patients who develop chronic myeloid leukemia (CML). The disease in children is similar in behavior to that of adults, however the outcome of treatment with stem cell transplant is better in young individuals. The aim of our study was to see the molecular response of CML with imatinib mesylate therapy.

Materials and Methods
During the period from January 2003 to December 2007 we selected 56 cases of pediatric chronic myeloid leukemia who could not afford bone marrow transplant treatment in the pediatric Haemato-Oncolgy Department of Netaji Subhash Chandra Bose Cancer Research Institute, a tertiary cancer center from eastern India. All cases were Philadelphia chromosome and bcr/abl molecular transcript positive. The distribution of patients in the age group 1-5, 6-12 & 12-18 were 4 (7.14%), 15 (26.79%) and 37 (66.07%) respectively. The dose of imatinib mesylate (Veenat in Natco Pharma) given was 100 mg in 1-5 yrs, 200 mg in 6-12 yrs and 400 mg in older children. The maximum duration given was 5 years. bcr/abl molecular testing was done by RT-PCR method. In all patients it was done before diagnosis at 6 months, 1 year and then yearly up to 5years.

Result
With median follow up of 25 months (range 4 months - 48 months), Twenty-five children (44.64%) showed complete molecular response. Sixteen patients (28.57%) showed complete hematological, partial cytogenetic and partial molecular response. Eleven patients (19.64%) showed partial haematological response only. Four patients (7.14%) died during treatment because of blast crisis.

Conclusion
Imatinib is a good curative drug in chronic myeloid leukemia in pediatric patients.
Citation Information: Cancer Prev Res 2008;1(7 Suppl):A68.