tbuckley/cabot-search huggingface dataset:
Abstract 259: Modulation of doxorubicin actions on HCC cells by insulin-like growth factor-I
Authors: Brian I. Carr, Maria Grazia Refolo, Rosalba D’Alessandro, Nicola Carella, Caterina Messa, Aldo Cavallini
Journal: Cancer Research (2016)

Abstract Tumor microenvironment is increasingly understood to influence tumor biology in many tumor types, including HCC. We recently showed that platelets could modulate Doxorubicin (Dox)-mediated HCC growth inhibition (Refolo MG et al. Modulation of doxorubicin mediated growth inhibition of hepatocellular carcinoma cells by platelet lysates. Anticancer Agents Med Chem. 2014;14:1154-60). Platelets contain cytokines and growth factors, including IGF-1, PDGF, FGF, EGF and serotonin. We found that Insulin-like growth factor-1 (IGF-1) shifted the Dox growth-inhibitory dose-response in the range of 0.1-1.0 μM on Hep3B, HepG2, PLC/PRF/5 human HCC lines, all of which became less sensitive to both Dox-mediated inhibition of growth and apoptosis. Similar antagonism by IGF-1 was found for Dox-mediated inhibition of cell migration (scratch assay) and invasion (Boyden chamber). This antagonism of Dox effects on cell growth, migration and apoptosis by IGF1, was blocked by GSK1838705A, an IGF-1R inhibitor. Furthermore, when platelet extracts were used to antagonize Dox inhibition of growth and migration, the platelet effects were also blocked by addition of GSK1838705A to the cultures, showing that the platelet effects were largely mediated by IGF-1. Dox caused a decrease in the levels of anti-apoptosis markers Bcl-2, Bcl-xL and survivin as seen on WB, whereas levels of all three anti-apoptosis markers were increased by IGF-1 action. These actions of IGF-1 were also blocked by GSK 1838705A. Furthermore, Dox caused a decrease in the levels of P-ERK, P-p38 and P-STAT3 (ser727). These signaling molecule decreases were also reversed by the presence of IGF-1. Conclusions. Dox actions on HCC cells can be antagonized by platelets and specifically by platelet-associated IGF-1. IGF-1 antagonists appear to be attractive enhancers of sensitivity to Dox actions. Citation Format: Brian I. Carr, Maria Grazia Refolo, Rosalba D’Alessandro, Nicola Carella, Caterina Messa, Aldo Cavallini. Modulation of doxorubicin actions on HCC cells by insulin-like growth factor-I. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 259.
Decreasing Unintended Pregnancy
Authors: Jared Fox, Wanda Barfield
Journal: JAMA (2016)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Irene Davis
Authors: Johann Windt
Journal: British Journal of Sports Medicine (2016)

![Graphic][1]</img> Don't worry about J Edgar Hoover not letting you become an FBI agent (women weren't allowed in back then), you'll use your investigative passion in other ways! Watching the Red Sox win the World Series in McGreevy's, the oldest sports bar in the USA, with my husband, brother, sister and 85-year-old Dad—who drank more beers that night than I could believe! This was an especially emotional win as it was the year of the Boston Marathon bombings (my husband and I were in the finish line medical tent that day) and the Red Sox were playing for Boston Strong. McGreevy's is just a couple of blocks from the finish line so everyone migrated there to celebrate after the win. It was a magical night for Boston! Being willing to look at an issue in a completely different way and letting go of my preconceived ideas. We need to appreciate that the scientific truth of 10 years ago may not be the truth today, and the truth today may not be the truth 10 years from now. Honestly, my husband. After an amazing 25-year career in Special Forces, he came out of retirement to … [1]: /embed/inline-graphic-1.gif
A novel endoscopic technique for closure of a large esophageal perforation using the clip-and-snare method with the prelooping technique
Authors: Yasuaki Nagami, Masatsugu Shiba, Masaki Ominami, Kazunari Tominaga, Toshio Watanabe, Yasuhiro Fujiwara, Tetsuo Arakawa
Journal: Endoscopy (2016)

It is sometimes difficult to close a large perforation using endoclips and over-the-scope clips, and surgery may be required [1]. We report a novel endoscopic technique for closure of a large perforation using the clip-and-snare method with the prelooping technique.
Abstract 4401: Disclosing the Hippo signaling networks in castration-resistant prostate cancer
Authors: Damien Ready, Yuksel Yildiz, Vincent Funari, Serdar Bozdag, Bekir Cinar
Journal: Cancer Research (2016)

Abstract Prostate cancer often evolves as a metastatic castration-resistant disease, which is lethal. Despite recent advances, the molecular mechanisms contributing to this lethal disease are largely unknown. Our initial studies have indicated that the loss-of-function of the STK4-encoded MST1 protein kinase, a key component of the Hippo tumor suppressor pathway, may play a prominent role in the etiology of prostate cancer progression. Here, we establish cytoplasmic-, membrane- or nuclear-localized MST1 cell models to elucidate a possible mode of actions by which MST1 control the disease progression. We show that membrane or nuclear MST1 confers superior growth inhibitory effects on castration-resistant prostate cancer cells ex vivo and in vivo in comparison with cytoplasmic MST1, though they express the similar levels of MST1 protein. Consistently, a number of differentially expressed genes (2-fold with FDR ≤ 0.05) regulated by membrane or nuclear MST1 protein are much greater than cytoplasmic MST1, as assessed by RNA-sequencing and bioinformatics analysis. Functional annotation clustering reveals that genes affected by cytoplasmic MST1 protein are mostly associated with cell-cell interactions and membrane trafficking. However, expression of genes altered by membrane or nuclear MST1 involves much broader cellular biology that includes cell signaling, steroid biogenesis, lipid and cholesterol metabolisms, and developmental processes. In addition, Ingenuity Pathway analysis indicates that several genes effected by ectopic MST1 protein the defined cell location interact with androgen receptor pathway signaling, a critical regulator of prostate cancer pathogenesis. The results of this study suggest that the Hippo pathway signaling restricts prostate cancer progression by modulating the array of signaling networks, indicating important therapeutic implications for human disease. Citation Format: Damien Ready, Yuksel Yildiz, Vincent Funari, Serdar Bozdag, Bekir Cinar. Disclosing the Hippo signaling networks in castration-resistant prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4401.
Abstract 5188: Combination of radiofrequency ablation and Sunitinib in the treatment of experimental hepatocellular cancer
Authors: Xiaoqiang Qi, Guangfu Li, Dai Liu, Kevin F Staveley-O’Carroll, Eric Kimchi
Journal: Cancer Research (2016)

Abstract Radiofrequency Ablation (RFA) is one of current clinical option in the treatment of hepatocellular cancer (HCC); however, RFA monotherapy is often not curative as a consequence of tumor micro-metastases and recurrence. Thus, induction of systemic response with additive treatment is required. In the present study, we are exploring the combination of RFA and sunitinib, an FDA-approved multiple tyrosine kinase inhibitor, in the treatment of HCC. Using our established strategy a clinically relevant murine model of HCC is prepared which mimics human disease and reflect its typical features. The follow-up magnetic resonance imaging (MRI) is applied to monitor tumor progression until the cumulative tumor volume reaches 2000 mm3. Size-matched tumor-bearing mice are assigned into 3 groups and receive the following treatments: no treatment, RFA alone with our improved machine and optimized parameters, combination of sunitinib and RFA. The therapeutic efficacy is evaluated by measuring tumor volume with MRI every twice weeks. We demonstrate that tumors grow substantially in the mice without treatment. RFA alone effectively destroys tumors, but unable to prevent tumor recurrence and micro-metastasis. In contrast, &amp;gt; 50% size reduction in tumor size is detected in the combined group compared to that in control mice, even no detectable tumors are observed in some treated mice. In conclusion, combination of sunitinib and RFA powerfully suppress tumor growth and could be translate into clinic practice. Citation Format: Xiaoqiang Qi, Guangfu Li, Dai Liu, Kevin F Staveley-O’Carroll, Eric Kimchi. Combination of radiofrequency ablation and Sunitinib in the treatment of experimental hepatocellular cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5188.
Abstract 1107: miR-29b acts as an oncogene or tumor suppressor gene depending on the external stimulus
Authors: Erik Vassella, Stephanie Langsch
Journal: Cancer Research (2016)

Abstract microRNAs (miRNAs), short regulatory sequences at the posttranscriptional level, are important mediators of signaling pathways that act as backups of transcriptional control. To identify miRNAs implicated in epidermal growth factor receptor (EGFR) signaling, transformed bronchial epithelial BEAS-2B cells were retrovirally transduced with KRASG12V and alterations in miRNA expression were assessed by microarray analysis. Here we show that miR-29b is significantly induced by mutant KRAS in bronchial epithelial and non-small cell lung cancer (NSCLC) cell lines as well as in primary NSCLC tissue. In agreement with these results, inhibitors of EGFR and MEK resulted in reduced levels of miR-29b while inhibitors of PI3K had no effect. KRASG12V-transduced BEAS-2B cells were significantly more protected from extrinsic apoptosis than control transduced cells, but co-transduction of cells with KRASG12V and anti-miR-29b constructs sensitized cells to apoptosis indicating that miR-29b is a mediator of KRAS-induced resistance to apoptosis. Protection from extrinsic apoptosis was due to enhanced nuclear factor κB (NF-κB) activity. The ubiquitin-editing enzyme tumor necrosis factor alpha-induced protein 3 (TNFAIP3/A20) is a negative regulator of NF-κB signaling. Enhanced NF-κB activity elicited by miR-29b was due to targeting TNFAIP3/A20. Overexpression of miR-29b-refractory TNFAIP3 restored NF-κB activity as well as extrinsic apoptosis, demonstrating that TNFAIP3 is a relevant target of miR-29b. Interestingly, miR-29b conferred sensitivity to cisplatin-induced intrinsic apoptosis by targeting Mcl-1. Thus, miR-29b tips the balance from extrinsic apoptosis towards intrinsic apoptosis. Our results indicate that miR-29b can act either as an oncogene or tumor suppressor gene depending on the external stimulus. Citation Format: Erik Vassella, Stephanie Langsch. miR-29b acts as an oncogene or tumor suppressor gene depending on the external stimulus. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1107.
Multicentre trial of carboplatin/paclitaxel versus oxaliplatin/capecitabine, each with/without bevacizumab, as first line chemotherapy for patients with mucinous epithelial ovarian cancer (mEOC).
Authors: Martin Eric Gore, Allan Hackshaw, William E Brady, Richard T. Penson, Richard J Zaino, W. Glenn McCluggage, Raji Ganesan, Nafisa Wilkinson, Timothy Perren, Ana Montes, Jeffrey Summers, Rosemary Lord, Graham G. Dark, Gordon J. S. Rustin, Melanie J. Mackean, Nicholas Reed, Sean Kehoe, Helen Christensen, Jonathan A. Ledermann, David Marc Gershenson
Journal: Journal of Clinical Oncology (2015)

5528 Background: Advanced mEOC responds poorly to standard therapy. It comprises < 8% pts in ovarian cancer trials, so it is difficult to examine treatment effects in this subgroup. We conducted the first ever randomised trial specific for this rare subgroup (4 regimens). Methods: mEOC/GOG 241 is a multi-centre randomised phase II trial (UK, USA) in chemo- naive pts with advanced/recurrent disease. Six 21-day cycles of chemotherapy were given to each of 4 arms: (A) carboplatin (AUC 5/6) + paclitaxel (175mg/m2); (B) oxaliplatin (130 mg/m2) + capecitabine (850mg/m2 bd; D1-14); (C) carboplatin/paclitaxel with bevacizumab (15mg/kg); (D) oxaliplatin/capecitabine with bevacizumab. Bevacizumab was given concurrently, then alone 3-weekly for 12 more cycles. 332 pts required to detect 5 month increase in median PFS for oxaliplatin/capecitabine (B+D), or adding bevacizumab (C+D). Results: Trial stopped early (2013) due to poor accrual (median follow up 23 months; 31 progressions/deaths). 50 pts recruited: n = 13, 13, 11, 13 in arms A-D. Median age 54 yrs; FIGO stage II (n = 15), III (n = 25), IV (n = 4), recurrent (n = 6); ECOG 0 (n = 34), 1 (n = 15), 2 (n = 1). 62, 85, 82, 69% in arms A-D completed 6 cycles of combination therapy, and 36, 46% completed 12 maintenance cycles of bevacizumab (arms C,D). 2,2,4,2 pts (arms A-D) had complete/partial response. Median PFS 10.1 (B+D) vs 15.4 (A+C) months; hazard ratio (HR) 1.08, 95% CI 0.53-2.19, p = 0.83. Median PFS 17.4 (C+D) vs 8.8 (A+B) months, HR 0.88 95% CI 0.43-1.79, p = 0.72. Grade 3-4 toxicities (most common: neutropenia, & hypertension for bevacizumab) were seen in 62, 62, 55, 92% pts in arms A-D (total 4 pts with grade 4). After specialist pathology review n = 36 so far, 19 were considered to not have primary mEOC (many metastatic disease). Conclusions: Setting up & conducting this international trial was challenging in this rare group; correctly assigning histological diagnosis was difficult. Bevacizumab may delay progression (ITT analyses), but without sufficient pts no conclusions can be made. Primary mEOC is rarer than previously thought so different approaches are needed to evaluate new therapies. Clinical trial information: NCT01081262.
Exposure to inorganic arsenic can lead to gut microbe perturbations and hepatocellular carcinoma
Authors: Jonathan Choiniere, Li Wang
Journal: Acta Pharmaceutica Sinica B (2016)

Arsenic is a carcinogenic environmental factor found in food and drinking water around the world. The mechanisms in which arsenic alters homeostasis are not fully understood. Over the past few decades, light has been shed on varying mechanisms in which arsenic induces cancer. Such mechanisms include gut microbe perturbations, genotoxic effects, and epigenetic modification. Gut microbe perturbations have been shown to increase the level of pathogen-associated molecular patterns such as lipopolysaccharide (LPS) leading to uncontained inflammation. Increase in inflammation is the major factor in cirrhosis leading to hepatocellular carcinoma. Alterations in gut permeability and metabolites have also been observed as a fallout of arsenic induced gut microbe modification. The guts proximity and interaction through portal flow make the liver susceptible to gut perturbations and ensuing inflammatory responses. Genotoxic and epigenetic dysregulation induced by arsenic and its toxic metabolites present a more direct mechanism that works synergistically with gut microbe perturbations to induce the incidence of cancers. These pathways combined could be some of the main causes of arsenic-induced carcinogenesis.
Canakinumab reverses overexpression of inflammatory response genes in tumour necrosis factor receptor-associated periodic syndrome
Authors: Rebecca Torene, Nanguneri Nirmala, Laura Obici, Marco Cattalini, Vincent Tormey, Roberta Caorsi, Sandrine Starck-Schwertz, Martin Letzkus, Nicole Hartmann, Ken Abrams, Helen Lachmann, Marco Gattorno
Journal: Annals of the Rheumatic Diseases (2016)

Objective To explore whether gene expression profiling can identify a molecular mechanism for the clinical benefit of canakinumab treatment in patents with tumour necrosis factor receptor-associated periodic syndrome (TRAPS). Methods Blood samples were collected from 20 patients with active TRAPS who received canakinumab 150 mg every 4 weeks for 4 months in an open-label proof-of-concept phase II study, and from 20 aged-matched healthy volunteers. Gene expression levels were evaluated in whole blood samples by microarray analysis for arrays passing quality control checks. Results Patients with TRAPS exhibited a gene expression signature in blood that differed from that in healthy volunteers. Upon treatment with canakinumab, many genes relevant to disease pathogenesis moved towards levels seen in the healthy volunteers. Canakinumab downregulated the TRAPS-causing gene (TNF super family receptor 1A ( TNFRSF1A )), the drug-target gene (interleukin ( IL ) -1B ) and other inflammation-related genes (eg, MAPK14 ). In addition, several inflammation-related pathways were evident among the differentially expressed genes. Canakinumab treatment reduced neutrophil counts, but the observed expression differences remained after correction for this. Conclusions These gene expression data support a model in which canakinumab produces clinical benefit in TRAPS by increasing neutrophil apoptosis and reducing pro-inflammatory signals resulting from the inhibition of IL-1β. Notably, treatment normalised the overexpression of TNFRSF1A , suggesting that canakinumab has a direct impact on the main pathogenic mechanism in TRAPS. Trial registration number NCT01242813.
Abstract 900:In vivomodeling ofNRAS-mutant melanoma reveals differential preventative efficacy amongst SPF30 sunscreens
Authors: Andrea M. Holderbaum, Rebecca C. Hennessey, James E. Gillahan, Anamaria Bonilla, Conor Delaney, Raleigh D. Kladney, Kathleen L. Tober, Tatiana M. Oberyszyn, Christin E. Burd
Journal: Cancer Research (2016)

Abstract Cutaneous melanoma claims the life of one American every hour, and while the etiology of this tumor type is not entirely understood, exposure to ultraviolet (UV) radiation (280-340nm) is a major risk factor. For this reason, the use of UV-blocking sunscreens is strongly advocated; however, few studies have tested the relative efficacy of these agents in preventing melanoma formation in vivo. Here, we employed a new genetically engineered mouse model (TpN61R) to examine the ability of 6 chemically distinct SPF30 sunscreens to prevent melanoma. In this TpN61R model, topical 4-hydroxytamoxifen (4OHT) treatment induces the melanocyte-specific expression of oncogenic NRas as well as inactivation of the p16INK4a tumor suppressor. These genetic lesions co-occur in ∼24% of all human melanomas, making the TpN61R model biologically relevant. Since NRAS mutations are an early and UV-independent event in human melanoma, TpN61R mice were first painted with 4OHT and then exposed to a single dose of 4.5 kJ/m2 UVB light one day later. Exposed skin from TpN61R mice showed transient cyclobutane pyrimidine dimer (CPD) formation, however no evidence of edema or inflammation was observed. Despite these mild effects, UVB exposure reduced the melanoma-free survival of TpN61R mice by 80% and increased tumor incidence rate from 1.2 to 3.4 tumors/mouse. Further experiments using a variety of UVB doses (0.25, 1.0, 2.3 and 9.0 kJ/m2) in the TpN61R model revealed a dose-dependent increase in early melanoma incidence. Together, these data establish the exquisite cooperation of UV light and oncogenic NRas mutations in driving melanoma. Taking advantage of this unique model, we tested the preventative efficacy of SPF30 sunscreens with differing chemical composition. Sunscreens components included UVA (avobenzene), UVB (homosalate, octisalate) and broad spectrum (oxybenzone, octocrylene, zinc oxide) blocking agents. Application of sunscreen prior to UVB exposure decreased DNA damage, delayed melanoma onset and reduced tumor incidence in a sunscreen-dependent manner. Thus, SPF30 sunscreens do not equally prevent UVB-induced, NRAS mutant melanoma. This work establishes the first in vivo system to test sunscreen efficacy in NRAS-driven melanoma and will help direct the development of improved melanoma preventatives. Citation Format: Andrea M. Holderbaum, Rebecca C. Hennessey, James E. Gillahan, Anamaria Bonilla, Conor Delaney, Raleigh D. Kladney, Kathleen L. Tober, Tatiana M. Oberyszyn, Christin E. Burd. In vivo modeling of NRAS-mutant melanoma reveals differential preventative efficacy amongst SPF30 sunscreens. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 900.