tbuckley/cabot-search huggingface dataset:
Abstract 1938: Implantable nanosensor for non-invasive ovarian cancer biomarker detection with wearable interface
Authors: Daniel A. Heller, Ryan M. Williams, Douglas A. Levine
Journal: Cancer Research (2019)

Abstract Patients with high-grade serous ovarian carcinoma (HGSC) exhibit poor 5-year survival rates, which may be significantly improved by early-stage detection. The US FDA-approved biomarkers for HGSC—CA-125 and HE4—do not generally appear at detectable levels in the serum until advanced stages of the disease. An implantable device placed proximal to disease sites, such as in or near the fallopian tube, ovary, uterine cavity, or peritoneal cavity, may constitute a feasible strategy to improve detection of HGSC. Furthermore, a sensor implant under the skin may allow real-time measurements after diagnosis, to monitor treatment for example, via interrogation using a wearable device. We engineered a prototype optical sensor composed of an antibody-functionalized carbon nanotube complex, which responds quantitatively to HE4 via modulation of the nanotube optical bandgap. The complexes measured HE4 with nanomolar sensitivity to differentiate disease from benign patient biofluids. The sensors were implanted into four models of ovarian cancer, within a semipermeable membrane, enabling the optical detection of HE4 within the live animals. We thus present the first in vivo optical nanosensor capable of noninvasive cancer biomarker detection in orthotopic models of disease. This technology may potentially be implanted locally in the uterine cavity, for point-of-care measurement, or under the skin, to then interface with a wearable device. Citation Format: Daniel A. Heller, Ryan M. Williams, Douglas A. Levine. Implantable nanosensor for non-invasive ovarian cancer biomarker detection with wearable interface [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1938.
Prospective cohort study of chemotherapy-associated toxicity and supportive care in oncology practice.
Authors: Eva Culakova, David C. Dale, Marek S. Poniewierski, Nicole Maria Kuderer, Adane Wogu, Jeffrey Crawford, Gary H. Lyman
Journal: Journal of Clinical Oncology (2012)

9135 Background: Neutropenic complications remain important dose-limiting toxicities of cancer chemotherapy associated with considerable morbidity, mortality and cost. The risk of the initial neutropenic event is greatest in the first cycle when most patients are receiving full dose chemotherapy. Methods: A prospective cohort study of adult patients with solid tumors or lymphoma receiving a new chemotherapy regimen was conducted at 115 U.S. practice sites between 2002 and 2006. Chemotherapy-associated toxicities were captured in up to 4 cycles including severe neutropenia (SN), febrile neutropenia (FN), and infection. Documented interventions included colony-stimulating factor (CSF) and antibiotics use and reductions in chemotherapy relative dose intensity (RDI). Results: Results are available on 3,638 patients starting chemotherapy of which 3,301, 2,937, and 2,199 went on to cycles 2, 3, and 4, respectively. The majority of neutropenic and infection events occurred in cycle 1. A significant inverse relationship was observed between subsequent reductions in neutropenic and infectious events and efforts to reduce these complications (Table). Most patients with stage 4 solid tumors underwent reductions in chemotherapy RDI. Patients with lymphoma and stage 1-3 solid tumors were less likely to undergo dose reductions with half or more receiving prophylactic CSFs during treatment. Approximately 15% of patients also received prophylactic antibiotics. Conclusions: While the risk of neutropenic complications remains greatest during the initial cycle of chemotherapy, clinician efforts to reduce the risk of these events vary with cancer type and stage. Reduced dose intensity is evident in two-thirds of patients with advanced solid tumors whereas the CSFs are employed in half to two-thirds of patients with early stage solid tumors or lymphoma. [Table: see text]
Abstract 4382: Epigenetic deregulation in glycolysis genes for colorectal cancer
Authors: KuoHsing Chen, Liang-Chuan Lai, Liang-In Lin, Hsien-Fang Chang, Yu-Liang Chao, Been-Ren Lin, Jin-Tung Liang, Ann-Lii Cheng, Eric Y. Chuang, Kun-Huei Yeh
Journal: Cancer Research (2019)

Abstract Background Energy restriction may have influence on methylation of glycolysis genes and also be associated with decreased incidence of colorectal cancer (CRC) in Dutch Hunger Winter cohort. This study aimed to explore the roles of epigenetic deregulation in energy/glycolysis pathway for CRC. Materials and methods To perform a comprehensive analysis of methylation alterations in glycolysis pathway (67 genes in KEGG), we profiled 27 CRCs and 5 adjacent normal colon tissues (NTs) by using a powerful methylation array (Illumina Methylation EPIC Beadchips). We used Wilcoxon rank-sum test (p &amp;lt; 0.05) and β value difference (≧ 0.2 or ≦ -0.2) to define the differential methylated genes (DMGs). We also searched the open datasets to find the shared DMGs in CRC. The shared DMGs were validated by pyrosequencing in our samples. Results We found 17 hypomethylation genes and 2 hypermethylation genes involved in glycolysis pathway in our cohort. After comparing to the methylation profiles of CRC in 3 datasets (GSE42752, GSE25062 and TCGA), only hypermethylation of ALDH1A3 and hypomethylation of HKDC1 remained as shared DMGs. These findings were validated well by pyrosequencing in our cohort. The mRNA expression of HKDC1 and ALDH1A3 was negatively associated with the methylation status of each of them in TCGA dataset. RT-qPCR also showed the corresponding expression of HKDC1 and ALDH1A3 between CRCs and NTs. Conclusion Our study reveals that hypomethylation of HKDC1 and hypermethylation of ALDH1A3 exist in CRCs worldwide. Further exploratory study of biologic roles of them in CRC is ongoing. Citation Format: KuoHsing Chen, Liang-Chuan Lai, Liang-In Lin, Hsien-Fang Chang, Yu-Liang Chao, Been-Ren Lin, Jin-Tung Liang, Ann-Lii Cheng, Eric Y. Chuang, Kun-Huei Yeh. Epigenetic deregulation in glycolysis genes for colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4382.
Abstract 1629: Classification of cancer histology images using deep learning
Authors: Weidong Xie
Journal: Cancer Research (2019)

Abstract Pathological evaluation of tumor tissue images stained with hematoxylin and eosin (H&amp;E) is pivotal and specialists often disagree on the final diagnosis. Meanwhile, automated image analysis approaches have great potential to increase precision of diagnosis, help reduce human error and cut cost. In this study, we utilize various computational methods based on deep learning framework and build a stand-alone diagnostic tool to effectively classify different histopathology images across different types. The dataset of tissue slides from eligible patients with breast cancer/ thyroid cancer consists of 45,000 samples in our hospital. Available tissue samples above were split into a training set, for learning the CNN parameters, and test set, for evaluating its performance. An accuracy of 94% was obtained for non-cancer (i. e. normal or benign) vs malignant (i. e. invasive carcinoma or papillary thyroid carcinoma). In addition, we also demonstrated the utility of our model to discriminate between two subtypes of lung cancer. It provides pathologists or medical technicians a straightforward platform to use without requiring sophisticated computational knowledge, and cancerization would be identified which is not visible under a single microscope. Citation Format: Weidong Xie. Classification of cancer histology images using deep learning [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1629.
Abstract 2590: Nano-exosomes with miRNA: A new therapeutic approach
Authors: Sudeepti Kuppa, Balazs Rada, Arthur Roberts, Mandi M. Murph
Journal: Cancer Research (2019)

Abstract Access to reliable and effective therapeutics for patients suffering from aggressive triple-negative breast cancer (TNBC) has been clinically challenging to achieve due to lack of targetable mutations and high heterogeneity in the tumor cells. Therapeutic approaches to reduce mortality in the TNBC patient subset requires an innovative and targeted approach to drug delivery, which is presented here in the form of labeled-exosomes. In this study, we have developed a novel method to bioengineer exosomes, where an antibody is covalently bonded to a fatty acid, which is then anchored into the exosomal membrane to create labeled-exosomes. Our data demonstrate that labeled-exosomes can contain up to 700,000-fold higher miRNA concentrations and can deliver miRNA cargo with increased efficiency into MDA-MB-231 TNBC cells. Results further reveal that insertion of a specific antibody-label to the exosomal membrane significantly increases microRNA uptake into MDA-MB-231 cells, and is further enhanced in cells overexpressing that same antibody marker on their surface. The customizable bioengineering of the labeled-exosomes makes it a highly versatile tool to target cells based on surface marker expression and increase miRNA or other therapeutic cargo delivery. Most importantly, the relevancy of this model reaches far beyond its success in just TNBC cells and can also be translated to several different disease models that require specific targeting with an encapsulated miRNA or therapeutic. We believe this is a novel and exciting utilization of exosomes with a high degree of customization based on surface markers on the target cell, as well as microRNA cargo loaded into the exosome to inhibit a specific oncogene. Citation Format: Sudeepti Kuppa, Balazs Rada, Arthur Roberts, Mandi M. Murph. Nano-exosomes with miRNA: A new therapeutic approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2590.
Lupeol induces FAS-mediated apoptotic death of androgen-dependent LNCaP prostate cancer cells and inhibits tumor growth in athymic nude mouse model
Authors: Jung Mi Yun, Mohammad Saleem, Mee Hyang Kweon, Deeba Syed, Hasan Mukhtar
Journal: Cancer Research (2005)

4290  In prostate cancer (CaP) a fine balance between cell proliferation and apoptotic death is lost resulting in increased cellular mass and tumor progression. One approach to redress this imbalance and control this malignancy is its preventive intervention through use of dietary natural agents. Lupeol, a triterpene, is a potent anti-inflammatory agent and recently we have shown that it is an effective anti-tumor promoting agent in mouse skin tumor model (Saleem et al, Oncogene, 23: 5203-5214, 2004,). Here, we investigated the growth-inhibitory effect and associated mechanisms of Lupeol in androgen-dependent human prostate carcinoma LNCaP cells. Lupeol (5-30 μM) treatment resulted in significant inhibition of cell viability at 48 and 72 h post treatment in a time and dose dependent manner. Flow cytometric and immunoblot studies revealed that Lupeol mediated cell death was due to apoptosis. Lupeol was found to induce the cleavage of PARP protein and degradation of Acinus protein with no change in Bcl2, Bax and Caspase 7 protein expression suggesting involvement of a mitochondria-independent apoptotic pathway. In Lupeol treated cells, an increase in the expression of FADD protein was observed. Since FADD acts as an adapter protein for many death inducing signaling molecules such as TNFR-1, APO-3, DR-5, and FAS receptor proteins, we determined their expression levels to establish Lupeol specificity. Lupeol caused a significant increase in the expression of FAS receptor protein with no change in the protein expression of TRADD and TNFR-1, APO-3 and DR-5 receptors. In addition, no significant change in the expression of cell death-inducing receptor ligands such as FAS-L, APO-3L and TRAIL was observed. In parallel experiments, treatment of cells with a combination of a Fas-agonist and Lupeol resulted in an increased cell death as compared to the additive effect of the two compounds alone, suggesting a synergistic effect. A possible explanation for this observation could be that Lupeol might be directly activating FAS protein. Next, we determined whether Lupeol could inhibit the CaP cell tumor growth in an athymic nude mouse xenografts model. The mice were implanted with androgen-dependent CWR22Rν1 cells and received an i.p. injection of Lupeol (1 mg/animal) three times a week. A significant reduction in tumor growth was observed in Lupeol treated mice as compared with untreated control. Taken together, these molecular alterations provide an insight into Lupeol-caused growth inhibition and apoptotic death of human CaP cells. Because early clinical CaP growth is an androgen-dependent response, the results of the present study employing androgen-dependent LNCaP cells suggest that Lupeol has promise and potential to be an effective agent against CaP.
Abstract 4441: Discovery of potent and selective inhibitors of USP7 with anti-tumor activity in vitro and in vivo
Authors: Yamini M. Ohol, Michael Sun, Paul Leger, Dennis Hu, Berenger Biannic, Payal Rana, Cynthia Cho, Scott Jacobson, Steve Wong, Jerick Sanchez, Xinping Han, Kyle Young, Akinori Okano, Jack Maung, Gene Cutler, Nick Shah, Lavanya Adusumilli, Deepika Kaveri, Oezcan Talay, Deepa Pookot, Betty Abraham, Delia Bradford, Nathan Kozon, Christophe Colas, Andrea Kim, Jacob Schwarz, David Wustrow, Dirk Brockstedt, Paul Kassner
Journal: Cancer Research (2019)

Abstract USP7 is a deubiquitinase that regulates the levels of multiple downstream targets with roles in cancer progression and immune response. Inhibitors of USP7 may thus decrease oncogene function, increase tumor suppressor function, enhance immune function and sensitize tumor cells to DNA damaging agents. We have discovered a novel chemical series that potently and selectively inhibits USP7 in biochemical and cellular assays. Our inhibitors reduce the viability of multiple p53-wild type cell lines, including several blood cancer and MYCN-amplified neuroblastoma cell lines, as well as a subset of p53-mutant tumor cell lines in vitro. Further, oral administration of our USP7 inhibitors inhibits MM.1S (multiple myeloma; p53-wild type) and H526 (small cell lung cancer; p53-mutant) tumor growth in vivo. Our work confirms that USP7 is a pharmacologically tractable target and future studies will aim to further understand the mechanism of action of USP7 inhibitors in p53-mutant cancers. Citation Format: Yamini M. Ohol, Michael Sun, Paul Leger, Dennis Hu, Berenger Biannic, Payal Rana, Cynthia Cho, Scott Jacobson, Steve Wong, Jerick Sanchez, Xinping Han, Kyle Young, Akinori Okano, Jack Maung, Gene Cutler, Nick Shah, Lavanya Adusumilli, Deepika Kaveri, Oezcan Talay, Deepa Pookot, Betty Abraham, Delia Bradford, Nathan Kozon, Christophe Colas, Andrea Kim, Jacob Schwarz, David Wustrow, Dirk Brockstedt, Paul Kassner. Discovery of potent and selective inhibitors of USP7 with anti-tumor activity in vitro and in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4441.
Abstract 1816: Tumor suppressor LINC02487 inhibits oral cancer cell migration and invasion through directly binding protein USP17
Authors: Lu Feng, Feng Qiu, Jianjun Zhang, Minglei Sun, Wantao Chen, Weiliu Qiu
Journal: Cancer Research (2019)

Abstract Objective: The aim of this study is to explore the functions and mechanisms of long non-coding RNA LINC02487 in oral squamous cell carcinoma(OSCC). Materials and methods: Relative expression level of LINC02487 in OSCC cell lines and samples were examined by qRT-PCR. Intracellular localization was done using RNA fluorescence in situ hybridization. LINC02487 was cloned into pCMV-puro vector, and transfected into OSCC cell lines HN6 and HN30 by lentivirus. Cell functions as proliferation, apoptosis, cell cycle, migration and invasion were examined subsequently. RNA binding protein was explored by ChIRP-MS. And protein expression was determined by western-blotting assay. Results: Previous data showed a downregulation of LINC02487 in OSCCs. Here we confirmed the lower expression of LINC02487 in 6 OSCC cell lines comparing with immortalized normal oral epithelial cell lines, and in 50 OSCC samples comparing with paired adjacent normal tissue. LINC02487 was located in cytoplasm, aggregated around nuclei membrane. Overexpression of LINC02487 significantly suppressed cell migration and invasion, increased the ratio of cells in G1 phase, with a minor influence on cell proliferation and apoptosis. Furtherly, LINC02487 was found directly binding to USP17, a deubiquitinating enzyme, and regulating cell migration and invasion through USP17 expression. Conclusion: Our study confirmed that long non-coding RNA LINC02487 was downregulated in paired OSCC samples and cell lines. It acts as a tumor suppressor through its directly binding protein USP17. Citation Format: Lu Feng, Feng Qiu, Jianjun Zhang, Minglei Sun, Wantao Chen, Weiliu Qiu. Tumor suppressor LINC02487 inhibits oral cancer cell migration and invasion through directly binding protein USP17 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1816.
Survival of Patients With Liver Transplants Donated After Euthanasia, Circulatory Death, or Brain Death at a Single Center in Belgium
Authors: Nicholas Gilbo, Ina Jochmans, Daniel Jacobs-Tulleneers-Thevissen, Albert Wolthuis, Mauricio Sainz-Barriga, Jacques Pirenne, Diethard Monbaliu
Journal: JAMA (2019)

This study compares graft and patient survival rates after transplantation of livers donated after euthanasia vs after circulatory death or brain death at a hospital in Belgium, where euthanasia is legalized.
Abstract 5012: Targeting CD39 with a first-in-class inhibitory antibody prevents ATP processing and increases T-cell activation
Authors: Alana G. Lerner, Maria Kovalenko, Megan Welch, Tracy dela Cruz, Jeff Jones, Clifford Wong, Bradley Spatola, Meghan Eberhardt, Andrew Wong, Wanchi Fung, Leanna Lagpacan, Karolina Losenkova, Gennady Yegutkin, Vanessa Soros, John Corbin, Courtney Beers, Achim K. Moesta
Journal: Cancer Research (2019)

Abstract The ATP/Adenosine pathway in the tumor microenvironment (TME) has emerged as an important immune-regulatory pathway. The ATPase CD39 is highly expressed in the TME, both on infiltrating immune cells and tumor cells across a broad set of cancer indications. CD39 processes pro-inflammatory extracellular ATP to ADP and AMP, which is then processed by CD73, to immunosuppressive adenosine. Inhibiting the enzymatic function of CD39 has the potential to shift the immunosuppressive milieu of the TME in a 2-pronged fashion: 1) Enhancement of immunostimulatory extracellular ATP released by damaged and/or dying tumor cells and 2) Inhibition of the generation and accumulation of suppressive adenosine within the TME, thereby unleashing an immune-mediated anti-tumor response. Tizona has generated a novel first-in-class fully human anti-CD39 antibody, TTX-030, that inhibits CD39 ATPase enzymatic function with sub-nanomolar affinity and potency. TTX-030 is specific for CD39 and binds to CD39+ cancer cell lines and primary human leukocytes with high affinity. TTX-030 is capable of inhibiting CD39 at elevated ATP concentrations reported in the TME. Enzymatic inhibition by TTX-030 has demonstrated: preservation of pro-inflammatory extracellular ATP, reduction of adenosine accumulation, and inhibition of phosphate release by a variety of CD39-expressing cells, including tumor cells and immune cells. In vitro functional assays using stimulated PBMCs exposed to exogenous ATP demonstrated increased proliferation of both CD4+ and CD8+ T cells in the presence of TTX-030 and increased secretion of the pro-inflammatory cytokines IFN-γ, TNF-α, and IL-2. Treatment of mice with a mouse-specific CD39 inhibitory antibody in a syngeneic tumor model significantly decreased tumor growth. In summary, TTX-030 is a selective and potent CD39 enzymatic inhibitor, capable of preventing adenosine-mediated immune suppression and increasing T-cell activation. Inhibition of CD39 with TTX-030 represents a unique therapeutic target aimed at modulating the immunosuppressive TME in cancer. Citation Format: Alana G. Lerner, Maria Kovalenko, Megan Welch, Tracy dela Cruz, Jeff Jones, Clifford Wong, Bradley Spatola, Meghan Eberhardt, Andrew Wong, Wanchi Fung, Leanna Lagpacan, Karolina Losenkova, Gennady Yegutkin, Vanessa Soros, John Corbin, Courtney Beers, Achim K. Moesta. Targeting CD39 with a first-in-class inhibitory antibody prevents ATP processing and increases T-cell activation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5012.
药物引发的史蒂文斯‐约翰逊综合征/中毒性表皮坏死松解症患者血清及水泡液中高迁移率族蛋白 B 的蛋白含量高迁移率族
Authors: D.F. Carr, C.‐W. Wang, T. Bellón, L. Ressel, G. Nwikue, V. Shrivastava, W. Bergfeld, A.L. Jorgensen, W.‐H. Chung, M. Pirmohamed
Journal: British Journal of Dermatology (2019)

史蒂文斯‐约翰逊综合征 (SJS) 和中毒性表皮坏死松解症 (TEN) 是一种罕见的、严重的、皮肤起泡的疾病,其中皮肤的某些部位会死亡和脱落。它们实际上代表着严重程度不同的同一种疾病:SJS 患者的体表脱皮面积低于 10%,而 TEN 患者超过 30%。 在英国,每年约有 500 人感染此病,最常见的原因是对多种常用处方药产生反应。这项研究汇集了来自英国、西班牙、台湾地区和美国的研究人员和患者,目的是检测 SJS/TEN 患者血清(部分血液)、水泡液和皮肤活检组织中一种名为高迁移率族蛋白B1 (HMGB1) 的水平。HMGB1 是一种蛋白,它被认为是发生在 SJS/TEN 中的 a) 组织/细胞损伤和 b) 免疫反应激活的标志物(生物学标志)。 作者在三个独立的患者群体中检测到 SJS/TEN 患者在反应时血清 HMGB1 水平升高,患者水泡液中 HMGB1 水平也非常高。SJS/TEN 患者的皮肤表皮(上)层 HMGB1 水平明显降低,但未出现健康对照或药物引起的皮疹。 皮肤表皮中 HMGB1 水平的下降似乎发生在起水泡之前,这可能是一个早期指标。此外,HMGB1 水平似乎保留在表皮和下一层皮肤(被称为真皮层)之间的交界处,这可能表明 HMGB1 在 SJS/TEN 患者的脱层机制中可能发挥作用。作者的结论是,血清 HMGB1 可能不是 SJS/TEN 的良好临床标志物,但皮肤中 HMGB1 水平的降低可能是皮肤起水泡的早期症状,并可能在产生水泡的机制中发挥关键作用。