The aim of this study was to elucidate the diagnostic and prognostic roles of the mean platelet volume (MPV) in various malignant tumors through a systematic review and meta-analysis. The current study included 2,053 patients and 1,396 healthy subjects in 18 eligible studies. We performed a meta-analysis of MPV levels and the mean difference between healthy subjects and pre- and post-treatment patients. Subgroup analysis was conducted based on specific organs and platelet counts. In addition, the correlation between MPV and survival was investigated. The pooled MPVs of healthy subjects, pre-treatment, and post-treatment patients were 8.428 fL (95% confidence interval [CI] 8.118-8.738), 8.831 fL (95% CI 8.582-9.087), and 8.521 fL (95% CI 8.162-8.880), respectively. The mean difference in MPV between healthy subjects and pre-treatment patients was 0.502 (95% CI 0.285-0.719, P < 0.001). However, in lung cancer, the mean difference between pre-treatment patients and healthy subjects was -0.352 (95% CI -0.763-0.060, P = 0.094). The pooled MPV of post-treatment patients was significantly decreased compared to pre-treatment patients. There was no correlation between MPV and disease-free survival rate (hazard ratio 1.033, 95% CI 0.369-2.895). Our results showed that the MPV level was significantly higher in malignant tumors than in healthy subjects and was decreased after treatment. Further cumulative studies will be required before MPV levels can be applied for screening malignant tumors and predicting prognosis.

PurposeThe molecular mechanisms that are responsible for the initiation and progression of breast cancers are largely unknown. This study was to analyze the cyclin B1, cdc2, p53 and p16 tumor suppressor genes in human breast cancer.Materials and MethodsTo investigate the role of cyclin B1, cdc2, p53 and p16 in the pathogenesis and progression of breast carcinomas, 98 cases of breast cancers were examined by immunohistochemical method. The correlations of cyclin B1, cdc2, p53 and p16 expression with various clinico-pathologic findings were analysed.ResultsIn the normal breast tissues, cyclin B1, cdc2 and p16 were weakly expressed, while p53 was not expressed. On the other hand, cyclin B1, cdc2, p53 and p16 were overexpressed in breast cancer, showing correlation between the expression of cyclin B1 and cdc2 and breast cancers (p=0.00). The overexpressions of cdc2 and p16 were correlated with an infiltrative tumor border pattern and this was statistically significant (p<0.05). In addition, the overexpression of cdc2 was correlated with histologic high grade carcinomas (p=0.00).ConclusionCyclin B1 and cdc2 appeared to be involved in the genesis or progression of breast cancers. In addition, the overexpressions of p16 and p53 may play important roles in more aggressive tumor and the overexpression of cdc2 is associated with progression of tumor to a higher grade of breast carcinomas. The deranged overexpressions of cyclin B1, cdc2, p16 and p53 may play an important role in human breast carcinogenesis.

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Background/Objectives This meta-analysis is aimed at investigating the prognostic roles of the inflammatory markers neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with pancreatic cancer. Methods The correlations between high inflammatory marker expression levels and prognosis in 7105 patients with pancreatic cancer from 34 eligible studies were investigated. Additionally, subgroup analyses based on study location, tumor stage, treatment, and value cutoffs were performed. Results High NLR and PLR values were considered to be 2.0–5.0 and 150–200, respectively. Using a random-effects model, the estimated rates of high NLR and PLR were 0.379 (95% confidence interval [CI] 0.310–0.454) and 0.490 (95% CI 0.438–0.543), respectively. High NLRs were frequently found in patients with lower tumor stages and in those who underwent surgery. There were significant correlations between high NLR and PLR and poor survival rates (hazard ratio [HR] 1.737, 95% CI 1.502–2.009 and HR 1.143, 95% CI 1.037–1.259, resp.). Interestingly, the NLR and PLR had no prognostic value in patients who underwent chemoradiotherapy. Conclusion Taken together, our results showed that inflammatory markers are useful for predicting prognosis in patients with pancreatic cancer. The NLR is a more suitable parameter for predicting prognosis regardless of the patient's condition.

PurposeWe previously reported that forkhead transcription factors of the O class 1 (FOXO1) expression in gastric cancer (GC) was associated with angiogenesis-related molecules. However, there is little experimental evidence for the direct role of FOXO1 in GC. In the present study, we investigated the effect of FOXO1 on the tumorigenesis and angiogenesis in GC and its relationship with SIRT1.Materials and MethodsStable GC cell lines (SNU-638 and SNU-601) infected with a lentivirus containing FOXO1 shRNA were established for animal studies as well as cell culture experiments. We used xenograft tumors in nude mice to evaluate the effect of FOXO1 silencing on tumor growth and angiogenesis. In addition, we examined the association between FOXO1 and SIRT1 by immunohistochemical tissue array analysis of 471 human GC specimens and Western blot analysis of xenografted tumor tissues.ResultsIn cell culture, FOXO1 silencing enhanced hypoxia inducible factor-1α (HIF-1α) expression and GC cell growth under hypoxic conditions, but not under normoxic conditions. The xenograft study showed that FOXO1 downregulation enhanced tumor growth, microvessel areas, HIF-1α activation and vascular endothelial growth factor (VEGF) expression. In addition, inactivated FOXO1 expression was associated with SIRT1 expression in human GC tissues and xenograft tumor tissues.ConclusionOur results indicate that FOXO1 inhibits GC growth and angiogenesis under hypoxic conditions via inactivation of the HIF-1α–VEGF pathway, possibly in association with SIRT1. Thus, development of treatment modalities aiming at this pathway might be useful for treating GC.

Purpose: This study aimed to elucidate the clinicopathological significance and prognostic role of tumor-infiltrating lymphocytes in colorectal cancer. Methods: The immunohistochemistry of CD3 and CD8 was performed on 265 human colorectal cancer tissues to investigate the tumor-infiltrating lymphocytes using Immunoscore. The correlation between Immunoscore and clinicopathological characteristics, including survival rates, was elucidated. In addition, the impact of tumor-infiltrating lymphocytes on programmed death-ligand 1 (PD-L1) protein expression was evaluated through immunohistochemistry. Results: Of the 265 colorectal cancer tissues, 40.8% had high Immunoscore, while 59.2% had low Immunoscore. A high Immunoscore was significantly correlated with favorable tumor behaviors, including lower rates of vascular, lymphatic, and perineural invasion; lymph node metastasis; and distant metastasis. PD-L1 expressions of tumor and immune cells were significantly higher in patients with high Immunoscore than in those with low Immunoscore. In addition, colorectal cancer tissues with high CD8-positive lymphocytes showed higher PD-L1 expressions of tumor and immune cells than colorectal cancer tissues with low CD8-positive lymphocytes. There was a significant correlation between high Immunoscore and better overall survival. However, there was no significant difference in survival rate according to PD-L1 expressions of tumor and immune cells in high and low Immunoscore subgroups. Conclusions: Taken together, our results showed that high tumor-infiltrating lymphocytes were significantly correlated with favorable tumor behaviors and better survival. In addition, there was a significant correlation between PD-L1 expression and tumor-infiltrating lymphocytes.

Background/Aims: To assess the efficacy of intravesical hyaluronic acid (HA) and HA/chondroitin sulfate (CS) instillation in patients with interstitial cystitis/painful bladder syndrome by systematic review and meta-analysis. Methods: A systematic literature search was performed using the keywords: ‘interstitial cystitis' or ‘painful bladder syndrome' or ‘bladder pain syndrome' and ‘hyaluronic acid', up to March 31, 2016. The primary outcome was visual analogue scale related pain symptom (VAS). Secondary outcomes were the O'Leary-Sant Interstitial Cystitis Symptom Index (ICSI) and Problem Index (ICPI), frequency, nocturia, bladder volume, and voided urine volume. Results: Ten articles involving 390 patients were retrieved and assessed in analysis. A significant improvement in mean VAS on fixed-effect and random-effect models (mean difference [MD] -3.654, 95% confidence interval [CI] -3.814 to -3.495, and MD -3.206, 95% CI -4.156 to -2.257, respectively) was found. Significant improvements were found in the ICSI (MD -3.223, 95% CI -4.132 to -2.315) and ICPI (MD -2.941, 95% CI -3.767 to -2.116). Similarly, the other outcomes were significantly improved. Conclusion: Intravesical HA and HA/CS instillation improved pain symptom, quality of life, and other outcomes and could be included as therapeutic modality of interstitial cystitis/painful bladder syndrome.

The findings of the present study suggest that the presence of PB may be a useful prognostic indicator of aggressive PTC behaviors. In addition, confirmation of ultrasonographic intratumoral calcification would be a useful decision-making criterion when determining the need for preoperative or intraoperative surveillance of nodal metastasis.