Sirtuin1 (SIRT1) is a nicotinamide adenine dinucleotide-dependent deacetylase. Recently, it is suggested that SIRT1 may be involved in the development of malignant tumors including mouse lymphoma. Therefore, we investigated the prevalence and the prognostic impact of SIRT1 expression in diffuse large B-cell lymphoma (DLBCL). Immunohistochemical expression of SIRT1, p53, bcl2, CD10, bcl6, and multiple myeloma-1 (MUM1) were evaluated by using a 2 mm core from 104 DLBCL patients for tissue microarray. Positive expression of SIRT1 was seen in 74% (77/104) of patients. In total DLBCL patients, SIRT1 and p53 expression were significantly associated with shorter overall survival (OS) by univariate analysis (P=0.001 and P=0.011, respectively). SIRT1 was also an independent prognostic factor by multivariate analysis (P=0.01). According to the expression patterns of CD10, bcl6, and MUM1, germinal center B cell (GCB) types were represented in 38 cases (37%) and non-GCB types were represented in 66 cases (63%). In the GCB type, only p53 expression was associated with a significantly shorter OS (P=0.032). In the non-GCB type, expression of SIRT1 correlated with shorter OS by univariate analyses (P=0.005) and multivariate analyses (P=0.049). In conclusion, we showed that SIRT1 expression is a clinically significant prognostic indicator for DLBCL patients.

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Tumor-infiltrating immune cells perform a crucial function in host immune reactions against diffuse large B-cell lymphoma (DLBCL). In this study, we have identified a subset of tumor-infiltrating FOXP3-positive regulatory T cells (Tregs) in the initial DLBCL biopsy specimens, and have evaluated their prognostic significance. Ninety six patients with DLBCL were evaluated retrospectively. The pattern of FOXP3 protein expression was evaluated using standard immunohistochemistry in paraffin-embedded tissue samples. Sixty seven of all 96 specimens were stained with antibodies for CD-10, bcl-6 and MUM1 via tissue microarray (TMA) to classify the cases into a germinal center B-cell like (GCB) group and a non-GCB group. The median overall survival (OS) was 28 months. As compared with the others, the patients with higher percentages of FOXP3-positive Tregs on initial tumor biopsy evidenced a significantly longer OS (p = 0.003). Patients classified into the GCB group evidenced a significantly longer OS as compared with the non-GCB group (p = 0.008). When the prognostic factors were evaluated via a multivariate model, the international prognostic index and the percentage of infiltrating FOXP3-positive Tregs in the initial biopsy were identified as independent predictors of OS. In conclusion, the presence of an increased percentage of FOXP3-positive Tregs in DLBCL is predictive of better prognoses.

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BackgroundDrug-induced nephrotic syndrome (NS) can be resolved by eliminating the causative agents. However, patients with metastatic cancer have not been previously reported to achieve complete recovery from anticancer drug-induced NS after discontinuation of treatment, because many patients die of cancer progression before NS is restored.Case presentationA 67-year-old man presented with edema of both lower extremities. He received pazopanib therapy for recurrent metastatic renal cell carcinoma (mRCC) for 17 months. Laboratory examinations revealed 7484.58 mg/day of 24-h urine protein, 434 mg/dL of serum cholesterol, and 2.9 g/dL of serum albumin. He was diagnosed with NS, and pazopanib treatment was discontinued. Four months later, he completely recovered from NS. He was then treated with temsirolimus and nivolumab sequentially for > 26 months. Pazopanib was re-introduced following disease progression, and demonstrated antitumor effects for 7 months without NS recurrence.ConclusionPazopanib-induced NS can occur late in patients with mRCC, and its subsequent discontinuation can enable patients to completely recover from its adverse effects. Moreover, pazopanib treatment may be re-introduced without the recurrence of NS.