bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4282: Crosstalk between apoptosis and autophagy induced by docetaxel-magnetic nanoparticles with different surface in prostate cancer cells
Authors: Watanabe Masatoshi , Takahashi Sanai , Usugi Eri , Ishii Kenichiro , Hirokawa Yoshifumi 
Published: August 2019

Abstract
Although docetaxel-based chemotherapy prolongs life and relieves symptoms in patients with castration resistant prostate cancer (CRPC), this needs to be improved because of limitations such as systemic toxicity, and progression of docetaxel-resistance. Nanotechnology including nanoparticles has served a new role in medical sciences, leading to theranostics. Fe3O4 magnetic nanoparticles (MgNPs) have potential applications in drug delivery, cancer diagnosis and hyperthermia. We have already reported that MgNPs would modify the effect of docetaxel (DTX) in prostate cancer cells by oxidative DNA damage in prostate cancer cell lines. Combined treatment of docetaxel and MgNPs has also shown to induce apoptosis and autophagic cell death in DU145 cells. In this study, we analyzed the combined effect of DTX-carboxyl-modified MgNPs (MgNPs-COOH) on DU145 cells in a view of crosstalk between apoptosis and autophagy. The combination treatment of DTX and MgNPs-COOH more effectively inhibited cancer cell growth and induced apoptosis and autophagic cell death although MgNPs-COOH did exert no ROS production. This combination preferred autophagic cell death than apoptosis. These results suggest that MgNPs-COOH may induce different responses compared with MgNPs, and result in favorable development of current chemotherapy for CRPC.
Citation Format: Masatoshi Watanabe, Sanai Takahashi, Eri Usugi, Kenichiro Ishii, Yoshifumi Hirokawa. Crosstalk between apoptosis and autophagy induced by docetaxel-magnetic nanoparticles with different surface in prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4282.
Abstract 4283: The tumor suppressive effects of HPP1 in colorectal cancer are mediated by its EGF-like domain
Authors: Elahi Abul , Ajidahun Abidemi , Hussain Mazher S. , Hendrick Leah , Getun Irina , Becker Andreas , Yang Yan , Glazer Evan S. , Shibata David 
Published: August 2019

Abstract
Introduction: We have previously demonstrated that HPP1 is an epigenetically-silenced tumor suppressor gene that exerts its effects via an erbB4-JAK-STAT signaling pathway. Although identified as a secreted multi-moiety transmembrane protein, the specific component responsible for its growth suppressive function has not been elucidated. Notably, HPP1 contains a single Epidermal Growth Factor (EGF)-like domain that differs from EGF by the substitution of arginine (R) for histidine (H) at the critical 299 position. We sought to investigate the isolated biologic effects of HPP1’s EGF-like domain.
Methods: Synthetic wild type (WT; H299) and mutant (MUT; R299) peptides were prepared at our crystallographic core facility. The change in amino acid did not alter the predicted 3D structure of the peptide. A total of 50ng/ml of each peptide per well (6-well plate) was used to treat the HPP1 non-expressing HCT116 colon cancer cell line. Cells were starved for 24 hours with a peptide exposure time of 7 minutes. We subsequently examined alterations in relevant erbB-, JAK- and STAT-family proteins as well as associated changes in cell growth in soft agar.
Results: Treatment of HCT116 with WT peptide resulted in increased phosphorylation of erbB4, JAK1, JAK2, STAT1 and STAT2 with a concomitant downregulation of STAT3 activation as compared to untreated controls. Mutant peptide delivery did not result in any alterations in erbB4-JAK-STAT signaling components. WT peptide treatment resulted in a dramatic reduction in colony formation in soft agar as compared to mutant peptide-treated (p=0.0002) and control cells (p=0.0019). Significant increase in colony formation was observed in the mutant vs. control cells (p=0.0047).
Conclusion: The isolated effects of HPP1’s EGF-like domain mimic the observed signaling and growth suppressive alterations observed with full-length HPP1. This EGF-like domain along with its histidine residue at position 299 appear critical for HPP1 downstream signaling and its tumor suppressive effects. Further elaboration of these findings may have therapeutic implications.
Citation Format: Abul Elahi, Abidemi Ajidahun, Mazher S. Hussain, Leah Hendrick, Irina Getun, Andreas Becker, Yan Yang, Evan S. Glazer, David Shibata. The tumor suppressive effects of HPP1 in colorectal cancer are mediated by its EGF-like domain [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4283.
Abstract 4287: Peroxiredoxin 2 has a crucial role in the survival of gastric cancer cells by regulating β-catenin and TNF signaling
Authors: Kim Hee Sung , Lee Tae Hyeong , Kang Dong Hoon , Lee Peter Chang-Whan , Kim Byung Sik 
Published: August 2019

Abstract
Gastric cancer (GC) is globally the fifth most common cancer and third leading cause of cancer death. Functional activation of β-catenin is necessary for early events in gastric carcinogenesis and GC with mutation of APC gene, similar to colorectal tumorigenesis, occur during the early stages of gastric adenoma development. Mammalian 2-Cys peroxiredoxin (Prx) enzymes are overexpressed in most cancer tissues, but the effect of Prx2 expression on GC survival remains unclear. Here, we demonstrate that Prx2 deletion markedly reduces the active β-catenin levels and the expression of β-catenin target genes in GC cells. Furthermore, the TNF α-induced activation of ERK1/2 was inhibited and reciprocally, JNK phosphorylation and cleaved caspase3 was increased in Prx2-knockdown GC cells. Prx2 deletion also can suppress the viability, invasion and colony formation of GC cells. The proof-of-concept experiment using conoidinA as a Prx2 inhibitor shows it can significantly ablates the growth of 5-FU-resistant SNU620. Thus, our findings reveal that Prx2 is a key regulator of β-catenin and TNF signaling pathway in GC, and also suggest a pharmacologic strategy to effectively overcome drug-resistant GC.
Note: This abstract was not presented at the meeting.
Citation Format: Hee Sung Kim, Tae Hyeong Lee, Dong Hoon Kang, Peter Chang-Whan Lee, Byung Sik Kim. Peroxiredoxin 2 has a crucial role in the survival of gastric cancer cells by regulating β-catenin and TNF signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4287.
Abstract 4290: Simultaneous inhibition of Atypical Protein Kinase-C and mTOR impedes bladder canSimultaneous inhibition of atypical protein kinase-C and mTOR impedes bladder cancer cell progression of bladder cancer cell progression
Authors: Islam S M Anisul , Patel Rekha S. , Bommareddy Raja Reddy , Smalley Tracess P. , Acevedo-Duncan Mildred 
Published: August 2019

Abstract
Despite enormous scientific advancements in cancer treatment, there is still so much to do to combat cancer particularly bladder cancer. Drugs once proved to be effective in treating bladder cancer showed reduced efficacy, hence, cancer recurrence rate is increasing. To overcome this situation, several attempts have been considered such as the development of a new effective drug or modify therapeutic regimens by combining two or more existing drugs. In recent years, atypical protein kinase C (aPKC), a phospholipid-dependent serine/threonine kinase, is considered as a central regulator of various cancer-causing signaling pathways and controls cell cycle progression, tumorigenesis, and metastatic determinant. In addition, the biologically important mammalian target of rapamycin (mTOR) pathway is altered in many cancers including bladder and can stimulate the activation of the aPKC pathway. In this study, we examined whether the concurrent inhibition of aPKC and mTOR using a combination of a novel aPKC inhibitor (ICA-I, an inhibitor of PKC-ι, or ζ-Stat, an inhibitor of PKC-ζ) and rapamycin blocks bladder cancer progression. The cell lines tested were MC-SV-HUCT2 normal bladder and TCCSUP bladder cancer cells. Our observed data showed that the combination therapy induced a significant reduction of human bladder cancer cells’ viability, also, individual treatment of aPKC inhibitor and rapamycin brought a similar effect. Moreover, the concurrent inhibition of aPKC and mTOR retards the metastasis of bladder cancer cells. These findings indicate that the administration of aPKC inhibitor together with rapamycin would be a useful therapeutic option in treating bladder cancer.
Citation Format: S M Anisul Islam, Rekha S. Patel, Raja Reddy Bommareddy, Tracess P. Smalley, Mildred Acevedo-Duncan. Simultaneous inhibition of Atypical Protein Kinase-C and mTOR impedes bladder canSimultaneous inhibition of atypical protein kinase-C and mTOR impedes bladder cancer cell progression of bladder cancer cell progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4290.
Abstract 4297: MYC HIF-2 alpha embryonic stemness genes mediate a transcriptional network to maintain asymmetric self-renewal in oral cancer
Authors: Pal Bidisha , Tasabehji Wael , Sorra Sandhya , Talukdar Joyeeta , Das Bikul 
Published: August 2019

Abstract
Cancer Stem Cells (CSCs) explains therapeutic failure across several tumor types. Despite being evolutionarily successful, the extreme ability to self-renew is asymmetric and limited to CSCs in heterogeneous tumor population. Thus, understanding molecular mechanisms maintaining CSCs asymmetric self-renewal would be therapeutically critical.Here, we identified putative molecular transcriptional network that may regulate CSCs asymmetric self-renewal. We developed 4-NQO (4-Nitroquinoline 1-oxide) induced mouse model of oral carcinogenesis that exhibited similar phenotype as human oral cancer. ABCG2+ CSCs enriched from 4-NQO derived mouse tumors and human oral cancer (n=7) patients indicated high expression of embryonic stemness genes such as Nanog, Sox-2, and Oct-4 in addition to MYC and HIF-2a. Higher engraftment potential was observed when ABCG2+ cells were injected to NOD/SCID mice, while HIF-2a silencing markedly increased mice survival during engraftments. ChIP assay revealed preferential binding of MYC to HIF-2a promoter regions in ABCG2+ vs ABCG2- cells. Nanog and Oct4 facilitated MYC binding to HIF-2a while gene silencing of Nanog and Sox2 led to loss of MYC and HIF-2a expression, indicating the possible regulation by MYC and HIF-2a. Further, we utilized clinical data from The Cancer Genome Atlas (TCGA) and demonstrated significant correlation between HIF-2a/MYC and embryonic stemness genes on Structural Equation Modeling Analysis (SEMA) platform, thereby confirming our in vitro/in vivofindings. Thus,our results may provide evidence of a biologically robust stemness transcriptional network regulating the asymmetric self-renewal of ABCG2+ CSCs.
Note: This abstract was not presented at the meeting.
Citation Format: Bidisha Pal, Wael Tasabehji, Sandhya Sorra, Joyeeta Talukdar, Bikul Das. MYC HIF-2 alpha embryonic stemness genes mediate a transcriptional network to maintain asymmetric self-renewal in oral cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4297.
Abstract 4300: Overexpression of PARP is an independent prognostic marker for poor survival in Middle Eastern breast cancer and its inhibition can be enhanced with embelin co-treatment
Authors: Ahmed Maqbool , Siraj Abdul K. , Pratheeshkumar Poyil , Parvathareddy Sandeep , Divya Sasidharan Padmaja , Al-Dayel Fouad , Tulbah Asma , Ajarim Dahish , Al-Kuraya Khawla S. 
Published: August 2019

Abstract
Patients with aggressive breast cancer (BC) subtypes usually don’t have favorable prognosis despite the improvement in treatment modalities. These cancers still remain a major cause of morbidity and mortality in females. This has fostered a major effort to discover actionable molecular targets to treat these patients. Poly ADP ribose polymerase (PARP) is one of these molecular targets that are under comprehensive investigation for treatment of such tumors. However, its role in the pathogenesis of BC from Middle Eastern ethnicity has not yet explored. Therefore, we examined the expression of PARP protein in a large cohort of over 1000 Middle Eastern BC cases by immunohistochemistry. Correlation with clinico-pathological parameters were performed. Nuclear PARP overexpression was observed in 44.7% of all BC cases and was significantly associated with aggressive clinico-pathological markers. Interestingly nuclear PARP overexpression was an independent predictor of poor prognosis. PARP overexpression was also directly associated with XIAP overexpression, with PARP and XIAP co-expression in 15.8% (159/1008) of our cases. We showed that combined inhibition of PARP by olaparib and XIAP by embelin significantly and synergistically inhibited cell growth and induced apoptosis in BC cell lines. Finally, co-treatment of olaparib and embelin regressed BC xenograft tumor growth in nude mice. Our results revealed the role of PARP in Middle Eastern BC pathogenesis and prognosis. Furthermore, our data support the potential clinical development of combined inhibition of PARP and XIAP, which eventually could extend the utility of olaparib beyond BRCA deficient cancer.
Citation Format: Maqbool Ahmed, Abdul K. Siraj, Poyil Pratheeshkumar, Sandeep Parvathareddy, Sasidharan Padmaja Divya, Fouad Al-Dayel, Asma Tulbah, Dahish Ajarim, Khawla S. Al-Kuraya. Overexpression of PARP is an independent prognostic marker for poor survival in Middle Eastern breast cancer and its inhibition can be enhanced with embelin co-treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4300.
Abstract 4301: Hypoxia-induced Nur77 activates PI3K-p110a/Akt/mTOR via suppression of Dicer/let-7i-5p to induce epithelial-to-mesenchymal transition in colon cancer cells
Authors: To Sally K. Y. , Deng Shan , Zeng Jin-Zhang , Wong Alice Sze Tsai 
Published: August 2019

Abstract
Cancer cells reside in the hypoxic niches of tumors easily undergo epithelial-to-mesenchymal transition (EMT). We have recently shown that hypoxia-induced EMT to enhance colon cancer cell invasive growth is dependent on the orphan nuclear receptor Nur77 and is mediated by Akt signaling. However, its underlying molecular mechanisms remain elusive. Here we found that hypoxia-induced Nur77 reduced Akt phosphorylation and its downstream mediator mTOR by decreasing the mRNA stability of p110α, the catalytic subunit α of phosphatidylinositol 3-kinase. Further analyses revealed that this effect could be mediated by down-regulation of Dicer, an important microRNA (miR) processor, and decreased biogenesis of the miR, let-7i-5p. Luciferase reporter assays confirmed that let-7i-5p could directly target the 3’UTR of p110α mRNA. Knockdown of Dicer or overexpression of let-7i-5p inhibited Nur77-induced EMT phenotypes. These data uncover a novel mechanistic link connecting Nur77, Akt, and invasive properties of colon cancer in the hypoxic microenvironment.
Citation Format: Sally K. Y. To, Shan Deng, Jin-Zhang Zeng, Alice Sze Tsai Wong. Hypoxia-induced Nur77 activates PI3K-p110a/Akt/mTOR via suppression of Dicer/let-7i-5p to induce epithelial-to-mesenchymal transition in colon cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4301.
Abstract 4305: AMPK-RUNX2-mTORC2 axis involved in EMT of MDA-MB-231 breast cancer cells
Authors: Reddy Aramati Bindu , Gayatri Meher B. , Chava Suresh 
Published: August 2019

Abstract
Metformin is one of the most widely used biguanides for the treatment of type 2 diabetes, whose role as a potent anti-cancer drug has emerged in recent times. Its function as an anti-tumor agent is attributed to its ability to inhibit mTORC1, which is a key player in regulating cell proliferation. However, the use of metformin as an anti-cancer drug is hampered by several limitations. Hence, in order to elucidate the detailed mechanistic properties of metformin in cell growth and metastasis, we investigated the effect of metformin on mTORC2 activity in MDA-MB-231 cells. We report a novel mechanism by which metformin can increase the activity of mTORC2 in a Runx2-dependent fashion, which requires AMPK mediated stabilization of RUNX2. Furthermore, we found that mTORC2 and RUNX2 have a feed forward relation whereby the knockdown of rictor, a key component in activating mTORC2, resulted in loss of RUNX2 through GSK3-β-mediated ubiquitination of RUNX2. Since both mTORC2 and RUNX2 have been found to be involved in activating the EMT, metformin treatment may contribute to this activation by stabilizing AMPK-RUNX2-mTORC2 axis. These results demonstrate that metformin-induced mechanisms can influence metastasis even if they inhibit cell growth, but the genetic heterogeneity of the malignancy may govern cell fate.
Citation Format: Aramati Bindu Reddy, Meher B. Gayatri, Suresh Chava. AMPK-RUNX2-mTORC2 axis involved in EMT of MDA-MB-231 breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4305.
Abstract 4306: JunD-induced cell proliferation requires MYC signaling in prostate cancer cells
Authors: (Elliott) Bethtrice Thompson , Millena Ana Cecilia , Matyunina Lilya , Zhang Mengnan , Zou Jin , Wang Guangdi , Zhang Qiang , Bowen Nathan , Eaton Vanessa , Webb Gabrielle , Thompson Shadyra , McDonald John , Khan Shafiq 
Published: August 2019

Abstract
JunD, a member of the AP-1 transcription factor family, is involved in a variety of biological processes including cell proliferation, inflammation, differentiation, apoptosis, and carcinogenesis. We previously showed that JunD is essential for cell proliferation and demonstrated that the knock-down (KD) of JunD in PCa cells resulted in cell cycle arrest in G1-phase concomitant with a decrease in the levels of Id1, c-MYC, and Ki67, but an increased in p21 protein levels. Furthermore, the over-expression of JunD significantly increased proliferation in these cells suggesting that JunD regulates the expression of genes which are required for cell cycle progression. In this present study, employing gene expression profiling, quantitative proteomics, and validation approaches, we demonstrated that JunD KD is associated with distinct gene and protein expression patterns. Comparison integrative analysis by Ingenuity Pathway Analysis (IPA) identified 1) cell cycle control/regulation as the top canonical pathway whose members exhibited a significant decrease in their expression following JunD KD including PRDX3, PEA15, KIF2C, and CDK2, and 2) JunD target genes are involved in cell proliferation, with MYC as the key downstream regulator. Conversely, JunD over-expression induced cell proliferation and the expression of the above JunD target genes including c-MYC. When treated with JQ1, a c-MYC inhibitor, these cells exhibited a significant reduction in cell proliferation and a decrease in JunD target genes. Our data suggest that JunD-mediated cell proliferation involves MYC signaling and inhibiting its target genes may be an effective approach to blocking prostate carcinogenesis
Citation Format: Bethtrice Thompson (Elliott), Ana Cecilia Millena, Lilya Matyunina, Mengnan Zhang, Jin Zou, Guangdi Wang, Qiang Zhang, Nathan Bowen, Vanessa Eaton, Gabrielle Webb, Shadyra Thompson, John McDonald, Shafiq Khan. JunD-induced cell proliferation requires MYC signaling in prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4306.
Abstract 4307: RAGE is the key receptor for LPA in lung and mammary cancer progression and metastasis
Authors: Jangde Nitish , Ray Rashmi , Rai Vivek 
Published: August 2019

Abstract
Lung and breast cancer signaling are very complex; receptor for advanced glycation end products (RAGE) is highly expressed in various cancers and is correlated with poorer outcome in lung and other cancers. It is an immunoglobulin like membrane receptor shows binding with various ligands sharing structural likeness such as amyloid beta, advanced glycation end products (AGEs), S100B proteins, amphoterin and HMGB1 and mediates numerous inflammatory and cellular events including diseases including various cancers. LPA a RAGE ligand is a biologically active phospholipid involved in cell proliferation, migration and survival via its different G protein couple receptors (GPCRs). LPA and its signalling pathways have been implicated in different pathological conditions of lung tissue, including inflammation, fibrosis and cancer activating various signalling pathways. Here, we have identified RAGE-LPA signaling mechanisms showing AKT, STAT3 and ERK as downstream signaling pathways gets activated upon LPA treatment via RAGE receptor in both lung and breast cancer cells. RAGE knockdown with multiple independent shRNAs in lung and breast cancer cells led to decreased transwell invasion and soft agar colony formation, and proliferation upon LPA stimulation. Our RAGE silencing study in lung and breast cancer cells upon LPA treatment showed upregulation of specific oncogenes Cyclin D1, c-Myc and VEGF via RAGE receptor. RAGE association with LPA induced epithelial to mesenchymal transition (EMT) in both lung and breast cancer cells have also been observed by the RAGE attenuation studies by examining the expression of some EMT markers. The physiological significance of LPA-RAGE axis was exposed by our xenograft study by nude mice intraperitoneal injections of control and RAGE inhibited lung and mammary tumors generated by LPA doses in alternative days, results the formation of tumor foci on peritoneum wall via RAGE receptor. This study provides novel therapeutic insights as the use of RAGE blocking antibodies and antagonists or competitive inhibitors of LPA against RAGE might be useful of breast cancer treatment. This study also suggests that RAGE and LPA can be used as biomarkers for the early detection of lung and breast cancers.
Citation Format: Nitish Jangde, Rashmi Ray, Vivek Rai. RAGE is the key receptor for LPA in lung and mammary cancer progression and metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4307.