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#33080623   2020/10/20 To Up

Isatuximab as monotherapy and combined with dexamethasone in patients with relapsed/refractory multiple myeloma.

This Phase 2 study evaluated isatuximab as monotherapy or combined with dexamethasone in relapsed/refractory multiple myeloma (RRMM). Patients had RRMM refractory to an immunomodulatory drug (IMiD) and a proteasome inhibitor (PI) or had received ≥3 prior lines of therapy incorporating an IMiD and PI. Patients received isatuximab either as monotherapy (20 mg/kg on days 1, 8, 15, and 22 [once weekly] of cycle 1 followed by 20 mg/kg on days 1 and 15 of subsequent cycles; Isa group) or in combination with dexamethasone (40 mg/day [20 mg/day in patients ≥75 years] once weekly; Isa-dex group). Treated patients (N = 164) had received a median of 4 (range, 2-10) prior treatment lines. Patients received a median of 5 (1-24) and 7 (1-22) treatment cycles; at data cut-off, 13/109 (11.9%) and 15/55 (27.3%) patients remained on treatment in the Isa and Isa-dex arms, respectively. Overall response rate (primary efficacy endpoint) was 23.9% in the Isa arm and 43.6% in the Isa-dex arm (odds ratio, 0.405; 95% confidence interval, 0.192-0.859, P = 0.008). Median progression-free survival and overall survival were 4.9 and 18.9 months for Isa, and 10.2 and 17.3 months for Isa-dex. Infusion reactions (mostly grade 1/2) and hematologic abnormalities were the most common adverse events. There was a similar incidence of grade ≥3 infections in both groups (22.0% and 21.8%). In conclusion, addition of dexamethasone to isatuximab increased response rates and survival outcomes with no detrimental effect on safety. This trial was registered at www.clinicaltrials.gov as NCT01084252.
Meletios A Dimopoulos, Sara Bringhen, Pekka M Anttila, Marcelo Capra, Michele Cavo, Craig Emmitt Cole, Cristina Gasparetto, Vania Tietsche de Moraes Hungria, Matthew W Jenner, Vladimir I Vorobyev, Eduardo Patricio Yanez Ruiz, Jian Y Yin, Rao Saleem, Maeva Hellet, Sandrine Macé, Bruno Paiva, Ravi Vij

2571 related Products with: Isatuximab as monotherapy and combined with dexamethasone in patients with relapsed/refractory multiple myeloma.

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#33080355   2020/10/17 To Up

Genotoxic effects of glyphosate on Physalaemus tadpoles.

Genotoxicity studies have revealed that pesticides bind to genetic material in non-target vertebrates, thereby impairing the genetic integrity of these animals. The main objective of this study was to determine the genotoxic damage in erythrocytes of two native South American amphibian Physalaemus cuvieri and Physalaemus gracilis, both species exposed to a glyphosate-based herbicide. We evaluated the presence of micronuclei (MN) and erythrocyte nuclear abnormalities (ENA) as biomarkers for potential genotoxic compounds. Tadpoles were exposed to doses permitted by Brazilian legislation and concentrations found naturally in Brazilian and Argentinian waters (500, 700 and 1000 µg/L). Glyphosate-based herbicide caused micronuclei formation and several types of erythrocyte nuclear abnormalities in both Physalaemus species. The total frequency of MN and ENA demonstrated the occurrence of cell damage at all tested concentrations. Glyphosate herbicide can be considered a genotoxic that may impact the genetic integrity of native populations of P. cuvieri and P. gracilis.
Jéssica Samara Herek, Luana Vargas, Suélen Andressa Rinas Trindade, Camila Fatima Rutkoski, Natani Macagnan, Paulo Afonso Hartmann, Marilia Teresinha Hartmann

1652 related Products with: Genotoxic effects of glyphosate on Physalaemus tadpoles.

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#33080146   2020/10/20 To Up

Prolactin-to-Testosterone Ratio Predicts Pituitary Abnormalities in Mildly Hyperprolactinemic Men with Symptoms of Hypogonadism.

We aimed to identify predictor variables associated with pituitary abnormalities in hypogonadal men with mild hyperprolactinemia. We also sought to develop a decision-making aid to select patients for evaluation with pituitary magnetic resonance imaging.
Bryan Naelitz, Anup Shah, Amy S Nowacki, Darren J Bryk, Nicholas Farber, Neel Parekh, Daniel Shoskes, Betul Hatipoglu, Sarah C Vij

2226 related Products with: Prolactin-to-Testosterone Ratio Predicts Pituitary Abnormalities in Mildly Hyperprolactinemic Men with Symptoms of Hypogonadism.

0.05 mg96T100 μg 100 G96tests100 μg32-50 Sample Kit100ug Lyophilized100 μg1 mg100ug

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#33080145   2020/10/20 To Up

Follow-Up of Men with PI-RADS 4 or 5 Abnormality on Prostate MRI and Nonmalignant Pathologic Findings on Initial Targeted Prostate Biopsy.

A benign MRI-targeted prostate biopsy (MRF-TB) in the setting of a PI-RADS 4/5 abnormality presents a clinical dilemma for future management. We evaluated benign histologic features on MRF-TB to determine if they predict the likelihood of missed cancer on subsequent biopsy.
Xiaosong Meng, Brian Chao, Fei Chen, Richard Huang, Samir S Taneja, Fang-Ming Deng

1776 related Products with: Follow-Up of Men with PI-RADS 4 or 5 Abnormality on Prostate MRI and Nonmalignant Pathologic Findings on Initial Targeted Prostate Biopsy.

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#33080140   2020/10/20 To Up

The Association of Aging Biomarkers, Interstitial Lung Abnormalities, and Mortality.

The association between aging and idiopathic pulmonary fibrosis is established. The associations between aging-related biomarkers and interstitial lung abnormalities (ILA) have not been comprehensively evaluated.
Jason L Sanders, Rachel K Putman, Josée Dupuis, Hanfei Xu, Joanne M Murabito, Tetsuro Araki, Mizuki Nishino, Emelia J Benjamin, Daniel L Levy, Vasan S Ramachandran, George R Washko, Jeffrey L Curtis, Christine M Freeman, Russell P Bowler, Hiroto Hatabu, George T O'Connor, Gary M Hunninghake

1965 related Products with: The Association of Aging Biomarkers, Interstitial Lung Abnormalities, and Mortality.

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#33080117   2020/10/20 To Up

Optic, trigeminal, and facial neuropathy related to anti-neurofascin 155 antibody.

To characterize the frequency and patterns of optic, trigeminal, and facial nerve involvement by neuroimaging and electrophysiology in IgG4 anti-neurofascin 155 antibody-positive (NF155 ) chronic inflammatory demyelinating polyneuropathy (CIDP).
Hidenori Ogata, Xu Zhang, Saeko Inamizu, Ken-Ichiro Yamashita, Ryo Yamasaki, Takuya Matsushita, Noriko Isobe, Akio Hiwatashi, Shozo Tobimatsu, Jun-Ichi Kira

2576 related Products with: Optic, trigeminal, and facial neuropathy related to anti-neurofascin 155 antibody.

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#33080054   2020/10/20 To Up

Effect of Orexin-A on Mitochondrial Biogenesis, Mitophagy and Structure in HEK293-APPSWE Cell Model of Alzheimer's Disease.

Mitochondrial dysfunction plays a key role in the pathogenesis and progression of Alzheimer's Disease. Our previous studies showed that over expression of AD-associated mutant APP led to abnormalities of mitochondrial biogenesis and mitophagy, leading to mitochondrial dysfunction. However the mechanism remains unclear. In this study, we investigated the effect of orexin-A on mitochondrial biogenesis, mitophagy and mitochondrial structure in over expression of AD-associated mutant APP cells. We used 20E2 cells as the AD cell model. 20E2 cells were treated with orexin-A (50, 100 nM). The effect of different concentrations of orexin-A on cell activity was detected by MTT. As compared with the non-treated 20E2 cells, orexin-A-treated 20E2 cells showed increased expression of APP, decreased cell viability and decreased adenosine triphosphate (ATP) level, decreased levels of regulatory proteins of mitochondrial biogenesis (peroxisome proliferator-activated receptor gamma coactivator 1-alpha [PGC-1α], nuclear respiratory factor 1/2 [NRF1/2], mitochondrial transcription factor A [TFAM]), increased levels of regulatory proteins of mitophagy (Parkin, PTEN-induced putative kinase 1 [PINK1], microtubule-associated protein light chain 3 II/I [LC3-II/LC3-I]) and decreased p62 level, with damaged mitochondrial structure. Orexin-A may reduce mitochondrial biogenesis, enhance mitophagy and damage mitochondrial structure in AD.
Zhengyu Zhu, DeYan Cao, LinLin Xu, ChaoYuan Song, YuZhen Wang, Maoyu Li, Jieke Yan, ZhaoHong Xie

2136 related Products with: Effect of Orexin-A on Mitochondrial Biogenesis, Mitophagy and Structure in HEK293-APPSWE Cell Model of Alzheimer's Disease.

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#33080012   2020/10/20 To Up

Effect of Therapeutic Hypothermia on the Outcome in Term Neonates with Hypoxic Ischemic Encephalopathy-A Randomized Controlled Trial.

To assess the effect of therapeutic hypothermia on the outcome in term neonates with hypoxic ischemic encephalopathy (HIE).
R Christina Catherine, Vishnu Bhat Ballambattu, Bethou Adhisivam, Shruthi K Bharadwaj, Chinnakali Palanivel

2392 related Products with: Effect of Therapeutic Hypothermia on the Outcome in Term Neonates with Hypoxic Ischemic Encephalopathy-A Randomized Controlled Trial.

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#33080007   // To Up

Morphologic remission status is limited compared to ΔN flow cytometry: a Children's Oncology Group AAML0531 report.

Risk stratification for acute myeloid leukemia (AML) uses molecular and cytogenetic abnormalities identified at diagnosis. Response to therapy informs risk, and morphology continues to be used more frequently than flow cytometry. Herein, the largest cohort of pediatric patients prospectively assessed for measurable residual disease (MRD) by flow cytometry (N = 784) is reported. The "difference from normal" (ΔN) technique was applied: 31% of all patients tested positive (AML range, 0.02% to 91%) after the first course of treatment on Children's Oncology Group study AAML0531. Detection of MRD following initial chemotherapy proved the strongest predicator of overall survival (OS) in univariable and multivariable analyses, and was predictive of relapse risk, disease-free survival, and treatment-related mortality. Clearance of MRD after a second round of chemotherapy did not improve survival. The morphologic definition of persistent disease (>15% AML) failed 27% of the time; those identified as MRD- had superior outcomes. Similarly, for patients not achieving morphologic remission (>5% blasts), 36% of patients were MRD- and had favorable outcomes compared with those who were MRD+ (P < .001); hence an increase in myeloid progenitor cells can be favorable when ΔN classifies them as phenotypically normal. Furthermore, ΔN reclassified 20% of patients in morphologic remission as having detectable MRD with comparable poor outcomes. Retrospective analysis using the relapse phenotype as a template demonstrated that 96% of MRD- patients had <0.02% of the relapse immunophenotype in their end of induction 1 marrow. Thus, the detection of abnormal myeloid progenitor cells by ΔN is both specific and sensitive, with a high predictive signal identifiable early in treatment. This trial was registered at www.clinicaltrials.gov as #NCT00372593.
Lisa Eidenschink Brodersen, Robert B Gerbing, M Laura Pardo, Todd A Alonzo, Dana Paine, Wayne Fritschle, Fan-Chi Hsu, Jessica A Pollard, Richard Aplenc, Samir B Kahwash, Betsy Hirsch, Susana Ramondi, Denise Wells, E Anders Kolb, Alan S Gamis, Soheil Meshinchi, Michael R Loken

2863 related Products with: Morphologic remission status is limited compared to ΔN flow cytometry: a Children's Oncology Group AAML0531 report.

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