bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3793: Overexpression of A20 and activated-Src result in TRAIL resistance in oral cancer cells
Authors: Hino Satoshi , Hamakawa Tomohiro , Nakashiro Koh-ichi , Hamakawa Hiroyuki 
Published: August 2015

Abstract
The 5-year survival rate for oral cancer patients is around 50%, and has remained unchanged for the last several decades. This poor survival rate is due to the delay in diagnosis, the high incidence of recurrence, and the difficulty of controlling metastases. It is considered that the acquisition of resistance to anoikis and apoptosis is an essential event to successfully metastasize. We have to withdraw these resistance of cancer cells to improve the survival ratio.
In this study, we have used oral squamous cell carcinoma cell lines with and without distinct metastatic ability, and revealed the relationship between their anoikis and apoptosis sensitivity and the metastatic ability. At first we examined their sensitivity to anoikis by using the low attachment culture condition. There was no apparent relation between their metastatic potential and the sensitivity to anoikis. SAS cells which have no metastatic potency showed modest sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), whereas SAS-T5 cells and SAS-L1 cells, a clone with high metastatic potential showed robust resistance. Fas ligand (Anti-Fas/CD95 monoclonal antibody) showed the similar effects for apoptosis induction as well as TRAIL, but TNF-α had no effect in these cells. We confirmed that the expression levels and the localization of TRAIL receptors were not correlated with TRAIL sensitivity. We found that the mechanisms underlying the differences in these resistance to TRAIL was an activity of Src kinase and the basal levels of A20. Phosphorylated Src (Tyr 416), the active form, was upregulated in SAS-T5 and SAS-L1 cells compared to parental SAS cells. Src inhibitor PP2 suppressed cell proliferation in response to dependence on Src signaling. Downregulation of Src or A20 with siRNA made metastatic cells dissolve the resistance to TRAIL-induced apoptosis. These results suggest that combination therapy with TRAIL and some drug inhibiting Src kinase and /or A20 expression may be a treatment strategy for oral squamous cell carcinoma.
Citation Format: Satoshi Hino, Tomohiro Hamakawa, Koh-ichi Nakashiro, Hiroyuki Hamakawa. Overexpression of A20 and activated-Src result in TRAIL resistance in oral cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3793. doi:10.1158/1538-7445.AM2015-3793
Abstract 3794: Mechanistic studies on the anti-tumor effect of jacaric acid on murine macrophage-like leukemia PU5-1.8 cells
Authors: Liu Wai Nam , Leung Kwok Nam 
Published: August 2015

Abstract
This study aims at demonstrating the in vitro and in vivo anti-tumor effect and action mechanisms of jacaric acid, a conjugated linolenic acid isomer which is present in jacaranda seed oil, on murine macrophage-like leukemia PU5-1.8 cells. Our results demonstrated the growth-inhibitory effect of jacaric acid on PU5-1.8 cells in a time- and concentration-dependent manner, as measured by MTT reduction and fluorometric cell proliferation assays, while it exerted minimal cytotoxicity on normal murine cells. Pre-treatment of PU5-1.8 cells with jacaric acid significantly decreased the leukemic cell growth in syngeneic BALB/c mice, while consumption of jacaric acid is apparently non-toxic to the mice. Flow cytometric analysis revealed the induction of G0/G1 cell cycle arrest, accompanied by a decrease in cyclin E and CDK2 proteins as demonstrated by Western blotting. Jacaric acid also triggered apoptosis in PU5-1.8 cells as reflected by induction of DNA fragmentation, phosphatidylserine externalization and mitochondrial membrane depolarization, which was quantified by ELISA, Annexin V assay and JC-1 dye staining method, respectively. Up-regulation of Bax and down-regulation of Bcl-2 and Bcl-xL proteins might account for the occurrence of apoptotic events. Collectively, our results suggest that the growth-inhibitory effect of jacaric acid on PU5-1.8 cells might be mediated through inducing cell cycle arrest and apoptosis of the leukemia cells. Therefore, jacaric acid represents a naturally-occurring potential candidate for the treatment of some forms of myeloid leukemia with minimal toxicity and fewer side effects.
Citation Format: Wai Nam Liu, Kwok Nam Leung. Mechanistic studies on the anti-tumor effect of jacaric acid on murine macrophage-like leukemia PU5-1.8 cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3794. doi:10.1158/1538-7445.AM2015-3794
Abstract 3802: Selective cytotoxicty and mechanism of Myrothamnus flabellifolius, an edible medicinal plant, on acute myeloid leukemia cells
Authors: Badiab Abeer , Dhillon Jasjit , Nabbie Fizal , Peethambaran Bela 
Published: August 2015

Abstract
Current therapies for acute myeloid leukemia involve chemotherapy and radiation, which cause damage to normal and cancerous cells. There is a dire need to discover novel drugs that target only cancer cells. Myrothamnus flabellifolius is a South African resurrection plant known for its anti-viral, anti-microbial and anti-inflammatory properties. Human myeloid leukemia (HL-60) cells and normal (TK-6) lymphocytes were treated with the methanolic extract of M. flabellifolius. Cancer cells treated with extract depicted a significant reduction in viability as compared to normal cells. The first part of this project involved fractionation of the methanolic extract using HPLC and testing each fraction on the normal and leukemic cell lines to find a fraction that selectively killed the cancer cells. A phytochemical analysis was also conducted for characterization of the anticancer compounds. In terms of mechanism, the loss in HL-60 viability was accompanied by the induction of caspase dependent apoptosis by way of caspase-7 cleavage. Heat shock proteins are molecular chaperones that aid in protein reassembly under stressful conditions and protect cells from apoptosis. TK-6 cells express heat shock protein 70 at a high level while HL-60 cells do not express the protein under normal conditions. The expression of HSP70 exhibits a positive correlation with the viability of cells post treatment with extract, indicating that this vital protein plays an important role in the survival of cells post treatment with M. flabellifolius extract.
Citation Format: Abeer Badiab, Jasjit Dhillon, Fizal Nabbie, Bela Peethambaran. Selective cytotoxicty and mechanism of Myrothamnus flabellifolius, an edible medicinal plant, on acute myeloid leukemia cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3802. doi:10.1158/1538-7445.AM2015-3802
Abstract 3803: Transcriptome analysis of MCF7 breast cancer cells with different expression profile of PAR-4 (prostate apoptosis response-4) in the presence and absence of docetaxel
Authors: de Bessa Garcia Simone A. , Pavanelli Ana C. , Melo Natalia C. , Nagai Maria A. 
Published: August 2015

Abstract
The ability of cancer cells to evade apoptosis is one of the essential alterations in cell physiology that dictate tumor growth and impact chemo- and radio-resistance. Experimental evidence indicates that protein kinase C apoptosis WT1 regulator (PAWR) gene, also known as prostate apoptosis response-4 (PAR-4), plays an important role in tumor cell survival, and may be considered a candidate for tumor cell selective therapy. This selective ability of Par-4 to directly cause apoptosis in most cancer cells is associated with its nuclear translocation and its phosphorylation state. PAR-4 acts in both intrinsic and extrinsic apoptotic pathways. In the present study, we sought to evaluate the effects of PAR-4 on the expression profile of MCF7 breast cancer cells in the presence and absence of docetaxel. MCF7 breast cancer cells were transfected with the expression vector pCMV6-PAR-4 or pCMV6-Neo. Real time PCR, western blot and immunofluorescence were used to characterize the clones over-expressing PAR-4. Using cDNA microarray analysis, we evaluated the transcriptome changes in the comparison between MCF7 cells with increased expression of PAR-4 and the control cells before and after docetaxel treatment. Several differentially expressed genes were identified as potentially involved in PAR-4-mediated chemosensitivity to docetaxel. Using the Ingenuity program, several gene networks were generated from the differentially expressed genes, including many genes direct and indirectly involved in the canonical WNT (Wingless-Type MMTV Integration 1) signaling pathway. The Wnt Signaling Pathway Human RT2 Profiler PCR Array was used to validate the differentially expressed genes involved in the Wnt pathway identified in MCF-7 cells with differences of Par-4 expression before and after exposure to docetaxel. The validation results confirm the data observed by cDNA microarray showing that the increase in PAR-4 expression modulates the expression of many genes involved in the Wnt signaling pathway in MCF7 breast cells. The results generated could be of particular interest for the understanding the action of PAR-4 in chemosensitivity, especially to increase the specificity and effectiveness of drug treatment and overcoming resistance to chemotherapy.
Supported by FAPESP and CNPq.
Citation Format: Simone A. de Bessa Garcia, Ana C. Pavanelli, Natalia C. Melo, Maria A. Nagai. Transcriptome analysis of MCF7 breast cancer cells with different expression profile of PAR-4 (prostate apoptosis response-4) in the presence and absence of docetaxel. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3803. doi:10.1158/1538-7445.AM2015-3803
Abstract 3804: Disruption of spindle microtubules by TTFields result in abnormal chromosomes segregation and subsequent caspase-dependent cell death
Authors: Voloshin Sela Tali , Schneiderman Rosa S. , Giladi Moshe , Porat Yaara , Munster Mijal , Blat Roni , Sherbo Shay , Bomzon Zeev , Urman Noa , Kirson Eilon D. , Weinberg Uri , Palti Yoram 
Published: August 2015

Abstract
Tumor Treating Fields (TTFields) are low intensity, intermediate frequency alternating electric fields. TTFields efficacy was demonstrated in vitro, in vivo and in clinical trials. The Optune device, designated to deliver TTFields to the tumor region, was approved by the FDA for the treatment of recurrent Glioblastoma multiforme (GBM). While there is a growing body of evidence demonstrating TTFields effect on mitotic cells, little is known about the mechanisms by which TTFields act to induce cancer cell death. The aim of the present study was to provide a mechanistic insight into the mode of action of TTFields.
Cancerous cell lines were treated with TTFields using the inovitro system. Disruption of spindle microtubules was demonstrated by confocal microscopy. Divergence from normal chromosome number was evaluated using SKY analysis and chromosome spreads. Induction of apoptosis was examined using flow cytometry based on Annexin V and Propidium Iodide staining. Detection of caspase activity was carried using poly caspase assay kit. Broad-spectrum caspase inhibitor was used in combination with TTFields to evaluate to what extent caspase dependent apoptosis was accountable for treatment efficacy.
Our results demonstrate that TTFields application prevents proper mitotic spindle assembly by interfering with microtubule polymerization. We also show that the outcomes of mitosis under TTFields application include abnormal chromosome segregation and caspase dependent apoptosis of daughter cells. Addition of caspase inhibitor completely abrogated apoptosis confirming that TTFields induced cell death is caspase dependent manner.
Taken together, our results demonstrate that TTFields treatment interfere with normal mitotic spindle formation thereby promoting mitotic catastrophe which result in caspase dependent apoptosis.
Citation Format: Tali Voloshin Sela, Rosa S. Schneiderman, Moshe Giladi, Yaara Porat, Mijal Munster, Roni Blat, Shay Sherbo, Zeev Bomzon, Noa Urman, Eilon D. Kirson, Uri Weinberg, Yoram Palti. Disruption of spindle microtubules by TTFields result in abnormal chromosomes segregation and subsequent caspase-dependent cell death. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3804. doi:10.1158/1538-7445.AM2015-3804
Abstract 3805: Effect of Imatinib mesylate in gastric cancer cell progression
Authors: Kim Jung Lim , Kim Bo Ram , Na Yoo Jin , Park Seong Hye , Jeong Yoon A , Oh Sang Cheul 
Published: August 2015

Abstract
Imatinib is a powerful tyrosine kinase inhibitor that specifically targets BCR-ABL, KIT, and PDGFR kinases that is used in the treatment of chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GIST), and other cancers. But, imatinib mesylate has not yet been reported about anti-cancer effect in gastric cancer. This study was undertaken to evaluate the in vitro effect of imatinib mesylate in gastric cancer cells and to define molecular mechanism underlying these effects.
This study was to determine the expression of PDGFR molecules in gastric cancer cells (AGS, MKN28, MKN45, SNU638) by semi-quantitative polimerase chain reaction (PCR). The effects of imatinib mesylate on gastric cancer cells were examined in four human gastric cancer cell lines. The results showed expression of PDGFR in all four gastric cancer cells. We measured the sensitivity of gastric cancer cell line (AGS, MKN28, MKN45, SNU638) to imatinib mesylate using MTT assay. Cell viability of cell treated with imatinib mesylate was decreased in high dose. But cell viability was not change in high dose. Next, the results showed expression of PDGFR and suppression of its phosphorylation by imatinib mesylate in all four gastric cancer cells. Cell cycle analysis for sub-G1 and G2/M fraction also detected the increased cell death in the cells treated with imatinib mesylates. Results by Western blotting indicated that imatinib mesylates promotes apoptosis of gastric cancer cells by both activating caspase-3 and -9 and inducing PARP cleavage. And expression of p-AKT level was decreased. Cell migration and invasion that imatinib treated cells is decreased in low dose. Cell viability assay revealed that the combination of imatinib mesylate and chemo-reagent synergistically inhibited cell growth compared to cells treated with any of the agent alone.
In conclusion, inhibition the PDGFR by imatinib mesylates lead to apoptosis of gastric cancer cell lines. And Imatinib suppressed motility and invasion of gastric cancer cells. The results suggest that imatinib mesylate may be useful in the treatment of gastric cancer.
Note: This abstract was not presented at the meeting.
Citation Format: Jung Lim Kim, Bo Ram Kim, Yoo Jin Na, Seong Hye Park, Yoon A Jeong, Sang Cheul Oh. Effect of Imatinib mesylate in gastric cancer cell progression. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3805. doi:10.1158/1538-7445.AM2015-3805
Abstract 3811: Arsenic trioxide induces cell cycle arrest, apoptosis through interaction of DAXX and degradation of MDM2 in acute leukemia cells
Authors: Kumar Sanjay , Tchounwou Paul B. 
Published: August 2015

Abstract
Arsenic trioxide (ATO) alone or combination with all trans retinoic acid (ATRA) has been successfully used in the treatment of all age group of acute promyelocytic leukemia (APL) patients. Recent human clinical trails result of ATO and their combination with ATRA shown complete remission in both de novo and relapsed APL patients. However, the detailed molecular mechanisms of its anti-leukemic action through cell cycle arrest and apoptosis are poorly known. We have used APL cell line and transgenic mice model to elucidate the anti-cancer properties of arsenic trioxide. We hypothesized that ATO arrests cell cycle and apoptosis through activation of p53 and interaction of death domain-associated protein (DAXX), which disrupted the MDM2-DAXX-HAUSP interactions. It also promoted MDM2 self-ubiquitination and degradation. To test the hypothesis, we used western blotting, confocal imaging and other molecular techniques to identify detailed cellular and molecular mechanisms of ATO action in APL cells and transgenic mice hepatocytes as well as bone marrow cells. We found that the expression levels of p53 and p21 increased significantly, whereas MDM2, DAXX and HAUSP decreased dose dependent manner. Our immunoprecipitation (IP) studies shown that they are well associated each other in cells and ATO disrupts associations. After 21 days treatment of ATO different doses (1.25, 2.5, 5.0 and 7.5 mg/kg body wt) in transgenic mice, we have collected liver tissue and isolated hepatocytes and bone marrow. In liver tissue, we found p53 nicely activated dose dependent ATO treated mice. On the basis of these findings, we conclude that ATO induces cell cycle arrest and apoptosis in APL cell line as well as mice hepatocytes through p53 activation, MDM2 self-ubiquitination and disruption of MDM2-DAXX-HAUSP interaction. It is novel target for treatment of APL patients through designing of new anti-leukemic drugs.
Keywords: Arsenic trioxide, HL-60 cells, cell cycle arrest, apoptosis, mitochondrial pathway, Mice hepatocytes and bone marrow.
Acknowledgements: This research was financially supported by National Institutes of Health NCRR Grant No. 5G12RR013459 and MIMHD Grant No. 8G12MD007581, through the RCMI-Center for Environmental Health at Jackson State University.
Citation Format: Sanjay Kumar, Paul B. Tchounwou. Arsenic trioxide induces cell cycle arrest, apoptosis through interaction of DAXX and degradation of MDM2 in acute leukemia cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3811. doi:10.1158/1538-7445.AM2015-3811
Abstract 3814: Metformin induces ER stress-dependent apoptosis through miR-708-5p/NNAT pathway in prostate cancer
Authors: Yang Jian , Wei Juncheng , Wu Yushi , Wang Zhilin , Guo Yuqi , Li Xin 
Published: August 2015

Abstract
Previous studies showed that metformin is associated with lower risk of tumorigenesis for several cancer types including prostate cancer. However, the molecular basis of anti-tumor effect induced by this biguanide agent is still unclear. In this study, we identified miR-708-5p as a novel downstream effector of metformin in prostate cancer. By increasing the expression of miR-708-5p, metformin suppresses the expression of endoplasmic reticulum (ER) membrane protein neuronatin (NNAT) and subsequently induces apoptosis of prostate cancer cells through ER stress pathway. Notably, down-regulated NNAT is associated with down-regulated intracellular calcium level and induces malformation of endoplasmic reticulum-ribosome structure which is revealed by electronic microscopy. Furthermore, western blot shows that the unfolded-protein response (UPR) proteins including CHOP, p-eIF2α, Calreticulin, GRP78 and ATP2A1, all of which are also considered as the ER stress markers, were up-regulated by metformin and miR-708-5p. Importantly, an increased apoptosis of prostate cancer cells is also observed when miR-708-5p mimic or NNAT siRNA was introduced. In summary, our findings clearly reveals that metformin stimulates miR-708-5p to target on NNAT mediated response to ER stress and apoptosis. This novel regulatory mechanism of metformin in prostate cancer cells not only advances our knowledge on the molecular mechanism of metformin in cancer progression, but also provide a promising therapeutic target for prostate cancer treatment.
Citation Format: Jian Yang, Juncheng Wei, Yushi Wu, Zhilin Wang, Yuqi Guo, Xin Li. Metformin induces ER stress-dependent apoptosis through miR-708-5p/NNAT pathway in prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3814. doi:10.1158/1538-7445.AM2015-3814
Abstract 3820: Ultrasensitive DNA methylation detection using sputum and plasma for early detection of NSCLC
Authors: Chen Chen , Hulbert Alicia , Stark Alejandro , Rodgers Kristen , Lee Beverly , Brock Malcolm , Herman James 
Published: August 2015

Abstract
Purpose:
The National Lung Cancer Screening Trial provides hope that early detection can result in a reduction of mortality from lung cancer. This study was to determine if molecular alterations of sputum and plasma in patients with CT detected pulmonary nodules could predict patients with malignancy from those without.
Materials and Methods: We conducted a prospective case-control study obtaining cases and controls from the Lung Cancer Spore Trial at Johns Hopkins Hospital. Plasma, sputum and pre-operative CT scans were obtained from all patients. We processed the plasma, sputum and tumor by using promoter Methylation on beads followed by quantitative methylation specific real-time PCR to investigate promoter methylation status of six cancer-related genes, CDO1, TAC1, HOXA7, HOXA9, SOX17 and ZFP42.
Results:
223 patients were analyzed, including 162 patients with NSCLC and 61 patients with benign lesions. The sensitivity and specificity values for lung cancer detection in plasma, sputum or in both are shown. Plasma methylation seems to be more specific than sputum methylation. Both concomitant methylation in both plasma and sputum yielded the highest specificity for all gene combinations. Promoter methylation of CDO1, TAC1, HOXA9 and SOX17 has a high specificity but low sensitivity to detect lung cancer.
Sensitivity and specificity for lung cancer detection using methylation changes in plasma and sputumPlasmaPlasmaSputumSputumPlasma & SputumPlasma & SputumGeneSpecificitySensitivitySpecificitySensitivitySpecificitySensitivityCDO180%45%67%63%93%26%TAC167%52%40%65%80%31%HOXA7100%11%80%27%100%6%HOXA960%66%7%90%67%60%SOX1767%56%73%52%93%27%ZFP4247%69%33%74%60%52%4 or more genes67%50%67%63%97%26%CDO1, TAC1, HOXA9, SOX1787%39%80%40%93%15%
Conclusion: Our gene panel of promoter methylation has a high enough specificity to be clinical useful but its sensitivity is low. The integration of this panel with other biomarkers would be needed to create a platform of high enough specificity and sensitivity to be clinically applicable.
Citation Format: Chen Chen, Alicia Hulbert, Alejandro Stark, Kristen Rodgers, Beverly Lee, Malcolm Brock, James Herman. Ultrasensitive DNA methylation detection using sputum and plasma for early detection of NSCLC. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3820. doi:10.1158/1538-7445.AM2015-3820