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82,158 results for

Anti-Topoisomerase I Antibody

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1. Topoisomerase I inhibitor, irinotecan, depletes regulatory T cells and up-regulates MHC class I and PD-L1 expression, resulting in a supra-additive antitumor effect when combined with anti-PD-L1 antibodies (PubMed)

Topoisomerase I inhibitor, irinotecan, depletes regulatory T cells and up-regulates MHC class I and PD-L1 expression, resulting in a supra-additive antitumor effect when combined with anti-PD-L1 antibodies Anti-PD-L1 antibodies inhibit interactions between PD-L1 and PD-1 and interactions between PD-L1 and B7-1, thereby reinvigorating anticancer immunity. Although there are numerous ongoing clinical studies evaluating combinations of standard chemotherapies and anti-PD-L1 antibodies, irinotecan (...) class I expression on tumor cells and concurrently increased PD-L1 expression on tumor cells and tumor-infiltrating immune cells. These results indicate that irinotecan may enhance the effect of T cell activation caused by anti-PD-L1 treatment by reducing Tregs and augmenting MHC class I-mediated tumor antigen presentation, and concurrent upregulation of PD-L1 expression can be blocked by the anti-PD-L1 antibody. These interactions may contribute to the superior combination effect.

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2018 Oncotarget

2. RXRB is a MHC-encoded susceptibility gene associated with anti-topoisomerase I antibody-positive systemic sclerosis. (PubMed)

RXRB is a MHC-encoded susceptibility gene associated with anti-topoisomerase I antibody-positive systemic sclerosis. Systemic sclerosis is a systemic autoimmune and connective tissue disorder associated with the human leukocyte antigen locus. However, the functional relationship between human leukocyte antigen gene(s) and disease development remains unknown. To elucidate major histocompatibility complex-linked systemic sclerosis genetics, we performed genotyping of major histocompatibility (...) complex-borne microsatellites and HLA-DPB1 alleles using DNA obtained from 318 anti-topoisomerase I antibody-positive patients and 561 healthy controls, all of Japanese descent. Those results revealed two major histocompatibility complex haplotypes associated with systemic sclerosis. Exome sequencing and targeted analysis of these risk haplotypes identified rs17847931 in RXRB as a susceptibility variant (P = 1.3 × 10-15; odds ratio [OR] = 9.4) with amino acid substitution p.V95A on the risk haplotype

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2017 Journal of Investigative Dermatology

3. Confirmation of CCR6 as a risk factor for anti-topoisomerase I antibodies in systemic sclerosis.

Confirmation of CCR6 as a risk factor for anti-topoisomerase I antibodies in systemic sclerosis. The current knowledge of the influence of systemic sclerosis (SSc) risk loci in the clinical sub-phenotypes is still limited. The main limitation lies in the low frequency of some sub-phenotypes which could be solved by replication studies in independent cohorts and meta-analysis between studies. In this regard, CCR6 gene variants have been recently associated with anti-topoisomerase I positive (ATA

2017 Clinical and experimental rheumatology

4. Anti-Topoisomerase I Antibody

Anti-Topoisomerase I Antibody Anti-Topoisomerase I Antibody Toggle navigation Brain Head & Neck Chest Endocrine Abdomen Musculoskeletal Skin Infectious Disease Hematology & Oncology Cohorts Diagnostics Emergency Findings Procedures Prevention & Management Pharmacy Resuscitation Trauma Emergency Procedures Ultrasound Cardiovascular Emergencies Lung Emergencies Infectious Disease Pediatrics Neurologic Emergencies Skin Exposure Miscellaneous Abuse Cancer Administration 4 Anti-Topoisomerase I (...) Antibody Anti-Topoisomerase I Antibody Aka: Anti-Topoisomerase I Antibody , Anti-Topoisomerase1 Antibody , Anti-Scl-70 Antibody , Anti-Topoisomerase I , Topoisomerase 1 Antibody , Anti-DNA-Topoisomerase I , Anti-Scl-70 II. Causes: Negative Normal III. Causes: Positive (Percentage refers to sensitivity) (20-30% sensitivity) Anti-Scl-70 is highly specific for Implies a poor prognosis Associated with renal involvement IV. References Gladman in Klippel (1997) Rheumatic Diseases p. 255-6 Peng in Ruddy (2001

2018 FP Notebook

5. Detection of Anti-Cardiolipin and Anti-β2glycoprotein I Antibodies Differs between Platforms without Influence on Association with Clinical Symptoms. (PubMed)

Detection of Anti-Cardiolipin and Anti-β2glycoprotein I Antibodies Differs between Platforms without Influence on Association with Clinical Symptoms.  The anti-phospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy morbidity with persistent presence of anti-phospholipid antibodies (aPL). Laboratory criteria include aPL detection by coagulation tests for lupus anticoagulant (LAC) or solid phase assays measuring anti-β2 glycoprotein I (aβ2GPI) or anti-cardiolipin (aCL (...) ) immunoglobulin (Ig) G/IgM antibodies. External quality control programs illustrate that commercially available aPL assays produce variable results. We aimed to investigate the agreement and diagnostic accuracy of solid phase assays. In this multi-centre study, 1,168 patient samples were tested on one site for aCL and aβ2GPI IgG/IgM antibodies by four solid phase test systems. Samples included APS patients, controls and monoclonal antibodies (MoAB) against different epitopes of β2GPI. LAC was determined

2019 Thrombosis and haemostasis

6. The (non-)sense of detecting anti-cardiolipin and anti-β2glycoprotein I IgM antibodies in the antiphospholipid syndrome. (PubMed)

The (non-)sense of detecting anti-cardiolipin and anti-β2glycoprotein I IgM antibodies in the antiphospholipid syndrome. The antiphospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy morbidity with the persistent presence of lupus anticoagulant (LAC), anti-cardiolipin (aCL) and/or anti-β2glycoprotein I (aβ2GPI) antibodies of the immunoglobulin G/immunoglobulin M (IgG/IgM) isotype. However, the role of aCL and aβ2GPI IgM as a serologic marker in APS is debated.We aimed (...) to assess the diagnostic and clinical value of IgM antiphospholipid antibodies (aPL) in APS within the classification criteria.Our multicenter study comprised 1008 patients, including APS patients and controls. Anti-CL and aβ2GPI IgG and IgM antibodies were detected with four commercially available solid phase assays.Positivity for aCL and/or aβ2GPI antibodies was significantly correlated with thrombosis and pregnancy morbidity, independent of the isotype and solid phase assay. Higher odds ratios were

2019 Journal of Thrombosis and Haemostasis

7. A phase 1, randomized, single ascending-dose study to investigate the safety, tolerability, and pharmacokinetics of DSTA4637S, an anti-<i>Staphylococcus aureus</i> THIOMAB™ antibody-antibiotic conjugate, in healthy volunteers. (PubMed)

A phase 1, randomized, single ascending-dose study to investigate the safety, tolerability, and pharmacokinetics of DSTA4637S, an anti-<i>Staphylococcus aureusi> THIOMAB™ antibody-antibiotic conjugate, in healthy volunteers. BACKGROUND:Staphylococcus aureus causes serious bacterial infections with high morbidity and mortality, necessitating the discovery of new antibiotics. DSTA4637S is a novel antibody-antibiotic conjugate designed to target intracellular S. aureus not adequately eliminated (...) meaningful or dose-related changes in laboratory parameters or vital signs occurred. Pharmacokinetics of plasma DSTA4637S conjugate and serum DSTA4637S total antibody was dose proportional. Systemic exposure of unconjugated dmDNA31 was low. No DSTA4637S-induced anti-drug antibody responses were observed.CONCLUSIONS: DSTA4637S was generally safe and well tolerated as a single i.v. dose in healthy volunteers. DSTA4637S has a favorable safety and pharmacokinetic profile that supports future development

2019 Antimicrobial Agents and Chemotherapy

8. Case Report: Disseminated <i>Mycobacterium kansasii</i> Disease in a Patient with Anti-IFN-Gamma Antibody. (PubMed)

Case Report: Disseminated <i>Mycobacterium kansasiii> Disease in a Patient with Anti-IFN-Gamma Antibody. Disseminated nontuberculous mycobacterial (NTM) infections usually occur in severely immunosuppressed patients. These infections may also occur in previously immunocompetent patients with acquired anti-IFN-gamma antibodies (anti-IFN-γ Abs). A previously healthy 33-year-old man presented with a 3-week history of cough and fever. Chest computed tomography showed air-space consolidation (...) an increased titer. Antimycobacterial drug treatments were initiated after diagnosis. His symptoms improved over 2 months, and he remains well on outpatient management. Disseminated M. kansasii disease is a very rare condition suggestive of immunosuppression. Testing for anti-IFN-γ antibodies might be important in all cases of disseminated M. kansasii disease.

2019 American Journal of Tropical Medicine & Hygiene

9. Phase I study of TrasGEX, a glyco-optimised anti-HER2 monoclonal antibody, in patients with HER2-positive solid tumours (PubMed)

Phase I study of TrasGEX, a glyco-optimised anti-HER2 monoclonal antibody, in patients with HER2-positive solid tumours TrasGEX is a second-generation monoclonal antibody of trastuzumab, glyco-optimised to enhance antibody-dependent cellular cytotoxicity while fully retaining trastuzumab's antigen-binding properties to human epidermal growth factor receptor 2 (HER2). A phase I dose-escalation study was conducted to establish the optimal TrasGEX dose and regimen for phase II studies

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2018 ESMO open

10. Anti-GD2 antibody-containing immunotherapy postconsolidation therapy for people with high-risk neuroblastoma treated with autologous haematopoietic stem cell transplantation. (PubMed)

Anti-GD2 antibody-containing immunotherapy postconsolidation therapy for people with high-risk neuroblastoma treated with autologous haematopoietic stem cell transplantation. Neuroblastoma is a rare malignant disease that primarily affects children. The tumours mainly develop in the adrenal medullary tissue, and an abdominal mass is the most common presentation. High-risk disease is characterised by metastasis and other primary tumour characteristics resulting in increased risk for an adverse (...) outcome. The GD2 carbohydrate antigen is expressed on the cell surface of neuroblastoma tumour cells and is thus a promising target for anti-GD2 antibody-containing immunotherapy.To assess the efficacy of anti-GD2 antibody-containing postconsolidation immunotherapy after high-dose chemotherapy (HDCT) and autologous haematopoietic stem cell transplantation (HSCT) compared to standard therapy after HDCT and autologous HSCT in people with high-risk neuroblastoma. Our primary outcomes were overall

2019 Cochrane

11. First-line, Non-criterial Antiphospholipid Antibody Testing for the Diagnosis of Antiphospholipid Syndrome in Clinical Practice: a Combination of Anti-beta2-glycoprotein I Domain I and Phosphatidylserine-dependent Antiprothrombin Antibodies. (PubMed)

First-line, Non-criterial Antiphospholipid Antibody Testing for the Diagnosis of Antiphospholipid Syndrome in Clinical Practice: a Combination of Anti-beta2-glycoprotein I Domain I and Phosphatidylserine-dependent Antiprothrombin Antibodies. To assess the value of a combination of anti-β2 -glycoprotein I (anti-β2 GPI) domain I antibody and anti-phosphatidylserine/prothrombin complex (anti-PS/PT) antibody tests for the diagnosis of antiphospholipid syndrome (APS).This cross-sectional study (...) involved a cohort of the patients who visited our clinic from April 2005 to March 2013. Tests for anti-β2 GPI domain I antibodies, IgG anti-PS/PT antibodies, and IgM anti-PS/PT antibodies, together with tests for criteria-defined antiphospholipid antibodies (aPL), were performed in all patients. The total antiphospholipid score (aPL-S) was calculated for each patient according to titers of and positivity for aPL.The study enrolled 157 patients (51 patients with APS and 106 with non-APS autoimmune

2017 Arthritis care & research

12. <b>Therapy of Small-cell Lung Cancer (SCLC) With a Topoisomerase-I-inhibiting Antibody-Drug Conjugate (ADC) Targeting Trop-2, Sacituzumab Govitecan</b>. (PubMed)

Therapy of Small-cell Lung Cancer (SCLC) With a Topoisomerase-I-inhibiting Antibody-Drug Conjugate (ADC) Targeting Trop-2, Sacituzumab Govitecan. Purpose: We evaluated a Trop-2-targeting antibody conjugated with SN-38 in metastatic small cell lung cancer (mSCLC) patients.Experimental Design: Sacituzumab govitecan was studied in patients with pretreated (median, 2; range, 1-7) mSCLC who received either 8 or 10 mg/kg i.v. on days 1 and 8 of 21-day cycles. The primary endpoints were safety (...) . No antibodies to the drug conjugate or its components were detected on serial blood collections.Conclusions: Sacituzumab govitecan appears to have a safe and effective therapeutic profile in heavily pretreated mSCLC patients, including those who are chemosensitive or chemoresistant to first-line chemotherapy. Additional studies as a monotherapy or combination therapy are warranted. Clin Cancer Res; 23(19); 5711-9. ©2017 AACR.©2017 American Association for Cancer Research.

2017 Clinical Cancer Research

13. Identification of high thrombotic risk triple positive antiphospholipid syndrome patients is dependent on anti-cardiolipin and anti-β2glycoprotein I antibody detection assays. (PubMed)

Identification of high thrombotic risk triple positive antiphospholipid syndrome patients is dependent on anti-cardiolipin and anti-β2glycoprotein I antibody detection assays. Essentials Triple-positivity is associated with a high risk for a first thrombotic event and recurrence. Identification of triple-positives is dependent on the solid phase assay used. In triple-positivity, IgM only adds value in thrombotic risk stratification together with IgG. Thrombotic risk in triple-positive patients (...) with IgM only, depends on the platform.Background The antiphospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy morbidity with the persistent presence of antiphospholipid antibodies (aPL). Triple-positivity (i.e. positivity for lupus anticoagulant [LAC], anti-cardiolipin [aCL] and anti-β2glycoprotein I [aβ2GPI] antibodies) is associated with a high thrombotic risk. Objectives We investigated the variability in triple-positivity detection by measuring the same samples with four

2018 Journal of Thrombosis and Haemostasis

14. First-in-Human, First-in-Class Phase I Trial of the Anti-CD47 Antibody Hu5F9-G4 in Patients With Advanced Cancers. (PubMed)

First-in-Human, First-in-Class Phase I Trial of the Anti-CD47 Antibody Hu5F9-G4 in Patients With Advanced Cancers. To evaluate the safety, pharmacokinetics, and pharmacodynamics of Hu5F9-G4 (5F9), a humanized IgG4 antibody that targets CD47 to enable phagocytosis.Adult patients with solid tumors were treated in four cohorts: part A, to determine a priming dose; part B, to determine a weekly maintenance dose; part C, to study a loading dose in week 2; and a tumor biopsy cohort.Sixty-two patients (...) smear (36%), fatigue (64%), headaches (50%), fever (45%), chills (45%), hyperbilirubinemia (34%), lymphopenia (34%), infusion-related reactions (34%), and arthralgias (18%). No maximum tolerated dose was reached with maintenance doses up to 45 mg/kg. At doses of 10 mg/kg or more, the CD47 antigen sink was saturated by 5F9, and a 5F9 half-life of approximately 13 days was observed. Strong antibody staining of tumor tissue was observed in a patient at 30 mg/kg. Two patients with ovarian/fallopian tube

2019 Journal of Clinical Oncology

15. Randomized phase I clinical trial of anti-α-synuclein antibody BIIB054. (PubMed)

Randomized phase I clinical trial of anti-α-synuclein antibody BIIB054. Pathological and genetic evidence implicates toxic effects of aggregated α-synuclein in the pathophysiology of neuronal dysfunction and degeneration in Parkinson's disease. Immunotherapy targeting aggregated α-synuclein is a promising strategy for delaying disease progression.This study (NCT02459886) evaluated the safety, tolerability, and pharmacokinetics of BIIB054, a human-derived monoclonal antibody that preferentially

2019 Movement Disorders

16. A Phase I Study of the Anti-CC Chemokine Receptor 4 Antibody, Mogamulizumab, in Combination with Nivolumab in Patients with Advanced or Metastatic Solid Tumors. (PubMed)

A Phase I Study of the Anti-CC Chemokine Receptor 4 Antibody, Mogamulizumab, in Combination with Nivolumab in Patients with Advanced or Metastatic Solid Tumors. Regulatory T cells (Tregs) expressing CC chemokine receptor 4 (CCR4) can suppress antitumor immune responses and are associated with poor prognoses in several cancers. We assessed the safety and efficacy of combined mogamulizumab (anti-CCR4 antibody) and nivolumab [anti-programmed death-1 (PD-1) antibody] in immunotherapy-naïve patients (...) responses among 15 patients with hepatocellular carcinoma, and one confirmed and two unconfirmed responses among 15 patients with pancreatic adenocarcinoma. During treatment, populations of effector Tregs (CD4+CD45RA-FoxP3high) decreased and CD8+ T cells in tumor-infiltrating lymphocytes increased.Combining an anti-PD-1 antibody, nivolumab, with a Treg-depleting anti-CCR4 antibody, mogamulizumab, provides an acceptable safety profile, antitumor activity, and a potentially effective option in cancer

2019 Clinical Cancer Research

17. Fulminant Type 1 Diabetes Mellitus Accompanied by Positive Conversion of Anti-insulin Antibody after the Administration of Anti-CTLA-4 Antibody Following the Discontinuation of Anti-PD-1 Antibody (PubMed)

Fulminant Type 1 Diabetes Mellitus Accompanied by Positive Conversion of Anti-insulin Antibody after the Administration of Anti-CTLA-4 Antibody Following the Discontinuation of Anti-PD-1 Antibody An 80-year-old woman with malignant melanoma received 20 cycles of anti-programmed death 1 (PD-1) antibody (nivolumab) treatment and showed normal glucose tolerance. Three weeks after switching to anti-cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) antibody (ipilimumab), her plasma glucose level (...) was elevated to 639 mg/dL, her HbA1c was 7.7%, and her fastening serum C-peptide immunoreactivity was undetectable. Anti-glutamic acid decarboxylase and insulinoma-associated protein-2 antibodies were negative. She was diagnosed with fulminant type 1 diabetes mellitus (F1DM). Remarkably, her anti-insulin antibody was positively converted, and her Sialylated Carbohydrate Antigen, Krebs von den Lungen-6 levels increased after ipilimumab therapy. She possessed F1DM-susceptible Human Leukocyte Antigen-DR4

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2018 Internal Medicine

18. First-in-human phase I study of single-agent vanucizumab, a first-in-class bi-specific anti-Ang-2/anti-VEGF antibody, in adult patients with advanced solid tumors. (PubMed)

First-in-human phase I study of single-agent vanucizumab, a first-in-class bi-specific anti-Ang-2/anti-VEGF antibody, in adult patients with advanced solid tumors. Purpose: Vanucizumab is an investigational antiangiogenic, first-in-class, bispecific mAb targeting VEGF-A and angiopoietin-2 (Ang-2). This first-in-human study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of vanucizumab in adults with advanced solid tumors refractory to standard

2017 Clinical Cancer Research

19. Phase I trial of anti-GD2 monoclonal antibody hu3F8 plus GM-CSF: Impact of body weight, immunogenicity and anti-GD2 response on pharmacokinetics and survival (PubMed)

Phase I trial of anti-GD2 monoclonal antibody hu3F8 plus GM-CSF: Impact of body weight, immunogenicity and anti-GD2 response on pharmacokinetics and survival Fifty-seven stage 4 patients with refractory/relapsed neuroblastoma were enrolled in a phase I trial (Clinicaltrials.gov NCT01757626) using humanized anti-GD2 monoclonal antibody hu3F8 in combination with granulocyte-macrophage colony-stimulating factor. The influence of body weight and human anti-human antibody (HAHA (...) and overall survival was estimated by the Kaplan-Meier method. Despite dosing being based on body weight, smaller patients had consistently lower area-under-the-curve and faster clearance over the 15 dose levels (0.9 to 9.6 mg/kg per treatment cycle) in this trial. Positive HAHA, defined by the upper limit of normal, when measured within 10 days from the last hu3F8 dose received, was associated with significantly lower serum hu3F8. Despite prior sensitization to other anti-GD2 antibody, e.g. mouse 3F8

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2017 Oncoimmunology

20. Targeting Anti-TGF-<i>β</i> Therapy to Fibrotic Kidneys with a Dual Specificity Antibody Approach. (PubMed)

Targeting Anti-TGF-<ii> Therapy to Fibrotic Kidneys with a Dual Specificity Antibody Approach. Targeted delivery of a therapeutic agent to a site of pathology to ameliorate disease while limiting exposure at undesired tissues is an aspirational treatment scenario. Targeting diseased kidneys for pharmacologic treatment has had limited success. We designed an approach to target an extracellular matrix protein, the fibronectin extra domain A isoform (FnEDA), which is relatively restricted

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2017 Journal of the American Society of Nephrology

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