bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 4559: A novel rotational Raman imaging device for early cancer detection
Authors: Garai Ellis , Zavaleta Cristina 
Published: August 2012

Abstract
A novel Raman imaging device that is capable of rotationally scanning hollow structures has been developed to be used in conjunction with tumor targeting Surface enhanced Raman scattering (SERS) nanoparticles. SERS nanoparticles can act as excellent contrast agents in that they offer ultra high sensitivity, and multiplexing capabilities due to the unique spectral signatures associated with them. One key advantage of multiplexing includes the ability to utilize several targeted SERS probes to target and localize a multitude of unique biomarkers associated with a specific disease, and effectively increasing cancer specificity. The device can potentially be used to distinguish a variety of tissues of interest in the colon such as: flat lesions, varying types of adenomas and carcinomas. There are also applications beyond the colon, such as the esophagus, stomach, oral cavity and bladder. In addition, multiplexing can allow for real-time functional imaging. A 45-degree scanning mirror, actuated with micromotor, is used to perform circumferential scans of the lumen of the colon at a rate of 1 revolution per second and a spatial resolution or approximately 1.5 mm. The device is able to be used with currently available endoscopes by inserting it into the working channel of an endoscope. The use of many (36) multi-mode fibers is used to increase the flexibility of the fiber bundle so that it can be inserted and used in a fully articulating endoscope while still being able to collect a sufficient amount scattered Raman light. When in the circumferential scanning mode, American National Standards Institute (ANSI) regulations will allow us to increase the laser illumination power to about 580 mW, resulting in a detection limit of approximately 1 pM of SERS nanoparticles. One of the key features of our Raman device is that it has been designed for efficient use over a wide range of working distances. This is necessary to accommodate for imperfect centering of the device within the colon, as well as variable working distances due to folds and bends within the colon. These techniques could allow endoscopists to distinguish between normal and cancerous tissues instantly, as well as to identify flat lesions that are easily missed during conventional screening endoscopy. After a suspicious region has been identified, the rotating mirror can be held at a certain angle, and used to help guide biopsies or resection of tissues in real-time.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4559. doi:1538-7445.AM2012-4559
Abstract 4562: Comprehensive analysis of the TMPRSS2-ERG translocation during prostate cancer progression
Authors: Ruiz Christian , Braun Martin , Scheble Veit J. , Zellweger Tobias , Rentsch Cyrill A. , Bachmann Alexander , Dodi Albert , Perner Sven , Sesterhenn Isabell A. , Srivastava Shiv , Bubendorf Lukas 
Published: August 2012

Abstract
Introduction. Approximately half of the diagnosed prostate carcinomas (PC) are characterized by a chromosomal rearrangement fusing the androgen regulated gene TMPRSS2 to the oncogenic ETS transcription factor ERG. Aim of this study was to comprehensively analyze the impact of this translocation on the expression of the ERG gene in hormone-naïve (untreated) and castration-resistant prostate cancers and to define the influence of AR protein expression and genomic amplification in this context. Methods. We constructed a tissue microarray (TMA) containing 915 tissue cores from 107 hormone-naïve PC and from 101 castration-resistant (CR) PC. In addition, we included 56 specimens from distant metastases. We analyzed the TMPRSS2-ERG translocation status by fluorescence in-situ hybridization and the expression profiles of ERG, AR and the proliferation marker Ki67 by immunohistochemistry. Results. Nearly half of the analyzed PC tissue specimens (untreated: 38%, castration-resistant: 46%) harbored a TMPRSS2-ERG gene fusion. Untreated PC with positive translocation status showed increased tumor cell proliferation (p&lt;0.05). As expected, TMPRSS2-ERG gene fusion was strongly associated with increased ERG protein expression in untreated, as well as in castration-resistant PC (both p&lt;0.0001). However, we detected a subgroup of CR PCs with the gene fusion, but without detectable ERG protein expression. This subgroup showed significantly lower levels of AR protein expression and of the androgen regulated serum PSA (both p&lt;0.05). Conclusions. This comprehensive study comparing the TMPRSS2-ERG gene and ERG protein expression status in a large cohort of hormone-naïve and CR PC, identifies a subgroup of translocated CR PCs without ERG protein expression. Our results suggest that this subgroup may represent CR PCs with a dispensed AR pathway. Further analyses may help to explain if these tumors represent a distinct subgroup of AR independent CR PCs.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4562. doi:1538-7445.AM2012-4562
Abstract 4681: Inhibition of poly (ADP-ribose) polymerase-1 (PARP-1) as a strategy for targeted therapy in Ewing's sarcoma
Authors: Brenner J. Chad , Feng Felix Y. , Han Sumin , Bou-Maroun Laura M. , Patel Sonam , Goyal Siddharth V. , Liu Meilan , Lonigro Robert , Prensner John R. , Tomlins Scott A. , Chinnaiyan Arul M. 
Published: August 2012

Abstract
The Ewing's sarcoma family of tumors (ESFTs) are aggressive malignancies which frequently harbor EWS-FLI1 or EWS-ERG genomic fusions. Here, we demonstrate that these fusion products interact with, and depend on, poly (ADP-ribose) polymerase 1 (PARP1), a DNA damage response protein and transcriptional co-regulator. This interaction occurs in a DNA-independent manner. ESFT cell lines and xenografts are preferentially sensitive to PARP1 inhibition, and the addition of a PARP1 inhibitor to the second-line chemotherapeutic agent temozolamide resulted in complete response of all treated tumors in an EWS-FLI1 ESFT xenograft model. PARP inhibition blocked Ewing's cell line, but not control osteosarcoma or rhabdomyosarcoma cell line invasion, as well as the formation of lung metastasis in a xenograft model of ESFT. Mechanistically, the EWS-FLI1 and EWS-ERG fusions induce DNA damage, which is potentiated by PARP1 inhibition in ESFT cell lines. In a positive feedback loop, EWS-FLI1 fusions maintain the expression of PARP1 by direct regulation of the PARP1 promoter. This regulation is independently supported by a gene expression array data set of 20 ESFT patient tumors (Spearman r = 0.8165). Finally, because front-line therapy for this disease includes an intense regimen of five cytotoxic chemotherapy agents from which patients can quickly relapse with even more aggressive disease, we studied the effect of PARP inhibition in two Ewing's sarcoma cell line models derived after patient relapse. Importantly, these two cell lines maintained a preferential sensitivity to PARP1 inhibition despite their general chemoresistance. These findings suggest that targeting the EWS-FLI1: PARP1 interaction axis is a promising therapeutic strategy for the Ewing's sarcoma family of tumors.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4681. doi:1538-7445.AM2012-4681
Abstract 4692: ABT-888 synergizes treatment of colon cancer cell lines with irinotecan
Authors: Davidson David , Wang Yunzhe , Aloyz Raquel , Panasci Lawrence 
Published: August 2012

Abstract
Numerous studies have associated poly [ADP-ribosolose] polymerase 1 (PARP1) with DNA-damage repair. PARP1 rapidly localizes to DNA damage sites where it alters target proteins, (e. g. histones, topoisomerase I and DNA dependent protein kinase (DNA-PK)), through the addition of poly-ADP ribose side chains. By this mechanism, PARP1 plays a role in diverse repair pathways including homologous recombination/non-homologous end joining (HRR/NHEJ). Presently, third generation PARP inhibitors are in use clinically. These drugs have resulted in meaningful clinical responses and an increase in survival in metastatic breast and ovarian cancer patients bearing BRCA-deficient or triple negative tumors. The Abbott lead compound, ABT-888, is a potent PARP1 inhibitor that sensitizes many cancer cells in-vitro and in-vivo to temozolomide. In the present work, we hypothesized that colon cancers would be sensitized to the DNA damaging chemotherapeutic agent, irinotecan by ABT-888. Since PARP1 is involved in DNA repair, we propose that its inhibition would increase irinotecan-induced DNA damage and cell death in colon cancer cells lines. Using the sulforhodamine B assay (SRB), significant synergy (I&lt;1 indicates synergy) was observed between ABT-888 and irinotecan at concentrations as low as 0.06 μM (Table 1). Levels of synergy observed in the SRB assay correlated with levels of PARP1 inhibition measured biochemically in cell lysates. Furthermore, 24h post treatment combinations of ABT-888/SN38 resulted in increased G2/M cell cycle arrest and increased levels of DNA damage as determined by γH2AX staining and comet assay. Additionally, 48h post treatment increased levels of apoptosis were associated with this drug combination. In conclusion this study suggests that ABT-888 may be a clinically effective adjuvant to current colon cancer therapies that include the use of irinotecan.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4692. doi:1538-7445.AM2012-4692
Abstract 4703: SAHA downregulation of HuR expression is responsible for reduction of cyclin D1 mRNA stability and cell transformation by EGF in Cl41 cells
Authors: Zhang Jingjie , Ouyang Weiming , Li Jingxia , Yu Yonghui , Li Xuejun , Huang Chuanshu 
Published: August 2012

Abstract
Previous studies have reported that anti-cancer activity of suberoylanilide hydroxamic acid (SAHA) is associated with its downregulation of cyclin D1 protein expression at transcription and translation levels. In current studies, we demonstrated that SAHA downregulation of cyclin D1 expression mainly via modulation of cyclin D1 mRNA stability in EGF-induced mouse epidermal Cl41 cell transformation (anchorage-independent colony formation) model. We found that SAHA treatment resulted in dramatic inhibition of EGF-induced cell transformation and cyclin D1 expression. Further studies showed that SAHA downregulation of cyclin D1 expression was only observed in endogenous cyclin D1, but not in reconstitutional cyclin D1 in same cells, excluding the possibility of SAHA regulation of cyclin D1 expression at levels of protein degradation. Moreover, we found that SAHA was able to inhibit EGF-induced cyclin D1 mRNA expression, whereas it did not show any inhibitory effect on cyclin D1 promoter-deriven luciferase reporter activity under same experimental conditions, suggesting that SAHA might downregulate cyclin D1 mRNA stability. This notion was greatly supported by the results showing that co-treatment of cells with SAHA and actinomycin D increased the cyclin D1 mRNA degradation in comparison to that in cells treated with actinomycin D alone. Consistent with downregulation of cyclin D1 mRNA stability, SAHA treatment also attenuated HuR protein expression, which is a well-characterized cyclin D1 mRNA-binding protein. Taken together, our results demonstrated that SAHA treatment resulted in downregulation of cyclin D1 expression by inhibition of HuR expression, which led to reduction of cyclin D1 mRNA stability and protein expression, and further in turn caused the inhibition of EGF-induced cell transformation in Cl41 cells.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4703. doi:1538-7445.AM2012-4703
Abstract 4716: The antitumor effect of HDAC inhibitor Tenovin-6 for gastric cancer cells
Authors: Ueno Takunori , Hirai Sachiko , Hirose Mitsuaki , Endo Shinji , Suzuki Hideo , Yamato Kenji , Hyodo Ichinosuke 
Published: August 2012

Abstract
Aim: Tenovin-6 is one of the small molecule inhibitors of Histone Deacetylase (HDAC), which have been to shown to suppress cancer cell growth and angiogenesis. In Japan, the mortality of gastric cancer is still high and innovative strategies are required for patients with advanced unresectable gastric cancer. We conducted this study to verify anti-tumor effect of Tenovin-6 as a single agent for gastric cancer cells and also in combination with cytotoxic agents including 5-fluorouracil (5-FU) and cisplatin (CDDP) in vitro. Moreover, we validated the effectiveness of Tenovin-6 on animal xenografted model.Methods: 4 gastric cancer cell lines, MKN-45, NUGC-4 (p53 wild), NUGC-3 (p53 mutant) and Kato-III (p53 null), were incubated with Tenovin-6 in dose and time dependent manner. Cell viability was calculated by WST-8 assay after treatment with Tenovin-6 alone or in combination with 5-FU or CDDP. Protein expression of Sirt-1, p53, p21, DR5 and Caspase-3 were monitored by western blotting to reveal mechanism of antitumor effects by Tenovin-6. In vivo xenograft model established with human gastric cancer cell line MKN-45 was treated with intraperitoneal administration of Tenovin-6 at dose of 50 mg/kg/day for 2 weeks. Results: All 4 gastric cancer cells decreased dramatically by addition of Tenovin-6 with 2.3 to 4.3 μM of IC50. The decreasing trend was not different among cell lines. The additive and synergic effects were shown with combination of 5-FU or CDDP. The expression of Caspase-3, p21 and DR5 were increased by Tenovin-6 in time dependent manner. In contrast, the expression of Sirt-1 and p53 was not changed in all periods. Also in vivo, single agent therapy with Tenovin-6 significantly reduced subcutaneous xenograft tumor growth in nude mice. Conclusion: Tenovin-6 showed excellent anti-tumor effects in all gastric cancer cells via induction of apoptosis and cell cycle arrest. It may be promising therapeutic material for gastric cancer patients.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4716. doi:1538-7445.AM2012-4716
Abstract 4724: Anti-tumor effects of SC-2001, a novel STAT3 inhibitor, in breast cancer cells
Authors: Tseng Ling-Ming , Liu Chun-Yu , Kao Yuan-Ping , Shiau Chung-Wai , Su Jung-Chen , Chang Kung-Chi , Chen Kuen-Feng 
Published: August 2012

Abstract
Background: STAT3 has been shown to play an important role in breast carcinogenesis and is often overexpressed in primary breast tumors. STAT3 has emerged as a novel potential anti-cancer target. Previously, we have designed SC-2001 ((Z)-2-((3-methoxy-2H-pyrrol-2-ylidene)methyl)-1H-pyrrole) and reported its efficacy in HCC cells (AACR 2011, abstract#4516). SC-2001 is structurally related to the Mcl-1 inhibitor obatoclax, and showed better antitumor effects than obatoclax in HCC cells. Here, we examined the efficacy and drug mechanism of SC-2001 in breast cancer cells. Methods: breast cancer cell lines were used for in vitro studies. Apoptosis was examined by both flow cytometry and Western blot. Signal transduction pathways in cells were assessed by Western Blot. Tyrosine Phosphatase Assay Kit was used for SHP-1 activity assay. Gene silencing was done by small interference RNA (siRNA). Results: SC-2001 inhibited tumor cell growth (by MTT assay) and induced apoptosis in several breast cancer cell lines (MDA MB-468, MDA MB-231, MDA MB-453, MCF-7). SC-2001 inhibited the protein-protein interactions between Mcl-1 and Bak similar to obatoclax. In addition, SC-2001 downregulated Mcl-1 expression by reducing its transcription, whereas obatoclax had no such effect. SC-2001 downregulated the phosphorylation of STAT3 (Tyr 705) and subsequently inhibited its transcriptional activities in a dose-dependent manner. Moreover, STAT3-regulated proteins, including Mcl-1, survivin and cyclin D1, were also repressed by SC-2001. Over-expression of STAT3 in MDA MB-468 cells protected cells from SC-2001-induced apoptosis. Importantly, SC-2001 enhanced the expression of SHP-1, a negative regulator of STAT3. Inhibition of SHP-1 by either specific inhibitor or siRNA reduced the apoptotic effects of SC-2001, indicating that SHP-1 plays a key role in mediating SC-2001-induced cell death. Conclusions: our results suggest that SC-2001 induced apoptosis in breast cancer cells, and that this effect is mediated through SHP-1-dependent STAT3 inactivation. (Supported by NSC100-2325-B-002-036, NSC98-2320-B-010-005-My3 and NSC-100-2325-B-010-007, VGHTPE V100D-005-4, 101DHA0100318, and 101DHA0100230.) Keyword: obatoclax, breast cancer, STAT3, SHP-1, apoptosis
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4724. doi:1538-7445.AM2012-4724
Abstract 4728: Fatostatin, a novel SREBP inhibitor, suppresses cell growth and induces apoptosis in prostate cancer
Authors: Li Xiangyan , Chen Yi-Ting , Chung Leland W.K. , Huang Wen-Chin 
Published: August 2012

Abstract
Sterol regulatory element-binding proteins (SREBPs), SREBP-1 and SREBP-2, are transcription factors mainly controlling lipogenesis and cholesterogenesis via the regulation of genes related to fatty acid and cholesterol biosynthesis. We previously showed that SREBP-1 was highly elevated in clinical prostate cancer specimens compared with non-tumor prostate tissues. Also, SREBP-1 promoted cell viability and progression through alterations of the metabolic and signaling networks involving lipogenesis, androgen receptor (AR) and oxidative stress in prostate cancer cells. In the present study, we evaluated the therapeutic benefit of targeting the aberrant SREBP signaling in prostate cancer by using a novel SREBP inhibitor, fatostatin. Fatostatin significantly inhibited cell proliferation and suppressed anchorage-independent colony formation in soft agar in LNCaP and C4-2B prostate cancer cells. Fatostatin also reduced the abilities of in vitro migration and invasion in both cells. The results of flow cytometric analyses with annexin V/propidium iodide staining showed that fatostatin caused G2/M arrest and induced cell death. Additionally, apoptosis was observed by inducing caspase-3 and poly (ADP-ribose) polymerase cleavages and increasing caspase activities in fatostatin-treated prostate cancer cells. In the animal study, fatostatin significantly inhibited C4-2B xenograft tumor growth and markedly decreased serum PSA level compared to control group in immune-compromised mice. The results of fatostatin action in prostate cancer cells in vitro and in vivo are due to specific interruption of the proteolytic process of mature SREBP-1, -2 and their regulated gene expressions including HMG-CoA reductase, fatty acid synthase and further inhibition of lipid biosynthesis and AR signaling network. In summary, our study demonstrates for the first time that fatostatin will be developed as a novel anti-prostate cancer drug and provides new insights into cancer therapy by targeting SREBP.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4728. doi:1538-7445.AM2012-4728
Abstract 4750: Overcoming DDP resistance using folic acid-heparin-DDP nanoparticles
Authors: Peng Xianghong , Wang Yiqing , Chen Zuo (Georgia) , Nie Shuming , Shin Dong M. 
Published: August 2012

Abstract
Cisplatin (DDP) has been widely used in the treatment of different cancers. However, resistance to DDP limits its clinical application. Since reduced intracellular DDP accumulation is one of the main causes for DDP resistance, increasing the accumulation of DDP may overcome drug resistance. The folate receptor (FR) is overexpressed on the surface of many human tumors including breast, ovarian and lung cancer, but is found at low levels in normal tissues. In this study, folic acid (FA) was conjugated to heparin-DDP (FHDDP) nanoparticles to target FR. In vitro cellular uptake experiments showed that the accumulation of FHDDP nanoparticles in FR-expressing DDP-resistant KB-CP.5 cancer cells (selected from KB3-1 cells, and showing a 36-fold increase in resistance to DDP compared with KB3-1) was significantly higher than that of free DDP (9.31±2.2 ng Pt/106 cells vs 0.98±0.25 ng Pt/106 cells, Pt:0.5ug/ml, 4 hrs at 37°C). Further, the level of platinum DNA-adducts in the resistant cells treated with FHDDP nanoparticles was about 4-fold greater than in cells treated with free DDP (24.21±5.32 pg Pt/ug DNA vs 97.9±22.5 pg Pt/ug DNA). Nude mice bearing KB-CP.5 cell tumors receiving FHDDP nanoparticles (2.5mg/kg, tail vein injection, twice weekly, 5 times) showed enhanced antitumor effects as compared with mice treated with free DDP (tumor volume: 823±221mm3 vs 1450±392mm3, 21 days after treatment), while non-targeted heparin-DDP nanoparticles did not show significant difference compared with free DDP. Our results suggest that FHDDP nanoparticles have the potential to be used for overcoming DDP resistance.(This research was supported by the National Cancer Institute award 5 P50 CA128613)
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4750. doi:1538-7445.AM2012-4750