bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 765: Drug discovery for targeting the tumor microenvironment from propolis
Authors: Nagasawa Hideko K. , Hattori Hisanori , Narise Kosuke , Watarai Tatsuya , Ueda Satoshi , Okuda Kensuke 
Published: February 2011

Abstract
The tumor microenvironment, characterized by regions of hypoxia, low nutrition, and acidosis due to incomplete blood vessel networks, has been recognized as a major factor that influences not only the response to conventional anti-cancer therapies but also malignant progression and metastasis. However, exploiting such a cumbersome tumor microenvironment for cancer treatment could provide tumor-specific therapeutic approaches. In particular, hypoxia is now considered a fundamentally important characteristic of the tumor microenvironment in which HIF-1 mediated gene regulation being essential for angiogenesis and tumor development. This has led to the current extensive interest in the drug discovery for tumor microenvironment including tumor specific potential molecular targets for cancer therapeutics. Propolis has pleiotropic effects and contains a variety of bioactive polyphenolic compounds. Some flavonoids of them have been reported to inhibit HIF-1α. We therefore evaluated the effects of composition of Brazilian propolis on cellular responses to hypoxia or nutrition deprivation stress for the development of novel anti-cancer drug targeting the tumor microenvironment.
Materials and Method: The ethanol extract of Brazilian propolis was subjected to a series of chromatographic separations to examine HIF-1 inhibition and cytotoxicity under hypoxic and/or glucose deprived condition. The HIF-1α trans-activation effect was evaluated by HIF-1 reporter assay using stable cell lines expressing p2.1. The effect on unfolded protein response (UPR) activation in tumor cell induced by glucose deprivation or 2-deoxyglucose was also examined by GRP78 promoter reporter assay. We performed Immunoblot analysis of the HIF-1α and UPR target genes. The effects on HIF-1α dependent gene expression were investigated by RT-PCR using HCT116 cells.
Result: The propolis whole extract increased HRE-dependent luciferase activity in a dose-dependent manner. From a series of chromatographic separations, we obtained fractions 3, 5 and 8 that inhibited HIF-1-dependent induction of luciferase, while fractions 6 and 10-13 increased the luciferase activity. Cinnamic acid derivative, GPU-215 was isolated from Fr.6 reduced HIF1 transactivation activity, expression of HIF-1α protein and GLUT1 mRNA under hypoxia, while flavonoid, GPU-216 from Fr.8 increased HIF-1α transactivation activity and UPR activation.
Conclusion: We discovered promising compounds from Brazilian propolis for novel anti-cancer drug targeting tumor microenvironment. GPU-215 has inhibitory effect on HIF-1α expression and function, while GPU-216 increased HIF-1α transactivation and UPR activation.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 765.
Abstract 767: The effects of triptolide on human breast cancer cells
Authors: Halaby Reginald , Messina Michael 
Published: February 2011

Abstract
This research seeks to investigate how triptolide, an extract from the Chinese herb Tripterygium wilfordii Hook F, induces apoptosis in MCF-7 and SK-BR-3 human breast cancer cells. Triptolide is known to have anti-proliferative, anti-inflammatory, and anticancer properties. It has been used for over two centuries in Chinese medicine and is now used to treat certain autoimmune diseases. With breast cancer plaguing the United States as the second leading cause of cancer related deaths amongst women, as well as the adverse effects of current treatment methods to patients, there is a need for the development of safer and noninvasive treatments. Triptolide induces apoptosis in human breast cancer cells, but the exact mechanism is still largely unknown. In this study, we examined the ability of triptolide to regulate the protein expression levels of caspase-7 and caspase-9, PARP, and Bcl-2 via western analysis and the Pierce UnBlot In-Gel Chemiluminescent Detection Kit. Apoptosis was monitored using the MTT cell viability assay, LysoTracker™ staining, and measuring tumor volumes in nude mice bearing MCF-7 and SK-BR-3 xenograft tumors. Preliminary results indicate that the amount of apoptosis, which was significantly increased by triptolide in these cells, is both time- and dose-dependent, suggesting that there may be an optimal triptolide concentration for maximal anticancer efficacy. Triptolide differentially regulated the expression of pro- and anti-apoptotic proteins. Furthermore, triptolide decreased tumor volumes in vivo. Further investigation is warranted to determine if and how triptolide is activating the intrinsic apoptotic pathway.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 767.
Abstract 770: The orphan receptor Nur77 overexpression and translocation induced by PCH4 may inhibit malignant brain tumor growth and induce cell apoptosis
Authors: Li-Fu Chang , Lin Po-Cheng , Chiou Tzyy-Wen , Harn Horng-Jyh 
Published: February 2011

Abstract
N-butylidenephthalide(BP), a nature compound from Angelica sinensis, has the antitumor effect in vitro and in vivo. Further, we modified the chemical structure of BP for increasing the antitumor effect and one derivative is (Z)-N-(2-(dimethylamino)ethyl)-2-(3-((3-oxoisobenzofuran-1(3H)-ylidene)methyl)phenoxy)acetamide, PCH4, has 4 times tumor inhibition on human glioblastoma multiform DBTRG-05MG cells. The IC50 of PCH4 on DBTRG-05MG cells is 50 μg/ml. The PCH4 induced apoptosis was related to Nur77 expression and translocation from nucleus to cytosol. Furthermore, the inhibition of PCH4-induced Nur77 expression by Nur77 siRNA can reduce the PCH4-induced apoptosis. In addition, The PCH4-induced apoptosis was associated with JNK pathway. The JNK inhibitor, SP600125, inhibited the Nur77 mRNA expression and reduced the PCH4-induced apoptosis. In conclusion, It suggesting us that the PCH4, the derivatives of BP, induce the Nur77-mediated apoptosis through the JNK pathway and this mechanism different from BP may increase the antitumor effect on GBM cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 770.
Abstract 771: The antimetastasis mechanism of curcumin in colorectal cancer cells
Authors: LIN YU-SHUANG 
Published: February 2011

Abstract
Colon cancer has become a more serious threat to public health due to the changes of the dietary habits in many developed countries. In clinic, the proper therapeutic strategies for colon cancers are complete surgery resection for local diseases, and systematic chemotherapy and radiotherapy for metastatic diseases. However, tumor metastasis is the primary cause resulting in cancer death. Curcumin has been used as an important traditional medicine in almost any kind of illness including cancers. Over the past years, curcumin has been proved to be a multifunctional chemotherapeutic agent. However, the anti-tumor mechanism of curcumin is not completely understood yet. In this study, we investigate the underlying anti-metastasis mechanism of curcumin in colon cancer. Our results showed that curcumin inhibits cell proliferation (IC20 at 20 μM), cell migration (99% of inhibition at 20 μM), cell invasion (99% of inhibition at 20 μM), and colony formation (100% of inhibition at 20 μM) in a dose-dependent manner in colon cancer cells. Additionally, the differentially expressed genes of colon cancer cells treated with 20 μM curcumin were analyzed by Affymetrix genechip compared with mocks. There are 1,239 genes with greater than 2-fold change (p&lt;0.05, FPR). The pathway analysis by using MetaCore and IPA software indicated that cell adhesion and cytoskeleton remodeling pathways may be involved in the anti-metastasis activity of curcumin. Several metastasis-related genes were found to be regulated by curcumin including integrin α2, integrin β5, paxillin and fibronectin. These findings suggest that curcumin may execute anti-metastasis activity by altering cell adhesion/cytoskeleton remodeling pathways in colon cancer cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 771.
Abstract 773: Identification and characterization of natural product-based inhibitors of hypoxia inducible factor-2 alpha
Authors: Rabe Daniel C. , McKee Tawnya , Woldemichael Girma M. , Vasselli James R. , McMahon James , Linehan W Marston , Bottaro Donald P. 
Published: February 2011

Abstract
Clear cell renal cell carcinoma (RCC) is the most prevalent form of kidney cancer and is frequently associated with loss of von Hippel Lindau (VHL) gene function, resulting in the aberrant transcriptional activation of hypoxia response genes that contribute to tumor growth, angiogenesis and metastasis. Prior studies have shown that normoxic stabilization of hypoxia inducible factor (HIF)-1-alpha alone, while capable of mimicking some aspects of VHL loss, are not sufficient to reproduce tumorigenesis, indicating that it is not the most critical oncogenic substrate of VHL protein. To isolate compounds that selectively modulate HIF2-alpha for use as research tools and drug development leads, a cell-based high throughput screen of the NCI Natural Products Repository was performed. Stably transformed clones of the human renal clear cell carcinoma cell line 786-0 expressing a luciferase reporter construct under the control of the human vascular endothelial growth factor (VEGF) promoter-enhancer were used to identify natural product samples with inhibitory activity and minimal cellular toxicity. Leads from initial high throughput screen were chromatographically separated into component structures yielding several pure compounds with micromolar or submicromolar IC50 values, &gt;80% inhibition and &lt;5% cell toxicity. These compounds were then characterized biologically for their ability to inhibit VEGF protein secretion by intact 786-0 cells; several compounds showed &gt;90% inhibition of VEGF secretion at micromolar doses under normoxic conditions. Studies to establish HIF selectivity and effects on RCC cell proliferation, survival, motility and anchorage independent growth are underway.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 773.
Abstract 775: The antiproliferative effects of Mucuna macrocarpa stem extract on HL-60 leukemia cells
Authors: Chi Chin-Wen , Lu Kuan-Hung , Chang Yuh-Fang , Yi Pen-Hui , Chen Ting-Ting , Ho Yu-Ling , Chang Yuan-Shiun 
Published: February 2011

Abstract
Mucuna macrocarpa Wallich (Leguminosae) is believed to hold blood circulation activating effects, and has been used as a folk remedy in Southeast Asia for the treatment of various hematologic and circulatory related ailments. The objective of this study was to investigate whether crude methanolic extract of M. macrocarpa (CMEMM) possessed antileukemic effects on HL-60 human leukemia cells. CMEMM was prepared from dried stems of this plant, and phytochemical analyses of CMEMM revealed major components included lipids (tetracosanoic acid), sterols (mixture of β-sitosterol and stigmasterol), carbohydrates (sucrose and D-pinitol), triterpenoids (friedelin) and isoflavones (medicarpin, calycosin, afrormosin and genistein). The apoptosis-inducing effects of CMEMM were investigated using HL-60 cells in vitro and in vivo. With treatment of 25 to 75 µg/ml CMEMM, the in vitro antiproliferative effect on HL-60 cells increased in a dose- and time-dependent manner during the 72 h treatment period. The concentration of CMEMM that exhibited a 50% growth inhibition (IC50) for 72 h exposure was 36.4 μg/ml. Apoptosis triggered by CMEMM in HL-60 cells was confirmed by the following observations: (1) characteristic apoptotic nuclear fragmentation, (2) dose-dependent accumulation of sub-G1 phase in cell cycle analyses, (3) increased percentages of annexin V-positive apoptotic cells, and (4) dose-dependent elevation of active caspase-3. Additionally, the in vivo effect of CMEMM (500 mg/kg/day i.p.) on suppression of HL-60 tumor growth was observed in mouse xenografts. Moreover, CMEMM exerted anti-inflammatory activities by suppressing production of proinflammatory cytokines, TNF-α and IL-6, in lipopolysaccharide-activated RAW264.7 macrophages. These results together suggest that CMEMM exerted a novel antileukemic effects via an apoptotic pathway on HL-60 cells. Further characterization of the active components in CMEMM and their action in antitumor response will be important for future clinical application.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 775.
Abstract 778: Implication of MAP kinases in the induction of G1 arrest and gadd45 expression by fucoxanthin, a natural carotenoid
Authors: Nishino Hoyoku 
Published: February 2011

Abstract
We have recently demonstrated that fucoxanthin, a natural carotenoid, induces G1 cell cycle arrest in human cancer cells. Up to date, the action mechanism of fucoxanthin has not been elucidated yet. In the present study, we demonstrate that action mechanism of fucoxanthin is very complicated and different depending on the type of cancer cells. Never the less, the induction of gadd45 seems to be important, which is regulated by mitogen-activated protein kinases (MAPKs); p38 MAPK and ERK.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 778.
Abstract 780: Dimethyl cardamonin induces G1-phase cell cycle arrest, apoptosis, and autophagy in HCT116 cells
Authors: ko Hyeonseok , Kim Young-Joo , Park Jin-Soo , Amor Evangeline C , Lee Jong Wha , Yang Hyun Ok 
Published: February 2011

Abstract
Dimethyl cardamonin (2’,4’-dihydroxy-6’-methoxy-3’,5’-dimethylchalcone; DMC) is a naturally occurring chalcone, and it is the major compound isolated from the leaves and/or fruits of Syzygium samarangense (Blume) Merr. & L.M. Perry (Myrtaceae). DMC has been reported to have anti-diabetic, anti-bacterial, spasmolitic and anti-tumor properties. Furthermore, it has been used as an antipyretic and a diuretic agent in Taiwan folk medicine. However, the underlying mechanisms of its anti-tumor effects have not been studied. Here, we report that DMC induced G1 phase arrest, apoptosis and autophagy in HCT116 cell line. In this study, DMC decreased the expression of the phospho-Rb, CDK4 and cyclin D1 expression level, which is correlated with G1 phase. We also found that DMC-induced apoptosis occurred through the p53 dependent manner and the mitochondrial death pathway as evidenced by reduction of the Bcl2, XIAP and caspase-9 activation, and by induction of Bims. And, we showed that DMC up-regulates activity of JNK and p38. Interestingly, we found that DMC elicits autophagy, a process that participates in apoptotic response, in a JNK and p53-dependent manner, in HCT116 cell line. We also found that the increased activation of JNK by DMC is partially regulated by p53, highlighting the relationship of JNK and autophagy to p53 signaling pathway. The treatment of HCT116 (p53 -/-) cell line with DMC resulted in reduction in both apoptotic and autophagic effects relative to HCT116 (p53 +/+) cell line. This study suggested that DMC induced the multiple effects of G1 phase arrest, apoptosis and autophagy through JNK and p53 in HCT 116 cell line.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 780.
Abstract 790: Mutations and copy number gains of EGFR and KRAS genes in lung adenocarcinomas
Authors: Soh Junichi , Toyooka Shinichi , Yamamoto Hiromasa , Shigematsu Hisayuki , Asano Hiroaki , Yamane Masaomi , Tsukuda Kazuhiro , Oto Takahiro , Gazdar Adi F. , Miyoshi Shinichiro 
Published: February 2011

Abstract
Background: Activating mutations or copy number gains (CNGs) of epidermal growth factor receptor (EGFR) and KRAS genes are major oncogenic alterations in lung adenocarcinomas. While mutations of these genes are well-known to be mutually exclusive each other, the interrelationship of four genetic alterations (mutations or CNGs of EGFR or KRAS gene) has never been investigated.
Material and methods: We determined these four genetic alterations in 314 lung adenocarcinoma cases including 176 Asians and 138 Non-Asians from four countries with complete clinical information. Mutational and CNG statuses of EGFR or KRAS gene were determined by direct sequencing and quantitative PCR method, respectively.
Results: EGFR mutations (mEGFR), EGFR CNGs (gEGFR), KRAS mutations (mKRAS) and KRAS CNGs (gKRAS) were present in 25%, 35%, 23% and 6% of 314 cases, respectively (Table 1). Either alteration of EGFR or KRAS gene was present in 41% and 20% of all cases, respectively. Alterations of either EGFR or KRAS gene were observed in 67% of 314 cases, that was significantly more frequent in Asian never smokers (84%) than other groups (61%, P = 0.0001). Of note, CNGs of both genes preferentially occurred in their respective mutant case (P = 0.001 in EGFR and P = 0.04 in KRAS). mEGFR and mKRAS were completely mutually exclusive each other while gEGFR and gKRAS were not. Either alteration of EGFR was also exclusively present with either alteration of KRAS (P &lt; 0.0001) while 19 cases (6%) had alterations of both genes. Interestingly, gKRAS was detected in one case among 79 mEGFR cases (1.3%) while gEGFR could be observed in 10 cases among 71 mKRAS cases (14.1%, P = 0.003).
Conclusion: Activations of EGFR and/or KRAS genes are present in about 70% of lung adenocarcinomas. Activations of EGFR or KRAS gene are almost exclusive and activating mutation of EGFR rarely accompanies KRAS activation, suggesting that two genetic alterations independently associate with oncogenesis of lung adenocarcinomas.Table 1.Activated pathway of 314 lung adenocarcinomasActivated pathwayTypes of activationn%Both genesSubtotal196.1 m, gEGFR + gKRAS10.3 gEGFR + m, gKRAS51.6 gEGFR + mKRAS51.6 gEGFR + gKRAS82.5 EGFR gene aloneSubtotal12941.1 mEGFR3912.4 m, gEGFR3912.4 gEGFR5116.2 KRAS gene aloneSubtotal6219.7 mKRAS5818.5 m, gKRAS31.0 gKRAS10.3 NoneSubtotal10433.1
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 790.
Abstract 792: Prognostic significance of four molecular markers in relation to fatal prostate cancer after prostatectomy
Authors: Weinmann Sheila , Haque Reina , Kallakury Bhaskar , Richert-Boe Kathryn , Berry Deborah , Van Den Eeden Stephen 
Published: February 2011

Abstract
Aside from Gleason grade, there are no established biomarkers to differentiate aggressive from indolent disease in early-stage prostate cancer. Such markers are needed to stratify patient selection for radical or conservative treatment. In the population of three managed care organizations, we conducted a case-control study to evaluate the predictive value of immunohistochemical expression of four molecular markers in formalin-fixed paraffin-embedded tumor tissue from prostatectomy specimens. Cases included 286 men whose prostate cancers progressed to death between 1971 and 2001; 344 controls with non-fatal prostate cancer were closely matched to cases on age, race, tumor stage, diagnosis year, and patterns of health plan membership. One expert prostate cancer pathologist reviewed all pathology slides to determine Gleason grade and select the highest grade tumor specimen for analysis. Formalin-fixed paraffin embedded tissue sections from the above specimens were immunostained by an automated method using antibodies against Ki-67, p53, p27kip1 and BCl-2. Immunoreactivity was semi-quantitatively scored based on intensity and percentage of positive cells in both tumor and adjacent benign tissue, and results were correlated with clinicopathologic variables. Using unconditional logistic regression analysis, we identified Ki-67, P53, P27kip1, and BCl-2 as statistically significant predictors of prostate cancer mortality after adjustment for age, group, race, health plan, diagnosis year, and tumor stage. Marker expression was classified as presence yes/no (P53, BCl-2) or absence yes/no (P27kip1) of any staining or 10%+ expression vs. less (Ki-67). After further adjustment for Gleason grade, marker associations with mortality were as follows: Ki-67 odds ratio = 12.3, 95% confidence interval (CI) 5.3-28.3, p&lt;0.0001; P53 odds ratio = 1.6, 95% CI 1.1-2.3, p=0.02; P27kip1 odds ratio = 2.1, 95% CI 0.90-4.9, p=0.09; BCl-2 odds ratio = 1.3, 95% CI 0.77-2.1, p=0.35. When we combined the four markers into one multivariate model including the matching variables and Gleason grade, only the association with the Ki-67 marker reached statistical significance (odds ratio = 10.6, 95% CI 4.2-26.8, p&lt;0.0001). We conclude that the proliferative index as assessed by Ki-67 immunoreactivity is an independent predictor of aggressive prostate cancer and may have an important role in the selection of the most appropriate therapeutic option in patients with this disease.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 792.