bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4036: Curcumin induces ER stress-mediated apoptosis through cell type-specific interruption of redox balance in cervical cancer cells.
Authors: Kim Boyun , Jung Eun-Ji , Song Yong Sang 
Published: August 2014

Abstract
Prolonged accumulation of misfolded or unfolded proteins prompts a cellular stress condition known as ER stress which activates unfolded protein response (UPR). The ER stress is usually sustained at higher level in cancers than in normal cells due to altered metabolism of the cancer. Recent studies have shown that curcumin, a major yellow pigment of tumeric derived from Curcuma longa plant, triggers apoptosis through induction of ER stress in several cancer cells. Here, we found that ER stress was induced by interruption of redox balance when cervical cancer cells were exposed to curcumin. We used four cervical cancer cell lines, C33A, CaSki, HeLa and ME180. Curcumin inhibited proliferation of cervical cancer cells in a dose- and time-dependent manner and induced apoptotic cell death (increase of AnnexinV-positive and SubG1 fraction). Additionally, proteolytic activation of caspase-9 and -3 and PARP cleavage were shown in cervical cancer cells. We next evaluated activation of unfolded protein response (UPR) in response to curcumin. Three ER-resident sensors (PERK, IRE1α and ATF6) and their down-signaling proteins (XBP1, ATF4 and eIF2α) were activated in all cervical cancer cells (C33A, CaSki, HeLa and ME180), but not in normal cervical epithelial cell. Also, one of UPR down-signaling proteins CHOP/GADD153, which is a transcription factor inducing ER stress-mediated apoptosis, was up-regulated by curcumin. CHOP/GADD153 decreased anti-apoptotic protein Bcl2 and subsequently promoted apoptosis of cervical cancer cells exposed to curcumin. Furthermore, curcumin led to elevation of intracellular ROS in CaSki and ME180 cells, but not in C33A, HeLa and normal cervical epithelial cell. Pretreatment of N-acetyl-cysteine (ROS scavenger) resulted in inhibition of ER stress and cell death at least in part. Taken together, these results show that curcumin promotes ER stress-mediated apoptosis through cell type-specific ROS generation in cervical cancer cells.
Citation Format: Boyun Kim, Eun-Ji Jung, Yong Sang Song. Curcumin induces ER stress-mediated apoptosis through cell type-specific interruption of redox balance in cervical cancer 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 4036. doi:10.1158/1538-7445.AM2013-4036
Abstract 4057: Functional domain of Annexin A4: which domain is indispensable for chemoresistance to platinum drugs.
Authors: Morimoto Akiko , Enomoto Takayuki , Matsuzaki Shinya , Hiramatsu Kousuke , Ueda Yutaka , Yoshino Kiyoshi , Fujita Masami , Yokoyama Takuhei , Serada Satoshi , Naka Tetsuji , Kimura Tadashi 
Published: August 2014

Abstract
Background: Platinum drugs are often used for the postoperative adjuvant therapy or treatment in advanced and recurrent ovarian cancer. We have previously reported that ovarian clear cell carcinoma (CCC) has increased expression of Annexin A4 (Anx A4) in comparison with other subtype of ovarian cancer. Enhanced expression of Anx A4 has been shown to induce chemoresistance via extracellular efflux of carboplatin.
Purpose: To identify the domain of Anx A4 relevant to chemoresistance.
Materials and methods: Anx A4 possesses the NH2-terminal domain and four annexin repeat domains with one Ca2+-binding site in each domain. Deleting annexin repeat domains one by one from C-terminal site, we generated four deletion mutants of Anx A4 named R1, 2, 3, and 4 (arabic figure shows the number of annexin repeat domains). Stable cell lines overexpressing each deletion mutants were established in NUGC3 cells. Chemosensitivity to platinum drugs was evaluated using the MTT assay.
Results. Compared with mock transfected cells, all the four deletion mutants induced chemoresistance to both cisplatin and carboplatin.
Conclusions. The deletion derivative covering only one annexin repeat domain can induce chemoresistance to platinum drugs. Further study is underway to determine the specific site for chemoresistance of Anx A4.
Citation Format: Akiko Morimoto, Takayuki Enomoto, Shinya Matsuzaki, Kousuke Hiramatsu, Yutaka Ueda, Kiyoshi Yoshino, Masami Fujita, Takuhei Yokoyama, Satoshi Serada, Tetsuji Naka, Tadashi Kimura. Functional domain of Annexin A4: which domain is indispensable for chemoresistance to platinum drugs. [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 4057. doi:10.1158/1538-7445.AM2013-4057
Abstract 4059: Annexin A4-conferred platinum resistance is mediated by the copper transporter ATP7A.
Authors: Matsuzaki Shinya , Morimoto Akiko , Serada Satoshi , Yokoyama Takuhei , Kimura Toshihiro , Kobayashi Eiji , Ueda Yutaka , Yoshino Kiyoshi , Fujita Masami , Enomoto Takayuki , Naka Tetsuji , Kimura Tadashi 
Published: August 2014

Abstract
Because platinum drugs are often used for the chemotherapy of human cancers, when platinum resistance occurs it is a major issue. We recently reported that enhanced expression of Annexin A4 (Anx A4) increases chemoresistance to Carboplatin via increased extracellular efflux of the drug. However, the precise mechanisms of that chemoresistance, and the relationship of Anx A4 to platinum resistance in vivo, remain unclear. In this report we investigate in vitro the mechanism of platinum resistance induced by Anx A4 in endometrial carcinoma cells (HEC1 cells) which normally have a low level of expression of Anx A4. Forced expression of Anx A4 in HEC1 cells resulted in chemoresistance to platinum drugs. In addition, we compared HEC1 control cells with Anx A4-overexpressing HEC1 cells when both were xenografted to mice, Anx A4-overexpressing xenografted mice presented with significantly greater chemoresistance to Cisplatin in vivo. By immunofluorescence analysis we found that exposure to platinum drugs induced relocation of Anx A4 from the cytoplasm to the cellular membrane, where it became co-localized with ATP7A, a copper transporter also well known to be a platinum effluxer. When the expression of ATP7A was suppressed by small interfering RNA in HEC1 control cells, they showed no change of chemosensitivity to platinum drugs. However, suppressed ATP7A in Anx A4 overexpressing platinum-resistant cells, they showed improved chemosensitivity to platinum drugs, to a level comparable of that of control cells. Our results indicate that enhanced expression of Anx A4 confers platinum resistance by promoting efflux of platinum drugs via ATP7A.
Citation Format: Shinya Matsuzaki, Akiko Morimoto, Satoshi Serada, Takuhei Yokoyama, Toshihiro Kimura, Eiji Kobayashi, Yutaka Ueda, Kiyoshi Yoshino, Masami Fujita, Takayuki Enomoto, Tetsuji Naka, Tadashi Kimura. Annexin A4-conferred platinum resistance is mediated by the copper transporter ATP7A. [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 4059. doi:10.1158/1538-7445.AM2013-4059
Abstract 4067: Detection of S-nitrosylated protein in renal cell cancer.
Authors: Hongo Fumiya , Ueda Takashi , Ito-Ueda Saya , Oishi Masakatsu , Nakamura Terukazu , Naya Yoshio , Miki Tsuneharu 
Published: August 2014

Abstract
Purpose: Nitric oxide (NO) is a versatile signaling molecule. Its roles in a variety of physiological functions in mammals are beginning to be understood. It has been demonstrated that NO up-regulates the expression of the Fas receptor on human tumor cells via specific inactivation of transcription repressor YY1 DNA binding activity to the silencer region of the Fas promoter (Hermes G., et al. 2001). We also showed that inactivation of YY1 via protein S-nitrosylated by NO in prostatic cancer could be identified (Hongo F., et al. 2005). This post-translational modification, known as S-nitrosylation, has emerged as a highly conserved and spatiotemporally specific signaling mechanism. The objective of our study was to examine the effect of NO donor treatment on renal cell cancer.
Methods: We examined the effect of the NO donor DETA-NONOate (100-500uM) on the following renal cell cancer cell lines; CAKI-1, NC65, and ACHN. Anti-S-nitroso-Cysteine antibody in the rabbit (SIGMA-ALDRICH) was applied as a primary antibody for immunohistochemistry. The biotin-switch technique was applied to detect specific S-nitrosylated proteins. Whole cell lysates were extracted from ACHN cells employed with DETA-NONOate. Using an S-nitrosylated detection kit (Cayman Chemical Company), S-NO was replaced by Biotin. Cell lysates were incubated at 4 oC with 30 μL of Dynabeads M-280 Streptavidin (Invitrogen) for 3 hrs. After five washes with wash buffer (S-Nitrosylation Wash buffer), the protein complex was eluted from anti-biotin dynabeads by incubation with 1x volume of elution buffer (0.1M glycine (pH2.0)) twice for 15 min. Each sample was added to an SDS-polyacrylamide gel for mass spectrometry.
Results: Significant up-regulation of S-nitrosylated proteins employed with DETA-NONOate was observed by immunohistochemistry. Specific S-nitrosylated proteins in ACHN cells were detected by the biotin-switch technique and included HSP90 (heat shock protein 90), GRP78 (HSP70 family), HSP70, and pyruvate kinase M2.
Conclusions: Our data showed that NO treatment significantly increased S-nitrosylation of several proteins. S-nitrosylation should be considered as one of the mechanisms by which NO acts on cancer cells.
Citation Format: Fumiya Hongo, Takashi Ueda, Saya Ito-Ueda, Masakatsu Oishi, Terukazu Nakamura, Yoshio Naya, Tsuneharu Miki. Detection of S-nitrosylated protein in renal cell 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 4067. doi:10.1158/1538-7445.AM2013-4067
Abstract 407: Urinary C-reactive protein: A biomarker of metastatic kidney cancer.
Authors: Morrissey Jeremiah , Kharasch Evan D. 
Published: August 2014

Abstract
Background: Approximately one-third of patients with kidney cancer who do not have detectable metastatic disease at the time of diagnosis and/or nephrectomy will nonetheless go on to develop metastasis. Presently, there is no method to predict which patients with kidney cancer and no evidence of metastases; will later develop metastatic disease. This investigation evaluated pre-nephrectomy urine C-reactive protein as an early diagnostic predictor of subsequent metastatic kidney cancer, and its use for tumor staging by molecular pathology to supplement conventional observational pathology.
Methods: C-reactive protein was measured by a sensitive ELISA in the pre- and post-nephrectomy urine of 31 patients with a pathologic diagnosis of clear cell or papillary carcinoma (tumor size 1-11 cm) and in 23 surgical control patients matched for age and sex. C-reactive protein in the tumors was determined by immunohistochemistry.
Results: By immunohistochemistry, kidney tumors synthesize C-reactive protein, thus making it available for potential excretion into the urine. The urine C-reactive protein of all control patients was 0.6 (0.2, 1.0) ng/ml (median, (1st and 3rd quintile)) while in the pre-nephrectomy urine of 31 patients with clear cell or papillary carcinoma was 3.9 (2, 11) ng/ml (P&lt;0.0001, Wilcoxon rank sum test). The c-statistic for all controls and patients with kidney cancer was 0.89 (95% CI, 0.80 to 0.97) while the Spearman regression coefficient to tumor size was 0.72 (95% CI, 0.57-0.83). There was a significant 82% decrease in the urinary C-reactive protein concentration in the post-nephrectomy urine (P=0.0156, Wilcoxon test for paired samples). All stage 3 tumors and almost half of the stage 1 tumors excreted high amounts of biomarker. Four patients with stage 1 tumors and with concentrations of urine C-reactive protein significantly above the control range and no noted metastases at the time of partial nephrectomy subsequently developed clinical metastases over 32-34 months. Four patients with stage 1 tumors and urinary C-reactive protein concentrations equivalent to the controls had not developed metastatic disease in the same time frame.
Conclusion: The measurement of C-reactive protein in the urine may be a non-invasive biopsy of the renal tumor indicating sub-clinical metastatic potential and may pre-surgically stage the tumor by molecular pathology.
Citation Format: Jeremiah Morrissey, Evan D. Kharasch. Urinary C-reactive protein: A biomarker of metastatic kidney 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 407. doi:10.1158/1538-7445.AM2013-407
Abstract 4072: Wnt1 gene expression alters heterogeneous population of prostate cancer cells; decreased expression pattern observed in CD133+/CD44+prostate cancer stem cells.
Authors: Goksel Gamze , Bilir Ayhan , Uslu Ruchan , Akbulut Hakan , Guven Ummu , Oktem Gulperi 
Published: August 2014

Abstract
Tumor mass contains a complex and heterogeneous phenotypic population including a rare group of cancer cells that are capable of serving cancer- initiating cells or cancer stem cells (CSCs). Established cancer cell lines contain CSCs, which can be propagated, to form in vitro 3D tumor spheroids. Spheroids reflect differentiation properties of CSCs in serum contained medium and more accurately reflect the complex in vitro microenvironment than simple two-dimensional monolayer. Aberrant activation of Wnt signaling is strongly implicated in the progression of cancer and controls CSCs properties. In this study we hypothesize that when cells maintained as spheroids the structure of CSCs could be show differentiation between CSCs and non- CSCs counterpart. It is possible to determine target molecules for CSCs eradication and specify a clue in therapeutic strategies of cancer. With this aim, CD133+/CD44+ cancer-initiating cells were isolated from DU-145 human prostate cancer cell line monolayer cultures and propagated as tumor spheroids and compared with remained heterogeneous cancer cells bulk population. Wnt1, Fzd1, Adar, Apc, Axin, Btrc, Frat1 gene expression analysis was applied and protein expression levels of Wnt1, Fzd and Axin were shown by immunohistochemistry. Results show that Wnt1 expression significantly higher in non cancer stem cells compared to CSCs. Nevertheless Fzd1, Adar, Apc, Axin, Btrc, Frat1 gene expressions were higher in CSCs group than the other population. Increased Wnt1 immunoreactivity was demonstrated in the non-cancer stem cells. It is possible to assume that intracellular signaling of Wnt pathway and related molecules in the nucleus and/or cytoplasm might play an important role independent of Wnt ligand. This unexpected expression could be important for CSCs behavior and targeting of this pathway could have therapeutic value in cancer.
Citation Format: Gamze Goksel, Ayhan Bilir, Ruchan Uslu, Hakan Akbulut, Ummu Guven, Gulperi Oktem. Wnt1 gene expression alters heterogeneous population of prostate cancer cells; decreased expression pattern observed in CD133+/CD44+ prostate cancer stem 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 4072. doi:10.1158/1538-7445.AM2013-4072
Abstract 4075: Regulation of NKX3.1 by RMND5 proteins.
Authors: Louw Alison , Thomas Marc A. , Harvey Jennet , Bentel Jacqueline M. 
Published: August 2014

Abstract
Expression of the prostatic tumour suppressor, NKX3.1 is reduced or undetectable in a large proportion of advanced human prostate tumours. Although loss of heterozygosity (LOH) is common at the 8p21.2 locus which encompasses the NKX3.1 gene, mutations of the remaining NKX3.1 allele that would account for loss of NKX3.1 expression have not been identified. Indeed, the documented discordance between NKX3.1 mRNA and protein expression suggests that translational or posttranslational mechanisms contribute to the loss of NKX3.1 expression in prostate tumour tissues. We have identified two novel NKX3.1 binding proteins in LNCaP cells, RMND5A and RMND5B. The RMND5A gene locus at 2p11.1 is deleted or amplified in a variety of cancers, while the RMND5B locus at 5q35.3 undergoes frequent LOH in breast tumours from BRCA1 and BRCA2 mutation carriers and is located within an uncharacterised prostate cancer heritability locus. RMND5 proteins are widely expressed, multidomain proteins that each contain a putative RING domain, suggesting that they are able to function as E3 ubiquitin ligases. In in vitro ubiquitin assays, the RING domain of RMND5A was able to associate with UbcH2, UbcH5b and UbcH5c, while the RING domain of RMND5B interacted with UbcH5b and UbcH5c to mediate ubiquitin transfer. Both RMND5A and RMND5B were associated with ubiquitinated proteins in vivo and the increased expression of RMND5A or RMND5B augmented cellular levels of ubiquitinated proteins, providing further evidence of their E3 ubiquitin ligase activity. Overexpression of either RMND5A or RMND5B in LNCaP cells resulted in dose-dependent declines in endogenous NKX3.1 levels, which were attenuated following proteasome inhibition. In addition, RMND5A or RMND5B overexpression enhanced cellular levels of ubiquitinated NKX3.1. In LNCaP cells, RMND5 proteins were diffusely distributed in the cytoplasm and nucleus, with RMND5B occasionally exhibiting a punctate cytoplasmic distribution. When NKX3.1 and RMND5A or RMND5B were overexpressed, RMND5 proteins became predominantly nuclear, while the nuclear levels of NKX3.1 were markedly reduced. Together, these findings indicate that RMND5 proteins promote NKX3.1 ubiquitination and proteasome-dependent degradation and additionally modify the intracellular localisation of NKX3.1, potentially regulating its function as a transcription factor.
Citation Format: Alison Louw, Marc A. Thomas, Jennet Harvey, Jacqueline M. Bentel. Regulation of NKX3.1 by RMND5 proteins. [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 4075. doi:10.1158/1538-7445.AM2013-4075
Abstract 4078: Novel 3D co-cultural model for epithelial-stromal cells interaction in prostate cancer.
Authors: Fang Xiaolan , Sivanandane Sittadjody , Gyabaah Kenneth , Balaji K.C. 
Published: August 2014

Abstract
Paracrine function is a major mechanism of cell-cell communication within tissue microenvironment in both normal development and disease. In vitro cell culture models simulating tissue or tumor microenvironment are necessary tools to delineate epithelial stromal interactions including paracrine function. Yet an ideal 3-dimensional (3D) tumor model specifically studying paracrine function is currently lacking. In order to fill this void we developed a novel 3D co-culture model, using double layered alginate hydrogel microspheres to incorporate prostate cancer epithelial and stromal cells. The cells remained confined and viable within their respective spheres for over 30 days. As a proof of principle regarding paracrine function of the model, we measured shedded component of E-cadherin (sE-cad) in the conditioned media, a major membrane bound cell adhesive molecule that is highly dysregulated in cancers including prostate. In addition to demonstrating that sE-cad can be reliably quantified in the conditioned media, the time course experiments also proved that the amount of sE-cad is influenced by epithelial stromal interaction. In conclusion, the study establishes a novel 3D in vitro co-culture model that can be used to study cell-cell paracrine interaction.
Citation Format: Xiaolan Fang, Sittadjody Sivanandane, Kenneth Gyabaah, K.C. Balaji. Novel 3D co-cultural model for epithelial-stromal cells interaction in prostate 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 4078. doi:10.1158/1538-7445.AM2013-4078
Abstract 4083: Inhibition of constitutive aryl hydrocarbon receptor (AhR) signaling attenuates androgen indepenent signaling and growth in (C4-2) prostate cancer cells.
Authors: Tran Cindy , Richmond Oliver , Aaron LaTayia , Powell Joann B. 
Published: August 2014

Abstract
The aryl hydrocarbon receptor is a member of the basic-helix-loop-helix family of transcription factors. AhR mediates the biochemical and toxic effects of a number of polyaromatic hydrocarbons such as 2,3,7,8,-tetrachloro-dibenzo-dioxin (TCDD). AhR is widely known for regulating the transcription of drug metabolizing enzymes involved in the xenobiotic metabolism of carcinogens and therapeutic agents, such as cytochrome P450-1B1 (CYP1B1). Additionally, AhR has also been reported to interact with multiple signaling pathways during prostate development. Here we investigate the effect of sustained AhR signaling on androgen receptor function in prostate cancer cells. Immunoblot analysis shows that AhR expression is increased in androgen independent (C4-2) prostate cancer cells when compared to androgen sensitive (LNCaP) cells. RT-PCR studies revealed constitutive AhR signaling in C4-2 cells without the ligand induced activation required in LNCaP cells. A reduction of AhR activity by pharmacologic inhibitors or short RNA mediated silencing in C4-2 cells reduced expression of both AhR and androgen responsive genes. The decrease in androgen responsive genes correlates to a decrease in phosphorylated androgen receptor and androgen receptor expression in the nucleus. Furthermore, the forced decrease in AhR expression resulted in a 50% decline in the growth rate of C4-2 cells. These data indicates that AhR is required to maintain hormone independent signaling and growth by the androgen receptor in C4-2 cells. Collectively, these data provide evidence of a direct role for AhR in androgen independent signaling and provides insight into the molecular mechanisms responsible for sustained androgen receptor signaling in hormone refractory prostate cancer.
Citation Format: Cindy Tran, Oliver Richmond, LaTayia Aaron, Joann B. Powell. Inhibition of constitutive aryl hydrocarbon receptor (AhR) signaling attenuates androgen indepenent signaling and growth in (C4-2) prostate cancer 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 4083. doi:10.1158/1538-7445.AM2013-4083