tbuckley/cabot-search huggingface dataset:
Gold nanoparticles inhibit activation of cancer-associated fibroblasts by disrupting communication from tumor and microenvironmental cells
Authors: Yushan Zhang, Chandra Kumar Elechalawar, Md Nazir Hossen, Emmy R. Francek, Anindya Dey, Stefan Wilhelm, Resham Bhattacharya, Priyabrata Mukherjee
Journal: Bioactive Materials (2020)

Cancer-associated fibroblasts (CAFs) are a major constituent of the tumor microenvironment (TME) and an important contributor to cancer progression and therapeutic resistance. Regulation of CAF activation is a promising strategy to influence cancer outcomes. Here, we report that ovarian cancer cells (OCs) and TME cells promote the activation of ovarian CAFs, whereas gold nanoparticles (GNPs) of 20 nm in diameter inhibit the activation, as demonstrated by the changes in cell morphology, migration, and molecular markers. GNPs exert the effect by altering the levels of multiple fibroblast activation or inactivation proteins, such as TGF-β1, PDGF, uPA and TSP1, secreted by OCs and TME cells. Thus, GNPs represent a potential tool to help understand multicellular communications existing in the TME as well as devise strategies to disrupt the communication.
The potential roles of exosomes in pancreatic cancer initiation and metastasis
Authors: Wei Sun, Ying Ren, Zaiming Lu, Xiangxuan Zhao
Journal: Molecular Cancer (2020)

Abstract Pancreatic cancer (PaCa) is an insidious and highly metastatic malignancy, with a 5-year survival rate of less than 5%. So far, the pathogenesis and progression mechanisms of PaCa have been poorly characterized. Exosomes correspond to a class of extracellular nanovesicles, produced by a broad range of human somatic and cancerous cells. These particular nanovesicles are mainly composed by proteins, genetic substances and lipids, which mediate signal transduction and material transport. A large number of studies have indicated that exosomes may play decisive roles in the occurrence and metastatic progression of PaCa. This article summarizes the specific functions of exosomes and their underlying molecular mechanisms in mediating the initiation and metastatic capability of PaCa.
Inhaled bosentan microparticles for the treatment of monocrotaline-induced pulmonary arterial hypertension in rats
Authors: Hyo-Jung Lee, Yong-Bin Kwon, Ji-Hyun Kang, Dong-Won Oh, Eun-Seok Park, Yun-Seok Rhee, Ju-Young Kim, Dae-Hwan Shin, Dong-Wook Kim, Chun-Woong Park
Journal: Journal of Controlled Release (2020)
Abstract CT217: POLO: Homologous recombination repair gene mutations (HRRm) in metastatic pancreatic cancer (mPaC) tumors
Authors: Zhongwu Lai, Talia Golan, Hedy L. Kindler, Brian Dougherty, Athena Matakidou, Liqin Dong, Gershon Locker, Elizabeth A. Harrington
Journal: Cancer Research (2020)

Abstract mPaC patients (pts) with HRRm, including BRCA1 and/or BRCA2 mutations (BRCAm), derive benefit from platinum-based treatment (Pishvaian. J Clin Oncol 2019). In the Phase III POLO trial (NCT02184195) maintenance olaparib conferred a progression-free survival benefit over placebo in pts with a germline (g) BRCAm and mPaC. A prespecified exploratory analysis was conducted to determine the prevalence of tumor tissue biomarkers in pts screened for inclusion in POLO. Archival tumor samples were provided if available and, irrespective of subsequent pt randomization, DNA was analyzed using a gene panel from Foundation Medicine Inc. (FMI) or exome sequencing by Human Longevity Inc. (HLI). Results were compared with cohorts from FMI (mPaC; FoundationOne CDx panel) and The Cancer Genome Atlas (TCGA; primary and mPaC; exome sequencing). Tumor samples from 187/3315 (5.6%) pts screened for entry into POLO were available and sequenced. Prevalence of tumor HRRm in the POLO, FMI and TCGA cohorts are presented in the Table. The higher BRCAm prevalence observed in the POLO and FMI cohorts compared with TCGA may be due to sample size or differences in ethnicity or tumor sample location (primary vs metastatic). Mutations in BRCA2, BRCA1 and ATM were most common and were generally mutually exclusive. The prevalence of somatic (s) BRCAm in POLO was consistent with the FMI dataset (~2%); g and s BRCAm were mutually exclusive. Of the HRRm observed in non-BRCA genes, mutations in ATM were most prevalent. Prevalence of mutations in non-HRR genes (CDKN2A, SMAD4, KRAS, TP53) in POLO was consistent with that seen in other pancreatic cancer cohorts. TablePrevalence, %*POLO (N=187)FMI (N=1046)TCGA (N=146)BRCA24.84.32.1BRCA13.22.10ATM5.32.55.5PALB21.10.90.7CDK1200.50RAD51C00.10RAD51B00.20RAD54L00.20RAD51D00.20BRIP10.50.30.7FANCI00.30FANCL0.50.10BARD10.50.20.7CHEK100.20CHEK200.62.1Any HRR15.512.011.0Non-BRCA HRR7.55.68.9*Some tumors had a mutation in &amp;gt;1 gene In summary, based on the subgroup of pts with analyzed tumor tissue, the genetic profile of the screened POLO population is reflective of that seen in the overall pancreatic cancer population. ~8% of pts had tumors harboring a BRCAm, with mutations in BRCA2 more prevalent than BRCA1; ~7% of pts had tumors harboring a non-BRCA HRRm, most commonly in ATM (~5%). Citation Format: Zhongwu Lai, Talia Golan, Hedy L. Kindler, Brian Dougherty, Athena Matakidou, Liqin Dong, Gershon Locker, Elizabeth A. Harrington. POLO: Homologous recombination repair gene mutations (HRRm) in metastatic pancreatic cancer (mPaC) tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT217.
Abstract 6157: Hypoxia increases motility of neuroblastoma cells induced by the neuropeptide Y/Y5 receptor pathway and exacerbates their metastatic potential
Authors: Nouran Abualsaud, Lindsay Caprio, Sung Hyeok Hong, Susana Galli, Joanna Kitlinska
Journal: Cancer Research (2020)

Abstract Neuroblastoma (NB) is a pediatric malignancy that originates from precursors of sympathetic neurons and expresses neuronal proteins, such as neuropeptide Y (NPY) and its receptors. NB cells constitutively express NPY Y2 receptor (Y2R), which maintains their proliferation and tumor vascularization. However, pro-apoptotic conditions additionally induce expression of Y5 receptor (Y5R), which acts as a survival factor for tumor cells. High Y5R expression was also observed in angioinvasive NB cells surrounding blood vessels, suggesting a role for this receptor in NB dissemination. Indeed, in NB patients, high serum levels of NPY associated with the presence of metastases. Hence, the goal of this study was to identify mechanisms that may underlie potential pro-metastatic effects of NPY. We have found that NPY, acting via Y5R, stimulates NB cell motility and acts as a chemotactic factor for these cells in a concentration-dependent manner. Hypoxia, a known condition promoting metastasis, increased expression of Y5R in SK-N-BE(2) and SK-N-AS NB cell lines. Consequently, hypoxic NB cells had increased motility and a chemotactic response to NPY. This increase in NPY-driven migration was fully blocked by Y5R antagonist. Pre-incubation of NB cells in hypoxia before orthotopic injections into adrenal glands of SCID/bg mice exacerbated metastasis in xenografts from both NB cell lines. In mice bearing non-MYCN amplified SK-N-AS tumors, the hypoxia-driven metastases were located in soft tissues, while MYCN-amplified SK-N-BE(2) xenografts derived from hypoxic cells exhibited enhanced dissemination to lungs. The latter pattern of metastases is also observed in NB patients with MYCN amplification. Further studies are required to determine if the hypoxia-driven increase in NB metastasis is Y5R-dependent. Altogether, our data support the role of tumor hypoxia and NPY/Y5R axis in NB dissemination. Since this pathway is also activated during chemotherapy and promotes NB cells resistance to treatment, NPY/Y5R may also be involved in the secondary dissemination of the recurrent tumors. If the role of Y5R in NB metastasis is validated in preclinical models, this NPY receptor may become a potential therapeutic target preventing the disease dissemination. Citation Format: Nouran Abualsaud, Lindsay Caprio, Sung Hyeok Hong, Susana Galli, Joanna Kitlinska. Hypoxia increases motility of neuroblastoma cells induced by the neuropeptide Y/Y5 receptor pathway and exacerbates their metastatic potential [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6157.
Call to Action to All Surgery Journal Editors for Diversity in the Editorial and Peer Review Process
Authors: Melina R. Kibbe, Julie Freischlag
Journal: JAMA Surgery (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Abstract 2575: Mechanoactivation of NOX2-generated ROS elicits persistent TRPM8 Ca2+ signals that are inhibited by oncogenic KRas
Authors: Stephen JP Pratt, Rachel M. Lee, Erick O. Hernandez-Ochoa, Eleanor C. Ory, Keyata N. Thompson, Patrick C. Bailey, Trevor J. Mathias, Julia A. Ju, Michele I. Vitolo, Martin F. Schneider, Joseph P. Stains, Christopher W. Ward, Stuart S. Martin
Journal: Cancer Research (2020)

Abstract Changes in the mechanical microenvironment and mechanical signals are observed during tumor progression, malignant transformation, and metastasis. In this context, understanding the molecular details of mechanotransduction signaling may provide unique therapeutic targets. Here we report that normal breast epithelial cells are mechanically sensitive, responding to mechanical stimuli through a two-part calcium signaling mechanism. We observed an immediate, robust rise in intracellular calcium (within seconds) followed by a persistent extracellular calcium influx (up to 30 minutes). This persistent calcium was sustained via microtubule-dependent mechano-activation of NADPH oxidase 2 (NOX2)-generated reactive oxygen species (ROS), which acted on TRPM8 channels to prolong calcium signaling. In contrast, the introduction of a constitutively-active oncogenic KRas mutation inhibited the magnitude of initial calcium signaling and severely blunted persistent calcium influx. The identification that oncogenic KRas suppresses mechanically-induced calcium at the level of ROS provides a novel mechanism for how KRas could alter cell responses to tumor microenvironment mechanics and may reveal new chemotherapeutic targets for cancer. Moreover, we find that expression changes in both NOX2 and TRPM8 mRNA predicts poor clinical outcome in estrogen receptor (ER) negative breast cancer patients, a population with limited available treatment options. The clinical and mechanistic data demonstrating disruption of this mechanically-activated calcium pathway in breast cancer patients and by KRas activation reveal novel signaling alterations that could influence cancer cell responses to the tumor mechanical microenvironment and impact patient survival. Citation Format: Stephen JP Pratt, Rachel M. Lee, Erick O. Hernandez-Ochoa, Eleanor C. Ory, Keyata N. Thompson, Patrick C. Bailey, Trevor J. Mathias, Julia A. Ju, Michele I. Vitolo, Martin F. Schneider, Joseph P. Stains, Christopher W. Ward, Stuart S. Martin. Mechanoactivation of NOX2-generated ROS elicits persistent TRPM8 Ca2+ signals that are inhibited by oncogenic KRas [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2575.
Haemodynamic effects of acute PDE-5A inhibition in a porcine model of hypertensive heart disease
Authors: A. Alogna, M. Schwarzl, B. Zirngast, M. Manninger-Wuenscher, J. Vederber, D. Zweiker, P. Steendijk, H. Maechler, B. Pieske, H. Post
Journal: European Journal of Heart Failure (2014)
Abstract 4645: Lifestyle and dietary oxidative balance scores and risk for incident colorectal cancer among older women: The Iowa Women's Health Study
Authors: Ziling Mao, Anna E. Prizment, DeAnn Lazovich, David C. Gibbs, Roberd M. Bostick
Journal: Cancer Research (2020)

Abstract Background: Basic science literature strongly supports a role of oxidative stress in colorectal cancer (CRC) etiology; however, in epidemiologic studies, associations of individual lifestyle and dietary anti- and pro-oxidant exposures with CRC have been largely inconsistent. However, recent epidemiologic evidence suggests that the collective effects of these exposures on oxidative balance and CRC risk may be substantial. Methods: From lifestyle and food frequency questionnaire data from the prospective Iowa Women's Health Study (1986 - 2012), we calculated equal-weight, 4-component lifestyle and 11-component dietary oxidative balance scores (OBS), and investigated their separate and joint associations with incident CRC using multivariable Cox proportional hazards regression. Results: Of the 34,135 cancer-free women aged 55 to 69 at baseline, 1,635 developed CRC during follow-up. Among participants in the highest lifestyle and dietary OBS quintiles (higher anti-oxidant relative to pro-oxidant exposures) relative to the lowest, the multivariable-adjusted hazard ratios (HRs) were, respectively, 0.63 (95% confidence interval (CI), 0.54-0.73; Ptrend &amp;lt; 0.0001) and 0.77 (95% CI, 0.64-0.94; Ptrend = 0.01. The lowest risk was among those in the highest relative to the lowest joint lifestyle/dietary OBS quintile (HR = 0.47; 95% CI, 0.29-0.76). Conclusions: Our findings suggest that a predominance of antioxidant over pro-oxidant lifestyle and dietary exposures–especially lifestyle separately and jointly with dietary exposures–may be inversely associated with CRC risk among older women. Citation Format: Ziling Mao, Anna E. Prizment, DeAnn Lazovich, David C. Gibbs, Roberd M. Bostick. Lifestyle and dietary oxidative balance scores and risk for incident colorectal cancer among older women: The Iowa Women's Health Study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4645.
RNA G-quadruplex structures exist and function in vivo in plants
Authors: Xiaofei Yang, Jitender Cheema, Yueying Zhang, Hongjing Deng, Susan Duncan, Mubarak Ishaq Umar, Jieyu Zhao, Qi Liu, Xiaofeng Cao, Chun Kit Kwok, Yiliang Ding
Journal: Genome biology (2020)

Abstract Background Guanine-rich sequences are able to form complex RNA structures termed RNA G-quadruplexes in vitro. Because of their high stability, RNA G-quadruplexes are proposed to exist in vivo and are suggested to be associated with important biological relevance. However, there is a lack of direct evidence for RNA G-quadruplex formation in living eukaryotic cells. Therefore, it is unclear whether any purported functions are associated with the specific sequence content or the formation of an RNA G-quadruplex structure. Results Using rG4-seq, we profile the landscape of those guanine-rich regions with the in vitro folding potential in the Arabidopsis transcriptome. We find a global enrichment of RNA G-quadruplexes with two G-quartets whereby the folding potential is strongly influenced by RNA secondary structures. Using in vitro and in vivo RNA chemical structure profiling, we determine that hundreds of RNA G-quadruplex structures are strongly folded in both Arabidopsis and rice, providing direct evidence of RNA G-quadruplex formation in living eukaryotic cells. Subsequent genetic and biochemical analyses show that RNA G-quadruplex folding is able to regulate translation and modulate plant growth. Conclusions Our study reveals the existence of RNA G-quadruplex in vivo and indicates that RNA G-quadruplex structures act as important regulators of plant development and growth.
Association of Chemoradiotherapy With Thoracic Vertebral Fractures in Patients With Esophageal Cancer
Authors: Kota Fujii, Katsuyuki Sakanaka, Ryuji Uozumi, Yuichi Ishida, Hiroyuki Inoo, Shigeru Tsunoda, Shin’ich Miyamoto, Manabu Muto, Takashi Mizowaki
Journal: JAMA Network Open (2020)

The association of chemoradiotherapy (CRT) with a thoracic vertebral fracture in patients with esophageal cancer is unknown.To determine whether CRT is associated with thoracic vertebral fractures in patients with esophageal cancer.This retrospective cohort study included patients with clinical stages I to III thoracic esophageal cancer who visited the Kyoto University Hospital, Kyoto, Japan, from January 1, 2007, to December 31, 2013. Data were analyzed from April 6, 2018, to June 4, 2020.Chemoradiotherapy (CRT group) or surgery or endoscopic treatment (non-CRT group).The main outcome of this study was the cumulative incidence rate of thoracic vertebral fractures in 36 months. The incidence rate was calculated taking censoring into account. Possible risk factors, including CRT, were explored in the multivariable analysis. The association of irradiated doses with fractured vertebrae was also evaluated.A total of 315 patients (119 for the CRT group and 196 for the non-CRT group) were included. The median age of patients was 65 (range, 32-85) years. Fifty-six patients (17.8%) were female and 259 (82.2%) were male. The median observation time was 40.4 (range, 0.7-124.1) months. Thoracic vertebral fractures were observed in 20 patients (16.8%) in the CRT group and 8 patients (4.1%) in the non-CRT group. The 36-month incidence rate of thoracic vertebral fractures was 12.3% (95% CI, 7.0%-19.1%) in the CRT group and 3.5% (95% CI, 1.3%-7.5%) in the non-CRT group (hazard ratio [HR], 3.41 [95% CI, 1.50-7.73]; P = .003). The multivariable analysis showed that the HR of the thoracic vertebral fracture in the CRT group to non-CRT group was 3.91 (95% CI, 1.66-9.23; P = .002) with adjusting for sex, 3.14 (95% CI, 1.37-7.19; P = .007) with adjusting for age, and 3.10 (95% CI, 1.33-7.24; P = .009) with adjusting for the history of vertebral or hip fractures. The HR of the thoracic vertebral fracture for a 5-Gy increase in the mean radiation dose to the single vertebra was 1.19 (95% CI, 1.04-1.36; P = .009).This study found that chemoradiotherapy was associated with thoracic vertebral fractures in patients with esophageal cancers. A reduced radiation dose to thoracic vertebrae may decrease the incidence of fractures.
Lack of FGF21 promotes NASH-HCC transition <i>via</i> hepatocyte-TLR4-IL-17A signaling
Authors: Qianqian Zheng, Robert C. Martin, Xiaoju Shi, Harshul Pandit, Youxi Yu, Xingkai Liu, Wei Guo, Min Tan, Ou Bai, Xin Meng, Yan Li
Journal: Theranostics (2020)

Hepatocellular carcinoma (HCC) has been increasingly recognized in nonalcoholic steatohepatitis (NASH) patients. Fibroblast growth factor 21 (FGF21) is reported to prevent NASH and delay HCC development. In this study, the effects of FGF21 on NASH progression and NASH-HCC transition and the potential mechanism(s) were investigated.
Abstract 5544: Newcastle Disease Virus in human derived tumors: Understanding immune recruitment and activation via virally delivered IL-12
Authors: Nicholas M. Durham, Kelly McGlinchey, Shannon Burke, Todd Creasy, Nicola Rath, Noel Monks, Ravinder Tammali, Kevin Schifferli, Nick Holoweckyj, Susie Hayes, Emma Jones, Elizabeth J. Kelly, Danielle Carroll, James Harper, Katie Streicher
Journal: Cancer Research (2020)

Abstract Oncolytic viruses (OV) are defined by their intrinsic or engineered tropism for tumor cells. Understanding the drivers of susceptibility to infection as well as the downstream intracellular signaling and immune activation profile is critical in identifying the patients that will respond to OV therapy. Newcastle Disease Virus (NDV) is a negative stranded RNA avian paramyxovirus, here modified to encode human GM-CSF or IL-12. Patient derived xenografts (PDX) can more accurately reflect the genetic, epigenetic, and architectural heterogeneity of human tumors and were therefore selected to model the in vivo activity of NDV:GM-CSF. Eighty-nine independent models derived from patients with Bladder, Colorectal, Head and Neck, Kidney, Liver, Lung, Ovarian, Pancreatic, and Breast tumors were studied. Mice were dosed intravenously with NDV:GM-CSF, monitored for pharmacodynamic and pharmacokinetic changes 48 hours after the first dose, and followed for tumor growth inhibition. Objective response was observed in 68% of treated mice, with responses observed in all indications. Using total stranded RNAseq, we were able to assess changes in human tumor, murine immune infiltrate, and viral RNA. Results showed that NDV:GM-CSF treatment leads to increases in transcripts of inflammatory chemokines and cytokines such as RANTES and CXCL9, with induction directly correlated to level of viral replication. Additionally, we saw increases in NKp46 and IL-12R, markers of NK cells. To assess if IL-12 would augment immune activation, we treated surgically resected human tumors with NDV:IL-12. NDV:IL-12 was capable of infecting tumor cells, generating IL-12 protein, and driving a strong IFNγ response. Here we show that NDV can infect a wide variety of human tumors across multiple indications and drive a potent immune activation which can be modulated by transgenes. This data provides insight into what types of tumors could be treated with NDV:GM-CSF or NDV:IL-12. Citation Format: Nicholas M. Durham, Kelly McGlinchey, Shannon Burke, Todd Creasy, Nicola Rath, Noel Monks, Ravinder Tammali, Kevin Schifferli, Nick Holoweckyj, Susie Hayes, Emma Jones, Elizabeth J. Kelly, Danielle Carroll, James Harper, Katie Streicher. Newcastle Disease Virus in human derived tumors: Understanding immune recruitment and activation via virally delivered IL-12 [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5544.