Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

BXSB mice spontaneously develop an autoimmune syndrome characterized by hypergammaglobulinemia, autoantibody production, and the development of fatal glomerulonephritis that closely resembles systemic lupus erythematosus (SLE) in humans. While blocking positive T cell co-stimulation has shown effectiveness in preventing the onset of murine lupus, deliberate delivering negative co-stimulation to halt unwanted T and B cell activation has not been tested. We developed a recombinant adenovirus containing the full-length mouse PD-L1 gene (Ad.PD-L1) to engage the immunoinhibitory receptor PD-1 on activated lymphocytes to prevent lupus nephritis in BXSB mice. This strategy was further reinforced by concomitant injection of anti-ICOSL(B7h) mAb to block ICOS-mediated co-stimulation. The combined therapy dramatically delayed the onset of proteinuria, effectively inhibited IgG autoantibody production, and significantly reduced hypercellularity and deposition of IgG in glomeruli, resulting in almost complete amelioration of lupus nephritis in these animals. Our results indicate the therapeutic potential of simultaneous stimulation of PD-1-mediated pathway and blockade of ICOS-B7h co-stimulation in the prevention of human lupus nephritis.
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PMID:Delivering PD-1 inhibitory signal concomitant with blocking ICOS co-stimulation suppresses lupus-like syndrome in autoimmune BXSB mice. 1638 62

Programmed cell death receptor-1 and its ligand-1 (PD-1/PD-L1) inhibitors have been applied to many cancers, but the difference of treatment-related adverse events (AEs) across cancer types remains unknown. We performed a meta-analysis and systemic review to compare the incidences of commonly reported all-grade AEs across cancer types and found that the most frequent AEs were fatigue, rash/pruritus, loss of appetite/nausea and diarrhea. However, each cancer type also had its higher incidences of AEs involving a relevant system, such as melanoma with epidermal AEs (rash, diarrhea and enterocolitis), lung cancer with dyspnea and pneumonitis, digestive system cancers with amylase and lipase elevation; and renal cell and urothelial cancer with kidney injury (creatinine elevation and proteinuria). However, the incidence of hepatitis did not follow the pattern to show a difference. We did another comparison between PD-1 and PD-L1 inhibitors in lung cancer and urothelial cancer respectively, and found that the risk of most AEs did not differ much, except for more hypothyroidism in PD-1 inhibitors, and more kidney injury in PD-L1 inhibitors. Besides possible immunological mechanisms for treatment-related AEs, the influence of previous radiotherapy and the clinical characteristics of the diseases themselves should also be considered and is worth further investigation. With the result of this meta-analysis, clinicians could estimate the risk of certain AE in certain cancer type, to make treatment options and to customize monitor strategies.
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PMID:Different patterns of treatment-related adverse events of programmed cell death-1 and its ligand-1 inhibitors in different cancer types: A meta-analysis and systemic review of clinical trials. 3277 83

The main therapeutic strategy for metastatic Myxofibrosarcoma (MFS) is palliative chemotherapy. A number of studies have demonstrated that anti-angiogenic therapy and immunotherapy could improve the survival rate of patients with metastases. However, the effectiveness of the combination of anti-angiogenic therapy and immunotherapy for the therapy of MFS is undetermined. The current study reports a case of metastatic myxofibrosarcoma that was treated with combination Nivolumab (monoclonal antibody, PD-1 inhibitor) and Bevacizumab (monoclonal antibody, anti-VEGF) after progression from the single use of Nivolumab. The aim of the current study is to assess the efficacy and safety of Nivolumab and Bevacizumab for metastatic myxofibrosarcoma and to review the literature. Up to the termination of the follow-up, the patient achieved a partial response for 16 months, had an overall survival for over 29 months since the metastasis and demonstrated a sustained benefit from treatment. The most frequent adverse events were fatigue, abnormality of Alanine aminotransferase (ALT), hypertension and proteinuria. Nivolumab and Bevacizumab treatment indicate beneficial clinical effects and are indicated to be safe to use in patients with metastatic myxofibrosarcoma.
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PMID:Combination nivolumab and bevacizumab for metastatic myxofibrosarcoma: A case report and review of the literature. 3290 14

In the REGONIVO study, regorafenib combined with nivolumab was effective in the treatment of microsatellite stable (MSS) metastatic colorectal cancer (mCRC), which indicated anti-angiogenic drugs may enhance the efficacy of immune checkpoint inhibitors. Therefore, we designed a single-arm, single-center, open-label, phase II trial to determine the toxicity and efficacy of SHR-1210 (an anti-PD-1 antibody) plus apatinib in MSS mCRC. The sample size was estimated using a Simon Optimum two-stage design. 10 patients were included at the first stage and if one effective patient observed, an additional 19 patients would be added. Patients with MSS mCRC who refractory to second-line treatment or intolerant to standard treatment were given SHR-1210 200 mg every 2 weeks and apatinib 250-375 mg once daily until unacceptable toxicity or disease progression occurred. In our study, the objective response rate was 0% and the disease control rate was 22.2%. The median progression-free survival was 1.83 months (95% confidence interval (CI) 1.80-1.86 months), and the median overall survival was 7.80 months (95% CI 0-17.07). Treatment-related adverse events (AEs) occurred in all patients (100%). The most common treatment-related AEs were hypertension and proteinuria (70% each). Grade 3 AEs were observed in nine patients (9/10, 90%), and the commonest was hypertension (30%). In conclusion, SHR-1210 combined with apatinib has failed to improve the efficacy of treatment of MSS mCRC, and the intolerable toxicity may be the leading cause.
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PMID:Anti-PD-1 antibody SHR-1210 plus apatinib for metastatic colorectal cancer: a prospective, single-arm, open-label, phase II trial. 3304 28