tbuckley/cabot-search huggingface dataset:
Induction of G1-phase arrest and apoptosis by erlotinib, a specific and clinically active EGFR tyrosine kinase inhibitor, in human H322 non-small cell lung cancer cells
Authors: Yi-He Ling
Journal: Cancer Research (2004)

4654  Erlotinib (TarcevaTM, OSI-774), a specific small-molecule EGFR tyrosine kinase inhibitor, has shown antitumor activity in patients with non-small cell lung cancer (NSCLC) relapsing after chemotherapy. This activity was not correlated with the level of EGFR expression as assessed by immunohistochemistry. From a panel of 9 human NSCLC cell lines, H322 cells showed the highest in vitro sensitivity to erlotinib. H322 cells also display high EGFR expression and are p53 mutant. We selected H322 cells as a model of EGFR inhibitor-sensitive cells to investigate the mechanisms of erlotinib-induced cytotoxicity. Flow cytometric analysis showed that treatment with erlotinib at 1 μM caused an accumulation of H322 cells at G1 phase and a decrease in number of cells at S and G2-M phase in a time-dependent fashion. Western blot analysis demonstrated that the G1 phase arrest caused by erlotinib was accompanied by a reduction in intracellular levels of cyclin A and E, but no change in the levels of cyclin D1 and D2. In addition, erlotinib treatment induced the expression of p27KIP1 and p21WAF1/CIP1, but did not affect p16INK4a expression. Using γ-32P-ATP incorporation into histone H1 in the presence of cyclin-E/cdk2 and cyclin-D/cdk-4 kinase, Erlotinib markedly inhibited cyclin-E/cdk-2 kinase activity, but only slightly affected cyclin-D/cdk-4 kinase activity. As expected, erlotinib treatment resulted in the inhibition of phosphorylation of Rb protein, and the extent of Rb hypophosphorylation was correlated with drug-induced G1 phase arrest. erlotinib-induced G1 phase arrest started at 16 h, reaching the maximum after 24-36 h of drug exposure. In contract, erlotinib-induced apoptosis was first observed at 36 h and increased with time thereafter. Interestingly, erlotinib treatment caused a dose- and time-dependent downregulation of bcl-2 protein, up-regulation of bax protein, and activation of caspase-3. These data indicate that, in the context of a panel of NSCLC cell lines, sensitivity to the EGFR inhibitor erlotinib is mediated by blockade of cell-cycle progression at G1 phase through disruption of the regulatory mechanism of G1 to S phase transition, followed by triggering of the apoptotic cascade. Supported by NIH grant CA50270 and OSIP Pharmaceuticals.
Effects of low dose tamoxifen on circulating levels of hormones, C-telopeptide and HER2 extracellular domain in women with primary breast cancer
Authors: Harriet Johansson, Massimiliano Cazzaniga, Bernardo Bonanni, Serena Mora, Frédérique Mariette, Giuseppe Pelosi, Ernst Lien, Chris Robertson, Andrea Decensi
Journal: Cancer Research (2006)

3194  Tamoxifen reduces the risk of breast cancer in women at high risk for disease but increases the risk for endometrial tumors and venous thromboembolisms, possibly in a dose-dependent fashion. Within a double-blind, randomized phase II preoperative trial women with early hormone responsive breast cancer were randomized to the standard dose of tamoxifen at 20 mg/day, 5 mg/day or 1 mg/day for four weeks treatment prior to surgery. The primary objective was to assess the effect of a dose reduction on tumor cell proliferation. Ki-67 expression decreased in all of the three treatment groups, independently of the dose. The purpose at this point was to determine the biologic differences between different doses of tamoxifen on the endocrine milieu. Circulating levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex-hormone binding globulin (SHBG), dehydroepiandrosterone-sulfate (DHEA-S), estrone-sulfate (E1-S), estradiol (E2), C-erbB2 extracellular domain (HER2ECD) and C-terminal telopeptide (CTX), were determined at baseline and the day before surgery in 115 women. All levels were compared with those in two nonrandomized control groups (29 women with ER-negative breast cancer and 11 with ER-positive breast cancer). When considering postmenopausal women only (n=120), LH and FSH decreased with increasing doses of tamoxifen. The linear trend for a dose-response relationship was p=0.023 and p=0.020, respectively. Conversely, SHBG increased with increasing doses of tamoxifen (p=0.005). CTX levels increased in control groups and this trend was compensated by tamoxifen in a dose-dependent fashion (p=0.003). We also looked at correlations between these circulating markers. Apart from a strong positive correlation between E2 and DHEA-S (r=0.356) or E1-S (r=0.539) we found relatively low correlations between the other variables. Our results provide further evidence for an early endocrine effect of low doses of tamoxifen which may contribute to its favorable impact on breast cancer. The effects of lower doses of tamoxifen in breast cancer prevention warrant further studies.
Re: Stephanie Guillaumier, Max Peters, Manit Arya, et al. A Multicentre Study of 5-year Outcomes Following Focal Therapy in Treating Clinically Significant Nonmetastatic Prostate Cancer. Eur Urol 2018;74:422–9
Authors: Zhien Zhou, Yi Zhou, Weigang Yan
Journal: European Urology (2018)
Myeloablative Haploidentical Transplantation Is Superior to Chemotherapy for Patients with Intermediate-risk Acute Myelogenous Leukemia in First Complete Remission
Authors: Meng Lv, Yu Wang, Ying-Jun Chang, Xiao-Hui Zhang, Lan-Ping Xu, Qian Jiang, Hao Jiang, Jin Lu, Huan Chen, Wei Han, Feng-Rong Wang, Jing-Zhi Wang, Yao Chen, Chen-Hua Yan, Yuan-Yuan Zhang, Yu-Qian Sun, Xiao-Dong Mo, Hong-Hu Zhu, Jin-Song Jia, Ting Zhao, Jing Wang, Kai-Yan Liu, Xiao-Jun Huang
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Although myeloablative HLA haploidentical hematopoietic stem cell transplantation (haplo-HSCT) following pretransplant anti-thymocyte globulin (ATG) and granulocyte colony-stimulating factor (G-CSF) stimulated grafts (ATG+G-CSF) has been confirmed as an alternative to HSCT from HLA-matched sibling donors (MSD), the effect of haplo-HSCT on postremission treatment of patients with acute myeloid leukemia (AML) with intermediate risk (int-risk AML) who achieved first complete remission (CR1) has not been defined. Patients and Methods: In this prospective trial, among 443 consecutive patients ages 16–60 years with newly diagnosed de novo AML with int-risk cytogenetics, 147 patients with molecular int-risk AML who achieved CR1 within two courses of induction and remained in CR1 at 4 months postremission either received chemotherapy (n = 69) or underwent haplo-HSCT (n = 78). Results: The 3-year leukemia-free survival (LFS) and overall survival (OS) were significantly higher in the haplo-HSCT group than in the chemotherapy group (74.3% vs. 47.3%; P = 0.0004 and 80.8% vs. 53.5%; P = 0.0001, respectively). In the multivariate analysis with propensity score adjustment, postremission treatment (haplo-HSCT vs. chemotherapy) was an independent risk factor affecting the LFS [HR 0.360; 95% confidence interval (CI), 0.163–0.793; P = 0.011], OS (HR 0.361; 95% CI, 0.156–0.832; P = 0.017), and cumulative incidence of relapse (HR 0.161; 95% CI, 0.057–0.459; P = 0.001) either in entire cohort or stratified by minimal residual disease after the second consolidation. Conclusions: Myeloablative haplo-HSCT with ATG+G-CSF is superior to chemotherapy as a postremission treatment in patients with int-risk AML during CR1. Haplo-HSCT might be a first-line postremission therapy for int-risk AML in the absence of HLA-MSDs. Haplo-HSCT might be superior to chemotherapy as a first-line postremission treatment of intermediate-risk AML in CR1.
Deconstructing Immune Microenvironments of Lymphoid Tissues for Reverse Engineering
Authors: Ini‐Isabée Witzel, Rasha Nasser, Anna Garcia‐Sabaté, Jiranuwat Sapudom, Chao Ma, Weiqiang Chen, Jeremy C. M. Teo
Journal: Advanced Healthcare Materials (2018)

Abstract The immune microenvironment presents a diverse panel of cues that impacts immune cell migration, organization, differentiation, and the immune response. Uniquely, both the liquid and solid phases of every specific immune niche within the body play an important role in defining cellular functions in immunity at that particular location. The in vivo immune microenvironment consists of biomechanical and biochemical signals including their gradients, surface topography, dimensionality, modes of ligand presentation, and cell–cell interactions, and the ability to recreate these immune biointerfaces in vitro can provide valuable insights into the immune system. This manuscript reviews the critical roles played by different immune cells and surveys the current progress of model systems for reverse engineering of immune microenvironments with a focus on lymphoid tissues.
Author Correction: Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis
Authors: Yinghong Wang, Diana H. Wiesnoski, Beth A. Helmink, Vancheswaran Gopalakrishnan, Kati Choi, Hebert L. DuPont, Zhi-Dong Jiang, Hamzah Abu-Sbeih, Christopher A. Sanchez, Chia-Chi Chang, Edwin R. Parra, Alejandro Francisco-Cruz, Gottumukkala S. Raju, John R. Stroehlein, Matthew T. Campbell, Jianjun Gao, Sumit K. Subudhi, Dipen M. Maru, Jorge M. Blando, Alexander J. Lazar, James P. Allison, Padmanee Sharma, Michael T. Tetzlaff, Jennifer A. Wargo, Robert R. Jenq
Journal: Nature Medicine (2018)
A Positive Feedback Loop of SLP2 Activates MAPK Signaling Pathway to Promote Gastric Cancer Progression
Authors: Wenhui Ma, Zhuoluo Xu, Yutian Wang, Wenyi Li, Zhigang Wei, Tao Chen, Tingyu Mou, Mingzhen Cheng, Jun Luo, Tingyue Luo, Yuehong Chen, Jiang Yu, Weijie Zhou, Guoxin Li
Journal: Theranostics (2018)

Rationale: This study is to validate the clinicopathologic significance and potential prognostic value of SLP2 in gastric cancer (GC), to investigate the biological function and regulation mechanism of SLP2, and to explore potential therapeutic strategies for GC.Methods: The expression of SLP2 in GC tissues from two cohorts was examined by IHC.The biological function and regulation mechanism of SLP2 and PHB was validated via loss-of-function or gain-of-function experiments.In vitro proliferation detection was used to evaluate the therapeutic effects of Sorafenib.Results: We validated that SLP2 was significantly elevated in GC tissues and its elevation was associated with poor prognosis of patients.Loss of SLP2 drastically suppressed the proliferation of GC cells and inhibited the tumor growth, while SLP2 overexpression promoted the progression of GC.Mechanistically, SLP2 competed against E3 ubiquitin ligase SKP2 to bind with PHB and stabilized its expression.Loss of SLP2 significantly suppressed phosphorylation of Raf1, MEK1/2, ERK1/2 and ELK1.Furthermore, phosphorylated ELK1 could in turn activate transcription of SLP2.Finally, we demonstrated that a Raf1 inhibitor, Sorafenib, was sufficient to inhibit the proliferation of GC cells.Conclusion: Our findings demonstrated a positive feedback loop of SLP2 which leads to acceleration of tumor progression and poor survival of GC patients.This finding also provided evidence for the reason of SLP2 elevation.Moreover, we found that sorafenib might be a potential therapeutic drug for GC and disrupting the interaction between SLP2 and PHB might also serve as a potential therapeutic target in GC.
Abstract 20306: Dual vs Single Antiplatelet Therapy in Patients With Peripheral Artery Disease: Meta-Analysis of Randomized Trials
Authors: Eliano Navarese, Kevin Bliden, Udaya Tantry, Paul A Gurbel
Journal: Circulation (2017)

Introduction: Peripheral artery disease (PAD) is a common manifestation of atherosclerosis, being associated with severe cardiovascular events. It has been shown that dual antiplatelet therapy (DAP...
Transience and hierarchy: ending the doctor-nurse game
Authors: George C Greenlees
Journal: BMJ (2018)

Darbyshire and Thompson make a powerful case for flattening hierarchies across the health service.1 They present the “doctor-nurse game” as one of power dynamics, where doctors have the power, historically at least. But this dynamic may be reversed between transient junior doctors and senior nursing staff.

I currently teach final year medical students, and many feel …
Dupilumab reduces local type 2 pro‐inflammatory biomarkers in chronic rhinosinusitis with nasal polyposis
Authors: Karin Jonstam, Brian N. Swanson, Leda P. Mannent, Lars‐Olaf Cardell, Nian Tian, Ying Wang, Donghui Zhang, Chunpeng Fan, Gabriele Holtappels, Jennifer D. Hamilton, Annette Grabher, Neil M. H. Graham, Gianluca Pirozzi, Claus Bachert
Journal: Allergy (2018)

Abstract Background Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a type 2‐mediated inflammatory disease associated with significant clinical, social, and economic burdens and high unmet therapeutic need. Dupilumab, a fully human monoclonal antibody targeting the interleukin‐4 receptor α (IL‐4Rα) subunit, demonstrated efficacy and acceptable safety in CRSwNP and other type 2 diseases (eg, atopic dermatitis and asthma). We now report the local effects of dupilumab on type 2 inflammatory biomarkers in nasal secretions and nasal polyp tissues of patients with CRSwNP in a randomized, placebo‐controlled, phase 2 trial (NCT01920893). Methods Cytokines, chemokines, and total immunoglobulin E (IgE) levels were measured using immunoassay techniques in nasal secretions and nasal polyp tissue homogenates of CRSwNP patients receiving dupilumab 300 mg or placebo weekly for 16 weeks. Results With dupilumab, type 2 biomarker concentrations decreased in nasal secretions (least squares mean area under the curve from 0 to 16 weeks for the change from baseline) vs placebo for eotaxin‐3 (−30.06 vs −0.86 pg/mL; P = 0.0008) and total IgE (−7.90 vs −1.86 IU/mL; P = 0.022). Dupilumab treatment also decreased type 2 biomarker levels in nasal polyp tissues at Week 16 vs baseline for eosinophilic cationic protein ( P = 0.008), eotaxin‐2 ( P = 0.008), eotaxin‐3 ( P = 0.031), pulmonary and activation‐regulated chemokine ( P = 0.016), IgE ( P = 0.023), and IL‐13 ( P = 0.031). Conclusions Dupilumab treatment reduced multiple biomarkers of type 2 inflammation in nasal secretions and polyp tissues of patients with CRSwNP, demonstrating that antagonism of IL‐4Rα signaling suppresses IL‐4‐/IL‐13‐dependent processes, such as mucosal IgE formation, as well as the expression of chemokines attracting inflammatory cells to the nasal mucosa.
Developing a Delphi survey in MD/APP’s for distress level after supportive care inpatient consults.
Authors: Marieberta Vidal
Journal: Journal of Clinical Oncology (2018)

125 Background: Physicians caring for patients with terminal cancer are at particular risk for compromised well-being due to the nature and intensity of the clinical stresses they face. The factors contributing to professional burnout severity included younger age, working in isolation, and working longer hours a shown by a survey conducted by Kamal et al. For patient encounter distress multiple factor have been mention as a source of distress for providers including patient factors, physician factors and environmental factors. No documented evidence of the distress level in palliative care (PC) providers after patient encounter is available. We intend to identify the most common predictors for high distress level after patient encounter in order to identify ways to support our staff. Methods: A group of 28 PC faculty physicians and mid-level providers in the Department of PC at the M. D. Anderson Cancer Center were invited to participate in the study by email with Qualtrics link e-online questionnaire. The questionnaire seek their opinion on the most important interaction or situations that increase their distress level during a PC consult. A 5-point Likert scale of agreement was used, ranging from “strongly disagree” to “strongly agree”. We will conduct the procedure to generate the question prompt sheet with 3 Delphi rounds. Results: After the first round of the Delphi the situations that could cause distress after a consult with more than 80% agreement were identify as: difficult family, manipulative family/patient, angry patient/family, primary team in denial, time of the consult, and number of consults. Situations like patient's terminal diagnosis, patient/family religious beliefs, cultural background, or presence of observer or trainee were less likely consider as source of distress with a less than 20% agreement. Conclusions: For PC specialists situations that affect the communication or rapport with patients as well as amount/burden of clinical work seems to be more a source of distress. Other situations related to uncontrolled symptoms, EOL issues or patient background were less likely a source of distress what could be explain by the expertise of the specialist with these EOL discussions and symptom management.
Potential therapy strategy: targeting mitochondrial dysfunction in sepsis
Authors: Hui Zhang, Yong-wen Feng, Yong-ming Yao
Journal: Military Medical Research (2018)

Recently, the definition of sepsis was concluded to be a life-threatening organ dysfunction caused by a dysregulated host response to infection. Severe patients always present with uncorrectable hypotension or hyperlactacidemia, which is defined as septic shock. The new definition emphasizes dysregulation of the host response and multiple organ dysfunction, which is partially attributed to metabolic disorders induced by energy crisis and oxidative stress. Mitochondria are a cellular organelle that are well known as the center of energy production, and mitochondrial damage or dysfunction is commonly induced in septic settings and is a predominant factor leading to a worse prognosis. In the present review, we determine the major mitochondrial disorders from morphology to functions in sepsis. In the following, several clinical or pre-clinical assays for monitoring mitochondrial function are demonstrated according to accumulated evidence, which is the first step of specific therapy targeting to modulate mitochondrial function. Accordingly, various reagents used for regulating mitochondrial enzyme activities and promoting biogenesis have been documented, among which mitochondria-targeted cation, TPP-conjugated antioxidants are the most valuable for future trials and clinical treatment to improve mitochondrial function as they may take advantage of the prognosis associated with septic complications.
Increased expression of L‐plastin in nasal polyp of patients with nonsteroidal anti‐inflammatory drug‐exacerbated respiratory disease
Authors: Tetsuji Takabayashi, Yukie Tanaka, Dai Susuki, Kanako Yoshida, Kaori Tomita, Masafumi Sakashita, Yoshimasa Imoto, Yukinori Kato, Norihiko Narita, Tsugihisa Nakayama, Shinichi Haruna, Robert P. Schleimer, Shigeharu Fujieda
Journal: Allergy (2018)

Abstract Background Most patients with nonsteroidal anti‐inflammatory drug‐exacerbated respiratory disease ( NERD ) suffer from recurrence of nasal polyps. However, little is known about the specific cellular and molecular mechanisms contributing to the pathogenesis of nasal polyp development in patients with NERD in particular, especially at baseline when cyclooxygenase 1 inhibitors are not present. The objectives of this study were to identify proteins involved in the pathogenesis of nasal polyps in patients with NERD . Methods We collected nasal polyp tissue from patients with NERD and from patients with aspirin‐tolerant chronic rhinosinusitis with nasal polyps ( CRS w NP ). Protein profiles were analyzed by 2‐dimensional electrophoresis and identified several proteins, including L‐plastin, as highly expressed. We examined L‐plastin and tissue factor ( TF ) expression by immunohistochemical and immunofluorescence analyses. To examine the role of L‐plastin in eosinophils, we knocked down L‐plastin expression in Eol‐1 cells by using si RNA transfection. Results L‐plastin protein levels in nasal polyp tissue were increased in patients with NERD relative to those in patients with aspirin tolerant CRS w NP . Immunofluorescence analysis revealed that L‐plastin was dominantly expressed in eosinophils and L‐plastin and TF were co‐expressed in eosinophils in NERD nasal polyp tissue. Knockdown of L‐plastin in Eol‐1 cells disrupted the cell surface distribution of TF by stimulation with granulocyte macrophage colony‐stimulating factor. Conclusion Increased expression of L‐plastin by eosinophils may contribute to abnormal fibrin deposition through TF translocation to the eosinophil cell surface in NERD nasal polyp tissue, which in turn may contribute to the pathogenesis of NERD .
Baseline Genotype Testing to Assess Drug Resistance Before Beginning HIV Treatment
Authors: Juan Ambrosioni, Mar Mosquera, José M. Miró
Journal: JAMA (2018)

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Improving Dermatologic Care for Sexual and Gender Minority Patients Through Routine Sexual Orientation and Gender Identity Data Collection
Authors: Matthew D. Mansh, Andy Nguyen, Kenneth A. Katz
Journal: JAMA Dermatology (2018)

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 Dermatology 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 Dermatology journal