bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2179: Macrolide toxin Mycalolide B is a potent inhibitor of HER2 cancer cell invasion and is the basis of actin targeted therapy for metastatic cancers
Authors: Williams Rodette N. , Craig Andrew W. , Allingham John S. 
Published: July 2016

Abstract
Breast and ovarian cancers are among the leading causes of cancer related deaths in women worldwide. Human epidermal growth factor receptor 2 (HER2) is highly expressed in a subset of these cancers that show high rates of progression to metastatic disease. Metastasis is driven by filamentous actin (F-actin) based protrusions that penetrate and degrade extracellular matrix (ECM) to facilitate tumor invasion. In this study, we tested an actin-depolymerizing macrolide toxin Mycalolide B, as a potential suppressor of highly metastatic HER2+ breast and ovarian cancer cell models. Dose responses with Mycalolide B in SKBR3 breast cancer and SKOV3 ovarian cancer cells resulted in similar cytotoxicity (∼65 nM IC50) profiles. In addition, Mycalolide B doses well below the IC50 showed potent suppression of leading edge protrusions, and motility in SKBR3 and SKOV3 cancer cells. This also correlated with reduced ECM degradation and Transwell invasion at low nanomolar doses of Mycalolide B. In contrast, other F-actin based processes such as endocytosis of HER2 and EGFR, were less sensitive to Mycalolide B treatment. However, Mycalolide B treatment did skew the size of endocytic vesicles, which may reflect defects in F-actin based vesicle motility or maturation. Given that HER2 cancers have been effectively targeted by Trastuzumab and Trastuzumab-based antibody-drug conjugates, we are currently testing the compatibility of combined treatments with Mycalolide B and Trastuzumab, for their effects on F-actin based invasion of HER2+ cancers. This strategy may yield a novel class of antibody-drug conjugate, and lead to new HER2 targeted therapies that suppress tumor metastasis by disrupting early steps that are dependent on efficient F-actin polymerization.
Citation Format: Rodette N. Williams, Andrew W. Craig, John S. Allingham. Macrolide toxin Mycalolide B is a potent inhibitor of HER2 cancer cell invasion and is the basis of actin targeted therapy for metastatic cancers. [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 2179.
Abstract 218: Ewing sarcoma gene, EWS, role in mitochondrial homeostasis
Authors: Park Jun Hong 
Published: July 2016

Abstract
Peroxisome proliferator-activated receptor γ coactivator (PGC-1α) is a central regulator of mitochondria biogenesis, function and cellular energy metabolism. PGC-1α protein is intrinsically unstable but the mechanism by which PGC-1α stability is regulated is not well understood. Here, we report that a multifunctional protein EWS (Ewing sarcoma) is critical for PGC-1α protein stability and mitochondrial homeostasis. EWS inactivation results in a rapid degradation of PGC-1α via ubiquitin-dependent proteasome pathway and reduces mitochondrial abundance. Re-introduction of EWS in Ews-deficient cells restores PGC-1α expression and mitochondrial anomalies. In the absence of Ews, expression of E3 ubiquitin ligase, FBXW7 (F-box/WD40 domain protein 7), is increased and depletion of Fbxw7 in Ews-null cells restores PGC-1α expression and mitochondrial density. Consistent with these findings, mitochondrial abundance and activity are significantly reduced in brown fat and skeletal muscles of Ews-deficient mice and expression of slow myosin heavy chain is significantly decreased in skeletal muscles of Ews-/- mice compared to controls. Furthermore, Ews-null mice display reduced expression of mitochondrial biogenesis, respiration and fatty acid β-oxidation genes in the liver and abnormally high serum lactate levels. These results demonstrate a novel role of EWS in mitochondrial and cellular energy homeostasis by controlling PGC-1α protein stability.
Citation Format: Jun Hong Park. Ewing sarcoma gene, EWS, role in mitochondrial homeostasis. [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 218.
Abstract 2183: Baicalein and meformin decrease small cell lung cancer growth by inhibiting the mTOR pathway in itro
Authors: Marcinkowski Emily F. , Raz Dan , Shen Bing , Xing Quanhua , Yan Jin , Wen Wei , Han Ernest , Yim John 
Published: July 2016

Abstract
Background: Metformin use has been associated with decreased lung cancer risk in several observational studies and is currently in clinical trial in conjunction with standard chemotherapeutics. One possible antitumor mechanism is the negative regulation of the mTOR pathway. We previously reported that the natural product Baicalein has antitumor effects through targeting mTOR pathway. We hypothesized that Baicalein to have antitumor effects in small cell lung cancer. Methods: H1417 small cell lung cancer cells were cultured and treated with increasing doses of Baicalein or Metformin. The cells were harvested at 24 hours and subjected to Western blotting staining for the downstream products of the mTOR pathway. Cell proliferation was determined by MTT assay at 24, 48, and 72 hours. MTT conversion to formazan dye correlates with the number of living cells. Results: We found a dose dependent decrease in the downstream mTOR1 targets pS6K1 and pS6 using both Baicalein and Metformin. There was also an increase in the expression of the mTOR inhibitors DDIT4 and IRF-1. Using the MTT assay, we were able to demonstrate a marked dose dependent decrease in cell proliferation that was sustained over 72 hours from treatment. Interestingly, Baicalein has a markedly higher potency working at micromolar doses verses Metformin which required millimolar doses. Conclusions: Both Baicalein and Metformin effectively decrease cell proliferation in small cell lung cancer cells in vitro. We have shown these drugs to target the mTOR pathway. Cell proliferation is inhibited at a markedly smaller dose by Baicalein compared with Metformin. Baicalein may be useful in cancer chemotherapy and chemoprevention.
Citation Format: Emily F. Marcinkowski, Dan Raz, Bing Shen, Quanhua Xing, Jin Yan, Wei Wen, Ernest Han, John Yim. Baicalein and meformin decrease small cell lung cancer growth by inhibiting the mTOR pathway in itro. [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 2183.
Abstract 2184: The effects of specific heterocyclic compounds on angiogenesis and apoptosis factors in cancer cells
Authors: Kosova Funda , Temiz-Arpacı Özlem , TUĞLU İbrahim , ÖLMEZ Ercüment , ÖZDAL KURT Feyzan , KISMALI Gorkem , Ari Zeki , ARISOY Mustafa 
Published: July 2016

Abstract
Introduction: Benzoxazole have received considerable attention during last few decades as they are endowed with variety of biological activities and have wide range of therapeutic properties. The present study aimed to evaluate cytotoxic and antiapoptotic activities of new synthesize benzoxazole derivative in breast cancer cell lines.
Material and Method: In this study, the breast cancer cell lines MDA-MB and MCF-7 were used. Cytotoxic activities of novel benzoxazole-derived compound were analyzed with MTT assay. Additionally, the level of its effects on NF-κB and apoptosis-related proteins were examined by the western blot. Immunohistochemical stainings were done for VEGF, eNOS proteins and Tunnel assay was performed to show DNA damage.
Results: The structure of the compound synthesized in our study 5-amino-2-(p-bromophenyl)-benzoxazole was proved by elemental analysis, IR, 1H NMR and mass
spectroscopy analysis methods. Novel benzoxazole analogue detected cytotoxic on breast cancer cells dose dependent manner, MCF-7 cells were found more sensitive by MTT assay. When the protein was examined in immunohistochemistry with regard to VEGF, eNOS and TUNEL, it was observed that it caused a reduction in VEGF and an increase in eNOS and TUNEL. We observed that it wasn't between groups in Apaf-1 and BCL-2 levels, but down regulation was observed in caspase 3 and Nfkβ levels compared to control group. Novel benzoxazole compound increased Cytochrome C level in treated cells compared to the control group in MDA-MB cells but not in the MCF-7 cells.
Conclusion: In summary, It is felt that this newly synthesized heterocyclic compound increases apoptozis by reducing the activation of Nfkβ, and in this way has shown an effect of inhibiting tumor growth in cancer treatment.
Key Words: Heterocyclic Compounds, NF-κB, APAF-1, Cytochrome C, Caspase-3, bcl-2
Citation Format: Funda Kosova, Özlem Temiz-Arpacı, İbrahim TUĞLU, Ercüment ÖLMEZ, Feyzan ÖZDAL KURT, Gorkem KISMALI, Zeki Ari, Mustafa ARISOY. The effects of specific heterocyclic compounds on angiogenesis and apoptosis factors in 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 2184.
Abstract 2185: Sann-Joong-Kuey-Jian-Tang can inhibit human breast cancer cells through dural- blocking both the Ras/Raf/MEK/ERK and Ras/PI3K/Akt/mTOR pathways
Authors: SU. CHIN CHENG 
Published: July 2016

Abstract
Sann-Joong-Kuey-Jian-Tang (SJKJT) consists of 17 species of medicinal herbs, is a traditional Chinese medicine prescription, and has been used as complementary medication for a number of types of solid cancer in Taiwan. Transmembrane tyrosine kinase has been strongly implicated in the growth, survival, and metastasis of a wide variety of human tumors. The phosphoinositide-3-kinase (PI3K)/AKT/ mammalian target of rapamycin (mTOR) and RAS/RAF/MEK/ERK pathways are two of the most frequently dysregulated kinase cascades in human cancer were well documented. Both pathways represent important signal transduction mechanisms that facilitate the proliferation and survival of cancers driven by growth factor receptors, such as vascular endothelial growth factor receptor (VEGFR), insulin-like growth factor-I receptor (IGF-IR), human epidermal growth factor receptor 2 (HER2) or epidermal growth factor receptor (EGFR).The individual downstream components of these signaling cascades either through somatic mutation or epigenetic modification, are also known to be frequently altered in cancer, thus contributing to tumorigenesis and resistance to anticancer therapies. Targeting both the Ras/Raf/MEK/ERK and Ras/PI3K/Akt/mTOR Pathways for suppressing Inhibitor Resistant Cells is necessary. In the present study, the human breast cancer BT-20 and MCF-7 cells were treated with SJKJT in vitro. The cytotoxicity of SJKJT were evaluated by 3–(4,5–dimethylthiazol–2–y1)–2,5–diphenyltetrazolium bromide (MTT) assay. The effects of SJKJT on the protein expressions of VEGFR, IGF-IR, PI3K, AKT, mTOR, Ras, Raf, MEK and ERK and β-actin in the BT-20 and MCF-7 cells were examined by western blot analysis. The results showed that SJKJT can induce the proliferation inhibition with time and dose dependent. As a potential mechanism, it was noted that SJKJT treatment significantly inhibited the activity of the Ras/Raf/MEK/ERK and Ras/PI3K/Akt/mTOR pathways, which played a protective role against the cytotoxicity. In addition, it was demonstrated that SJKJT treatment inhibited the protein expressions of VEGFR, EGFR and IGF-IR significantly. These results suggest that one of the molecular mechanisms for SJKJT to inhibit breast cancer BT-20 and MCF-7 cells maybe through inhibiting the protein expressions of VEGFR, EGFR, IGF-IR and both Ras/Raf/MEK/ERK and Ras/PI3K/Akt/mTOR pathways. The use of traditional chinese medicine prescription SJKJT may become a feasible novel therapy option. Further studies are warranted to fully elucidate its mechanisms of action.
Citation Format: CHIN CHENG SU. Sann-Joong-Kuey-Jian-Tang can inhibit human breast cancer cells through dural- blocking both the Ras/Raf/MEK/ERK and Ras/PI3K/Akt/mTOR pathways. [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 2185.
Abstract 2187: Garcinone inhibits nasopharyngeal carcinoma cell growth and arrests cell cycle via modulating the expression of ATR/Stat3/4E-BP1
Authors: Xia Yudui , Liu Xia , Zou Chunllin , Guo Hongwei , Yang Yeguo , Lei Yong , Zhang Jian , Lu Yi 
Published: July 2016

Abstract
Nasopharyngeal carcinoma (NPC) is one of the common head and neck malignancies. Radiotherapy and chemotherapy are the standard treatments for NPC. Garcinone, a natural compound isolated from Garcinia oblongifolia Champ., is a xanthone derivative and has been shown to have potential cytotoxic effects on certain cancer types. However, there have been limited studies performed on its effects on NPC cells and the mechanisms of these effects remain unknown. In this study, we firstly found that garcinone significantly inhibited cell viability of human NPC cell lines CNE1, CNE2, HK1, and HONE1. This inhibition was in a time- and dose-dependent manner. Then, flow cytometry analysis was performed on cell cycle analysis. We observed that garcinone arrested cell cycle at S phase. With 10μM of high-dose garcinone treatment, the cells exhibited necrotic morphology changes including cell swelling, rough endoplasmic reticulum (ER) degranulation, ER dilatation, mitochondria swelling, and vacuolar degeneration. Finally, we found that garcinone stimulated the expression levels of ATR and 4E-BP1, while efficiently inhibited the expression levels of Cyclin B1, Cyclin D1, Cyclin E2, cdc2, CDK7, and Stat3. Collectively, the ability of garcinone to inhibit NPC in vitro suggested that garcinone might be a novel agent for the management of NPC. Supported by NSFC Key Project 81130046; NSFC Project 81171993 and NSFC81272415; Guangxi Key Projects 2013GXNSFEA053004 and 2012GXNSFCB053004; Guangxi Ministry of Education 201202ZD022 and 201201ZD004.
Citation Format: Yudui Xia, Xia Liu, Chunllin Zou, Hongwei Guo, Yeguo Yang, Yong Lei, Jian Zhang, Yi Lu. Garcinone inhibits nasopharyngeal carcinoma cell growth and arrests cell cycle via modulating the expression of ATR/Stat3/4E-BP1. [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 2187.
Abstract 219: PHF20 induced necrotic like cell death mediated by ROS via enhanced mitochondrial biogenesis
Authors: Park Jisoo , Li Yuwen , Kong Gyeyeong , Mun Kisun , Lee Hyunji , Kim Dohoon , Tran Quangdon , Wang Ming , Peng Bingjie , Hong Youngeun , Hur Gang Min , Park Jongsun 
Published: July 2016

Abstract
The importance of PHD finger protein 20 (PHF20) in the cellular process is recently emerging as a regulator for the p53 and NF-kB signaling as well as the reprograming process of induced pluripotent stem cell. In this study, we have provided the clear evidence that PHF20 exhibit the novel function in tumorigenesis by regulating the mitochondria biogenesis. Overexpression of PHF20 increases mitochondria biogenesis via up-regulation of peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC1-α) in HCT116 cells. PHF20 overexpression enhances mitochondrial respiratory capacity and oxygen consumption, leading to the accumulation of reactive oxygen species (ROS). Accumulated ROS by PHF20 causes the necrotic like cell death in HCT116 cells. The measurement of mitochondrial ROS in the cells expressing PHF20 revealed that excessive production of mitochondrial ROS facilitates the formation of mitochondrial permeability transition pore, resulting in the loss of mitochondrial membrane potential. PHF20-mediated ROS accumulation damages DNA and leads to over-activation of PARP but not caspase. Antioxidants and PARP-1 inhibitor are able to rescue PHF20 induced cell death, whereas z-VAD, pan-caspase inhibitor, had no effects. Immunohistochemical analysis of various human cancer revealed that PHF20 expression is highly elevated in most of tumor compared to normal tissue. Taken together, PHF20 appears to be tumor-specific antigen and PHF20-mediated PGC1-α upregulation is responsible for the elevation of intracellular ROS generation, resulting the necrotic like cell death. Thus, this study provided the new concept for treating glioma patients and novel pharmacological target in various cancers including glioblastoma and hepatocellular carcinoma
Citation Format: Jisoo Park, Yuwen Li, Gyeyeong Kong, Kisun Mun, Hyunji Lee, Dohoon Kim, Quangdon Tran, Ming Wang, Bingjie Peng, Youngeun Hong, Gang Min Hur, Jongsun Park. PHF20 induced necrotic like cell death mediated by ROS via enhanced mitochondrial biogenesis. [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 219.
Abstract 220: SR4 uncouples mitochondrial oxidative-phosphorylation, modulates AMPK-mTOR signaling, and inhibits proliferation of HepG2 hepatocarcinoma cells
Authors: Singhal Sharad S. , Figarola James , Singhal Jyotsana , Tompkins Joshua , Horne David , Awasthi Sanjay , Riggs Arthur 
Published: July 2016

Abstract
Mitochondrial oxidative phosphorylation produces most of the energy in aerobic cells by coupling respiration with the production of ATP. Mitochondrial uncouplers, which reduce the proton gradient across the mitochondrial inner membrane, create a futile cycle of nutrient oxidation without generating ATP. Regulation of mitochondrial dysfunction and associated cellular bioenergetics has been recently identified as promising targets for anticancer therapy. Here, we show that SR4 is a novel mitochondrial uncoupler that causes dose-dependent increase in mitochondrial respiration and dissipation of mitochondrial membrane potential (MMP) in HepG2 hepatocarcinoma cells. These effects were reversed by the recoupling agent 6-ketocholestanol, but not cyclosporin A, and were non-existent in mitochondria-DNA depleted HepG2 (po) cells. In isolated mouse liver mitochondria, SR4 similarly increased oxygen consumption independent of adenine nucleotide translocase (ANT) and uncoupling proteins, decreases MMP, and promotes swelling of valinomycin-treated mitochondria in potassium acetate media. Mitochondrial uncoupling in HepG2 cells by SR4 results in the reduction of cellular ATP production, increased ROS production, activation of the energy-sensing enzyme AMPK, and inhibition of acetyl-CoA carboxylase and mammalian target of rapamycin (mTOR) signaling pathways, leading to cell cycle arrest and apoptosis. Global analysis of SR4-associated differential gene expression confirms these observations, including significant induction of apoptotic genes and down regulation of cell cycle, mitochondrial and oxidative-phosphorylation pathway transcripts at 24 h post treatment. Collectively, our studies demonstrate that SR4's previously reported indirect activation of AMPK and in-vitro anticancer properties, as well as its beneficial effects in both animal xenograft and obese mice models could be a direct consequence of its mitochondrial uncoupling activity (Supported by NIH grant CA 77495 and Beckman Research Institute of the City of Hope).
Citation Format: Sharad S. Singhal, James Figarola, Jyotsana Singhal, Joshua Tompkins, David Horne, Sanjay Awasthi, Arthur Riggs. SR4 uncouples mitochondrial oxidative-phosphorylation, modulates AMPK-mTOR signaling, and inhibits proliferation of HepG2 hepatocarcinoma 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 220.
Abstract 2201: Tea nanoparticle, a safe and biocompatible nanocarrier, greatly potentiates the anticancer activity of doxorubicin
Authors: Wang Yi-Jun , Huang Yujian , Anreddy Nagaraju , Zhang Guan-Nan , Zhang Yun-Kai , Xie Meina , Lin Derrick , Yang Dong-Hua , Zhang Mingjun , Chen Zhe-Sheng 
Published: July 2016

Abstract
An infusion-dialysis based procedure has been developed as an approach to isolate organic nanoparticles from green tea. Tea nanoparticle (TNP) can effectively load doxorubicin (DOX) via electrostatic and hydrophobic interactions. We established an ABCB1 overexpressing tumor xenograft mouse model to investigate whether TNP can effectively deliver DOX into tumors and bypass the efflux function of the ABCB1 transporter, thereby increasing the intratumoral accumulation of DOX and potentiating the anticancer activity of DOX. MTT assays suggested that DOX-TNP showed higher cytotoxicity toward CCD-18Co, SW620 and SW620/Ad300 cells, as compared to DOX. Animal study revealed that DOX-TNP resulted in a greater inhibitory effect on the growth of SW620 and SW620/Ad300 tumors than DOX alone. The cTnI levels in mice showed that TNP had no cardiotoxicity and DOX-TNP had moderate cardiotoxicity. Blood Smear tests demonstrated that TNP and DOX-TNP did not cause neutropenia or thrombocytopenia in mice. Therefore, TNP is a safe nanocarrier with excellent biocompatibility and minimal toxicity. In pharmacokinetics study, DOX-TNP greatly increased the SW620 and SW620/Ad300 intratumoral concentrations of DOX, as compared to DOX alone. But DOX-TNP had no effect on the plasma concentrations of DOX up to 240 min after administration. Furthermore, ex vivo IHC analysis of SW620 and SW620/Ad300 tumor sections revealed evidence of prominent antitumor activity of DOX-TNP. In conclusion, our findings suggested that natural nanomaterials could be useful in combating multidrug resistance (MDR) in cancer cells and potentiating the anticancer activity of chemotherapeutic agents in cancer treatment.
Citation Format: Yi-Jun Wang, Yujian Huang, Nagaraju Anreddy, Guan-Nan Zhang, Yun-Kai Zhang, Meina Xie, Derrick Lin, Dong-Hua Yang, Mingjun Zhang, Zhe-Sheng Chen. Tea nanoparticle, a safe and biocompatible nanocarrier, greatly potentiates the anticancer activity of doxorubicin. [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 2201.