tbuckley/cabot-search huggingface dataset:
Association of lymphatic vessel invasion and progression of cervical cancer with focused expression of CD9
Authors: G. Sauer, T. Ach, C. Kurzeder, J. Windisch, R. Kreienberg, H. Deissler
Journal: Journal of Clinical Oncology (2004)

5036 Background: Lymphovascular space invasion plays a critical role in the progression of cervical cancer. It is responsible for an unfavorable prognosis even in patients with early stage disease. The identification and functional characterization of molecules that are differently expressed in tumors with lymphatic vessel involvement in comparison to those without are of particular interest. For a number of malignant diseases, the level of CD9 expression a transmembrane protein involved in various fundamental cellular processes was found to be inversely correlated with tumor invasiveness, ability to form metastases, and poor clinical outcome. We demonstrate that carcinomas of the cervix locally re-express CD9 at sites of lymphatic space invasion. This suggests its functional involvement in transendothelial migration as a crucial step in the formation of lymph node metastases. Methods: Formalin-fixed, paraffin-embedded surgical specimens of 44 consecutive patients with invasive cervical cancer were examined. These consisted of 11 patients without lymph node metastases, 15 patients with metastases to pelvic lymph nodes, and 18 patients with lymphangiogenesis and lymph node metastases. To determine the role of CD9 in lymphovascular space invasion, immunohistochemical doublestaining was performed with monoclonal mouse antibodies binding to CD9 and CD34. Results: CD9 was frequently found to be downregulated in the main tumor mass whereas it was still highly expressed at sites of tumor cell invasion (CD9 hotspots). The appearance of CD9 hotspots turned out to be a high significant (p < 10–5) indicator of lymphatic vessel and invasion disease recurrence. Conclusions: Our observation that CD9 is predominately expressed by clusters of cervical carcinoma cells close to vessels and in the process of transendothelial transition evidently supports a key function of tumor cell CD9 at heterologous cell-cell contacts. This parameter may be used as an indicator of poor prognosis in cases with unclear or unknown histopathological assessment and may define a subgroup of patients that may benefit from additional treatment. No significant financial relationships to disclose.
TLR4 genetic variation is associated with inflammatory responses in Gram-positive sepsis
Authors: N. Chantratita, S. Tandhavanant, S. Seal, C. Wikraiphat, G. Wongsuvan, P. Ariyaprasert, P. Suntornsut, N. Teerawattanasook, Y. Jutrakul, N. Srisurat, P. Chaimanee, W. Mahavanakul, P. Srisamang, S. Phiphitaporn, M. Mokchai, J. Anukunananchai, S. Wongratanacheewin, P. Chetchotisakd, M.J. Emond, S.J. Peacock, T.E. West
Journal: Clinical Microbiology and Infection (2016)

To identify important pathogen recognition receptor (PRR) pathways regulating innate immune responses and outcome in Staphylococcus aureus sepsis.
NAD+ Kinase as a Therapeutic Target in Cancer
Authors: Philip M. Tedeschi, Nitu Bansal, John E. Kerrigan, Emine E. Abali, Kathleen W. Scotto, Joseph R. Bertino
Journal: Clinical Cancer Research (2016)

NAD+ kinase (NADK) catalyzes the phosphorylation of nicotinamide adenine dinucleotide (NAD+) to nicotinamide adenine dinucleotide phosphate (NADP+) using ATP as the phosphate donor. NADP+ is then reduced to NADPH by dehydrogenases, in particular glucose-6-phosphate dehydrogenase and the malic enzymes. NADPH functions as an important cofactor in a variety of metabolic and biosynthetic pathways. The demand for NADPH is particularly high in proliferating cancer cells, where it acts as a cofactor for the synthesis of nucleotides, proteins, and fatty acids. Moreover, NADPH is essential for the neutralization of the dangerously high levels of reactive oxygen species (ROS) generated by increased metabolic activity. Given its key role in metabolism and regulation of ROS, it is not surprising that several recent studies, including in vitro and in vivo assays of tumor growth and querying of patient samples, have identified NADK as a potential therapeutic target for the treatment of cancer. In this review, we will discuss the experimental evidence justifying further exploration of NADK as a clinically relevant drug target and describe our studies with a lead compound, thionicotinamide, an NADK inhibitor prodrug. Clin Cancer Res; 22(21); 5189-95. ©2016 AACR.
Site of metastasis in metastatic clear cell renal cell carcinoma (mccRCC) and outcome of treatment with sunitinib.
Authors: B. Beuselinck, O. Rixe, S. Oudard, P. Wolter, J. Ayllon, R. Elaidi, P. Schoffski, F. Scotte, J. Zucman-Rossi, J. Medioni
Journal: Journal of Clinical Oncology (2010)

e15065 Background: A retrospective study was performed to determine whether the site of metastasis affects the response rate (RR), progression-free survival (PFS) and overall survival (OS) of patients (pts) with mccRCC treated with sunitinib. Methods: We reviewed the charts of all pts in whom sunitinib as first-line anti-VEGF-targeted treatment was started between 01/2005 and 12/2008 at 50 mg/day, 4 weeks on 2 weeks off, in two academic hospitals. Response and PFS were determined by CT scan according to RECIST. Univariate analysis was conducted using Maentel Hetzel test. Presence of liver metastases, bone metastases, metastasis limited to lung- and/or lymph node, interval between nephrectomy and systemic therapy >12 months, corrected serum calcium >10 mg/dl, >1 metastatic site, lactate deshydrogenase >1.5xULN, ECOG performance status >1 or more, platelets >400.000/mm3 and neutrophils >4.500/mm3 were taken into account for multivariate analysis using Cox regression. Results: In the total population of 139 pts, the RR was 49%, median PFS 12 mo and median OS 26 mo, with a median follow-up of 36.7 mo. We observed a RR of 37% in pts with bone metastases vs 55% in pts without bone metastases (95% confidence intervals 25-51% and 44-66%) with a significant difference in median PFS (7 vs 18 mo; p<0.0001) and median OS (18 vs 38 mo; p=0.0001). On multivariate analysis, bone metastasis was the major independent variable associated with poor PFS (p<0.003) and OS (p=0.04). Pts with lung- and/or lymph node metastases only have the best RR (60%), the best median PFS (19 vs 11 mo; p=0.011) and the best median OS (21 mo vs not yet reached; p=0.026). On multivariate analysis, lung- and/or lymp node metastases were independent factors associated with the best PFS and OS (p=0.04). The presence of liver metastases did not affect the median PFS (11 vs 12 mo; p=0.398) and OS (19 vs 26 mo; p=0.213). Conclusions: The presence of bone metastases in mccRCC treated with sunitinib is associated with poor RR, PFS and OS. Pts with exclusive lung and/or lymph node metastases have the best RR, PFS and OS. No significant financial relationships to disclose.
Interleukin-1R8: balancing inflammation and hemostasis in platelets
Authors: Kristina Heinig, Markus Sperandio
Journal: Cardiovascular Research (2016)

This editorial refers to ‘Expression and function of IL-1R8 (TIR8/SIGIRR): a regulatory member of the IL-1 receptor family in platelets’, by A. Anselmo et al. , pp. 373-384. 

Pro-inflammatory cytokines are released during inflammation and exert their action by binding to their respective receptors on cells of the innate immune system. They elicit intracellular signalling events leading to leukocyte activation, which in turn initiates and enforces the protective host response against invading pathogens. However, excessive activation of pro-inflammatory cytokine receptors contributes to autoimmunity and acute and chronic inflammatory diseases including atherosclerosis.1,2 Therefore, these cytokine receptors must be kept under tight control to shut down inflammatory responses to avoid tissue and organ damage.

Several mechanisms exist to control pro-inflammatory cytokine receptors. Among these, anti-inflammatory cytokines like interleukin (IL)-10 or transforming growth factor-β play an important role in negatively modulating the inflammatory response. Additional mechanisms include decoy receptors like IL-1R2 that lacks an intracellular signalling domain acting as scavenger receptor for IL-1β3 or inhibitory cytokine receptors like IL-1R8 that interferes with intracellular signal transduction pathways of pro-inflammatory cytokine receptors.4

Recently, a growing number of studies highlighted the role of platelets in immunity and inflammation.5 Platelets express functional Il-1R1 and several members of the Toll-like receptors (TLRs) family, which …
Abstract 60: Cardiac-specific Deletion of HuR Reduces Pathological Hypertrophy and Ventricular Remodeling Following Transverse Aortic Constriction
Authors: Michael Tranter, Stephen Kraynik, Sarah R Anthony, Samuel Slone, Michelle L Nieman, Lorenz N John, Jack Rubinstein
Journal: Circulation Research (2015)

The RNA binding protein HuR (Human antigen R) interacts with specific AU-rich domains in target mRNAs and is highly expressed in many cell types, including cardiomyocytes. However, the role of HuR in cardiac physiology is largely unknown. Our results show that HuR undergoes cytoplasmic translocation, indicative of its activation, in hypertrophic mouse cardiac myocytes at 8 weeks post-transverse aortic constriction (TAC). To determine the role of HuR in the development of cardiac hypertrophy, we have created a novel mouse model of cardiac myocyte-specific deletion of HuR. While cardiac-specific HuR deletion mice do not show an overt basal phenotype, they have preserved ejection fraction and reduced ventricular remodeling (hypertrophy and chamber dilation) compared to wild-type littermates at 8 weeks following TAC. Furthermore, HuR activation in the hypertrophic heart is strongly co-localized with regions of fibrosis. To this end, we show that HuR knockdown reduced hypertrophy and pro-fibrotic TGF-β gene expression in a phenylephrine treated neonatal rat ventricular myocyte (NRVM) model of hypertrophy. Thus, our results suggest that HuR activation in cardiac myocytes promotes pathogical hypertrophy and initiation of cardiac fibrosis via myocyte expression of TGF-β. These findings are significant as we have identified HuR as a novel mediator of pathological hypertrophy and suggest a pro-fibrotic role as a potential mechanism for this effect.
The Challenge of Latent TB Infection
Authors: Henry M. Blumberg, Joel D. Ernst
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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Late phase II study of amrubicin in previously untreated patients with non-Hodgkin's lymphoma (NHL).
Authors: J. Suzumiya, K. Suzuki, N. Uike, F. Kawano, T. Takeo, S. Okamura, C. Sakai, M. Mori, K. Tamura
Journal: Journal of Clinical Oncology (2010)

8097 Background: We evaluated the efficacy and safety of amrubicin, a third generation synthetic anthracycline, in combination with cyclophosphamide, vincristine and prednisolone (ACOP) in patients with previously untreated aggressive non-Hodgkin's lymphoma (NHL). Methods: Previously untreated patients with intermediate or high grade NHL were treated with 8 cycles of amrubicin, 100 mg/m2, cyclophosphamide, 750 mg/m2, and vincristine, 1.4 mg/m2 (maximum 2.0 mg), on day 1, and prednisolone, 60 mg/m2/day day 1-5 every 21 days. Patients were evaluated for response and left ventricular ejection fraction (LVEF) every 2 cycles, and electrocardiogram at every cycle. The primary endpoint was response rate; secondary endpoints were survival, cardiac safety, and general safety. Results: Fifty-six patients were eligible and received a median of 8 treatment cycles. The median follow- up period was 57.1 months. Most patients had diffuse large B-cell lymphoma (76.8%). The response rate was 92.9%; the complete response (CR) and CRu rate was 69.6%. The 2- and 5-years survival rates were 76.2% and 58.7%, respectively. Reversible myelosuppression was the most common adverse event. Grade 3/4 neutropenia, anemia, thrombocytopenia and febrile neutropenia were reported in 82.5%, 19.3%, 8.8% and 7% of patients, respectively. There were no treatment-related deaths or patients experiencing cardiomyopathy. LVEF did not change during the course of treatment. Conclusions: The response rate and survival in non-Hodgkin's lymphoma patients treated with ACOP were comparable to those achieved with CHOP in other studies, but ACOP had virtually no reduction of LVEF up to a cumulative amrubicin dose of 800 mg/m2. This suggests that amrubicin has little chronic cardiotoxicity. ACOP should be evaluated in combination with rituximab (R) and then compared to R-CHOP. No significant financial relationships to disclose.
Chronic myelomonocytic leukemia patients with RAS pathway mutations show high in vitro myeloid colony formation in the absence of exogenous growth factors
Authors: K Geissler, E Jäger, A Barna, T Alendar, E Ljubuncic, T Sliwa, P Valent
Journal: Leukemia (2016)

Chronic myelomonocytic leukemia patients with RAS pathway mutations show high  in vitro  myeloid colony formation in the absence of exogenous growth factors
The molecular pathogenesis of morphoea: from genetics to future treatment targets
Authors: A.M. Saracino, C.P. Denton, C.H. Orteu
Journal: British Journal of Dermatology (2016)

A number of immunoinflammatory and profibrotic mechanisms are recognized in the pathogenesis of broad sclerotic skin processes and, more specifically, morphoea. However, the precise aetiopathogenesis is complex and remains unclear. Morphoea is clinically heterogeneous, with variable anatomical patterning, depth of tissue involvement and sclerotic, inflammatory, atrophic and dyspigmented morphology. Underlying mechanisms determining these reproducible clinical subsets are poorly understood but of great clinical and therapeutic relevance. Regional susceptibility mechanisms (e.g. environmental triggers, mosaicism and positional identity) together with distinct pathogenic determinants (including innate, adaptive and imbalanced pro- and antifibrotic signalling pathways) are likely implicated. In the age of genetic profiling and personalized medicine, improved characterization of the environmental, systemic, local, genetic and immunopathological factors underpinning morphoea pathogenesis may open the door to novel targeted therapeutic approaches.
Association of Infection in Early Life and Risk of Developing Type 1 Diabetes
Authors: Ossie Ferdinand Uzoigwe
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
MicroRNA-139-5p regulates proliferation of hematopoietic progenitors and is repressed during BCR-ABL–mediated leukemogenesis
Authors: Jinwook Choi, Young-Kook Kim, Kyungsoo Park, Jinwoo Nah, Sung-Soo Yoon, Dong-Wook Kim, V. Narry Kim, Rho Hyun Seong
Journal: Blood (2016)
Development of RP-HPLC method for simultaneous determination of docetaxel and curcumin in rat plasma: Validation and stability
Authors: Dong Wuk Kim, Abid Mehmood Yousaf, Dong Xun Li, Jong Oh Kim, Chul Soon Yong, Kwan Hyung Cho, Han-Gon Choi
Journal: Asian Journal of Pharmaceutical Sciences (2016)

The purpose of the present research was to develop a suitable, simple, precise, accurate, robust, and reproducible RP-HPLC method for a reliable simultaneous quantification of docetaxel (DTX) and curcumin (CCM) in rat plasma samples using paclitaxel (PTX) as an internal standard. The samples were assayed by the Agilent 1260 Infinity HPLC instrument using a Capcell Pak C8 column (4.6 mm × 150 mm, 5 µm) under isocratic conditions. The mobile phase consisted of acetonitrile and triple distilled water (40/60, v/v) with a flow rate of 1.0 ml/min. The eluent was monitored at 230 nm for simultaneous measurement of curcumin and docetaxel. The method was validated by determining system suitability, selectivity, sensitivity, linearity, inter-day and intra-day precision, accuracy, robustness, and stability in accordance with the guidelines of the United States Food and Drug Administration (FDA). The developed chromatographic method proved to be simple, precise, accurate, robust and reproducible. Moreover, the samples showed stability at room temperature over a period of 48 h. Thus, this method would be employed for routine simultaneous quantification of docetaxel and curcumin in rat plasma samples.
Cutaneous features of dermatomyositis associated with myositis-specific antibodies
Authors: M.L. Daly, P.A. Gordon, D. Creamer
Journal: British Journal of Dermatology (2016)

Myositis specific antibodies (MSAs) are autoantibodies present in the serum of a subset of patients with Dermatomyositis (DM). Target autoantigens are involved in gene transcription, protein translocation and innate immunity1. It remains to be established what role MSAs have in the pathogenesis of DM. However, it is envisaged that MSAs will aid in the subclassification of DM into homogenous clinical phenotypes.

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Expression of JAK2-V617F Kinase in Myeloid Progenitors and Proerythroblasts Induces Differential Patterns of Hypersensitivity in Activation of Key Signaling Nodes upon Incubation with Low-Dose, Physiologic EPO Concentrations
Authors: Christian Mueller, Nibedita Gupta, Felix C Saalfeld, Rolf Findeisen, Nadine Rudolph, Steffen Klamt, Sandra Heise, Fred Schaper, Thomas Fischer
Journal: Blood (2014)
A Simple, Powerful, and Widely Applicable Micro-RNA Scoring System in Prognostication of De Novo Myeloid Leukemia Patients
Authors: Ming-Kai Chuang, Yu-Chiao Chiu, Wen-Chien Chou, Hsin-An Hou, Eric Y. Chuang, Hwei-Fang Tien
Journal: Blood (2014)
Targeted Sequencing Reveals Low-Frequency Variants in <i>EPHA</i> Genes as Markers of Paclitaxel-Induced Peripheral Neuropathy
Authors: María Apellániz-Ruiz, Héctor Tejero, Lucía Inglada-Pérez, Lara Sánchez-Barroso, Gerardo Gutiérrez-Gutiérrez, Isabel Calvo, Beatriz Castelo, Andrés Redondo, Jesús García-Donás, Nuria Romero-Laorden, María Sereno, María Merino, María Currás-Freixes, Cristina Montero-Conde, Veronika Mancikova, Elisabeth Åvall-Lundqvist, Henrik Green, Fátima Al-Shahrour, Alberto Cascón, Mercedes Robledo, Cristina Rodríguez-Antona
Journal: Clinical Cancer Research (2016)

Purpose: Neuropathy is the dose-limiting toxicity of paclitaxel and a major cause for decreased quality of life. Genetic factors have been shown to contribute to paclitaxel neuropathy susceptibility; however, the major causes for interindividual differences remain unexplained. In this study, we identified genetic markers associated with paclitaxel-induced neuropathy through massive sequencing of candidate genes.Experimental Design: We sequenced the coding region of 4 EPHA genes, 5 genes involved in paclitaxel pharmacokinetics, and 30 Charcot-Marie-Tooth genes, in 228 cancer patients with no/low neuropathy or high-grade neuropathy during paclitaxel treatment. An independent validation series included 202 paclitaxel-treated patients. Variation-/gene-based analyses were used to compare variant frequencies among neuropathy groups, and Cox regression models were used to analyze neuropathy along treatment.Results: Gene-based analysis identified EPHA6 as the gene most significantly associated with paclitaxel-induced neuropathy. Low-frequency nonsynonymous variants in EPHA6 were present exclusively in patients with high neuropathy, and all affected the ligand-binding domain of the protein. Accumulated dose analysis in the discovery series showed a significantly higher neuropathy risk for EPHA5/6/8 low-frequency nonsynonymous variant carriers [HR, 14.60; 95% confidence interval (CI), 2.33-91.62; P = 0.0042], and an independent cohort confirmed an increased neuropathy risk (HR, 2.07; 95% CI, 1.14-3.77; P = 0.017). Combining the series gave an estimated 2.5-fold higher risk of neuropathy (95% CI, 1.46-4.31; P = 9.1 × 10-4).Conclusions: This first study sequencing EPHA genes revealed that low-frequency variants in EPHA6, EPHA5, and EPHA8 contribute to the susceptibility to paclitaxel-induced neuropathy. Furthermore, EPHA's neuronal injury repair function suggests that these genes might constitute important neuropathy markers for many neurotoxic drugs. Clin Cancer Res; 23(5); 1227-35. ©2016 AACR.