The prognostic role of Ki-67/MIB-1 in meningioma: A systematic review with meta-analysis.

BACKGROUND: Ki-67 is a typical immunohistochemical marker for cell proliferation. Higher expression of Ki-67 is correlated with poor clinical outcomes in several cancers. However, the prognostic value of Ki-67 on the prognosis of meningiomas is still controversial. The purpose of this meta-analysis was to evaluate the prognostic value of Ki-67 in meningiomas. METHODS AND MATERIALS: We searched Medline and EMBASE from inception to December 31, 2018, to identify relevant articles. Using a fixed or random effects model, pooled hazard ratios (HRs) for overall survival (OS) and disease/progression/recurrence-free survival (D/P/RFS) were estimated. RESULTS: A total of 43 studies, comprising 5012 patients, were included in this analysis. Higher Ki-67 expression levels were significantly associated with worse OS (HR = 1.565; 95% CI: 1.217-2.013) and D/P/RFS (HR = 2.644; 95% CI: 2.264-3.087) in meningiomas. Subgroup analysis revealed that all the included factors (ethnicity, tumor grade, HR sources, definition of cutoffs, cutoff values) for heterogeneity investigation can affect the pooled results. Among them, the definitions of cutoffs and cutoff values factor are the two main contributors toward heterogeneity. Multivariable meta-regression analysis also showed that methodologies used for cutoff value definition contributed to the high inner-study heterogeneity. CONCLUSIONS: Higher Ki-67 expression levels negatively influenced survival in meningiomas. A higher cutoff value (>4%) is more appropriate for prognosis prediction. It is highly recommended that Ki-67 expression profile could be assessed in meningiomas treatment for predicting survival. And patients with elevated expression of Ki-67 need to have close follow-ups.

Prognostic role of pretreatment red blood cell distribution width in patients with cancer: A meta-analysis of 49 studies.

Red blood cell distribution width (RDW) has been recently demonstrated to be a predictor of inflammation. High pretreatment RDW level is associated with poor survival outcomes in various malignancies, although the results are controversial. We aimed to investigate the prognostic role of RDW. A systematic literature search was performed in MEDLINE and EMBASE till April 2018. Pooled hazard ratios (HRs) were estimated for overall survival (OS) and combined disease-free survival, progression-free survival, and recurrence-free survival (DFS/PFS/RFS). 49 studies with 19,790 individuals were included in the final analysis. High RDW level adversely affected both OS and DFS/PFS/RFS. For solid cancers, colorectal cancer (CRC) had the strongest relationship with poor OS, followed by hepatic cancer (HCC). Negative OS outcomes were also observed in hematological malignancies. Furthermore, patients at either early or advanced stage had inverse relationship between high pretreatment RDW and poor OS. Studies with cut-off values between 13% and 14% had worse HRs for OS and DFS/PFS/RFS than others. Furthermore, region under the curve (ROC) analysis was used widely to define cut-off values and had relatively closer relationship with poorer HRs. In conclusion, our results suggested that elevated pretreatment RDW level could be a negative predictor for cancer prognosis.

Prognostic role of pretreatment circulating MDSCs in patients with solid malignancies: A meta-analysis of 40 studies.

Myeloid-derived suppressor cells (MDSCs) have been shown to contribute to tumor progression, mainly through immune suppression. Inverse correlations have been observed between MDSC levels and patient survival for various malignancies. The purpose of this meta-analysis was to evaluate the prognostic value of pretreatment circulating MDSCs. We searched MEDLINE and EMBASE from their inceptions to September 2017 to identify relevant articles. Using a fixed or random effects model, pooled hazard ratios (HRs) were estimated for overall survival (OS) and combined disease-free survival, progression-free survival, and recurrence-free survival (DFS/PFS/RFS). A total of 40 studies comprising 2721 were included. For solid tumors, high levels of pretreatment circulating MDSCs were significantly associated with worse OS (HR = 1.796, 95% CI = 1.587-2.032) and DFS/PFS/RFS (HR = 2.459, 95% CI = 2.018-2.997). Breast cancer showed the largest association between high MDSC levels and worse OS (pooled HR = 3.053). Elevated MDSCs were also associated with worse OS for mixed-stage tumors (pooled HR = 1.659) and advanced-stage tumors (pooled HR = 2.337). Furthermore, both monocytic-MDSCs (M-MDSCs) and granulocytic or polymorphonuclear (PMN-MDSCs) showed negative associations with survival outcomes. Overall, high levels of pretreatment circulating MDSCs negatively influenced survival in most cancers. Pretreatment circulating MDSCs should be taken into account to further improve prognostic evaluation and develop novel therapeutic strategies.

The expression profile of PD-L1 and CD8+ lymphocyte in pituitary adenomas indicating for immunotherapy.

BACKGROUND: Pituitary adenomas (PAs) are the second most common brain tumors, and mostly are benign tumors. However, there exists subtypes of PAs refractory to common treatments, and need novel therapy. Programmed death 1 (PD-1) blockade has shown durable objective response in a variety of malignancies, and the key predictive markers for this immunotherapy were PD-L1 and CD8+ tumor-infiltrating lymphocyte (TILs) expression. To evaluate the potential immunotherapy for PAs, we investigated the expression of these two immune markers in PAs. METHODS: Immunohistochemistry (IHC) was performed to detect the expression of PD-L1 and CD8+ TILs in PAs. The ratio of positive expression of PD-L1 and CD8+ TILs was compared with chi-squared tests among different subtypes of PAs. The association between their expression profile and clinical parameters was analyzed using a chi-squared test, or Fisher's exact probability test when appropriate. RESULTS: One hundred and ninety one patients with PAs were retrospectively involved in this study, consisting of 106 non-functioning PAs (NF-PAs, 55.5%), 40 PRL-secreting PAs (PRL-PAs, 20.9%), 31 GH-secreting PAs (GH-PAs, 16.2%), 9 ACTH-secreting PAs (ACTH-PAs, 4.7%) and 5 plurihormonal adenomas (2.6%) respectively. 36.6% of them were PD-L1 positive and 86.9% were CD8+ TILs positive. The positive PD-L1 immunostaining presented more frequently in functioning PAs (58.8%), compared with that (34.3%) in nonfunctioning group (p = 0.000). Moreover, the rates of PD-L1 expression were more associated with increased blood levels of PRL, GH, ACTH and cortisol. Contrastly, positive CD8+ TILs immunostaining was only correlated with elevated blood level of GH. For the analysis of immune markers with pathological results, PD-L1 expression was associated with PRL and GH immunostaining and higher Ki-67 index. But CD8+ TILs was only correlated with PRL immunostaining. CONCLUSION: Our results showed that PD-L1 was frequently expressed in functioning PAs with association of aggressive behaviors in PAs. The immunotherapy could be a promising treatment option of PAs.

Immune-Related Adverse Events Associated with Anti-PD-1/PD-L1 Treatment for Malignancies: A Meta-Analysis.

Background: Treatment of cancers with programmed cell death protein 1 (PD-1) pathway inhibitors can lead to immune-related adverse events (irAEs), which could be serious and even fetal. Therefore, clinicians should be aware of the characteristics of irAEs associated with the use of such drugs. Methods: The MEDLINE, EMBASE, and Cochrane databases were searched to find potential studies using the following strategies: anti-PD-1/PD-L1 treatment; irAEs; and cancer. R© package Meta was used to pool incidence. Results: Forty-six studies representing 12,808 oncologic patients treated with anti-PD-1/PD-L1 agents were included in the meta-analysis. The anti-PD-1/PD-L1 agents included nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, and BMS-936559. The tumor types were melanomas, Hodgkin lymphomas, urothelial carcinomas, breast cancers, non-small cell lung cancers, renal cell carcinomas (RCC), colorectal cancers, and others. We described irAEs according to organ systems, namely, the skin (pruritus, rash, maculopapular rash, vitiligo, and dermatitis), endocrine system (hypothyroidism, hyperthyroidism, hypophysitis, thyroiditis, and adrenal insufficiency), digestive system (colitis, diarrhea, pancreatitis, and increased AST/ALT/bilirubin), respiratory system (pneumonitis, lung infiltration, and interstitial lung disease), and urinary system (increased creatinine, nephritis, and renal failure). In patients treated with the PD-1 signaling inhibitors, the overall incidence of irAEs was 26.82% (95% CI, 21.73-32.61; I2, 92.80) in any grade and 6.10% (95% CI, 4.85-7.64; I2, 52.00) in severe grade, respectively. The development of irAEs was unrelated to the dose of anti-PD-1/PD-L1 agents. The incidence of particular irAEs varied when different cancers were treated with different drugs. The incidence of death due to irAEs was around 0.17%. Conclusion: The occurrence of irAEs was organ-specific and related to drug and tumor types.

[The effects of graphene quantum dots on hematopoietic system in rats].

OBJECTIVE: To study the effects of graphene quantum dots (GQDs) on hematopoietic system in rats. METHODS: Thirty male SD rats were randomly divided into three groups (n = 10): control group, high dose group (10 mg/kg · d), low dose group (5 mg/kg · d), The rats in experimental group were intravenous injected with GQDs for 28 days and those in control group were injected with normal saline at the same volume. Routine blood and the function of liver and kidney were detected by instrument analysis. The cycle and apoptosis of bone marrow mononuclear cells (BMCs) were detected by FCM. The other three only healthy male SD rat bone marrow mononuclear cells (BMCs) were cultured by joining GQDs for 24 h, 48 h,72 h in vitro, the proliferation was assayed by CCK-8, the content of granulocyte macrophage colony stimulating factor (GM-CSF) from cultural supernatants were detected by ELISA. RESULTS: The amount of red blood cell and concentration of hemoglobin from experimental group were increased significantly compared with those of control groups (P < 0.05), the concentration of triglyceride and high density lipoprotein were decreased. DNA synthesis period was prolonged (P < 0.01), there was no significant difference in apoptosis. BMCs were promoted proliferation clearly after using GQDs for 72 h (P < 0.05). The content of GM-CSF was increased (P < 0.01) . CONCLUSION: GQDs may promote hematopoietic function in rats.