BackgroundAtopic dermatitis (AD) is a common skin disease, but treatment of this disease has been challenging. Dupilumab is a new biological agent for AD that has been proven to be safe and effective in clinical trials. Although dupilumab was approved for listing in China in June 2020, real-world data about the application of dupilumab in China are lacking. This study aimed to collect and analyze real-world data on dupilumab among Chinese AD patients.MethodsDemographic and clinical data for 116 AD patients receiving dupilumab treatment were reviewed. The Eczema Area and Severity Index (EASI), SCORing Atopic Dermatitis (SCORAD), Numerical Rating Scale (NRS), Patient Oriented Eczema Measure (POEM), and Dermatology Quality of Life Index (DLQI) of patients were evaluated every 2 weeks from baseline to 16 weeks of treatment. Any adverse events during treatment were recorded.ResultsAmong the 116 patients in this study, baseline levels of IgE, eosinophils, and LDH were elevated in 62.79% (n = 86), 45.30% (n = 86), and 54.20% of patients (n = 48), respectively. The SCORAD index and POEM, DLQI, and NRS scores were significantly improved in all patients at 2 weeks (p < 0.0001), 4 weeks (p < 0.01), and 16 weeks (p < 0.001). EASI scores also improved significantly in all patients at 2 weeks (p < 0.01), 4 weeks (> 0.05), and 16 weeks (p < 0.01). However, 11 patients (9.48%) had no response. IgE and LDH levels (p > 0.05), Eosinophil counts (p < 0.01) in blood increased temporarily in the first 4 weeks and then decreased and stabilized during dupilumab treatment. Conjunctivitis was the most common adverse event (2.59%) among the patients. We found that the curative efficacy of dupilumab at 4th weeks was related to the patient’s age and course of disease. Nevertheless, there is no relationship between levels of eosinophils, IgE, LDH and the therapeutic efficacy of dupilumab.ConclusionThe real-world data in China showed that dupilumab can effectively treat AD and is well tolerated with a low incidence of adverse events.
Objective: Pancreatic cancer is one of the most malignant tumors, with rapid metastasis, high mortality rate, and difficult early screening. Currently, gemcitabine is a first-line drug for pancreatic cancer patients, but its clinical effect is limited due to drug resistance. It is particularly important to further identify biomarkers associated with gemcitabine resistance to improve the sensitivity of gemcitabine treatment. Methods: Drug sensitivity data and the corresponding transcript data derived from the Genomics of Drug Sensitivity in Cancer (GDSC) database for correlation analysis was adopted to obtain genes related to gemcitabine sensitivity. Moreover, the survival model of pancreatic cancer patients treated with gemcitabine in The Cancer Genome Atlas (TCGA) database was utilized to obtain key genes. Multiple in vitro assays were performed to verify the function of the key biomarker. Results: Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) was identified as a biomarker promoting gemcitabine resistance, and its high expression resulted in a worse prognosis. Besides, gemcitabine significantly increased the mRNA and protein levels of ERAP2 in pancreatic cancer cells. Additionally, ERAP2 knockdown suppressed tumorigenesis and potentiated gemcitabine-induced growth, migration and invasion inhibition in human pancreatic cancer cells. Conclusions: ERAP2 may be a novel key biomarker for gemcitabine sensitivity and diagnosis, thus providing an effective therapeutic strategy for pancreatic cancer treatment. AGING Table 1. IC50 values of pancreatic cancer cells treated with gemcitabine in GDSC1. CELL_LINE_NAME DRUG_NAME Log2_IC50
Preclinical and early clinical mechanistic studies of antitumor activity from the beta-adrenergic receptor (β-AR) blocker propranolol have revealed both cell signaling and immune function pathway effects. Intertumoral studies were performed using propranolol, a β1-AR selective agent (atenolol) and a β2-AR selective agent (ICI 118,551) in a preclinical in vivo model, as a step to dissect the contribution of cell signaling and CD8+ immunological effects on anticancer activity. We found that repression of β2-AR but not β1-AR signaling selectively suppressed cell viability and inhibited xenograft growth in vivo. Moreover, Western blot analysis indicated that the phosphorylation levels of AKT/MEK/ERK were significantly decreased following the inhibition of β2-AR. Furthermore, propranolol was found to activate tumor microenvironment with increased intratumoral frequency of CD8+ T cells, whereas neither selective β1 nor β2-AR blockers had a significant effect on the tumor immune microenvironment. Thus, the results of this mechanistic dissection support a predominant role of cell signaling, rather than the activation of CD8+ T cells, as the basis for propranolol antitumor activity.
Background Pancreatic cancer is one of the most malignant tumors, with rapid metastasis, high mortality rate, and difficult early screening. Currently, gemcitabine is a first-line drug for pancreatic cancer patients, but its clinical effect is limited due to drug resistance. It is particularly important to further identify biomarkers associated with gemcitabine resistance to improve the sensitivity of gemcitabine treatment. Methods Drug sensitivity data and the corresponding transcript data derived from the Genomics of Drug Sensitivity in Cancer (GDSC) database for correlation analysis was adopted to obtain genes related to gemcitabine sensitivity. Moreover, the survival model of pancreatic cancer patients treated with gemcitabine in The Cancer Genome Atlas (TCGA) database was utilized to obtain key genes. Multiple in vitro assays were performed to verify the function of the key biomarker. Results Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) was identified as a biomarker promoting gemcitabine resistance, and its high expression resulted in a worse prognosis. Besides, gemcitabine significantly increased the mRNA and protein levels of ERAP2 in pancreatic cancer cells. Additionally, ERAP2 knockdown suppressed tumorigenesis and potentiated gemcitabine-induced growth, migration and invasion inhibition in human pancreatic cancer cells. Conclusions ERAP2 may be a novel key biomarker for gemcitabine sensitivity and diagnosis, thus providing an effective therapeutic strategy for pancreatic cancer treatment.
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