tbuckley/cabot-search huggingface dataset:
236. Microwave Ablation Assisted Liver Gene Transfection in Rats
Authors: Xianghui He, Ruoyu Jiang, Lingkai Meng, Xiaoyu Liang, Jie Zhang, Zhixiang Zhang, Liwei Zhu
Journal: Molecular Therapy (2015)

BACKGROUNDS: Thermal ablation has been widely used to manage liver tumor. This study was designed to determine histological change of rat liver after microwave ablation, investigate the effect of microwave ablation on gene transfection. METHODS: In this study, microwave ablation was applied to rat liver, tissue demarcation was evaluated. Green fluorescent protein (GFP) and Renilla luciferase-expressing plasmids were administrated to the liver by percutaneous or intravenous injection pre-ablation. The expression of transgene in the reactive inflammatory zone was evaluated. GFP expression was determined with the inverted fluorescence microscope in frozen section, and Renilla luciferase expression in target tissue was determined using Renilla luciferase plasmid kit. The effect of hydrodynamic portal vein injection was also evaluated. RESULTS: GFP expression was observed in the tissue of reactive inflammatory zone after microwave ablation and plasmid injection. Green fluorescence in targeted area was visible on till the seventh day post ablation under inverted fluorescence microscope. On the first day postablation and Renilla luciferase plasmid injection, luminescence value of the experimental group was higher than the control group, but lower than the portal hypertension injection group. CONCLUSIONS: Direct injection of plasmid vector to inflammatory reaction zone after microwave ablation can achieve effective gene transfection, but the transfection efficiency is lower than hydrodynamic portal injection. These results provide some experimental basis for exploring microwave ablation assistant target gene transfer for cancer gene therapy.
Correlation of FOXA1 expression with Oncotype Dx recurrence scores
Authors: F. O. Ademuyiwa, M. Thorat, H. Nakshatri, S. Badve
Journal: Journal of Clinical Oncology (2009)

11058 Background: Oncotype Dx assay (ODX) is a diagnostic assay that predicts the benefit of chemotherapy and assesses the likelihood of breast cancer (BC) recurrence in patients with estrogen receptor (ER) positive BC. The forkhead-box A1 (FOXA1) transcription factor is linked to ER regulated gene transcription and its expression is associated with ER positive luminal A type BC. Since higher FOXA1 expression is associated with ER positive luminal A BC, we investigated whether FOXA1 expression levels show a correlation with ODX recurrence scores in BC patients. Methods: 120 cases of BC from IU and affiliated hospitals had ODX performed on tumor blocks. 78 patient tumor blocks with ODX recurrence score have been analyzed for FOXA1 using IHC. FOXA1 expression was measured using intensity X percentage scoring. The correlation of FOXA1 scores and ODX recurrence scores with each other and with other variables was examined. Other variables included age, progesterone receptor (PR) status, tumor size, grade, histological type, and race. All p values are two-sided and have been adjusted for multiple comparisons using Bonferroni-Holm's method. Results: Twenty-one of 78 cases analyzed were &lt; 50 years. ODX recurrence scores were low, intermediate, and high in 55.1%, 32.1%, and 12.8% of cases, respectively. Ductal carcinomas accounted for 73.1% of tumors, while 11.5% were lobular. Fifty percent of tumors were histologic grade II, 37% and 13% were grade I and III, respectively. PR was negative in 9 cases. Caucasians accounted for 78.2% of cases vs 7.7% African-Americans. FOXA1 expression correlated negatively with ODX recurrence score (p=.003), and histologic type (p=.024). ODX recurrence score also correlated negatively with PR (p=.034) with 78% of the PR negative cases having a high or intermediate ODX score. The correlation between FOXA1 expression and ODX recurrence score remained significant after adjusting for multiple comparisons and controlling for confounders such as histological type, grade, and PR. Conclusions: We demonstrate that FOXA1 expression has an inverse correlation with ODX recurrence scores. FOXA1 expression can potentially be used as a prognostic marker in low risk ER positive BC patients who lack access to ODX assays. This observation needs to be confirmed with a larger sample size. No significant financial relationships to disclose.
Abstract LB-098: Antitumor studies: Design, synthesis, antitumor activity and molecular docking study of novel 2-deoxo-2-substituted-5-deazaalloxazines
Authors: Sawsan A. Mahmoud, Mosaad S. Mohamed, Nageh A. Abou Taleb, Tomohisa Nagamatsu, Hamed I. Ali
Journal: Cancer Research (2015)

Abstract Cancer is the major threat to the public health worldwide, thereby we have a considerable interest to get potential antitumor agents via computational design, synthesis, functional elucidation, and biological evaluation of different deazaalloxazine analogs. Many of these compounds revealed higher selectivities against different tumor cell lines. In the study the structure activity relationships (SAR) of the proposed derivatives was investigated, by applying structure based drug design (SBDD) using most advanced molecular modeling tool programs, namely: AutoDock 4.2 and Accelrys Discovery studio 2.0. These computational approaches aim to increase the speed and efficiency in the drug discovery process. The reasonable drug candidates were subjected to the chemical synthesis and biological in vitro test against different tumor cell lines. The docking study of the synthesized and the rationally designed derivatives was carried out using PTKs as target enzymes which was early reported as a proposed pathway for inhibition of cancer. The main outcome of this study is the synthesis of novel 2-methylthio, 2-(substituted alkyl amino), 2-(heterocyclic substituted), 2-amino, 2,4-dioxo and 2-deoxo-5-deazaalloxazine derivatives. Their antitumor activities against human T-cell acute lymphoblastoid leukemia cell line (CCRF-HSB-2), human oral epidermoid carcinoma cell line (KB), human breast cancer cell line (MCF-7) and human cervical cancer cell line (Hela) have been investigated in vitro. Many compounds showed promising antitumor activities. Furthermore, AutoDock study has been done by binding of the 5-deazaalloxazine analogs into c-kit PTK (PDB code: 1t46), where a good correlation between their IC50 and AutoDock binding free energy was exhibited. Citation Format: Sawsan A. Mahmoud, Mosaad S. Mohamed, Nageh A. Abou Taleb, Tomohisa Nagamatsu, Hamed I. Ali. Antitumor studies: Design, synthesis, antitumor activity and molecular docking study of novel 2-deoxo-2-substituted-5-deazaalloxazines. [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 LB-098. doi:10.1158/1538-7445.AM2015-LB-098
Bendamustine in Combination with Thalidomide and Prednisolone (BPT) in Patients with Refractory or Relapsed Multiple Myeloma after Conventional Chemotherapy: Final Results of a Phase I Study.
Authors: Wolfram Poenisch, Marta Rozanski, Sabine Leiblein, Hartmut Goldschmidt, Franz A. Hoffmann, Thomas Boldt, Robert Rohrberg, Elke Schwalbe, Jens Uhlig, Dietger Niederwieser
Journal: Blood (2005)
Abstract 5572: Tracking the functional analysis of cancer risk variants
Authors: Sharna Tingle, Danielle Carrick, Sheri Schully, Mindy Clyne, Stefanie A. Nelson
Journal: Cancer Research (2015)

Abstract Genome-wide association studies (GWAS) have identified thousands of alleles associated with cancer risk, but understanding the functional effects of these variants has proceeded more slowly. In addition, although catalogs of variants exist, tracking progress to determine variant function is challenging. We conducted a literature search and review to assess the trajectory of functional characterization of GWAS results and describe the types of analysis conducted and tools and databases used. We used the PubTator Web-based tool, which uses advanced text-mining techniques to accelerate manual literature curation, to search the literature for articles describing functional annotation of cancer GWAS hits. We generated a list of 646 unique SNPs from the Cancer Genomics and Epidemiology Navigator (CGEN) and imported the list to PubTator. We identified a total of 292 articles that included both variant discovery by GWAS and functional analysis, and reviewed the articles for information including cancer type, variant functional class (e.g., intron, exon, intergenic, etc.), and type of functional analysis conducted. These articles included 40 different cancer types or subtypes. The majority of cancer risk variants were intronic or intergenic, with only a small number located in coding regions. Most of the functional analyses were focused on the potential modification/disruption of regulatory processes by the risk allele (e.g., alteration of transcription factor binding sites, putative expressed quantitative trait loci), in line with current hypotheses regarding cancer risk variant function. Most studies also described effects of variants at the molecular, or cellular, rather than organismal level. We also reviewed the literature pertaining to variants identified for three cancers with possible pleiotropy - ovarian, breast, and prostate - to understand the trajectory of functional analyses beyond the initial discovery of the variants. We describe our use of the PubTator tool and provide a literature-based overview of progress in understanding the function of cancer risk variants identified via GWAS. Citation Format: Sharna Tingle, Danielle Carrick, Sheri Schully, Mindy Clyne, Stefanie A. Nelson. Tracking the functional analysis of cancer risk variants. [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 5572. doi:10.1158/1538-7445.AM2015-5572
Abstract 1801: Biological validation of a novel high-throughput irradiator for predictive radiation sensitivity bioassays
Authors: Alison Bailey, Tyler Fowler, Kwangok P. Nickel, Bryan Bednarz, Randall J. Kimple
Journal: Cancer Research (2015)

Abstract Purpose: To improve our ability to study radiation response and screen for radiosensitizing compounds, we have developed a high-throughput variable dose rate microirradiator. We sought to use several assays of radiation induced cellular damage to validate the ability of this system to be used for high-throughput assays. Methods: Immortalized human tonsillar epithelial cells were cultured in 96-well microtiter plates and irradiated in groups of eight wells to absorbed doses of 0, 1, 2, 4, and 8 Gy. Chloromethyl-H2DCFDA, a fluorescent reactive oxygen species (ROS) marker, was used to measure relative changes in ROS. Single cell gel electrophoresis (aka Comet assay, neutral) was used to detect physical DNA double-strand breaks. High-throughput immunofluorescent microscopy was used to detect γH2AX foci, a early marker of DNA double-strand breaks. Results: Over the range of radiation doses tested, we confirmed increasing ROS generation as measured by CM-H2DCFDA fluorescence (R2 = 0.969). Over 1,450 comets were analyzed over a range of radiation doses and the Olive Tail Moment (OTM) calculated. A linear increase in OTM with radiation dose was seen (R2 = 0.991). A linear increase in γH2AX foci was seen with increasing radiation dose as measured by cell average γH2AX fluorescence (R2 = 0.999) Conclusions: We have developed a robust platform for high-throughput assays of radiation sensitivity allowing rapid assessment of effects over a range of radiation doses. This system provides a powerful tool for increasing the efficacy of genetic and pharmacologic modifiers of radiation response. Citation Format: Alison Bailey, Tyler Fowler, Kwangok P. Nickel, Bryan Bednarz, Randall J. Kimple. Biological validation of a novel high-throughput irradiator for predictive radiation sensitivity bioassays. [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 1801. doi:10.1158/1538-7445.AM2015-1801
Nongastric Marginal Zone B-Cell Lymphoma: Analysis of 247 Cases - Clinical Presentation and Treatment Outcomes of Nongastric Marginal Zone B-Cell Lymphoma.
Authors: Sung Yong Oh, Baek-Yeol Ryoo, Won Seog Kim, Yeon Hee Park, Kihyun Kim, Hyun Jung Kim, Jung Mi Kwon, Jeeyun Lee, Yong H. Ko, Yong Chan Ahn, Suk Jung Oh, Soon Lee, Hyo Jin Kim, Hyuk Chan Kwon, Soo-Mee Bang, Jung Han Kim, Jinny Park, Seung-Sook Lee, Ho Yong Kim, Keunchil Park
Journal: Blood (2005)
Long‐term outcome in liver transplantation candidates with portopulmonary hypertension
Authors: Laurent Savale, Caroline Sattler, Audrey Coilly, Filoména Conti, Sébastien Renard, Claire Francoz, Hélène Bouvaist, Cyrille Feray, Patrick Borentain, Xavier Jaïs, David Montani, Florence Parent, Caroline O'Connell, Philippe Hervé, Marc Humbert, Gérald Simonneau, Didier Samuel, Yvon Calmus, Christophe Duvoux, François Durand, Jean Charles Duclos‐Vallée, Olivier Sitbon
Journal: Hepatology (2016)

Portopulmonary hypertension (PoPH) is diagnosed in 2‐6% of liver transplantation (LT) candidates. We studied outcomes of candidates for LT suffering from PoPH. Data were collected retrospectively from a prospective registry. Pulmonary hemodynamic variables were collected at the time of PoPH diagnosis, at last evaluation before LT, and within 6 months and beyond 6 months after LT. Forty‐nine patients (35 males, 48 ± 8 years) were analyzed (median Model for End‐Stage Liver Disease score 20). At baseline, mean pulmonary artery pressure (mPAP) was 44 ± 10 mm Hg (range 26‐73 mm Hg), cardiac index was 3.5 ± 0.9 L/min/m 2 , and pulmonary vascular resistance was 5.6 ± 2.8 Wood units. Hemodynamic reassessment performed in 35 patients who were treated with pulmonary arterial hypertension–targeted therapies before LT resulted in significant decreases in both mPAP (36 ± 7 versus 47 ± 10 mm Hg, P &lt; 0.0001) and pulmonary vascular resistance (3.0 ± 1.4 versus 6.1 ± 3.1 Wood units, P &lt; 0.0001). Fourteen patients (29%) died without having had access to LT. Thirty‐five patients underwent LT and were followed up for a median of 38 months. Eight patients (23%) died after LT including 5 due to PoPH (after 1 day to 6 months). Among survivors (n = 27), all patients treated with intravenous epoprostenol were weaned off post‐LT, and endothelin receptor antagonist or phosphodiesterase type 5 inhibitors were continued in 15/27 patients (55%). At last evaluation, 20/27 patients (74%) had mPAP &lt;35 mm Hg and 8 of them (30%) had mPAP &lt;25 mm Hg. Overall survival estimates after LT were 80%, 77%, and 77% at 6 months, 1 year, and 3 years, respectively. Conclusion : Stabilization or reversibility of PoPH seems to be an attainable goal using the combination of pulmonary arterial hypertension–targeted therapies and LT in patients who are transplantation candidates. (H epatology 2017;65:1683‐1692).
Abstract 3211: Heterogeneity of PPARβ/δ expression in colorectal tumor stroma
Authors: Eddie Han Pin Tan, Ming Keat Sng, Jeremy Soon Kiat Chan, Nguan Soon Tan
Journal: Cancer Research (2015)

Abstract Background: The role of PPARβ/δ in colorectal cancer has been a hot topic for debate, with both tumor-promoting and anti-tumor roles been reported. Current studies on colorectal cancer have focused on either the whole intestine or on the major tissue type, the intestinal epithelium. In recent years, various studies have emphasized the pro-inflammatory and tumor promoting effects of tumor stroma in various cancers. However, the involvement of tumor stroma in adenocarcinoma development remains a largely unexplored realm of colorectal research. Hence, we hypothesized that PPARB/D expression in colorectal tumor stroma may play an important role in colorectal carcinogenesis. Methods: In this study, we aimed to investigate the role of PPARβ/δ in the colorectal tumor stroma. To study the role of the tumor stroma in vivo, we have adopted a model organism approach involving adult APCmin mice and AOM/DSS-treated wild-type mice models. We collected intestinal adenocarcinomas from these mice and extracted tumor stroma using microscopy-directed laser capture micro-dissection. The collected stroma were recovered for mRNA and analyzed for gene expression levels using real-time PCR. Results and conclusion: We observed contrasting trends in the PPARβ/δ mRNA expression, with elevated levels in stroma of APCmin adenocarcinoma but decreased in AOM/DSS-induced tumors. Our results to date demonstrate the heterogeneity of colorectal tumor stroma and provide an insight to the distinct differences between the two often co-studied murine models of colorectal carcinogenesis. We therefore plan to study if this trend is also observed in human colorectal tumor samples and in murine colorectal cancer models carrying stromal-specific deletion of PPARβ/δ expression. Citation Format: Eddie Han Pin Tan, Ming Keat Sng, Jeremy Soon Kiat Chan, Nguan Soon Tan. Heterogeneity of PPARβ/δ expression in colorectal tumor stroma. [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 3211. doi:10.1158/1538-7445.AM2015-3211
Haploidentical Allogeneic Hematopoietic Cell Transplantation in Adults Using Reduced Intensity Conditioning and CD3/CD19-Depleted Grafts: Interim Analysis of a Phase I/II Study.
Authors: Birgit Federmann, Martin Bornhauser, Dietrich W. Beelen, Gernot Stuhler, Lambros Kordelas, Rainer Schwerdtfeger, Matthias Stelljes, Christoph Faul, Wichard Vogel, Rupert Handgretinger, Lothar Kanz, Wolfgang A. Bethge
Journal: Blood (2008)
Abstract 1252: Arginylation as a new link between oxidative stress response and prostate cancer progression
Authors: Fangliang Zhang, Michael D. Birnbaum, Akhilesh Kumar, William M. Morgan
Journal: Cancer Research (2015)

Abstract In this study, we evaluate the role of post-translational arginylation in prostate cancer, and introduce its potential as a biomarker of prostate cancer progression. Arginylation has not yet been studied in cancer. Our lab has observed Aringyltransferase (Ate1) is required for oxidative stress-mediated apoptosis. Our preliminary data in multiple eukaryotic cell models demonstrate that a downregulation of Ate1 increases resistance to oxidative stress, and elevated Ate1 is sufficient to induce cell death. Preliminary data mining shows that a downregulation of Ate1 correlates with a poorer prognosis in prostate cancer. Because prostate cancer cells produce a high amount of oxidative stress, the decrease of Ate1 likely increases their survival. We hypothesize that Ate1 is essential for the normal cellular response to insurmountable oxidative stress leading to apoptosis, and that a downregulation of Ate1 will promote cancer cell progression. We found that a loss of Ate1 in a nontumorigenic fibroblast cell line promotes spontaneous tumorigenicity within immunocompromised mice, a disruption of normal cell-cell interactions, and loss of contact inhibition. Also consistent with our hypothesis, prostate cancer cell line PC-3 with stably knocked down Ate1 exhibit higher invasiveness in the Boyden Chamber invasion assay, and higher resistance to H2O2-induced cell death during a 12-hour variable dose treatment. Similarly, the highly metastatic subpopulation of PC-3, PC3-ML, has naturally reduced Ate1 and exhibits higher invasiveness and resistance to H2O2. Finally, histological analysis of primary patient prostate cancer samples show a dramatic reduction of Ate1 compared to normal prostate tissue. These findings warrant further study of Ate1 as a metastasis suppressor, as well as a potential biomarker for prostate cancer progression. Citation Format: Fangliang Zhang, Michael D. Birnbaum, Akhilesh Kumar, William M. Morgan. Arginylation as a new link between oxidative stress response and prostate cancer progression. [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 1252. doi:10.1158/1538-7445.AM2015-1252
Genome-Wide lncRNA Microarray Profiling Identifies Novel Circulating lncRNAs for Detection of Gastric Cancer
Authors: Kecheng Zhang, Hongzhi Shi, Hongqing Xi, Xiaosong Wu, Jianxin Cui, Yunhe Gao, Wenquan Liang, Chong Hu, Yi Liu, Jiyang Li, Ning Wang, Bo Wei, Lin Chen
Journal: Theranostics (2016)

Long non-coding RNAs (lncRNAs) can serve as blood-based biomarkers for cancer detection.To identify novel lncRNA biomarkers for gastric cancer (GC), we conducted, for the first time, genome-wide lncRNA screening analysis in two sets of samples: five paired preoperative and postoperative day 14 plasma samples from GC patients, and tissue samples from tumor and adjacent normal tissues.Candidate tumor-related lncRNAs were then quantitated and evaluated in three independent phases comprising 321 participants.The expression levels of lncRNAs were also measured in GC cell lines and the corresponding culture medium.Biomarker panels, lncRNA-based Index I and carcinoembryonic antigen (CEA)-based Index II, were constructed using logistic regression, and their diagnostic performance compared.Fagan's nomogram was plotted to facilitate clinical application.As a result, we identified five novel plasma lncRNAs (TINCR, CCAT2, AOC4P, BANCR and LINC00857), which, when combined in the lncRNA-based Index I, outperformed the CEA-based Index II (P < 0.001) and could distinguish GC patients from healthy controls with an area under the receiver-operating curve (AUC) of 0.91 (95% confidence interval (CI): 0.88-0.95).The lncRNA-based index decreased significantly by postoperative day 14 (P = 0.016), indicating its ability to monitor tumor dynamics.High values of the lncRNA-based index were correlated with tumor size (P = 0.036), depth of invasion (P = 0.025), lymphatic metastasis (P = 0.012) and more advanced tumor stages (P = 0.003).The lncRNA-based index was also able to discriminate GC patients from precancerous individuals and patients with gastrointestinal stromal tumor with AUC values of 0.82 (95% CI: 0.71-0.92)and 0.80 (95% CI: 0.68-0.91),respectively.Taken together, our findings demonstrate that this panel of five plasma lncRNAs could serve as a set of novel diagnostic biomarkers for GC detection.