Б1.В.ОД.15.4 Этология и зоопсихология 2018 очная

Increased apoptotic activity in xenograft tumors (day 35) treated with miR-410 relative to miR-NC, assessed by caspase 3/7 ELISA assay (Promega). (PPTX 50.3 kb

Table_1_Safety and efficacy of immune checkpoint inhibitor cancer therapy in patients with preexisting type 1 diabetes mellitus.pdf

IntroductionImmune checkpoint inhibitors (ICI) produce dramatic tumor shrinkage and durable responses in many advanced malignancies, but their use is limited by the development of immune-related adverse events (IRAEs) that occur in up to 60% of patients and often affect endocrine organs. Concern for more severe IRAEs in patients with preexisting autoimmune diseases, including type 1 diabetes mellitus (T1DM), has led to the exclusion of such individuals from clinical trials of ICI therapy. As a result, little is known about the safety and efficacy of ICI in this population. Here, we report safety and treatments outcomes in ICI-treated patients with preexisting T1DM.MethodsThis retrospective case-controlled study evaluated adult patients with T1DM who received ICI therapy for solid malignancies from 2015 to 2021 at four academic medical centers. Patients with prior ICI therapy, bone marrow transplantation, or pregnancy were excluded. We collected data on demographics, cancer diagnosis and treatment, IRAE incidence and severity, and diabetes management. Controls were matched 2:1 by age, sex, cancer diagnosis, and ICI therapy class.ResultsOf 12,142 cancer patients treated with ICI therapy, we identified 11 with a preexisting confirmed diagnosis of T1DM prior to starting ICI therapy. Mean age was 50.6 years, 63.6% were women, and most received anti-PD1/PDL1 monotherapy (10/11) compared with combination therapy (1/11). Grade 3/4 IRAEs were seen in 3/11 subjects with preexisting T1DM and were hepatitis, myositis, and myasthenia gravis. All three cases had interruption of ICI therapy and administration of adjunct therapies, including steroids, IVIG, or mycophenolate mofetil with resolution of the IRAE. The odds of all-grade IRAEs and of severe IRAEs were comparable between cases and controls matched for age, sex, cancer type, and ICI therapy [OR 0.83 (95% CI 0.2–3.56), p = 0.81, and OR 1.69 (0.31–9.36), p = 0.55, respectively]. Overall survival was not different between patients with T1DM and controls (p = 0.54). No patients had hospitalizations for diabetes-related complications during therapy.DiscussionThese data suggest that ICI monotherapy can successfully be used in patients with preexisting T1DM, with IRAE rates comparable with individuals without preexisting T1DM. Larger, prospective studies of these potentially life-saving ICI therapies that include patients with preexisting autoimmunity are warranted.</p

Additional file 1 of Associations of quantitative whole-body PSMA-PET metrics with PSA progression status under long-term androgen deprivation therapy in prostate cancer patients: a retrospective single-center study

Additional file 1. Supplementary Materials

Supplementary Figures 1-3. Supplmentary Tables 1-4. Supplementary Materials and Methods. from MKAD-21 Suppresses the Oncogenic Activity of the miR-21/PPP2R2A/ERK Molecular Network in Bladder Cancer

Supplementary Figure S1. PPP2R2A mRNA levels in the excised tumors from 5637 bearing mouse xenografts. Supplementary Figure S2. PPP2R2A mRNA and protein levels upon transient silencing.Supplementary Figure S3. PPP2R2A protein levels upon transient overexpression. Supplementary Table S1. Bioinformatics prediction of the top networks regulated by PPP2R2A. Supplementary Table S2. Bioinformatics prediction of the top canonical pathways regulated by PPP2R2A. Supplementary Table S3. Xcelligence Cell Index and P values of siPPP2R2RA-treated versus control BC cells. Supplementary Table S4. Xcelligence Cell Index and P values of PPP2R2A-overexpressing versus control BC cells, all treated with miR-21 mimic.</p

Supplementary Data from Microdose-Induced Drug–DNA Adducts as Biomarkers of Chemotherapy Resistance in Humans and Mice

Chemical structures, patient data, mouse survival curves, additional biomarker data</p