bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1830: Role of heat shock factor 1 (HSF1) on metabolic reprogramming of T -cells
Authors: Pandya Bhaumik D. , Mivechi Nahid M. , Moskophidis Dimitrios 
Published: August 2019

Abstract
Heat shock transcription factor 1 (HSF1) is normally activated in response to a variety of environmental stressors. Higher levels of HSF1 expression has been shown in many tumor types and this is associated with poor prognosis. Previous data from our laboratory indicate that genetic inactivation of HSF1 significantly delays ERBB2-induced mammary tumorigenesis and hepatocellular carcinoma induced by chemical carcinogen in mouse models. We have also shown that HSF1 is involved in controlling cellular bioenergetics. CD8-positive T cells plays an important role in anti-tumor immunity response. Our preliminary results show that genetic inactivation of HSF1 in T-cells leads to reduced oxygen consumption rate (OCR) as well as Extracellular Acidification Rate (ECAR). We have also observed that deletion of HSF1 from T cells delayed in-vitro activation of purified CD8-positive T cells upon stimulation with anti-CD3 and anti-CD28. Above characteristics corresponds to reduced cellular glycolysis and T cell proliferation. Further studies will be directed towards exploring the effects of HSF1 deletion in T cell activation induced anti-tumor immunity. This study is supported by the NCI grants; NCICA062130 and NCICA132640.
Citation Format: Bhaumik D. Pandya, Nahid M. Mivechi, Dimitrios Moskophidis. Role of heat shock factor 1 (HSF1) on metabolic reprogramming of T -cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1830.
Abstract 1865: Buserelin trisphenylmethanol derivatives as anti-cancer prodrugs
Authors: Beni Ryan , Boadi William , Antwi Renner 
Published: August 2019

Abstract
Buserelin (BUS) is a synthetic nonapeptide agonist analog of LH-RH, first reported by Hoechst in 1976. It is used for the treatment of advanced prostate cancer. Side effects of buserelin include musculoskeletal pain, hearing disorders, increased thirst, worsening hypertension, anxiety, memory and concentration disturbances, fatigue, nervousness, palpitations, leukopenia, thrombocytopenia, altered blood lipids, and glucose intolerance. Therefore, improving of the biological activity of BUS by increasing the cellular uptake and retention is a remedy to this end. In this research, tris(4-methoxyphenyl)methanol (TPM) derivatives were synthesized and linked to BUS through hydrophobic linkers to enhance and optimize the hydrophobicity of this drug with the expectation to improve the cellular uptake. In this regard, several BUS conjugates of TPM derivatives with optimized hydrophobicity were synthesized by the reaction of methoxy benzenes (e.g. anisole, 2-fluoroanisole, 2-trifluoromethylanisole, 2-methylanisole, or 1,2-dimethoxybenzene, and 1,3,5-trioxane, followed by the conjugation with BUS and lauric acid in the presence of HBTU/DIPEA/DIC in moderate yields. Comparative antiproliferative assays between TPM-BUS conjugates and the corresponding non-covalent physical mixtures of the TPM derivatives and BUS were performed against human acute lymphoblastic leukemia (CCRF-CEM), human ovarian adenocarcinoma (SK-OV-3), and mouse pre adipocytes (3T3-L1) cells. TPM-BUS conjugates inhibited the cell proliferation of CCRF-CEM, SK-OV-3 and 3T3-L1 cells by 48-86%, 32-77%, 42-67%, respectively, at a concentration of 1-25 µM after 24-72 h of incubation. These data suggest that TPM-BUS derivatives with optimized hydrophobicity can be used to improve the biological activity of BUS.
Note: This abstract was not presented at the meeting.
Citation Format: Ryan Beni, William Boadi, Renner Antwi. Buserelin trisphenylmethanol derivatives as anti-cancer prodrugs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1865.
Abstract 1870: Polyphenols from Korean artemisia annua L (pKAL) showed anti-cancer effects by multiple mechanisms on HCT116 human colorectal cancer cells
Authors: Lee Won Sup , Paramanantham Anjugam , Jeong Eun Joo , Raha Suchismita , Kim Hye Jung , Kim GonSup , Shin Sung Chul 
Published: August 2019

Abstract
Artemisia annua L., (Gaddongsook in Korean), an annual herb, has been used for a long time in Korean folk medicine for the treatment of infectious or chronic disorder In addition, it possesses anti-inflammatory, and anti-cancer activity. However, the molecular mechanism for anti-cancer properties of Korean Artemisia annua is still unclear. Here, we investigated the anti-cancer effects of we investigated the anti-cancer effects of polyphenols from Korean Artemisia annua (pKAL) on HCT116 human colon cancer cells. pKAL induced cell death associated with the alteration of cell morphology and DNA content. Annexin V and PI staining revealed that late phase apoptosis. pKAL induced ROS generation and the cell death was recovered by NAC. Western blot revealed that pKAL significantly up-regulated the gamma-H2AX, p21, p53, p62 and cleavage of caspases-3 and PARP in HCT116 cells. pKAL induced changes in the expression of p53-dependent targets (p53, p21, Bax, Bak, and Fas). It also induced alteration of the expression of autophagy-related proteins (beclin1, p62, LC3-I, and LC3-II) posttranslational modification of proteins (Lamin A/C, HSP90, GM130) involved in the maintenance of intracellular membrane integrity. Unexpectedly, the effect of pKAL on cell death pKAL was similar in both the P53 wild-type and p53-null HCT116 colon cancer cells, although there was some difference in cell cycle arrest; in P53 wild-type cells, pKAL appeared to induce G1 arrest at lower concentration (50 μg/mL), whereas in p53-null cells, pKAL induced G2/M arrest. The cell death was regulated by JNK and p38 MAPK signaling. The cancer effects of pKAL was similar in p53-null NCI-H1299 cells. We also investigated the protein changes that is related to cell death and cell integrity with anti-body array, which revealed that pKAL induced changes in NF-Kb, PI3K, Ras, TGF-beta signaling too. In conclusion, these findings suggest that pKAL induced anticancer effects by inducing late phase apoptotic cell death at least in part through p38 MAPK and JNK pathways in HCT 1116 human colon cancer cells. It also induced alteration of cell morphology mimic to necrosis in some cells with changes of proteins involved in the maintenance of intracellular membrane integrity. These effects was p53-independent.
Citation Format: Won Sup Lee, Anjugam Paramanantham, Eun Joo Jeong, Suchismita Raha, Hye Jung Kim, GonSup Kim, Sung Chul Shin. Polyphenols from Korean artemisia annua L (pKAL) showed anti-cancer effects by multiple mechanisms on HCT116 human colorectal cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1870.
Abstract 1873: Water-pipe smoking induces epithelial-mesenchymal transition and enhances cell invasion of human breast cancer cells
Authors: Moustafa Ala-Eddin Al 
Published: August 2019

Abstract
Water-pipe smoking (WPS) has been recently recognized as an emerging risk factor for human health. The exact role of WPS in human breast cancer development and progression has not been investigated yet. We herein explored for the first time the impact of WPS on epithelial-mesenchymal transition (EMT) and cell invasion, which are considered crucial for cancer progression and metastasis in human carcinomas including breast. Our data revealed that WPS can initiate EMT in two human breast cancer cell lines, MCF-7 and BT20. WPS enhanced the cell invasion ability of both cell lines compared with their matched controls. We also found that WPS provoke a down- and up-regulation of two important regulator genes of cancer progression: E-cadherin and focal adhesion kinase (FAK). In addition, our data pointed out that WPS induces the activation of Erk1/Erk2 signaling pathways, which could be behind the stimulation of EMT and deregulation of E-cadherin and FAKgenes. Taken together, our results imply the significant effects of WPS on several cellular processes and genes involved in breast cancer progression and metastasis. Further studies are necessary to identify the clinical relevance and exact role of WPS in human carcinogenesis and metastasis. Key words: Water-pipe smoking, breast cancer, EMT, cell invasion, cell adhesion
Citation Format: Ala-Eddin Al Moustafa. Water-pipe smoking induces epithelial-mesenchymal transition and enhances cell invasion of human breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1873.
Abstract 1886: Zygote arrest 1 like (ZAR2): An EMT (epithelial-mesenchymal transition) modulator in breast cancer
Authors: Misra Smita , Singha Tanushree , Chaudhuri Gautam 
Published: August 2019

Abstract
Breast cancer is the most common cancer in women and distant site metastasis is the main cause of death in breast cancer patients. EMT is a natural phenomenon in development and wound healing. EMT is also one of the “Hallmarks of cancer”. EMT is involved in tumor cell progression, invasion, and metastasis. During the process of EMT, epithelial cancer cells acquire molecular alternations that facilitate the loss of epithelial features and gain of mesenchymal phenotype. Such transformation promotes cancer cell migration and invasion. Decrease in E-cadherin expression and gain of N-cadherin and vimentin expression is indicative of EMT phenotype. Working with our recently characterized C4 zinc finger containing RNA binding protein ZAR2 we observed that levels of ZAR2 are significantly lower in the invasive breast cancer cells compared to non-invasive cells. Knockdown of ZAR2 in the non-invasive breast cancer cells increased the in-vitro invasiveness of these cells whereas forced expression of ZAR2 in the invasive breast cancer cells reduced their invasiveness. To understand the possible mechanism of ZAR2-mediated regulation of invasiveness of the breast cancer cells we studied differential gene expression in the ZAR2 knocked down non-invasive breast cancer cells by RNA-seq analysis. One of the genes that are significantly elevated in the ZAR2 knocked down cells is the invasion determining enzyme ATP6V0A4 along with ERBIN and ABCA12. Here we present our observation regarding ZAR2 regulation of ATP6V0A4 and its effect on metastasis and invasion potential of the breast cancer cells. Supported in part by NIH grant 1U54RR026140, Meharry Bridge and 2U54MD007586-32Revised from Meharry RCMI Program in Women’s Health funds to SM and DOD grants BC990678 and BC050641 to GC.
Citation Format: Smita Misra, Tanushree Singha, Gautam Chaudhuri. Zygote arrest 1 like (ZAR2): An EMT (epithelial-mesenchymal transition) modulator in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1886.
Abstract 1892: Dysfunction of resident memory CD8+ T cells facilitates breast cancer lung metastasis
Authors: Song Erwei , Xing Yue , Su Shicheng 
Published: August 2019

Abstract
Resident memory T cells (TRM) are generally intraepithelially located and manifesting defence potential in diverse existing virus infection models. However, their roles in cancer development, especially metastasis, are poorly understood. Herein, by using a murine model orthotopically inoculated with 4T1 mammary carcinoma cells, we demonstrated the dynamic distribution and functional changes of lung TRM during the formation of lung pre-metastatic niche. Peri-alveolar accumulation of CD8+ T cells, which constitutively express early activation marker CD69 and epithelial-resident marker CD103, is identified. These draining lymph nodes originated and tumor-specific TRM cells, with high expression of IFN-γ and other cytotoxic cytokines, patrol along blood stream and infiltrate in the pre-metastatic lung. IFN-γ coverts alveolar macrophages in the pre-metastatic lung into a immunosuppressive phenotype with high expression of IDO1, which reciprocally compromises the anti-tumor effects of TRM. In conclusion, our study revealed the alteration of lung TRM during the process of metastasis and its interaction with lung pre-metastatic niche, indicating that by finding possible approaches to enhancing TRM function or strengthening local defenses could decrease breast cancer lung-tropic metastasis.
Citation Format: Erwei Song, Yue Xing, Shicheng Su. Dysfunction of resident memory CD8+ T cells facilitates breast cancer lung metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1892.
Abstract 1895: Identification of therapeutic targets in peritumoral microenvironment by single-cell assays using impedance spectroscopy
Authors: Maercker Christian 
Published: August 2019

Abstract
Metastasis and tumor growth are very much dependent on the peritumoral microenvironment. Cells in the peripheral cortex send out growth factors and generate an extracellular matrix which is decisive for infiltration of neoplastic cells and, finally, the formation of a functioning tumor tissue. To figure out specific functions of different cell types and their various interactions in in vitro or in vivo assays, which are possibly relevant for the identification of new drug targets, is a challenge, because we deal with a very complex multifactorial network. Therefore, our goal is to develop test systems with a limited complexity, but which still are informative in terms of molecular tumor development. To reach this, we first have to singularize cells from tumor tissue. Within surgical tissue, tumor core tissue has to be discriminated from surrounding tissue by MRI or immunohistochemistry. Afterwards, microdissected tissue samples have to be dissociated by protease digest. In a next step, the mixture of cells has to be separated into the different cell types by immunopanning and/or FACS sorting. RNAseq helps to identify gene expression profiles specific for individual cells within the tumor compared to the tumor microenvironment. For us the most important parameters are the adhesion and migration activities of the various cell types of different origin on different matrices. To establish a test system as a starting point for a more sophisticated experimental setup to characterize tumorigenic tissues, we firstly isolated mesenchymal stem cells (MSC) from fat tissue or bone marrow, before transfer to microwells covered with electrodes to monitor cell adhesion by electrochemical impedance sensing. We found that pre-coating of the microwells with either collagen type I or IV induced different impedance profiles, corresponding to distinct differentiation pathways which was confirmed by histochemical staining as well as protein and gene expression analyses. In another approach, we used impedance sensing to measure prostate or breast cancer cell migration towards the secretome of mesenchymal stem cells. MSC cell culture supernatant was fractionated by size exclusion and ion exchange chromatography. We identified type I and III collagen, fibronectin and Laminin 421 as extracellular matrix proteins to be the main drivers of rapid cancer cell migration requiring as little as two hours for a full migration response. The challenge now is to adjust this experimental approach to individual cell types isolated from different tumor types and also to different matrices simulating the tumor microenvironment.
Citation Format: Christian Maercker. Identification of therapeutic targets in peritumoral microenvironment by single-cell assays using impedance spectroscopy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1895.
Abstract 1900: A tension-mediated glycocalyx feedback loop promotes glioblastoma
Authors: Kaushik Shelly , Barnes James Matthew , Bainer Russell O. , Sa Jason K. , Woods Elliot C. , Kai Fuiboon , Lakins Jonathon N. , Phillips Joanna J. , Weaver Valerie M. 
Published: August 2019

Abstract
A considerable challenge in glioblastoma (GBM) therapy is treatment resistance and tumor recurrence, resulting in dismal patient prognosis. GBM aggression and recurrence is often associated with a mesenchymal phenotype, increased expression of glycoproteins and the presence of glioma-initiating “stem-like” cells. Using patient-derived xenograft models, and immune competent syngeneic and transgenic glioma mouse models, we show that aggressive mesenchymal-like GBMs, reminiscent of recurrent GBM, are mechanically stiffer, present with a bulky glycocalyx and demonstrate a stem-like phenotype. We report that the more aggressive mesenchymal GBMs show increased mechanical signaling and contractility, and their tumors are surrounded by a stiffer ECM that maintains and even further enhances integrin mechanosignaling. Since a large proportion of these bulky glycoproteins are also stem markers, upregulation of the glycoproteins and their modulators leads to enhanced GBM stem-ness. This was evident both in our mesenchymal models of GBM as well as multiple patient datasets which compared paired primary and recurrent GBM RNA sequencing and protein data. In addition to stem-ness, we show that the mechanically “enhanced” GBMs also foster a differential immune landscape, infiltrated by type 2 macrophages, believed to be pro-tumorigenic and immune evasive. Our findings suggest that there is a dynamic and reciprocal link between integrin mechanosignaling, the GBM immune landscape and a bulky glycocalyx, which promotes a mesenchymal, stem-like phenotype and likely recurrence in GBM patients. Thus, therapeutic strategies to target GBM tissue tension could prevent recurrence, reduce mortality and improve patient outcome.
Citation Format: Shelly Kaushik, James Matthew Barnes, Russell O. Bainer, Jason K. Sa, Elliot C. Woods, Fuiboon Kai, Jonathon N. Lakins, Joanna J. Phillips, Valerie M. Weaver. A tension-mediated glycocalyx feedback loop promotes glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1900.
Abstract 1907: Tenascin-C promotes the activation of mammary fibroblasts to calponin-expressing myofibroblasts
Authors: Katoh Daisuke , Noro Aya , Imanaka-Yoshida Kyoko , Ogawa Tomoko , Yoshida Toshimichi 
Published: August 2019

Abstract
[Introduction] Tenascin-C (TN-C), an extracellular matrix molecules, is highly expressed in cancer stroma. Recent studies have demonstrated that cancer associated fibroblasts (CAFs) expressed TN-C in many tumors, including breast cancer. Here, we clarified the effects of TN-C on phenotype changes of the fibroblasts. [Methods] We examined the cell morphology, expression of CAFs markers, and contractile ability in the fibroblasts after TNC treatment in vitro, using human mammary gland fibroblasts (HMFs) and dermal ones (HDFs). We also investigated the correlation between the expression of the CAF markers and TNC deposition in human breast cancer tissues, using immunohistochemical staining. [Results] TN-C (10μg/mL) induced morphological changes of HMFs from spindle-shaped cells to stellate-shaped cells on plastic as well as on glass coverslips. After the treatment of TN-C, the protein expressions of α-SMA and calponin were significantly increased. Immunofluorescence analysis revealed TN-C increased the actin-stress fiber formation and the expression of α-SMA and calponin. Furthermore, TN-C promoted contraction of collagen gel by HMFs. These results indicated TN-C induces transformation of HMFs into high-contractile myofibroblasts. In human breast cancer tissues, α-SMA and calponin-positive fibroblasts were localized in TN-C-positive cancer stroma. Interestingly, calponin-expressing fibroblasts were not observed in the skin metastatic lesions of breast cancer. In addition, the increased expression of α-SMA and calponin after TN-C treatment in HDFs were significantly lower compared to HMFs in vitro. These results suggested the responses of TN-C on fibroblasts differs according to the residential tissues. Next, we examined the receptor to TNC and signaling pathway for TNC-induced change of HMFs. TN-C increased the colocalization of integrin αv and β1 in focal adhesion. Furthermore, phosphorylation of SMAD2 and SMAD3 were significantly increased and SMAD3 translocated from cytoplasm to nucleus after TN-C addition. Inhibition of TGF-β type I receptor (SB-505124) or SMAD3 (SIS3) suppressed the expression of α-SMA and calponin after TN-C treatment. [Conclusion] TNC could contribute cancer stroma formation characteristics of breast cancer tissues, following induction of phenotypical change to myofibroblasts and enhanced stromal contraction via integrin αvβ1/TGF-β/SMAD signaling. Phenotypic differences between HMFs and HDFs after TN-C administration may be present.
Citation Format: Daisuke Katoh, Aya Noro, Kyoko Imanaka-Yoshida, Tomoko Ogawa, Toshimichi Yoshida. Tenascin-C promotes the activation of mammary fibroblasts to calponin-expressing myofibroblasts [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1907.