tbuckley/cabot-search huggingface dataset:
Neoadjuvant Chemotherapy First, Followed by Chemoradiation and Then Surgery, in the Management of Locally Advanced Rectal Cancer
Authors: Andrea Cercek, Karyn A. Goodman, Carla Hajj, Emily Weisberger, Neil H. Segal, Diane L. Reidy-Lagunes, Zsofia K. Stadler, Abraham J. Wu, Martin R. Weiser, Philip B. Paty, Jose G. Guillem, Garrett M. Nash, Larissa K. Temple, Julio Garcia-Aguilar, Leonard B. Saltz
Journal: Journal of the National Comprehensive Cancer Network (2014)

Standard therapy for locally advanced rectal cancer (LARC) is preoperative chemoradiotherapy and postoperative chemotherapy. At Memorial Sloan-Kettering Cancer Center (MSKCC) the authors began offering FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) as initial treatment for patients with high-risk LARC to target micrometastases while treating the primary tumor. The purpose of this study is to report the safety and efficacy of initial FOLFOX given before chemoradiotherapy on tumor downsizing and pathologic complete response (pathCR) in LARC. The records of patients with stage II/III rectal cancer treated at MSKCC between 2007 and 2012 were reviewed. Of approximately 300 patients with LARC treated at MSKCC, 61 received FOLFOX as initial therapy. Of these 61 patients, 57 received induction FOLFOX (median 7 cycles) followed by chemoradiation, and 4 experienced an excellent response, declined chemoradiation, and underwent total mesorectal excision (TME). Twelve of the 61 patients did not undergo TME: 9 had a complete clinical response (CCR), 1 declined despite persistent tumor, 1 declined because of comorbidities, and 1 developed metastatic disease. Among the 61 patients receiving initial FOLFOX, 22 (36%) had either a pathCR (n=13) or a CCR (n=9). Of the 49 patients who underwent TME, all had R0 resections and 23 (47%) had tumor response greater than 90%, including 13 (27%) who experienced a pathCR. Of the 28 patients who received all 8 cycles of FOLFOX, 8 experienced a pathCR (29%) and 3 a CCR (11%). No serious adverse events occurred that required a delay in treatment during FOLFOX or chemoradiation. FOLFOX and chemoradiation before planned TME results in tumor regression, a high rate of delivery of planned therapy, and a substantial rate of pathCRs, and offers a good platform for nonoperative management in select patients.
Abstract IA18: Epigenetic addiction in pediatric high-grade gliomas
Authors: Nada Jabado
Journal: Cancer Research (2015)

Abstract A remarkably rapidly expanding body of literature points to the epigenome as a new previously unsuspected mechanism of oncogenesis and another “hallmark of cancer.” Indeed, in a large number of cancers, aberrant epigenetic states occur through different mechanisms including altered DNA methylation, covalent histone modification, the reading of these histone modifications by protein regulation modules, histone exchange, chromatin remodelers, or via the effects of non-coding RNAs. Although mutations are also found in canonical signaling pathway genes, we and others identified chromatin-associated proteins to be more commonly altered by somatic alterations than any other class of oncoprotein in several subgroups of childhood high-grade brain tumors. Furthermore, as these childhood malignancies carry fewer non-synonymous somatic mutations per case in contrast to most adult cancers, these mutations are likely drivers in these tumors. Herein, we will use as examples of this novel hallmark of oncogenesis high-grade astrocytomas, including glioblastoma, and a subgroup of embryonal tumors, embryonal tumor with multilayered rosettes (ETMR) to describe the novel molecular defects uncovered in these deadly tumors. We will further discuss evidence for their profound effects on the epigenome and their links to brain development. Importantly, the type, timing and spatial clustering of these molecular alterations provide a better understanding of the pathogenesis of the respective brain tumor they target as well as critical markers for therapy that will help refine pathological grading.The relative genetic simplicity of these tumors promises general insights into how mutations in the chromatin machinery modify downstream epigenetic signatures to drive transformation, and how to target this plastic genetic/epigenetic interface. Citation Format: Nada Jabado. Epigenetic addiction in pediatric high-grade gliomas. [abstract]. In: Proceedings of the AACR Special Conference: Advances in Brain Cancer Research; May 27-30, 2015; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2015;75(23 Suppl):Abstract nr IA18.
Genomic Aberrations Dramatically Improve The Strong Prognostic Impact Of IGHV Mutational Status In Chronic Lymphocytic Leukemia (CLL)
Authors: Giovanni Del Poeta, Dario Ragusa, Francesco Buccisano, Michele Dal Bo, Luca Maurillo, Antonella Zucchetto, Maria Ilaria Del Principe, Pasquale Niscola, Davide Rossi, Alessio Pio Perrotti, Adriano Venditti, Paolo de Fabritiis, Valter Gattei, Gianluca Gaidano, Sergio Amadori
Journal: Blood (2013)
Inflammation in AKI
Authors: Hamid Rabb, Matthew D. Griffin, Dianne B. McKay, Sundararaman Swaminathan, Peter Pickkers, Mitchell H. Rosner, John A. Kellum, Claudio Ronco
Journal: Journal of the American Society of Nephrology (2015)

Inflammation is a complex biologic response that is essential for eliminating microbial pathogens and repairing tissue after injury. AKI associates with intrarenal and systemic inflammation; thus, improved understanding of the cellular and molecular mechanisms underlying the inflammatory response has high potential for identifying effective therapies to prevent or ameliorate AKI. In the past decade, much knowledge has been generated about the fundamental mechanisms of inflammation. Experimental work in small animal models has revealed many details of the inflammatory response that occurs within the kidney after typical causes of AKI, including insights into the molecular signals released by dying cells, the role of pattern recognition receptors, the diverse subtypes of resident and recruited immune cells, and the phased transition from destructive to reparative inflammation. Although this expansion of the basic knowledge base has increased the number of mechanistically relevant targets of intervention, progress in developing therapies that improve AKI outcomes by modulation of inflammation remains slow. In this article, we summarize the most important recent developments in understanding the inflammatory mechanisms of AKI, highlight key limitations of the commonly used animal models and clinical trial designs that may prevent successful clinical application, and suggest priority approaches for research toward clinical translation in this area.
Liver natural killer cells: subsets and roles in liver immunity
Authors: Hui Peng, Eddie Wisse, Zhigang Tian
Journal: Cellular and Molecular Immunology (2015)

The liver represents a frontline immune organ that is constantly exposed to a variety of gut-derived antigens as a result of its unique location and blood supply. With a predominant role in innate immunity, the liver is enriched with various innate immune cells, among which natural killer (NK) cells play important roles in host defense and in maintaining immune balance. Hepatic NK cells were first described as 'pit cells' in the rat liver in the 1970s. Recent studies of NK cells in mouse and human livers have shown that two distinct NK cell subsets, liver-resident NK cells and conventional NK (cNK) cells, are present in this organ. Here, we review liver NK cell subsets in different species, revisiting rat hepatic pit cells and highlighting recent progress related to resident NK cells in mouse and human livers, and also discuss the dual roles of NK cells in liver immunity.
Phosphorylation of RhoC GTPase by Akt/protein kinase B (PKB) is required for breast cancer cell migration and invasion.
Authors: Unger Heather, Kate Groh, Galina Radunsky, Cynthia van Golen, Kenneth van Golen
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

2833 

Recent evidence has suggested a role for Akt/protein kinase B (PKB) in cellular motility and invasion. Previously, we have demonstrated a role for RhoC GTPase in conferring a highly motile and invasive phenotype to inflammatory breast cancer (IBC) cells. RhoC contains a putative Akt phosphorylation site at serine 71, similar to the other members of the Rho subfamily. Studies have suggested that Akt phosphorylation of RhoC prevents GTP binding and subsequent activation of RhoC, thus leading to cellular motility. In this present study we examined the role of Akt phosphorylation of RhoC in breast cancer cell invasion. The SUM 149 inflammatory breast cancer cell line overexpresses RhoC, lacks the PTEN gene, and consequently expresses a constitutively active Akt. Using this SUM 149 IBC cell line, we demonstrate that RhoC is a reputed substrate for Akt phosphorylation. We are able to decrease phospho-RhoC levels and inhibit SUM 149 cellular motility through inhibiting Akt activation with commercially available Akt inhibitors. We are also able to inhibit cellular motility by inhibiting the phosphoinositide-3 kinase pathway with LY294002 or decreasing total levels of Akt with siRNA. In contrast, the MDA435 breast cancer cell line expresses RhoC but has normal expression of PTEN and low active Akt levels. By introducing activated Akt into these MDA435 breast cancer cells, increased phospho-RhoC levels result, along with increased cell motility and invasion. These results suggest that Akt phosphorylation of RhoC in breast cancer cells is required for cellular migration and invasion.
Fresh vs Cryopreserved Donor Oocytes
Authors: James A. Grifo, David H. McCulloh, Lauren Y. Statman
Journal: JAMA (2015)

To the Editor The report by Dr Kushnir and colleagues1 concluded that the use of cryopreserved donor oocytes was inferior to the use of fresh donor oocytes for in vitro fertilization and embryo transfer. We have concerns about their methods.
Deleterious Effect of Altered Myocardial Fatty Acid Metabolism in Kidney Disease⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Vasken Dilsizian, Jeffrey C. Fink
Journal: Journal of the American College of Cardiology (2008)
Disseminating Justified, Well-Designed, and Well-Executed Studies With Nonsignificant Tests—Reply
Authors: Helena Chmura Kraemer
Journal: JAMA Psychiatry (2015)

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 Psychiatry 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 Psychiatry journal
Treg17 cells are programmed by Stat3 to suppress Th17 responses in systemic lupus
Authors: Malte A. Kluger, Simon Melderis, Anna Nosko, Boeren Goerke, Michael Luig, Matthias C. Meyer, Jan-Eric Turner, Catherine Meyer-Schwesinger, Claudia Wegscheid, Gisa Tiegs, Rolf A.K. Stahl, Ulf Panzer, Oliver M. Steinmetz
Journal: Kidney International (2015)
Comment on Rasmussen et al. A Randomized Controlled Trial Comparing Telemedical and Standard Outpatient Monitoring of Diabetic Foot Ulcers. Diabetes Care 2015;38:1723–1729
Authors: Marie Muller, Sandra David-Tchouda, Jennifer Margier, Maurine Oreglia, Pierre-Yves Benhamou
Journal: Diabetes Care (2015)

Rasmussen et al. (1) report the results of a Danish randomized controlled trial on the use of telemonitoring (TM) in diabetic foot ulcers (DFUs). They found no statistical differences in terms of wound healing or amputation between two similar groups of DFU patients followed either with TM or with standard care including regular outpatient visits. However, they found a significantly higher rate of mortality in the telemedicine group.

Our diabetology department at Grenoble University Hospital (France) has used TM since 2008 (2). On the basis of this expertise, we conducted a pilot monocentric randomized trial entitled Medico-economical Assessment of Telemedicine During Chronic Diabetes-related Foot Wound Management (AIRPEDIA) that compared the outcome of DFUs exclusively followed by TM …
The Perilipins: Major Cytosolic Lipid Droplet–Associated Proteins and Their Roles in Cellular Lipid Storage, Mobilization, and Systemic Homeostasis
Authors: Alan R. Kimmel, Carole Sztalryd
Journal: Annual Review of Nutrition (2016)

The discovery by Dr. Constantine Londos of perilipin 1, the major scaffold protein at the surface of cytosolic lipid droplets in adipocytes, marked a fundamental conceptual change in the understanding of lipolytic regulation. Focus then shifted from the enzymatic activation of lipases to substrate accessibility, mediated by perilipin-dependent protein sequestration and recruitment. Consequently, the lipid droplet became recognized as a unique, metabolically active cellular organelle and its surface as the active site for novel protein-protein interactions. A new area of investigation emerged, centered on lipid droplets' biology and their role in energy homeostasis. The perilipin family is of ancient origin and has expanded to include five mammalian genes and a growing list of evolutionarily conserved members. Universally, the perilipins modulate cellular lipid storage. This review provides a summary that connects the perilipins to both cellular and whole-body homeostasis.
Prostate cancer cell-specific targeting using cisplatin-encapsulated and peptide ligand-coated nanoparticles
Authors: Rajesh Singh, Shailesh Singh, James Lillard
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

4743 

Prostate cancer is one of the most common male malignancies and one of the most frequent causes of cancer-related deaths in men in the western world. Patients initially respond to androgen-ablation, but eventually progress to hormone refractory disease. Therefore, alternative strategies are required for treatment of hormone-refractory prostate cancer; chemotherapy has long been used for this purpose. Of the various cytotoxic drugs, cis-di amine platinum (II) dichloride (cisplatin), a member of platinum complexes, has been shown to exhibit therapeutic efficacy in patients with prostate cancer. However, its clinical effectiveness is compromised by its high systemic toxicity, which is an inherent problem for many chemotherapeutic agents. In this study we have tested the hypothesis that nanoparticles containing cisplatin in a starch-polyethylene glycol and coated with polycaprolactone-peptide and/or -folic acid conjugates enhance the therapeutic efficacy of platinum-based therapy. We have investigated the possibility of a more selective delivery of cisplatin to prostate cancer cells using nanoparticles as a cisplatin carrier. The induction of apoptosis and anti-proliferative activity of cisplatin or nanoparticles, containing cisplatin along with folic acid alone and/or prostate cancer cell specific homing peptide coatings, was determined on normal prostatic epithelial cells (PrEC) and human prostate cancer cell lines (PC3, DU145 and LNCaP) in vitro. Nanoparticles showed a selective ability to induce apoptosis and inhibit prostate cancer cells proliferation at lower cisplatin doses compared to cisplatin solution. In conclusion, prostate cancer cell-targeted delivery of cisplatin using nanoparticles demonstrated a greater efficiency and reduced the toxicity associated with this chemotherapeutic.
A Systems Biology Approach Reveals Converging Molecular Mechanisms that Link Different POPs to Common Metabolic Diseases
Authors: Patricia Ruiz, Ally Perlina, Moiz Mumtaz, Bruce A. Fowler
Journal: Environmental Health Perspectives (2015)

Background:A number of epidemiological studies have identified statistical associations between persistent organic pollutants (POPs) and metabolic diseases, but testable hypotheses regarding underlying molecular mechanisms to explain these linkages have not been published.Objectives:We assessed the underlying mechanisms of POPs that have been associated with metabolic diseases; three well-known POPs [2,3,7,8-tetrachlorodibenzodioxin (TCDD), 2,2´,4,4´,5,5´-hexachlorobiphenyl (PCB 153), and 4,4´-dichlorodiphenyldichloroethylene (p,p´-DDE)] were studied. We used advanced database search tools to delineate testable hypotheses and to guide laboratory-based research studies into underlying mechanisms by which this POP mixture could produce or exacerbate metabolic diseases.Methods:For our searches, we used proprietary systems biology software (MetaCore™/MetaDrug™) to conduct advanced search queries for the underlying interactions database, followed by directional network construction to identify common mechanisms for these POPs within two or fewer interaction steps downstream of their primary targets. These common downstream pathways belong to various cytokine and chemokine families with experimentally well-documented causal associations with type 2 diabetes.Conclusions:Our systems biology approach allowed identification of converging pathways leading to activation of common downstream targets. To our knowledge, this is the first study to propose an integrated global set of step-by-step molecular mechanisms for a combination of three common POPs using a systems biology approach, which may link POP exposure to diseases. Experimental evaluation of the proposed pathways may lead to development of predictive biomarkers of the effects of POPs, which could translate into disease prevention and effective clinical treatment strategies.Citation:Ruiz P, Perlina A, Mumtaz M, Fowler BA. 2016. A systems biology approach reveals converging molecular mechanisms that link different POPs to common metabolic diseases. Environ Health Perspect 124:1034–1041; http://dx.doi.org/10.1289/ehp.1510308
Abstract 17853: Activation of AMP-activated Protein Kinase (AMPKα) by AICAR Attenuates Klotho Deficiency-induced Endothelial Dysfunction, Arterial Stiffening and Hypertension
Authors: Yi Lin, Zhongjie Sun
Journal: Circulation (2014)

Background: Arterial stiffening and hypertension are progressive aging-related disorders. Klotho (KL) is a recently-discovered anti-aging gene but its role in the pathogenesis of endothelial dysfunction, arterial stiffening and hypertension is not fully understood. Methods and Results: Heterozygous Klotho deficiency ( KL +/- ) mice and WT littermate mice were fed on high fat diet (HFD) or normal diet (ND). Plasma KL in KL heterozygeous mice (+/-) is about a half of that of the WT mice. Pulse wave velocity (PWV), an index of arterial stiffening, was increased in KL +/- mice but not in WT mice fed on HFD for 4 weeks. Systolic blood pressure and blood glucose levels were increased earlier with greater magnitudes in KL +/- mice than in WT mice fed on HFD. Notably, protein expression of collagen I, Runx2, and TGFβ1 were increased but protein expression of phosphorylated AMPKα (pAMPKα), phosphorylated eNOS (peNOS), and Mn-SOD were decreased in aortas of KL +/- mice fed on HFD for 5 weeks. Interestingly, daily injection of AICAR, an activator of AMPK, abolished the increases in PWV, blood pressure, and blood glucose in KL +/- mice fed on HFD. AICAR not only abolished the downregulation of pAMPKα, peNOS, and Mn-SOD levels but also attenuated the increased levels of collagen I, Runx2, TGFβ1 and superoxide, elastic lamellae breaks, and calcification in aortas in KL +/- mice fed on HFD. Conclusions: Klohto deficiency promotes HFD-induced endothelial dysfunction, arterial stiffening and hypertension. The promoting effects of klotho deficiency on arterial stiffening may be due to downregulation of endothelial AMPKα activity.
Safety of everolimus in estrogen receptor–positive advanced breast cancer.
Authors: Alejandra T. Perez
Journal: Journal of Clinical Oncology (2012)

103 Background: Despite advances in treatment of estrogen receptor–positive (ER+) breast cancer (BC), resistance to endocrine therapy remains a frequent cause of disease recurrence. The mTOR pathway has been identified as a point of deregulation in patients resistant to standard therapy. Everolimus (EVE), an oral mTOR inhibitor, was evaluated as a potential antitumor therapy. Treatment-emergent adverse events (AEs) and their management are presented. Methods: BOLERO-2 (NCT00863655), a phase III trial, evaluated EVE in postmenopausal women with ER+ advanced BC refractory to letrozole or anastrozole. Patients with documented recurrence or progression were randomized 2:1 to receive daily oral EVE (10 mg) or matching placebo, in addition to exemestane (EXE; 25 mg/d), stratified by sensitivity to prior hormonal therapy and the presence of visceral metastasis. Results: At 12.5 months’ follow-up, PFS was 7.4 months in the EVE + EXE arm (n = 485) vs 3.2 months in the EXE-only arm (n = 239) (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.36-0.53; p &lt; 1 × 10 -l6 ). Notable AEs (all grades) in the EVE + EXE vs EXE-only treated patients included stomatitis (59% vs 11%), rash (39% vs 6%), pneumonitis (15% vs 0), and hyperglycemia (14% vs 2%). Grade 3-4 AEs of interest in the EVE + EXE vs EXE-only treated patients were stomatitis (8% vs &lt;1%), anemia (7% vs &lt;1%), hyperglycemia (5% vs &lt;1%), pneumonitis (3% vs 0), and rash (1% vs 0). EVE doses could be reduced or interrupted for the management of AEs. Exploratory analyses of antitumor effects of EVE in patients who received time-averaged EVE doses &lt;7.5 mg/d compared with ≥7.5 mg/d were consistent (HR, 0.4 [95% CI, 0.31-0.52] vs HR, 0.45 [95% CI, 0.37-0.56], respectively). Stomatitis was managed with topical corticosteroids and/or mouthwashes containing nonsteroidal anti-inflammatories or anesthetics. Noninfectious pneumonitis was managed by a combination of radiographic imaging, oral corticosteroids, and temporary cessation of treatment. Conclusions: Addition of EVE to EXE significantly prolonged PFS and was generally well tolerated. AEs were manageable with appropriate care. Knowledge of AE management strategies is essential to optimize EVE tolerability and patient outcomes.