bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1684: The potential role of HER3 on HER2-driven biliary carcinogenesis and the possibility for targeted therapy with pertuzumab
Authors: Kawamoto Toru , Onuki Ken-ichiro , Sugiyama Hiroaki , Thomas Melanie , Yamashita-Kashima Yoriko , Shu Sei , Harada Naoki , Fujimoto-Ouchi Kaori , Ariizumi Shun-ichi , Yamamoto Masakazu , Shoda Jun-ichi 
Published: August 2012

Abstract
HER2 has been implicated in biliary carcinogenesis, because gene amplification of HER2 has been observed in 20% of gallbladder carcinoma (GBC) (Kawamoto, et al. GCR 2007). The first-in-class HER2 dimerization inhibitor (HDI) pertuzumab is a humanized monoclonal antibody that binds HER2 at an epitope that prevents HER2 from dimerizing with ligand-activated HER family receptors, In this study, we determined the expression of HER family proteins in GBC, cholangiocellular carcinoma(CC), and examined whether treatment with pertuzumab would affect GBC and CC cell lines. Methods: HER family expression was examined in surgical or biopsied specimens from 47 GBCs and 57 CCs by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Using 6 GBC and 8 CC cell lines, heregulin-stimulated cell proliferation and its inhibition by pertuzumab, were tested in vitro by MTT assay. The phosphorylated HER family proteins and their respective downstream molecules were examined by Western blot analysis. Anti-tumor activity of pertuzumab in vivo was evaluated in the CC cell line KMCH-1 xenograft model with weekly intraperitoneal administration. Results: Over-expression of HER2 or HER3 was observed in 14-34% of all patients (Table 1). Six of 14 cell lines demonstrated over-expression of both HER2 and HER3, and heregulin stimulation increased the proliferation in 3 of them. In the HER2- and HER3- over-expressing KMCH-1, pertuzumab significantly inhibited cell proliferation in a dose-dependent manner. Pertuzumab completely blocked heregulin-induced phosphorylation of HER3. Furthermore, suppression of downstream pathway molecules including pAKT and pS6 were observed. The xenograft model also revealed tumor growth inhibition with pertuzumab. Conclusions: Pertuzumab demonstrated significant antitumor activities in HER2 and HER3 over-expressing cancer cells. Thus, pertuzumab may provide a new therapy option for both HER2- and HER3- positive GBC and CC.

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 1684. doi:1538-7445.AM2012-1684
Abstract 1685: Ginsenoside compound K inhibits colorectal tumorigenesis via multiple pathways including ATM/p53-p21
Authors: Zhang Zhiyu , Du Guang-Jian , Wang Chong-Zhi , Li Zejuan , Yuan Chun-Su 
Published: August 2012

Abstract
To date, colorectal cancer (CRC) remains one of the most prevalent malignancies in the United States. Health benefits derived from medicinal plants have been investigated for years. Ginseng has been shown to induce diverse pharmacological effects mediated predominantly by saponins, a type of ginsenoside contained in ginseng. Compound K (20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol, CK), an intestinal bacterial metabolite of ginseng protopanaxadiol saponins, has been shown to inhibit cell growth in a variety of tumors. However, the detailed mechanism, especially the effects of CK on cell cycle regulation in CRC cells, has not been examined. In addition, it is uncertain whether CK can inhibit colorectal tumor growth in vivo. In this study, we observed that CK significantly inhibited the growth of HCT-116 cells in athymic nude mouse xenograft models. Quantitative analysis revealed that CK significantly inhibited xenograft tumor growth from the 3rd week after CK administration (p&lt;0.001); the higher dose (30mg/kg) of CK treatment exhibited a stronger effect than the lower dose (15mg/kg)(p&lt;0.001). Using MTS assay, we showed that CK significantly inhibited the viability of human colorectal cancer cell lines HCT-116, HT-29 and SW480 in a dose- and time-dependent manner(with IC50 at around 10, 25, and 25uM respectively, p&lt;0.01). In a flow cytometry assay, it was shown that CK could significantly induce HCT-116 cell apoptosis and arrest the cell cycle in the G1 phase. By screening with cell cycle and cell signal PCR arrays, some of the most relevant genes(such as CDKs/cyclins, BCL2, E2F4, p21CDKN1A, p15CDKN2B, TP53, etc.) and signal transduction pathways(such as p53, TGF-β, PI3K/AKT, pathways) were shown to be transcriptionally regulated after CK exposure. Western blots showed that the major regulated targets of CK are cyclin dependent inhibitors, including p21, p27, and p15. CK-induced colorectal cancer cell apoptosis and cell cycle arrest were related to the up-regulation of p53/p21, FoxO3a-p27/p15, Smad3, etc and down-regulation of cdc25A, CDK4/6 and cyclin D1/3 as well. Taken together, the results indicate that CK inhibits transcriptional activation of multiple tumor-promoting pathways in colorectal cancer, which suggest that CK could be useful for the prevention or treatment of CRC. Key words: Colorectal cancer, Ginsenoside, xenograft tumor, p53/p21, cell cycle arrest
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 1685. doi:1538-7445.AM2012-1685
Abstract 1686: Identification of potential prostate cancer biomarkers associated with TMPRSS2-ERG fusion and PTEN deletions
Authors: Almami Amal A. 
Published: August 2012

Abstract
Background: ERG gene rearrangements and PTEN genomic deletions have been shown to be associated with specific molecular subtype of prostate cancer (PCA). It has been also suggested that tumors showing those two genetic aberrations are associated with worse prognosis compared to tumors with none of those genetic aberrations. In this study, we investigated gene expression differences between those two classes of tumors to identify potential genetic targets and pathways Material and Methods: 6144 informative genes belonging to 59 HRPCA samples were previously studied using the DASL platform. We used Singular Value Decomposition (SVD), as an effective method for analyzing gene expression data based on their ERG and PTEN status. We used the normal prostate cell line RWPE-1 as well as different prostate cancer cell lines (LNCaP, VCaP, DU145 and PC-3) to validate the results of microarray expression profiling. We screened for the expression of the different proteins by means of real time PCR and western blot studies. Results: MMP1 and LEF1 protein expression was much higher in VCaP cells and almost absent in RWPE-1 cells while MEIS2, CHD5 and Syntenin were expressed differently between cell lines and were not specifically in VCaP which is only cell line that harbor the ERG fusion. Conclusion: In this preliminary study we show that MPP1 and LEF-1 might be associated with the TMPRSS2-ERG fusion since their expression was much higher in VCaP cell line compared to other cell lines. However, further studies are still needed to confirm these results in TMPRSS2-ERG knockdown VCaP 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 1686. doi:1538-7445.AM2012-1686
Abstract 1687: Expression of DAB2IP is related with cancer progression and prognosis of gastric cancer
Authors: Wang Xiangyang , Min Jiang , Yao Xingfeng , Zhao Min , Jiang Jianwu , Wang Jingtao , Liu Liang , Zhang Bo , Li Xiaolan , Tao Deding , Wang Jing , Hu Junbo , Hsieh Jer-Tsong , Xie Daxing , Gong Jianping 
Published: August 2012

Abstract
Background: Gastric cancer remains the fourth most common cancer and the second leading cause of cancer-related death worldwide. DAB2IP, a novel member of the Ras GTPase-activating protein family, is down-regulated in various human cancers and functions as a bona fide tumor suppressor in cancer development. In gastric cancer, the expression of DAB2IP and its relation to tumor progression and prognosis has not been investigated. Therefore, we undertook a clinicpathologic study of gastric cancer to investigate the correlation between the expression of DAB2IP and clinical characteristics. Results: Immunohistochemistry was performed in 120 cases of gastric cancer tissues and corresponding adjacent normal mucosas, 36 cases of non-metastatic lymph node and 68 cases of metastatic lymph node. Overall results showed that 69 of 104 gastric cancer tissues expressed low level of DAB2IP, and 94 of 104 adjacent normal mucosas expressed high level of DAB2IP. We also scored the expression level of DAB2IP based on both the intensity of staining and the percentage of positive cell… The expression of DAB2IP in gastric cancer tissues or lymphatic metastatic tissues was clearly lower than that in normal mucosas (p&lt;0.01). DAB2IP expression was obviously decreased in gastric cancer tissues with lymphatic metastasis compared to those without lymphatic metastasis (p&lt;0.01). The expression of DAB2IP was correlated with gender, serosal invasion, lymphatic metastasis, remote metastasis, tumor grade, and carcinoembryonic antigen (CEA) levels (p&lt;0.05). DAB2IP expression appears to be an independent prognostic marker for survival of patients with gastric cancer (p&lt;0.05). Patients with lower expression of DAB2IP had worse overall survival than those with higher expression of DAB2IP (p&lt;0.01). Conclusions: DAB2IP is a potential new marker for predicting the progression and prognosis of gastric cancer. Loss of DAB2IP expression is related with poor overall survival of patients in gastric cancer, indicating its potent role in gastric carcinogensis.
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 1687. doi:1538-7445.AM2012-1687
Abstract 1692: Expression of argininosuccinate synthetase protein and correlation with response to the novel therapeutic pegylated arginine deiminase (ADI-PEG20) in osteosarcoma
Authors: Sowers Rebecca , Bomalaski John , Gorlick Richard 
Published: August 2012

Abstract
The amino acid arginine is involved in protein synthesis and tumor metabolism and is essential for the growth of human cancer cells. Pegylated arginine deiminase (ADI-PEG20) is a novel therapy that lowers extracellular arginine levels and has shown evidence of clinical response and low toxicity in patients with tumors lacking argininosuccinate synthetase (ASS1) protein expression, including melanoma and hepatocellular carcinoma. Recently it has been shown that ASS1 expression was deficient in 63% (39/62) of Japanese osteosarcoma patient samples, and reduced ASS1 was associated with pulmonary metastases. In addition, they showed that ASS1 deficient, but not ASS1 expressing, osteosarcoma cells lines did not grow in arginine-deficient media, and recommended evaluation of arginine depletion with ADI-PEG20 in osteosarcoma. Because ADI-PEG20 efficacy appears to correlate with ASS1 protein expression, a cohort of osteosarcoma tissue sections (n=171) was stained immunohistochemically to determine the presence or absence of ASS1 protein. Sixty-four percent (n=109) indicated negligible or no staining for ASS1 protein suggesting further that osteosarcoma might be a candidate for ADI-PEG20 sensitivity. Western blots were performed on patient-derived osteosarcoma cell lines (n=18) to determine levels of ASS1 protein expression prior to treatment with ADI-PEG20. Of the 18 cell lines studied, four cell lines had noticeably diminished ASS1 protein expression. The remaining 13 cell lines exhibited varying amounts of ASS1 protein expression with five of these cell lines appearing strongly positive indicating possible overexpression of ASS1 protein. Cytotoxicity assays were performed on a subset of cell lines representing both elevated and decreased ASS1 protein expression to determine the in vitro effectiveness of ADI-PEG20 in patient-derived osteosarcoma cell lines and its correlation with ASS1 protein expression. Some of the ASS1 deficient cell lines showed decreased cell viability in response to arginine depletion with ADI-PEG 20. These findings suggest that arginine depletion with ADI-PEG 20 may be a potential targeted treatment for osteosarcoma patients deficient in ASS1 expression. In addition, further preclinical studies are ongoing, including xenograft models, to understand better the mechanism of this agent in osteosarcoma.
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 1692. doi:1538-7445.AM2012-1692
Abstract 1694: Imaging cell cycle progression in gastric cancer lymph node metastasis indicates large fraction of proliferating cancer cells
Authors: Suetsugu Atsushi , Hassanein Mohamed , Moriwaki Hisataka , Yano Shuya , Fujiwara Toshiyoshi , Bouvet Michael , Saji Shigetoyo , Hoffman Robert M. 
Published: August 2012

Abstract
We report here a mouse model of lymph node metastasis of stomach cancer and imaging cell cycle progression in the metastasis. FUCCI (fluorescent ubiquitination-based cell cycle indicator)-expressing human MKN45 gastric cancer cells were used to establish the lymph node metastasis nude mouse model. In this model, cell-cycle dynamics of the metastatic cells could be imaged in vivo. FUCCI cells are labeled orange in the G1 phase nuclei (monomeric Kusabira-Orange2: mKO2) and labeled green in the S/G2/M phases (monomeric Azami-Green1: mAG1). FUCCI MKN45 were injected into the mouse stomach mucosa from the serosal side. Lymph node metastasis to the para-aortic or hepatic portal region, left armpit, and brachial lymph nodes were observed. Green-yellow (G2/S) cells were predominant compared to red (G1) fluorescent FUCCI cells as observed in the lymph-node metastases using an FV1000 confocal microscope, indicating that the lymph-node metastatic cells were actively cycling. The origin of lymph node or vessel metastases was confirmed by H.E. staining. Mouse FUCCI gastric metastasis models will be used to visualize cell cycle dynamics in metastasis in lymphoid as well as hematogenous metastasis in order to optimize drug treatment.
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 1694. doi:1538-7445.AM2012-1694
Abstract 1697: Gadd45A expression is high in luminal A and her2 human breast cancers, but frequently absent in triple negative breast cancers
Authors: Tront Jennifer S. , Willis Alliric , Huang Yajue , Smith Geoffery , Powers Benjamin , Hoffman Barbara , Liebermann Dan 
Published: August 2012

Abstract
Gadd45a is a stress sensor, playing an important role in tumorigenesis. Generation and side by side analysis of breast cancer prone MMTV-myc and MMTV-ras mice highlight a unique role for Gadd45a as either a suppressor or promoter of breast cancer development, employing distinct signaling pathways in response to distinct oncogenic stress stimuli. Thus, it appears that gadd45a can function to either promote or suppress breast tumor development in mice via engagement of different signaling pathways depending on the molecular nature of the activated oncogene. Extending the work to human breast cancer has provided initial, novel data, showing that Gadd45a, which is not expressed in normal breast tissue, is expressed at high levels in less aggressive breast cancers and is low or absent in more aggressive subtypes. Notably, Gadd45a is expressed at very high levels in luminal A and her2 positive breast cancers, but frequently is absent in triple negative breast cancers. Experiments are currently underway to elucidate the functional role of Gadd45a in human breast cancer.
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 1697. doi:1538-7445.AM2012-1697
Abstract 170: Thymoquinone-mediated suppression of NF- αB activity causes inhibition of cell viability and induces apoptosis in activated B-cell sub-type of diffuse large B-cell lymphoma
Authors: Hussain Azhar R. , Ahmed Saeeda O. , Ahmed Maqbool , Khan Omar S. , Uddin Shahab , Al-Kuraya Khawla S. 
Published: August 2012

Abstract
Diffuse Large B-cell Lymphoma (DLBCL) is the most common lymphoid malignancy and constitutes approximately 40% of all cases of non-Hodgkin's lymphoma (NHL). Despite improvement in treatment protocols, a large number of DLBCL cases remain refractory to treatment. DLBCL can be further classified as three distinct subtypes: germinal center B cell-like (GCB)-, activated B cell-like (ABC)-, and primary mediastinal B-cell lymphoma (PMBL). ABC DLBCL has a worse survival after upfront chemotherapy and is characterized by constitutive activation of the anti-apoptotic nuclear factor-kappa B (NF-κB) pathway. Yet the implication of NF-κB inhibition in ABC DLBCL need to be further elucidated. We have previously shown that Thymoquinone (TQ), a natural compound isolated from Nigella sativa, induces growth inhibition and induces apoptosis in several NHL cell lines. However its role in inhibition of growth and apoptosis has not been fully elucidated in ABC sub-type of DLBCL cell lines. We found that TQ treatment inhibits cell viability and induces apoptosis in a dose dependent manner in various ABC cell lines. Further more, we found that TQ treatment causes inactivation of IκBα and consequently inhibits NF-κB activity by decreasing the expression of p65 subunit of NF-κB in the nuclear compartment of ABC cell lines. In-activation of NF-κB survival pathway leads to induction of apoptosis via the mitochondrial apoptotic pathway initiated by conformational changes in the Bax protein leading to changes in the mitochondrial membrane potential and release of cytochrome c in the cytosole. Once cytochrome c is released, it leads to activation and cleavage of caspases-9 and -3 and cleavage of PARP. This leads to caspase dependent apoptosis in ABC cell lines. In addition, we also found that TQ treatment causes up-regulation of death receptor 5 (DR5), an important and essential receptor for tumor necrosis factor related apoptosis inducing ligand (TRAIL). However, up-regulation of DR5 does not play a role in TQ-induced apoptosis in ABC cell lines. Interestingly, combination of sub-toxic doses of TQ and TRAIL induces efficient significant apoptosis in ABC cell lines. These data show that TQ can be used alone or in combination with TRAIL to induce apoptosis in these aggressive sub-types of DLBCL and may play an important role in the management of DLBCL in the future.
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 170. doi:1538-7445.AM2012-170
Abstract 1701: Clinical significance of serum and tissue Dickkopf-1 in patients with gastric cancer
Authors: Park Kyoung Un , Park Do Joong , Kim Hyung Ho , Kim Woo Ho , Lee Hye Seung 
Published: August 2012

Abstract
Background: Dickkopf-1 (DKK-1) is a secreted protein known as a negative regulator of the Wnt signaling pathway and involved in embryonic development and tumorigenesis. Clinical significance of serum DKK-1 and tissue DKK-1 expression in gastric cancer has not been clarified. Methods: Serum concentrations of DKK-1 were assessed by enzyme-linked immunosorbent assay in 153 gastric cancer patients and 33 healthy controls. We also obtained serum CEA (ng/mL) and CA19-9 (U/mL) values by chemiluminescence immunoassay. For tissue DKK-1, we performed immunohistochemical staining for DKK-1 in 144 cancer specimens of 153 patients and in additional 265 consecutive gastric cancer specimens. Results: Serum DKK-1 concentrations were significantly higher in gastric cancer patients (56.27 pg/mL) than in healthy controls (30.50 pg/mL, p=0.018). With 36.3150 pg/mL of cut-off value, sensitivity and specificity for gastric cancer diagnosis were 80.4% and 78.8%, respectively. Gastric cancer patients with a serum DKK-1 of 60.0 pg/mL or higher had a significantly diminished survival compared with patients whose serum DKK-1 were lower (p=0.033). By immunohistochemistry, DKK-1 overexpression in cancer specimens was significantly correlated with increased serum DKK-1 concentrations (correlation coefficient, 0.395; p&lt;0.001). The cancer patients with DKK-1 overexpression had a significantly worse prognosis than the patients without DKK-1 expression in this cohort (p=0.004) and additional consecutive cases (p=0.030). By multivariate Cox regression model, DKK-1 expression status predicted patient prognosis independently of pTNM stage and histologic differentiation in consecutive cases (p=0.018). Conclusion: Increased serum DKK-1 concentrations and overexpression of DKK-1 in gastric cancer tissue may contribute to diagnosing gastric cancer and predicting cancer patient outcome.
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 1701. doi:1538-7445.AM2012-1701