tbuckley/cabot-search huggingface dataset:
Abstract 4329: Expression of serpin B2, neuroserpin and L1CAM in association with metastasis and survival in non-small cell lung cancer
Authors: Maria Ramnefjell, Lars Helgeland, Lars A. Akslen
Journal: Cancer Research (2015)

Abstract Background: Lung cancer is a leading cause of cancer related deaths worldwide, and finding new prognostic and predictive biomarkers are of utmost importance. Previous studies have shown that different serpins and adhesion molecules have an impact on disease progression and development of metastasis, especially to the brain. Here, we examined whether expression of the anti-plasminogen activators Serpin B2 and Neuroserpin, and the adhesion molecule L1CAM was associated with patient prognosis, brain metastasis or other clinicopathologic characteristics, in non-small cell lung cancer (NSCLC). Study design: The material consists of surgical specimens from 100 NSCLC patients treated during 1993-1999 at Haukeland University Hospital, Bergen, Norway. Sections from tumor blocks were stained with antibodies to Serpin B2, Neuroserpin, and L1CAM. Results: There were 66 men and 34 women, with a mean age at diagnosis of 65.7 (41 adenocarcinomas, 38 squamous cell carcinomas, and 21 carcinomas of other types). Observation time ranged from 0 to 254 months (mean 74 months). 12 patients were fully recovered, 46 died of lung cancer, and 34 died from other causes. 11 of 89 patients developed brain metastasis. Low expression of Serpin B2 was associated with reduced overall survival (p&amp;lt;0.05) in adenocarcinomas, and with a trend for all types combined (p = 0.10), whereas there was no significant difference in survival related to expression of Neuroserpin or L1CAM. Expression of Neuroserpin was associated with adrenal metastasis (OR 13.3 (95%CI 1.5-119.7), p&amp;lt;0.05), and there were trends for associations between expression of Serpin B2 and metastases to skin and bone (p = 0.072 and p = 0.068, respectively). There were no significant associations between these markers and presence of brain metastasis. Conclusions: Low expression of Serpin B2 in lung adenocarcinoma was associated with reduced overall survival in our cohort. In contrast to previous findings by others, we did not find a relationship between L1CAM expression and overall survival or metastasis. Neither was there any association between expression of Neuroserpin and survival, although we found an increase in adrenal metastasis in this group. Low expression of Serpin B2 could be a biomarker for prognosis in lung adenocarcinomas and should be studied in other cohorts. Citation Format: Maria Ramnefjell, Lars Helgeland, Lars A. Akslen. Expression of serpin B2, neuroserpin and L1CAM in association with metastasis and survival in non-small cell lung cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4329. doi:10.1158/1538-7445.AM2015-4329
Abstract 661: Increasing sensitivity of SAIT301, a specific monoclonal antibody of c-Met, with paclitaxel combination in c-Met positive gastric cancer
Authors: Sun Kyoung Kang, Jeong Min Kim, Won Suk Lee, Woo Sun Kwon, Tae Soo Kim, Seon-hui Shim, Kyung-Ah Kim, Ho-Yeong Lim, Hyun Cheol Chung, Sun Young Rha
Journal: Cancer Research (2015)

Abstract The c-Met is frequently overexpressed and related to a worse prognosis in gastric carcinoma (GC). This study aimed to determine a c-Met targeting monoclonal antibody (SAIT301) with effects on the proliferation and to increase efficacy of SAIT301 administered in combination with paclitaxel in gastric cancer cell lines. Anticancer effect of SAIT301 was assessed using CCK-8 assay in 52 GC cell lines. c-Met status was identified using RTK array and qPCR. Cell cycle distribution was determined with flow cytometry. Expression levels of c-Met and cleaved PARP, apoptosis induction marker, were determined by western blot analysis. Combination index (CI) evaluated by CalcuSyn software. We screened 52 cell lines for growth inhibition by SAIT301.Among 11 c-Met positive GC cells, 5 cell lines were sensitive to SAIT301 (5/11, 45%) with 40∼60% inhibition rate at 5 μg/ml.SAIT301 sensitivity of 5 cell lines has a tendency of correlation between MET amplification, c-Met/p-Met co-expression, low Cbl level or exon14 deletion of MET. Next, we performed combination treatment with SAIT301 and paclitaxel in 5 cell lines. The results exhibited increasing anti-proliferative effects with synergism. In cell cycle analysis, SAIT301 increased the percentage of cells in the G1 phase, while paclitaxel increased the G2/M phase(3-19%). Combination of SAIT301 and paclitaxel significantly increased in sub G1(2-17%) and G2/M arrest(4-19%). Western blot analysis showed paclitaxel induced c-Met expression. In addition, SAIT301 and paclitaxel combination down-regulated c-Met expression and enhanced PARP cleavage more than monotherapy. Our results indicate that the SAIT301 combined with paclitaxel therapy had synergistic effects in the treatment of c-Met positive gastric cancer. Citation Format: Sun Kyoung Kang, Jeong Min Kim, Won Suk Lee, Woo Sun Kwon, Tae Soo Kim, Seon-hui Shim, Kyung-Ah Kim, Ho-Yeong Lim, Hyun Cheol Chung, Sun Young Rha. Increasing sensitivity of SAIT301, a specific monoclonal antibody of c-Met, with paclitaxel combination in c-Met positive gastric cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 661. doi:10.1158/1538-7445.AM2015-661
151. EGFR-Directed Micellar Nanoparticles for Cancer Theranosis
Authors: Seong Jae Kang, Hwa Yeon Jeong, Min Woo Kim, In Ho Jung, Moon Jung Choi, Yong Serk Park
Journal: Molecular Therapy (2015)

In this study, we have prepared lipid micellar nanoparticles encapsulating quantum dots (QDs) as a diagnostic agent and incorporating cholesterol-siRNA (Cho-siRNA) as a therapeutic agent. Furthermore, for targeted co-delivery of QDs and Cho-siRNA, anti-EGFR antibodies or aptamers were conjugated to the surface of the nanoparticles. Firstly, to optimize the nanostructure of lipid micelles, we determined an optimal molar ratios of lipids, QDs, and Cho-siRNA as 350:1:0.35. The size of QD micelles was about 50 nm that is suitable for efficient localization in tumors via enhanced permeability and retention (EPR) effect. Their serum stability and pH stability suggest that the QD micelle structure is stable enough to be applied to biological conditions. The RNase protection assay showed that Cho-siRNA molecules in the QD micelles were effectively protected by sterically shielding of hydrophilic polyethylene glycol molecules. The analyses with a flow cytometry and a confocal microscope showed that the nanoparticles can effectively deliver Cho-siRNA to the target cells, followed by effective residing of siRNA molecules in the cytoplasm. These results suggest that the micellar nanoparticles established in this study would be widely utilized as a theranostic vehicle.
Abstract 2017: Development of ultrasensitive Singulex immunoassays for CCL3 and CCL4, important biomarkers for the BTK inhibitor studies
Authors: Jenny Q. Wu, Luciana Burton, Rajiv Raja, Ian McCaffery, Elicia Penuel, Walter Darbonne
Journal: Cancer Research (2015)

Abstract Disregulation of B-Cell Receptor (BCR) leading to activation has been associated with a number of B-cell malignancies including Chronic Lymphocytic Leukemia (CLL) [1]. In response to BCR activation, B-cells secrete chemokines CCL3 and CCL4 that foster interactions between CLL cells and the leukemia microenvironment and to recruit T-cells. High levels of CCL3 have also been correlated with poor prognosis in CLL [2]. Bruton tyrosine kinase (BTK) has long been known to be a key component of B cell receptor (BCR) signaling that regulates B cell proliferation and survival. BTK inhibitors such as lbrutinib have been shown to disrupt secretion of BCR-dependent chemokines (CCL3/CCL4) and thereby reduce plasma concentrations in patients [3]. Consequently, these chemokines have been measured as pharmacodynamic biomarkers in a number of studies of molecules that inhibit BCR signaling [3]. However, baseline CCL3/CCL4 levels in CLL patients vary widely and are less than 10 pg/ml in a large proportion of patient samples, making detection of these cytokines in clinical samples challenging using existing immunoassays. In an effort to improve sensitivity of CCL3/CCL4 measurements in plasma samples, we developed ultrasensitive assays for CCL3 and CCL4 using the Singulex immunoassay platform. A direct comparison of multiple, commercially available immunoassays technologies and our optimized CCL3/CCL4 Singulex assay were performed using plasma samples from both healthy donors and CLL patients. Singulex proprietary Single Molecule Counting (SMCTM) technology combining digital counting enables the quantification of CCL3 and CCL4 with sensitivity of 0.37pg/ml and 0.15pg/ml respectively in plasma. This ultrasensitive assay has the potential to enable more robust and quantifiable measurements of CCL3 and CCL4 in the context of clinical studies testing BTK inhibitors. Citation Format: Jenny Q. Wu, Luciana Burton, Rajiv Raja, Ian McCaffery, Elicia Penuel, Walter Darbonne. Development of ultrasensitive Singulex immunoassays for CCL3 and CCL4, important biomarkers for the BTK inhibitor studies. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2017. doi:10.1158/1538-7445.AM2015-2017
Reduced Intensity Conditioning Allogeneic Hematopoietic Stem Cell Transplantation for Low Grade Non Hodgkin's Lymphoma: Preliminary Results at Hospital De Clínicas De Porto Alegre (HCPA), Porto Alegre, RS, Brazil.
Authors: Beatriz Stela Gomes de Souza Pitombeira Araujo, Alessandra Aparecida Paz, Clarissa Barros Ferreira, Manoela Santos Boffo, Erica Lammerhirt Ottoni, Gustavo Brandão Fischer, Liane Esteves Daudt, Lucia Silla
Journal: Blood (2010)
Abstract 1269: Role of ribosomal protein, Rpl22 in regulating leukemic transformation
Authors: Nehal Solanki Patel, Noa Greenberg Kushnir, Shuyun Rao, Suraj Peri, Michele Rhodes, Panduka Nagahawatte, Charles Mullighan, David L. Wiest
Journal: Cancer Research (2015)

Abstract Inactivation of ribosomal proteins (RP) is known to cause diseases called ribosomopathies, which are often associated with abnormal hematopoiesis and an increased risk for development of leukemia. Our laboratory has recently reported an important link between inactivation of one such ribosomal protein, Rpl22, and poor survival in T cell acute lymphoblastic leukemia (T-ALL) patients. Preliminary bioinformatic analysis shows that RPL22 is lost in ∼10% of pediatric T-ALL patients, who exhibit a more aggressive disease course. Deletion of the RPL22 locus is also enriched in the early T-cell precursor (ETP-ALL) subset of T-ALL patients, which exhibit a more aggressive disease course. Thus, RPL22 loss appears to be a marker for poor outcome in pediatric T-ALL patients. While RP inactivation has previously been linked to increased cancer risk, the mechanistic basis for this linkage remained unclear. We have recently demonstrated that inactivation of Rpl22 promotes leukemic transformation by activating NF-κB and inducing the stem cell gene, LIN28B. Nevertheless, the molecular link between Rpl22 inactivation and the induction of NF-κB activity remained unclear. We have now determined that inactivation of Rpl22 activates NF-κB signaling by exacerbating ER stress responses. Indeed, Rpl22 loss results in hyperactivation of the PERK-EIF2a-ATF4 stress pathway, which is known to activate NF-κB. We have demonstrated that knockdown of PERK using shRNA abrogates the activation of NF-κB in Rpl22 mutant cells and returns Lin28B expression levels to baseline. This reduction in Lin28B eliminates the predisposition to transformation exhibited by Rpl22 mutant cells, as evidenced by decreased formation of colonies in soft agar. Taken together, these data suggest that RPL22 inactivation may serve as a negative prognostic indicator in T-ALL and that pharmacologic targeting of ER stress pathways may represent a novel therapeutic alternative in this molecularly-defined subclass of T-ALL. Citation Format: Nehal Solanki Patel, Noa Greenberg Kushnir, Shuyun Rao, Suraj Peri, Michele Rhodes, Panduka Nagahawatte, Charles Mullighan, David L. Wiest. Role of ribosomal protein, Rpl22 in regulating leukemic transformation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1269. doi:10.1158/1538-7445.AM2015-1269
Genetic Polymorphism of Cytochrome P450 1B1 (C432G) Is Associated with An Increased Treatment-Related Mortality and Lower Overall Survival in Patients Undergoing Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Michael Koldehoff, Ahmet H. Elmaagacli, Dietrich W. Beelen
Journal: Blood (2008)
Abstract 1340: Antitumor effector B cells directly kill tumor cells involving the CXCL12/CXCR4 pathway and their therapeutic efficacy is enhanced by IL-2
Authors: Yang Xia, Huimin Tao, Yangyang Hu, Li Zhou, Yangyi Bao, Steven K Lundy, Shiang Huang, Qiao Li, Alfred E Chang
Journal: Cancer Research (2015)

Abstract In cancer immunotherapy, effector B cells can inhibit spontaneous tumor metastases as well as local tumor growth in animal models. We have previously reported that antitumor effector B cells generated from tumor-draining lymph node (TDLN) could directly kill tumor cells via the Fas/FasL pathway and are regulated by IL-10. Trafficking of TDLN B cells in vivo suggested that they were recruited to the tumor and lung as well as secondary lymphoid organs. The number of TDLN B cells increased following transfer. As a result, adoptive transfer of TDLN B cells conferred tumor regression in a spontaneous pulmonary metastasis mouse model of breast cancer, 4T1. Removal of IL-10, either by using IL-10-/- TDLN B cells or by systemic neutralization of IL-10 using anti-IL-10 antibody, significantly augmented the therapeutic efficacy of adoptively transferred TDLN B cells. In recent studies, we found that tumor cell death mediated by effector B cells involves the CXCR4/CXCL12 as well as Fas/FasL interactions. Blockade of CXCR4 and FasL using a CXCR4-specific inhibitor, AMD3100, and anti-FasL antibody, respectively, reduced the killing of 4T1 tumor cells by 4T1 TDLN B cells. Of note, blockade of CXCR4 and FasL concurrently inhibited B cell-mediated direct killing of tumor cells in an additive fashion, suggesting that both CXCL12/CXCR4 and Fas/FasL pathways are involved in the direct killing of 4T1 tumor cells by 4T1 TDLN B cells. In other experiments, we found that TDLN B cells express IL-2 receptors (IL-2R) and the ability of the TDLN B cells to inhibit metastasis was significantly enhanced with exogenous IL-2 administration. Besides our previously reported Fas/FasL pathway and IL-10-mediated suppression, our recently identified CXCL12/CXCR4 pathway and IL-2-mediated augmentation of the biological function of effector B cells suggests these B cells may represent an important component of the host immune response against tumor. Citation Format: Yang Xia, Huimin Tao, Yangyang Hu, Li Zhou, Yangyi Bao, Steven K Lundy, Shiang Huang, Qiao Li, Alfred E Chang. Antitumor effector B cells directly kill tumor cells involving the CXCL12/CXCR4 pathway and their therapeutic efficacy is enhanced by IL-2. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1340. doi:10.1158/1538-7445.AM2015-1340
Isotype-Selective HDAC Inhibitor MGCD0103 Decreases Serum TARC Concentrations and Produces Clinical Responses in Heavily Pretreated Patients with Relapsed Classical Hodgkin Lymphoma (HL).
Authors: Anas Younes, Barbara Pro, Michelle Fanale, Peter McLaughlin, Sattva Neelapu, Luis Fayad, Amanda Wedgwood, Daniela Buglio, Tracy Patterson, Marja Dubay, Zuomei Li, Robert E. Martell, M. Renee Ward, R. Gregory Bociek
Journal: Blood (2007)
Detection of ERG and MN1 Gene Expression in Adult Patients with De Novo Acute myeloid Leukemia(AML) by Real-Time Quantitative Polymerase Chain Reaction and Its Clinical Significance.
Authors: Bing Xu, Xutao Guo, Guoshu Chen, Xiaoyan Song, Pengcheng Shi, Pingnan Xiao, Shuyun Zhou
Journal: Blood (2009)
Abstract 729: The role of skp2 in paclitaxel-resistant prostate cancer cells
Authors: Yeguo Yang, Qiong Song, Yi Lu, Jian Zhang, Jiejun Fu
Journal: Cancer Research (2015)

Abstract Prostate cancer is the most common cancer and the second most frequent cause of cancer-related death of men in the United States. It has been shown that the F-box protein Skp2(S-phase kinase associated protein 2) plays an important role in the development and progression of prostate cancer. The molecular mechanism responsible for paclitaxel-resistant in prostate cancer cells remain unclear. Interestingly, we found that the expression of Skp2 is higher in the paclitaxel-resistant prostate cancer cells DU145-TXR or PC-3-TXR compared with their parental cells DU145 or PC-3 respectively.This study was aimed to investigate the role of Skp2 in prostate cancer cell resistance to paclitaxel and the progress of epithelial-to-mesenchymal transition(EMT). Skp2 encoding plasmid was stably transfected into PC-3 and DU145 cells. Meanwhile, Skp2 was silenced by shRNA in DU145-TXR or PC-3-TXR cells. MTS assay was used to measure the cytotoxicity effect of Skp2 overexpression or knockdown of Skp2 in cells after treatment with paclitaxel. We found that when downregulating Skp2 in DU145-TXR and PC-3-TXR, the cells showed a more sensitive response to paclitaxel. Moreover, Overexpression of Skp2 enhances prostate cancer cells resistance to paclitaxel. EMT markers E-cadherin was decreased while vimentin was increased in PC-3-TXR or DU145-TXR cells. The further study showed that when downregulating Skp2 in PC-3 or DU145, the expression of E-cadherin was increased. However, E-cadherin has no significant change when knockdown of Skp2 in PC-3-TXR or DU145-TXR cells. CyclinD1, P21 and P27 were found to increase while CyclinB1 and CyclinE2 to decrease when downregulating Skp2 in PC-3-TXR or DU145-TXR cells. These data provide evidence that Skp2 is associated with prostate cancer cell resistance to paclitaxel. Skp2 could be a potential therapeutic target for prostate cancer. This study is supported by NSFC key project 81130046, NSFC projects 81201669, 81171993 and 81272415. Note: This abstract was not presented at the meeting. Citation Format: Yeguo Yang, Qiong Song, Yi Lu, Jian Zhang, Jiejun Fu. The role of skp2 in paclitaxel-resistant prostate cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 729. doi:10.1158/1538-7445.AM2015-729
Sirolimus, Tacrolimus and Reduced-Dose Methotrexate as Graft Versus Host Disease (GVHD)Prophylaxis after Non-Myeloablative Stem Cell Transplantation: Low Incidence of Acute GVHD Compared with Tacrolimus/Methotrexate or Cyclosporine/Prednisone.
Authors: Edwin P. Alyea, Shuli Li, Haesook Kim, Corey Cutler, Vincent Ho, Stephanie J. Lee, John Gribben, Jerome Ritz, David C. Fisher, Robert J. Soiffer, Joseph H. Antin
Journal: Blood (2004)
650. Development of Combination Therapy of Bifidobacterium-Based Oral Vaccine Displaying HCV-NS3 with Interferon-α
Authors: Koichi Kitagawa, Hiroki Ishikawa, Tsugumi Oda, Hiroki Saito, Naoya Morishita, Kouske Shimamoto, Norihisa Nishida, Yoichi Matsuura, Hak Hotta, Toshiro Shirakawa
Journal: Molecular Therapy (2015)

INTRODUCTION: Hepatitis C virus (HCV) is a major cause of chronic liver diseases, such as liver cirrhosis and hepatocellular carcinoma. The efficacy of the standard-of-care including interferon-α and ribavirin for chronic HCV infection is limited, especially in HCV genotype 1, the most prevalent genotype in Japan. It is considered that chronic HCV infection correlates strongly with failure of host immune response against HCV. Although HCV specific immune responses play an especially significant role in clearing virus, no effective vaccine against HCV was approved at present. We had successfully developed a recombinant Bifidobacterium based novel oral vaccine against HCV infection, displaying a HCV-nonstructural protein 3 (NS3) fusion peptide on the bacterial cell surface. We had found that this oral vaccine could induce HCV-NS3 specific CTL in mice. Then, in this study, to determine the therapeutic efficacy of this oral vaccine, the functional HCV specific cellular immune response was investigated by using HCV-NS3/4A antigen expressing tumor mouse model. Furthermore, to enhance the therapeutic efficacy, we combined interferon-α therapy with this oral vaccine in the mouse model. EXPERIMENTAL SUMMARY: Bifidobacterium longum (B. longum 2165) expressing NS3 fusion peptide derived HCV-genotype 1b was prepared and then heat inactivated for 5 min at 65 ° C for oral vaccination. For the tumor challenge, C57BL/6N mice were subcutaneously injected EL-4 lymphoma cells stably expressing HCV-NS3/4A, and then orally administered 2.4×108 CFU of inactivated B. longum 2165, active B. longum 2165, active B. longum transfected control vector (B. longum 2012), or PBS every other day for 4 weeks. In addition, for the combination therapy with interferon-α, inactivated B. longum 2165 and PBS groups were combined with 20,000 units of interferon-α subcutaneous injection every 4 days during vaccination. In the results, B. longum 2165 with interferon-α combination therapy significantly delayed tumor growth compared with the other treatments. For in vitro cytotoxicity assay, splenocytes were collected from immunized mice and restimulated with EL4-NS3/4A and IL-2. In the B. longum 2165 with interferon-α treated group, the cytotoxicity of splenocytes against EL4-NS3/4A was significantly higher than that of the other groups. CONCLUSION: This study demonstrated multiple oral vaccinations of B. longum 2165 could induce functional NS3 specific cellular immune responses in mice. Moreover, interferon-α combination therapy with the vaccine could strongly enhance the therapeutic efficacy of this vaccine. These findings support the feasibility of this therapeutic oral vaccine as additional agent of interferon based standard therapy against chronic HCV infection.