Validity of combination active specific immunotherapy for colorectal cancer: a meta-analysis of 2993 patients.

BACKGROUND AIMS: The aim of this study was to investigate whether active specific immunotherapy (ASI) is able to demonstrate therapeutic efficacy against colorectal cancer. METHODS: We conducted a systematic review of published papers from MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, the Wanfang Database, the China Science and Technology Periodical Database and China Journal Net. Published data were extracted independently by two authors who used predefined database templates. The effects of ASI were compared with those of surgery alone, and a pooled analysis was performed with the use of the data from random- or fixed-effect models. RESULTS: Twelve trials matched our inclusion criteria (n = 2993, including 1842 control subjects). The overall analysis showed a significant survival benefit [1-, 2-, 3-, 4-, 5-, 6- and 7-year overall survival (OS), P < 0.05; 10-year OS, P < 0.001] in favor of ASI immunotherapy combined with surgery, but there was not an improvement in the 8- or 9-year OS (P > 0.05). The disease-free survival (DFS) rate was improved after the combination of ASI immunotherapy (2-, 3-, 5- and 10-year DFS, P < 0.05), but no significant improvement was noted for the 1-, 4-, 6-, 7-, 8- or 9-year DFS (P > 0.05). In addition, the disease-specific survival (DSS) was improved at some time points after the combination of ASI immunotherapy and surgery (2-, 3-, 4-, 5- and 6-year DSS, P < 0.05, but not the 1-, 7-, 8- or 9-year DSS, P > 0.05). An improved 2-, 3-, 4-, 5- and 6-year recurrence-free interval (RFI) (P < 0.05) was also observed in patients who received ASI therapy, but this was not observed for the 1-year RFI (P > 0.05). Furthermore, an analysis of the recurrence-free survival (RFS) showed that it was significantly increased in the ASI plus surgery group (1-, 2-, 3-, 4-, 5- and 6-year RFS, P < 0.001). The funnel plots showed that the analyses were relatively reliable and the publication bias was small. CONCLUSIONS: The combination of ASI immunotherapy and surgery was superior in prolonging the overall survival time and enhancing the recurrence-free survival rate compared with surgery alone.

Clinical efficacy of autologous stem cell transplantation for the treatment of patients with type 2 diabetes mellitus: a meta-analysis.

BACKGROUND AIMS: In this study, we investigate whether bone marrow mononuclear cells (BM-MNC) or peripheral blood mononuclear cells (PB-MNC) have therapeutic efficacy in type 2 diabetes (T2D). METHODS: Search terms included stem cell, bone marrow cell, peripheral blood cell, umbilical cord blood and T2D in MEDLINE, the Cochrane Controlled Trials Register, EMBASE, the Wanfang Database, the China Science and Technology Periodical Database and China Journal Net. RESULTS: Fifteen trials met our inclusion criteria (n = 497). One group included 266 cases with BM-MNC therapy and the other group contained 231 cases with PB-MNC treatment. Glycosylated hemoglobin was decreased after BM-MNC or PB-MNC therapy compared with that before (12 months: P < 0.001; 6 months: P < 0.001; 3 months: P < 0.05). Fasting plasma glucose was reduced in BM-MNC therapy group compared with control after 12-month follow-up (P < 0.001) and after BM-MNC therapy compared with that before (9 months: P < 0.001) but was not obvious in other stages. Meanwhile, the analysis showed that C-peptide level increased after BM-MNC and PB-MNC therapy compared with the control therapy (12 months: P < 0.001) and with that before therapy (6 months: P < 0.05). Insulin requirement reduction was also observed in patients receiving BM-MNC therapy (3, 6, 9 and 12 months: P < 0.05). CONCLUSIONS: To a certain extent, BM-MNC or PB-MNC therapy for T2D demonstrated superiority of glycemic control, increased insulin biosynthesis and elevated insulin secretion from existing ß-cells and might prevent islet cell loss.

Evaluation of tumour vaccine immunotherapy for the treatment of advanced non-small cell lung cancer: a systematic meta-analysis.

OBJECTIVES: Our meta-analysis performed a systematic evaluation on the therapeutic efficacy and safety of tumour vaccines for the treatment of advanced non-small cell lung cancer (NSCLC). DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCT). DATA SOURCES: PubMed, the Cochrane Center Register of Controlled Trials, Science Direct and EMBASE were searched from January 1980 until January 2015. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: RCT were included; the control arm had to receive either placebo or chemotherapy or no treatment. MAIN OUTCOME MEASURES: The quality of the data from individual papers was assessed for overall survival (OS), clinical response rate and side effects. RESULTS: Overall, 11 RCT of advanced NSCLC with a total of 3986 patients were conducted for meta-analysis. The results showed that the vaccine arm significantly extended primary endpoint median overall survival compared with control group (p<0.00001) (HR 0.760; 95% CI 0.644 to 0.896; p=0.001). Three subgroup patients with tumour vaccine at 1-year, 2-year and 3-year survival rates also gained significant benefits compared with their corresponding control group (p=0.0004, 0.03 and 0.19, respectively). Besides, a significant improvement in median time to progression (TTP), median progression-free survival (PFS) and a trend of improvement in objective response rate were observed after tumour vaccine treatment (p=0.001, 0.005 and 0.05, respectively; median PFS HR 0.842; 95% CI 0.744 to 0.954; p=0.007). A few severe adverse effects occurred in the tumour vaccine group, but fewer side effects were observed in the vaccine group compared with the control group (p<0.00001). CONCLUSIONS: Taken together, NSCLC tumour vaccines markedly prolong median OS (p<0.00001), median TTP (p=0.001) and median PFS (p=0.005), improve clinical response rate (p=0.05) and lessen adverse side effects (p<0.00001). Our meta-analysis suggests tumour vaccines improve the efficacy of the treatment, and also provide superiority in treatment of patients with advanced NSCLC among a variety of immunotherapy strategies.

Active components alignment of Gegenqinlian decoction protects ulcerative colitis by attenuating inflammatory and oxidative stress.

ETHNOPHARMACOLOGICAL RELEVANCE: Gegenqinlian Decoction (GQD) has been used as a folk remedy for gastrointestinal diseases in China over thousands of years. It has significant treatment efficacy for patients with inflammatory bowel disease (IBD). We analyzed and showed that the active components alignment of Gegenqinlian Decoction (ACAG) possesses broad pharmacological effects including analgesic, antipyretic, anti-inflammatory, antibacterial, antiviral and antidiarrhea, as well as the effect of adjusting gastrointestinal function in our preliminary experiments. However, the exact molecular mechanisms on how ACAG exerts these pharmacological effects still remain elusive. In the present study, the plausible pharmacological effects of ACAG on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis were investigated. MATERIALS AND METHODS: Male Sprague-Dawley (SD) rats with TNBS/ethanol-induced colitis were used. The colonic wet weight, macroscopic and histological colon injury, superoxide dismutase (SOD), malonyldialdehyde (MDA), and inducible nitric oxide synthase (iNOS) activity were observed. Pro-inflammation cytokines were determined by ELISA methods, semi-quantitative RT-PCR and Immuno-histochemistry. RESULTS: We showed administration of ACAG was able to improve colitis. This was manifested by a decreased in the score of macroscopic and histological colonic injury, by lowered colonic wet weight, accompanied by significant increased of SOD activity, and decreased of MDA and iNOS activities. The treatment also significantly reduced tumor necrosis factor-alpha (TNF-α) and interleukin-1ß (IL-1ß) levels in colon and serum as well as the colonic mRNA levels for several inflammatory cytokines such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), macrophage inflammatory protein-2 (MIP-2), intercellular adhesion molecule-1 (ICAM-1) and toll-like receptor 2, 4 (TLR2, TLR4). In addition, we also showed that ACAG was able to inhibit the activation and translocation of transcription factors, nuclear factor kappaBp65 (NF-κBp65) in colon. CONCLUSIONS: Our results suggest that ACAG exhibits protective effect in TNBS-induced ulcerative colitis. We postulate that this might be due to its modulation of oxidant/anti-oxidant balance, downregulation of productions, expressions of pro-inflammatory cytokines and inhibition of NF-κBp65 signal transduction pathways.

Adoptive immunotherapy of cytokine-induced killer cell therapy in the treatment of non-small cell lung cancer.

AIM: The aim of this study was to systemically evaluate the therapeutic efficacy of cytokine-induced killer (CIK) cells for the treatment of non-small cell lung cancer. MATERIALS AND METHODS: A computerized search of randomized controlled trials for CIK cell-based therapy was performed. The overall survival, clinical response rate, immunological assessment and side effects were evaluated. RESULTS: Overall, 17 randomized controlled trials of non-small cell lung cancer (NSCLC) with a total of 1172 patients were included in the present analysis. Our study showed that the CIK cell therapy significantly improved the objective response rate and overall survival compared to the non-CIK cell-treated group. After CIK combined therapy, we observed substantially increased percentages of CD3+, CD4+, CD4+CD8+, CD3+CD56+ and NK cells, whereas significant decreases were noted in the percentage of CD8+ and regulatory T cell (Treg) subgroups. A significant increase in Ag-NORs was observed in the CIK-treated patient group (p = 0.00001), whereas carcinoembryonic antigen (CEA) was more likely to be reduced to a normal level after CIK treatment (p = 0.0008). Of the possible major side effects, only the incidence of fever in the CIK group was significantly higher compared to the group that received chemotherapy alone. CONCLUSION: The CIK cell combined therapy demonstrated significant superiority in the overall survival, clinical response rate, and T lymphocytes responses and did not present any evidence of major adverse events in patients with NSCLC.

Cytokine-induced killer cells in the treatment of patients with renal cell carcinoma: a pooled meta-analysis.

Cytokine-induced killer cells (CIKs) have been applied in multifarious cancer. Here, we address the connection between immune therapy and clinical responses by a systematic meta-analysis. A total of 385 patients (including 183 controls) were identified for renal cell cancer (RCC) in the seven selected trials. The estimated pooled complete response and partial response showed a significant improvement for patients receiving CIK immunotherapy compared with non-CIK therapy (p < 0.0001), which was up to 62% of clinical response. The overall analysis showed a significant survival benefit (1-year overall survival [OS]: p = 0.0002; 3-year OS: p < 0.0001) in favor of CIK-based therapy in RCC, thus a statistically significant effect of OS and clinical response was demonstrated in RCC patients.

Clinical efficacy of tumor antigen-pulsed DC treatment for high-grade glioma patients: evidence from a meta-analysis.

BACKGROUND: The effectiveness of immunotherapy for high-grade glioma (HGG) patients remains controversial. To evaluate the therapeutic efficacy of dendritic cells (DCs) alone in the treatment of HGG, we performed a systematic review and meta-analysis in terms of patient survival with relevant published clinical studies. MATERIALS AND METHODS: A total of 409 patients, including historical cohorts, nonrandomized and randomized controls with HGG, were selected for the meta-analysis. RESULTS: The treatment of HGG with DCs was associated with a significantly improved one-year survival (OS) (p<0.001) and 1.5-, 2-, 3-, 4-, and 5-year OS (p<0.001) compared with the non-DC group. A meta-analysis of the patient outcome data revealed that DC immunotherapy has a significant influence on progression-free survival (PFS) in HGG patients, who showed significantly improved 1-,1.5-, 2-, 3- and 4-year PFS (p<0.001). The analysis of Karnofsky performance status (KPS) demonstrated no favorable results for DC cell therapy arm (p = 0.23).The percentages of CD3+CD8+ and CD3+CD4+ T cells and CD16+ lymphocyte subset were not significantly increased in the DC group compared with the baseline levels observed before treatment (p>0.05), whereas CD56+ lymphocyte subset were significantly increased after DC treatment (p = 0.0001). Furthermore, the levels of IFN-γ in the peripheral blood of HGG patients, which reflect the immune function of the patients, were significantly increased after DC immunotherapy (p<0.001). CONCLUSIONS: Thus, our meta-analysis showed that DC immunotherapy markedly prolongs survival rates and progression-free time, enhances immune function, and improves the efficacy of the treatment of HGG patients.

Efficacy of autologous bone marrow mononuclear cell therapy in patients with peripheral arterial disease.

AIM: Peripheral arterial disease (PAD), particularly critical limb ischemia (CLI), is a severe cause of amputation and mortality. More than 50% of diabetic patients with CLI die within four to five years. The development of novel stem cell therapies may bring new hope to these patients. We aimed to assess the efficacy of autologous bone marrow cell therapy for treating CLI using a meta-analysis. METHODS: We searched the literature in PubMed, the Cochrane Central Registry of Controlled Trials, the Elsevier database and EBSCO for trials of autologous cell therapy in patients with severe PAD published before October 30, 2013. We chose objective clinical endpoints to assess the efficacy of therapy in the meta-analysis, including changes in the ankle-brachial index (ABI), transcutaneous oxygen tension (TcO2), pain scale (0-10 scale) and amputation-free survival (AFS). RESULTS: Thirty-one articles reporting clinical trials involving a total of 1,214 patients treated with bone marrow stem cell-based therapy were collected for the meta-analysis, in which the randomized controlled trials (RCTs) and other trials (non-RCTs) were classified into two groups. Regarding the efficacy of stem cell therapy, the ABI showed significant increases (P＜0.05) at 12 , 24 and 48 weeks after therapy in the non-RCT and RCT groups, but not after four to eight weeks in the non-RCT group. The TcO2 values also increased in the RCT group at four to eight weeks after therapy and 24 weeks after therapy (P＜0.001) and in the non-RCT group at four to eight weeks after therapy (P= 0.01), although no significant increases were observed in the RCT group at 12 weeks after therapy or the non-RCT group at 24 weeks after therapy. Meanwhile, pain was significantly reduced (P＜0.05) at four to eight weeks and 24 weeks after therapy in both the non-RCT and RCT groups, but not at four to eight weeks or 12 weeks after therapy in the RCT group. In addition, the long-term clinical trials demonstrated that the AFS rate improved after therapy with bone marrow stem cells (one-year AFS, P＜0.00001; three-year AFS, P=0.0003). CONCLUSIONS: The present results suggest that autologous bone marrow stem cells have an advantageous therapy effect in PAD patients who are not eligible for revascularization.