ABSTRACT
Objective: To investigate the strong expression (S+) of P53 and BCL2 proteins in MYC/BCL2 double-expression DLBCL (DEL) and whether they can be used for the prognostic evaluation and stratified diagnosis of DELs. Methods: Tissue microarray were made by filed FFPE blocks of 174 DLBCL cases. The translocation of MYC, BCL2 and BCL6 genes were detected by FISH, and the proteins were detected by IHC. Data of clinicopathologic features and follow up of patients were collected and OS (overall survival) and PFS (progression free survival) were analyzed by statistics. Results: Eight double-hit lymphomas (DHLs) were identified in all cases, and 45 DELs were selected from 166 remaining cases, which have no significant difference in OS and PFS compared with non-DEL cases (P=0.668 and P=0.790) . Of 42 DEL-cases with follow up data, 24 cases with P53+ or/and BCL2 (S+) are significantly shorter OS and PFS than others (P=0.003 and P=0.000) , in which the cases with P53+/BCL2 (S+) co-expression were the worst prognosis, and P53/BCL2 co-weaker positive DEL cases even have superior OS and PFS than those non-DELs. Although statistics showed that the cases of P53+ or/and BCL2 (S+) have a lower OS and PFS in total cases (P=0.063 and P=0.024) , it is not the case when the DEL-cases take out from total cases, that is the cases with P53+ or/and BCL2 (S+) are as similar OS and PFS as others in non-DEL group (P=0.590 and P=0.550) . Conclusion: The strong expression of P53 and BCL2 proteins can be used as indicators of stratified diagnosis and poor prognosis of DEL.
Subject(s)
Humans , Lymphoma, Large B-Cell, Diffuse/genetics , Prognosis , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-myc/genetics , Tumor Suppressor Protein p53/geneticsABSTRACT
<p><b>OBJECTIVE</b>To explore the prognostic value of regulatory T cells (Tregs) and M2 macrophages in diffuse large B-cell lymphoma (DLBCL) tissues.</p><p><b>METHODS</b>The expression of CD163 and Foxp3 was detected by immunohistochemistry in 92 cases of DLBCL, and it was statistically analyzed whether their expressions correlate with clinical data and prognosis in patients with DLBCL.</p><p><b>RESULTS</b>The density of M2 macrophage and regulatory T cells in DLBCL tumor tissues was significantly higher than that in the adjacent tissues (P = 0.02, P = 0.04). The expression of M2 macrophages was significantly positively correlated with regulatory T cells expression (r = 2.012, P < 0.05). High density of M2 or Tregs had a relationship with extranodal involvement (P < 0.05). Cox regression analysis showed that the expressions of CD163 and Foxp3 were independent prognostic factors of DLBCL (P < 0.05).</p><p><b>CONCLUSIONS</b>Combined detection of the expression of CD163 and Foxp3 proteins and then evaluation of the amount of M2 macrophages and Tregs can be used to more closely predict the prognosis for DLBCL patients.</p>
Subject(s)
Humans , Immunohistochemistry , Lymphoma, Large B-Cell, Diffuse , Diagnosis , Macrophages , Physiology , Prognosis , T-Lymphocytes, Regulatory , PhysiologyABSTRACT
Honokiol is an active compound purified from magnolia that has been shown to induce cell differentiation, apoptosis, and anti-angiogenesis effects, as well as an enhancement in tumor growth delay in combination with chemotherapeutic agents in several mouse xenograft models. Our goal was to investigate the radiosensitization effect of honokiol on lung carcinoma. The radiosensitization effect of liposomal honokiol in Lewis lung carcinoma cells (LL/2) was analyzed using an in vitro clonogenic survival assay. For an in vivo study, Lewis lung carcinoma-bearing C57BL/6 mice were treated with either liposomal honokiol at 25 mg/kg or 5 Gy of single tumor radiation, or a combination of both over 12 days of treatment. The tumor growth delay and the survival time were evaluated. In addition, histological analysis of tumor sections was performed to examine changes by detecting the microvessel density and apoptosis in tumor tissues. In the clonogenic survival assay, LL/2 cells treated with IC50 Lipo-HNK for 24 h showed a radiation enhancement ratio of 1.9. After 12 days of combination treatment, the tumor volume decreased 78% and produced an anti-tumor activity 1.3-fold greater than a predicted additive effect of honokiol and radiation alone. This combination treatment also caused an 8.7 day delay in tumor growth. The cell cycle distribution and histological analysis demonstrated that liposomal honokiol has an anti-tumor effect via inducing apoptosis and inhibiting angiogenesis. Liposomal honokiol can enhance tumor cell radiosensitivity in vitro and in vivo, indicating that radiotherapy combined with liposomal honokiol can lead to greater anti-tumor efficacy.