bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1975: The mitochondrial pathway in baicalein and wogonin-induced apoptosis in human colorectal cancer cells
Authors: Wang Chong-Zhi , Somogyi Jacqueline , Yuan Chun-Su 
Published: August 2012

Abstract
Treating colorectal cancer patients commonly involves several conventional modalities, including surgery, radiation, and chemotherapy. The complexity of colorectal cancer, however, requires additional alternatives to improve the therapeutic efficacy of conventional treatment and the quality of life of cancer patients. Medicinal botanicals have recently gained attention as additions to colorectal cancer management. Numerous effective anticancer drugs have been developed from botanicals, and identifying new herbal sources for ideal chemoprevention remains essential to advance the treatment of colorectal cancer. Scutellaria baicalensis extract (SbE) has chemopreventive effects on several cancers. Baicalin, a major constituent of SbE, also may have the negative effect of decreasing the anti-tumor potential of SbE. In this study, we prepared a baicalin knockout fraction (BKF) of SbE and evaluated its antiproliferative activity and mechanism of action. The constituents of BKF, baicalin fraction (BF), and SbE were quantified by HPLC. We then used an MTS assay to determine the effects of BKF, BF, SbE, and the representative flavonoids on the proliferation of human colorectal cancer cells (HCT-116 and HT-29). Cell cycle, cyclin A expression and cell apoptosis were assayed by flow cytometry. Apoptosis-related gene expression was visualized by quantitative real-time polymerase chain reaction (PCR), and mitochondrial membrane potential was estimated after staining with JC-1. HPLC analysis showed that BKF contained baicalein and wogonin; BF contained only baicalin. SbE had little antiproliferative effect on cancer cells, even increasing cancer cell growth at certain concentrations. BF increased cancer cell growth. BKF showed potent antiproliferative effects on cancer cells. BKF arrested cells in the S and G2/M phases, increased expression of cyclin A, and significantly induced cell apoptosis. Multiple genes in the mitochondrial pathway were involved in BKF-induced apoptosis, and subsequent cellular functional analysis validated the pathway. These results suggest that knocking out baicalin from SbE produces a BKF that significantly inhibits the growth of colorectal cancer cells. The active anticancer compounds in SbE are flavonoid aglycons, baicalein and wogonin, and the mitochondrial apoptotic pathway is part of baicalein and wogonin-induced apoptosis. (This work was supported in part by the NIH/NCCAM grants AT004418 and AT005362).
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 1975. doi:1538-7445.AM2012-1975
Abstract 1985: Omega-3 polyunsaturated fatty acids induce cell cytotoxicity through apoptosis and autophgy in brain cancer in vitro and in vivo
Authors: Oh Hye-rim , Jing Kaipeng , Shin Soyeon , Kim Nayeong , Jeong Soyeon , Cho Eun-ah , Heo Jun-Young , Park Ji-Hoon , Seo Kang-Sik , Han Jeong-su , Park Jong-Il , Kweon Gi-Ryang , Park Seung-Kiel , Yoon Wan-Hee , Hwang Byung-Doo , Lim Kyu 
Published: August 2012

Abstract
One of the most common and biologically aggressive of malignant astrocytic gliomas is glioblastoma (GBM). Studies have revealed a significant role of phosphatidylinositol-3-OH kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling activation during GBM development. Omega-3 polyunsaturated fatty acids (≥3-PUFAs) have been shown to inhibit several cancer cells growth such as breast cancer cells. Here, we examined the anticancer effect of α3-PUFAs in D54 malignant glioma (D54MG) cells. We show that docosahexaenoic acid (DHA), a α3-PUFA, induced apoptosis in D54MG cells, as confirmed by the formation of cleaved PARP, TUNEL assay and cytofluorometric analysis. DHA-treated D54MG cells also showed a significant increase in autophagic activity as revealed by LC3-II elevation, autophagic vesicles formation and autophagy flux assays, suggeting that both apoptosis and autophagy contribute to the DHA-induced tumor cell death. The DHA-induced cell death in D54MG cells was accompained by the activation of AMPK and decrease in the Akt phosphorylation. DHA also decreased the activity of mTOR and the level of its downstream molecule 4EBP as analyzed by the Western blot assay. DHA-induced apoptosis and autophagy were partially blocked by transient overexpression of Akt, supporting the inhibition of Akt being beneficial to the death of GBM cells. In in vivo studies, the growth of implanted murine GBM cells in Fat-1 transgenic mice, that can produce high levels of α3-PUFA, was significantly inhibited, and the apoptotic index was higher compared with wild type mice. Together, these results suggest that α3-FUFAs induce cell cytotoxicity through apoptosis and autophgy in brain cancer. [This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology(2011-0006232).]
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 1985. doi:1538-7445.AM2012-1985
Abstract 1988: Increased expression of eukaryotic protein synthesis initiation factor eIF4G by the daidzein metabolite equol may contribute to breast cancer malignancy
Authors: de la Parra Columba , Otero-Franqui Elisa , Dharmawardhane Suranganie 
Published: August 2012

Abstract
The role of dietary soy in cancer has been the subject of intense investigation and is thought to be cancer preventive. However, the beneficial effects of soy on established breast cancer is controversial. We recently demonstrated that dietary daidzein and combined soy isoflavones (genistein, daidzein, and glycitein) promoted breast cancer progression in a nude mouse model by increasing both primary mammary tumor growth and metastasis. Dietary daidzein significantly upregulated cancer promoting molecules including eukaryotic protein synthesis initiation factors (eIF) eIF4G and eIF4E. Herein, using tumors from mice treated orally with daidzein, we show that increased eIF expression is associated with expression of mRNAs with long structured 5′ untranslated regions and internal ribosomal entry sites (IRES) that are sensitive to eIF4E and eIF4G levels. We then tested the hypothesis that daidzein upregulates protein synthesis initiation in breast cancer, but found that daidzein treatment did not affect the levels of eIFs in the same MDA-MB-435 cell line in vitro. Therefore, we tested the effect of equol that is metabolized from daidzein by the gut bacteria in mice and humans. Results show that equol specifically upregulated eIF4G, but not eIF4E, in MDA-MB-435 and MDA-MB-231 human breast cancer cells. Equol treatment also increased gene and protein expression of c-MYC and protein expression of other cell survival and proliferation promoting molecules with IRES sites. The elevated eIF4G in response to equol was not associated with eIF4E in a cap binding co-capture assay. Therefore, upregulation of eIF4G by equol may regulate cap-independent protein synthesis initiation resulting in cancer cell survival, proliferation, and thus, tumor progression. This research was supported by grant numbers US Army/BCRP W81XWH-11-1-0199 to CD, to NIH/NIGMS SC3GM084824 to SD
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 1988. doi:1538-7445.AM2012-1988
Abstract 2000: Curcumin prevents human prostate cancer cell invasion by inhibiting of matriptase activity
Authors: Cheng Tai-Shan , Chen Wen-Chi , Lin Ya-Yun , Liao Chia-I , Ko Chun-Jung , Lee Ming-Shyue 
Published: August 2012

Abstract
Curcumin has been shown with potent chemopreventive and antitumor effects on prostate cancer. However, the molecular mechanism how curcumin suppresses prostate cancer cell migration and invasion is not well understood. In this study we showed that curcumin could significantly suppress prostate cancer PC3 cell migration and invasion. Moreover, our data also showed that curcumin was able to suppress EGF- or heregulin-stimulated PC-3 cell invasion, as well as androgen-induced LNCaP cell invasion. Curcumin treatment resulted in not only significant reductions on MMP-9 and MMP-2 activities, but also on activated level of matriptase which is a membrane-bound serine protease and has been proposed to play important roles in tumor invasion and malignancy. Matriptase is synthesized as a full length zymogen, which is rapidly stepped into the maturation process, mature form through a cleavage within the SEA domain to from a latent matriptase. Our data further showed that curcumin can inhibit the latent matriptase formation in the maturation process to affect matriptase activity. Furthermore, the reduction of activated matriptase by curcumin was also partly due to curcumin promoting the shedding of activated matriptase into extracellular environment, but not due to curcumin effect on matriptase gene expression. In addition, we established the stable pools of CWR22Rv1 cells with matriptase overexpression and found that expression of matriptase in CWR22Rv1 cells enhanced their invasive ability. With curcumin treatment, the invasive ability induced by matriptase overexpression was significantly suppressed. In summary, the data indicated that curcumin exhibits a suppressive effect on prostate cancer cell invasion, at least in part by down-regulating matriptase activity.
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 2000. doi:1538-7445.AM2012-2000
Abstract 2004: Ribonucleotide reductase subunit M2 regulates Bcl-2 in human cancer: A potential target for cancer therapy
Authors: Rahman Mohammad Aminur , Amin A.R.M. R. , Koenig Lydia , Nannapaneni Sreenivas , Chen Zhuo G. , Shin Dong M. 
Published: August 2012

Abstract
Ribonucleotide reductase subunit M2 (RRM2) is an essential regulator of DNA synthesis and replication that plays an active role in tumor progression. B-cell lymphoma-2 (Bcl-2) is an anti-apoptotic protein known to promote cell survival. Elevated levels of Bcl-2 have been observed in many cancer types that predict clinical drug resistance. Both RRM2 and Bcl-2 were identified as prognostic factors and indicators of poor patient outcome in several cancers. Therefore, we hypothesized that RRM2 and Bcl-2 proteins might have cooperative functions in cancer progression. We examined correlations of RRM2 and Bcl-2 protein in tissue samples of head and neck squamous cell carcinoma (HNSCC) and non small cell lung cancer (NSCLC) patients by using quantum dots (QDs)-immunofluorescence (IHF) which allows quantification of biomarkers simultaneously in the same tissue slide. A total of 19 cases in each of HNSCC and NSCLC were analyzed. Spearman's correlation coefficient was estimated to measure the relationship between these two proteins. Our data demonstrate highly significant positive correlation between RRM2 and Bcl-2 in both types of cancer (HNSCC: R=0.98, p-value &lt;0.0001; NSCLC: R=0.85, p-value &lt;0.0001). We further investigated the action mechanism of RRM2 and Bcl-2 in cancer progression and explored the role of RRM2 by utilizing siRNA-mediated gene silencing. siRNA knockdown of RRM2 strongly inhibited cell growth and led to apoptosis. Our results demonstrated that overexpression of Bcl-2 protected cells from apoptosis triggered by RRM2 knockdown, indicating that Bcl-2 is a key determinant in controlling intrinsic apoptosis. We further analyzed whether Bcl-2 was regulated by RRM2 at the transcriptional level or at the protein level by post-translational modification. RRM2 most likely regulates Bcl-2 not only at a transcriptional level but also at the post-translational level. We found that RRM2 and Bcl-2 proteins were co-localized and directly interacted. RRM2 depletion significantly increased the rate of Bcl-2 protein degradation, reducing its half-life from ∼9 hours to ∼2 hours. Our study offers a promising approach to Bcl-2 inhibition through targeting RRM2 with siRNA in HNSCC and NSCLC. A protein network-based functional mechanism is defined by which RRM2 regulates Bcl-2-mediated apoptosis. Our novel findings add to the emerging regulatory effects of RRM2 on tumor growth by modulation of Bcl-2. (This work is supported by grants from NIH U01CA151802, P50CA128613 and DOD W81XWH-07-1-0306).
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 2004. doi:1538-7445.AM2012-2004
Abstract 2216: SUMOylated CPAP contributes to NF-kB activation in cancer cells
Authors: Yang Shu-Ting , Hung Liang-Yi 
Published: August 2012

Abstract
Nuclear factor kappa-B (NF-κB) is a transcription factor which involves in hepatocellular carcinoma (HCC). The development of therapeutic drugs to specifically target NF-κB signaling pathway is imperative to achieve. Centrosomal and P4.1-associated protein (CPAP) is a novel co-activator of NF-κB. The effects of CPAP on NF-κB activation pathway were determined by over-expression and knockdown approaches. CPAP increased the expression of NF-κB target genes by enhancing the transcriptional activaty of NF-κB. Through recruiting more IkappaB kinase beta (IKKα) to the inactivated NF-κB complex, CPAP augmented the phosphorylation of inhibitor of NF-κB (IαBβ) and NF-κB. Chromatin immunoprecipitation assay further showed that CPAP is recruited to IL-8 and ICAM-1 promoter under TNF-α treatment. CPAP was covalently modified by SUMO-1 (small ubiquitin-related modifier-1) protein at the C-terminal region. SUMO-deficient CPAP mutants lost the co-activator activity on NF-κB activation pathway and failed to enter the nucleus upon TNF-α treatment. By immunohistochemistry (IHC) analysis, CPAP was detected in the nucleus of HBV-associated HCC. Activation of NF-κB was synergically augmented by CPAP overexpression in HBx-expressing Hep3B (Hep3BX) and HepG2 (HepG2X) cells lines. SUMOylation of CPAP could modulate the activity of NF-κB, and CPAP may serve as a target for therapeutic purpose in HBV-associated HCC.
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 2216. doi:1538-7445.AM2012-2216
Abstract 2472: Peritoneal mechanobiology and metastatic success in epithelial ovarian cancer
Authors: Burkhalter Rebecca J. , Liu Yueying , Marszow Michael , Sun Zhe , Meininger Gerald , Wagner Diane , Stack M. Sharon 
Published: August 2012

Abstract
Less than 30% of women diagnosed with epithelial ovarian cancer (EOC) survive for 5 years due to metastatic disease. EOC progression is accompanied by accumulation of ascites (up to 4 liters), changing intraperitoneal (i.p.) fluid pressure from subatmospheric (-5 mmHg) to &gt;20 mmHg with tense ascites. The overall consequence of altered peritoneal mechanobiology on EOC metastatic success is currently unknown. Due to altered i.p. fluid dynamics the peritoneal mesothelium, an elastic soft tissue, may be modified by exposure to tensional force (strain). Mechanical strain (stretching) on intact murine mesothelial explants causes increased tissue stiffness, as determined by atomic force microscopy, and enhances ovarian tumor cell adhesion. To approximate the compressive force environment on EOC cells in tense ascites, cells were seeded in suspension in polystyrene bags and cultured under a compressive load (Instron, 25mmHg, 8h). Increased fluid pressure enhances proliferation in multiple cell lines and increases expression of N-cadherin, a mesenchymal marker, in Dov13 cells. These data suggest that ascites-induced changes in peritoneal mechanobiology may potentiate EOC metastatic success. Support: NIH-R01CA109545, NIH R01CA086984, NIH F31 R01CA086984-12S1.
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 2472. doi:1538-7445.AM2012-2472
Abstract 2621: Relative excess risk due to interactions between GWAS-identified susceptibility loci and other breast cancer risk factors
Authors: Joshi Amit D. , Hüsing Anika , Campa Daniele , Canzian Federico , VanderWeele Tyler J. , Kraft Peter ,   Breast and Prostate Cancer Cohort Consortium.
Published: August 2012

Abstract
Background: The characterization of the joint effects of multiple susceptibility loci identified in genome wide association studies (GWAS) and known breast cancer risk factors has the potential to inform functional mechanisms of carcinogenesis, public health guidelines and disease risk prediction. Additive interactions- departures from additivity on the absolute risk scale- can have public health and etiologic implications, but are infrequently reported. Methods: We assessed additive interactions among 11,043 non Hispanic White breast cancer cases and 11,665 similar controls within the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3). Logistic regression models were used to calculate estimates and confidence intervals for risk excess due to interactions (RERI) between 34 GWAS identified breast cancer susceptibility SNPs and 10 established breast cancer risk factors (age at menarche, parity, age at first full term pregnancy, age at menopause, family history, Gail score, height, body mass index (BMI), alcohol consumption and smoking status). All analyses were adjusted for age (5 year intervals) and cohort. Results and conclusions: After correction for multiple comparisons, we identified a statistically significant RERI (estimate = 0.48, CI=0.24,0.72, uncorrected p-value = 0.0000877) between a SNP in RAD51L1 gene, rs10483813, and BMI (&lt;30 vs. &gt;=30 kg/ m2). Among non-carriers of the risk allele, high BMI was found to significantly protect against breast cancer, but no difference in risks was observed due to BMI among carriers of at least one risk allele. This intriguing result requires replication.
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 2621. doi:1538-7445.AM2012-2621
Abstract 2649: Maternal and offspring folate metabolic genes and the risk of childhood acute lymphoblastic leukemia (ALL)
Authors: Lupo Philip J. , Nousome Darryl , Kamdar Kala Y. , Okcu Mehmet F. , Bondy Melissa L. , Scheurer Michael E. 
Published: August 2012

Abstract
Introduction: Childhood ALL is the most common type of cancer in children. Although the survival rate is relatively high, there are significant clinical sequelae associated with treatment and little is known about the etiology of this condition. Family studies suggest a genetic component to ALL, and the peak incidence between 2 and 4 years of age indicates factors during pregnancy may influence risk. The folate metabolic pathway is a strong candidate for genetic epidemiologic studies due to its role in DNA synthesis and methylation. Objective: The purpose of this study was to conduct a case-parent triad analysis to assess both maternal and offspring genetic effects of the folate metabolic pathway on childhood ALL risk. Methods: We recruited pediatric ALL case-parent triads (n = 120) from Texas Children's Hospital. DNA samples were genotyped in the Human Genetics Center at The University of Texas School of Public Health using the Sequenom iPLEX MassARRAY for 80 tagSNPs in six folate metabolic pathway genes (MTHFR, MTRR, MTR, DHFR, BHMT, and TYMS). Log-linear modeling was used to examine the associations between ALL and both maternal and offspring genotypes. Results: After controlling for the false discovery rate (&lt;0.10), there were 19 significant maternal effects in the following genes: BHMT (n = 3), MTR (n = 12), and TYMS (n = 4). For instance, maternal genotypes for BHMT rs558133 (RR = 0.51, 95% CI: 0.30-0.88, p = 0.008, q = 0.08), MTR rs2282369 (RR = 0.46, 95% CI: 0.26-0.79, p = 0.003, q = 0.08), and TYMS rs699517 (RR = 1.92, 95% CI: 1.17-3.17, p = 0.006, q = 0.08) were all associated with ALL. There were no significant offspring effects after controlling for the false discovery rate. Conclusions: This is one of the few studies conducted to evaluate maternal genetic effects in the context of pediatric ALL risk. Furthermore, we employed a family-based design (i.e., case-parent triad) that is robust to confounding due to population structure and allows for the evaluation of both maternal and offspring genotypes. These results provide additional evidence that the risk of pediatric ALL is influenced by variation within folate pathway genes and indicate that studies to explore these relationships further are warranted. We plan to extend these analyses to the evaluate folate pathway haplotypes, as well as other relevant genetic pathways (e.g., DNA repair).
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 2649. doi:1538-7445.AM2012-2649