bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 5466: Butyrate effect on expression of quinone oxidoreductase (NQO1) and cytochrome P450 CYP1A1 enzymes
Authors: Tesfamichael Aron B. 
Published: August 2012

Abstract
Butyrate is a small chain fatic acid formed by bacterial fermentation of plant foods in guts. It has been shown to induce Quinone Oxidoreductase (NQO1) enzyme in tumor cell lines, which may contribute to the detoxification of dietary carcinogens with out any effect to the expression of carcinogen activation enzymes, such as cytochrome P450 CPY1A1 and epoxide hydrolase. The risk from chemical carcinogens and environmental toxins is dependent on the metabolic balance between bioactivation and detoxification enzymes. Cancer chemoprevention therefore may be achieved through alterations in the expression of these enzymes. There is substantial evidence that chemoprevention comprises multiple intervention methods to impede, arrest, or reverse carcinogenesis at various stages. Transcriptional regulation of activation and detoxification enzymes competing for the carcinogen substrate is strongly affected by intracellular oxidation reduction potential change. Treatment of cells with butyrate causes a change in intracellular redox potential which results in transcriptional regulation of activation and detoxification enzymes. Indicators of redox potential may include the concentration ratio of glutathione (GSH): glutathione disulfide (GSSG), cysteine (CYH): cystine (CYSS) and other redox couples. Treatment of human liver HepG2 cells with sodium butyrate (5mM, 48-72Hr) results in an oxidation of both GSH: GSSG and CYH: CYSS to approximately the same extent up on calculation based on Nernst equation of concentrations determined by HPLC analysis. The present study shows that both the steady-state redox potential of the cysteine/cystine couple (Eh = -155 mV) and GSH/GSSG couple (Eh = -255 mV) in cells are sufficiently oxidized (&gt;40 mV) up on treatment of cells with butyrate. The GSH oxidation, in response to 5mM butyrate at 48 -72 Hr for HepG2 cells were associated with an approximately 3-4-fold increase in mRNA for NQO1 as measured by quantitative PCR and 40-85 fold increase as a luciferase measure for relative change in a of transcriptional activation of NQO1 as comparing to the control respectively. However, CYP1A1 expression was not significantly different from controls. Changes in redox potential may directly release transcriptional proteins from within the cytoplasm for traslocation to the nucleus or alter their affinity for transcription response elements. These possibilities are under investigation using nuclear extracts of HepG2 and HT29 cells treated to alter intracellular redox potential. Surface-enhanced laser desorption/ionization (SELDI) allows rapid identification and quantitation of changes in transcription proteins in response to intracellular redox potential change.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5466. doi:1538-7445.AM2012-5466
Abstract 5470: Genotoxic effect and epigenetic alterations induced by the environmental carcinogen dibenzo[a, l]pyrene in oral tissues of mice
Authors: Zhang Shang-Min , Sun Yuan-Wan , Chen Kun-Ming , Aliaga Cesar , Gowdahalli Krishnegowda , Amin Shantu , El-Bayoumy Karam 
Published: August 2012

Abstract
Oral cancer is the major form of head and neck squamous cell carcinoma, which is the fifth most common cancer worldwide. Tobacco smoking is one of the leading causes of oral cancer. Dibenzo[a, l]pyrene (DB[a, l]P) is the most potent carcinogenic polycyclic aromatic hydrocarbon found in tobacco smoke. Recently we developed a novel mouse model of oral cancer induced by DB[a, l]P; we also showed the remarkable carcinogenicity and specificity of the fjord region diol epoxide metabolite, (±)-anti-11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydrodibenzo[a, l]pyrene (DB[a, l]PDE). Using immunohistochemistry (IHC), we have shown over-expression of p53 protein in mice oral squamous cell carcinoma and dysplastic tissues induced by DB[a, l]P and DB[a, l]PDE. Current understanding of molecular pathogenesis of oral cancer in humans suggests that both genetic and epigenetic alterations are crucial and complement each other. Our hypothesis is that both genetic and epigenetic alterations induced by DB[a, l]P can contribute to the development of oral cancer. P53 protein overexpression detected by IHC may result from p53 gene mutation or exposure to genotoxic stress. To determine whether p53 over-expression is in part due to p53 mutations, Exons 5 to 8 of p53 from 5 tumor tissues were analyzed by polymerase chain reaction single-strand conformation polymorphisms (PCR-SSCP) and direct sequencing. G to T transversion was detected in Exon 5, leading to mutation of codon 155 Arg to Leu; A to T transversion was detected in Exon 7, resulting in mutation of codon 232 Lys to stop codon. To test the epigenetic effect of DB[a, l]P, methylation specific PCR and bisulfate sequencing were used to detect methylation alteration of p16 and RAR-β promoters. Promoter hypermethylation of both p16 and RAR-β were detected in tumors induced by DB[a, l]PDE; also in oral tissues of mice treated with DB[a, l]P (24nmol, 3 times per week, for 5 weeks, sacrificed at 48 h, 1, 2 and 4 weeks after last dose). These results suggested that genotoxic DNA adducts derived from DB[a, l]P can induce mutations in critical genes, such as tumor suppressor gene p53; this environmental carcinogen also can induce p16 and RAR-β promoter hypermethylation at early stage, which can contribute to the promotion and progression of oral carcinogenesis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5470. doi:1538-7445.AM2012-5470
Abstract 5486: Reliability of biomarkers of inflammation from repeated measures in healthy individuals
Authors: Navarro Sandi L. , Brasky Theodore M. , Song Xiaoling , Wang C.Y. , Kristal Alan R. , Kratz Mario , White Emily , Lampe Johanna W. 
Published: August 2012

Abstract
Biomarkers of low-grade systemic inflammation are used to study the associations of inflammation with chronic diseases, including cancers. However, little is known about the reliability (i.e., intraindividual variability) of most of these measures. Fasting (12-hour) serum samples, which were collected at the end of ≥3 week washout periods in a 4-diet crossover feeding trial, were used to measure the inflammatory markers hsCRP, IL-6, TNF-α, IL-8 and sTNFRI and II. Participants included 32 men and 31 women (5 men and 2 women were missing from analyses of IL-8, TNF-α, and sTNFR I and II), aged 20-40, who were free of factors known to influence inflammation, e.g., chronic disease, medication use, heavy alcohol use, smoking and obesity (body mass index &gt;30 kg/m2). Intraclass correlations (ICC) were estimated using random effects analysis of variance, across all 4 time points (∼5 weeks apart). For TNF-α and sTNFRI & II, the ICCs were very high (ICC= 0.92, 95% CI: 0.89 - 0.96; 0.92, 95% CI: 0.88 - 0.95; and 0.90, 95% CI: 0.85 - 0.94, respectively). The ICCs for IL-8 and hsCRP were 0.73 (95% CI: 0.63-0.83 and 0.68 (95% CI: 0.58-0.78), respectively. The ICC for IL-6 was considerably lower, (ICC = 0.48, 95% CI: 0.36-0.62). With the exception of IL-6, reliability of all inflammatory markers in our panel over 4 time points was high, suggesting that a single measure accurately captures the variability within an individual and is a good measure for use in epidemiologic studies.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5486. doi:1538-7445.AM2012-5486
Abstract 5526: Lymphangiogenesis in regional lymph nodes is an independent prognostic marker in rectal cancer patients after neoadjuvant treatment
Authors: Jakob Christiane , Aust Daniela E. , Baretton Gustavo B. , Datta Kaustubh , Muders Michael H. 
Published: August 2012

Abstract
One of the major prognostic factors in rectal cancer is lymph node metastasis. The formation of lymph node metastases is dependent on the existence of a premetastatic niche. An important factor preceding metastasis are lymph vessels which are located in the lymph node. Accordingly, the occurrence of intranodal lymphangiogenesis is thought to indicate distant metastasis and worse prognosis. To evaluate the significance of lymph node lymphangiogenesis, we studied formalin fixed, paraffin embedded adenocarcinomas and regional lymph nodes of 203 rectal cancer patients who were treated with neoadjuvant radiochemotherapy and consecutive surgery. Regional lymph node lymph vessels were detected by immunohistochemistry for podoplanin (D2-40). Our results show that the presence of lymphatic vessels in regional lymph nodes significantly affects the disease-free survival in univariate and multivariate analyses. In contrast, there was no correlation between peritumoral or intratumoral lymph vessel density and prognosis. Indeed, our study demonstrates the importance of lymphangiogenesis in regional lymph nodes after neoadjuvant radiochemotherapy and consecutive surgery as an independent prognostic marker. Staining for intranodal lymphangiogenesis and methods of intravital imaging of lymphangiogenesis and lymphatic flow may be a useful strategy to predict long-term outcome in rectal cancer patients. Furthermore, addition of VEGF-blocking agents to standardized neoadjuvant treatment schemes might be indicated in advanced rectal cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5526. doi:1538-7445.AM2012-5526
Abstract 5531: Lumican as a novel differential diagnostic maker for Bowen's disease and actinic keratosis
Authors: Takayama Ryoko , Ishiwata Toshiyuki , Ansai Shin-ichi , Yamamoto Tetsushi , Matsuda Yoko , Kawana Seiji , Naito Zenya 
Published: August 2012

Abstract
BACKGROUND: Lumican is a member of the small leucine-rich proteoglycan (SLRP) family and regulates the assembly and diameter of collagen fibrils in the extracellular matrix in human tissue. Mice homozygous for a null mutation in lumican display corneal opacification and skin laxity. Recent studies have shown that lumican is expressed in various types of malignant tumors including breast, colorectal, and pancreatic cancer, and osteosarcoma and malignant melanoma, and that it plays an important role in the growth of tumors. However, little has been studied about the expression pattern and role of lumican in non-melanoma skin cancer. In this study, we examined the expression levels of lumican in in situ lesions of squamous cell carcinoma (SCC) of the skin, actinic keraotsis and Bowen's disease, to discover whether lumican can be used as a novel differential diagnostic marker for such skin tumors, particularly for bowenoid actinic keratosis and Bowen's disease in sun-exposed areas of the body. Bowenoid actinic keratosis and Bowen's disease are often difficult to distinguish in both the clinical setting and commonly prepared pathological specimens. Furthermore, invasive SCC arising in actinic keratosis is considered low-risk clinically, while Bowen's disease with invasion is considered high-risk. Thus, it is important to distinguish between actinic keratosis and Bowen's disease, and reliable differential markers for these diseases are required.METHOD: Twenty-nine cases of actinic keratosis, including 4 of the bowenoid sub-type, and 37 cases of Bowen's disease, including 6 in sun-exposed areas of the body, were selected from among patients undergoing surgical resection at the Department of Dermatology at the Nippon Medical School from 2006 to 2010. We evaluated lumican expression and mRNA in these cases using immunohistochemistry and in situ hybridization analysis, respectively. RESULTS: Immunohistochemical analysis indicated that Lumican was expressed in 34 of 37 patients with Bowen's disease (91.8%), but was not detected in any of the cases of actinic keratosis. In situ hybridization analysis revealed that lumican mRNA was expressed in the cytoplasm of immunohistochemically lumican-positive tumor cells in Bowen's disease. CONCLUSION: These findings suggest that lumican plays an important role in the pathogenesis of Bowen's disease and will be a useful marker for the differential diagnosis between Bowen's disease and actinic keratosis, particularly for bowenoid actinic keratosis and Bowen's disease occurring in sun-exposed areas of the body.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5531. doi:1538-7445.AM2012-5531
Abstract 5541: Molecular diagnostic tests to augment cytomorphologic diagnosis of lung cancer
Authors: Yeo Jiyoun , Crawford Erin L. , Zyrek-Betts Jill , Khuder Sadik A. , Austermiller Bradley , Willey James C. 
Published: August 2012

Abstract
Morphologic analysis of cytology samples obtained by transthoracic needle aspiration (TTNA) is one of the primary methods for diagnosing bronchogenic carcinoma. However, across multiple studies the false negative rate for cytomorphological analysis ranges from 0.2-0.3, and among those diagnosed with lung cancer, the false positive rate for diagnosing the sub-class of small cell carcinoma averages 0.09. These false results lead to additional invasive diagnostic studies and delay treatment. In an effort to augment accuracy and utility of cytopathologic evaluation of TTNA lung samples, we measured the previously reported c-myc x E2F-1/p21WAF1/CIP1 (p21 hereafter) gene expression index in cDNA samples from 78 non-malignant lung tissues and 57 lung cancer tissues. Using the optimal cut-off value, this test correctly classified 72/78 non-malignant and 50/57 malignant samples for a correct classification rate of 90% (95% CI 83.6% - 94.3%), sensitivity of 88%, and specificity of 92%. A CDKN2C/FOSL1 test for distinguishing non-small cell lung cancer (NSCLC) from small cell lung cancer (SCLC) had a PPV of 100% with 63% sensitivity. In order to optimize the robustness and utility of these tests, we developed qPCR methods that enable simultaneous measurement of each target gene and reference gene transcript relative to a known number of internal standard competitive template (CT) molecules using two-color flurometric analysis on real-time platform. For each gene, the native template was quantified with a sequence-specific FAM-labeled probe and the CT was quantified with a sequence-specific Quasar670 labeled probe. Results for each gene thus far demonstrate excellent linearity (R2 &gt; 0.99, slope 1.0 +/- 0.05), relative accuracy (variance &lt; 0.2), signal-to-analyte response (1.0 +/- 0.05) and precision (CV &lt; 30%) over six orders of magnitude, and reliable detection of as few as 10 molecules. Assessing both the c-myc x E2F-1/p21 index and the CDKN2C/FOSL1 test promises to augment cytomorphologic diagnosis of bronchogenic carcinoma in TTNA samples biopsy samples.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5541. doi:1538-7445.AM2012-5541
Abstract 5548: High copy number of the MET gene predicts resistance to EGFR-TKI in non-small cell lung cancer patients.
Authors: Noro Rintaro , Seike Masahiro , Soeno Chie , Matsuda Kuniko , Sugano Teppei , Nishijima Nobuhiko , Toyokawa Masaru , Kitamura Kazuhiro , Kosaihira Seiji , Minegishi Yuji , Yoshimura Akinobu , Kubota Kaoru , Gemma Akihiko 
Published: August 2012

Abstract
Background Non-small cell lung cancer (NSCLC) patients with EGFR gene mutations have shown a dramatic responses to EGFR tyrosine kinase inhibitor (EGFR-TKI). However, it is recognized that, clinically, drug resistance eventually emerges and this limits the mean duration of response. Although mechanisms of acquired resistance to EGFR-TKI, such as T790M secondary mutation and MET amplification, have recently been described, other mechanisms of resistant to EGFR-TKI should be identified to broaden the therapeutic strategy for NSCLC in patients with EGFR gene mutations. Patients and Methods We evaluated 26 lung tumor samples from NSCLC patients who had received EGFR-TKI treatment from 2009 to 2011 at Nippon Medical School Hospital. Status of copy numbers and amplification of the MET gene were examined by fluorescence in situ hybridization (FISH) and estimated by high throughout automated image analysis. Results High copy number (&gt;4 copies/cell) was observed in 6 patients (27%) and amplification (MET/CEP7 ≥2.0) was seen in 0 of 26 NSCLC patients. MET gene copy number status was not correlated with EGFR gene mutation, gender, histology, or smoking history. In 2 of the 6 cases with high copy number, high copy numbers were found at both the pre- and post-treatment stages. Among the 6 patients with high copy number, 5 patients achieved partial response (PR) and one patient showed stable disease (SD) with EGFR-TKI therapy. However, the 6 patients with high copy number had statistically significantly shorter progression-free survival (PFS) than the 20 patients with low copy numbers. (p=0.048, log-rank test). The median PFS of patients with High copy number and low copy numbers was 9.5 months and 24.4 months, respectively. Conclusion Detection of high copy number of the MET gene by FISH may be useful for predicting response to EGFR-TKI. The correlation between MET gene copy number and response to EGFR-TKI should be further evaluated using larger sample sizes.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5548. doi:1538-7445.AM2012-5548
Abstract 5680: Bortezomib-induced quiescence of multiple myeloma cells is associated with changes in the expression of p21(CIP/KIP) and the H3K27-methyltransferase EZH2
Authors: Adomako Alfred , Aguirre-Ghiso Julio A. 
Published: August 2012

Abstract
Bortezomib-induced quiescence of multiple myeloma cells is associated with changes in the expression of p21CIP/KIP and the H3K27-methyltransferase EZH2. Most multiple myeloma (MM) patients respond positively to the proteasome inhibitor (PI) bortezomib (Velcade). However, there are high rates of relapse after variable remission periods. It is still unclear whether these periods of remission are due to residual cells that after bortezomib treatment enter dormancy or simply due to a small residual population that slowly proliferate until patients becoming symptomatic. It is therefore important to determine whether minimal residual disease (MRD) can be rendered quiescent by bortezomib. We had shown that in MM cells, bortezomib induced ER-stress and quiescence. However, the mechanism for the induction and maintenance of this quiescent state is unclear. We hypothesized that the prolonged quiescence might involve prototypical cell cycle inhibitors and that epigenetic mechanisms sustain the growth arrest. Quantification of viable cells using immunofluorescence microscopy showed a 6-fold increase in p21 protein after a 24-hour pulse treatment with bortezomib followed by washout. p21 and p27 were also persistently induced 2-fold and 1.5-fold respectively along with the downregulation of CDK6 3 days after the drug washout. This suggests that quiescence onset is triggered by cell cycle inhibitor induction that block the G1 to S transition. This correlated with the previously reported reduction in Rb phosphorylation in bortezomib-surviving MM cells. When we tested the levels of the histone H3 methyl-transferase EZH2 and H3K27me3, these were strongly downregulated in the quiescent MM cells. EZH2 depletion was previously linked to p21-mediated senescence in melanoma. Our results suggest that changes in histone methylation and cell cycle inhibitor induction may be a mechanism regulating bortezomib-induced quiescence. Further studies will validate whether these mechanisms are active in patients by analyzing clinical samples from MM patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5680. doi:1538-7445.AM2012-5680
Abstract 5697: Multistage vectored nanotherapeutics of breast cancer lung metastasis
Authors: Shen Haifa 
Published: August 2012

Abstract
Breast cancer metastasis to remote organs is the major cause of cancer death. Although significant progresses have been made on survival of patients with Stage I-III breast cancer, the situation with breast cancer metastasis is discouraging. Nanotechnology has played an important role in the fight against breast cancer in the last decade. The first nano-liposomal formulation of doxorubicin (Dox), Doxil, was FDA approved in 1994, and is currently used to treat multiple cancer types including recurrent and refractory breast cancers. More nano-formulated drugs have since been approved. These nanotherapeutics work based on the enhanced permeability and retention (EPR) effect, and still cause severe toxicity to the body, however. To overcome these defects of the first generation of nanotherapeutics, we have developed a silicon-based multistage vector (MSV) system with the aim to specifically delivery drugs to cancer tissues with the least toxicity to the normal organs. We have demonstrated highly reproducible therapeutic efficacy with this system to deliver the conventional chemotherapy drugs and siRNA oligos in nanoparticles. We have generated mouse lung metastasis models with the human breast cancer cell line MDA-MB-231 which was engineered with a luciferase gene, and used multiple doxorubicin formulations to treat the tumor mice. These included free doxorubicin (3 mg/kg weekly), Doxil (6 mg/kg biweekly), a doxorubicin prodrug (proDox, 6 mg/kg biweekly), and proDox in MSV (MSV/proDox, 6 mg/kg biweekly). Tumor growth in the lung was monitored by bioluminescence with a Xenogen IVIS200 optical in vivo imaging system. As expected, treatment with free Dox caused significant weight loss indicating drug toxicity, most likely to the heart. Tumor growth in the free Dox treatment group halted initially, but resumed two weeks later. The tumor cells in these animals might have developed resistance to Dox during the treatment. Doxil treatment also triggered weight loss initially. This correlates with reduced the cardiac side effect of the drug observed in clinic comparing to free Dox. Neither proDox nor MSV/proDox caused weight loss. Fifty percent of the untreated mice died of lung metastasis by 11 weeks. The free Dox- and proDox-treated mice extended life by 2 weeks. Half of Doxil-treated mice died by 15 weeks, when all MSV/proDox-treated mice have survived. These results indicate that we have developed a powerful system for tumor-specific delivery of therapeutic in the treatment of breast cancer metastasis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5697. doi:1538-7445.AM2012-5697