bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 2591: Differential oncolysis by vesicular stomatitis virus in prostate cancers arising in transgenic mice
Authors: Moussavi Maryam , Fazli Ladan , Tearle Howard , Cox Michael E. , Bell John C. , Ong Christopher , Jia William , Rennie Paul S. 
Published: February 2011

Abstract
Prostate cancer (PCa) is the most prevalent malignancy and the second leading cause of cancer related mortality in North American men. Survival prospects for patients with locally advanced or metastatic prostate cancer are low and the side effects associated with current therapies seriously compromise quality of life in PCa patients. Oncolytic viral therapy provides an opportunity to efficiently target and kill primary and metastatic cancer cells while sparing normal cells. Vesicular Stomatitis Virus (VSV) is an oncolytic virus which can infect and kill cells that have defects in their cellular anti-viral immunity such as the interferon (IFN) response pathway. In this study VSV (AV3) strain with enhanced IFN sensitivity was injected intra-prostatically into two different transgenic mouse models (prostate specific PTEN null mice and transgenic adenocarcinoma mice [TRAMP]) and monitored for tissue bioluminescence over 96 h. While the virus readily dispersed throughout the body of each group after only 3 h, it persisted &gt;72 h in prostates of tumor bearing mice compared to low levels ∼48 h in control mice. Plaque assay provided a similar pattern, with much higher concentrations of replicating virus in tumor bearing transgenic mice than in control. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analysis of paraffin embedded tissues demonstrated that VSV(AV3) is capable of selectively infecting and killing malignant prostate cells while sparing normal cells, specifically at the 48h time point. This cell death is due to disrupted IFN response in the PTEN null prostates. Moreover, &gt; 60 % of TRAMP mice treated with VSV(AV3) did not present any metastasis while approximately 70% of TRAMP mice treated with inactivated virus presented metastatic lesions either in lymph nodes or lungs. In summary, our data demonstrates that VSV(AV3) may be used as a potential oncolytic viral therapy to target prostate cancer.
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 2591.
Abstract 2626: Phospho-Akt is the molecular determinant of bortezomib sensitivity to head and neck squamous cells
Authors: Yu-Chin Lin , Chen Kuen-Feng , Chen Kui-Chiu , Chen Ching-Chow , Cheng Ann-Lii 
Published: February 2011

Abstract
Introduction: Head and neck squamous cell carcinoma (HNSCC) is a worldwide prevalent cancer with aggressive clinical courses and dismal outcomes. Incorporation of cetuximab, an antibody against epidermal growth factor receptor, had led to advance of treatment, but the efficacy is modest. Therefore, new treatment for HNSCC is needed. Bortezomib, a proteasome inhibitor approved for treatment of myeloma and lymphoma, demonstrated activities for various solid tumors. Here, we report the differential sensitivity of bortezomib for HNSCC cells and identify the major molecular determinant responsible for activity. Material and method: HNSCC cells, including Ca9-22, SAS, SCC-25 and FaDu, were treated with bortezomib and evaluated for viability, apoptosis, and signal transduction. MTT assay was used for viability. Flow cytometry and Western blotting were performed for apoptosis and signal transduction analysis. Gene silencing was done by small interference RNA (siRNA). Results: Four HNSCC cells showed differential sensitivities to bortezomib. Thorough comparison of molecular change before and after treatment of bortezomib, we found that Akt played a significant role in mediating bortezomib sensitivity to HNSCC cells. Our data demonstrated that bortezomib down-regulated phospho-Akt (Ser473) in dose- and time-dependent manner, and significantly correlated with apoptosis. Knocking down Akt1 by small interference RNA enhanced sensitivity of bortezomib whereas ectopic expression of Akt conferred resistance to bortezomib, suggesting that Akt is indispensible in mediating bortezomib's effect on HNSCC cells. Conclusion: Down-regulation of phospho-Akt represents a molecular determinant of bortezomib-induced apoptosis in HNSCC cells and may be a biomarker for predicting clinical response to HNSCC treatment. Targeting Akt signaling enhances sensitivity to bortezomib in HNSCC cells, which might provide a new approach for the combinational therapy of HNSCC.
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 2626.
Abstract 2628: BU32: A novel proteasome inhibitor for treatment of multiple myeloma and other types of cancer
Authors: ROY SUDIPA SAHA , KIRMA NAMEER , NAIR HAREESH , TEKMAL RAJESHWAR RAO , AGYIN JOSEPH 
Published: February 2011

Abstract
Background: Multiple myeloma (MM) is an incurable neoplasm characterized by devastating and progressive bone destruction. Standard chemotherapeutic agents have not been effective at significantly prolonging the survival of MM patients and these agents are typically associated with often severe, dose-limiting side effects. Proteasome inhibition provides an attractive approach to cancer therapy and may have application in the treatment of MM and also other types of cancers. However, results of recent clinical trials to evaluate the effect of the proteasome inhibitor bortezomib (Velcade®, also called PS-341) in MM patients have shown limited activity when used as a single agent. This underscores the need to find new and more efficacious proteasome inhibitors for treatment of MM. We have recently synthesized a novel proteasome inhibitor BU-32 and tested its growth inhibitory effects in different MM cells including RPMI8226 (human) and 5TGM1 (mouse) and other types of cancer cells.
Methods and Results: In this study, we evaluate the efficacy of the novel proteasome inhibitor BU-32 (NSC D750499) using in vitro and in vivo MM models. BU-32 exhibits strong cytotoxicity in a panel of MM cell lines - RPMI8226 and 5TGM1. Furthermore, proteasome inhibition assay reveals that BU-32 potently inhibits the chymotryptic- and caspase-like activities of the 26S proteasome. Results from our studies using real-time PCR array analyses show that BU-32 effectively down-regulates an array of angiogenesis and inflammatory markers. We show from Annexin V FITC binding studies that BU-32, like bortezomib, induces apoptosis in different MM cell lines but the effect is more prominent in case of BU-32 treated cells. Studies using an in vivo MM model show significant effect and marked reduction in osteolytic bone lesions in radiography with 0.3 mg/kg body weight dose of BU-32. Further testing of BU-32 on pancreatic cancer and various hormone regulated cancers like ovarian and prostate are currently under way. Preliminary cell viability studies on these cancer cell lines indicate BU-32 is highly effective against other cancer cells also. Annexin V FITC binding analyses show that BU-32 drug induces apoptosis to these cell lines. These studies elucidate that BU-32 is a most promising candidate drug for clinical trial as a novel treatment modality for MM and other types of cancer.
Conclusion: Our results suggest that BU-32 might be a potential chemotherapeutic agent with promising antitumor activity for the treatment of MM and other types of cancer.
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 2628.
Abstract 2644: Advanced nanoparticles with anticancer and MRI function for liver cancer in rats and rabbits
Authors: Hong Soon-Sun , Maeng Jin-Hee , Lee Ju-Hee , Choi Myung-Joo , Lee Hyunseung , Jung Kyung Hee , Lee Jeong-Sang 
Published: February 2011

Abstract
Recently drug delivery systems are focusing on the improvement of efficacy, the reduction of side effect, and diagnostics. In the current research, we developed a novel polymeric nanoparticle (YCC) with anticancer effect as well as magnetic resonance (MR) imaging, which encapsulate doxorubicin and superparamagnetic iron oxide (Fe3O4) with the size of 86.4 nm. The efficacy of the nanoparticles was evaluated in hepatocellular carcinoma (HCC) rats induced by the treatment of diethylnitrosamine for 13 weeks as well as in rabbit model with VX2 carcinoma in the liver, comparing with free doxorubicin (FD) and a commercial liposome drug DOXIL®. Each formula was administered intravenously at a dose of 2 mg/kg as doxorubicin three times with 5 day intervals, and anticancer efficacy of YCC were confirmed by MRI (T2) and hematoxylin-eosin (H&E) staining. The tumor size using MRI and the change of body weight were monitored for 10 days after the last administration of each formula. On the end of the study (Day 20th), all the formulas containing doxorubicin suppressed the tumor growth compared with the saline-treated group (control). Especially the relative tumor volume of YCC group was decreased three and four fold compared with the FD and DOXIL® group, respectively. Nevertheless, the loss of body weight as a side effect in YCC group was lower than FD or DOXIL® group. The results from Perls staining and transmission electron microscopy (TEM) confirmed that YCC was distributed in the liver, especially in tumor region rather than non-tumor region. In rabbit model with VX2 carcinoma in the liver, the relative tumor volume in YCC group was decreased two and four fold compared with the FD and DOXIL® group, respectively, as a result of MRI and tissue staining. Like in rat model, the loss of body weight as a side effect in YCC group was lower than FD or DOXIL® group. In both rat and rabbit model, YCC showed the MRI sensitivity comparable to a conventional MRI contrast agent (Resovist®) even in its lower iron content. In the immunohistochemical analysis, YCC group showed the lower expression of CD34 and Ki-67, markers of angiogenesis and cell proliferation, respectively, while apoptotic cells were significantly rich in the YCC group in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Taken together, a novel nanoparticle YCC had anticancer efficacy better than conventional doxorubicin formulas (free doxorubicin and DOXIL®) with the function of MR imaging in rat and rabbit model with carcinoma in the liver. It was considered to a good candidate for the treatment of liver cancer monitoring the progress of the cancer using MRI.
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 2644.
Abstract 2658: Anti-GD3 antibodies are targeting molecules for delivery of RNAi to melanoma
Authors: Michael Wu W. , Pare Genevieve , Tron Victor A. 
Published: February 2011

Abstract
Passive non-targeted delivery of RNAi therapy into tumours has been shown to be neither very effective, nor selective in vitro and in vivo. Consequently in this study, siRNA will be linked to a drug delivery system that will express a ligand that specifically targets melanoma cells. It has been previously shown that melanoma over-expresses the cell surface ganglioside GD3, thus, the anti-GD3 R24 monoclonal antibody can function as a targeting molecule. To do so, a targeting antibody was conjugated to a coated cationic liposome (CCL) exterior to effectively deliver RNAi to melanoma. Cell surface expression of GD3 on Malme 3M, LOX IMVI and SK-MEL-5 cells was verified by flow cytometry. Internalized levels of siRNA within CCLs were the quantified via spectrometry. Encapsulation efficiency of siRNA was calculated to be greater than 70%. The quantification of antibody expression on CCLs was measured, illustrating that while non-targeted CCLs showed insignificant values of antibody as expected, antibody-conjugated CCLs presented a decreasing trend of expression that can be explained by the multi-step purification process for the final CCL products. Fluorescent microscopy results, from the combination of internalized siRNA and Tex615 RNA within CCLs, displayed greater fluorescence with antibody-conjugated CCLs than non-targeted CCLs when Malme 3M, LOX IMVI, and SK-MEL-5 cells were treated. Taken together, these results conclude that the use of GD3-targeted liposomes can promote siRNA delivery to melanoma 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 2658.
Abstract 2673: In silico design of E2F1 mimics as potential anticancer agents
Authors: Kerrigan John E. , Abali Emine E. , Banerjee Debabrata , Hsieh Yi-Ching , Xie Xiaoqi , Bertino Joseph R. 
Published: February 2011

Abstract
Introduction. We report the construction of a homology model of the human E2F1-DP1 transcription factor complex with DNA to be used as a tool for design of drugs targeted to the promoter of this oncogene based on interference of transcription factor binding. Using shape-based docking and force field calculations, we investigate the development of novel penetratin-based (PED) peptides, obtained by phage display, (E2F1 mimics) as potential binders to the major groove of GC-rich regions of DNA.
Computational Procedures. The homology model of E2F1-DP1 complex with DNA was built using the Modeller (9v5) program. We used the DNA binding domains of the E2F1 and DP1 sequences (NCBI accession #'s AAC50719 and NP009042 respectively), and the x-ray crystal structure of the E2F4-DP2 complex with DNA (1CF7.pdb) as the primary template. The DNA from the crystal structure was modeled in place using the default spatial constraints in Modeller.
The PED based peptide models were built using the x-ray crystal structure of the antennapedia homeodomain-DNA complex (9ANT.pdb) as a template. The alignment is shown below (The penetratin portion is shown in bold and the variable portion is in italics.).
_aln.pos 10 20 30 40 50 60
9antA RQTYTRYQTLELEKEFHFNRYLTRRRRIEIAHALSLTERQIKIWFQNRRMKWKK—–EN
brt1 ————————————–RQIKIWFQNRRMKWKKHHHRLSH
_consrvd ****************
The PatchDock program was used to dock the peptides to the DNA structure from 1CF7.pdb based on shape complementarity. The best shape scoring major-groove binding orientation was selected and refined via energy minimization using the Amber ff99SB force field. Interaction energy scores were computed from the non-bonded energy terms of the Amber force field (Eint = ∑ Evdw + ∑ Eelec).
Data Summary. The HHHRLSH sequence is predicted to form a more stable complex compared to the GGGALSA sequence. The PED-HHHRLSH peptide was shown to have potent activity against several cancer cell lines (Xie, et al. AACR 2009). In the case of the HHHRLSH sequence, the model predicts enhanced stability in going from L-Arg (−646.0 kcal/mol) to D-Arg (−688.0 kcal/mol).
Conclusions. The α3 helix of E2F1 composed of KRRIYDITNVLEGI binds to the major groove of GC-rich DNA. The PED-HHHRLSH peptide complex with DNA (−646.0 kcal/mol) has similar interaction energy to that of the E2F1-DNA complex (−653.0 kcal/mol), is a stable α-helical structure, and is a potential E2F1 mimic.
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 2673.
Abstract 2680A: Small molecule induces apoptosis through the inhibition of signal transducers and activators of transcription 3 in hepatocellular carcinoma cells
Authors: Chen Kuen-Feng , Chen Wei-Lin , Tai Wei-Tien , Cheng Ann-Lii , Chen Pei-Jer , Shiau Chung-Wai 
Published: February 2011

Abstract
Sorafenib, a multiple kinase inhibitors, shows therapeutic effects in renal carcinoma (RCC) and hepatocellular carcinoma (HCC). Our data shows that the inhibition of signal transducers and activators of transcription 3, a transcription factor involving in cell proliferation and survival, represents a major mechanism whereby sorafenib induces apoptosis in HCC cells. Sorafenib inhibits the phosphorylation of STAT3 and subsequently reduced the STAT3-regulating protein, Mcl-1, survivin and cyclinD1. In addition, the activity of SHP-1, a protein tyrosine phosphatase, is increased in HCC cells by the treatment of sorafenib. We hypothesize that the antitumor effect of sorafenib can be attributed to the level STAT3 and the activity of SHP-1. Therefore, we design and synthesize a sorafenib derivative, SC-1, which is devoid of kinase activity. SC-1 shows higher potency in inducing apoptosis than sorafenib. Therefore, SC-1 provides a proof of concept for the design of a new class of agents that enhance SHP-1 activity along and synergize with therapeutic agent in HCC.
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 2680A.
Abstract 2691: Prognostic significance of heat shock protein 90 expression in patients with advanced gastric cancer
Authors: Dote Hideaki , Nishimura Rieko , Yamamoto Tamami , Iguchi Haruo , Nozaki Isao , Hato Shinji , Kobatake Takaya , Ohta Kouzi , Aogi Kenjiro , Kubo Yoshiro , Tanada Minoru , Kurita Akira 
Published: February 2011

Abstract
Purpose: Heat shock protein 90 (HSP90) is a chaperone mediating the folding and stabilization of many oncoproteins. Considerable attention has been focused on the role of the HSP90 in the therapeutic strategy of molecular targeting HSP90. Recently it has reported that Trastuzumab, a recombinant monoclonal antibody against HER2, plus chemotherapy improved survival in HER2-positive gastric cancer patients. This study was designed to delineate the clinical implications of Hsp90 and HER2 immunoexpression in advanced gastric cancer.
Material and Methods: The study group comprised 47 patients who underwent gastrectomy at Shikoku Cancer Center Hospital excluding patients with stage I. According to the TNM classification, 18 tumors were identified as being stage II, 25 stage III, 4 stage IV. Using immunohistochemical techniques, we analyzed the expressions of HSP90 and HER2 on formalin-fixed paraffin-embedded specimens of surgically removed primary tumors. Immunostaining was graded as follows: low-HSP90 (defined as weaker staining compared with adjacent normal gastric mucosa), moderate-HSP90 (defined as equal), high-HSP90 (defined as stronger). HER2 expression was graded using a 4-point scale according to the criteria of HER2 membranous staining, which have been widely accepted. Chi-square test, Kaplan-Meier and Cox regression analysis were used for statistical analysis.
Results: Low-HSP90 expression was found in 13 tumors (28%) and HER2 high-expression (moderate to strong membrane staining in &gt; 10% of tumor cells) in 13 tumors (28%). Low-HSP90 was significantly detected in diffuse type (p = 0.0047) and was associated with clinicopathological parameters involved with tumor progression, including the depth of tumor invasion (p = 0.049) and advanced stage tumor (p = 0.029). Of note, High-HSP90 and HER2 overexpression (3+) were mutually exclusive (P=0.031). Kaplan-Meier survival analysis determined that tumors with low-HSP90 expression were statistically associated with worse disease-free survival (p = 0.036), and tended to detect poor postoperative survival (p = 0.084). Multivariate survival analysis showed that HSP90-negative expression [hazard ratio (HR) 3.05, 95% confidence interval (95% CI) 1.02-9.18; p = 0.046] and lymph node metastasis (HR 5.55; 95% CI 1.68-18.2; p = 0.005) were significant predictors of poor postoperative survival.
Conclusions: Our results indicate that low-HSP90 expression correlated with more aggressive disease and poor prognosis, and that HSP90 and HER2 overexpression might separately be molecular targets in gastric cancer.
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 2691.
Abstract 2795: Serum IGF-I, IGF-II, IGFBP-3, and IGF-I/IGFBP-3 molar ratio and risk of pancreatic cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
Authors: Douglas Jason B. , Silverman Debra T. , Pollak Michael N. , Tao Yuzhen , Soliman Amr S. , Stolzenberg-Solomon Rachael Z. 
Published: February 2011

Abstract
Experimental evidence suggests that an overexpression of insulin-like growth factor-I (IGF-I) is implicated in human pancreatic tumors. Moreover, increased IGF-II and decreased insulin-like growth factor binding protein-3 (IGFBP-3) concentrations are found in a number of cancers. We conducted a nested case-control study in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort of men and women 55-74 years of age at baseline, to test whether pre-diagnostic circulating IGF-I, IGF-II, IGFBP-3, and IGF-I/IGFBP-3 molar ratio concentrations were associated with exocrine pancreatic cancer risk. Between 1994 and 2006, 187 incident cases of pancreatic adenocarcinoma occurred (follow-up to 11.7 years). Two controls (n=374),who were alive at the time the case was diagnosed, were selected for each case and matched by age, race, sex and date of blood draw. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression, adjusting for smoking. In the multivariable adjusted model, IGF-I, IGF-II, and IGFBP-3 concentrations were not associated with pancreatic cancer (highest compared with lowest quintile, OR=1.23, 95% CI 0.67-2.25, p-trend=0.12; OR=0.98, 95% CI 0.52-1.85, p-trend=0.52; and OR=1.15, 95% CI 0.62-2.16, p-trend=0.90). However, a significant positive trend was observed with high IGF-I/IGFBP-3 molar ratio levels in the smoking-adjusted model (OR=1.46, 95% CI 0.78-2.74, p-trend=0.04). A higher IGF-I/IGFBP-3 molar ratio may represent increased free IGF-I and be a risk factor for pancreatic cancer.
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 2795.