ABSTRACT
AIM: An evaluation of the effectiveness of immunosuppressive therapy (IST) and tonsillectomy (TE) in patients with IgA nephropathy (IgAN). MATERIALS AND METHODS: A retrospective cohort of the study included cases with biopsy proven primary IgAN (n=367, age 3412 years, men 55%). We used demographic and clinical and morphological parameters at the time of biopsy. Median followup period was 26 (10; 61) months. Outcomes were remission (complete or partial) and the progression of IgAN (defined as the start of dialysis or a decrease in glomerular filtration rate 50% from baseline). All patients received treatment with renin angiotensin system blockers. Evaluation of the effectiveness of therapy was carried out using propensity score (PS) methods matching, conventional double robust regression models with PS as independent covariate, and inverse probability weighting. Following patient subgroups were used for comparative analyses: with IST (n=176) and without IST (n=191); with TE (n=63) and without TE (n=304); without IST and without TE (IST-TE-; n=162); with TE and without IST (IST-TE+; n=29); with IST and without TE (IST+TE-; n=142); with IST and with TE (IST+ TE+; n=34). RESULTS: All PS methods used gave close estimates of the comparative effectiveness of treatment in different subgroups: 1) patients on monotherapy with corticosteroids (CS) and combination of CS with other immunosuppressants did not have significant differences in probabilities of IgAN progression (hazard ratio 0.919; 95% CI 0.3332.950) and remission (odds ratio 0.919; 95% CI 0.3792.344) and were further combined into a group of IST; 2) IST was significantly associated with the lower risk of disease progression and increased odds ratio for remission; 3) the positive effects of IST were limited to cases with proteinuria 2 g/24 h; 4) the likelihood of IgAN remission and progression did not differ significantly between TE+ and TE-, IST-TE+ and IST-TE- groups. There were no cases of disease progression in the IST+TE+ group. The cumulative renal survival was higher in the IST+TE+ group compared to IST+ TE- group (p=0.010), while the probability of remission did not differ. CONCLUSION: IST was associated with a lower risk of IgAN progression and increased probability of remission, while these effects of IST were limited to patients with proteinuria 2 g/24 h. TE in combination with IST is associated with an additional reduction in the risk of disease progression.
Subject(s)
Glomerulonephritis, IGA , Glomerular Filtration Rate , Glomerulonephritis, IGA/diagnosis , Glomerulonephritis, IGA/drug therapy , Humans , Immunoglobulin A , Male , Proteinuria , Retrospective StudiesABSTRACT
Cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and polyubiquitination by SCF(FBX4-alphaB crystallin). Inhibition of cyclin D1 proteolysis has been implicated as a causative factor leading to its overexpression in breast and esophageal carcinomas; however, the contribution of stable cyclin D1 to the genesis of such carcinomas has not been evaluated. We therefore generated transgenic mice wherein expression of either wild-type or a stable cyclin D1 allele (D1T286A) is regulated by MMTV-LTR. MMTV-D1T286A mice developed mammary adenocarcinomas at an increased rate relative to MMTV-D1 mice. Similar to human cancers that overexpress cyclin D1, D1T286A tumors were estrogen receptor-positive and exhibited estrogen-dependent growth. Collectively, these results suggest that temporal control of cyclin D1 subcellular localization and proteolysis is critical for maintenance of homeostasis within the mammary epithelium.
Subject(s)
Active Transport, Cell Nucleus/genetics , Cyclin D1/genetics , Cyclin D1/metabolism , Mammary Neoplasms, Animal/etiology , Mammary Neoplasms, Animal/metabolism , Mammary Neoplasms, Experimental/etiology , Mammary Neoplasms, Experimental/metabolism , Adenocarcinoma/etiology , Adenocarcinoma/metabolism , Adenocarcinoma/virology , Animals , Cell Line, Tumor , Cell Transformation, Neoplastic/genetics , Cell Transformation, Neoplastic/metabolism , Cells, Cultured , Cyclin D1/physiology , Female , Homeostasis/genetics , Humans , Hydrolysis , Mammary Neoplasms, Animal/virology , Mammary Neoplasms, Experimental/virology , Mammary Tumor Virus, Mouse/pathogenicity , Mice , Mice, Transgenic , Phosphorylation , Subcellular Fractions/metabolism , Ubiquitination/geneticsABSTRACT
A case-control study was carried out in 59 patients with newly diagnosed hepatocellular carcinoma and 101 control subjects, who were all male hepatitis B carriers. The odds ratios of hepatocellular carcinoma occurring among hepatitis B carriers in the lowest quartile and those highest quartile of dietary and serum status were 5.3 (1.9 to 15.0) and 86.9 (20.0 to 377.2), respectively. The odds ratios for hepatitis B carriers in the lowest quartile and those in the highest quartile of dietary and serum beta-carotene status were 1.7 (0.7 to 4.1) and 5.0 (1.9 to 13.2). Vitamin E status did not differ in case patients and control subjects. Low education level, heavy consumption of alcohol, and smoking status were also associated with increased odds of hepatocellular carcinoma. Serum retinol, positively associated with dietary retinol, demonstrated an independent effect on hepatocellular carcinoma. This effect may reflect changes in the physiologic condition of the patients at the time of entering the hospital.
