bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4898: Association of CD44 expression and ALDH1 activity in thyroid cancer.
Authors: Okada Toshihiro 
Published: August 2014

Abstract
Background: Anaplastic thyroid cancer (ATC) is considered to be one of the most aggressive human malignancies, and the mean survival time (MST) after diagnosis is approximately six months, regardless of treatments. ATC is known to arise from differentiated thyroid cancers such as papillary (PTC) or follicular (FTC) cancers. The purpose of this study is to examine whether the characteristics of cancer stem cell are associated with ATC.
Materials and methods: One PTC cell line (TPC1), one FTC cell line (FTC-133), and two ATC cell lines (FRO, ACT-1) were analyzed for surface markers (CD24/CD44, CD44 variant isoform, EpCAM), and ALDH1 enzymatic activities (ALDEFLUOR) by FACS. In addition, relative mRNA expression of these molecules were determined by real-time RT-PCR.
Results: CD44s (standard form) expressions in the PTC cell line (TPC1) and the FTC cell line (FTC-133) were higher than those in the ATC cell lines (FRO and ACT-1). On the other hand, ALDH1 activities of ATC cell lines were higher than those of the PTC and the FTC cell lines. An inverse correlation between the expression of CD44s and ALDH1 activity was observed in the thyroid cancer cell lines. As for the expressions of CD44 variant forms, ACT-1 showed a higher and FRO showed a moderate expressions of CD44v6. On the other hand, either TPC1 or FTC-133 showed negative expression of CD44v6. The expressions of EpCAM in the ATC cell lines were higher than those in the differentiated cancer cell lines, and EpCAM expressions were inversely correlated with the expressions of CD44s. ATC cell lines showed higher levels of ALDH1 enzymatic activities and EpCAM expressions compared with those in the differentiated cancer cell lines. A strong positive correlation was observed between the expression of EpCAM and ALDH1 activity in the thyroid cancer cell lines. Both ALDH1 and EpCAM mRNA expressions were higher in the ATC cell lines compared with those in the differentiated cancer cell lines in the RT-PCR analyses.
Conclusion: In our present study, the expressions of CD44 and EpCAM, and ALDH1 enzymatic activity were different between the differentiated thyroid cancer cell lines and the anaplastic thyroid cancer cell lines. Our data suggest that these molecules might be involved in the development and aggressive phenotype of anaplastic thyroid cancer.
Citation Format: Toshihiro Okada. Association of CD44 expression and ALDH1 activity in thyroid cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4898. doi:10.1158/1538-7445.AM2013-4898
Abstract 4920: EcSOD overexpression inhibits the growth and invasion by affecting extracellular matrix in PC3 human prostate cancer cells.
Authors: Kim Jungim 
Published: August 2014

Abstract
It has been shown that EcSOD (extracellular superoxide dismutase, SOD3) can attenuate tissue damage and cancer cell invasion but so far its function in prostate cancer cells has not been completely clarified. Thus, we investigated the effect of EcSOD for cell growth and invasion in PC3 human prostate cancer cells. We stably transfected PC3 cells with pCMV-EcSOD cDNA and observed its overexpression in mRNA and protein levels through RT-PCR and Western Blot, respectively. To check out the influence for the growth rate of EcSOD, we analyzed Cell Viability and Cytotoxicity Assay as a colorimetric and fluorometric format via MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) reagent and cell-permeable polyanionic calcein acetoxymethyl (Calcein AM) and ethidium homodimer (EthD-1) dye. And we performed EcSOD Activity Assay and ELISA. Moreover, we time-dependently carried out Wound-healing Assay by monitoring the down-regulated growth rate of EcSOD overexpression PC3 cells. Furthermore, we verified low EcSOD expression compared to other types of SODs by IHC and Patients Tissue Microarray. Meanwhile, we accomplished Invasion Assay and MMP-2 and-9 Activity Assay with Zymography. Herein, it elucidated that EcSOD abrogates cell growth, proliferation, and invasion by associating with extracellular matrix in PC3 human prostate cancer cells. Taken together, these findings suggest that EcSOD can potentially have beneficial future strategy for the treatment of prostate cancer.
Citation Format: Jungim Kim. EcSOD overexpression inhibits the growth and invasion by affecting extracellular matrix in PC3 human prostate cancer cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4920. doi:10.1158/1538-7445.AM2013-4920
Abstract 4924: Connective tissue growth factor (CTGF) mediates metastases of breast cancer stem cells.
Authors: Zhong Jing , Zhu Xiaoping , Zhao Hong , Wong Stephen Tc , Wong Stephen Tc 
Published: August 2014

Abstract
Background: Recent studies on various cancer types suggest that the mere acquisition of cancer stem-like cells (CSCs) phenotype is not sufficient to confer metastatic potential. Epithelial-Mesenchymal transition (EMT) has been implicated in enhancing cancer metastatic dissemination, and generating CSCs, which may be a key determinant in imparting metastatic potential to CSCs. Our goal is to determine the metastasis potential of the CSCs generated from EMT and to explore critical molecules involved in the metastatic cascade process.
Experimental design and methods: The metastatic ability of the EMT-generated-CSCs (HMLE-Ras-Snail) and the control cell line (HMLE-Ras-vector) were compared by the migration, invasion and chemotaxis assays in vitro, as well as experimental and spontaneous metastases mice models in vivo. A microarray gene profiling analysis was performed to explore signaling molecules involved in the EMT-CSCs-metastasis. Functional assays were used to verify the identified molecule in vitro and in vivo.
Results: HMLE-Ras-Snail cells showed significant high migration, invasive behaviors, especially under the different organ protein as chemo-attractants (lung, brain and liver). Experimental lung and brain metastasis mice study showed a significant enhancement of tumor extravasation and outgrowth of HMLE-Ras-Snail cells compared with the control cells. Spontaneous metastases mice studies showed that 7 out of 9 mice developed lung metastasis, and 2 out of 9 with brain metastasis for the HMLE-Ras-Snail model, while none of the HMLE-Ras-vector cell-injected mice were detected with metastases. Two-photon live animal imaging also showed enhanced single cell adhesion and movement in the lung or brain micro-vessels in the HMLE-Ras-Snail cell-injected mice. The differential gene expression analyses and western blot indicated that the CTGF is up-regulated in the EMT-generated-CSCs. Knockdown of CTGF in the HMLE-Ras-Snail cells not only enhanced the expression of epithelial marker and decreased the mesenchymal marker, but also decreased the in vitro proliferation, migration, invasion, mammosphere formation and in vivo lung metastases.
Conclusions: CTGF may play an important role in breast cancer metastasis, with enhancing cell motility, invasiveness and also give cell self-renewal stem cell-like characteristic to facilitate EMT-CSCs-Metastasis.
Citation Format: Jing Zhong, Xiaoping Zhu, Hong Zhao, Stephen Tc Wong, Stephen Tc Wong. Connective tissue growth factor (CTGF) mediates metastases of breast cancer stem cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4924. doi:10.1158/1538-7445.AM2013-4924
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 4930: A commensal relationship between tumor cell subpopulations promotes collective invasion.
Authors: Pearson Gray , Prechtl Amanda , Westcott Jill , Dang Tuyen , Maine Erin 
Published: August 2014

Abstract
The invasion of tumor cells out of ductal epithelium is a poorly understood process that dramatically increases the odds of patient death. We have defined a new non cell-autonomous control mechanism for neoplastic invasion that trigger tumors to switch from a benign to a malignant stage of growth. Using high resolution live-imaging and functional studies we show that an epigenetically distinct and autonomously invasive subpopulation of tumor cells induces the invasion of a large bulk population of autonomously noninvasive tumor cells by adopting migratory principles observed during sprouting angiogenesis. The molecular dissection of this cooperative interaction revealed a new “invasion signature” of 29 genes that is distinct from traditional epithelial-to-mesenchymal transition markers. Patients expressing this invasion signature had a worse clinical outcome, which suggests that this commensal relationship between tumor cell subpopulations contributes to tumor progression. Functional analysis showed that multiple components of the invasion signature were specifically required for the cooperative induction of invasion, but not cell motility, thus revealing new roles for these genes as non-cell autonomous regulators of invasion. These results are of broad interest because they are the first demonstration of a commensal relationship between tumor cell subpopulations during the induction of invasion. Further, these findings establish a mechanistic underpinning that obviates the notion that the exclusive role of heterogeneity in tumors is to act as a source for unique traits that can be selected for and expanded to improve the cell autonomous fitness of neoplastic cell populations. Thus, our results support a paradigm shift towards identifying both the cell autonomous and the non cell-autonomous regulatory mechanisms of cell biological processes within heterogeneous tumors to understand neoplastic progression and develop new intervention modalities.
Citation Format: Gray Pearson, Amanda Prechtl, Jill Westcott, Tuyen Dang, Erin Maine. A commensal relationship between tumor cell subpopulations promotes collective invasion. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4930. doi:10.1158/1538-7445.AM2013-4930
Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Abstract 4938: Free β-subunit of human chorionic gonadotropin stimulates choriocarcinoma cell invasion independent of LH/hCG receptor.
Authors: Lee Cheuk-Lun , Chiu Philip CN , Hautala Laura , Yeung William SB , Stenman Ulf-Håkan , Koistinen Hannu 
Published: August 2014

Abstract
Human chorionic gonadotropin (hCG) is a heterodimer consisting of an α- and a β-subunit (hCGα and hCGβ) that are non-covalently linked. Intact hCG, but not free subunits, bind to the LH/hCG receptor. Expression of hCG and hCGβ has been observed in several cancers. Most trophoblastic tumors of placental and germ cell origin produce hCG, while many non-trophoblastic tumors, including bladder, renal and gastrointestinal cancers, often produce hCGβ, and increased serum concentrations of these are associated with adverse prognosis. hCG has been found to stimulate trophoblast invasion. The stimulatory activity has especially been ascribed to a hyperglycosylated form of hCG (hCG-h) expressed in early pregnancy. hCG-h is also a major form of hCG produced by choriocarcinoma and by testicular cancers, although tumor-derived hCG-h is often glycosylated differently than that produced by the placenta. We aimed to compare different forms of hCG in their stimulatory activities on the invasion of JEG-3 choriocarcinoma cells. Various forms of hCG and hCGβ were purified from urine of one patient with nonseminomatous testicular cancer, one with invasive molar disease, and pregnant women. Both hCG and hCGβ, and their hyperglycosylated forms stimulated the invasion of JEG-3 cells. However, cancer-derived hCG-h was more effective than “regular” hCG in stimulating the invasion. Down-regulation of the LH/hCG receptor by RNA-interference did not significantly reduce the effect of hCGβ and hCG on cell invasion. Increased invasion was associated with increased activity of MMP-2, MMP-9 and uPA in conditioned culture medium from JEG-3 cells. Our findings suggest that hCG and hCGβ stimulates the invasion of choriocarcinoma cells independent of the classical LH/hCG-receptor.
Citation Format: Cheuk-Lun Lee, Philip CN Chiu, Laura Hautala, William SB Yeung, Ulf-Håkan Stenman, Hannu Koistinen. Free β-subunit of human chorionic gonadotropin stimulates choriocarcinoma cell invasion independent of LH/hCG receptor. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4938. doi:10.1158/1538-7445.AM2013-4938
Abstract 4940: Prognostic significance of Fbw7 in human melanoma and its role in cell migration.
Authors: Cheng Yabin 
Published: August 2014

Abstract
The E3 ubiquitin ligase Fbw7 (F-box and WD repeat domain-containing 7) is broadly considered as a tumor suppressor because of its role in turnover of several well-known onco-proteins. However, the role of Fbw7 in melanomagenesis is not clear. To investigate the expression profile and biological functions of Fbw7 in melanoma, we examined Fbw7 expression level using melanoma tissue microarray and immunohistochemistry. Our data showed that Fbw7 expression is significantly reduced in primary melanoma compared with dysplastic nevi (P = 0.020) and further reduced in metastatic melanoma compared with primary melanoma (P = 0.011). Furthermore, we observed a strong correlation between negative Fbw7 expression and a worse 5-year survival of melanoma patients (P = 0.015). We also found that both Fbw7 protein and mRNA expression was significantly reduced in 9 melanoma cell lines compared with normal melanocytes. Moreover, our in vitro studies showed a remarkable increase of cell migration and stress fibre formation in Fbw7 knockdown cells, and treatment of selective MEK inhibitor abrogated Fbw7α knockdown induced melanoma cell migration. Taken together, our findings indicate that Fbw7 plays an important role in melanoma progression, and Fbw7 inhibits melanoma cell migration through MAPK-ERK signalling pathway and may serve as a prognostic marker.
Citation Format: Yabin Cheng. Prognostic significance of Fbw7 in human melanoma and its role in cell migration. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4940. doi:10.1158/1538-7445.AM2013-4940
Abstract 4948: Pirfenidone as a potential therapeutic treatment for CAFs and cancer cells in NSCLC.
Authors: Mediavilla-Varela Melanie , Luddy Kimberly , Noyes David , Boateng Kingsley , Antonia Scott 
Published: August 2014

Abstract
Lung cancer is the leading cause of cancer death in the United States. Due to limited efficacy of current conventional chemotherapy, the majority of patients face poor prognosis and eventually succumb the disease. Until recently, the main focus in cancer research has been targeting the neoplastic cell. However, the importance of the tumor microenvironment, including cancer associated fibroblasts (CAFs), in cancer progression is now clear and targeting both, the neoplastic cell as well as the CAF, is being recognized as an important therapeutic approach. We have recently discovered that pirfenidone might be the drug to target these cells. Pirfenidone is a small molecule that has been shown to decrease fibrosis in a variety of fibrotic diseases. The exact mechanism responsible for its anti-fibrotic effects remains to be elucidated. Our hypothesis is that pirfenidone (by targeting the CAFs) in combination with standard chemotherapy (by targeting the cancer cells) will act synergistically and proffer a more potent therapeutic strategy for non-small cell lung cancer (NSCLC). Our studies show that in the presence of pirfenidone NSCLC associated CAF viability decreases in vitro. Furthermore, pirfenidone was able to induce apoptotic cell death as well as cell cycle arrest in NSCLC associated CAFs. In addition, we were able to observe that CAFs treated with pirfenidone decreased active TGFβ when compared to the control. Moreover, in a spheroid model, pirfenidone was able to affect the crosstalk between the cancer cells and CAFs leading to increased apoptosis and decreased viability. Currently, pirfenidone is being used in Phase II and III clinical trials for idiopathic pulmonary fibrosis. Our lab is the first one to recognize the potential of pirfenidone as a potential treatment of NSCLC.
Citation Format: Melanie Mediavilla-Varela, Kimberly Luddy, David Noyes, Kingsley Boateng, Scott Antonia. Pirfenidone as a potential therapeutic treatment for CAFs and cancer cells in NSCLC. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4948. doi:10.1158/1538-7445.AM2013-4948
Abstract 4979: Multidimensional crosstalk regulates myeloid cell hyperplasia, immune escape, and tumor progression.
Authors: Younos Ibrahim H. , Dafferner Alicia J. , Britton Holly , Talmadge James E. 
Published: August 2014

Abstract
Myeloid-derived suppressor cells (MDSCs) encompass a heterogeneous class of cells in different maturation states that proliferate and accumulate in tumors, secondary lymphoid organs and some epithelial organs during tumor growth. Tumor secretion of growth factors and chemokines regulate myeloid cell proliferation, apoptosis, differentiation, circulation and biodistribution both locally and systemically. There is a reciprocal interaction that occurs between tumor and myeloid cells, which can facilitate tumor growth and metastasis and myeloid cell proliferation and survival via unique and tumor specific arrays of growth factors and chemokines. The tumor microenvironment, a complex, highly dynamic environment composed of host-derived MDSCs, endothelial cells, and fibroblasts; contributes to the microenvironmental crosstalk regulating host immunity and tumor progression. However, the macroenvironment is also a critical to myeloid cell expansion, tumor invasion and immune escape and tumor progression. The primary site of MDSC expansion and immune suppression is splenic extramedullary hematopoiesis, which is regulated by growth factors secreted by the distant primary tumor cells. Similarly, regulation of tumor infiltration by myeloid cells is by tumor secretion of CCL2; however, this occurs at the macroenvironmental level as CCL2/CCR2 blockade inhibits medullary myeloid cell mobilization and recruitment from secondary lymphoid organs and not at the tumor. Further, regulatory crosstalk is bidirectional with tumor-secreted factors differentially upregulating myeloid and lymphoid cell growth factors and enzymes (G-CSF, CXCL1, CCL2, arginase) by medullary myeloid cells and splenic lymphocytes. In tumor bearing, mice the tumor-secreted growth factors support hematopoietic stem/progenitor cell proliferation, limit their apoptosis and inhibit T-cell function. Conversely, leukocyte-secreted cytokines limit immune and hematopoietic growth factor transcript levels by tumor cells (G-CSF, IL-23, CXCL1 and NOS-2) with associated effects on tumor malignancy and leukocyte proliferation and differentiation. In summary, tumors form both local and systemic, bidirectional, regulatory loop(s) between metastatic tumor cells and MDSCs that regulates their proliferation and differentiation supporting tumor metastasis and systemic and regional T-cell suppression.
Citation Format: Ibrahim H. Younos, Alicia J. Dafferner, Holly Britton, James E. Talmadge. Multidimensional crosstalk regulates myeloid cell hyperplasia, immune escape, and tumor progression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4979. doi:10.1158/1538-7445.AM2013-4979
Abstract 4981: PI3K/AKT/mTOR pathway activation drives expression of the immune inhibitory ligand PD-L1 in NSCLC.
Authors: Lastwika Kristin , Wilson Willie , Dennis Phillip A. 
Published: August 2014

Abstract
Despite the development of targeted drug therapies, lung cancer remains the leading cause of cancer-related death worldwide. Targeting immune checkpoints altered in cancer, such as the T cell inhibitory receptors programmed death 1 (PD-1) or CTLA4, represent promising new approaches to lung cancer treatment. Here we investigated the relationship of activation of the PI3K/Akt/mTOR signaling pathway and expression of the immune suppressive ligand, PD-L1, in non-small cell lung cancer (NSCLC). NSCLC cell lines with mutations in KRas, EGFR, BRaf, ALK or RET had high levels of PI3K/Akt/mTOR pathway activation as well as increased expression of PD-L1. Cell lines that lacked these mutations had low PI3K/Akt/mTOR pathway activation and less PD-L1 expression. In murine cell lines derived from tobacco carcinogen (NNK)-induced lung tumors, high levels of active Akt correlated with high PD-L1 expression. Agonists of the PI3K/Akt/mTOR pathway activation such as EGF or the carcinogen NNK, as well as knockdown of PTEN or induction of Kras induced PD-L1 expression. Conversely, treatment of high PD-L1 expressing NSCLC cell lines with inhibitors of PI3K (LY294002), AKT (triciribine) or mTOR (rapamycin) decreased PD-L1 expression. These inhibitors decreased PD-L1 protein levels, but did not alter PD-L1 mRNA. Rapamycin-mediated PD-L1 loss was partially blocked by pre-treatment with a lysosomal, but not a proteosomal inhibitor. In vivo, increased expression of PD-L1 and activation of mTOR was an early event after exposure to NNK and was blocked by rapamycin. To test the efficacy of blocking PD-1 while reducing the expression of PD-L1 in tumor tissue, rapamycin and a murine anti-PD-1 receptor antibody were administered to A/J mice bearing syngeneic lung tumor xenografts. The combination decreased the tumor growth rate to a greater degree than either agent alone and decreased mTOR pathway signaling, PD-L1 expression, and increased cleaved caspase 3. Tumor associated activated CD8+ T cells were also increased in the tumors. These data support a relationship between activation of PI3K/Akt/mTOR signaling, PD-L1 expression and the development of an immune resistant phenotype in lung cancer. Combination regimens using PI3K/Akt/mTOR inhibitors may enhance the efficacy of immune therapies targeting PD-1.
Citation Format: Kristin Lastwika, Willie Wilson, Phillip A. Dennis. PI3K/AKT/mTOR pathway activation drives expression of the immune inhibitory ligand PD-L1 in NSCLC. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4981. doi:10.1158/1538-7445.AM2013-4981