bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2123: Tetrandrine impairs prostate cancer cell survival in part by inhibiting AR signaling pathway.
Authors: Koul Sweaty , Koul Hari K. 
Published: August 2014

Abstract
Prostate cancer (PCa) is the second leading cause of cancer deaths in men, and the majority of prostate cancer deaths are a result of emergence of castrate resistant phenotype. Our previous studies indicated that Tetrandrine (TET), a bis-benzylisoquinoline alkaloid isolated from the root of Stephania tetrandra inhibited cell cycle progression and promoted growth arrest at lower concentrations and promoted apoptosis at higher concentrations and at longer time points. AR signaling is known to play a critical role in androgen responsive prostate cancer cells. In the present studies we evaluated the effects of TET on AR signaling in androgen dependent (LNCaP cells) as well as castrate resistant (C4 and C42B cells, castrate resistant lineages of LNCaP cells) prostate cancer cells. Exposure of LNCaP cells to Tet resulted in a dose and time dependent decrease in PSA protein (cell associated as well as secreted PSA). Further analysis revealed that Tet also decreased PSA mRNA as well as PSA promoter activity, suggesting that Tet induced decrease in PSA was a result of inhibition of PSA transcription. Since PSA is known to be an AR responsive gene, these results led us to investigate the effects of Tet on AR signaling. Results from these studies revealed that Tet inhibited AR activity as measured by TARP promoter assay. Taken together these studies suggest that Tet targets AR signaling pathway effectively blocking AR target genes. In summary our results suggest that Tet by inhibiting AR signaling pathway may work as an effective therapeutic agent in prostate cancer, for which there is no cure to date.
Grant Support: Studies supported in part by VA Merit Award-01BX001258 (HK), NIH/NCI R01CA161880 (HK) and Department of Surgery, School of Medicine chair commitment (HK).
Citation Format: Sweaty Koul, Hari K. Koul. Tetrandrine impairs prostate cancer cell survival in part by inhibiting AR signaling pathway. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2123. doi:10.1158/1538-7445.AM2013-2123
Abstract 2127: Synergistic effect of carboxyl-modified magnetic nanoparticles and docetaxel on prostate cancer cells in vitro.
Authors: Watanabe Masatoshi , Sato Akiko , Okamoto Daiki , Kurioka Daisuke , Ishiguro Hitoshi , Uemura Hiroji , Kubota Yoshinobu 
Published: August 2014

Abstract
Chemotherapy is used for castration-resistant prostate cancer as one of treatment options. In this regard, docetaxel-based chemotherapy has been shown to improve the quality of life in patients with the advanced disease. However, this needs to be improved because of limitations by lack of specificity, systemic toxicity, and progression of docetaxel-resistance. Nanotechnology has served a new role in medical sciences by a variety of nanotechnology platforms, leading to therapy and diagnostics. Among these platforms, magnetic nanoparticles (Fe3O4) have potential applications in drug delivery, cancer diagnosis and therapy. We have shown that magnetic nanoparticles (MgNPs) would modify the effect of chemotherapy in cancer cells. In this study, we analyzed the combined effect of docetaxel and carboxyl-modified magnetic nanoparticles (MgNPs-COOH) on a prostate cancer cell line, DU145 and their mechanisms compared with the effect of MgNPs and docetaxel. The combination of docetaxel and MgNPs/MgNPs-COOH more effectively inhibited cancer cell growth and induced apoptosis. While only MgNPs produced reactive oxygen species (ROS) and inhibited cancer cell growth slightly, MgNPs-COOH did neither produce ROS nor inhibit cancer cell growth. In addition, these two MgNPs appear to inhibit the different cellular pathways involving apoptosis and inflammation. These results suggest that MgNPs-COOH may induce different responses compared with MgNPs, and result in favorable development of current chemotherapy for the advanced disease and leading to new tumor ablation therapies.
Citation Format: Masatoshi Watanabe, Akiko Sato, Daiki Okamoto, Daisuke Kurioka, Hitoshi Ishiguro, Hiroji Uemura, Yoshinobu Kubota. Synergistic effect of carboxyl-modified magnetic nanoparticles and docetaxel on prostate cancer cells in vitro. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2127. doi:10.1158/1538-7445.AM2013-2127
Abstract 2132: Analysis of adenylate cyclase 6 in HMBA induced K562 cell megakaryocyte differentiation.
Authors: Jiang Shin Hua , Ho Chiu Yi , Lee Tai Lin , Chang Yun Shiang , Huang Wei Tung , Tsai Meng Feng , Yuan Ang 
Published: August 2014

Abstract
Leukemia is a hematopoietic stem cell disorder and leukemia patients suffer their lost in functional blood cell and the ratio of non-function cell increased. K562 cell was isolated from the pleural effusion of the leukemia patient and was used as
a model cell line to study the relationship between the blood cell differentiation and signal transduction. In this report, three different inducers, huangqi (Astragalus membranaceus) extract, chemicals Hemin and HMBA were used to induce K562 cell differentiation and several cluster of differentiation (CD) marker were used to identify the cell linage. Two megakaryocyte markers were up-regulated in these treatments. The CD61, a late marker, was highly expressed in HMBA treated cell and CD41, an earlier marker, was identified in huangqi and HMBA treated cell. In former report, the Gi2α and Gsα was induced by the HMBA administration. Since both G proteins affect their downstream effector, adenylate cyclases (ADCYs), the
ADCYs that could be participated in the pathway were examined by RT-PCR. The
ADCY1 and ADCY6 were up-regulated in the HMBA-induced K562 cell. The ADCY6 was further studied because it coupled to calcium ion channel. The recombinant
ADCY6 transfected cells were treated with three inducers, the results showed that all inducers induceed CD61 expression especially in HMBA treated sample.
Also, the CD61 gene was 25 times higher expression as the parental cell. The results imply that the signals activated from HMBA and ADCY6 together may participate in the megakaryocyte differentiation. The study suggested that K562 cells can change the cell destination through the ADCY isoforms expression and other signal genes. These results may be used as the reference of the drug discover for leukemia treatment.
Citation Format: Shin Hua Jiang, Chiu Yi Ho, Tai Lin Lee, Yun Shiang Chang, Wei Tung Huang, Meng Feng Tsai, Ang Yuan. Analysis of adenylate cyclase 6 in HMBA induced K562 cell megakaryocyte differentiation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2132. doi:10.1158/1538-7445.AM2013-2132
Abstract 2146: Development of functional assays for p97/VCP inhibition.
Authors: Shi Yihui , Liu Xiaohe , Calaoagan Joy , Samuelsson Steven , Chou Tsui-Fen , Deshaies Raymond J. , Sambucetti Lidia C. 
Published: August 2014

Abstract
p97 (also called VCP in metazoans and CDC48 in yeast) is a highly conserved, ubiquitously expressed, and essential AAA ATPase. p97 plays a key role in endoplasmic reticulum-associated degradation of misfolded secretory and membrane proteins as well as ubiquitin-dependent turnover of a subset of cytoplasmic substrates of the ubiquitin-proteasome system. p97 also plays a critical role in specific cellular processes including Golgi membrane reassembly, membrane fusion, autophagy and DNA repair mechanisms. p97 expression is elevated in a number of cancer types including prostate cancer, non-small-cell lung carcinoma and leukemia. Given its cellular functions in protein homeostasis and the successful clinical development of proteasome inhibitors, p97 has emerged as an exciting new target for cancer therapy. We used p97 siRNA and a recently identified small molecule p97 inhibitor, N2,N4-dibenzylquinazoline- 2,4-diamine (DBeQ) as tools to develop functional assays suitable for further evaluating the activity of potential p97 inhibitors. A panel of unfolded protein response marker genes that are consistently modulated by p97 siRNA or DBeQ treatment has been identified. In addition, methods to monitor autophagic activity have been developed, including high content analysis of LC3B-GFP puncta formation. Cell viability assays were used to determine the susceptibility of various cancer cell lines to p97 inhibition. These assays will be used to evaluate the effects of potential p97 inhibitors on p97-dependent pathways and anti-proliferative activity.
Acknowledgement: Funded by NExT Chemical Biology Consortium, NCI Contract No. HHSN261200800001E.
Citation Format: Yihui Shi, Xiaohe Liu, Joy Calaoagan, Steven Samuelsson, Tsui-Fen Chou, Raymond J. Deshaies, Lidia C. Sambucetti. Development of functional assays for p97/VCP inhibition. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2146. doi:10.1158/1538-7445.AM2013-2146
Abstract 2158: Evaluation of the efficacy of dasatinib, a Src/Abl inhibitor, in a preclinical model of colorectal cancer.
Authors: Song Eun-Kee , Purkey Alicia , Quackenbush Kevin , Cross Benjamin , Bagby Stacey , Arcaroli John J. , Messersmith Wells 
Published: August 2014

Abstract
Background: Dysregulation of c-Src has been shown to modulate many different tumor cell processes. Downstream targets of Src include focal adhesion kinase (FAK), which is important for migration and invasion, and Stat-3, a kinase that enhances survival of cells and angiogenesis. Dysregulation of Src has been shown to be important at various stages of cancer development. Dasatinib is a potent Src/Abl inhibitor and has been shown to have anti-proliferative and anti-invasive activity in many preclinical models. The objective was to determine the anti-proliferative and anti-tumor effects of dasatinib in our preclinical model of colorectal cancer (CRC). Experimental Design: We used colorectal cancer cell lines and patient-derived explants to investigate the efficacy of dasatinib. We treated 45 CRC cell lines with dasatinib for 72 hours and proliferation was assayed by a sulforhodamine B (SRB) assay; an IC50 &lt; 0.1 μM was considered sensitive. We treated 10 patient-derived CRC explants with dasatinib (50 mg/kg/day, administered once-daily) for 28 days to determine in vivo efficacy; a tumor growth inhibition inhibition (TGI) ≥ 50% was considered sensitive. Results: We found that 17 out of 41 CRC cell lines reached an IC50 &lt; 1 uM with dasatinib treatment. The cell lines: HCT116, LS174T, SW1417, WiDR, KM20 and SNU977 all reached an IC50 &lt; 0.08 μM, which is considered to be an achievable dose in the clinic setting. Of 10 CRC explants, grown as xenografts, one showed sensitivity to dasatinib, with a tumor growth inhibiton of 55%. Conclusion: Dasatinib has significant anti-proliferative activity in a subset of CRC cell lines in vitro, but shows moderate efficacy in one out of ten explants treated. We plan on treating an additional 10 CRC explants (20 total) with dasatinib and developing biomarkers of sensitivity or resistance.
Citation Format: Eun-Kee Song, Alicia Purkey, Kevin Quackenbush, Benjamin Cross, Stacey Bagby, John J. Arcaroli, Wells Messersmith. Evaluation of the efficacy of dasatinib, a Src/Abl inhibitor, in a preclinical model of colorectal cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2158. doi:10.1158/1538-7445.AM2013-2158
Abstract 216: HMGB1 regulates homing capacity of human mesenchymal stromal cells into colon cancer.
Authors: Hoshino Go , Yagi Hiroshi , Hasegawa Hirotoshi , Ishii Yoshiyuki , Endo Takashi , Okabayashi Koji , Yasuda Akimasa , Nakamura Masaya , Okano Hideyuki , Matsuzaki Yumi , Kitagawa Yuko 
Published: August 2014

Abstract
Recently a growing corpus of studies has highlighted the important aspect of Mesenchymal Stem Cell (MSC) therapy: systemically administered MSCs home to sites of cancer. In this study, we focused on a homing mechanism of human MSCs into cancer. First, we examined if cultured medium from cancer cell lines could modulate migration of MSCs, the secretion level of HMGB1 from six different colon cancer cell lines affected the migration capacity of MSCs. In addition, recombinant HMGB1 could increase the migration capacity in dose dependent manner. Finally, we applied MSCs intracutaneously into mice bearing colon cancer using a cell line which secreted high level of HMGB1. The in vivo bioluminescence live-image showed that MSCs surrounded the tumors within 48hours after their injection, additionally the immunohistochemistry revealed the existence of MSCs in the tumors. These findings are critical in understanding the role of MSCs in solid cancer, further they might facilitate therapeutic application of MSCs in the treatment of cancer.
Citation Format: Go Hoshino, Hiroshi Yagi, Hirotoshi Hasegawa, Yoshiyuki Ishii, Takashi Endo, Koji Okabayashi, Akimasa Yasuda, Masaya Nakamura, Hideyuki Okano, Yumi Matsuzaki, Yuko Kitagawa. HMGB1 regulates homing capacity of human mesenchymal stromal cells into colon cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 216. doi:10.1158/1538-7445.AM2013-216
Abstract 2168: Dual targeting of the AKT/mTOR signaling pathwayinhibits mesothelioma: Targeted therapies against multiple activated receptor tyrosine kinases.
Authors: Zhou Shengmei , Liu Li , Hu Weijiang , Li Hailong , Meng Fanguo , Zhou Haimeng , Fletcher Jonathan A. , Ou Wenbin 
Published: August 2014

Abstract
Mesothelioma is a notoriously chemotherapy-resistant neoplasm, as is evident in the dismal overall survival for patients with this asbestos-associated disease. The receptor tyrosine kinases EGFR and MET are activated in subsets of mesothelioma, suggesting these kinases might represent novel therapeutic targets. However, clinical trials have not shown activity for EGFR inhibitors in mesothelioma. We had previously demonstrated activation of multiple receptor tyrosine kinases, including EGFR, MET, and AXL, in individual mesothelioma cell lines, targeting HSP90 suppressed the multiple activated RTKs in mesothelioma cell lines, resulting in apo-apoptotic and anti-proliferative effects. Thus, we hypothesized that a coordinated network of multi-RTK activation contributes collectively to activate PI3-K/AKT/mTOR and/or RAF/MAPK signalings for the tumorigenesis of mesothelioma. Herein, we demonstrate abnormal activation of the PI3-K/AKT/p70S6K and RAF/MEK/MAPK pathways in mesothelioma, as compared with normal mesothelial cells. Multiple receptor tyrosine kinases, including EGFR, MET, and AXL, in individual mesothelioma cell lines, collectively activated survival signaling intermediate AKT, but not MAPK. The anti-proliferative responses of the coordinate inhibition of these multi-kinase signaling were comparable with suppression of PI3-K/AKT/mTOR pathway. Dual targeting AKT/mTOR signaling has substantially greater effect on mesothelioma proliferation and survival, compared to inhibition of individual activated kinases and downstream signaling alone, suggesting that no one activated RTK is the predominant oncogenic control mechanism in mesothelioma and PI3-K/AKT/mTOR is a crucial survival pathway. The AKT/mTOR signaling inhibition by BEZ235 resulting in pro-apoptotic and anti-proliferative effects in mesothelioma, was associated with the blockage of MDM2-p53 interaction.
Citation Format: Shengmei Zhou, Li Liu, Weijiang Hu, Hailong Li, Fanguo Meng, Haimeng Zhou, Jonathan A. Fletcher, Wenbin Ou. Dual targeting of the AKT/mTOR signaling pathwayinhibits mesothelioma: Targeted therapies against multiple activated receptor tyrosine kinases. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2168. doi:10.1158/1538-7445.AM2013-2168
Abstract 2172: Effects of RAD001 on the protein expression pattern and function of tumor and immune cells.
Authors: Stehle Franziska , Schulz Kristin , Kalich Jana , Fahldieck Corinna , Seliger Barbara 
Published: August 2014

Abstract
The crucial role of the PI3K/Akt/mTOR pathway in the pathogenesis of cancer has led to the development of various therapeutics targeting this signaling cascade. The serine/threonine kinase mTOR is involved in the regulation of the different growth properties of both tumor and immune cells. Furthermore, mTOR forms two macromolecular complexes: (i) the rapamycin-sensitive mTORC1, which contains RAPTOR and (ii) mTORC2, which is rapamycin-insensitive and contains RICTOR. Downstream targets of these complexes like HIF-1alpha and HIF-2alpha or cyclin D1 are responsible for the activation of various intracellular processes leading to the activation of cell proliferation, induction of angiogenesis, and metastasis. The effects of mTOR inhibitors have been most studied in T cells, although recently it has been shown that renal cell carcinoma (RCC) is tightly controlled by mTOR and that mTOR pathway activation represents an adverse prognostic factor. Thus targeted inhibition of mTOR represents a promising therapeutic approach for the treatment of RCC patients. Since it is currently discussed whether the RAD001-mediated effect on T cells might negatively interfere with its anti-tumoral activity in RCC we here analyzed the effects of RAD001 on the immune cell repertoire as well as the growth properties and protein expression pattern of RCC cells. We could show a decrease in the frequency of T cells which was associated with an altered expression of chemokines/ chemokine receptors suggesting an altered T cell homing. Furthermore, RAD001 exerts a dose-dependent growth inhibitory effect in RCC cells. This was accompanied by distinct expression levels of various proteins in RCC cells. So far, 11 differentially expressed proteins were identified by MALDI-TOF analysis, which are involved in cell proliferation and gene regulation. Currently functional analysis of RAD001-regulated proteins in T lymphocytes and RCC cells are performed providing better insights into the consequences of the mTOR inhibition.
Citation Format: Franziska Stehle, Kristin Schulz, Jana Kalich, Corinna Fahldieck, Barbara Seliger. Effects of RAD001 on the protein expression pattern and function of tumor and immune cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2172. doi:10.1158/1538-7445.AM2013-2172
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 2175: Src homology region 2 domain-containing phosphatase-1 is a major target of sorafenib in hepatocellular carcinoma.
Authors: Tai Wei-Tien , Shiau Chung-Wai , Chen Pei-Jer , Cheng Ann-Lii , Chen Kuen-Feng 
Published: August 2014

Abstract
Sorafenib is the only clinical approved drug in hepatocellular carcinoma (HCC). Previously, we have investigated that Signal transducer and activator of transcription 3 (STAT3) is a kinase-independent target of sorafenib (Journal of Hepatology, 2012). Here, we report that sorafenib relieves the anto-inhibited Src homology region 2 domain-containing phosphatase-1 (SHP-1) to increase its phosphatase activity and inhibit p-STAT3-related signaling. Sorafenib increases SHP-1 activity either in HCC cell-based test or purified recombinant SHP-1 protein directly. Deletion of N-SH2 domain (dN1) or point mutation (D61A) of SHP-1 abolished the effect of sorafenib on SHP-1 and phospho-STAT3 (p-STAT3) and apoptosis in HCC, suggesting that sorafenib may affect SHP-1 by switching the transformation from auto-inhibition to the active form. The significant correlation between inhibited SHP-1 and overexpression of p-STAT3 was demonstrated in immunohistochemistry of clinical HCC samples. Novel sorafenib derivatives, SC-43 and SC-40, showed more potent effects than sorafenib on enhancing the activity of SHP-1 activity, inhibiting p-STAT3, induction apoptosis and overcoming sorafenib resistance in HCC. SC-43 showed better survival benefits than sorafenib in orthotopic HCC tumors. SHP-1 represents a major target of sorafenib in HCC. Sorafenib derivatives (SC-43 and SC-40) show better anti-HCC effects than sorafenib by targeting SHP-1. Further clinical investigations may be warranted.
Citation Format: Wei-Tien Tai, Chung-Wai Shiau, Pei-Jer Chen, Ann-Lii Cheng, Kuen-Feng Chen. Src homology region 2 domain-containing phosphatase-1 is a major target of sorafenib in hepatocellular carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2175. doi:10.1158/1538-7445.AM2013-2175
Abstract 2182: Novel ATP-competitive protein kinase D inhibitors: in vitro characterization and SAR analysis.
Authors: Tandon Manuj , Johnson James , Farber Elisa , Carder Evan , Wipf Peter , Wang Qiming J. 
Published: August 2014

Abstract
Protein Kinase Ds (PKDs) are serine/threonine kinases targeted by the second messenger diacylglycerol. The three isoforms of PKD (PKD1, PKD2, and PKD3) have emerged as key mediators in diverse cellular processes pertaining to cancer development including proliferation, apoptosis, migration/invasion and angiogenesis. Potent and selective PKD inhibitors are powerful tools in dissecting PKD-mediated cellular pathways and promising leads for developing effective anticancer agents. From targeted kinase inhibitor library screens we identified three highly potent novel ATP-competitive PKD inhibitors, IKK 16, 1-naphthyl PP1 and SD 208 with in vitro PKD inhibitory activity in low nanomolar range. All inhibitors except IKK 16 showed high selectivity for PKD relative to the related kinase family PKC and CAMK. When tested in LNCaP prostate cancer cells the compounds inhibited phorbol ester-induced PKD1 activation in a concentration dependent manner. SD 208 was found to be most specific for PKD and it did not affect the PKC mediated trans-phosphorylation of PKD1 at S744/748. Importantly, 1-naphthyl PP1 and SD 208 potently blocked prostate cancer cell proliferation and concentration-dependently induced cell death. SAR analysis of SD 208 and 1-naphthyl PP1 led to identification of key structural elements that are important for PKD inhibitory activity. In summary, we have identified and evaluated a panel of structurally divergent novel ATP-competitive PKD small molecule inhibitors with potent PKD inhibitory activities that could be further developed as potential antitumor agents in prostate cancer.
Citation Format: Manuj Tandon, James Johnson, Elisa Farber, Evan Carder, Peter Wipf, Qiming J. Wang. Novel ATP-competitive protein kinase D inhibitors: in vitro characterization and SAR analysis. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2182. doi:10.1158/1538-7445.AM2013-2182