bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3753: Copper-chelator exerts synergistic interaction with platinum drugs through modulating copper transporters in oxaliplatin-resistant human gastric cancer cell
Authors: Chen Szu-Jung , Chang Jang-Yang , Kuo Ching-Chuan , Pan Hsin-Yi 
Published: May 2015

Abstract
Although platinum-based chemotherapy drugs including cisplatin, carboplatin, and oxaliplatin are commonly used in the treatment of human solid tumor, patients ultimately develop drug-resistance and result in treatment failure. Combination copper-chelator with platinum drugs has been reported to successfully treat a subset of cisplatin- resistant ovarian cancer patients. However, the underlying mechanisms of action remain unknown. We have previously established an oxaliplatin-resistant subclone from human gastric adenocarcinoma TSGH cells, S3. The mechanisms responsible for oxaliplatin resistance of S3 cells included down-regulation of hCtr1 and over-expression of ATP7A. In contrast to displaying additive to antagonistic interaction with platinum drugs in parental, TSGH cells, our studies showed that copper-chelator, D-penicillamine, exerts synergistic interaction with platinum drugs through increasing platinum- DNA adduct formations in S3 cells. D-penicillamine promotes copper uptake transporter hCtr1 expression via activation of transcription factor Sp1. In addition, Sp1 overexpression promotes p53 translocation from nucleus to cytosol and binds to ubiquitin, and finally causes p53 degradation, which further suppressed the expression of copper efflux transporter, ATP7A. Combination of D-penicillamine and oxaliplatin significantly inhibited S3 cell growth in animal model. Immunohistochemical analysis showed that up-regulation of hCtr1 and down-regulation of ATP7A were found in both D-penicillamine- and D-penicillamine/ Oxalipatin- treated S3 tumors, which were consistence to in vitro results. In conclusion, our results showed that D-penicillamine increases hCtr1 expression through regulating Sp1 level. Notably, D-penicillamine could down-regulate ATP7A expression through regulation of p53. Our finding demonstrated a new treatment strategy for cancer patient resistant to oxaliplatin treatment with low expression of hCtr1 and overexpression of ATP7A in tumor tissues. (This work was partially supported by the following grants: Department of Health, Taiwan DOH99-TD-C-111-004, National Health Research Institutes CA-101-PP-22, National Research Program for Biopharmaceuticals 100CAP015-5 and National Science Council 102-2325-B-400 -007)
Citation Format: Szu-Jung Chen, Jang-Yang Chang, Ching-Chuan Kuo, Hsin-Yi Pan. Copper-chelator exerts synergistic interaction with platinum drugs through modulating copper transporters in oxaliplatin-resistant human gastric cancer cell. [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 3753. doi:10.1158/1538-7445.AM2014-3753
Abstract 376: P-cadherin overexpression is associated with poor prognosis in pancreatic carcinoma and is regulated by its promoter hypomethylation
Authors: Sakamoto Keita , Imai Katsunori , Nakagawa Shigeki , Nitta Hidetoshi , Hayashi Hiromitsu , Chikamoto Akira , Ishiko Takatoshi , Beppu Toru , BaBa Hideo 
Published: May 2015

Abstract
[Background] P-cadherin belongs to the family of classic cadherin, and accumulating evidences shows hat P-cadherin is strongly associated with carcinogenesis and confers alignant phenotype of various cancers. Pancreatic cancer has a poor prognosis, with an overall 5-year survival rate of only 5%. Despite advances in therapy recently, its survival rate still remains poor. This study aimed to analyze P-cadherin expression and its prognostic value in pancreatic carcinoma and to validate the P-cadherin gene (CDH3) promoter methylation status as the mechanism of this gene regulation.
[Methods] Seventy-three patients diagnosed with pancreatic cancer were enrolled in this study. P-cadherin expression was examined by immunohistochemistry, and correlated with various clinicopathological features and prognosis. Furthermore, P-cadherin expression and its promoter methylation status were analyzed in pancreatic cancer cell lines.
[Results] In pancreatic tissues, 50.7% (37/73) of cases shows a high expression of P-cadherin by immunohistochemical analysis, and high expression of P-cadherin was significantly correlated with gender, posterior tissue invasion and other organs invasion. In multivariate analyses, P-cadherin expression was the independent prognostic factors for disease-free survival (relative risk:2.68, p=0.005). P-cadherin expression was found to be related to its promoter methylation status in pancreatic cancer cell lines. Furthermore, when P-cadherin was down-regulated by specific siRNA, cell migration and invasion were significantly reduced.
[Conclusion] These results suggested that expression of P-cadherin is a useful prognostic marker and seems to be important in the malignant behavior in pancreatic cancer. We are now conducting experiments to validate the CDH3 methylation status in the cancerous tissues and their adjacent normal counterpart, and investigating the biological role of P-cadherin in pancreatic cancer.
Note: This abstract was not presented at the meeting.
Citation Format: Keita Sakamoto, Katsunori Imai, Shigeki Nakagawa, Hidetoshi Nitta, Hiromitsu Hayashi, Akira Chikamoto, Takatoshi Ishiko, Toru Beppu, Hideo BaBa. P-cadherin overexpression is associated with poor prognosis in pancreatic carcinoma and is regulated by its promoter hypomethylation. [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 376. doi:10.1158/1538-7445.AM2014-376
Abstract 3760: Role of epithelial to mesenchymal transition in response to cisplatin in patient-derived ovarian carcinomas
Authors: Ricci Francesca , Guffanti Federica , Maddalena Fratelli , Perego Patrizia , Fruscio Robert , Baldo Romina , Magni Sonia , Broggini Massimo , Damia Giovanna 
Published: May 2015

Abstract
Epithelial ovarian cancer has the highest mortality rate in the western world among gynecological malignancies. Approximately 70% of patients achieve complete remission after first-line cisplatin (DDP)-based therapy, but almost all patients relapse with resistant disease. Understanding the mechanisms at the basis of the resistance to therapy is of pivotal importance and xenografts models are instrumental to address this topic.
We have recently been able to stabilize a panel of ovarian cancer xenografts that represent human tumors of origin both at the histological and molecular level.
Seven xenografts were characterized for their sensitivity to DDP given once a week for 3 weeks at the dose of 5 mg/kg. A second DDP cycle was given to the regrowing tumors, mimicking clinical conditions. Xenografts were classified as “Responder” (R) or “Non-Responder” (NR) on the basis of their DDP-response. Interestingly, almost all xenografts were less sensitive to the second cycle of DDP. In an attempt to study the role of genes involved in Epithelial-Mesenchymal Transition (EMT), we evaluated by RT-PCR (by the Qiagen RT2 ProfilerTM PCR Array System) in untreated and DDP-treated R and NR xenografts the expression level of 86 EMT genes.
By these analysis we wanted to investigate if some EMT genes could be predictive for DDP response, and if DDP treatment could itself induced EMT genes responsible for the observed DDP resistance. 12 genes (KRT14, BMP1, JAG1, PPPDE2, TFPI2, MSN, ITGA5, ITGAV, KRT7, FGFBP1, AHNAK and ESR1) were found to be more expressed in “NR” then “R” xenografts, and few were validated (i.e. AHNAK, JAG1). To address the second point, the fold change of gene expression was considered in DDP-treated versus control samples. 8 genes (ZEB2, TGFB1, WNT5B, MST1R, COL3A1, FN1,PLEK2, FGFBP1) involved in EMT activation were found to be upregulated by the DDP treatment, and are currently under validation.
These studies would suggest a predictive role of upregulation of specific EMT genes in response to DDP treatment, and possibly in the development of its resistance. The validation of these genes in patients whose clinical response to a DDP based therapy is known, will help in defining predictive markers to tailor DDP therapy in ovarian cancer patients.
Citation Format: Francesca Ricci, Federica Guffanti, Fratelli Maddalena, Patrizia Perego, Robert Fruscio, Romina Baldo, Sonia Magni, Massimo Broggini, Giovanna Damia. Role of epithelial to mesenchymal transition in response to cisplatin in patient-derived ovarian carcinomas. [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 3760. doi:10.1158/1538-7445.AM2014-3760
Abstract 3764: Antibody therapy against granulin-epithelin precursor sensitizes liver cancer to chemotherapy
Authors: Wong Nicholas , Cheung Phyllis , Yip Chi Wai , Chan Kui Fat , Ng Irene , Fan Sheung Tat , Cheung Siu Tim 
Published: May 2015

Abstract
The novel growth factor granulin-epithelin precursor (GEP, also named progranulin, acrogranin, or PC-derived growth factor) has shown to be upregulated in breast, ovary, prostate, liver and various human cancers. Our group has shown that GEP associated with chemo-resistance, recurrence and cancer stem cell properties in liver cancer [Gastroenterology 2011 and PLoS One 2011]. In the current study, we demonstrated that, both in vivo and in vitro, liver cancer cells that survived after chemotherapeutic agents demonstrated up-regulation of hepatic cancer stem cell marker CD133/GEP/ABCB5, and enhanced cancer stem cell properties, including colony formation and spheroid formation abilities. Importantly, combination of GEP antibody therapy and chemotherapy reversed the phenotypes induced by chemotherapy alone in the liver cancer cells and also the chemo-resistant subpopulations. Notably, combination of GEP antibody and cisplatin resulted in the eradication of all established intrahepatic human xenografts. This preclinical study demonstrated that combination treatment has the potential to be effective therapeutic regimen for GEP positive cancers.
Citation Format: Nicholas Wong, Phyllis Cheung, Chi Wai Yip, Kui Fat Chan, Irene Ng, Sheung Tat Fan, Siu Tim Cheung. Antibody therapy against granulin-epithelin precursor sensitizes liver cancer to chemotherapy. [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 3764. doi:10.1158/1538-7445.AM2014-3764
Abstract 3776: Identification of gene regulatory networks mediating melanoma cell resistance to temozolomide
Authors: Zhang Tongwu , Xu Mai , Chow Donald , Sereduk Chris , Trent Jeffrey M. , Yin Hongwei , Brown Kevin M. 
Published: May 2015

Abstract
Melanoma is the most dangerous type of skin cancer and the leading cause of death from skin cancer. While there are multiple promising new immunotherapeutic and targeted approaches for treating melanoma, not all patients are eligible for these therapies and most of those that are ultimately relapse, highlighting a critical need for improved chemotherapeutics. Temozolomide (TMZ) is an orally administered DNA-alkylating agent used in the treatment of advanced cancers including melanoma. TMZ has shown some advantage in the clinic in terms of preventing central nervous system relapse and patient quality of life. In order to find novel vulnerabilities that may be exploited to sensitize melanoma cells to TMZ, we utilized mRNA expression and TMZ-sensitivity profiling in a panel of 18 melanoma cell lines to develop a classifier of TMZ-sensitivity using the support vector machine (SVM) method. We subsequently applied this classifier to predict the TMZ-sensitivity in 47 independent melanoma cell lines. TMZ sensitivity profiling in smaller set of 22 of these lines resulted in a prediction accuracy of approximately 80%. We analyzed the genes differentiating TMZ-sensitive and -resistant melanoma cells using both microarray data in 40 cell lines, and more recently RNA-sequencing from the original 18 cell line training set. We found no correlation between TMZ sensitivity and expression of the DNA repair gene (MGMT), base excision repair gene (PARP1, PARG, etc.), and DNA mismatch repair gene (MLH1, MSH2, etc.). Instead, analysis using the Ingenuity IPA pathway analysis tool found that upregulation of MITF and a large set of MITF target genes, as well as downregulation TGFB1 and TGFB1 targets were strongly associated with TMZ resistance in melanoma cell line (p = 2.82E-67 and p = 1.17E-52, respectively in the microarray analysis; similar results observed in RNA sequencing data). E-cadherin (CDH1), which is know to play a key role in invasion and transition from radial to vertical growth in melanoma, was found to be one of the genes most significantly correlated with TMZ resistance. Finally, we also analyzed exome-sequencing data from these cell lines (n=55) and found that TMZ-sensitivity did not significantly correlate with the presence or absence of mutations to genes commonly mutated in melanoma. In conclusion, our gene expression data suggest that TMZ resistance in melanoma cells in vitro is likely mediated by large gene regulatory networks governed by MITF and TGFB1.
Citation Format: Tongwu Zhang, Mai Xu, Donald Chow, Chris Sereduk, Jeffrey M. Trent, Hongwei Yin, Kevin M. Brown. Identification of gene regulatory networks mediating melanoma cell resistance to temozolomide. [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 3776. doi:10.1158/1538-7445.AM2014-3776
Abstract 379: TARBP1, a member of the SPOUT methyltransferase family, is involved in human carcinogenesis
Authors: Nakakido Makoto , Nakamura Yusuke , Hamamoto Ryuji 
Published: May 2015

Abstract
It has recently been recognized that protein methylation plays a critical role in many biological processes, and its deregulation has been observed in various kinds of diseases, including cancer. To date, a number of protein methyltransferases have already been reported to be associated with human carcinogenesis. Although many protein methyltransferases belong to the SET-domain containing protein family or the protein arginine methyltransferase (PRMT) family, a series of other methyltransferase families have also been discovered by bioinformatics-based approaches. On the contrary, physiological functions of these methyltransferases, especially, the significance in human disease like cancer, still remains unknown. In this study, we demonstrated that expression levels of TARBP1 (TAR RNA-Binding Protein 1), a member of the SPOUT methyltransferase family, are significantly up-regulated in many types of cancer tissues compared to corresponding non-tumor tissues. In addition, knockdown of TARBP1 resulted in the suppression of cancer cell growth, indicating that TARBP1 seems to regulate the proliferation of cancer cells. Since expression levels of TARBP1 in normal tissues are significantly low, TARBP1 may be a good new target for anti-cancer therapy.
Citation Format: Makoto Nakakido, Yusuke Nakamura, Ryuji Hamamoto. TARBP1, a member of the SPOUT methyltransferase family, is involved in human carcinogenesis. [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 379. doi:10.1158/1538-7445.AM2014-379
Abstract 3797: Efficacy and pharmacokinetics of gold nanorods coupled with laser-induced photoplasmonic therapy in solid tumor bearing mice
Authors: Al-Abd Ahmed M. , Shabaka Ali A. , El-Shabrawy Osama A. , Yassin Nemat A. , Mahmoud Sawsan S. , El-Shenawy Siham M. , Al-Ashqar Emad , Eisa Wael H. , Farag Niveen M. , El-Shaer Marwa A. , Salah Nabila , El-Sayed Mostafa A. 
Published: May 2015

Abstract
Gold nanorods (GNR) are characterized by absorbing near IR beams and emitting heat which is called photoplasmonic response. Yet, the efficacy of nanoparticles is limited due to intratumoral tissue distribution reasons. In addition, distribution of GNRs to normal tissue might result in non specific toxicity. In the current study, we assessed the intratumoral and tissue distribution of PEGylated GNRs as well as its antitumor efficacy (coupled with laser photoplasmonic sessions) when given intravenously or intratumoral to solid tumor bearing mice. PEGylated GNRs with a longitudinal size of less than 100 nm were prepared with aspect ratio of 4.6 and showed strong surface plasmon absorption at wave length 800 nm. Pharmacokinetics of GNR after single I.V. administration (0.1 mg/kg) showed very short systemic circulating time (less than 3 h). On the other hand, tissue distribution of I.V. GNR (0.1 mg/kg) to normal animals showed preferential deposition in spleen tissue. Repeated administration of I.V. GNR resulted in preferential accumulation in both liver and spleen tissues. In addition, I.V. administration of GNR to Ehrlich carcinoma tumor bearing mice resulted in similar tissue distribution; tumor accumulation and anti-tumor effect compared to intratumoral administration. In conclusion, the concentration of GNR achieved within tumors microregions after I.V. administration was comparable to I.T. administration and sufficient to elicit tumoral growth arrest when coupled with laser-aided photoplasmonic treatment.
Citation Format: Ahmed M. Al-Abd, Ali A. Shabaka, Osama A. El-Shabrawy, Nemat A. Yassin, Sawsan S. Mahmoud, Siham M. El-Shenawy, Emad Al-Ashqar, Wael H. Eisa, Niveen M. Farag, Marwa A. El-Shaer, Nabila Salah, Mostafa A. El-Sayed. Efficacy and pharmacokinetics of gold nanorods coupled with laser-induced photoplasmonic therapy in solid tumor bearing mice. [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 3797. doi:10.1158/1538-7445.AM2014-3797
Abstract 3798: Shift of Cx43 isoform expression by PQ1 in SW480 human colorectal cancer cells
Authors: Bigelow Kristina M. , Nguyen Thu Annelise 
Published: May 2015

Abstract
Colorectal cancer is one of the most common cancers in men and women in the United States. On average, the risk of developing colorectal cancer is about 1 in 20 over an individuals' lifetime. Cancer cells exhibit many deficiencies in cell-to-cell communication, particularly gap junctional intercellular communication (GJIC). GJIC has been reported to diminish as cancer cells progress. Gap junctions are intercellular channels composed of connexin proteins, which mediate the direct passage of small molecules from one cell to the next. They are involved in the regulation of cell cycle, cell differentiation, and cell signaling. Previously, a class of substituted quinolines, known as PQs, demonstrated to increase GJIC in cancer cells and subsequently attenuated tumor growth. The goal of this study is to determine whether the mode of PQ1 is by directly regulating the connexin protein. The results show that the low expression of connexin 43 (Cx43) in SW480 human colorectal cancer cells remains constant in the presence of PQ1. However, PQ1 caused a change in isoform expression of Cx43 in which there was a shift of Cx43 expression from P0 to P1 and P2 isoforms. This suggests that the trafficking of Cx43 from the Golgi to the membrane occurs in the presence of PQ1. Furthermore, the results show that Cx43 interacts with PKCα in SW480 cells; however, PQ1 does not affect the interaction of Cx43 and PKCα, suggesting that the shift in Cx43 isoforms is not due to PKCα phosphorylation. These findings provide in part that the increase of GJIC by PQ1 is due to the shift in Cx43 from P0 to P1 and P2 isoforms in SW480 colorectal cancer cells.
Citation Format: Kristina M. Bigelow, Thu Annelise Nguyen. Shift of Cx43 isoform expression by PQ1 in SW480 human colorectal 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 3798. doi:10.1158/1538-7445.AM2014-3798
Abstract 3801: Small molecule inhibitor of Stat3 induces antitumor cell effects in vitro and antitumor effects in vivo against human glioma or breast cancer model
Authors: Yue Peibin , Lopez-Tapia Francisco , Tius Marcus , Turkson James 
Published: May 2015

Abstract
Aberrant activation of signal transducer and activator of transcription 3 (Stat3) is prevalent in many human cancers. Compelling evidence shows that constitutively-active Stat3 constitutes a point of convergence in oncogenic tyrosine kinase signaling, functioning as a master regulator of events crucial for tumorigenesis and malignant progression. We show herein that the small-molecule, SH5-07 abrogates constitutive activation of Stat3 and Stat3-dependent functions in human glioma and breast cancer cells. SH5-07 inhibits in vitro Stat3 DNA-binding activity with an IC50 value of 3.9 μM. Treatment of human glioma U251MG and breast cancer MDA-MB-231 cells that harbor aberrantly-active Stat3 with low micromolar SH5-07 blocks Stat3 phosphorylation, DNA-binding, and transcriptional activities in a time and dose-dependent manner. By contrast, SH5-07 shows little or no effect on the induction of pJAK2, pSrc, pErk1/2, and pShc in glioma and breast cancer cells. SH5-07 preferentially inhibited viability of human glioma and breast cancer cells that harbor aberrant Stat3 activity, with IC50 of 1.1-5.2 µM, compared to IC50 of 6.0-10.8 µM for cells that do not. Inhibition of aberrantly-active Stat3 by SH5-07 preferentially suppresses the anchorage-dependent and independent growth, induces apoptosis, and blocks migration and invasion in vitro of human glioma and breast cancer cells that harbor constitutively-active Stat3. Moreover, oral administration of SH5-07 inhibits the growth of human breast tumor xenografts in mice. Data together indicates SH5-07 is a promising small-molecule Stat3 inhibitor and a suitable drug candidate for clinical development.
Citation Format: Peibin Yue, Francisco Lopez-Tapia, Marcus Tius, James Turkson. Small molecule inhibitor of Stat3 induces antitumor cell effects in vitro and antitumor effects in vivo against human glioma or breast cancer 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 3801. doi:10.1158/1538-7445.AM2014-3801