bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PR04: Prostate cancer risk and dietary folate in a multiethnic population: Higher intake increases risk in the California Collaborative Prostate Cancer Study.
Authors: Rowland Glovioell W. , John Esther M. , Ingles Sue A. 
Published: August 2014

Abstract
Background: High intake of dietary folate has been associated with both increased and decreased risk of prostate cancer in some previous epidemiologic studies which included mostly non-Hispanic white men. Timing of high folate intake may determine its impact on lesion development. In studies of colon cancer, for instance, high dietary folate appears protective in prelesion men, whereas high folate consumption in postlesion men accelerates cancer cell proliferation. We investigated the association between dietary folate intake and risk of advanced and localized prostate cancer among African American and White men from the California Collaborative Prostate Cancer Study.
Methods: We examined 737 African American cases (233 advanced stage at diagnosis; 264 localized) and controls (N=240); and 1357 White cases (905 advanced stage; 452 localized) and controls (N=855). Folate intake during the reference year (1 year prior to diagnosis for cases or study selection for controls) was assessed by modified Block Food Frequency Questionnaire and categorized by quartiles. Risk was estimated by fitting conditional logistic regression models adjusted for race/ethnicity, age, and family history of prostate cancer.
Results: Dietary folate intake was linearly related to risk of prostate cancer (p&lt;0.001). Risk increased by 16% for each increase of one quartile. Men in the upper quartile of intake (&gt;632 mg/day) were at 45% increased risk compared to men in the lowest quartile (OR=1.45, 95% CI 1.16-1.81). The associations for advanced (OR=1.41, 95% CI 1.11, 1.81) and localized (OR=1.57, 95% CI 1.17, 2.11) disease were similar. The results were similar for African Americans and Whites.
Conclusions: Recent high folate intake appears to be a risk factor. Men who consume high levels of dietary folate in the postlesion period may be at substantially greater risk for both advanced stage and localized prostate cancer in this multi-ethnic study.
This abstract is also presented as Poster B43.
Citation Format: Glovioell W. Rowland, Esther M. John, Sue A. Ingles. Prostate cancer risk and dietary folate in a multiethnic population: Higher intake increases risk in the California Collaborative Prostate Cancer Study. [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr PR04.
Abstract A01: KRAS molecular profiling in non-squamous non-small cell lung cancer (NSCLC).
Authors: Karim Nagla Abdel , Starnes Sandra , Morris John , Pathrose Peter , Perry Ashley , Fathallah Hassana 
Published: August 2014

Abstract
Recent studies suggest that patients with KRAS-mutant NSCLC fail to benefit from standard systemic therapies and do not respond to EGFR inhibitors. Therefore, there is a clear need for therapies specifically developed for these patients. Molecular profiling has the potential to identify potential targets that might provide a better treatment and novel targeted therapy for KRAS-mutated NSCLC. In this study, we purified RNA from archived tumor and normal lung tissue obtained from 20 patients with wild type (wt) and 17 patients with mutant (mt) KRAS tumors undergoing resection for stage I and stage II NSCLC, and assessed by reverse transcriptase-real time polymerase chain reaction (RT-PCR) the expression of four genes involved in DNA synthesis and repair including thymidylate synthase (TS), BRCA1, ECCR1 and RAP80, and the proto-oncogene SRC. Our results show that in mt KRAS tumors, the levels of expression of ERCC1, TS and SRC were significantly increased in comparison to paired-normal lung tissue (p ≤ 0.04). Expression of BRCA1 and RAP80 were similar in both mt KRAS tumors and paired-normal tissue. Furthermore, the expression of BRCA1, TS and SRC were significantly increased in wt KRAS tumors relative to their expression in normal lung (p ≤ 0.044). Expression of ERCC1 and RAP80 was similar in wt KRAS tumors and paired normal tissue. Interestingly, SRC expression in mt KRAS tumors was decreased in comparison to wt KRAS tumors. Our results suggest that greater ERCC1 expression in mt KRAS tumors might increase platinum resistance in this group of patients, whereas the greater expression of BRCA1 in wt KRAS tumors might be suggestive for the sensitivity to taxanes. Our data also suggests that the combination of a SRC inhibitor with a TS inhibitor such as pemetrexed might improve the outcome of patients with wt KRAS tumors. In conclusion, these results suggest that the most effective treatment strategy for KRAS-mutant NSCLC is combined targeting of oncogenic KRAS in addition to other therapeutic agents specific to the molecular profile of the tumor.
Citation Format: Nagla Abdel Karim, Sandra Starnes, John Morris, Peter Pathrose, Ashley Perry, Hassana Fathallah. KRAS molecular profiling in non-squamous non-small cell lung cancer (NSCLC). [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr A01.
Abstract A04: Recurrent oncogenic mutations in the small GTPase RIT1 activate PI3K and MEK.
Authors: Berger Alice H. , Duke Fujiko , Imielinski Marcin , Kaplan Nathan , Wala Jeremiah , Shi Geng-Xian , Andres Douglas A. , Meyerson Matthew 
Published: August 2014

Abstract
This abstract is being presented as a short talk in the scientific program. A full abstract is printed in the Proffered Abstracts section (PR02) of the Conference Proceedings.
Citation Format: Alice H. Berger, Fujiko Duke, Marcin Imielinski, Nathan Kaplan, Jeremiah Wala, Geng-Xian Shi, Douglas A. Andres, Matthew Meyerson. Recurrent oncogenic mutations in the small GTPase RIT1 activate PI3K and MEK. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr A04.
Abstract A09: Selector (HaloPlex) targeted resequencing of formalin-fixed paraffin-embedded (FFPE) specimens for mutation diagnostics in NSCLC.
Authors: Botling Johan , Moens Lotte N.J. , Falk-Sorqvist Elin , LaFleur Linnea , Sundstrom Magnus , Micke Patrick , Nilsson Mats 
Published: August 2014

Abstract
In recent years, the advent of massively parallel “next-generation” sequencing technologies (NGS) has enabled substantial advances in the study of cancer. In combination with targeted DNA enrichment methods, high sequence coverage can be obtained for many different genes simultaneously, creating unique opportunities for clinical cancer diagnostics. However, the process of formalin fixation and paraffin embedding (FFPE) of tissue samples results in DNA-fragmentation by cross-linking to other biomolecules, posing a number of technical challenges for downstream mutation analyses.
In this study, we have evaluated the HaloPlex target enrichment system for somatic mutation detection in DNA-extracts prepared from surgical non-small cell lung cancer (NSCLC) specimens with available paired tumor and normal tissue in FFPE blocks and matched fresh-frozen tumor and normal samples. In the design of the 56 gene panel, covering the most common mutations in lung colon cancer, several modifications to the standard method were introduced, including a reduced target fragment length, molecular barcoding, and “two strand capturing.
We show that FFPE material can be used for HaloPlex based target enrichment and NGS using as little as 50 ng of DNA, i.e. compatible with yields readily available from small biopsies. By specifically capturing both strands for each target fragment, we were able to reduce the number of false positive errors due to FFPE induced artifacts by a factor of 4. Furthermore, the combined approach of molecular barcoding and two strand capturing allowed us to identify two low frequency variants, demonstrating a sensitive and accurate detection of somatic mutations.
We believe that the HaloPlex method, provided some modifications are made, will be broadly applicable as a tool for somatic mutation detection. Genetic profiling of NSCLC FFPE tissues will add a new dimension to thoracic tumor pathology and will open vast opportunities for research as large, population-based cohorts of advanced stage NSCLC will be available for comprehensive molecular characterization.
Citation Format: Johan Botling, Lotte N.J. Moens, Elin Falk-Sorqvist, Linnea LaFleur, Magnus Sundstrom, Patrick Micke, Mats Nilsson. Selector (HaloPlex) targeted resequencing of formalin-fixed paraffin-embedded (FFPE) specimens for mutation diagnostics in NSCLC. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr A09.
Abstract A16: Induction of activating transcription factor 3 is associated with cisplatin responsiveness in NSCLC: A potential predictive biomarker of response.
Authors: Bar Jair , Stewart David , Glenwood Goss D. , Villeneuve Patrick J. , Dimitroulakos Jim 
Published: August 2014

Abstract
The goal of this study was to identify treatment induced biomarkers of platin activity that may predict response to this important class of chemotherapeutic agents. We employed RNAseq transcriptome analysis comparing two parental NSCLC cell lines Calu6 and H23 to their resistant sub-lines, Calu6cisR1 and H23cisR1, derived following exposure to high dose cisplatin. To this end, we identified a stress pathway consisting of GADD45α, ATF3 and DDIT3/CHOP that was induced specifically in cisplatin treated parental but not their resistant sub-lines. Furthermore, ATF3 in particular was not expressed in untreated parental or resistant clones but was robustly induced only in the parental sensitive cell lines following cisplatin treatment. Cisplatin-induced MAPKinase activation, particularly the JNK pathway was abrogated in Calu6cisR1 cells that regulates ATF3 induction in Calu6 cells. In ex-vivo NSCLC tumors, ATF3 was induced in 2/4 tumors evaluated but not in their corresponding normal adjacent lung tissue (0/4) following cisplatin treatment. Thus, the lack of significant expression in untreated NSCLC cells and normal lung tissue but a robust induction following cisplatin treatment in sensitive parental NSCLC cell lines and a cohort of ex-vivo tumor samples suggest potential utility as a predictive biomarker of platin response that requires further study.
Citation Format: Jair Bar, David Stewart, Goss D. Glenwood, Patrick J. Villeneuve, Jim Dimitroulakos. Induction of activating transcription factor 3 is associated with cisplatin responsiveness in NSCLC: A potential predictive biomarker of response. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr A16.
Abstract A17: A blood test for early detection of lung cancer using a mixed panel of tumor proteins and autoantibodies.
Authors: Doseeva Victoria , Woodcock Juliana , Freedy James , James William , Knezevic Vladimir 
Published: August 2014

Abstract
Lung cancer is the second most common non-cutaneous cancer and a leading cause of cancer-related mortalities worldwide, resulting in over 156,000 deaths per year in the United States alone (1). Tobacco use has been identified as the primary causal factor for lung cancer and is thought to account for some 90% of cases. Thus, individuals over 50 years of age with a smoking history of greater than 20 pack-years have a 1 in 7 lifetime risk of developing the disease.
20/20 GeneSystem's PAULA test (Protein Assays Utilizing Lung Cancer Analytes), a multiplex immunoassay clinical blood test that detects four tumor proteins and autoantibodies, determines the risk that lung cancer is present in asymptomatic individuals from the high risk population described above. The test has been developed and tested using over 1,500 patient samples, including patients from 6 different regional cancer centers as well as age- and smoking history-matched controls. Here we report a new retrospective study of PAULA test using a total of 380 patients from 3 different cohorts, consisting of 190 confirmed diagnoses of lung cancer and 190 age- and smoking history matched controls. The PAULA test demonstrated 74% clinical sensitivity and 80% specificity, with an AUC value of 0.85 using Receiver Operating Characteristic (ROC) analysis.
This study confirms the value of using both tumor proteins and autoantibodies in the early detection of lung cancer, and is the first demonstration of a diagnostic multiplex immunoassay using this kind of mixed panel. We believe that the clinical performance of the PAULA test makes it suitable for use as an aid to determine which high-risk patients need to be directed to appropriate non-invasive diagnostic follow-up, especially chest CT scan for patients at high-risk for lung cancer.
Citation Format: Victoria Doseeva, Juliana Woodcock, James Freedy, William James, Vladimir Knezevic. A blood test for early detection of lung cancer using a mixed panel of tumor proteins and autoantibodies. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr A17.
Abstract A30: Melatonin suppresses invasion and epithelial to mesenchymal transition in non-small cell lung cancer cells via inhibition of ZNF746 signaling.
Authors: Kim Bonglee , Lee Duckgue , Kim Sunghoon 
Published: August 2014

Abstract
Though ZNF 746 known as Parkin-interacting substrate (PARIS) was reported to repress PGC-1α and its target gene NRF-1 leading to the neurodegeneration in Parkinson's disease, its function in tumorigenesis has not been investigated until now. Thus, in the present study, the role of ZNF746 was investigated in the invasion and epithelial to mesenchymal transition (EMT) in ZNF746 overexpressed H460 non-small cell lung cancer (NSCLC) cells. Invasion assay showed that inhibition of ZNF 746 using siRNA transfection method inhibited the invasion of H460 cells using Boyden chamber. Real-time quantitative RT-PCR (RT-qPCR) revealed that the silencing of ZNF 746 attenuated the expression of matrix metalloproteinase (MMP) 1, MMP2 and MMP 9, but not MMP7 in H460 cells. Immunoblotting assay revealed that the expressions of E-cadherin of epithelial phenotype were up-regulated, while Slug was down-regulated in ZNF746 siRNA transfected H460 cells. Consistently, mRNA expression of E-cadherin was up-regulated while Vimentin or Slug, Twist, ZEB as EMT key transcriptional factors were suppressed in ZNF746 siRNA transfected H460 cells. Also, mRNA expression of transcriptional marker Nanog and Octamer-binding transcriptional factor 4 (OCT4) known to enhance malignancy and metastasis in lung adenocarcinoma was suppressed in ZNF746 siRNA transfected H460 cells. Interestingly, the endogenous expression of ZNF746 was induced in parallel with Twist at protein level during hypoxia. Moreover, we found that ZNF746 overexpressed cell lines, A549 and H460 were inhibited invasion and migration along with ZNF746 by melatonin.
Overall, our findings suggest that ZNF746 can be an important target molecule in metastasis of lung cancer and melatonin may have the potential as an inhibitor of ZNF746 in NSCLC cells
Citation Format: Bonglee Kim, Duckgue Lee, Sunghoon Kim. Melatonin suppresses invasion and epithelial to mesenchymal transition in non-small cell lung cancer cells via inhibition of ZNF746 signaling. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr A30.
Abstract B03: Identification of R-spondin fusions in NSCLC.
Authors: Karkera Jayaprakash , Martinez Gabriela , Bell Katherine , Portale Joseph , Gaffney Dana , Lorenzi Matthew V. , Platero Suso 
Published: August 2014

Abstract
Autocrine Wnt signaling has been reported in a significant fraction of NSCLC. The R-spondin (RSPO) protein family is a small family of four secreted growth factors. The four paralogs share 40–60% pairwise amino acid sequence identity and are predicted to share substantial structural homologies. RSPO proteins are involved in vertebrate development and their ligand-type activities overlap substantially with those of canonical Wnt ligands. A characteristic feature of all four RSPO members is their ability to activate β-catenin signaling and enhance WNT-mediated β-catenin activation. It has recently been described that recurrent gene fusions involving RSPO family members of RSPO2 and RSPO3 that occur in ~10% of colon tumors and are mutually exclusive with other WNT pathway genetic alterations. In this study we developed a TaqMan qRT-PCR-based approach to evaluate systematically the expression of these three (3) RSPO fusion transcripts in formalin-fixed paraffin embedded tissue (FFPET) samples. We examined 324 NSCLC samples that included 197 squamous and 127 adenocarcinoma subtypes for the presence of EIF3E(e1)-RSPO2(e1), PTPRK(e1)-RSPO3(e2), PTPRK(e7)-RSPO3(e2). EIF3E(e1)-RSPO2(e1) was identified in 1% and this fusion transcript is expected to produce a functional RSPO2 protein driven by the EIF3E promoter. The PTPRK(e1)–RSPO3(e2) transcript found in 2% and is an in-frame fusion that preserves the entire coding sequence of RSPO3 and replaces its secretion signal sequence with that of PTPRK. Interestingly, all the fusions were detected only in the squamous subtype of NSCLC. These findings suggest an important role for dysregulated Wnt-β-catenin signaling in lung cancer and identify a new driver segment in NSCLC for therapeutic intervention.
Citation Format: Jayaprakash Karkera, Gabriela Martinez, Katherine Bell, Joseph Portale, Dana Gaffney, Matthew V. Lorenzi, Suso Platero. Identification of R-spondin fusions in NSCLC. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr B03.
Abstract B06: Development of novel thiobarbituric acid derivative compounds for treatment of lung cancers.
Authors: Lee Sang Y. , Ramisetti Srinivasa , Slagle-Webb Becky , Sharma Arun K. , Connor James R. 
Published: August 2014

Abstract
Previously, we reported the identification of a cytotoxic chemotype compound CC-I (a derivative of thiobarbituric acid) that is effective against chemotherapy resistant glioblastomas (GBMs) and neuroblastoma in an in vitro cell culture and in vivo mouse tumor models. In this study, we determined the cytotoxicity of CC-I and structurally similar compounds along in lung cancers to determine whether CC-I is toxic to lung cancers and to identify additional analog compounds that could be more toxic than CC-I. We designed several CC-I analog compounds by manipulating functional substitutions at N1-, N3- and C5-positions (either furan ring or benzene ring) of CC-I. For example, the novel compounds were synthesized starting from substituted thioureas, key precursors for the synthesis of substituted thiobarbituric acids, and finally by condensing cinnamaldehyde (CMC-2 series: benzene ring compound) or trans-3-(2-furyl)-acrolein (CC-I series: furan ring compound) with appropriately substituted thiobarbituric acids in the presence of catalytic amounts of pyridine. We used MTS cell proliferation or SRB cytotoxicity assay to determine the toxic level of compounds on the human lung cancer cell lines (e.g., A549, H520, H460, H69). The data suggest that the functional group at N1-, N3- and C5 sites is important for toxicity. Among the compounds with similar structures, CC-I-v3 and CC-I-v4 are the two most cytotoxic compounds to lung cancer cells and also the cisplatin resistant lung cancer cell lines such as H1993 and H520. In some of the cell lines we investigated, CC-I-v1 and CMC-2 compounds showed greater toxicity than CC-I compound. Currently, we are studying the anti-tumor effect of these compounds in an in vivo nude mouse tumor model. In summary, this structure-activity study clearly indicates that we can develop more efficacious compounds compared to our original compounds by rational modifications of the chemotype compounds.
[This project is supported by the Elsa U. Pardee Foundation]
Citation Format: Sang Y. Lee, Srinivasa Ramisetti, Becky Slagle-Webb, Arun K. Sharma, James R. Connor. Development of novel thiobarbituric acid derivative compounds for treatment of lung cancers. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr B06.
Abstract B26: Design and synthesis of furoquinoline derivatives as potential drug candidates for the treatment of lung cancers.
Authors: Tzeng Cherng-Chyi , Tseng Chih-Hua , Chen Yeh-Long 
Published: August 2014

Abstract
Quinoline moiety is present in many classes of biologically active compounds. Recently, we have synthesized certain quinolone, 2-phenylquinoline, 2-furanylquinoline, and 4-anilinofuro[2,3-b]quinoline derivatives for biological evaluations. Among them, 1-[4-(furo[2,3-b]quinolin-4-ylamino)phenyl]ethanone (CIL-102) was the most potent with a mean GI50 value of 0.025 μM against the growth of nine types of cancer cells and therefore, was further evaluated on its effects of cell cycle distribution. Results indicated CIL-102 induces cell cycle arrest in G2/M followed by apoptosis. CIL-102 bounds to tubulin at a single site with a dissociation constant of 0.4 μM. An analysis of the modified Dixon plot suggested that CIL-102 competitively inhibited the binding of podophyllotoxin, a colchicine-binding site agent, to tubulin. However, some drawbacks such as lack of selective cytotoxicity, poor oral bioavailability, and poor water solubility exhibited by CIL-102 prompted us to search for newer derivatives. Through extensive structural optimization, the new lead compound named as CYW-1865 which possesses aminoalkoxyimino side chain, exhibited selective anticancer activity, higher oral bioavailability, and higher water solubility than that of CIL-102. Xenographic studies indicated the tumor size with CYW-1865 treated nude mice was significantly lower than control. Further evaluation in an orthotopic lung cancer model indicated that CYW-1865 can be absorbed readily through oral administration, distributed to lung tissue, and exhibited significant efficacy in inhibiting the growth of lung cancers. Strategies for design and synthesis of CYW-1865 and its further structural optimization will be presented.
Citation Format: Cherng-Chyi Tzeng, Chih-Hua Tseng, Yeh-Long Chen. Design and synthesis of furoquinoline derivatives as potential drug candidates for the treatment of lung cancers. [abstract]. In: Proceedings of the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer; 2014 Jan 6-9; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2014;20(2Suppl):Abstract nr B26.
CHK It Out! Blocking WEE Kinase Routs TP53 Mutant Cancer
Authors: Bauman Julie E. , Chung Christine H. 
Published: August 2014

Abstract
Mutations in TP53, encoding the master tumor suppressor p53, have posed a developmental therapeutic dilemma due to inability to target loss of function. Inhibition of WEE1 or CHK1 kinase, negative regulators of the G2–M checkpoint, selectively sensitizes p53-deficient cells to exogenous DNA damage, abrogating G2 arrest and precipitating mitotic catastrophe. Clin Cancer Res; 20(16); 4173–5. ©2014 AACR.