MicroRNAs (miRNAs) are small non-coding and highly conserved RNAs that act in biological processes including cell proliferation, invasion, apoptosis, metabolism, signal transduction, and tumorigenesis. The previously identified miRNA-326 (miR-326) has been reported to participate in cellular apoptosis, tumor growth, cell invasion, embryonic development, immunomodulation, chemotherapy resistance, and oncogenesis. This review presents a detailed overview of what is known about the effects of miR-326 on cell invasion, metastasis, drug resistance, proliferation, apoptosis, and its involvement in signaling pathways.
Abstract. Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. BCL2 apoptosis regulator (BCL2) and marker of proliferation are established prognostic markers, which have traditionally been assessed separately in DLBCL. However, no studies have evaluated the prognostic value of the combination of BCL2 and Ki-67 index. Thus, the present study aimed to analyze the prognostic value of combination of these two markers. Immunohistochemical analysis was used to assess the expression of BCL2 and Ki-67 in 274 cases of DLBCL. The BCL2/Ki-67 index demonstrated a significant association with decreased overall and progression free survival of patients with DLBCL, particularly for the germinal center B-cell-like subtype of DLBCL. Following multivariate analysis, the BCL2/Ki-67 index retained prognostic significance. Patients with coexpression of BCL2 and Ki-67 constituted a unique group with poor survival, thus novel therapies targeting BCL2 protein and high proliferative activity may improve the outcome of these patients. IntroductionDiffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL), accounting for 30-40% of all NHL patients (1-3), which is considered to be a heterogeneous entity based on its biological characteristics and clinical outcomes (3-5). The survivals of DLBCL patients have notably improved since addition of rituximab to CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy (6,7). However, some DLBCL patients continue to present an inferior prognosis under standard R-CHOP therapy (1).Ki-67, a nuclear nonhistone protein, is synthesized at the beginning of cell proliferation (8). Ki-67 expression has been widely used in clinical practice as an index to evaluate the proliferative activity of lymphoma. High Ki-67 expression was highly associated with worse OS for NHL (9). However, the relationship between Ki-67 expression and outcome with DLBCL are still contradictory and inconclusive in various studies (10-12).BCL2 protein functions as an antiapoptotic protein inhibiting cells from programmed cell death (13). Both gene amplification and translocation are common mechanisms causing BCL2 protein overexpression in DLBCL. The clinical significance of BCL2 protein expression in DLBCL is still controversial. The impact of BCL2 overexpression on survival in DLBCL is still debatable in previous studies. Additionally, the prognostic value of BCL2 protein overexpression is also different between GCB and ABC subtypes (14,15).Moreover, the predictive significance of some prognostic factors changed following the introduction of a CD20 monoclonal antibody, rituximab, underscores the necessity for revaluating the prognostic value of predictive factors after the introduction of rituximab (7,16).In the present study, we intended to investigate the optimal prognosis cut off value of Ki-67 index in DLBCL patients, and to confirm the specific prognostic value of BCL2 and its association with cell of origin classification (CO...
Abstract. In the present study, quercetin (QUR)-loaded mixed micelles (QUR-M) were prepared with the aim of improving the physicochemical and anticancer efficacy of QUR in lung cancer cells. The mixed micelles comprised tocopheryl polyethylene glycol 1000 succinate (TPGS) and a 1,2-distearoyl-sn-glycero-3-phosphatidylethanolamine derivative of polyethylene glycol. The nanosized QUR-M exhibited a pH-responsive and controlled release of QUR that is likely to be beneficial in cancer treatment. The results of an MTT assay clearly demonstrated that the anticancer effect of QUR-M in A549 cancer cells was stronger compared with that of free QUR at 24 and 48 h time points. The half-maximal inhibitory concentrations of QUR and QUR-M were observed to be 12.45 and 6.42 µg/ml, respectively. When stained with Hoechst 33342 and observed using a confocal laser scanning microscope, A549 cells treated with QUR-M exhibited severe chromatin condensation and apoptotic body formation of the nuclei. Overall, high intracellular uptake, sustained drug release and the presence of TPGS in the mixed micelles may result in an increased inhibitory effect against cell proliferation and improved therapeutic efficacy in lung cancers. IntroductionLung cancer is one of the prevalent causes of cancer-related mortality across the world in males and females (1,2). In the United States alone, lung cancer accounts for >30% of cancer-related mortalities (3). The total number of mortalities due to lung cancer exceeds the mortality rate of colon, prostate and breast cancers combined with a poor 5-year survival rate of ~15% (4). Among lung cancers, non-small cell lung cancer (NSCLC) constitutes 80% of cases (5). The present treatment options for lung cancer include chemotherapy, radiation and surgery. Chemotherapy is one of the prominent options for the effective treatment of lung cancers. However, cancer treatment with routine chemotherapeutic agents results in severe drug-related systemic side effects, which limits the potential clinical benefits (6-8).In this regard, natural components from plant resources offer numerous options for the effective replacement of routine chemotherapeutic agents. Quercetin (QUR; 3,5,7,3' ,4'-pentahydroxyflavone) is a naturally occurring flavonoid that is widely present in fruits, vegetables and leaves (9,10). QUR is considered an excellent antioxidant owing to its high number of hydroxyl groups (11). The numerous applications of QUR include the treatment of allergy, inflammation, arteriosclerosis and bleeding (12). QUR has also received attention as a chemoprotective agent exhibiting a potent antiproliferative effect on cancer cells without any effect on normal cells (13,14). QUR has been indicated to induce the apoptosis of cancer cells by blocking cell cycle progression at different phases of the cell cycle and modulating signaling pathways (15). QUR actively suppresses cancer-related processes such as apoptosis, proliferation and cancer metastasis (16). Despite its promising anticancer applications, the therapeutic ac...
The prognostic effect of chemoradiotherapy in gastric cancer has been evaluated for decades while the results are still in debate and heterogeneous.We thus comprehensively updated the evidence through systematic review and meta-analysis to evaluate chemoradiotherapy in gastric cancer to determine its effect. Pubmed, EMBASE, and Cochrane Library from the earliest possible year to April 2017 were searched. Randomised controlled trials (RCTs) that assessed the effects of combined chemoradiotherapy for patients with gastric cancer compared with that of single chemotherapy were included. The main outcome measure was 5-year overall survival (OS) and the second was disease-free survival (DFS) or recurrence-free survival (RFS).Fifteen RCTs involving 3347 patients were included into this meta-analysis. Compared with single chemotherapy, the relative risk (RR) for 5-year OS for chemoradiotherapy was 1.05 (95% CI 0.88 to 1.25), with moderate heterogeneity across eligible trials (I2 = 55.7%, p = 0.016). Subgroup analyses and sensitivity analyses confirmed the consistent findings. We found that significant survival benefit for 5-year DFS/RFS for chemoradiotherapy over single chemotherapy (RR 0.89 95% CI 0.81 to 0.98) for patients with gastric cancer. This updated meta-analysis does not provide strong evidence for a 5-year survival benefit of chemoradiotherapy over chemotherapy alone in patients with gastric cancer. A clear advantage of chemoradiotherapy over chemotherapy has not been established. Further larger RCTs should be conducted to determine its true effect.
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