bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2019: Photoimmunotherapy with an anti-EGFR antibody conjugated to an IRDye700 results in extensive and rapid cell death in vitro and in vivo in human pancreatic cancer cell lines
Authors: de Magalhães Nzola , Murakami Takashi , Heim Roger , Makings Lew , Garcia-Guzman Miguel , Kobayashi Hisataka , Hoffman Robert M. , Bouvet Michael 
Published: August 2015

Abstract
Photoimmunotherapy (PIT) of cancer utilizes tumor-specific monoclonal antibodies conjugated to a photosensitizer phthalocyanine dye IR700 which becomes cytotoxic upon irradiation with near infrared light. In this study, we aimed to evaluate the efficacy of PIT on human pancreatic cancer cells in vitro and in vivo in a nude mouse model. An in vitro cytotoxicity assay was used to determine cell death following treatment with PIT for Panc-1, MiaPaCa2, and BxPC-3 human pancreatic cancer cells. For in vivo determination of PIT efficacy, nude mice were implanted with BxPC-3 pancreatic tumors expressing green fluorescent protein (GFP). After tumor engraftment, the mice were divided into two groups: treatment with anti-EGFR-IR700 + 690 nm laser and treatment with 690 nm laser only. Anti-EGFR-IR700 (100 μg) was administered to the treatment group via tail vein injection 24 hours prior to therapy. Tumors were then exposed and treated with phototherapy at an intensity of 150 mW/cm2 for 30 minutes. Whole body imaging was done using an OV-100 small animal imaging system. Anti-EGFR-IR700 antibody bound to the BxPC3 cells to a high degree based on image co-localization. Anti-EGFR-IR700 caused extensive cancer cell killing after light activation compared to control cells in cytotoxicity assays. In the mouse experiments, the treatment group had significantly smaller tumors as measured by GFP than the control after just 96 hours. The present results indicate the high potential of PIT for pancreatic cancer therapy.
Citation Format: Nzola de Magalhães, Takashi Murakami, Roger Heim, Lew Makings, Miguel Garcia-Guzman, Hisataka Kobayashi, Robert M. Hoffman, Michael Bouvet. Photoimmunotherapy with an anti-EGFR antibody conjugated to an IRDye700 results in extensive and rapid cell death in vitro and in vivo in human pancreatic cancer cell lines. [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 2019. doi:10.1158/1538-7445.AM2015-2019
Abstract 2021: Integrin-alpha 8 as a potential therapeutic target in multiple myeloma early relapse
Authors: Ryu Jiyeon , Koh Youngil , Lee Hyun Jung , Chung Hyun Sub , Yoon Sung-Soo 
Published: August 2015

Abstract
Introduction: Multiple myeloma (MM) is an incurable neoplastic plasma cell disorder and many studies about MM biologic complexity have been reported. Despite the advances of treatment for MM, still many patients of MM exhibit early relapses and the mechanism of MM relapse is not well understood Patient with early relapse after autologous bone marrow transplantation need to be biologically characterized to better understand and reach complete remission.
Materials and Methods: To define altered gene expression and pathways, we performed microarray with bone marrow from 16 relapsed MM patients who underwent autologous bone marrow transplantation. Gene expression profile was compared (P &lt; 0.01) in 16 MM patients divided into two groups on the basis of their progression-free survival (PFS) at the point of 12 months or only four patients with shortest and longest duration of PFS.
Results: 77 genes over two fold up-regulated were identified and inputted in pathway enrichment analysis. To ascertain of the result, only four patients with shortest and longest duration of PFS were examined with same way of analysis that 163 genes over two fold up-regulated were inputted in KEGG pathway database. Interestingly, both of the analysis showed common up-regulated Integrin-α8 (ITGA8) and its associated pathway, ECM receptor interaction and focal adhesion, was identified (P &lt; 0.05). Several integrin family members are well documented to involve in MM disease progression but ITGA8 in MM is largely unknown. Functionally, we have investigated ITGA8 in MM cell lines that ITAG8 mediates MM cell adhesion, migration and drug resistance through bone marrow microenvironment which is regarded as leading events of MM relapse. Furthermore, its expression in MM is correlated with poor survival outcomes after autologous bone marrow transplantation.
Conclusion: Our study demonstrated that gene expression in MM patients showed distinctly different pattern between early relapse and late relapse. Additionally, our speculated specific gene up-regulated in early relapse in MM, ITGA8, is a potential prognostic marker and suggests attractive target for future research.
Citation Format: Jiyeon Ryu, Youngil Koh, Hyun Jung Lee, Hyun Sub Chung, Sung-Soo Yoon. Integrin-alpha 8 as a potential therapeutic target in multiple myeloma early relapse. [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 2021. doi:10.1158/1538-7445.AM2015-2021
Abstract 2026: G0S2 functions as a tumor suppressor gene through inhibition of c-Myc
Authors: Yim Christina Y. , Sekula David J. , Freemantle Sarah J. , Dmitrovsky Ethan , Spinella Michael J. 
Published: August 2015

Abstract
G0/G1 switch gene 2 (G0S2) is a direct retinoic acid target gene that is widely expressed in diverse organs and has been reported to have a role in adipose lipolysis by negatively regulating adipose triglyceride lipase (ATGL). G0S2 is also commonly silenced by DNA methylation in a variety of solid tumors including glioma, head and neck and lung cancers, and G0S2 induction is associated with retinoic acid-mediated clinical remissions in acute promyelocytic leukemia. This evidence suggests that G0S2 may possess tumor suppressor activity although definitive proof and mechanistic details are lacking. We now clearly demonstrate using G0S2 null immortalized mouse embryonic fibroblasts (MEFs) that G0S2 can function to oppose oncogene-induced transformation. G0S2 null MEFs were readily transformed with H-RAS or EGFR while wild-type MEFs were not. Importantly, re-introduction of G0S2 reversed H-RAS transformation of G0S2 null MEFs. Although G0S2 is a known regulator of fat metabolism through attenuating ATGL activity, we found that G0S2 repression of oncogene-induced transformation was independent of ATGL inhibition. Detailed microarray analysis demonstrated that G0S2 knockout alone upregulated gene signatures associated with transformation, proliferation and Myc transcriptional responses. G0S2 knockout also induced c-Myc expression at the transcript and protein level. Finally, transient and stable shRNA-mediated repression of c-Myc completely abrogated oncogene-induced transformation of G0S2 null MEFs. Taken together, these findings indicate that G0S2 can function as a tumor suppressor by opposing Myc. Studies to elucidate the mechanism underlying G0S2 regulation of Myc are ongoing. Understanding the functions and mechanisms of this novel tumor suppressor pathway may lead to new pharmacologic strategies for many cancers where G0S2 is silenced.
Citation Format: Christina Y. Yim, David J. Sekula, Sarah J. Freemantle, Ethan Dmitrovsky, Michael J. Spinella. G0S2 functions as a tumor suppressor gene through inhibition of c-Myc. [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 2026. doi:10.1158/1538-7445.AM2015-2026
Abstract 2028: RUNX3 knockdown inhibited oral cancer-induced bone destruction via reducing TGF-β-dependent responses
Authors: Park Junhee , Chung Won-Yoon , Park Kwang-Kyun 
Published: August 2015

Abstract
Oral cancer ranks among the top 10 commonly diagnosed cancers. It easily invades underlying jaw bones and causes severe psychological and physical problems. When oral cancer cells infiltrate into jaw bones, survival rate of the patient is significantly decreased. Therefore, attention has been focused on molecular diagnostics and targeted therapy for oral cancer-induced bone destruction. However, there remains a lack of reliable biomarkers that can distinguish between bone-invasive and non-invasive oral cancers despite the recent advances in the field. The Runt domain transcription factor, RUNX3, has been found to be a tumor suppressor in many cancers through promoting transforming growth factor-β (TGF-β)-induced growth inhibition. However, the role of RUNX3 in oral cancer remains controversial. Here, we investigated whether RUNX3 has a critical role in oral cancer-induced bone destruction. In mice inoculated with RUNX3 knockdown oral cancer cells, tumor growth and bone destruction were significantly reduced. In oral cancer cells, RUNX3 knockdown significantly reduced cell viability in TGF-β-stimulated cells compared to unstimulated cells. Cell cycle analysis revealed that RUNX3 knockdown induced G1-specific cell-cycle arrest in the cancer cells without TGF-β treatment but G2-specific cell-cycle arrest in response to TGF-β treatment. RUNX3 knockdown inhibited cell migration and invasion in the absence or presence of TGF-β by changing both basal and TGF-β-induced level of epithelial-to-mesenchymal transition-related proteins. Furthermore, RUNX3 knockdown reduced parathyroid hormone-like protein expression, a major osteolytic factor, in oral cancer cells with or without TGF-β. We confirmed that RUNX3 knockdown in cancer cells decreased receptor activator of nuclear factor-kappaB ligand/osteoprotegerin ratio in osteoblastic hFOB1.19 cells treated with cancer cell-derived conditioned media. In summary, RUNX3 promotes oral cancer-induced bone destruction by enhancing interactions between cancer cells and bone cells as well as promoting malignant behavior of cancer cells. Therefore, RUNX3 may be a useful biomarker and potential therapeutic target for bone invasion of oral cancer.
Citation Format: Junhee Park, Won-Yoon Chung, Kwang-Kyun Park. RUNX3 knockdown inhibited oral cancer-induced bone destruction via reducing TGF-β-dependent responses. [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 2028. doi:10.1158/1538-7445.AM2015-2028
Abstract 2035: Targeting the hyperactive polyisoprenylated monomeric G-proteins functions in pancreatic cancer
Authors: Nkembo Augustine T. , Salako Olufisayo , Poku Rosemary , Mazu Tryphon , Aguilar Byron , Flores-Rozas Hernan , Lamango Nazarius S. 
Published: August 2015

Abstract
Pancreatic cancer (PC) incidence is a major healthcare problem as the five-year survival rate remains below 5%. Over 90% of PC cases harbor the hyperactive K-Ras mutant protein. Polyisoprenylation processes facilitate the proper localization and signaling of K-Ras whose gain-in-function mutations drive uncontrolled cell survival, differentiation and proliferation. Efforts to target and disrupt this pathway and signaling for cancer therapy have been unsuccessful. The purpose of this study was to determine the effects of polyisoprenylated cysteinyl amide inhibitors (PCAIs) as a potential novel class of small molecules for PC therapy. The effects of the PCAIs on cell viability, proliferation, survival, apoptosis, migration, colony formation and cytoskeletal F-actin organization in four human PC cell lines representing wild type K-Ras (BxPC-3), Mutant K-Ras (MIAPaCa-2 and Panc10.05) and mucins (HPAF-II) were examined. PCAIs induced apoptosis with EC50 values ranging from 2.4 to 5.1, 2.0 to 7.3, 1.8 to 3.3 and 7.0 to 33 μM in MIAPaCa-2, BxPC-3, Panc10.05 and HPAF-II cells, respectively. At 0.2 μM, PCAIs arrested MIAPaCa-2 cells at the G0/G1 phase and significantly inhibited cell migration in the wound-healing assay. MIAPaCa-2 cells transfected with a plasmid expressing a protein that fluoresces red when interacting with F-actin were used to determine the PCAIs effects on F-actin organization. Treatment with PCAIs disrupted the F-actin structures causing the cells to shrink and become rounded upon treatment with PCAIs concentrations as low as 0.2 μM. The ability of PCAIs to disrupt these biological phenomena in pancreatic cancer cells shows that PCAIs may halt progression in tumors with the hyperactive K-Ras mutations.
Citation Format: Augustine T. Nkembo, Olufisayo Salako, Rosemary Poku, Tryphon Mazu, Byron Aguilar, Hernan Flores-Rozas, Nazarius S. Lamango. Targeting the hyperactive polyisoprenylated monomeric G-proteins functions in pancreatic 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 2035. doi:10.1158/1538-7445.AM2015-2035
Abstract 2048: Evidence that MTAP acts as a genetic switch to inhibit tumor formation
Authors: Tang Baqing , Kruger Warren 
Published: August 2015

Abstract
Methylthioadenosine Phosphorylase (MTAP) deficiency is widely observed in a variety of human tumor and tumor derived cell lines, suggesting that MTAP may play a role in tumorigenesis. It is an enzyme that catalyzes phosphorylation of 5′deoxy-5′-methylthioadenosine (MTA), a byproduct of in vivo polyamine biosynthesis. To elucidate the mechanism by which MTAP inhibits tumor formation, we created a MCF-7 breast cancer derived cell line that expresses MTAP under a doxycycline (DOX) regulated promoter. In this cell line MTAP expression was undetectable in the absence of DOX and could be detected as early as 4 hours after DOX induction. MTAP expression caused a decrease in cell proliferation, soft-agar colony formation, and cell migration. Microarray studies revealed several genes that were regulated by MTAP. For two of the genes that were identified, AGPAT4 and IGFBP1, we examined the relationship between their mRNA levels and MTAP mRNA levels by qRT-PCR. Surprisingly, a brief pulse of MTAP expression was able to alter mRNA levels of these genes and this change in mRNA persisted even when MTAP RNA levels were no longer detectable. Our findings show that MTAP expression suppresses tumorigenesis and it may act as a genetic switch.
Citation Format: Baqing Tang, Warren Kruger. Evidence that MTAP acts as a genetic switch to inhibit tumor formation. [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 2048. doi:10.1158/1538-7445.AM2015-2048
Abstract 2056: SIRT1 silencing suppresses prostate cancer growth and metastasis in an orthotopic prostate cancer mouse model
Authors: Dai Yan , Zhu Lijia , Cho Elizabeth , Hagiwara Audrey , Faller Douglas , Kim Sun-Jin , Fidler Isaiah J. , Amaro Marina 
Published: August 2015

Abstract
Tumor environment is critical for tumor growth and progression, and orthotopic mouse model allows accurately study tumor development in an appropriate tumor environment. SIRT1, a class III histone deacetylase, has been shown overexpressed in prostate cancer and is a biomarker for prostate cancer recurrence. Although these data have suggested the importance of the role SIRT1 plays in prostate cancer progression, the role of SIRT1 in tumor growth and progression within, specifically, a prostate tumor environment has not been established.
In this study, we established an advanced prostate cancer PC3MM2 orthotopic mouse model to study the effects of SIRT1 silencing on prostate cancer growth and progression. Our data has shown that SIRT1 knockdown greatly suppresses tumor formation within a prostate tumor environment, along with an inhibition of metastasis to bone and liver. To further study the mechanism by which SIRT1 controls tumor growth and progression, we demonstrated that SIRT1 silencing reduces prostate cancer cell adhesion to cell matrix, and that this silencing also suppresses cancer cell growth and colony formation in a cell matrix dependent manner. Moreover, our data showed that SIRT1 regulates integrin expression and focal adhesion complex formation. Furthermore, we shows that SIRT1 silencing from prostate cancer cell significantly inhibited human umbilical vein endothelial cell (HUVEC) tube formation, suggests an important role of SIRT1 in prostate cancer angiogenesis. Thus, we have reported for the first time that SIRT1 plays a critical role in prostate cancer growth and progression using orthotopic mouse model, and demonstrated for the first time that SIRT1 regulates integrin expression, focal adhesion formation, tumor cell and matrix interaction, and angiogenesis. These results suggest SIRT1 regulates prostate cancer growth and progression through multiple mechanisms and that SIRT1 is a potential target in prostate cancer treatment.
Citation Format: Yan Dai, Lijia Zhu, Elizabeth Cho, Audrey Hagiwara, Douglas Faller, Sun-Jin Kim, Isaiah J. Fidler, Marina Amaro. SIRT1 silencing suppresses prostate cancer growth and metastasis in an orthotopic prostate cancer mouse model. [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 2056. doi:10.1158/1538-7445.AM2015-2056
Abstract 206: Development of a molecular imaging system based on the transcriptional activity of the DD3/PCA3 non-coding RNA for imaging specifically the prostate cancer cells
Authors: Jain Pallavi , Neveu Bertrand , Fradet Yves , Pouliot Frederic 
Published: August 2015

Abstract
Development of a molecular imaging system based on the transcriptional activity of the DD3/PCA3 non-coding RNA for imaging specifically the prostate cancer cells
OBJECTIVE: Molecular imaging plays an important role in oncology for staging of tumors. Unfortunately, the specificity and sensitivity of current techniques remains low. This study aims to improve the existing imaging system based on transcriptional activation, named as “Two -Step- Transcriptional Amplification (TSTA) system”, with the goal to precisely image in vivo prostate cancer cells (PCa) by Positron Emission Tomography (PET). We have studied the potential of DD3/PCA3 promoter, a gene specifically expressed in PCa, to achieve this goal.
METHODS: Various adenovirus constructs incorporating the DD3 promoter, the TSTA system and the Firefly luciferase reporter gene were generated and their specificity for PCa cells was tested in transient infection. By molecular engineering, we have improved the TSTA system and generated the 3STA. The luciferase activities of DD3-TSTA, DD3-3STA and PSA-TSTA (Prostate Specific Antigen) were compared in vivo by bioluminescence in xenograft mouse models. Ex vivo prostate biopsy from RP (radical prostatectomy) specimen were exposed to DD3-3STA and luciferase expression was evaluated using bioluminescence and Immunohistochemistry.
RESULTS: The DD3 promoter activity is both specific to prostate and cancer cells. When DD3 promoter is incorporated in the amplification systems TSTA and 3STA, it is specific to PCa cells and its activity is amplified 32 and 95 times, respectively, when compared to the activity of the DD3 promoter alone. Moreover, activity of DD3-TSTA and DD3-3STA is androgen-independent. In vivo, DD3-3STA activity is comparable to that obtained with the PSA-TSTA whose activity can be imaged by PET. DD3-3STA could detect primary prostate cancer cells ex vivo in prostate biopsy obtained from RP specimen (Figure 1).
CONCLUSIONS: The new system DD3-3STA allows specific and sensitive imaging of PCa cells. The new amplification system 3STA allows the DD3 promoter to produce reporter signal high enough to be detected by PET, a technology available in the clinic.
Citation Format: Pallavi Jain, Bertrand Neveu, Yves Fradet, Frederic Pouliot. Development of a molecular imaging system based on the transcriptional activity of the DD3/PCA3 non-coding RNA for imaging specifically the prostate cancer 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 206. doi:10.1158/1538-7445.AM2015-206
Abstract 2066: Aberrant upregulation of 14-3-3 gamma promotes mononucleated polyploidization in human lung cancers
Authors: Gomes Cecil J. , Harman Michael , Martinez Jesse , Centuori Sara 
Published: August 2015

Abstract
Advanced non-small cell lung cancers (NSCLC), frequently display increased expression of 14-3-3 gamma (14-3-3γ); a scaffolding protein shown to have oncogenic capacity. This aberrant increase in expression has also been correlated with poorer survival, indicating that upregulation of 14-3-3γ results in a more aggressive tumor phenotype. Our lab is in pursuit of characterizing the mechanisms driving this more advanced cancer phenotype. One such mechanism currently being investigated is 14-3-3γ's ability to promote polyploidization in lung cancer cells. Polyploidization is a known mechanism observed to increase tumorigenicity, resistance to conventional therapies, and theorized to promote chromosomal instability. Our data shows that overexpression of 14-3-3γ results in a subpopulation of cells that harbor mono-nucleated tetraploid DNA content. This suggests that elevated expression of 14-3-3γ promotes aberrant cell cycle progression, either by mechanisms of an abortive mitosis known as endomitosis, or by means of endoreplication, a re-replication event occurring in the absence of mitosis. Further analyses have confirmed that these cells, in the absence of tumor suppressor p53, remain viable and undergo cellular division; supporting our hypothesis that upregulation of 14-3-3γ is resulting in an unstable, tumorigenic tetraploid cell state. Taken together, our data elucidates one role by which 14-3-3γ may be contributing to a more aggressive tumor phenotype in patients with advanced NSCLC.
Citation Format: Cecil J. Gomes, Michael Harman, Jesse Martinez, Sara Centuori. Aberrant upregulation of 14-3-3 gamma promotes mononucleated polyploidization in human lung cancers. [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 2066. doi:10.1158/1538-7445.AM2015-2066