IKIP downregulates THBS1/FAK signaling to suppress migration and invasion by glioblastoma cells.

Background: Inhibitor of NF-κB kinase-interacting protein (IKIP) is known to promote proliferation of glioblastoma (GBM) cells, but how it affects migration and invasion by those cells is unclear. Methods: We compared levels of IKIP between glioma tissues and normal brain tissue in clinical samples and public databases. We examined the effects of IKIP overexpression and knockdown on the migration and invasion of GBM using transwell and wound healing assays, and we compared the transcriptomes under these different conditions to identify the molecular mechanisms involved. Results: Based on data from our clinical samples and from public databases, IKIP was overexpressed in GBM tumors, and its expression level correlated inversely with survival. IKIP overexpression in GBM cells inhibited migration and invasion in transwell and wound healing assays, whereas IKIP knockdown exerted the opposite effects. IKIP overexpression in GBM cells that were injected into mouse brain promoted tumor growth but inhibited tumor invasion of surrounding tissue. The effects of IKIP were associated with downregulation of THBS1 mRNA and concomitant inhibition of THBS1/FAK signaling. Conclusions: IKIP inhibits THBS1/FAK signaling to suppress migration and invasion of GBM cells.

Effect of Cobalt on Lifetime of Sb4O5Cl2-Graphene Anode in Chloride-Ion Batteries.

Anode materials based on metal oxychlorides hold promise in addressing electrode dissolution challenges in aqueous-based chloride ion batteries (CIBs). However, their structural instability following chloride ion deintercalation can lead to rapid degradation and capacity fading. This paper investigates a cobalt-doped Sb4O5Cl2-graphene (Co-Sb4O5Cl2@GO) composite anode for aqueous-based CIBs. It exhibits significantly enhanced discharge capacity of 82.3 mAh g-1 after 200 cycles at 0.3 A g-1; while, the undoped comparison is only 23.5 mAh g-1 in the same condition. It also demonstrated with a long-term capacity retention of 72.8 % after 1000 cycles (65.5 mAh g-1) and a favorable rate performance of 25 mAh g-1 at a high current density of 2 A g-1. Undertaken comprehensive studies via in-situ experiments and DFT calculations, the cobalt (Co) dopant is demonstrated as the crucial role to enhance the lifetime of Sb4O5Cl2-based anodes. It is found that, the Co dopant improves electronic conductivity and the diffusion of chloride ions beside increases the structural stability of Sb4O5Cl2 crystal. Thus, this element doping strategy holds promise for advancing the field of Sb4O5Cl2-based anodes for aqueous-based CIBs, and insights gain from this study also offer valuable knowledge to develop high-performance electrode materials for electrochemical deionization.

Tumor-associated macrophage-related strategies for glioma immunotherapy.

High-grade glioma is one of the deadliest primary tumors of the central nervous system. Despite the many novel immunotherapies currently in development, it has been difficult to achieve breakthrough results in clinical studies. The reason may be due to the suppressive tumor microenvironment of gliomas that limits the function of specific immune cells (e.g., T cells) which are currently the primary targets of immunotherapy. However, tumor-associated macrophage, which are enriched in tumors, plays an important role in the development of GBM and is becoming a research hotspot for immunotherapy. This review focuses on current research advances in the use of macrophages as therapeutic targets or therapeutic tools for gliomas, and provides some potential research directions.

Silencing of lncRNA CRNDE attenuates nonsmall-cell lung cancer progression by mediating the miR-455-3p/HDAC2 axis.

Nonsmall-cell lung carcinoma (NSCLC) is one of the deadliest malignancies in the world. LncRNAs are confirmed to be involved in the progression of NSCLC. Meanwhile, lncRNA CRNDE is known to be upregulated in NSCLC; however, the mechanism by which CRNDE regulates the tumourigenesis of NSCLC remains unclear. To test the function of CRNDE in NSCLC, cell proliferation, invasion, and migration were investigated by colony formation and Transwell assays, respectively. qPCR and Western blotting were applied to test gene and protein levels. In addition, the relationship among CRNDE, miR-455-3p, and HDAC2 was explored by dual-luciferase and RIP assays. The data revealed that the expression of CRNDE was upregulated in NSCLC tissues, while miR-455-3p was downregulated. CRNDE knockdown inhibited the viability, migration and invasion of NSCLC cells or epidermal growth factor receptor gene (EGFR)-mutant NSCLC cells. Moreover, inhibition of miR-455-3p exhibited the opposite effect. CRNDE bound with miR-455-3p, and HDAC2 was found to be targeted by miR-455-3p. Meanwhile, miR-455-3p downregulation reversed the effect of CRNDE knockdown on NSCLC cell function. Furthermore, miR-455-3p notably inhibited the growth and invasion of NSCLC cells via downregulation of HDAC2. Knockdown of CRNDE attenuated NSCLC progression via modulation of the miR-455-3p/HDAC2 axis. Thus, those findings might provide a novel strategy against NSCLC.

Macrophage Polarization in Response to Varying Pore Sizes of 3D Polyurethane Scaffolds.

Activated macrophages dominate the progression of foreign-body response (FBR) and may be in a bimodal state, which determines the fate of biomaterials postimplantation. The purpose of this study was to investigate the phenotypic profile of macrophages polarized by waterborne biodegradable polyurethane (WBPU) scaffolds with different pore diameters (PU8, PU12, and PU16) both in vitro and in vivo. The results demonstrated that WBPU scaffolds with smaller pore sizes promoted the polarization of RAW 264.7 cells towards an M1 phenotypic profile at the early stage (24 and 48 h of in vitro cultivation), indicating a pro-inflammatory response. After being implanted subcutaneously, however, the WBPU scaffolds recruited more macrophages over time and polarized them towards an M2 phenotype on Day 3 and 14, presenting an anti-inflammatory response and tissue repair. When the internal pores were filled up (on Day 30 of implantation), the interaction between the scaffolds and macrophages decreased, indicating an endpoint of tissue repair. In general, WBPU scaffolds with tunable internal pore sizes have potential application prospects in the field of tissue engineering.

Elevated level of D-dimer increases the risk of stroke.

The aim of this study was to systematically evaluate the association between D-dimer level and the risk of stroke through performing a meta-analysis. PubMed, Web of Science, EMBASE and Cochrane Library were searched for potentially eligible literature. Prospective observational studies or case-control studies were included. The study characteristics and relevant data were extracted. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were pooled to estimate the association between D-dimer level and the risk of stroke. Seven prospective studies with 22,207 patients and three case-control studies with 2,248 patients were included. For the prospective studies, the pooled HRs of higher D-dimer level for all types of stroke, ischemic stroke and hemorrhagic stroke were 1.55 (95% CI, 1.28- 1.87), 1.62 (95% CI, 1.18-2.22) and 1.30 (95% CI, 0.63-2.68), respectively. The pooled HRs per SD increase in log D-dimer for all types of stroke, ischemic stroke and hemorrhagic stroke were 1.16 (95% CI, 1.06-1.26), 1.11 (95% CI, 1.03-1.21) and 1.11 (95% CI, 0.95-1.30), respectively. For the case-control studies, the pooled OR of higher D-dimer level for acute ischemic stroke was 2.06 (95% CI, 1.08-3.96). No significant publication bias was found in the meta-analysis. In conclusion, our results suggested that higher D-dimer level was associated with higher risk of stroke, especially ischemic stroke.

Diagnostic Performance of Increased Signal Intensity Within the Resection Cavity on Fluid-Attenuated Inversion Recovery Sequences for Detection of Progression in Patients with Glioma.

OBJECTIVE: To systematically evaluate the diagnostic performance of increased signal intensity within the resection cavity on fluid-attenuated inversion recovery (FLAIR) sequences for detection of progression in patients with glioma through performing a meta-analysis. METHODS: PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure were searched for potentially relevant literature. The study characteristics and relevant data were extracted. We estimated the pooled sensitivity, specificity, positive likelihood ratios, negative likelihood ratios, and diagnostic odds ratio and constructed summary receiver operating characteristics curves to identify the diagnostic value of FLAIR signal increase for detection of glioma progression. RESULTS: A total of 4 studies with 438 patients were included. The pooled sensitivity and specificity of increased signal intensity in FLAIR sequences in the resection cavity for detection of glioma progression were 0.36 (95% confidence interval 0.31-0.42) and 0.93 (95% confidence interval 0.86-0.97), respectively. The area under the curve was 0.7505. Subgroup analyses also were performed according to different patient sources, tumor grades, and definitions of progression. No significant publication bias was found in the meta-analysis (P = 0.85). CONCLUSIONS: Our results suggested that increased signal intensity within the resection cavity on FLAIR sequences could indicate tumor progression early with high specificity in patients with glioma. This readily accessible sign could implicate closer monitoring and could be crucial for therapeutic decisions and outcome. However, because of the limited number of studies, more well-designed studies are warranted to further verify our results and elucidate the underlining mechanisms.

Prognostic role of neutrophil-lymphocyte ratio in patients with acute ischemic stroke.

BACKGROUND: The aim of this study was to evaluate the prognostic role of neutrophil-lymphocyte ratio (NLR) in patients with acute ischemic stroke (AIS). METHODS: PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Infrastructure were searched for potential eligible literature. The study characteristics and relevant data were extracted. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled to estimate the prognostic role of NLR in patients with AIS. Poor functional outcome was defined as modified Rankin Scale ≥ 3. RESULTS: Nine studies with 2947 patients were included. The pooled OR of higher NLR for poor functional outcome at 3 months was 1.55 (95% CI, 1.21-2.00). The pooled ORs for death at 3 months, poor functional outcome at discharge, and symptomatic intracranial hemorrhage (sICH) were 2.35 (95% CI, 0.40-13.78), 2.38 (95% CI, 0.49-11.69), and 4.32 (95% CI, 2.46-7.61), respectively. CONCLUSION: For patients with AIS, higher NLR was associated with poorer functional outcome at 3 months and may be associated with a higher risk of developing sICH. This readily available and inexpensive marker may be helpful in future clinical and research work. However, due to the limited number of included studies, more well-designed studies are warranted to further clarify this issue.

Prognostic role of neutrophil lymphocyte ratio in patients with spontaneous intracerebral hemorrhage.

The aim of this study was to evaluate the prognostic role of neutrophil lymphocyte ratio (NLR) in patients with spontaneous intracerebral hemorrhage (ICH). PubMed, EMBASE, Web of Knowledge, Cochrane Library and China National Knowledge Infrastructure were searched for potentially relevant literature. The study and patient characteristics were extracted. Odds ratios (ORs) with 95% confidence intervals (CIs) were pooled to estimate the prognostic role of NLR in patients with ICH. Poor functional outcome was defined as modified Rankin Scale≥3. Four studies with 1,720 patients were included. The pooled OR of higher NLR for poor functional outcome at 3 months was 2.74 (95% CI, 1.33-5.65). The pooled OR of higher NLR for death at 3 months was 1.58 (95% CI, 0.44-5.68). Subgroup analysis and sensitivity analysis were also performed. Publication bias was not present. In conclusion, for patients with ICH, higher NLR was associated with poorer functional outcome at 3 months, while higher NLR was not associated with higher risk of death at 3 months.

Predictive value of preoperative retinal nerve fiber layer thickness for postoperative visual recovery in patients with chiasmal compression.

The aim of this study was to evaluate the predictive role of preoperative retinal nerve fiber layer (RNFL) thickness for postoperative visual recovery in patients with chiasmal compression through performing a meta-analysis. PubMed, EMBASE, Cochrane Library and China National Knowledge Infrastructure were searched for relevant studies. The study and patient characteristics were extracted. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to estimate the predictive value of RNFL thickness. Subgroup analyses were also performed. Four studies with 202 patients and 395 eyes were included. The pooled results showed that patients with normal RNFL thickness could achieve better visual recovery compared with those with thin RNFL with the OR of 15.61 (95% CI, 4.09-59.61). Significant heterogeneity was observed (I2 = 54.5%, P=0.086). Publication bias was not present. Normal preoperative RNFL thickness could predict better postoperative visual recovery than thin RNFL in patients with chiasmal compression.

Prognostic role of neutrophil lymphocyte ratio in patients with glioma.

The purpose of this study was to evaluate the prognostic role of neutrophil lymphocyte ratio (NLR) in patients with glioma. PubMed, EMBASE, Cochrane Library and China National Knowledge Infrastructure were searched for relevant literature. The study and patient characteristics were extracted. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled to estimate the prognostic role of NLR in patients with glioma. Subgroup analysis and sensitivity analysis were also performed. Six studies with 1,021 patients were included. The pooled HR of elevated NLR for OS in patients with glioma was 1.48 (95% CI, 1.25-1.76). Among the included studies, five studies used 4 as the cut-off value of NLR. The pooled HR for OS of the five studies was 1.67 (95% CI, 1.37-2.03). No significant heterogeneity was observed (I2 = 42.4%, P=0. 122). Publication bias was not present. Elevated NLR was associated with poorer overall survival in patients with glioma.

Microsurgery for intracranial arteriovenous malformation: Long-term outcomes in 445 patients.

BACKGROUND: The management of intracranial arteriovenous malformations(AVMs) poses challenges to the cerebrovascular specialists. OBJECTIVE: To review the long-term outcomes of intracranial AVMs treated with microsurgical resections. METHODS: We performed a retrospective review of 445 patients with intracranial AVMs treated in our hospital from January 1st, 2008 to December 31st, 2014. The extracted data included demographic characteristics, clinical presentations, Spetzler-Martin (SM) grades, Supplemented Spetzler-Martin (SM-Supp) Grades, treatment modalities, long-term outcomes, and obliteration rates. Outcome was assessed with a post-operative modified Rankin Scale (mRS) score at the last follow-up visit. RESULTS: Of the 445 patients treated with microsurgery, 298 (67.0%) patients initially presented with hemorrhage. Based on the SM grading system, the patients were graded as follows: 83(18.6%) Grade I, 156(35.1%) Grade II, 132(29.7%) Grade III, 61(13.7%) Grade IV and 13(2.9%) Grade V. Overall, 344(77.3%) patients had a favorable outcome (mRS score of 0-2). The favorable outcome for Grade I and II were 92.8% and 85.9%, respectively, sharply reducing to 52.5% in patients with Grade IV and 15.4% in patients with Grade V AVMs. 388(87.2%) patients achieved complete obliteration of the AVMs. 63(14.2%) patients experienced recurrent hemorrhage, and the frequency of rehemorrhage was highest in Grade V patients (77.0%), dropping to 3.6% and 3.8% in patients with Grade I and II lesions, respectively. Permanent neurological deficits occurred in 66(14.8%) patients and death in 35(7.9%) patients. There was no difference of AUROC values between SM grading system and SM-supp grading system (0.726 and 0.734, respectively, p = .715). CONCLUSION: The Spetzler-Martin grading system is a simple and effective method to estimate the risk of surgery and to evaluate the prognosis. Microsurgical resection for AVMs depends on the SM grades, and the morbidity-mortality rate increases with an increasing SM grade.

Progesterone for acute traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a leading cause of death and disability, and the identification of effective, inexpensive and widely practicable treatments for brain injury is of great public health importance worldwide. Progesterone is a naturally produced hormone that has well-defined pharmacokinetics, is widely available, inexpensive, and has steroidal, neuroactive and neurosteroidal actions in the central nervous system. It is, therefore, a potential candidate for treating TBI patients. However, uncertainty exists regarding the efficacy of this treatment. This is an update of our previous review of the same title, published in 2012. OBJECTIVES: To assess the effects of progesterone on neurologic outcome, mortality and disability in patients with acute TBI. To assess the safety of progesterone in patients with acute TBI. SEARCH METHODS: We updated our searches of the following databases: the Cochrane Injuries Group's Specialised Register (30 September 2016), the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 9, 2016), MEDLINE (Ovid; 1950 to 30 September 2016), Embase (Ovid; 1980 to 30 September 2016), Web of Science Core Collection: Conference Proceedings Citation Index-Science (CPCI-S; 1990 to 30 September 2016); and trials registries: Clinicaltrials.gov (30 September 2016) and the World Health Organization (WHO) International Clinical Trials Registry Platform (30 September 2016). SELECTION CRITERIA: We included randomised controlled trials (RCTs) of progesterone versus no progesterone (or placebo) for the treatment of people with acute TBI. DATA COLLECTION AND ANALYSIS: Two review authors screened search results independently to identify potentially relevant studies for inclusion. Independently, two review authors selected trials that met the inclusion criteria from the results of the screened searches, with no disagreement. MAIN RESULTS: We included five RCTs in the review, with a total of 2392 participants. We assessed one trial to be at low risk of bias; two at unclear risk of bias (in one multicentred trial the possibility of centre effects was unclear, whilst the other trial was stopped early), and two at high risk of bias, due to issues with blinding and selective reporting of outcome data.All included studies reported the effects of progesterone on mortality and disability. Low quality evidence revealed no evidence of a difference in overall mortality between the progesterone group and placebo group (RR 0.91, 95% CI 0.65 to 1.28, I² = 62%; 5 studies, 2392 participants, 2376 pooled for analysis). Using the GRADE criteria, we assessed the quality of the evidence as low, due to the substantial inconsistency across studies.There was also no evidence of a difference in disability (unfavourable outcomes as assessed by the Glasgow Outcome Score) between the progesterone group and placebo group (RR 0.98, 95% CI 0.89 to 1.06, I² = 37%; 4 studies; 2336 participants, 2260 pooled for analysis). We assessed the quality of this evidence to be moderate, due to inconsistency across studies.Data were not available for meta-analysis for the outcomes of mean intracranial pressure, blood pressure, body temperature or adverse events. However, data from three studies showed no difference in mean intracranial pressure between the groups. Data from another study showed no evidence of a difference in blood pressure or body temperature between the progesterone and placebo groups, although there was evidence that intravenous progesterone infusion increased the frequency of phlebitis (882 participants). There was no evidence of a difference in the rate of other adverse events between progesterone treatment and placebo in the other three studies that reported on adverse events. AUTHORS' CONCLUSIONS: This updated review did not find evidence that progesterone could reduce mortality or disability in patients with TBI. However, concerns regarding inconsistency (heterogeneity among participants and the intervention used) across included studies reduce our confidence in these results.There is no evidence from the available data that progesterone therapy results in more adverse events than placebo, aside from evidence from a single study of an increase in phlebitis (in the case of intravascular progesterone).There were not enough data on the effects of progesterone therapy for our other outcomes of interest (intracranial pressure, blood pressure, body temperature) for us to be able to draw firm conclusions.Future trials would benefit from a more precise classification of TBI and attempts to optimise progesterone dosage and scheduling.

Progesterone for Acute Traumatic Brain Injury: A Systematic Review of Randomized Controlled Trials.

OBJECTIVE: To evaluate the efficacy and safety of progesterone administrated in patients with acute traumatic brain injury (TBI). METHODS: PubMed/MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL), Clinicaltrials.gov, ISRCTN registry and WHO International Clinical Trials Registry Platform (ICTRP) were searched for randomized controlled trials (RCTs) comparing progesterone and placebo administrated in acute TBI patients. The primary outcome was mortality and the secondary outcomes were unfavorable outcomes and adverse events. A meta-analysis was conducted to evaluate the efficacy and safety of progesterone administrated in patients with acute TBI. RESULTS: A total of 6 studies met inclusion criteria, involving 2,476 patients. The risk of bias was considered to be low in 4 studies but high in the other 2 studies. The results of meta-analysis indicated progesterone did not reduce the mortality (RR = 0.83, 95% CI = 0.57-1.20) or unfavorable outcomes (RR = 0.89, 95% CI = 0.78-1.02) of acute TBI patients in comparison with placebo. Sensitivity analysis yielded consistent results. Progesterone was basically safe and well tolerated in TBI patients with the exception of increased risk of phlebitis or thrombophlebitis (RR = 3.03, 95% CI = 1.96-4.66). CONCLUSIONS: Despite some modest bias, present evidence demonstrated that progesterone was well tolerated but did not reduce the mortality or unfavorable outcomes of adult patients with acute TBI.

MUC1 Predicts Colorectal Cancer Metastasis: A Systematic Review and Meta-Analysis of Case Controlled Studies.

OBJECTIVE: To evaluate the predicting value of MUC1 expression in lymph node and distant metastasis of colorectal cancer (CRC). METHODS: Pubmed/ MEDLINE and EMBASE were searched to identify eligible studies that evaluated the correlation between MUC1 and CRC. A meta-analysis was conducted to evaluate the impact of MUC1 expression on CRC metastasis. RESULTS: A total of 18 studies (n = 3271) met inclusion criteria and the mean Newcastle-Ottawa Scale (NOS) score was 6.3 with a range from 4 to 8. The pooled OR in the meta-analysis of 15 studies indicated that positive MUC1 expression correlated with more CRC node metastasis (OR = 2.32, 95% CI = 1.63-3.29). The data synthesis of 6 studies suggested that MUC1 expression predicted more possibility of CRC distant metastasis (OR = 2.22, 95% CI = 1.23-4.00). In addition, the combined OR of 7 studies showed that MUC1 expression indicated higher Duke's stage (OR = 3.02, 95% CI = 2.11-4.33). No publication bias was found in the mate-analysis by Begg's test or Egger's test with the exception of the meta-analysis of MUC1 with CRC node metastasis (Begg's test p = 0.729, Egger's test p = 0.000). CONCLUSIONS: Despite of some modest bias, the pooled evidence suggested that MUC1 expression was significantly correlated with CRC metastasis.

Prognostic significance of interleukin-17 in solid tumors: a meta-analysis.

BACKGROUND: The prognostic significance of intratumoral and peripheral interleukin-17 (IL-17) in tumors has been studied worldwide during these years, providing un-uniformed conclusions. METHODS: We conducted a meta-analysis of published literatures that evaluated the correlation between IL-17 and clinical staging, overall survival (OS) and/or disease free survival (DFS). RESULTS: A total of 28 studies enrolling 2902 patients were included. For the overall population, a high expression of IL-17 was found significantly correlated with worse DFS (HR = 1.59, 95% CI: 1.24-2.03) in patients with solid tumors. For gastrointestinal tumors, patients with IL-17 high seemed to have worse OS (HR = 1.85, 95% CI: 1.24-2.75) and DFS (HR = 2.41, 95% CI: 1.98-2.92). Sub-group meta-analysis revealed that IL-17 indicated late clinical staging in non-small cell lung cancer (NSCLC) patients (HR = 2.33, 95% CI: 1.25-4.32), on the other hand, early clinical staging in patients with esophageal squamous carcinoma (HR = 0.63, 95% CI: 0.42-0.94). Negative impacts of IL-17 on OS were shown in patients with hepatocellular carcinoma (HCC) (HR = 1.87, 95% CI: 1.23-2.84) or NSCLC (HR = 1.55, 95% CI: 1.02-2.35). However, positive impacts on OS were provided in patients with esophageal squamous carcinoma (HR = 0.65, 95% CI: 0.50-0.84). Besides, a high expression of IL-17 predicted better DFS in ovarian cancer patients (HR = 0.33, 95% CI: 0.11-1.00). CONCLUSIONS: Our meta-analysis revealed that IL-17 might correlate with poor OS and DFS in gastrointestinal tumors. Specifically, IL-17 was a detrimental factor for HCC and NSCLC patients, whereas a beneficial factor for patients with esophageal squamous carcinoma and ovarian cancer.

Prognostic significance of STAT3/phosphorylated-STAT3 in tumor: a meta-analysis of literatures.

PURPOSE: The prognostic value of the expression of STAT3/phosphorylated-STAT3 on survival for cancer patients remains controversial. We performed a meta-analysis of the published literature in this field to identify its impact. METHODS: We conducted a meta-analysis of 26 studies (n=3877 patients) that evaluated the relationship between the prognostic value and the expression of STAT3/phosphorylated-STAT3 in 15 different kinds of carcinomas. Studies evaluated the correlation between STAT3/phosphorylated-STAT3, which detected mostly by immunohistochemistry and western blot, and clinical staging, overall survival (OS) and disease free survival (DFS) were included. The impact of STAT3 and phosphorylated-STAT3 was analyzed separately. RESULTS: A total of 26 studies (14 for STAT3 and 16 for phosphorylated-STAT3), comprising 3877 patients, were included for meta-analysis. The expression of STAT3 was strongly associated with a poor impact on overall survival (OS) in all eligible studies [hazard ratio (HR)=2.91, (95% confidence interval (CI), 1.91-4.42)], while a significant association was shown between the expression of phosphorylated-STAT3 and patients' outcome [HR=1.53, (95% CI, 0.86-2.70)]. No significant effect was shown between the expression of STAT3/phosphorylated-STAT3 and clinical staging, neither with DFS. CONCLUSION: High expression of STAT3 seems to be associated with poor OS in patients with carcinomas, while phosphorylated-STAT3 does not.

Monocyte chemotactic protein-1 expression as a prognosic biomarker in patients with solid tumor: a meta analysis.

PURPOSE: A great deal of studies have been performed on the prognostic value of monocyte chemotactic protein-1 (MCP-1) in solid tumors in recent years. However, no consistent outcomes are reported. Therefore, the prognostic value of MCP-1 still remains controversial in patients with solid tumors. Here we aimed to evaluate the prognostic value of MCP-1 expression for patients with solid tumors. METHODS: Comprehensive literature was selected from PUBMED and EMBASE and clinical studies which reported analysis of survival data about MCP-1 in solid tumors were included. Stata 11.0 was used for performing a meta-analysis on evaluating the relation between MCP-1 and clinical staging, overall survival (OS) and disease free survival (DFS). RESULTS: Eleven studies with a total of 1324 patients with solid tumors were included into our meta-analysis. The result showed that high concentration of MCP-1 was related to a worse OS (HR = 1.95, 95% CI 1.32-2.88). The subgroup analysis on different location of tumors showed that high concentration of MCP-1 meant bad prognosis in patients with digestive cancer (HR = 2.66, 95% CI 1.44-4.91) and urogenital cancer (HR = 2.23, 95% CI 1.61-3.10), even head and neck cancer (HR = 1.99, 95% CI 0.95-4.18) other than respiratory cancer (HR = 1.10, 95% CI 0.39-3.11). Another subgroup analysed on different sites of cancer and indicated a poor prognosis on adenocarcinoma (HR = 2.10, 95% CI 1.63-2.69). CONCLUSIONS: Our findings suggest that MCP-1 can be regarded as a poor prognostic maker for solid tumors and may represent important new therapeutic targets.

Prognostic significance of tumor-associated macrophages in solid tumor: a meta-analysis of the literature.

PURPOSE: Tumor associated macrophages (TAMs) are considered with the capacity to have both negative and positive effects on tumor growth. The prognostic value of TAM for survival in patients with solid tumor remains controversial. EXPERIMENTAL DESIGN: We conducted a meta-analysis of 55 studies (n = 8,692 patients) that evaluated the correlation between TAM (detected by immunohistochemistry) and clinical staging, overall survival (OS) and disease free survival (DFS). The impact of M1 and M2 type TAM (n = 5) on survival was also examined. RESULTS: High density of TAM was significantly associated with late clinical staging in patients with breast cancer [risk ratio (RR)  = 1.20 (95% confidence interval (CI), 1.14-1.28)] and bladder cancer [RR = 3.30 (95%CI, 1.56-6.96)] and with early clinical staging in patients with ovarian cancer [RR = 0.52 (95%CI, 0.35-0.77)]. Negative effects of TAM on OS was shown in patients with gastric cancer [RR = 1.64 (95%CI, 1.24-2.16)], breast cancer [RR = 8.62 (95%CI, 3.10-23.95)], bladder cancer [RR = 5.00 (95%CI, 1.98-12.63)], ovarian cancer [RR = 2.55 (95%CI, 1.60-4.06)], oral cancer [RR = 2.03 (95%CI, 1.47-2.80)] and thyroid cancer [RR = 2.72 (95%CI, 1.26-5.86)],and positive effects was displayed in patients with colorectal cancer [RR = 0.64 (95%CI, 0.43-0.96)]. No significant effect was showed between TAM and DFS. There was also no significant effect of two phenotypes of TAM on survival. CONCLUSIONS: Although some modest bias cannot be excluded, high density of TAM seems to be associated with worse OS in patients with gastric cancer, urogenital cancer and head and neck cancer, with better OS in patients with colorectal cancer.