bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B169: Antitumor activity of a new compound NBRI17671 produced by Acremonium sp. CR17671.
Authors: Kawada Manabu , Usami Ihomi , Someno Tetsuya , Watanabe Takumi , Abe Hikaru , Inoue Hiroyuki , Ohba Shun-ichi , Masuda Tohru , Nomoto Akio 
Published: June 2012

Abstract
Tumor microenvironment is now getting much attention as tumor therapeutic targets. We have been studying the tumor-stromal cell interactions and found new candidates for antitumor drugs. We have then reported various compounds that inhibit tumor growth through the modulation of the tumor-stromal cell interactions (Cancer Res 66, 4419, 2006; Int J Cancer 126, 810, 2010; J Antibiot 63, 319, 2010). In this report we have focused on the binding of cells to ligands.
Interaction between the receptor for advanced glycation end-product (RAGE) and amphoterin plays an important role in tumor growth and metastasis. Because the abrogation of the interaction results in the inhibition of the tumor growth and metastasis, we designed a screening system for an inhibitor of the interaction between RAGE and amphoterin. In the course of our screening of the inhibitor, we isolated a novel natural compound NBRI17671 (1) from the fermentation broth of Acremonium sp. CR17671. We also modified 1 into more active NBRI17671al (2). While 1 at 50 μg/ml weakly inhibited binding of various cells to amphoterin, 2 at 50 μg/ml inhibited it more than 50% of control. Compound 2 effectively inhibited the tumor growth of glioma and lung tumor xenografts in mice at 25 mg/kg. Furthermore, 2 was found to downregulate MAPK activity in the tumor cells. Collaborator: Meiji Seika Pharma.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B169.
Abstract B171: Involvement of Akt/NF-κ B pathway in antitumor effect of parthenolide on glioblastoma cells.
Authors: Nakabayashi Hiromichi , Shimizu Keiji 
Published: June 2012

Abstract
Background: Glioblastoma is the most common and aggressive form of malignant glioma and is very difficult to treat. Controlling glioblastoma cell invasion and angiogenesis is essential to improve the prognosis of glioblastoma patients. Constitutive activation of Nuclear factor-κB (NF-κB) is crucial for tumor progression. Inhibition of NF-κB may be an important pharmacological target for the control of tumor progression. Our study aimed to evaluate the antitumour effects of parthenolide, NF-κB inhibitor, on two human glioma cell lines (U87MG, U373) and the molecular mechanisms underlying these effects.
Methods: The anti-invasive effect of parthenolide was analysed by an in vitro invasion assay. An in vitro angiogenesis assay was also performed. In vitro growth inhibition of glioma cells by parthenolide was determined by the MTT assay. The effect of parthenolide on an orthotropic implantation model using athymic mice was also evaluated.
Results: Parthenolide suppressed the proliferation of glioblastoma cells. Parthenolide also suppressed both the invasion of glioblastoma cells and tumor-induced angiogenesis. Molecular-based studies demonstrated that parthenolide suppressed gene and protein expression of angiogenic factors. Furthermore, parthenolide reduced the phosphorylation of Akt and activated mitochondrial cascade, suggesting that the antitumor effect of parthenolide may be mediated by the inhibition of the Akt signal and the activation of apoptotic proteins. An in vivo intracerebral human glioblastoma xenograft mouse model demonstrated that parthenolide suppressed neovascularity and tumor growth.
Conclusions: The results of the present study suggest that parthenolide may be a new therapeutic agent for glioblastomas.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B171.
Abstract B172: Dietary administration of KIOM210091 attenuates xenograft tumor growth in H460 injected nude mice.
Authors: Kim Jinhee , Park Jong Shik , Oh Se Mi , Lee Jun , Kim No Soo , Bang Ok-Sun 
Published: June 2012

Abstract
KIOM210091 is an ethanol extract of seeds from one of Brassicaceae plant which has been widely used to relieve cough, prevent asthma, and reduce edema as traditional medicine in Korea and China. However, little is known about its chemical property, biological activity, and the molecular mechanism.
In our preliminary experiments, KIOM210091 showed potent cytotoxic effect on all of our 30 panels of different cancer cell lines originated from different tissue origins such as lung, kidney, intestine, prostate, uterine, and lymphocytes. It is previously unknown if KIOM210091 is effective against tumors when delivered as a dietary component, so we attempted to assess the anti-tumorigenic property of KIOM210091 in vivo xenograft tumor system.
Here our date showed that KIOM210091 attenuated tumor growth in H460-injected Balb/c athymic nude mice. A group of mice (n=6) was treated with 250mg/kg/d of KIOM210091 ad lib for 5 days/week for 3 week-period. This group of mice showed inhibited xenografted H460 cell tumor growth which was comparable to those groups treated with chemotherapeutic agents, rapamycin and 5-fluorouracil. However, low dose (50mg/kg/d) treatment had little or no effect on inhibition of tumor growth. Additionally, there was no adverse effect of KIOM210091 treatment during 3 week period administration.
Bioassy-guided fractionation revealed that the cytotoxic compound of KIOM210091 was found in ethyl acetate fraction and purification of single active compound is on the way. This fraction showed enhanced cytotoxic effects on tumor cells compared to the 80% ethanol extract. Our data also suggested that KIOM210091 as well as the active fraction had an effect on inhibiting the proliferative kinases and inducing apoptosis-related proteins.
Our data demonstrated the anti-tumorigenic effect of orally administrated KIOM210091, as well as the signaling pathway modulation. This study implicates this relatively safe, natural compound as a potential therapeutic and chemopreventive agent for lung cancer.
This research was supported by Korea Institute of Oriental Medicine Grant #K11062.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B172.
Abstract B174: KIOM 210102 inhibits proliferation of colon cancer cells by G2/M phase arrest.
Authors: Oh Se Mi , Yi Jin Mu , Kim Jinhee , Lee Jun , Bang Ok-Sun , Kim No Soo 
Published: June 2012

Abstract
KIOM210102 is ethanol extract, a medicinal plant belonging to the Aristolochiaceae that has been used to cure for pain and fever traditionally in Korea, Chinese and Japan. It has also been used for treatment of inflammation, allergy and histamine-related disease. Our preliminary study showed that KIOM210102 has a potent cytotoxic effects on several cancer cell lines including HCT116, a human colon carcinoma cell.
Here we attempted to assess the anti-carcinogenic mechanism of KIOM210102 in human colon carcinoma cell line. HCT116 cells were treated with different concentrations of KIOM210102 for 48 hrs for cell viability measured by MTS assay. At a concentration of 15.8×0.68 ug/ml, KIOM 210102 inhibited 50% of proliferation of HCT116. The cell cycle distribution and apoptosis were measured by flow cytometry using Propidium Iodide staining and immunoblotting method was used to study parameters associated with apoptosis and cell proliferation.
Our data revealed that there was an acute G2/M cell cycle arrest followed by massive cell death in the cells treated with KIOM210102. The effect of KIOM210102 was mediated by increased p53 and p21waf/cip expression and decreased cyclin B. These processes were accompanied by caspase-3 activation and PARP cleavage and down regulation of the anti-apoptotic protein Bcl-2.
These results suggest that KIOM210102 has a potential for a novel herbal anti-cancer therapeutics.
This research was supported by a grant from the Korea Institute of Oriental Medicine (KIOM, K11061).
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B174.
Abstract B179: Mechanism of antitumor activity of BET inhibitors in models of lymphomas and leukemia.
Authors: Sandy Peter , Mertz Jennifer , Conery Andy , Bryant Barbara , Biagini Linda , Balasubramanian Srividya , Lora Jose , Sims Robert , Bergeron Louise 
Published: June 2012

Abstract
Proteins of the BET family bind to acetylated histones and promote gene expression by recruiting transcriptional activators. We developed BET inhibitors and demonstrated a strong association between biochemical inhibition of BET-chromatin binding, MYC suppression and reduced proliferation in hematopoietic cancer cells. We assessed the gene loci affected by BET inhibition by integrating ChipSeq and gene expression profiling, and identified genes that are directly regulated by BRD4 binding, most notably MYC, or genes that are targets of MYC. BET inhibition resulted in robust suppression of MYC expression in tumor xenograft models. Moreover, based on the PK/PD relationships established for these compounds we designed dosing regimens that resulted in significant anti-tumor efficacy in xenograft models of Burkitt's lymphoma and acute leukemia. Compound doses and schedules resulting in sustained MYC suppression were most effective in inhibiting tumor growth and were well tolerated.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B179.
Abstract B180: Novel candidate tumor markers identified by a high-throughput “immuno-reverse-proteomics” approach.
Authors: Pileri Piero , Pierleoni Andrea , Campagnoli Susanna , Grandi Alberto , Parri Matteo , Nogarotto Renzo , De Camilli Elisa , Abrignani Sergio , Viale Giuseppe , Sarmientos Paolo , Grandi Guido , Grifantini Renata Maria 
Published: June 2012

Abstract
Cancer biomarker discovery is an extremely active research field in both academia and pharmaceutical companies. Here we present a group of candidate tumor markers identified by a high-throughput immunohistochemistry approach based on the use of a library of 1600 mouse antibodies raised against marginally-characterized human proteins. Tissue microarray (TMA) representing breast, lung colon ovary and prostate cancers were used to identify novel tumor markers. Eighty-nine proteins were found over-expressed in one or more of the five tumors under analysis. The validation process is still in progress and so far has been undertaken on twenty-six of the eighty-nine hits. They are confirmed over-expressed in TMAs carrying 50 tumor samples for each tumor type and, in particular, nineteen proteins were found expressed in one or more tumors with frequencies ranging from 20% to 96%. Interestingly, some of the proteins are simultaneously over-expressed in specific patients' groups, thus opening the possibility of tissue diagnostic/prognostic/predictive applications based on combinatorial markers. Moreover, in vitro characterization studies indicated that some markers play a pivotal role in tumor-related cell processes like cell proliferation (EXN32; EXN36; EXN7), invasiveness (EXN32; EXN36; EXN7; EXN4), clonal growth (EXN1) and pro-angiogenesis (EXN11). A panel of monoclonal antibodies highly specific the biomarkers is already available and proved to specifically detect the markers in tumor cells derived from surgical resections. The newly identified candidate markers are new tools for the development of specific drug therapies and diagnostic products.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B180.
Abstract B183: Nkd2 expression and survival in lung adenocarcinoma.
Authors: Lui Natalie , Sheng Qing , Li Hui , Do Hanh , Jablons David , He Biao 
Published: June 2012

Abstract
Objectives: Lung cancer is the leading cause of cancer mortality in the United States and worldwide, and Wnt signaling pathway abnormalities have been implicated in its development. We planned to study the expression of Naked cuticle 2 (Nkd2), a Wnt signaling pathway antagonist, in lung adenocarcinoma tissue specimens.
Methods: Two hundred patients with lung adenocarcinoma underwent surgical resection. Tumor and adjacent normal specimens were collected at the time of the procedure and stored in liquid nitrogen until analysis. Clinical data, including patient age, sex, vital status, smoking status, as well as tumor histology and stage, were obtained by review of electronic medical records. RNA was extracted using the Qiagen RNeasy Mini Kit, and cDNA was synthesized using the Bio-Rad iScript Kit. Nkd2 expression was measured using a microarray in 110 patients and quantitative polymerase chain reaction (qPCR) in 90 patients. We looked for differences in Nkd2 expression between patients of different sex, histologic subtype, or vital status; and among patients with different smoking status or stage. We described the distribution of Nkd2 expression in both the microarray and qPCR cohorts. We analyzed the relation between Nkd2 expression and survival using the Kaplan-Meier method and a Cox proportional hazards model.
Results: There was no difference in Nkd2 expression between patients of different sex, histologic subtype, or vital status; nor among patients with different smoking status or stage. Nkd2 expression in the tumor was upregulated in the microarray cohort, but downregulated in the qpCR cohort, compared to the adjacent normal. In the microarray cohort, Nkd2 expression was not significantly related to survival (p=0.71). In the qPCR cohort, after adjusting for age, sex, smoking status, bronchoalveolar carcinoma status, and stage, lower Nkd2 expression was significantly associated with longer survival (p=0.03). Stage was the only other significant predictor of survival (Wald test, p = 0.0002).
Conclusion: In one cohort in our study, lower Nkd2 expression was significantly associated with longer survival. It is unclear why lower expression of Wnt signaling pathway antagonist would be associated with longer survival, when higher Wnt signaling has been associated with carcinogenesis. One hypothesis is that there is a negative feedback mechanism, in which upregulation of Wnt signaling leads to upregulation of Nkd2. Molecular markers have a growing role in cancer research, and further studies on Nkd2 may lead to new diagnostic and therapeutic applications.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B183.
Abstract B196: Evaluation of the ubiquitin activating enzyme (UBA1) as a therapeutic target via inducible RNA interference in human tumor xenografts.
Authors: Li Zhi , Traore Tary , He Xingyue , Yang Yu , Li Ping , Bence Neil , Manfredi Mark , Smith Peter G. , Pulukuri Sai M. 
Published: June 2012

Abstract
The successful transition of the Nedd8-activating enzyme inhibitor, MLN4924, into clinical trials has greatly increased optimism for the application of other E1-activating enzyme inhibitor therapies in cancer. UBA1 is an essential E1 enzyme that controls the first step in the activation of ubiquitin. Ubiquitin is a 9 KDa protein that is involved in multiple cellular processes through conjugation to a large range of target proteins. Several of these processes are important in cancer including ubiquitin-dependent protein turnover, cell cycle progression, apoptosis and the DNA damage response. Thus, inhibiting UBA1 with small molecule inhibitors may prove to be a viable anticancer strategy. To validate UBA1 as an oncology target we utilized a lentiviral vector-mediated inducible knockdown of UBA1 by a microRNA-based shRNA (shRNAmir) in cells and xenografts derived from human cancer cells. Our data show that shRNAmir-mediated knockdown of UBA1 is tightly regulated by the inducer doxycycline in a concentration- and time-dependent manner in HCT-116 cells. Furthermore, UBA1 expression is restored upon withdrawal of the inducing agent, which coincides with decreased shRNAmir expression as marked by turboRFP. The shRNAmir-mediated depletion of UBA1 in cells resulted in reduced abundance of ubiquitin conjugates and decreased proliferation of HCT-116 cells, ultimately resulting in apoptosis. Next, we established inducible shRNAmir HCT-116 xenograft models in nude mice to examine the in vivo efficacy of inhibiting UBA1. Our results showed knockdown of UBA1 protein levels, decreased abundance of ubiquitin conjugates and apoptosis in vivo following doxycycline administration to mice. The effects of UBA1 knockdown and inhibition of ubiquitin conjugation resulted in tumor xenograft regressions in all mice. Withdrawal of doxycycline treatment resulted in regrowth of tumors with concomitant recovery of UBA1 levels and detectable ubiquitin conjugates in tumor xenografts. This study demonstrates that UBA1 knockdown effectively inhibits tumor growth and mediates tumor regression in a human xenograft model, implicating UBA1 as a novel therapeutic target for cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B196.
Abstract B198: Integrated genomic analysis of breast cancer CNS metastasis to the CNS.
Authors: Salhia Bodour , Ross Juli , Paquette Kim , Fowler Aaron , Van Cott Courtney , Metpally Raghu , Baker Angela , Nasser Sara , Kiefer Jeff , Ramanathan Ramesh , Resau James , Berens Michael , Carpten John , Tran Nhan 
Published: June 2012

Abstract
With improvements in systemic therapies, the brain is becoming an increasingly common sanctuary site of metastatic disease in patients with breast cancer. There have been limited improvements in the treatment of brain metastases and current treatment paradigms focus on resection and radiation therapy. As cancer dissemination to the brain currently leads to fatal outcomes developing new therapeutic approaches is paramount. We performed a deep integrated genomic and epigenomic analysis to catalogue the compendium of common and rare events that underlie breast cancer CNS metastasis. Our samples represent breast cancer CNS metastasis, primary breast cancer, non-neoplastic brain and non-neoplastic breast tissue. We performed copy number analysis using array-based comparative genomic hybridization (aCGH, Agilent SurePrint G3 Human High-Resolution Discovery Microarray Kit 1×1M platform); gene expression profiling (GEP) (Agilent, Human GE 4×44 v2 Microarray platform); and DNA methylation analysis (Illumina, HumanMethylation 27 BeadChip). Here we report frequent large chromosomal gains in 1q, 8q, 10p, 21q, and 22q. Frequent large chromosomal deletions were also seen on 8p, and 17p. Focal gains and losses occurred frequently on chromosomes 14, 17 and 22. The PAM50 breast cancer intrinsic classifier was used to classify CNS metastasis tumors. The most common molecular subtypes identified were Luminal B, Her2+/ER negative and Basal-like tumors. Although breast CNS metastasis tumors retained features of their original intrinsic subtype, additional changes were acquired. In addition, DNA methylation analysis of the most variable methylated genes demonstrated epigenetic similarities among the individual molecular subtypes and that overall CNS metastasis is associated with hypermethylation. On average 108 genes had alterations by copy number, gene expression and DNA methylation. Among these are candidate tumor suppressor genes SERPINF1 and SFRP1. Pathway enrichment using Ingenuity Systems revealed a large number of enrichment maps concentrated around cell cycle and G2/M transition. This enrichment contained important cancer genes such AURKA, AURKB and FOXM1. Current studies are ongoing to validate novel candidates genes using cross platform and independent sample cohorts. Characterization of such candidates is expected to lead to novel therapeutic approaches and an enhanced understanding of the biology mediating breast CNS metastasis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B198.
Abstract B21: The difference in the role of PI3K/Akt/mTOR pathway between oropharyngeal squamous cell carcinoma and oral cavity squamous cell carcinoma.
Authors: Won Hye Sung , Hong Ji Hyung , Jeon Eun Kyoung , Ko Yoon Ho , Chun Sang Hoon , Jung Chan-Kwon , Kang Jin-Hyoung 
Published: June 2012

Abstract
Recently, there is growing evidence to support that oral cavity and oropharyngeal squamous cell carcinoma are two distinct diseases with different etiology. The aim of this study was to evaluate the expression of EGFR, PI3K/Akt/mTOR pathway, and PTEN in oral cavity and oropharyngeal cancers, and to investigate their clinical significance as prognostic markers.
One hundred twenty-one patients who underwent curative surgery for oral cavity or oropharyngeal squamous cell carcinoma in Seoul St. Mary's Hospital between January 1995 and September 2009 were evaluated. The level of protein expression of EGFR, PIK3CA, pAkt, mTOR, and PTEN was assessed by immunohistochemistry. In situ hybridization was used for assessment of human papillomaviruses (HPV).
Nineteen of 61 patients with oropharyngeal cancer showed HPV-positive tumors, and 2 of 60 patients with oral cavity cancer showed HPV-positive tumors. EGFR and pAkt expression were significantly higher in oray cavity cancer than in oropharyngeal cancer. Loss of PTEN was significantly higher in oral cavity cancer than in oropharyngeal cancer. There were no significant differences in PIK3CA, mTOR, and p53 expressions. HPV-negative tumors overexpressed more EGFR and pAkt than HPV-positive tumors. Loss of PTEN expression was more frequent in HPV-negative tumors than in HPV-positive tumors. In multivariate cox regression analysis, pAkt expression showed a significant impact on relapse-free survival. There was a significantly negative correlation between PTEN and pAkt expression, and positive correlation between pAkt and mTOR expression.
We concluded that there were differences in expression of EGFR, pAkt, and PTEN between oropharyngeal and oral cavity cancer. It was attributed to etiologic role of human papillomaviruses in oropharyngeal cancer. The expression of pAkt may be a prognostic marker for relapse-free survival in oropharyngeal cancer.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B21.