bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 3862: In vivo chemopreventive of pseudosemiglabrin via inhibition of tumor angiogenesis and manipulation of hormones in estrogen-responsive breast cancer
Authors: Hassan Loiy E. Ahmed 
Published: July 2017

Abstract
Breast cancer is the most frequently diagnosed form of malignancy and the second leading cause of death in Western women. Mortality and most of the complications associated with breast cancer are due to metastasis developing in regional lymph nodes and in distant organs, including bone, lung, liver and brain. Chemopreventive is administration of chemical agents to prevent the initiational and promotional events associated with carcinogenesis. Some chemopreventive agents can prevent reaction or attacking molecules by different ways, these agents can suppress growth factors or signaling pathway. On this study we examined (-)-Pseudosemiglabrin (SSG) a natural compound extracted from Tephrosia apollinea on breast cancer cells and tumor vascularization in vitro and in vivo. Hormone sensitive breast cancer cell MCF-7 was found subtitle susceptible to SSG, it showed profound antitumorgeneis via inhibiting breast cancer cell migration, invasion and colony formation in vitro settings. In silico investigation of potential PARP inhibitor, SSG showed high binding affinity comparable to Rucaparib (standard PARP inhibitor). The natural compound significantly inhibited the sprouting of new blood vessels in ex vivo rat aorta ring assay; the antiangiogenic efficacy is perturbed by targeting VEGF expression and VEGFR phosphorylation. SSG completely inhibited the onset of breast cancer in animals pretreated with the compound. Molecular docking study showed that SSG binds to active site of Aromatase (the enzyme responsible for a key step in the biosynthesis of estrogens) with binding affinity better than standard aromatase inhibitor (Arimidex), moreover the compound has inhibitory activity against estrogen receptor in the breast cancer cells comparable to Tamoxifen. Our findings reveal that (-)-Pseudosemiglabrin can potentially be beneficial in preventing breast cancer in high-risk women or it can be adjuvant therapy with standard chemotherapy or even can be used for the treatment of women who have been diagnosed with breast cancer.
Note: This abstract was not presented at the meeting.
Citation Format: Loiy E. Ahmed Hassan. In vivo chemopreventive of pseudosemiglabrin via inhibition of tumor angiogenesis and manipulation of hormones in estrogen-responsive breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3862. doi:10.1158/1538-7445.AM2017-3862
Abstract 3866: Investigating the role of class I HDACs in Ewing sarcoma pathology
Authors: Heyking Kristina von , Hensel Tim , Singer Julia , Schmidt Oxana , Burdach Stefan , Richter Günther H. 
Published: July 2017

Abstract
Introduction: Recent evidence demonstrated that a low mutation rate seems a general feature of pediatric cancers. Ewing sarcoma (ES) is defined by balanced chromosomal EWS/ETS translocations, which give rise to oncogenic chimeric proteins (EWS-ETS). Other contributing somatic mutations involved in disease development have only been observed at low frequency. Thus, cancer in children is not solely a genetic disease and can neither be understood nor cured presumably without epigenetics. Previously, we identified the histone methyl-transferase enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2), the enzymatic subunit of the polycomb PRC2 complex, to be over-expressed in ES. RNA interference of EZH2 suppressed tumor development and metastasis in vivo and microarray analysis of EZH2 knock down revealed an EZH2-maintained, undifferentiated, reversible phenotype in ES.
Experimental procedures: The role of class I histone deacetylases (HDACs) was determined using different potent inhibitors like Trichostatin A (TSA), Romidepsin (FK22), Entinostat (MS-275) and PCI-34051 as well as a CRISPR/Cas9 approach to knock out specific HDACs. To analyze resulting changes qRT-PCR, Western Blotting, proliferation, apoptosis and invasion assays as well as immunofluorescence experiments were deployed.
Results: Interestingly, the effects of gene silencing after RNA interference of EZH2 could be mimicked by treatment of ES with TSA or MS-275. Microarray analysis revealed that treatment with MS-275 or TSA resulted in the induction of a similar pattern of differentiation genes as was previously observed after EZH2 blockade and seems to be dependent on histone deacetylase (HDAC) activity. Furthermore, in proliferation assays ES were more susceptible to treatment with HDAC inhibitors than other small round blue cell tumors such as neuroblastoma or pediatric cALL cells. Treatment of enzymatic inhibitors blocking EZH2 activity could not mimic the results observed after EZH2 RNA interference indicating that EZH2-containing PRC2 complexes may serve as a building block of class I HDAC activity in ES.
Conclusion: Class I HDACs seem to be important mediators of the pathognomonic EWS-ETS-mediated transcription program in ES and thus interesting new treatment opportunities for this malignant disease.
Citation Format: Kristina von Heyking, Tim Hensel, Julia Singer, Oxana Schmidt, Stefan Burdach, Günther H. Richter. Investigating the role of class I HDACs in Ewing sarcoma pathology [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3866. doi:10.1158/1538-7445.AM2017-3866
Abstract 3868: The stem cell factor LIN28B regulates proliferation and apoptosis in diffuse intrinsic pontine glioma
Authors: Guo Huizi , Akhtarkhavari Sepehr , Eberhart Charles G. , Kaur Harpreet , Raabe Eric H. 
Published: July 2017

Abstract
Diffuse Intrinsic Pontine Glioma (DIPG) is an incurable, invasive and aggressive pediatric brain tumor. Identifying molecular markers that regulate tumor growth and invasion are needed for developing efficient treatment strategies. LIN28B is a stem cell factor expressed during normal fetal development and re-expressed in cancer cells. We had previously shown that LIN28A, another family member of LIN28 proteins, regulates invasion and tumorigenicity in adult high grade gliomas. We observed increased LIN28B expression in patient-derived DIPG neurosphere cell lines using western blotting. We hypothesized that LIN28B promotes proliferation and prevents apoptosis in DIPG. Using two different lentiviral transduced short hairpin RNAs (shRNA), we suppressed LIN28B protein levels in DIPG neurospheres, as confirmed by western blotting. DIPG neurospheres that have been treated with LIN28B shRNA showed reduced proliferation as measured by BrdU incorporation (P&lt;0.01) and increased apoptosis as measured by cleaved caspase-3 (CC-3) expression (P&lt;0.01). To determine the molecular mechanism of LIN28B-mediated phenotypes in DIPG, we studied the canonical downstream effector of LIN28B called HMGA2, which is a DNA-binding protein that functions as a transcriptional regulator. Using western blotting, we found decreased HMGA2 protein levels in DIPG neurospheres infected with LIN28B shRNA. Taken together, our results suggest that LIN28B is important for promoting DIPG cell proliferation and preventing apoptotic cell death. Additionally, we also found that LIN28B regulates HMGA2 expression in DIPG neurospheres. Future studies will focus on expanding our understanding of the molecular mechanisms of LIN28B-regulated malignancy in DIPG.
Citation Format: Huizi Guo, Sepehr Akhtarkhavari, Charles G. Eberhart, Harpreet Kaur, Eric H. Raabe. The stem cell factor LIN28B regulates proliferation and apoptosis in diffuse intrinsic pontine glioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3868. doi:10.1158/1538-7445.AM2017-3868
Abstract 3879: Expression of sox2 and oct4 in human oral squamous cell carcinoma and its relationship with clinical factors
Authors: Tamatani Tetsuya , Takamaru Natsumi , Ohe Go , Kudo Keiko , Kudo Takaharu , Takahashi Akira , Yamamura Yoshiko , Fujisawa Kenji , Nagai Hirokazu , Miyamoto Youji 
Published: July 2017

Abstract
Background: A cancer stem cell (cancer initiating cell, CSC) is considered capable of self -replication, self-differentiation, drug resistance, and immune evasion. Recently, CSC has become increasingly important in the treatment of malignant tumors. Cancer stem cells express specific molecules termed CSC marker, including sex determining region Y-box2 (SOX2), and octamer-binding transcription factor 4 (Oct4), and their expression has been reported to be the potential prognostic values. However, the prognostic values of SOX2 and Oct4 expression in patients with oral cancer are less understood. [Purpose]The aims of present study were to evaluate the expression of SOX2 and Oct4 in oral squamous cell carcinoma (OSCC) and to elucidate the relationships among the CSC marker expression, clinical stages, histological differentiation, the classification of invasion mode, cerebral lymph node metastasis, distant metastasis, and disease-free survival rate.
Materials and Methods: Tissue specimens were obtains from 108 patients with OSCC after surgery or biopsy. Immunohistochemistry was used to assess SOX2 and Oct4 protein using at least 10% staining-positive cells as the definition of positive staining. Results: Immunohistochemical analysis of 108 cases showed that 42 cases (39%) expressed SOX2. There was no significant association between SOX2 expression and tumor size, invasion mode or histological differentiation. However, there was significant association between SOX2 expression and distant metastasis or disease-free survival rate at stage 1 and 2 patients (73 cases). Otherwise, seventy cases (65%) cases of 108 OSCC patients expressed Oct4. There was significant association between Oct4 expression and histological differentiation. There was no significant association between Oct4 expression and tumor size, invasion mode, metastasis, or disease-free survival rate.
Conclusions: These findings suggested that the expression of SOX2 may be good marker indicating survival in patients with OSCC.
Citation Format: Tetsuya Tamatani, Natsumi Takamaru, Go Ohe, Keiko Kudo, Takaharu Kudo, Akira Takahashi, Yoshiko Yamamura, Kenji Fujisawa, Hirokazu Nagai, Youji Miyamoto. Expression of sox2 and oct4 in human oral squamous cell carcinoma and its relationship with clinical factors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3879. doi:10.1158/1538-7445.AM2017-3879
Abstract 3902: Interleukin-6 blockade, a novel cancer stem cell targeted therapy, attenuates lung cancer tissue construction
Authors: Ogawa Hiroyuki , Koyanagi-Aoi Michiyo , Maniwa Yoshimasa , Aoi Takashi 
Published: July 2017

Abstract
Background: Lung cancer stem cells are considered to be responsible for lung cancer progression and metastasis. However, little is known about how they actually promote aggressive behaviors of lung cancer. Methods: We transduced OCT3/4, SOX2, and KLF4 (hereafter, OSK) into a KRAS-mutated (G12S) human lung adenocarcinoma cell line (A549) using retrovirus vectors. Dome-shaped colonies appeared in the OSK transduced A549 cells from 10 to 15 days after transduction. The colonies were picked up and sub-cultured. We named them OSK-A549-Colony cells. We evaluated cancer stem cell properties in the OSK-A549-Colony cells in terms of their chemo resistance, and sphere formation ability. We also assessed organoids constructing ability by co-culture with mesenchymal stem cells (MSCs) and human umbilical vein epithelial cells (HUVECs) on low attachment plates. To clarify the molecular mechanisms that determined the properties of the OSK-A549-Colony cells, we performed microarray analysis. We further analyzed the molecular mechanisms of organoids construction by OSK-A549-Colony cells and searched for a method to destroy them. Results: The induced OSK-A549-colony cells were significantly more resistant to cisplatin than the parental A549 cells. Sphere forming ability was enhanced in the OSK-A549-Colony cells. Co-culture with MSCs and HUVECs showed that only the OSK-A549-Colony cells were able to construct consolidated organoids in vitro that mimicked bona-fide human lung cancer tissues. We named them “lung cancer organoids”. We found that interleukin-6 (IL-6), which was the most differentially expressed gene in the OSK-A549-Colony cells by microarray analysis, facilitated the formation of lung cancer organoids via the conversion of MSCs into alpha-smooth muscle actin (αSMA)-positive cells. Surprisingly, the combination of anti-IL-6 antibody and cisplatin could destroy the lung cancer organoids, while cisplatin alone could not. Conclusion: By transducing defined factors, A549 cells acquired lung cancer stem cell like properties. Analysis of chemosensitivity using the lung cancer organoids showed that the combination of IL-6 blockade and cisplatin could be a novel therapy targeting lung cancer stem cells.
Citation Format: Hiroyuki Ogawa, Michiyo Koyanagi-Aoi, Yoshimasa Maniwa, Takashi Aoi. Interleukin-6 blockade, a novel cancer stem cell targeted therapy, attenuates lung cancer tissue construction [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3902. doi:10.1158/1538-7445.AM2017-3902
Abstract 3917: GenoCTC, a liquid biopsy device using microfluidic enrichment for affinity-based isolation of circulating tumor cells
Authors: Ryu Jiyeon , Kim Do Hyung , Kim Gyeong-Mi , Kim Jin Soo , Shin Youngkee , Lee Jaeku , Lee Hun Seok 
Published: July 2017

Abstract
To achieve a complete remission of cancer is still challenging that most patients with solid cancer ultimately experience metastasis. Detection of circulating tumor cells (CTCs) from the peripheral blood is promising key to solve the cancer cell dissemination and make accurate diagnosis, therefore, many efforts have been made to isolate the CTCs. Here, we newly developed the liquid biopsy device, GenoCTC, with microfluidic chips isolating CTCs from the patient whole blood. To isolate CTCs, EpCAM+ CTCs in the whole blood are first bound with magnetic beads conjugated with human-EpCAM antibody, and GenoCTC and its chip can isolate the EpCAM+ CTCs through magnetic based method. With 7.5 mL whole blood from lung cancer patient, we isolated EpCAM+ CTCs, and these CTCs were validated by immunofluorescence assay using anti-CK and anti-CD45. We also enumerated EpCAM+ CTCs in 17 whole blood samples from 10 lung cancer patients that various number, 2 to 114, of CTCs were found from each patient. The number of CTCs is known to have a correlation with disease progression and chemo-resistance, so the clinical meaning of this result is needed to be investigated. Furthermore, some CTCs are also found to be EpCAM independent which is regarded to have clinical utility involved in EMT. We used plastin-3 as its marker, and it was confirmed with HS 578T breast cancer cell line which shows low expression of EpCAM but high expression of plastin-3. The various molecules expressed on CTCs can be isolated with GenoCTC for further study. The characterization of CTCs is not only limited to EpCAM expression that it is important to be elucidated the complex biology of CTCs to apply companion diagnosis for personalized medicine.
Citation Format: Jiyeon Ryu, Do Hyung Kim, Gyeong-Mi Kim, Jin Soo Kim, Youngkee Shin, Jaeku Lee, Hun Seok Lee. GenoCTC, a liquid biopsy device using microfluidic enrichment for affinity-based isolation of circulating tumor cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3917. doi:10.1158/1538-7445.AM2017-3917
Abstract 3919: Isolation and characterization of viable pancreatic cancer circulating tumor cells using size-based filtration system
Authors: Yu Kenneth H. , Krempley Benjamin D. , McCarthy Brian 
Published: July 2017

Abstract
Introduction: Circulating tumor cells (CTCs) are important actors in metastasis, a key feature of pancreatic ductal adenocarcinoma (PDAC). The ability to isolate, characterize and culture viable CTCs holds promise for understanding biology, treatment response and resistance.
Methods: Peripheral blood samples from healthy donors and patients with advanced PDAC were processed using an innovative size filtration system (Viatar LLC, Lowell MA). Normal human blood samples were spiked with varying numbers of human PDAC organoid cells. The impact of buffy coat separation was studied. Isolated CTCs were cultured in Matrigel to generate organoids as previously described. Cells were imaged with fluorescently labeled antibody to EpCAM.
Data: Using spiked normal human blood samples, viable CTCs can be isolated and expanded reliably in 3D organoid culture from as few as 10 CTCs/mL. Separation and processing of the buffy coat enriched for the number of viable CTCs isolated. EpCAM positive CTCs were isolated from 6/6 blood samples from patients with advanced PDAC. Updated results will be presented.
Conclusions: The current size-based filtration system allows for collection of viable CTCs from human PDAC blood samples. Current work will use this system to grow, expand and characterize human PDAC CTCs in organoid culture. Genetic, transcriptional, and epigenetic characteristics will be compared with the primary tumor. CTC characteristics will be studied as biomarker of treatment response and resistance.
Citation Format: Kenneth H. Yu, Benjamin D. Krempley, Brian McCarthy. Isolation and characterization of viable pancreatic cancer circulating tumor cells using size-based filtration system [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3919. doi:10.1158/1538-7445.AM2017-3919
Abstract 3923: Oncogenic kinase-induced PKM2 Y105 phosphorylation promotes tumorigenesis and cancer stem cell-like property
Authors: Zhou Zhifen , Li Min , Zhang Lin , Yu Dihua 
Published: July 2017

Abstract
The role of pyruvate kinase M2 isoform (PKM2) in tumor progression is controversial. Previously, it was reported that PKM2 has an oncogenic function in promoting tumor growth in xenograft models; however, PKM2 was indicated non-oncogenic or even anti-oncogenic because depletion of PKM2 accelerates mammary tumor growth in the Brca1 knockout mouse model of breast cancer. Since tumors frequently harbor various abnormally activated oncogenic kinases, we hypothesized that phosphorylation of PKM2 by oncogenic kinases in tumor cells enables PKM2 to promote tumor growth, while unphosphorylated PKM2 in non-transformed cells cannot promote tumor growth. Here, we report that PKM2 proteins were largely unphosphorylated and formed tetramers in normal mammary epithelial cells (MCF10A, MCF12A). On the other hand, PKM2 proteins were phosphorylated at Y105 and formed dimers in breast cancer cells (MDA-MB-231, MDA-MB-435). Knocking down PKM2 didn’t affect normal mammary epithelial cell (MCF10A) growth but significantly decreased breast cancer cell MDA-MB-231 proliferation. In addition, introducing the PKM2-Y105D phosphomimetic mutant into MCF10A cells induced epithelial to mesenchymal transition, increased CD44Hi/CD24Neg stem cell-like cell population, and induced colony formation in soft agar, promoted cell migration and invasion. Interestingly, PKM2-Y105D increased YAP1 protein nuclear localization in MCF10A cells, whereas inhibiting YAP1 by siRNA or a chemical inhibitor (Verteporfin) decreased PKM2-Y105D-induced cancer stem cell-like population and colony formation ability. The data indicate that YAP1 is a novel downstream target of pY105-PKM2 in promoting the stem-like property and triggering mammary tumor initiation. Next, we performed receptor tyrosine kinase array and identified several oncogenic tyrosine kinases (AXL, EPHA2, FAK, Src, JAK3 and so on) that effectively phosphorylates PKM2 at Y105. Currently, we are testing the efficacy of targeting these oncogenic tyrosine kinases in reversing the phosphorylation of PKM2 and blocking its tumor-promoting function. Together, our data indicate that oncogenic kinases-induced phospho-Y105-PKM2, but not the unphosphorylated PKM2, promotes mammary tumor initiation by increasing cancer stem cell populations.
Citation Format: Zhifen Zhou, Min Li, Lin Zhang, Dihua Yu. Oncogenic kinase-induced PKM2 Y105 phosphorylation promotes tumorigenesis and cancer stem cell-like property [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3923. doi:10.1158/1538-7445.AM2017-3923
Abstract 3933: Characterization of oncogenic activity of interferon-induced protein with tetratricopeptide repeats 1 and 3 in human oral squamous cell carcinoma progression
Authors: Pidugu Vijaya Kumar , Yen Ai-Hsin , Chen Ying-Chen , Wu Mei-Maan , Liu Chung-Ji , Lee Te-Chang 
Published: July 2017

Abstract
Interferon-induced protein with tetratricopeptide repeats (IFITs) family has multiple tetratricopeptide repeats with helix-turn-helix structural motifs that mediate a variety of protein-protein interactions. There are four IFIT genes that have been identified namely, ISG56/IFIT1, ISG54/IFIT2, ISG60/IFIT3, and ISG58/IFIT5. IFIT proteins have been documented to involve in a variety of cellular functions, such as cell proliferation, migration, virus-induced translation initiation, replication and double-stranded RNA signaling. Our previous study has demonstrated that IFIT2 inhibits oral squamous cell carcinoma (OSCC) metastasis. However, little is known about IFIT1 and IFIT3 in the progression of OSCC.
In the present study, we are investigating the functional role of IFIT1 and IFIT3 genes in OSCC tumor progression. Immunohistochemical analysis of 147 patients derived tumor specimens with OSCC revealed a strong correlation between IFIT1 and IFIT3 proteins (p&lt;0.001). Clinicoplathological characteristics correlation of IFIT1 and IFIT3 expression levels were positively associated with regional lymph node invasion and nerve invasion. IFIT1 was also associated with venous invasion. Ectopic expression of IFIT1 and IFIT3 proteins in Ca9-22 and SAS cells inducing PKC, EGFR, and AKT activation, resulting in OSCC cells resistance to cisplatin but highly susceptible to tyrosine kinase inhibitor gefitinib, whereas IFIT1 and IFIT3 knockdown SCC25 cells have shown opposite effect. Interestingly, IFIT1 and IFIT3 expression is associated with enhanced cell invasion activity and altered expression of epithelial-mesenchymal transition markers. These data suggested that IFIT1 and IFIT3 may serve as potential biomarkers for the OSCC treatment. The study on how IFIT1 and IFIT3 cause PKC, EGFR, and AKT activation and resistance to DNA damaging agents is ongoing. Our further investigations may explain the molecular signaling mechanism of IFIT1 and IFIT3 in OSCC tumor progression.
Citation Format: Vijaya Kumar Pidugu, Ai-Hsin Yen, Ying-Chen Chen, Mei-Maan Wu, Chung-Ji Liu, Te-Chang Lee. Characterization of oncogenic activity of interferon-induced protein with tetratricopeptide repeats 1 and 3 in human oral squamous cell carcinoma progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3933. doi:10.1158/1538-7445.AM2017-3933