bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1430: Transcriptional regulatory loops among SNAI1, TWIST1, ZEB1, and ZEB2 defines the epithelial-mesenchymal transition (EMT) spectrum in epithelial ovarian cancer (EOC)
Authors: Tan Ming , Chuang Vin Yee , Tan Tuan Zea , Thiery Jean Paul , Huang Ruby Yun-Ju 
Published: August 2015

Abstract
Epithelial-mesenchymal transition (EMT) refers to a sequential phenotypic transformation process from epithelial to mesenchymal states, which is well defined in embryonic development. During cancer progression, cancer cells undergo EMT progressively loss epithelial characteristics and gain mesenchymal properties and are correlated with acquisition of increased capacity of metastasis and resistance to chemo- and immunotherapy. Although EMT is intensively studied in various types of cancers, its role in epithelial ovarian cancer (EOC), the most lethal gynaecological malignancy in the world, has yet to be elucidated. Previously, our group proposed the concept of an EMT Spectrum which encompasses the hybrid “intermediate” phenotype as well as the bona-fide epithelial and mesenchymal phenotypes. EOC cells harboring intermediate phenotypes showed distinct functional differences in in vitro aggressiveness. We hypothesize that EMT transcriptional drivers, SNAI1, TWIST1, ZEB1, and ZEB2, contribute to different biological consequences and show different hierarchy to induce step-wise phenotypic changes along the EMT Spectrum. EMT models were established by overexpressing classic EMT drivers in selected EOC cell lines with different EM phenotypes at different positions of EMT spectrum to test the intrinsic transcriptional regulation networks. Quantitative PCR (QPCR) was performed to examine the cross regulation among the EMT transcriptional drivers and their downstream targets. There was no cross regulation detected in the most epithelial cell line, PEO1, while a simple, repressive regulatory net was found in the OVCA420 cell line. The cell line with an intermediate phenotype, OVCA429, showed a complex double positive feedback loop among the EMT drivers. The divergence in the transcriptional regulatory loops correlated with the differences of in vitro EMT functions. These results indicate that there is a dynamic EMT transcriptional regulatory network to further define the EMT spectrum. In conclusion, this study demonstrates that cancer cells with an intermediate phenotype are more easily to be pushed along the EMT spectrum due to their ability to initiate a complex transcriptional feedback regulatory loop.
Citation Format: Ming Tan, Vin Yee Chuang, Tuan Zea Tan, Jean Paul Thiery, Ruby Yun-Ju Huang. Transcriptional regulatory loops among SNAI1, TWIST1, ZEB1, and ZEB2 defines the epithelial-mesenchymal transition (EMT) spectrum in epithelial ovarian cancer (EOC). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1430. doi:10.1158/1538-7445.AM2015-1430
Abstract 1443: BMP-2 induces motility and invasiveness of colon cancer through upregulation of cancer stem cell
Authors: Kim Bo Ram , Kim Jung Lim , Park Seong Hye , Jeoung Yoon A , Lee Sun Il , Min Byoung-Wook , Oh Sang Cheul 
Published: August 2015

Abstract
The majority of deaths in cancer patients are will present with metastasis and relapses. One of the key steps in metastasis is the migration, and Cancer stem cells(CSCs) activate migration. So, targeting of CSC is an important strategy for cancers. Bone morphogenetic protein(BMP) signaling, member of the TGF-β superfamily, plays an important role in development of bone and in regulation of stem cell properties. In Previous study, Bone morphogenetic protein(BMP) signaling has been associated with various types of cancers. BMPs contributes through autocrine and paracrine mechanisms to tumor development, invasion and metastasis. However, their roles and mechanisms are unclear. In this study, we investigated the function of BMP-2 and relevance BMP-2 and CSCs in Colon cancer cells.
First, We compared the endogenous protein level of parental and spheroid cells by western blotting. The spheroid cells showed higher level of EMT(Epithelial mesenchymal transition) markers N-Cadherin and Snail, CSC markers (EpCAM and CD133), and p Smad1/5 known BMP-2 downstream than the corresponding parental cells. Then expression of EpCAM and CD133 was confirmed by flow cytometry. We found that BMP-2 plays a key role in Cancer stem cell. To determine function of BMP-2 in Colon cancer cells, we stimulated the colon cancer cells with recombinant human BMP-2. Stimulation of BMP-2 increased EMT, CSC markers(EpCAM and CD133). In addition, BMP-2 enhanced cell motility, and invasiveness by wound healing and matrigel invasion assay. These results indicated BMP-2 signaling pathway enhance metastasis through increase of CSC portion. Blockade of BMP-2 pathway by Noggin(BMP2 antagonist) or Smad1/5 siRNA inhibited BMP2-induced EMT marker, MMP2, and CSC portion. The morphologic changes though the EMT process were monitored by immunofluorescence staining and Western blot for EMT markers. And Blockade of BMP-2 pathway inhibited cell motility and invasiveness.
Our findings suggest that BMP-2 signaling regulates metastatic potential through regulation of CSCs in colon cancer cell.
Citation Format: Bo Ram Kim, Jung Lim Kim, Seong Hye Park, Yoon A Jeoung, Sun Il Lee, Byoung-Wook Min, Sang Cheul Oh. BMP-2 induces motility and invasiveness of colon cancer through upregulation of cancer stem cell. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1443. doi:10.1158/1538-7445.AM2015-1443
Abstract 1444: Docosahexaenoic acid reduces cancer cell migration may link with actin binding proteins and miRNA 17-92 cluster expressions changes
Authors: Ali Mehboob , Heyob Kathryn M. , Rogers Lynette K. 
Published: August 2015

Abstract
Metastasis and progression, reflected by higher migration and longer cell survival, are major contributing factors in making cancers the leading cause of death worldwide. Cancer cells exhibit higher migration rates and greater cell viability facilitated by actin binding protein-mediated cytoskeletal remodeling and secondary messengers (cAMP and/or cGMP) signaling. Studies have shown that docosahexaenoic acid (DHA), a poly unsaturated fatty acid, inhibits cancer cell metastatic phenotype. Moreover, miRNA-17∼92 cluster has been reported to be highly expressed in metastasis. Therefore, we put forward a hypothesis that DHA will induce changes in actin binding protein dynamics and miRNA-17∼92 cluster expression to inhibit cancer cell migration and viability. Non-cance (MLE12) and cancer (A549) cells were treated with 8-Br-cAMP and/or DHA for 30 min, 3h, 6h and 24h. Actin binding proteins (profilin, cofilin, vimentin and gelsolin) and miRNA-17∼92 cluster expression were analyzed by western blot and qRT PCR respectively. Cell migration was estimated by wound assay and transwell apparatus. F-actin content and actin binding proteins were measured using confocal microscopy at the leading edges of wound. Proliferation and cell viability were estimated by flow cytometer, IF using ki-67, and cleaved-caspase-3 antibodies. F-actin content, cell migration and proliferation were increased while cell viability was decreased by cAMP. DHA treatment reverses the increase in actin content and cell migration in cancer cells but not in non-cancer cells. These findings correlate with changes in actin binding protein content and miRNA 17∼92 cluster expression. Thus, DHA specifically inhibits cancer cell migration, proliferation, and viability and this effect correlates with decreases in actin binding protein levels and miRNA-17∼92 cluster expression. In conclusion, DHA supplementation suppresses cellular changes related to metastatic potential in cancer cells and could provide therapeutic potential against cancer cell metastasis. Moreover, actin binding proteins and miRNA-17∼92 cluster expression could serve as innovative therapeutic targets and biomarkers for cancer progression.
Citation Format: Mehboob Ali, Kathryn M. Heyob, Lynette K. Rogers. Docosahexaenoic acid reduces cancer cell migration may link with actin binding proteins and miRNA 17-92 cluster expressions changes. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1444. doi:10.1158/1538-7445.AM2015-1444
Abstract 1453: Methods for developing patient derived xenografts in athymic nude mice
Authors: Marlow Laura A. , Miller James L. , Edenfield Brandy , Mathias Adam C. , Dawson Louis K. , Durham William F. , Mullin Robert J. , Small Daniel L. , Synnott Aidan J. , Wu Kevin , Copland John A. 
Published: August 2015

Abstract
Patient derived xenografts (PDX) mouse models for many types of cancer have been developed recapitulating therapeutic responses in the patient for which the PDX model was derived. Essentially, live surgically resected or biopsy tumor tissues are directly implanted into immune incompetent mice to develop in vivo models to test therapies, follow tumor progression (gene mutations that occur with patient tumor progression do so in mice) or to better understand drug resistance. However, the use of PDX models also has its limitations and challenges. Our laboratory has attempted to develop PDX models in athymic nude mice for numerous cancer histotypes such as bladder, brain, breast, colon, kidney, lung, melanoma, ovarian, pancreas, sarcoma and thyroid. While melanoma and colon cancers have very high tumor take rates (73 - 100%), the other cancer histotypes do not (14 - 50%). We share our experience for each cancer histotype and the techniques used to enhance the success rates in athymic nude mice. We also address the other challenges that include expansion of tumors after cryopreservation and conversion of human tumors to mouse tumors and spontaneous lymphomas. We provide methods to test for human versus mouse content that include QPCR and immunohistochemistry
Citation Format: Laura A. Marlow, James L. Miller, Brandy Edenfield, Adam C. Mathias, Louis K. Dawson, William F. Durham, Robert J. Mullin, Daniel L. Small, Aidan J. Synnott, Kevin Wu, John A. Copland. Methods for developing patient derived xenografts in athymic nude mice. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1453. doi:10.1158/1538-7445.AM2015-1453
Abstract 1456: Efficacy of photo-immunotherapy in combination with surgical resection on a pancreatic cancer patient derived orthotopic xenograft (PDOX)
Authors: Hiroshima Yukihiko , Maawy Ali , Murakami Takashi , Magalhães Nzola De , Kawaguchi Daisuke , Matsuo Kenichi , Tanaka Kuniya , Bouvet Michael , Hoffman Robert M. , Endo Itaru 
Published: August 2015

Abstract
Complete tumor resection improves overall survival of pancreatic cancer patients. We have previously showed that UVC irradiation in combination with fluorescence-guided surgery (FGS) completely cured metastatic pancreatic cancer by eradicating minimal residual cancer after FGS. Recently, photoimmunotherapy (PIT), that uses a target-specific photosensitizer based on a near-infrared (NIR) phthalocyanine dye, IR700, demonstrated in vivo tumor shrinkage after irradiation with NIR light without any side effects. In this study, we used a clinically applicable model of pancreatic cancer to examine the use of PIT to eradicate minimal residual cancer of a patient derived orthotopic xenograft (PDOX). We found that anti-CEA-IR700 could label and illuminate PDOX strongly enough for PIT in both subcutaneous and orthotopic models. Furthermore, we succeeded in detecting fluorescence from the minimal residual cancer of the PDOX. The local recurrence rate of BLS only and BLS + PIT group was 85.7% and 28.6%, respectively. BLS + PIT tended to reduce the recurrence rate compared to BLS only, and there was marginally significant difference (p = 0.051). The average recurrent tumor weight of BLS only and BLS + PIT group was 1149.0 ± 794.6 mg and 210.8 ± 336.9 mg, respectively. The average recurrent tumor weight of BLS + PIT group was significantly less than BLS only (p = 0.015). In conclusion, anti-CEA-IR700 is able to label and illuminate the PDOX strongly enough for PIT. PIT reduces recurrence by eradicating microscopic disease undetectable with BLS, and might be applicable to pancreatic cancer patients.
Citation Format: Yukihiko Hiroshima, Ali Maawy, Takashi Murakami, Nzola De Magalhães, Daisuke Kawaguchi, Kenichi Matsuo, Kuniya Tanaka, Michael Bouvet, Robert M. Hoffman, Itaru Endo. Efficacy of photo-immunotherapy in combination with surgical resection on a pancreatic cancer patient derived orthotopic xenograft (PDOX). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1456. doi:10.1158/1538-7445.AM2015-1456
Abstract 1458: Characterization of novel thyroid PDX models and their response to combination therapies
Authors: Marlow Laura A. , Mathias Adam C. , Dawson Louis K. , Durham William F. , Meshaw Kenneth A. , Mullin Robert J. , Small Daniel L. , Synnott Aidan J. , Milosevic Dragana , Netzel Brian C. , Grebe Stefan K. , Wu Kevin , Smallridge Robert C. , Copland John A. 
Published: August 2015

Abstract
Patient derived xenografts (PDX) mouse models for many types of cancer have demonstrated therapeutic responses similar to those seen in patients. Thus, resected patient tumor tissue directly implanted into immune compromised mice followed by therapy and tumor growth analysis is thought to be the closest preclinical model to predict patient therapeutic responses. To date, few models are available for the different histotypes of thyroid cancer derived from follicular thyrocytes; these include papillary, follicular, Hurthle cell, squamous and anaplastic thyroid carcinoma. We have developed eight PDX models in athymic nude mice representing all of these subtypes. The models have been extensively characterized for mutational status (i.e. BRAF, telomerase, RAS, PTEN, TP53, RB, etc) as well as validation by short tandem repeat (STR) analysis to match that of the originating patient tumor tissue. Squamous and anaplastic thyroid cancers are rare tumor types with no FDA approved therapies. Each model demonstrated their own unique responses to radiation, cytotoxic or molecular targeted therapies such as doxorubicin, sorafenib (tyrosine kinase inhibitor), cisplatin, paclitaxel, sunitinib (tyrosine kinase inhibitor), erlotinib (EGFR inhibitor), trametinib (MEK inhibitor) and vemurafenib (BRAF inhibitor). We expect that these models may provide useful in vivo models for thyroid cancer research as well as models for therapeutic guidance based upon histotype, mutational status and response to therapies.
Citation Format: Laura A. Marlow, Adam C. Mathias, Louis K. Dawson, William F. Durham, Kenneth A. Meshaw, Robert J. Mullin, Daniel L. Small, Aidan J. Synnott, Dragana Milosevic, Brian C. Netzel, Stefan K. Grebe, Kevin Wu, Robert C. Smallridge, John A. Copland. Characterization of novel thyroid PDX models and their response to combination therapies. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1458. doi:10.1158/1538-7445.AM2015-1458
Abstract 146: The long noncoding RNA MALAT1 promotes hypoxia-driven angiogenesis by upregulating pro-angiogenic gene expression in neuroblastoma cells
Authors: Tee Andrew E. , Liu Peiyan , Maag Jesper , Song Renhua , Li Jinyan , Cheung Belamy B. , Haber Michelle , Norris Murray D. , Marshall Glenn M. , Dinger Marcel , Liu Tao 
Published: August 2015

Abstract
Neuroblastoma is the most common solid tumour during early childhood, and accounts for 15% of all childhood cancer death. One of the key features of neuroblastoma is aggressive progression due to tumour-driven angiogenesis. However, the mechanism through which neuroblastoma cells drive angiogenesis is unclear. Here we showed that the long noncoding RNA MALAT1 was over-expressed in human neuroblastoma cells under hypoxic condition, the condition which triggers pro-angiogenic switch and angiogenesis. In vitro angiogenesis assays demonstrated that conditioned medium from neuroblastoma cells transfected with MALAT1 siRNAs, compared with conditioned medium from neuroblastoma cells transfected with control siRNAs, induced considerably less endothelial cell migration, invasion and vascular sprouting under hypoxic condition. Affymetrix microarray differential gene expression study showed that one of the genes most significantly down-regulated by MALAT1 siRNAs in human neuroblastoma cells under hypoxic condition, was fibroblast growth factor (FGF). RT-PCR and immunoblot analyses confirmed that MALAT1 siRNAs reduced FGF mRNA and protein expression, and in vitro angiogenesis assays demonstrated that forced over-expression of FGF in neuroblastoma cells blocked MALAT1 siRNA-mediated reduction in endothelial cell migration, invasion and vascular sprouting. Taken together, our data suggest that over-expression of MALAT1 in human neuroblastoma cells plays an important role hypoxia-driven angiogenesis by up-regulating FGF mRNA expression.
Citation Format: Andrew E. Tee, Peiyan Liu, Jesper Maag, Renhua Song, Jinyan Li, Belamy B. Cheung, Michelle Haber, Murray D. Norris, Glenn M. Marshall, Marcel Dinger, Tao Liu. The long noncoding RNA MALAT1 promotes hypoxia-driven angiogenesis by upregulating pro-angiogenic gene expression in neuroblastoma cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 146. doi:10.1158/1538-7445.AM2015-146
Abstract 1462: Characterization of patient-derived bladder cancer xenografts: role of xCT in response to cisplatin
Authors: Elbanna May F. , Ciamporcero Eric , Ramakrishnan Swathi , Adelaiye Remi , Shen Li , Orillion Ashley , Ku Sheng-Yu , Chintala Sreenivasulu , Pili Roberto 
Published: August 2015

Abstract
Background: A major challenge in cancer drug development has been largely attributed to the inability of cell lines to recapitulate the heterogeneity of human tumors. Patient derived xenografts (PDX) represent a major advance as they are more representative of the clinical setting. However, appropriate characterization of PDXs is necessary to guide biomarker driven drug discovery research. Methods: H&E staining was used to compare the original patient tumors with PDX developed from cystectomy specimens to validate morphological similarity. Immunohistochemical (IHC) staining for cytokeratins (CK) 5/6 & 20 and EMT markers E cadherin and vimentin were used to identify whether these tumors represent a basal or a luminal subtype. In addition, Western blot and RT-PCR analysis were performed to assess markers of epithelial-to-mesenchymal transition (EMT). Therapeutic response to cisplatin was evaluated both in vitro and in vivo. Furthermore, expression of xCT (cystine transporter), one of the known cisplatin resistance markers, was determined by RT-PCR, Western blot and IHC in PDXs and cells. Results: Morphologically, we observed that our PDX models (RP-B-01 and RP-B-02) did not drift from the original patient tumors and they still retained their characteristic stromal features. Based on cytokeratin (CK) staining, we found both models to be CK 5/6 positive and CK 20 negative, suggesting a basal subtype of bladder cancer. Both PDXs, similarly to the original tumors, were E cadherin positive. However, cells derived from these tumors and cultured in vitro lost E cadherin and acquired vimentin expression, suggesting an EMT phenotype. When cells from PDX were transplanted back into mice they re-expressed E cadherin and lost vimentin expression, suggesting a reversion to MET. Despite no difference in cytokeratins and EMT markers between the two models, both PDX and cells isolated from PDXs had differential expression of xCT and possessed differential response to cisplatin treatment. RP-B01 expressed higher levels of xCT and was less responsive to cisplatin as compared to RP-B-02 which expressed lower levels of xCT. Conclusion: Differential expression of xCT in bladder cancer PDXs and cells correlated with cisplatin response, suggesting that pharmacological targeting of xCT in combination therapies will enhance cisplatin efficacy in bladder cancer.
Citation Format: May F. Elbanna, Eric Ciamporcero, Swathi Ramakrishnan, Remi Adelaiye, Li Shen, Ashley Orillion, Sheng-Yu Ku, Sreenivasulu Chintala, Roberto Pili. Characterization of patient-derived bladder cancer xenografts: role of xCT in response to cisplatin. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1462. doi:10.1158/1538-7445.AM2015-1462
Abstract 148: Transcriptome sequencing reveals PCAT5 - new ERG-regulated non-coding transcript in prostate cancer
Authors: Ylipää Antti , Kivinummi Kati , Annala Matti , Kohvakka Annika , Latonen Leena , Scaravilli Mauro , Kartasalo Kimmo , Leppänen Simo-Pekka , Karakurt Serdar , Seppälä Janne , Yli-Harja Olli , Tammela Teuvo L.J. , Zhang Wei , Visakorpi Tapio , Nykter Matti 
Published: August 2015

Abstract
Background: Prostate cancer (PC) is the second most common cancer among men. Most PC-related deaths are due to invasive tumors that are treated with therapies inhibiting androgen production or androgen receptor (AR) activity. After an initial response, tumors invariably progress to castration resistant prostate cancers (CRPCs) for which no effective cure exists.
Methods and Results: We used transcriptome sequencing to study fresh-frozen tissue specimens from 12 benign prostatic hyperplasias (BPHs), 28 PCs, and 13 CRPCs. Reference-based transcriptome assembly uncovered 145 previously unannotated intergenic PC and CRPC associated long non-coding transcripts (lncRNAs) or isoforms. One third of the transcripts were CRPC-specific. We showed that one of the novel transcripts, Prostate Cancer Associated Transcript 5 (PCAT5), expressed in half of the tumors, was likely regulated by ERG, the key transcription factor in ∼50% of prostate cancers. Genome-wide expression analysis of a PCAT5-positive prostate cancer cell line after PCAT5 knockdown suggested significant alterations in proliferation pathways. In vitro validation of the pathway alterations revealed concordantly dramatic effects in phenotype: stalling of cell growth, migration, invasion, and colony forming potential, and increase in the rate of apoptosis.
Conclusions: We identified the key differences between PC and CRPC in transcriptome level, and validated the oncogenic potential of a novel lncRNA in ERG-positive prostate cancers, PCAT5. Our study presents a number of putative lncRNA biomarkers for CRPC, and opportunities for therapeutic intervention.
Citation Format: Antti Ylipää, Kati Kivinummi, Matti Annala, Annika Kohvakka, Leena Latonen, Mauro Scaravilli, Kimmo Kartasalo, Simo-Pekka Leppänen, Serdar Karakurt, Janne Seppälä, Olli Yli-Harja, Teuvo L.J. Tammela, Wei Zhang, Tapio Visakorpi, Matti Nykter. Transcriptome sequencing reveals PCAT5 - new ERG-regulated non-coding transcript in prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 148. doi:10.1158/1538-7445.AM2015-148