tbuckley/cabot-search huggingface dataset:
Abstract 361: Single cell detection of protein and RNA: Development of a novel method combining immunocytochemistry andin situhybridization in breast cancer cells
Authors: Lisa J. Ma, Richard T. Frank, Xiaoxiao Li, Steve Lai, Jeanette Schmidt, Peggy Just, Sara Becker-Catania
Journal: Cancer Research (2016)

Abstract Immunocytochemistry (ICC) utilizes antibodies to visualize the localization of specific proteins in cells while in situ hybridization (ISH) is a useful research tool for examining the presence and changes in levels of gene expression in cells. The ability to simultaneously visualize the co-localization of protein and RNA species in individual cells is necessary to address important biological questions. Additionally, studying both protein and RNA can be useful in cases where expression levels vary between mRNA and protein and to detect post-translational modifications. However, a combined technique has proved challenging due to the incompatibility of ICC and ISH protocols. Furthermore, traditional ISH methods have lacked sensitivity to detect low abundance RNA species and have limited multiplexing capability. Here, we describe a novel technique combining ICC staining with RNA ISH (based on the ViewRNA Assay), which utilizes branched DNA signal amplification technology allowing for single copy mRNA sensitivity. We demonstrate the utility and versatility of this technique using a variety of antibody and probe combinations relevant for cancer research. We compared expression of protein and mRNA of HER2, estrogen receptor alpha, and progesterone receptor in several breast cancer cell lines (MCF7, SKBR3, MDA-MB-175, MDA-MB-231, and BT474) known to express differential levels of these targets. We also compared expression of several microRNAs (let-7a, miR-17, miR-30d, miR-107, and miR-93) known to play a role in cancer development in combination with staining for proteins involved in proliferation (Ki-67), anti-apoptosis (survivin), and cell structure (tubulin). We show successful detection of low abundance RNA species together with various protein markers. This novel technique is a valuable tool not only for cancer researchers, but also for investigators across numerous fields in biological research. Citation Format: Lisa J. Ma, Richard T. Frank, Xiaoxiao Li, Steve Lai, Jeanette Schmidt, Peggy Just, Sara Becker-Catania. Single cell detection of protein and RNA: Development of a novel method combining immunocytochemistry and in situ hybridization in breast cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 361.
Abstract 1528: Selective gene-expression profiling of metastasizing breast tumor cell subpopulations complements the predictive power of Mammaprint Dx and Oncotype Dx
Authors: George S. Karagiannis, Sumanta Goswami, Joan G. Jones, Maja H. Oktay, John S. Condeelis
Journal: Cancer Research (2016)

Abstract Gene-expression profiling has yielded prognostic tests, such as MammaPrint and Oncotype Dx, which facilitate clinical decision-making in breast cancer patients. These tests are based on signatures constructed from whole tumor tissue, including tumor as well as stromal cells. Since metastatic tumor cells are not uniquely identified in these signatures, these tests may have reduced clinical specificity and sensitivity in predicting risk of metastasis. In contrast, we captured breast cancer cells in the act of migration/dissemination using an in vivo invasion assay and expression profiled these cells to create a distinct signature named the human invasion signature (HIS). A comparison between HIS and MammaPrint in the NKI295 cohort demonstrated that both signatures perform comparably in selecting a group of patients with significantly poorer outcomes. However, when compared to MammaPrint, the initial slope of the high-risk patients identified by the HIS is significantly steeper, suggesting that the HIS may identify patients at higher risk of early distant metastatic recurrence. Therefore HIS carries prognostic information beyond that captured by MammaPrint. Additionally, a more thorough examination of candidate genes present in HIS yielded two predictive tissue-based biomarkers: TMEM score which measures the density of cancer cell intravasation sites, and MenaCalc which measures the expression of invasive isoforms of the actin-regulatory protein Mena (MenaCalc = PanMena-Mena11a), thereby identifying tumor cells that disseminate. Both, TMEM density and MenaCalc independently predict the development of distant metastases in breast cancer patients. Here, we show that in a small patient cohort (n = 58), there is no correlation between TMEM density and the Oncotype recurrence score (RS). In particular, a subgroup of patients had tumors with high-Oncotype DX and low TMEM score while another subgroup had low Oncotype DX and high TMEM score. These findings indicate that TMEM and Oncotype Dx address different tumor biology and could be used in a complementary fashion for more accurate patient stratification, as well as better selection of systemic therapies to avoid over- and under-treatment. Citation Format: George S. Karagiannis, Sumanta Goswami, Joan G. Jones, Maja H. Oktay, John S. Condeelis. Selective gene-expression profiling of metastasizing breast tumor cell subpopulations complements the predictive power of Mammaprint Dx and Oncotype Dx. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1528.
Influence of dose adjustment on afatinib safety and efficacy in patients (pts) with advanced EGFR mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC)
Authors: A. Passaro, J.C. Yang, M. Ahn, N.J. Dickgreber, B. Halmos, V. Hirsh, M.J. Hochmair, B.P. Levy, F. de Marinis, T. Mok, K. O'Byrne, I. Okamoto, M. Schuler, M. Sebastian, R. Shah, E. Tan, N. Yamamoto, A. Märten, S. Wind, D.P. Carbone
Journal: Annals of Oncology (2015)
Endocrine-Disrupting Chemicals
Authors: Andrea C. Gore
Journal: JAMA Internal Medicine (2016)

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Abstract 3360: EB-virus latent membrane protein 1 potentiates the stemness of nasopharyngealcarcinoma via preferential activation of PI3K/AKT pathway by a positive feedback loop
Authors: Chang-Fu Yang, Guang-Da Yang, Tie-Jun Huang, Jia-Ling Huang, Chao-Nan Qian, Bi-Jun Huang
Journal: Cancer Research (2016)

Abstract Our previous study reported that Epstein-Barr virus(EBV)-encoded latent membrane protein 1 (LMP1) could induce development of CD44+/High stem-like cells in nasopharyngeal carcinoma (NPC). However, the molecular mechanisms that underlie modulation of cancer stem cells (CSCs) in NPC remain unclear. Here, we show that LMP1 induced CSC-like properties through promotion of the expression of epithelial-mesenchymal transition (EMT)-like cellular markers and through alterations in differentiation markers. Furthermore, LMP1 activated and triggered PI3K/AKT pathway, which subsequently stimulated expression of CSC markers, development of side population (SP) and tumor sphere formation. This suggests that PI3K/AKT pathway plays an important role in the induction and maintenance of CSC properties in NPC. Similarly, PI3K/AKT pathway was also activated by phosphorylase in LMP1-induced CD44+/High cells. In addition, LMP1 greatly increased expression of miR-21 and down-regulated expression of the miR-21 target, PTEN. Overexpression of miR-21 by transfection of miR-21 mimics into LMP1-transformed cells led to phosphorylase-mediated activation of the PI3K/AKT pathway and induction of CSCs. On the contrary, phosphorylation of the PI3K/AKT pathway and the expression of CSC were reversed by a miR-21 inhibitor. The specific inhibitor (Ly294002) of PI3K/AKT pathway significantly decreased expression of miR-21 and CSC markers and up-regulated the expression of PTEN, which indicates that miR-21 and PTEN are the downstream effectors of PI3K/AKT and that expression of these two effectors are related to development of NPC CSCs. Taken together, our novel findings indicate that LMP1, PI3K/AKT, miR-21 and PTEN constitute a positive feedback loop and play a key role in LMP1-induced CSCs in NPC. Citation Format: Chang-Fu Yang, Guang-Da Yang, Tie-Jun Huang, Jia-Ling Huang, Chao-Nan Qian, Bi-Jun Huang. EB-virus latent membrane protein 1 potentiates the stemness of nasopharyngealcarcinoma via preferential activation of PI3K/AKT pathway by a positive feedback loop. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3360.
Abstract 1338: Ferulic acid as a natural bioactive compound enhances PARP inhibitor sensitivity in breast cancer cells
Authors: Eunmi Park, Hyuna Lee
Journal: Cancer Research (2016)

Abstract Homologous-recombination (HR)-dependent repair defective cells are hypersensitive to poly (ADP-ribose) polymerase (PARP) inhibitors. Combinations of defective HR pathway and PARP inhibitors have been an effective chemotherapy strategy. We previously showed that knockdown of the WD40-repeat containing protein, Uaf1, is HR repair defect in mouse embryo fibroblast cells and is sensitive to ABT-888, a chemotherapy drug commonly used for inhibiting PARP. Consistent with the HR defective mouse genetic study, here, we show that ferulic acid inhibits Rad 51 foci formation and accumulates γ-H2AX in breast cancer cells. Ferulic acid treatment reduces HR repair and causes breast cancer cells to become hypersensitive to ABT-888 treatment. Our study indicates that ferulic acid with PARP inhibitor treatment may be useful for the combination chemotherapy as a natural bioactive compound. Citation Format: Eunmi Park, Hyuna Lee. Ferulic acid as a natural bioactive compound enhances PARP inhibitor sensitivity in breast cancer cells. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1338.
Abstract 426: Identifying a predictive biomarker for chemotherapy (taxane) in patients with metastatic castration resistance prostate cancer
Authors: Greg A. Rothchild, George Sandusky, Constance J. Temm, Costantine Albany
Journal: Cancer Research (2016)

Abstract In 2015, American Cancer Society predicts that 220,800 men will be diagnosed with prostate cancer (PC). Patients diagnosed with metastatic PC are first treated with androgen deprivation therapies (ADT) in order to lower testosterone to castration levels. Unfortunately, it is only a matter of time before becoming metastatic castration resistant prostate cancer (mCRPC). Subsequent treatments include combined androgen deprivation therapies such as (abiraterone, enzalutamide), immunotherapies, investigational drugs, and/or chemotherapy (docetaxel and cabazitaxel). Individualizing therapy for prostate cancer patients is an overarching goal of research. Currently, no valid practical biomarkers exist that can predict resistance to the taxane in PC. Identifying a marker that predicts taxane sensitivity would delineate patients who would benefit from taxane regimens from those who would suffer from added side-effects without any improved response. Previous studies have confirmed TLE3 is associated with a response to taxane therapy in breast and ovarian cancers. Preclinical studies have also shown that TLR4, RAGE, and HMGB1 confers chemo resistance to docetaxel on PC-3 human PC cells. After obtaining IRB approval (protocol IUCRO-0499), 8 metastatic castration resistant prostate cancer samples and 6 control samples were pulled for this study after scrutinous review of the H&amp;E slides from clinical cases. This study then consisted of investigating the proteins TLE3, TLR4, RAGE, and HMBG1. Immunostaining was performed using the automated immunostainer, Dako FLEX System, and the slides were scanned into the whole slide Aperio Scanscope CS digital imaging system. Computer-assisted morphometric analysis of digital images was then performed using the Aperio ImageScope software. Review of the TLE3 and TLR4 expression in metastatic castration resistance prostate cancer samples showed a difference between the expressions of these two proteins. TLR4 positivity was found to be 43.88% higher than the expression of TLE3. This is suggestive of resistance to docetaxel treatments. Review of the RAGE and HMGB1 expression in metastatic castration resistance prostate cancer samples compared to normal prostate epithelium showed a 32.9% increase in RAGE and 36.6% increase in HMGB1 expression. The findings of this study are suggestive that there is a possible correlation between the overexpression of these protein biomarkers and the patient's response to a specific drug treatment. Citation Format: Greg A. Rothchild, George Sandusky, Constance J. Temm, Costantine Albany. Identifying a predictive biomarker for chemotherapy (taxane) in patients with metastatic castration resistance prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 426.
Abstract 5080: Amylase overexpression promotes ovarian cancer invasion
Authors: Mai Mohamed, Patricia Kruk
Journal: Cancer Research (2016)

Abstract Introduction: Hyperamylasemia is an overexpression of amylase. Hyperamylasemia is associated with poor clinical outcome in ovarian cancer and reportedly serves as a prognostic biomarker for ovarian cancer. However, the function of hyperamylasemia in ovarian cancer is thus far unknown. Since amylase cleaves α1, 4-glycosidic bonds in carbohydrates, hyperamylasemia may play an active role in the etiology of ovarian cancer. Purpose: The purpose of this study was to characterize amylase expression in ovarian cancer cell lines and establish an active role for hyperamylasemia in ovarian cancer. Hypothesis: We hypothesized that secreted amylase enzymes cleave α1, 4-glycosidic bonds found in the carbohydrate shell which may result in a modified glycocalyx structure facilitating ovarian cancer cell invasion. Consequently, inhibiting amylase expression could abrogate ovarian cancer cell invasion/metastasis. Methods: To characterize amylase isozyme expression, we assayed amylase expression in normal and cancerous ovarian epithelial cell lines by western immunoblot, qPCR, amylase assays and computational analyses. We measured the ability of amylase to promote cellular proliferation by MTS assays. We assayed invasive capacity of cultured cells using collagen coated Boyden chambers and abrogated amylase expression with either amylase siRNA or treatment with the blue-green algae, Spriulina. Results: It was found that the amylase genes have identical or similar biochemical and bioinformatics properties: similar molecular weights, theoretical isoelectric points, disorder and hydropathy profiles, secondary structure and posttranslational modifications. In contrast to normal cell lines, ovarian cancer cell lines overexpress amylase at the messenger and protein levels and secrete high levels of metabolically active amylase. Amylase isozymes 1 and 2B were preferentially overexpressed in ovarian cancer cell lines. Inhibition of amylase abrogated ovarian cancer cell migration/invasion through collagen coated Boyden chambers which was associated with amylase-dependent alteration of extracellular carbohydrates. Further, the blue-green algae, Spirulina, was found to be a novel inhibitor of amylase. Conclusion: Herein, we describe for the first time an active function of amylase to promote ovarian cancer cell invasion potentially mediated by amylase-dependent alteration of extracellular carbohydrates. Further, transcriptional inhibition of amylase by Spirulina demonstrates its clinical potential as an adjuvant nutraceutical therapy. Citation Format: Mai Mohamed, Patricia Kruk. Amylase overexpression promotes ovarian cancer invasion. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5080.
Abstract 2886: KLF8 phosphorylation at Serine 48 by ERK2 is critical for its stability and function
Authors: Satadru Lahiri, Heng Lu, Debarati Mukherjee, Lin Yu, Jihe Zhao
Journal: Cancer Research (2016)

Abstract Krüppel-like factor 8 (KLF8) is a member of Krüppel like family transcription factor which was found to be upregulated in different types of cancers, primarily breast and ovarian cancer. It transcriptionally activates a host of downstream effectors like CyclinD1, EGFR, MMP9, and EPSTI1 to promote cell proliferation, cancer cell invasion and migration. Additionally, KLF8 transcriptionally represses E-cadherin to induce epithelial to mesenchymal transition and oncogenic transformation of cell. As such, KLF8 plays a central role in cancer progression. Several types of post-translational modifications including sumoylation, acetylation, ubiquitylation and PARylation have been discovered that regulate KLF8's function KLF8 has been shown to consistently migrate as doublet on SDS-PAGE. However, the reason for this motility shift of KLF8 has remained mysterious. We performed a series of experiments to determine the mechanism(s) behind this motility shift of KLF8. Truncation mutation showed that deletion of the first 50 amino acid residues, but not other regions, caused disappearance of the top band of the doublet, suggesting that the N50 region is responsible for the motility shift. Phosphatase treatment resulted in the same change in wild-type KLF8 protein, indicating that phosphorylation in the N50 region is causal to the motility shift. Further deletion and point mutation in this region identified Serine 48 as a novel phosphorylation site for KLF8. Interestingly, these experiments also identified KLF8 N terminal 31-40 region to play an important role in regulating the S48 phosphorylation and the motility shift. Our study identified that phosphorylation at Serine 48 is critical in maintaining KLF8 stability. Finally, we demonstrated that abolishing KLF8 S48 phosphorylation inhibits KLF8 mediated cancer cell migration. Kinase inhibitors treatment showed that ERK2 is the kinase responsible for KLF8 Serine 48 phosphorylation. Furthermore we identified that phosphorylated KLF8 acts as a mask to protect unphosphorylated KLF8. Overall this study identifies a novel phosphorylation site of KLF8 and a hitherto unknown link between ERK2 and KLF8 that is critical for maintaining its overall stability and function. Citation Format: Satadru Lahiri, Heng Lu, Debarati Mukherjee, Lin Yu, Jihe Zhao. KLF8 phosphorylation at Serine 48 by ERK2 is critical for its stability and function. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2886.
Abstract 634: Impact of tumor inoculation site on the development of cancer cachexia
Authors: Takashi Ando, Takeshi Ishikawa, Tastuzo Matsuyama, Tomoyo Yasuda, Toshifumi Doi, Tetsuya Okayama, Naoyuki Sakamoto, Satoshi Kokura, Yuji Naito, Yoshito Itoh
Journal: Cancer Research (2016)

Abstract Background and Aim The incidence of cancer cachexia varies greatly among tumor type. Although certain tumor types are more commonly associated with cachexia, even for the same tumor type, the degree to which patients exhibit cachexia varies. This is due to variations in tumor phenotype and host genotype that contributes to the development of cancer cachexia. The influence of the site of tumor growth on the development of cancer cachexia remains unclear. In this study, we evaluated if differences in tumor microenvironment would affect the development of cancer cachexia in a murine model. Methods The same number of colon26 cells (5×10⁁6 cells/mouse) was inoculated subcutaneously or intraperitoneally in 8-week-old male BALB/c mice. Body weight, food intake, and tumor size were monitored. On day 14 after the tumor inoculation, mice were anesthetized and blood collected, and the weight of peritesticular adipose tissue, gastrocnemius muscle and heart were measured. 23 plasma cytokines were determined by using the Bio-Plex array system and plasma Myostatin and Activin A levels were measured by ELISA. Expression of MuRF-1 and Antrogin-1, which are required for muscle atrophy, in gastrocnemius muscle or heart was assessed by RT-PCR. Results The body weight, adipose tissue and gastrocnemius muscle decreased in tumor-bearing mice. Interestingly, a reduction in heart weight was observed in the intraperitoneal tumor group but not in the subcutaneous group. The weight loss of the body, adipose tissue and gastrocnemius was more severe in the intraperitoneal group than in the subcutaneous group. Atrogin 1 and MuRF1 mRNA expressions in the gastrocnemius muscle increased significantly in both groups of tumor-bearing mice, however, in the myocardium, expression of these mRNAs increased in the intraperitoneal group but not in subcutaneous group. As for plasma cytokine levels, several cytokine levels including IL-6, TNF-α, and activing A of tumor-bearing mice were significantly higher than those of control mice. Eotaxin and G-CSF levels in the intraperitoneal tumor group were higher than in the subcutaneous group. Conclusion Based on these data, we believe that differences in microenvironment where tumor cells develop can affect the progression and phenotype of cancer cachexia through alterations in various circulating factors derived from the tumor microenvironment. Citation Format: Takashi Ando, Takeshi Ishikawa, Tastuzo Matsuyama, Tomoyo Yasuda, Toshifumi Doi, Tetsuya Okayama, Naoyuki Sakamoto, Satoshi Kokura, Yuji Naito, Yoshito Itoh. Impact of tumor inoculation site on the development of cancer cachexia. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 634.