Qiongwen Zhang

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.

Codelivery of curcumin and doxorubicin by MPEG-PCL results in improved efficacy of systemically administered chemotherapy in mice with lung cancer

Systemic administration of chemotherapy for cancer often has toxic side effects, limiting the doses that can be used in its treatment. In this study, we developed methoxy poly(ethylene glycol)-poly(caprolactone) (MPEG-PCL) micelles loaded with curcumin and doxorubicin (Cur-Dox/MPEG-PCL) that were tolerated by recipient mice and had enhanced antitumor effects and fewer side effects. It was shown that these Cur-Dox/MPEG-PCL micelles could release curcumin and doxorubicin slowly in vitro. The long circulation time of MPEG-PCL micelles and the slow rate of release of curcumin and doxorubicin in vivo may help to maintain plasma concentrations of active drug. We also demonstrated that Cur-Dox/MPEG-PCL had improved antitumor effects both in vivo and in vitro. The mechanism by which Cur-Dox/MPEG-PCL micelles inhibit lung cancer might involve increased apoptosis of tumor cells and inhibition of tumor angiogenesis. We found advantages using Cur-Dox/MPEG-PCL micelles in the treatment of cancer, with Cur-Dox/MPEG-PCL achieving better inhibition of LL/2 lung cancer growth in vivo and in vitro. Our study indicates that Cur-Dox/MPEG-PCL micelles may be an effective treatment strategy for cancer in the future.

A systemic administration of liposomal curcumin inhibits radiation pneumonitis and sensitizes lung carcinoma to radiation

Radiation pneumonitis (RP) is an important dose-limiting toxicity during thoracic radiotherapy. Previous investigations have shown that curcumin is used for the treatment of inflammatory conditions and cancer, suggesting that curcumin may prevent RP and sensitize cancer cells to irradiation. However, the clinical advancement of curcumin is limited by its poor water solubility and low bioavailability after oral administration. Here, a water-soluble liposomal curcumin system was developed to investigate its prevention and sensitizing effects by an intravenous administration manner in mice models. The results showed that liposomal curcumin inhibited nuclear factor-κB pathway and downregulated inflammatory factors including tumor necrosis factor-α, interleukin (IL)-6, IL-8, and transforming growth factor-β induced by thoracic irradiation. Furthermore, the combined treatment with liposomal curcumin and radiotherapy increased intratumoral apoptosis and microvessel responses to irradiation in vivo. The significantly enhanced inhibition of tumor growth also was observed in a murine lung carcinoma (LL/2) model. There were no obvious toxicities observed in mice. The current results indicate that liposomal curcumin can effectively mitigate RP, reduce the fibrosis of lung, and sensitize LL/2 cells to irradiation. This study also suggests that the systemic administration of liposomal curcumin is safe and deserves to be investigated for further clinical application.

Matrix Metalloproteinase-9 as a Prognostic Factor in Gastric Cancer: A Meta-Analysis

BACKGROUND Matrix metalloproteinase-9 (MMP-9) is associated with disruption of basement membranes of blood vessels and promotion of metastasis through the lymphatics. However, its prognostic value for survival in patients with gastric cancer remains controversial. METHOD We therefore conducted a meta-analysis of the published literature in order to clarify the impact of MMP-9. Clinical studies were selected for further analysis if they provided an independent assessment of MMP-9 in gastric cancer and reported analysis of survival data according to MMP-9 expression. RESULTS A total of 11 studies, covering 1700 patients, were included for meta- analysis. A summary hazard ratio (HR) of all studies and sub-group hazard ratios were calculated. The combined HR suggested that a positive MMP-9 expression had an impact on overall survival: 1.25 (95% confidence interval 1.11-1.40) in all eligible studies; 1.13 (1.06-1.20) in 8 studies detecting MMP-9 by immunohistochemistry; 1.36 (1.12-1.65) in 7 studies from Asia. Only one study for DFS showed a significant impact on disease free survival (HR 1.73, 95%CI 1.27-2.34). CONCLUSIONS Our findings suggested that MMP-9 protein expression might be a factor for a poor prognosis in patients with gastric cancer. However, the association was rather weak, so that more prospective studies should further explore the prognostic impact of MMP-9 mRNA and correlations between MMP-9 and clinicopathological characteristics.

Intratumoral vessel density as prognostic factors in head and neck squamous cell carcinoma: A meta‐analysis of literature

The purpose of this study was to comprehensively and quantitatively summarize the prognostic value of microvessel density (MVD) and lymphatic vessel density (LVD) for the survival of patients with head and neck squamous cell carcinoma (HNSCC).

The Effectiveness of Intensity Modulated Radiation Therapy versus Three-Dimensional Radiation Therapy in Prostate Cancer: A Meta-Analysis of the Literatures.

Background and Purpose Intensity modulated radiation therapy (IMRT) can deliver higher doses with less damage of healthy tissues compared with three-dimensional radiation therapy (3DCRT). However, for the scenarios with better clinical outcomes for IMRT than 3DCRT in prostate cancer, the results remain ambiguous. We performed a meta-analysis to assess whether IMRT can provide better clinical outcomes in comparison with 3DCRT in patients diagnosed with prostate cancer. Materials and Methods We conducted a meta-analysis of 23 studies (n = 9556) comparing the clinical outcomes, including gastrointestinal (GI) toxicity, genitourinary (GU) toxicity, biochemical controland overall survival (OS). Results IMRT was significantly associated with decreased 2–4 grade acute GI toxicity [risk ratio (RR) = 0.59 (95% confidence interval (CI), 0.44, 0.78)], late GI toxicity [RR = 0.54, 95%CI (0.38, 0.78)], late rectal bleeding [RR = 0.48, 95%CI (0.27, 0.85)], and achieved better biochemical control[RR = 1.17, 95%CI (1.08, 1.27)] in comparison with 3DCRT. IMRT and 3DCRT remain the same in regard of grade 2–4 acute rectal toxicity [RR = 1.03, 95%CI (0.45, 2.36)], late GU toxicity [RR = 1.03, 95%CI (0.82, 1.30)] and overall survival [RR = 1.07, 95%CI (0.96, 1.19)], while IMRT slightly increased the morbidity of grade 2–4 acute GU toxicity [RR = 1.08, 95%CI (1.00, 1.17)]. Conclusions Although some bias cannot be ignored, IMRT appears to be a better choice for the treatment of prostate cancer when compared with 3DCRT.

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.

Upregulated N-cadherin expression is associated with poor prognosis in epithelial-derived solid tumours: A meta-analysis

N‐cadherin is an important molecular in epithelial‐mesenchymal transition (EMT) and has been reported to be associated with aggressive behaviours of tumours. However, prognostic value of N‐cadherin in solid malignancies remains controversially.

Psychosocial response and symptom burden for male smokers with lung cancer.

PURPOSE Cigarette smoking causes many kinds of cancer, and it is more closely related with lung cancer, rather than other cancers. Smoking is the leading cause of lung cancer and ninety percent of the smokers are male in China, but there is little published data concerning the psychological responses in the male smokers with lung cancer and its influence on the symptom burden. The aim of the study was to verify the hypothesis that male smokers with lung cancer have more positive attitude and less symptom burden, comparing to male non-smokers. METHODS A total of 194 men with cancer in West China Hospital, Sichuan, China, were assessed by self-administered questionnaire. Psychological response was measured by the Chinese version of Mini-Mental Adjustment to Cancer scale (Mini-MAC), and symptom burden was measured by the physical symptom distress scale from the Rotterdam Symptom Checklist (RSCL). RESULTS We found that smokers with lung cancer got higher scores in positive attitude and a smaller symptom burden than non-smokers. Patients with education lower than high school got higher scores of positive attitude compared to college graduate patients (p=0.038). Smokers with lung cancer who knew the potential carcinogenicity of cigarette showed less negative emotions (p=0.011). The psychological response was not affected by age, clinical stage, cell type, smoking duration and amount. CONCLUSIONS Male smokers with lung cancer have a more positive attitude and fewer symptoms, comparing to male non-smokers. Appropriate psychological intervention for non-smokers with lung cancer deserves more attention.