tbuckley/cabot-search huggingface dataset:
Abstract 2464: Papillary renal cell carcinoma, proposal of a new classification system based on integrated molecular, histological and clinical analysis
Authors: Rola Saleeb, Mina Farag, Fadi Brimo, Fabio Rotondo, Pamela Plant, George Yousef
Journal: Cancer Research (2017)

Abstract Background: Papillary Renal Cell Carcinoma (PRCC) is divided into histological subtypes 1 and 2. Type 2 is known to have worse clinical behavior. A number of PRCC cases (~ 50%), fail to meet all reported morphological criteria for either type, hence are best characterized as PRCC not otherwise specified (NOS). There are yet no reliable markers to resolve the PRCC NOS category. That in turn reflects the clinical dilemma of how to manage these patients. Experimental Design: PRCC patient cohort of 115 cases was selected for the study. Cases were subtyped histologically into PRCC types 1, 2 and NOS. Potentially distinguishing markers ABCC2, CA9, SAll4, and BCL2 selected from our previous genomic analysis, were assessed by immunohistochemistry (IHC). A total of 24 cases were further selected for molecular analysis using miRNA expression and copy number variation (CNV). Univariate and multivariate survival analysis were performed using Log rank test and cox proportionate hazards. Results: Markers ABCC2, CA9 exhibited distinct staining patterns between the two classic PRCC subtypes; and successfully classified many of the PRCC NOS (45%) cases. Moreover, immunomarkers revealed a third distinct subtype of PRCC (35% of the PRCC cohort). Molecular testing using miRNA expression and CNV analysis confirmed the presence of three distinct molecular signatures corresponding to the 3 subtypes. On univariate analysis DFS was significantly enhanced in the type1 versus 2&amp; 3 (p value 0.047). PRCC subtyping retained significance on multivariate analysis (p value 0.025, HR:6, 95% CI 1.25 to 32.2) . Conclusion: We propose a new classification system of PRCC integrating morphological, immunophenotypical, and molecular analysis. Our classification reveals a 3rd PRCC subtype that was not previously described. This subtype has overlapping morphology of with PRCC types 1 and 2, hence would be subtyped as PRCC NOS in the current classification. Molecularly PRCC type 3 has a distinct signature and clinically it behaves similar to PRCC type 2. The new classification stratifies PRCC patients into clinically relevant subgroups and has significant future implications on the management of PRCC. Citation Format: Rola Saleeb, Mina Farag, Fadi Brimo, Fabio Rotondo, Pamela Plant, George Yousef. Papillary renal cell carcinoma, proposal of a new classification system based on integrated molecular, histological and clinical analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2464. doi:10.1158/1538-7445.AM2017-2464
Abstract 2210: Scavenging for lethal prostate cancer biomarkers in FFPE tissue
Authors: Håkon Ramberg, Peder R. Braadland, Maria E. Stensland, Mehrdad Rakaee, Ståle Nygård, Olov Øgren, Viktor Berge, Aud Svindland, Elin Richardsson, Gustavo A. de Souza, Sigve Andersen, Kristin A. Taskén
Journal: Cancer Research (2017)

Abstract The aim of this study was to identify protein biomarkers that can be used to stratify indolent and aggressive prostate cancer using formalin-fixed paraffin-embedded tissue (FFPE) from radical prostatectomy specimens. The protein expression profiles of benign and malign samples from 23 patients, who had either died of prostate cancer or were alive 10 years after diagnosis, were determined using an Easy nLC1000 Nano-LC system connected to a quadrupole-Orbitrap (Q Exactive) mass spectrometer equipped with a nanoelectrospray ion source. The generated MS raw files were submitted to MaxQuant software for protein identification. Differential expression of LFQ-normalized intensities was tested by Cox proportional hazards modeling and LASSO (least absolute shrinkage and selection operator) regression analysis within the R software environment. The label free Orbitrap analysis identified 3523 unique proteins from the FFPE tissue samples. LASSO of protein expression profiles of indolent and aggressive prostate cancer tissue samples identified ten proteins which could stratify the groups. Seven of the proteins were significantly correlated with time to prostate cancer specific mortality in Cox proportional hazards modeling (p-value &amp;lt; 0.05). The selected proteins were found to be linked to NFkappaB signaling, cell structure, translation and metabolic pathways. Finally, proteins capable of distinguishing benign from malignant prostate tissue were identified by LASSO, and 22 of these were significantly different between the groups (Bonferroni-adjusted p-value &amp;lt; 0.05). Selected candidate biomarkers are currently being validated by immunohistochemical analyses of 535 radical prostatectomy specimens from two independent Norwegian cohorts with long follow-up time. Citation Format: Håkon Ramberg, Peder R. Braadland, Maria E. Stensland, Mehrdad Rakaee, Ståle Nygård, Olov Øgren, Viktor Berge, Aud Svindland, Elin Richardsson, Gustavo A. de Souza, Sigve Andersen, Kristin A. Taskén. Scavenging for lethal prostate cancer biomarkers in FFPE tissue [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2210. doi:10.1158/1538-7445.AM2017-2210
Abstract 5640: The prognostic role of estrogen receptor beta in a female cohort of colorectal cancer
Authors: Geriolda Topi, Roy Ehrnström, Ingrid Palmquist, Marie-Louise Lydrup, Anita Sjölander
Journal: Cancer Research (2017)

Abstract Background: The estrogen receptor beta (ERβ) is the predominant estrogen receptor in the colon mucosa, and has been reported to have anti-proliferative and pro-apoptotic effects. However, the role of estrogen signaling in colorectal cancer (CRC) progression remains unclear. Aim: To investigate the prognostic role of ERβ in a female cohort of CRC. Methods: A tumor tissue microarray of primary CRCs from 333 female patients was stained with a mouse monoclonal anti-ERβ antibody. The intensity of staining was evaluated using immunohistochemistry technique. The expression of ERβ was scored using the semi-quantitative method [IRS (immune-reactive score) = SI (staining intensity) x PP (percentage of positive nuclei)]. Overall survival (OS) and disease-free survival (DFS) were the primary outcomes. Preliminary results are presented. Results: From 321 patients eligible for survival analysis only 315 had successful measurement of ERβ (141 with low expression and 174 with high expression). The univariate analysis showed no effect of ERβ on OS, but high ERβ was associated with lower risk of cancer recurrence as indicated by DFS (HR, 0.61; CI, 0.38-1.02). Cox multivariate analysis indicated that, compared to low expression, high expression of ERβ was significantly associated with a decreased risk of cancer recurrence (HR, 0.39; CI, 0.20-0.77), after adjustment for age, tumor stage, tumor intravascular invasion and hormonal contraception use. Likewise, high ERβ expression was associated with better OS in patients with cancer stage I-III (HR, 0.52; CI, 0.29-0.94) that did not receive adjuvant treatment after operation. Premenopausal women had a higher mean of IRS for ERβ compared to postmenopausal women (p = 0.03). Conclusion: High levels of ERβ significantly correlate with a decreased risk of cancer recurrence in CRC patients. We also noted longer overall survival in the subgroup of patients with cancer stage I-III that had not received adjuvant treatment after operation. The same results of OS were observed for colon cancer patients, but not for rectal cancer patients. A possible explanation could be that most of the rectal cancer patients have undergone radiotherapy before surgery, which might affect the status of ERβ. Citation Format: Geriolda Topi, Roy Ehrnström, Ingrid Palmquist, Marie-Louise Lydrup, Anita Sjölander. The prognostic role of estrogen receptor beta in a female cohort of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5640. doi:10.1158/1538-7445.AM2017-5640
US cancer groups call for more diverse populations to be included in trials
Authors: Michael McCarthy
Journal: BMJ (2017)

National cancer organizations in the United States have called for a new strategy to ensure that all populations benefit from advances in cancer care regardless of race, ethnicity, sexual orientation, or the communities they live in.1

“Unfortunately, cancer health disparities research has often been fraught with missing, inaccurate, or overly simplified patient-level data,” said a joint statement by the American Association for Cancer Research, the American Cancer Society, the American Society of Clinical Oncology, and the National Cancer Institute, published on 25 July.

It added, “The field of cancer health disparities has evolved into a complex science and an established multidisciplinary …
Phase I/II study of the deacetylase inhibitor panobinostat after allogeneic stem cell transplantation in patients with high-risk MDS or AML (PANOBEST trial)
Authors: G Bug, A Burchert, E-M Wagner, N Kröger, T Berg, S Güller, S K Metzelder, A Wolf, S Hünecke, P Bader, J Schetelig, H Serve, O G Ottmann
Journal: Leukemia (2017)

Phase I/II study of the deacetylase inhibitor panobinostat after allogeneic stem cell transplantation in patients with high-risk MDS or AML (PANOBEST trial)
In vitro and in vivo characterization of integrin targeted nanoparticle probes and small molecule probes
Authors: Narasimhan Danthi, Jianwu Xie, Christopher A. Burnett, Monica Bur, Finnie Hunter, King C. P. Li
Journal: Cancer Research (2005)

3856   Integrin α v β 3  is a cell surface heterodimeric protein and upregulated on tumor cells as well as angiogenic endothelial cells. Angiogenesis is associated with various pathological conditions like osteoporosis, rheumatoid arthritis, macular degeneration, and cancer. A variety of tumors as well as the endothelial cells associated with the tumors express α v β 3 . Our efforts are focused towards the development of imaging probes targeted to α v β 3 . In this presentation we will describe our efforts with the development of avb3 targeted optical probes for imaging angiogenesis in cancer. We have synthesized integrin targeted low molecular weight optical probe as well as nanoparticle based optical probe. We will present the physico chemical, in vitro, and in vivo characterization of these probes. The in vivo data clearly showed that both probes target tumor however, the nanoparticle probe confined to the vasculature and did not leak out of the vasculature where as the small molecule probe leaks out of the vasculature into the tumor.
EGLN1/c-Myc Induced Lymphoid-Specific Helicase Inhibits Ferroptosis through Lipid Metabolic Gene Expression Changes
Authors: Yiqun Jiang, Chao Mao, Rui Yang, Bin Yan, Ying Shi, Xiaoli Liu, Weiwei Lai, Yating Liu, Xiang Wang, Desheng Xiao, Hu Zhou, Yan Cheng, Fenglei Yu, Ya Cao, Shuang Liu, Qin Yan, Yongguang Tao
Journal: Theranostics (2017)

Ferroptosis is a newly discovered form of non-apoptotic cell death in multiple human diseases.However, the epigenetic mechanisms underlying ferroptosis remain poorly defined.First, we demonstrated that lymphoid-specific helicase (LSH), which is a DNA methylation modifier, interacted with WDR76 to inhibit ferroptosis by activating lipid metabolism-associated genes, including GLUT1, and ferroptosis related genes SCD1 and FADS2, in turn, involved in the Warburg effect.WDR76 targeted these genes expression in dependent manner of LSH and chromatin modification in DNA methylation and histone modification.These effects were dependent on iron and lipid reactive oxygen species.We further demonstrated that EGLN1 and c-Myc directly activated the expression of LSH by inhibiting HIF-1α.Finally, we demonstrated that LSH functioned as an oncogene in lung cancer in vitro and in vivo.Therefore, our study elucidates the molecular basis of the c-Myc/EGLN1-mediated induction of LSH expression that inhibits ferroptosis, which can be exploited for the development of therapeutic strategies targeting ferroptosis for the treatment of cancer.
Abstract 5007: Role of the interferon-gamma response pathway in immune escape of colorectal carcinoma
Authors: Nathalie Britzen-Laurent, Julia Straube, Philipp Tripal, Maximilian Waldner, Christoph Becker, Susanne Merkel, Roland S. Croner, Michael Sturzl
Journal: Cancer Research (2017)

Abstract The presence of an interferon-dominated Th1 immune response in colorectal carcinoma (CRC) has been associated with improved clinical outcome. We have previously identified the guanylate-binding protein 1 (GBP-1), one of the major IFN-γ-induced proteins, as a marker for the Th1 immune response and an independent positive prognostic factor in CRC. We also found that GBP-1 is a necessary mediator of the anti-tumorigenic effects of IFNγ. Interestingly, the expression of GBP-1 in CRC was observed more frequently in the desmoplastic stroma than in the directly adjacent tumor cells, suggesting that CRC tumor cells might become resistant to IFN-γ in the course of tumorigenesis. Indeed, we found that several colorectal carcinoma cell lines failed to express GBP-1 or other interferon-stimulated genes after treatment with IFN-γ, and were resistant to IFN-γ-induced apoptosis or proliferation inhibition. In these cell lines, the loss of IFN-γresponsiveness correlated either with the down-regulation of the IFN-γ receptor alpha chain (IFNγRα) or with the presence of a mis-glycosylated form of IFNγRα, which displayed an aberrant intracellular localization. We further validated these findings at the clinical level by showing that the expression of IFNγRα is decreased in CRC compared to normal tissue. In addition, the down-regulation of IFNγRα expression in CRC correlated with a reduced cancer-related survival together with a higher rate of distant metastasis. In addition, in-vivo colon tumorigenesis models using conditional knock-out mice revealed that the absence of IFNγRα expression by intestinal epithelial cells fosters tumor growth. Altogether, our data suggest that the loss of IFN-γ responsiveness is a common event in CRC and protects tumor cells against the anti-tumorigenic effects of IFN-γ. Citation Format: Nathalie Britzen-Laurent, Julia Straube, Philipp Tripal, Maximilian Waldner, Christoph Becker, Susanne Merkel, Roland S. Croner, Michael Sturzl. Role of the interferon-gamma response pathway in immune escape of colorectal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5007. doi:10.1158/1538-7445.AM2017-5007
Abstract 2315: Overcoming treatment resistance in cisplatin-resistant ovarian carcinoma cells by tissue-specific miRNAs
Authors: Michael Kleemann, Jeremias Bereuther, Simon Fischer, Kim Marquart, Simon Hänle, Kristian Unger, Verena Jendrossek, Christian U. Riedel, René Handrick, Kerstin Otte
Journal: Cancer Research (2017)

Abstract Ovarian cancer is a common human cancer with a poor outcome and a high risk of death. Due to resistances to current standard therapies (carboplatin and paclitaxel for 3 to 6 cycles) additional therapeutic approaches are required and novel specific biomarkers for ovarian cancer patients are necessary. MicroRNAs (miRNA) are conserved, small noncoding RNAs regulating gene expression by binding to their target mRNA which have been shown to regulate biological processes including apoptosis. Apoptosis is a conserved, irreversible process that allows cells to undergo a highly regulated form of cell death. However, the final role of miRNAs in apoptotic signaling has not yet been fully determined. Modulating the expression of key molecular components of the cell death machinery is an attractive strategy for cancer therapy overcoming chemo drug resistance. To extend the pool of potential miRNA as anticancer agents and biomarkers, we transferred a high content miRNA screening for pro-apoptotic miRNAs to human cancer cell lines. Based on the high recovery rate of apoptosis inducing miRNAs in SKOV3 cells analyses were extended to multiple ovarian carcinoma cell lines with different genetic background. After transfection of miR-1912-5p the apoptosis rate increased strongly in cisplatin-resistant cells. In combination treatment with carboplatin the apoptotic effect increased after transfection of miR-1912-5p in the cisplatin-resistant A2780 cells. Furthermore, miR-1912-5p, miR-147b and miR-3073a showed significant apoptosis induction in the various ovarian cancer cell lines alone and in combined therapy with carboplatin. Western Blot analysis revealed an enhanced expression of the pro-apoptotic proteins Bak1 and Bax and a decrease inBcl2 and Bcl-xL. We characterized the miRNAs in regard to their endogenous expression and detected an enhanced expression after apoptosis induction by chemotherapeutic drugs. Finally, analysis of The Cancer Genome Atlas data showed an influence on the median survival of ovarian cancer patients (&amp;gt; 69 years). Our data indicate a potential benefit of tissue specific pro-apoptotic miRNAs in regard to cisplatin-resistant cells. Furthermore the study identified novel pro-apoptotic miRNAs with their potential use as novel therapeutic entities or prognostic biomarkers for ovarian cancer. Citation Format: Michael Kleemann, Jeremias Bereuther, Simon Fischer, Kim Marquart, Simon Hänle, Kristian Unger, Verena Jendrossek, Christian U. Riedel, René Handrick, Kerstin Otte. Overcoming treatment resistance in cisplatin-resistant ovarian carcinoma cells by tissue-specific miRNAs [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2315. doi:10.1158/1538-7445.AM2017-2315
Abstract 2874: Inhibition of tumor angiogenesis by <i>Salmonella typhimurium</i> A1-R in the <i>in vivo</i> Gelfoam color-coded imaging assay
Authors: Tasuku Kiyuna, Yasunori Tome, Takashi Murakami, Ming Zhao, Fuminori Kanaya, Robert M. Hoffman
Journal: Cancer Research (2017)

Abstract We previously demonstrated a color-coded angiogenesis imaging model using Gelfoam® implanted in nestin-driven green fluorescent protein (ND-GFP) nude mice in which nascent blood vessels express GFP. In this assay, we demonstrated osteosarcoma promotes angiogenesis. We report here that Salmonella typhimurium A1-R (S. typhimurium A1-R) inhibits angiogenesis of osteosarcoma cells in the Gelfoam® angiogenesis assay in ND-GFP mice. Gelfoam® was transplanted subcutaneously in the flank of transgenic ND-GFP nude mice. Seven days after transplantation, skin flaps were made and 143B human osteosarcoma cells, expressing red fluorescent protein (RFP), were injected in the transplanted Gelfoam®. After establishment of tumor in the Gelfoam®, the control group mice were treated with PBS by tail vein injection. The treated group was treated by S. typhimurium A1-R, also by tail vein injection. Skin flaps were made at days 14, 21, and 28 after transplantation of the Gelfoam® in order to allow imaging of vascularization. The OV100 variable magnification small animal imaging system and FV1000 confocal fluorescence microscope were used to visualize vascularization. Nascent blood vessels grew in the Gelfoam® in a time-dependent manner. A random 3 fields were quantified in each group. The mean length of ND-GFP-expressing blood vessels in the Gelfoam® in mice were treated with S. typhimurium A1-R was 9.40, 12.40, and 10.12 mm/mm2, at days 14, 21, and 28, respectively. The mean total length of ND-GFP-expressing blood vessels in the Gelfoam® in mice of the control group were 8.86, 14.50, and 15.81 mm/mm2 on day 14, 21, and 28, respectively. ND-GFP expressing blood vessels of the mice in the osteosarcoma cells treated with S. typhimurium A1-R had shorter vessels than the control group (on day-28, P&amp;lt;0.05). There was not a significant difference in tumor size between the 2 groups, thereby indicating a specific inhibition of angiogenesis by S. typhimurium A1-R. In the present study, we reported that S. typhimurium A1-R inhibited angiogenesis of human osteosarcoma cells in the in vivo Gelfoam® color-coded imaging assay. Citation Format: Tasuku Kiyuna, Yasunori Tome, Takashi Murakami, Ming Zhao, Fuminori Kanaya, Robert M. Hoffman. Inhibition of tumor angiogenesis by Salmonella typhimurium A1-R in the in vivo Gelfoam color-coded imaging assay [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2874. doi:10.1158/1538-7445.AM2017-2874
Abstract 1475: miRNA-450a suppresses adhesion but promotes invasion through targeting of TMEM182 in oral squamous cell carcinoma
Authors: En-Wei Hsing, Shine-Gwo Shiah, Ching-Chuan Kuo, Jang-Yang Chang
Journal: Cancer Research (2017)

Abstract Our microRNA (miRNA) expression signatures of oral squamous cell carcinoma (OSCC) revealed that miR-450a was significantly increased in cancer tissues compared with normal epithelium. In this study, we focused on the functional significance of miR-450a in cancer cells and identification of miR-450a-regulated novel targets in OSCC. Overexpression of miR-450a in DOK and SAS cells showed significant inhibition of cell adhesion and induction of cell invasiveness, suggesting that miR-450a functions as an onco-miRNA. We performed genome-wide gene expression analysis to search for miR-450a-regulated molecular targets. Gene expression data and luciferase reporter assays revealed that TMEM182 was directly targeted by miR-450a. The miR-450a-reduced cellular adhesion was blocked by TMEM182 restoration, suggesting that miR-450a exhibits its oncogenic activity through negatively regulating TMEM182 level. Furthermore, miR-450a expression could be induced by the cytokine TNF-α primarily through activating extracellular signal-regulated kinase (ERK) signaling pathway. ERK inhibitor prevented the TNF-α-induced miR-450a expression and enhanced adhesion ability. Taken together, these data indicate that TNF-α/ERK-dependent expression of miR-450a plays an important role in mediating cellular adhesion and invasiveness, and scavenging miR-450a function using antagomir may have therapeutic potential for the treatment of OSCC. (The study was supported by the following grants: MOST 103-2320-B-006-036-MY3 and MOST 105-2325-B-400-001 from the Ministry of Science and Technology of Taiwan, ROC) Citation Format: En-Wei Hsing, Shine-Gwo Shiah, Ching-Chuan Kuo, Jang-Yang Chang. miRNA-450a suppresses adhesion but promotes invasion through targeting of TMEM182 in oral squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1475. doi:10.1158/1538-7445.AM2017-1475