bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2119: Regulation of T-type calcium channel expression during IL-6 induced neuroendocrine differentiation of prostate cancer cells
Authors: Weaver Erika , Hearne Jennifer L. , Martin-Caraballo Miguel 
Published: May 2015

Abstract
Prostate cancer is the most common cancer among men. At early stages, the growth of prostate cancers is androgen dependent and therefore therapies designed to reduce the androgen concentration/receptor activation are effective in promoting tumor regression. At later stages, however, the growth of prostate cancers becomes androgen independent, leading to increased mortality. The switch to an androgen-refractory state is associated with neuroendocrine differentiation of prostate cancer cells. Several factors including interleukin-6 (IL-6) and increased cAMP production promote neuroendocrine differentiation of prostate cancer cells. How these factors promote neuroendocrine differentiation is not completely understood. In this work we investigated whether IL-6 evoked neuroendocrine differentiation of prostate cancer cells results in the stimulation of T-type calcium channel expression in the prostate cancer cell line LNCaP. Treatment of LNCaP cells with IL-6 for four days evokes considerable morphological and molecular changes consistent with neuroendocrine differentiation, including the presence of rounded cell bodies, the appearance of long dendritic-like processes and the expression of chromogranin-A. IL-6 evoked neuroendocrine differentiation of LNCaP cells results in a 3-fold increase in the protein expression of the T-type calcium channel subunit Cav3.2. Transcripts for the Cav3.2 but not Cav3.1 or Cav3.3 subunits can be detected in IL-6-treated LNCaP cells. Real time PCR analysis indicates no change in Cav3.2 mRNA expression between control (non-stimulated) and IL-6 stimulated LNCaP cells, suggesting that T-type calcium channel expression is regulated by a post-transcriptional mechanism. Electrophysiological recordings reveal that increased Cav3.2 protein expression following IL-6 stimulation of LNCaP cells does not result in increased expression of functional channels in the membrane. Functional expression of Cav3.2 channels is facilitated by stimulation of LNCaP cells with forskolin an agent that increases intracellular cAMP. These results indicate that changes in T-type calcium channel expression and intracellular calcium during neuroendocrine differentiation of LNCaP cells are regulated by the interplay of multiple factors. Thus, it appears that T-type calcium channels could be a target for future therapeutic strategies against prostate cancers refractory to anti-androgen therapies.
Citation Format: Erika Weaver, Jennifer L. Hearne, Miguel Martin-Caraballo. Regulation of T-type calcium channel expression during IL-6 induced neuroendocrine differentiation of prostate cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2119. doi:10.1158/1538-7445.AM2014-2119
Abstract 2121: Resveratrol regulates phospho-serine 81 androgen receptor and its stability to inhibit growth of prostate cancer cells
Authors: Peng Yu-Ting , Chen Tzu-Yin , Chen Mei-Chih , Lin Eugene , Lin Ho 
Published: May 2015

Abstract
Resveratrol, a polyphenol, has been reported as a cell growth inhibitor of various types of cancer. The molecular mechanisms of resveratrol are involved in different cellular signal transductions such as anti-inflammation and anti-oxidation. Resveratrol inhibits growth of prostate cancer cells through regulating cyclin-dependent kinases, anti-apoptotic proteins, and pro-apoptotic proteins. Notably, resveratrol may down-regulate androgen receptor (AR) and its downstream gene to inhibit prostate cancer cell growth. In previous study, serine 81 phosphorylation of AR increases its protein stability and transcriptional activity, which promotes prostate cancer cell growth. The aim of this study is to investigate whether AR serine 81 phosphorylation would be a target of resveratrol in prostate cancer cells. Our data indicate that resveratrol inhibited the growth of prostate cancer cell line, LNCaP, with the decrease of AR phospho-serine 81 levels. Moreover, AR protein stability was declined by resveratrol without affecting AR mRNA expression. Indeed, resveratrol inhibited AR transcriptional activity in results of AR reporter assay and PSA level in LNCaP cells. In summary, the results suggest that resveratrol might inhibit growth of LNCaP cells, at least, via decreasing phospho-serine 81 of AR, AR protein stability, and AR transcriptional activity.
Citation Format: Yu-Ting Peng, Tzu-Yin Chen, Mei-Chih Chen, Eugene Lin, Ho Lin. Resveratrol regulates phospho-serine 81 androgen receptor and its stability to inhibit growth of prostate cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2121. doi:10.1158/1538-7445.AM2014-2121
Abstract 2122: Androgen decreases proliferation of thyroid cancer cells
Authors: MacEwan Melanie Elizabeth , O'Connell Timmy , Zhao Hong , Iacob Codrin , Suslina Nina , Moscatello Augustine , Shin Edward , Tiwari Raj , Darzynkiewicz Zbigniew , Geliebter Jan 
Published: May 2015

Abstract
The incidence of thyroid cancer in the United States has significantly increased over the past decade, with over 60,220 cases predicted for 2013. While premenopausal women have an approximately four fold higher incidence of papillary thyroid cancer (PTC) than men, once diagnosed, PTC in men exhibits increased aggressiveness and results in poorer clinical outcomes. These paradoxical observations led us to investigate the role that androgens and/or androgen receptors play in PTC. Analysis of AR expression in 24 PTC patient tissue samples indicated a 5.97 fold reduction in AR expression compared to matched, normal tissue (P&lt;0.0001). To more fully investigate the function of androgen/AR in thyroid cells in a more controlled experimental system, the AR cDNA (pSG5-AR) was subcloned into the pcDNA3.1+ expression vector and stably transfected into 8505C anaplastic/PTC cells. Addition of DHT to the 8505C-transfected clone, 84E7, resulted in AR translocation into the nucleus and a 48% reduction in proliferation (p=0.01) at 72 hours, as well as a shift in the cell cycle toward G1 arrest during the same time period. Transcription profiling using RNA-Seq and gene ontology analysis revealed significant changes in the process of cell proliferation (p=2.47e-24) possibly due to significant changes in CDK1A/p21 (up 3.42 fold), RhoB (up 50 fold), Jun (down 1.7 fold), SCF (down 3.31 fold) and NFKBIA (up 2.36). Additionally, expression levels of other cell cycle proteins, including CDK6 and multiple MCMs were also significantly reduced when AR was activated by DHT. FKBP5, the immunophilin which negatively regulates proliferation and is thought to play various roles in the neoplastic process, was up-regulated by androgen ∼8 fold and ∼4 fold on the mRNA and protein levels, respectively. Collectively, these data provide a molecular basis for the decreased proliferation noted. Further, these data suggest that the expression of androgen/AR in thyroid cells plays a protective, anti-proliferative role in normal thyroid tissue that is lost in neoplastic transformation resulting in dysregulation of cell cycle genes normally under negative AR control. The expression levels of AR, as well as available androgens, may play a role in the etiology of PTC, the differential incidence of the disease, as well as the different clinical presentations and outcomes between women and men.
Citation Format: Melanie Elizabeth MacEwan, Timmy O'Connell, Hong Zhao, Codrin Iacob, Nina Suslina, Augustine Moscatello, Edward Shin, Raj Tiwari, Zbigniew Darzynkiewicz, Jan Geliebter. Androgen decreases proliferation of thyroid cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2122. doi:10.1158/1538-7445.AM2014-2122
Abstract 2123: Her2 affects AR phosphorylation at serine 81 and suppresses cell proliferation of breast cancer cell line MDA-MB-453
Authors: Huang Pao-Hsuan , Huang Chen-Chuan , Lee Yueh-Tsung , Yue Chia-Herng , Lin Ho 
Published: May 2015

Abstract
Breast cancer is a hormone-related carcinoma and the most commonly diagnosed malignancy among women. Although human epidermal growth factor receptor-2 (Her2), estrogen receptor (ER), and progesterone receptor (PR) are the major diagnostic markers and therapeutic targets to breast cancer, searching for additional molecular targets becomes an important issue and one of the candidates is androgen receptor (AR). In recent studies, AR expresses in 70% breast cancer cases and its expression connects to low recurrence and high survival rate. Our previous study shows that S81 phosphorylation is critical for AR protein stability and modulated by Her2 in prostate cancer cells. In this study, we explore the roles of AR and Her2 in proliferation of breast cancer cell line, MDA-MB-453. The data show that AR which was activated by synthetic androgen R1881 decreased proliferation of MDA-MB-453 cells. AR knockdown increased both phosphorylation of Akt and ERK. Notably, AR activation decreased protein level of Early growth response 1 (Egr1) and increased protein level of cyclin-dependent kinase inhibitor p27, which suggests the correlation of AR activation and proliferation suppression. Besides, Her2 activation by Heregulin (HRG) decreased the levels of p-S81-AR. Her2 inhibition by small molecular inhibitor, Lapatinib, increased the levels of p-S81-AR and p27. In summary, our results indicate that Her2 might negatively regulate AR activation and contribute to suppressive proliferation of MDA-MB 453 cells.
Citation Format: Pao-Hsuan Huang, Chen-Chuan Huang, Yueh-Tsung Lee, Chia-Herng Yue, Ho Lin. Her2 affects AR phosphorylation at serine 81 and suppresses cell proliferation of breast cancer cell line MDA-MB-453. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2123. doi:10.1158/1538-7445.AM2014-2123
Abstract 2125: G-protein coupled receptors for cholecystokinin regulate transactivation of EGF receptors in lung cancer cells
Authors: Moody Terry W. , Lee Suk Hee , Perez Paola Moreno , Jensen Robert T 
Published: May 2015

Abstract
Cholecystokinin (CCK) receptors (CCK-AR and CCK-BR) are G-protein coupled receptors (GPCR) which are present on lung cancer cells (Yoder and Moody, Peptides 1987; 8: 103). CCK stimulates the proliferation of NCI-H345 cells, whereas the CCK-B receptor antagonist CI-988 inhibits proliferation (Moody et al., JPET 2001; 299: 1154). Peptide receptors for some gastrointestinal hormones/neurotransmitters mediate lung cancer growth by causing EGFR transactivation, but it is unknown if this occurs with CCK-BR. CCK-BR mRNA was detected in NCI-H345 and H727 lung cancer cells. Addition of CCK-8 or gastrin I (100 nM) to NCI-H345 or H727 cells, which have wild type EGFR, increased EGFR Tyr1068 phosphorylation after 5 min. The ability of CCK-8 to cause EGFR or ERK tyrosine phosphorylation was blocked by CI-988 (CCK-BR antagonist), gefitinib (EGFR tyrosine kinase inhibitor), PP2 (Src inhibitor), GM6001 (matrix metalloprotease inhibitor), tiron (superoxide scavenger) and U-73122 (phospholipase C inhibitor) but not H89 (protein kinase A inhibitor). U-73122 or CI-988 inhibited the ability of CCK to cause phosphatidylinositol turnover and elevate cytosolic Ca2+. CI-988 or gefitinib inhibited the growth of NCI-H345 or H727 cells. CI-988 and gefitinib synergistically inhibited the growth of lung cancer cells. The results indicate that the CCK-BR regulates lung cancer proliferation in an EGFR-dependent mechanism through activation of Src, MMP and reactive oxygen species.
Citation Format: Terry W. Moody, Suk Hee Lee, Paola Moreno Perez, Robert T Jensen. G-protein coupled receptors for cholecystokinin regulate transactivation of EGF receptors in lung cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2125. doi:10.1158/1538-7445.AM2014-2125
Abstract 2128: The effects of Quercetin on prostate cancer
Authors: Ward Ashley B. , Gupta Pranav , Kaur Gurpreet , Mir Hina , Lillard James W. , Singh Shailesh 
Published: May 2015

Abstract
Prostate cancer (PCa) affects nearly 80% of men worldwide and is the second leading killer after lung cancer. The efficacy of current treatments offered in the clinics is highly compromised due to indolent nature of PCa, which provides large window of opportunity for prevention. Hence, the major focus of this study is to determine the chemo-preventive effects of Quercetin, a bioflavonoid, on prostate cancer. Effect of Quercetin on cell viability and IC50 was determined by MTT assay. The effect of Quercetin on cell motility was determined by wound healing assay. Potential role of Quercetin on cell cycle, apoptosis as well as genes involved in cell motility and invasion was determined using flow cytometry, Real-time qPCR and ELISA. Furthermore, Quercetin induced changes in signaling molecules involved in cell survival/apoptosis, cell cycle and cytoskeletal rearrangement was determined using antibody microarray. Prostate cancer cells treated with Quercetin showed dose and time dependent inhibition of proliferation/viability, and induction of apoptosis as compared to normal prostatic epithelial cells and untreated controls. Prostate cancer cell motility was inhibited in Quercetin treated cells. Prostate cancer cells were arrested in G2 phase of the cell cycle following Quercetin treatment. In addition to these, we found differential expression of caspases, matrix metalloproteinases (MMPs) and tissue inhibitor of MMPs in different PCa cell lines compared to untreated controls. Furthermore, antibody microarray analysis demonstrated selective modulation of genes and associated signaling cascades responsible for apoptosis induction, cellular motility, adhesion and invasion in Quercetin treated cells compared to controls. These findings suggest Quercetin as a potent chemo-preventive agent. In addition to this it can be also used with chemotherapeutic agents directed to G2 phase of the cell cycle, which may improve the efficacy of chemotherapeutics offered in clinics to treat advance prostate cancer.
Citation Format: Ashley B. Ward, Pranav Gupta, Gurpreet Kaur, Hina Mir, James W. Lillard, Shailesh Singh. The effects of Quercetin on prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2128. doi:10.1158/1538-7445.AM2014-2128
Abstract 2133: Suppressing effect of a Kava fraction on two lineages of prostate carcinogenesis in the transgenic adenocarcinoma of mouse prostate model
Authors: Tang Su-Ni , Datta Palika , Jiang Peixin , Leitzman Pablo , Xing Cheng-guo , Jiang Cheng , Lu Junxuan 
Published: May 2015

Abstract
Kava (Piper methysticum Forest) is a crop historically originating from west Pacific Islands. The epidemiologic studies for Pacific Island populations indicated that their cancer incidence rates were inversely related to the local consumptions of kava. Whereas chemopreventive efficacy of Kava ethanol extract has been shown in chemically-induced lung carcinogenesis models, its efficacy against prostate carcinogenesis is not known. In this study, we aim to evaluate the efficacy of Kava Fraction B, which is mostly kavalactones and free of flavokawains and most potent in lung carcinogenesis models, on prostatic carcinogenesis in the well-characterized C57BL/6 transgenic adenocarcinoma of mouse prostate (TRAMP) preclinical model. Previous studies by us (The Prostate, 2011) and others have suggested a paradigm of distinct lineages of carcinogenesis in this model: i.e., at least, androgen receptor (AR)-dependent glandular epithelia lesions (usually arise from the dorsal-lateral prostate [DLP] lobes) and AR-independent neuroendorine (NE)-like poorly differentiated (PD) carcinomas (usually derive from the ventral prostate [VP] lobe).
Experimentally, male C57BL/6 TRAMP mice were fed AIN93M purified diet without or with 0.4% of Kava fraction B from 8 weeks of age (WOA). Mice were euthanized at either 16 WOA or 28 WOA unless large tumors necessitated earlier sacrifice. The growth of the DLP in Kava-treated TRAMP mice were inhibited by 70% (P&lt;0.05) from control TRAMP mice by 16 WOA. By 28 WOA, the inhibition of TRAMP DLP growth were 76% (P&lt;0.001). Furthermore, Kava-fed TRAMP mice cohort had lower incidence of palpable and dissectable tumors (2 out of 14 mice) than control mice (7 out of 14 mice). Therefore, Kava fraction B appeared to inhibit both epithelial lineage lesions and NE-carcinogenesis. Future work will focus on 1) profiling cellular processes and molecular targets of Kava fraction B and 2) identifying active compounds in Kava Fraction B that inhibit epithelial lineage lesions and NE-carcinogenesis.
Supported in part by NCCAM AT007395 R01 and NCI CA142649 R01 grants.
Citation Format: Su-Ni Tang, Palika Datta, Peixin Jiang, Pablo Leitzman, Cheng-guo Xing, Cheng Jiang, Junxuan Lu. Suppressing effect of a Kava fraction on two lineages of prostate carcinogenesis in the transgenic adenocarcinoma of mouse prostate model. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2133. doi:10.1158/1538-7445.AM2014-2133
Abstract 2136: Long-term metformin use reduces gastric cancer risk in type 2 diabetics without insulin treatment: a nationwide cohort study
Authors: Cho Soo-Jeong , Kim Young-Il , Kim So Young , Park Jong-Hyock , Choi Il Ju , Lee You Jin , Lee Eun Kyung , Kook Myeong-Cherl , Kim Chan Gyoo , Ryu Keun Won , Kim Young-Woo 
Published: May 2015

Abstract
Background: Metformin use has been associated with a decreased incidence and mortality of various cancers.
Aim: The aim of this study was to evaluate the association between metformin use and gastric cancer.
Methods: We randomy selected 100,000 type 2 diabetic patients from the 2004 Korean National Health Insurance claim database, and assessed gastric cancer incidence among 39,989 patients (aged 30-97 years) who were regularly treated with anti-diabetic drugs and followed-up from 2004 to 2010. In total, 26,690 patients had used metformin out of 32,978 diabetics who had not regularly used insulin (insulin non-users), and 5,855 patients had used metformin out of 7,011 regular insulin users.
Results: Patients who used metformin showed a lower incidence of gastric cancer than those who did not use metformin, in insulin non-users (P=0.047, log-rank test). However, in patients on regular insulin, there was no difference of gastric cancer incidence according to metformin use. In insulin non-users, the adjusted hazard ratio (AHR) for metformin use was 0.73 (95% confidential interval [CI], 0.53-1.01) with borderline statistical significance (P=0.059). Duration of metformin use was associated with the reduction of gastric cancer risk (AHR, 0.88; 95% CI 0.81-0.96, P=0.003), especially in patients that used metformin for more than 3 years (AHR, 0.57; 95% CI, 0.37-0.87; P=0.009).
Conclusion: Metformin use &gt;3 years in type 2 diabetics who do not use insulin is associated with significantly reduced gastric cancer risk.
Citation Format: Soo-Jeong Cho, Young-Il Kim, So Young Kim, Jong-Hyock Park, Il Ju Choi, You Jin Lee, Eun Kyung Lee, Myeong-Cherl Kook, Chan Gyoo Kim, Keun Won Ryu, Young-Woo Kim. Long-term metformin use reduces gastric cancer risk in type 2 diabetics without insulin treatment: a nationwide cohort study. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2136. doi:10.1158/1538-7445.AM2014-2136
Abstract 214: Androgen resistance in prostate cancer is associated with an enrichment of stem-like cells
Authors: Wu Lisa Y. , Bansal Nitu , Liu Tiancheng , Berkman Clifford E. , Bertino Joseph R. 
Published: May 2015

Abstract
Cancer Stem cells (CSCs) or tumor initiating cells (TICs) have recently been identified in solid tumors; however, the role of CSCs/TICs in metastasis remains poorly understood. In this study, we developed a pre-clinical model to study stem-like cells in prostate cancer metastasis. CS-5 and CS-10 cells were derived by growing parental LNCaP cells in androgen-depleted media for five and ten generations. The growth rate of CS-10 cells was similar to parenteral LNCaP cells while CS-5 cell growth was diminished. Interestingly, CS10 cells were the sole cells observed with CD44 expression, which also had the highest α2β1 expression. In addition, none of the cell lines expressed CD133. In contrast to parenteral LNCaP cells, CD44+ CS-10 cells displayed an increase in 5 min collagen-I attachment, cell migration, invasion, colony formation and sphere formation in an anchorage-independent environment, all attributes of TICs. Additional evidence for “stemness” was that CS-10 cells were capable of self-renewal in the secondary and tertiary spheroid assays. CS-10 cells expressed neuroendocrine and EMT markers and demonstrated resistance to anti-androgen drugs and most chemotherapeutic drugs compared to parenteral LNCaP cells.
In summary, the novel findings presented here provide evidence that castrate resistance may result in selection of CD44+/ α2β1+/CD24low/CD133 cells, which possesses stem cell properties. This cell line may serve as a model for evaluation of new targeted treatments in prostate CSCs.
Citation Format: Lisa Y. Wu, Nitu Bansal, Tiancheng Liu, Clifford E. Berkman, Joseph R. Bertino. Androgen resistance in prostate cancer is associated with an enrichment of stem-like cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 214. doi:10.1158/1538-7445.AM2014-214