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Fangxuan L.,Tianjin Medical University | Fangxuan L.,National Clinical Research Center for Cancer | Fangxuan L.,Key Laboratory of Cancer Prevention and Therapy | Fangxuan L.,Tianjins Clinical Research Center for Cancer | And 12 more authors.
International Immunopharmacology | Year: 2017

Indoleamine 2,3-dioxigenase 1 (IDO1) acts in pathogenic inflammatory processes and engender immune tolerance to tumor antigens. IDO1 can decrease the tryptophan and produce a series of toxic kynurenine metabolites to promote the immune toleration via GCN2 pathway, mTOR pathway, toxic effect of kynurenine and favoring differentiation of Tregs. IDO1 can be induced in most human cells, especially APCs and cancer cells through canonical and non-canonical NF-κB and Jak/STAT pathways, as well as PKC and TGF-β signaling pathways. A series of human cancers over-express IDO1 in a constitutive way. Thus, IDO1 is likely to be an attractive target for developing inhibitors of tumor treatments. Many preclinical and clinical trials have been underway and suggest that IDO1 inhibitor maybe an effective tool against a wide range of cancers. However, the IDO1 inhibitor alone had been verified that to be disappointment in achieving effective antitumor efficacy. Concentrating on its molecular mechanism in immune toleration and complex environments of cancer, IDO1 inhibitor could cooperate with chemotherapies and other immune target inhibitors to lessen the tumor. © 2017 Elsevier B.V.

Hui Z.,Tianjin Medical University | Hui Z.,National Clinical Research Center for Cancer | Hui Z.,Key Laboratory of Cancer Immunology and Biotherapy | Hui Z.,Key Laboratory of Cancer Prevention and Therapy | And 16 more authors.
Frontiers in Immunology | Year: 2015

We present the first clinical evidence of advanced squamous non-small cell lung cancer with severe thrombocytopenia showing dramatic improvement after first-line treatment with pembrolizumab plus autologous cytokine-induced killer cells. © 2015 Hui, Zhang, Ren, Li and Ren.

Li F.-X.,Tianjin Medical University | Li F.-X.,National Clinical Research Center for Cancer | Li F.-X.,Key Laboratory of Cancer Prevention and Therapy | Wei L.-J.,Tianjin Medical University | And 11 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2014

Purpose: We aimed to study the relationship between thrombocytosis and clinical features of gastric cancerfocussing on platelet counts and gastric cancer progression through different TNM stages. Methods: According to the normal range of platelet count in our institution, 1,596 patients were divided to two groups: a thrombocytosis group (120 patients, >400×1000/μL) and a control group (1,476 patients, ≤400×1000/μL). Results: The incidence of thrombocytosis was 7.5%. Higher platelet counts were observed in patients with older age, larger tumor size, deeper invasion, lymph node metastasis, distant metastasis and advanced TNM stage. In multivariate logistic regression, tumor size, depth of tumor invasion, lymph node metastasis and TNM stage were independent risk factors for thrombocytosis of gastric cancer patients. On prognostic analysis, age, tumor size, tumor location, histologic type, depth of tumor invasion, lymph node metastasis, distant metastasis and TNM stage and platelet count were important factors. Tumor size, invasion depth, lymph node metastasis, TNM stage and the platelet count were independent prognostic factors. Conclusion: Thrombocytosis is associated with clinical features of gastric cancer patients and correlates with a poor prognosis.

Hao J.,Tianjin Medical University | Hao J.,National Clinical Research Center for Cancer | Hao J.,Key Laboratory of Cancer Prevention and Therapy | Ding X.-L.,Tianjin Medical University | And 8 more authors.
Chinese Journal of Integrative Medicine | Year: 2016

Objective: To study the effects of Prunella vulgaris polysaccharide (PVP) on human breast carcinoma-associated fibroblasts (CAFs). Methods: Cell viability was detected by 3-[4,5-dimethylthiazol-2-yl]-2,5-(3-carboxymethoxyphenyl)-2-4-sulfophenyl)-2H-tetrazolium (MTS) assay. Wound healing experiment and transwell migration assay were used to investigate the anti-migration effects. Flow cytometry was applied to detect cell apoptosis and cell cycle distribution. Reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay were used to detect the expression of basic fifibroblast growth factor (bFGF) in CAFs. Culture SKBr-3 with CAFs conditioned medium (CAFs-CM) to evaluate the indirect function on the proliferation of breast cancer SKBr-3 cells. Results: PVP inhibited the viability of CAFs by inducing apoptosis (P <0.01) and arresting cell cycle (P <0.01). It also inhibited the migration of CAFs (P <0.01). bFGF promoted CAFs proliferation (P <0.01) and migration (P <0.01), protected CAFs from apoptosis (P <0.05) and reduced G0 phase to 49.06% (P <0.01). However, these effects of bFGF on CAFs could be abrogated by PVP. Culturing SKBr-3 with CAFs-CM, PVP could inhibit the viability of breast cancer SKBr-3 cells indirectly. Moreover, PVP reduced the mRNA expression (P <0.01) and protein secretion of bFGF (P <0.01) in CAFs. Conclusion: PVP could exert an anti-cancer effect on breast CAFs by inhibiting bFGF expression, thus inhibiting the growth of breast cancer SKBr-3 cells indirectly. © 2016 Chinese Association of the Integration of Traditional and Western Medicine and Springer-Verlag Berlin Heidelberg

Li X.,Tianjin Medical University | Li X.,National Clinical Research Center for Cancer | Li X.,Key Laboratory of Cancer Prevention and Therapy | Yu X.,Tianjin Medical University | And 11 more authors.
Oncotarget | Year: 2016

Extracellular matrix metalloproteinase inducer, also knowns as cluster of differentiation 147 (CD147) or basigin, is a widely distributed cell surface glycoprotein that is involved in numerous physiological and pathological functions, especially in tumor invasion and metastasis. Monocarboxylate transporters (MCTs) catalyze the proton-linked transport of monocarboxylates such as L-lactate across the plasma membrane to preserve the intracellular pH and maintain cell homeostasis. As a chaperone to some MCT isoforms, CD147 overexpression significantly contributes to the metabolic transformation of tumor. This overexpression is characterized by accelerated aerobic glycolysis and lactate efflux, and it eventually provides the tumor cells with a metabolic advantage and an invasive phenotype in the acidic tumor microenvironment. This review highlights the roles of CD147 and MCTs in tumor cell metabolism and the associated molecular mechanisms. The regulation of CD147 and MCTs may prove to be with a therapeutic potential for tumors through the metabolic modification of the tumor microenvironment.

Sang Y.,National Clinical Research Center for Cancer | Mei J.,National Clinical Research Center for Cancer | Yu W.,National Clinical Research Center for Cancer | Zhang X.,National Clinical Research Center for Cancer | And 4 more authors.
Chinese Journal of Cancer Biotherapy | Year: 2016

Objective: To analyze expressions of the mismatch repair proteins, MLH1, MSH2 and MSH6, and infiltration of T lymphocytes in tissues of non-small cell lung cancer (NSCLC) and to explore a relationship of microsatellite instability (MSI) with infiltration of T lymphocytes in NSCLC. Methods:One hundred samples of NSCLC tissues diagnosed in Cancer Institute and Hospital, Tianjin Medical University between 2004 and 2010 were collected. Expressions of the MLH1, MSH2 and MSH6, and infiltration of T lymphocytes in the carcinoma tissues were examined with immunohistochemical assay. The carcinoma tissues with one negative expression among the above proteins were determined as MSI, and clinical pathologic characteristics of MSI NSCLC were analyzed. Results: Petection rate of MSI in NSCLC tissues was 24%, that was lower than that in MSS. Infiltration of T lymphocytes in the tissues of MSI NSCLC was obviously higher than that in MSS. Results of the immunohistochemical assays showed that numbers of CD3+, CD4+ and CD8+ T lymphocytes infiltrated in the tissues of MSI NSCLC were significantly higher than those in the tissues of MSS NSCLC (P<0.05). MSI situation in the cases was related with their age (P<0.05) but not with their gender, pathological type of tumor, primary tumor size, involvement of regional lymph node and distant metastasis (P>0.05). Conclusion: MSI affects the tumor immune microenvironment of NSCLC, which might provide a novel predictive indicator for immunotherapy of NSCLC. © 2016, Editorial office of Chinese Journal of Cancer Biotherapy. All rights reserved.

Wei F.,Tianjin Medical University | Wei F.,National Clinical Research Center for Cancer | Wei F.,Tianjin Key Laboratory of Cancer Immunology and Biotherapy | Yang F.,Tianjin Medical University | And 17 more authors.
Oncotarget | Year: 2016

This study investigated the clinical significance of serum soluble Toll-like receptor 4 (sTLR4) in non-small cell lung cancer (NSCLC). A total of 54 NSCLC patients and 13 healthy volunteers were enrolled from January 2012 to December 2013. The patients with NSCLC were characterized by significantly higher serum levels of sTLR4 compared with those in healthy controls (P < 0.01). A positive correlation between serum sTLR4 and tumor stage was found in patients with stages I-III NSCLC. However, serum sTLR4 in patients with metastatic NSCLC was significantly decreased compared with those with stage III NSCLC (P < 0.05). Furthermore, low serum sTLR4 was identified as a prognostic marker for poor survival of early-stage NSCLC patients who received surgical resection. In conclusion, our present study identified sTLR4 as a potential serum biomarker of NSCLC.

Li S.,National Clinical Research Center for Cancer | Yang F.,National Clinical Research Center for Cancer | Ren X.,National Clinical Research Center for Cancer
Drug discoveries & therapeutics | Year: 2015

Hepatocellular carcinoma (HCC) is the most common type of hepatic malignancies, with poor prognosis. Treatment for HCC are limited, especially for patients with advanced disease who are not eligible for curative hepatectomy or hepatic transplantation. Mechanisms of immune response during tumor development have been investigated for decades. The efficacy and safety of immunotherapy have also been tested in clinical treatment of malignancies. Here we reviewed the immunotherapy strategies for HCC, as well as the particularity of liver immune system and the immune tolerance of HCC. Vaccines, adaptive therapy, immune checkpoint blockades and cytokines are included. We hope this review will give us an integral concept on HCC immunotherapy and help the readers to understand the mechanism of immune tolerance in liver cancer.

Fu H.,Tianjin Medical University | Fu H.,National Clinical Research Center for Cancer | Qi L.,National Clinical Research Center for Cancer | Qi L.,Tianjin Medical University | And 8 more authors.
OncoTargets and Therapy | Year: 2016

Metastasis involves epithelial–mesenchymal transition (EMT) and mesenchymal–epithelial transition. Ovol2 belongs to the Ovo-like family (Ovol) of evolutionarily conserved zinc-finger transcription factors that regulate gene expression in various differentiation pro­cesses. Recent studies have demonstrated that Ovols affect mesenchymal–epithelial transition by inducing the expression of miR-200 in a range of human cancers. Downregulated Ovol2 expression is involved in the invasion and metastasis of breast and prostate cancers, but little is known about its expression and prognostic value in other cancers, including hepatocellular carcinoma (HCC). This study was designed to explore the clinical and prognostic significance of Ovol2 in patients with HCC. The expression of Ovol2 in tumor samples from patients with HCC and HCC cell lines was examined using Western blotting, real-time polymerase chain reaction, and immunohistochemistry. The expression levels of EMT-related markers, including E-cadherin, N-cadherin, and vimentin, were detected in relation to Ovol2 expression. The prognostic significance of Ovol2 in patients with HCC was statistically analyzed by Kaplan–Meier and Cox regression analyses. Ovol2 expression was significantly lower in HCC tissues than in adjacent noncancerous tissues. Low expression of Ovol2 was detected in HCC tissues with poor histological differentiation, microvascular invasion, and cirrhosis. A significant relationship was observed between Ovol2 and EMT marker expression levels. Kaplan–Meier analysis showed that overall survival was significantly worse in patients with HCC with low Ovol2 expression, indicating that Ovol2 deletion was an independent predictor of unfavorable prognosis in patients with HCC. Elevated Ovol2 expression may suppress HCC cell invasion and metastasis via restricting EMT. © 2016 Fu et al.

PubMed | Tianjin Medical University and National Clinical Research Center for Cancer
Type: | Journal: Metabolic brain disease | Year: 2016

We investigated the effects of ulinastatin on early postoperative cognitive dysfunction (POCD) after one-lung ventilation (OLV) surgery in elderly patients receiving neoadjuvant chemotherapy. Eighty elderly patients with preoperative neoadjuvant chemotherapy scheduling for radical esophagectomy under OLV were recruited. They were randomly divided into an ulinastatin pretreatment group (U group, n=40) and a control group (C group, n=40). The U group received 10,000U/kg ulinastatin before anesthesia and 5000U/kg daily on postoperative days 1 to 3, while C group received saline. Levels of interleukin (IL)-6, IL-10, C-reactive protein (CRP), and S-100 protein were assayed before surgery, at the end of surgery, and on postoperative days 1 and 3. Patients underwent cognitive assessment 1day before and 7days after surgery. 38 patients in U group and 37 patients in C group completed the neuropsychological tests. The U group had a lower incidence of POCD than C group (23.7% versus 45.9%, P=0.043). The levels of S-100 protein, IL-6, IL-10, and CRP in both groups increased after surgery. The postoperative concentrations of S-100 protein, IL-6, and CRP in U group were lower than those in C group. On postoperative day 3, compared with C group, the level of CRP in U group was lower, while that of IL-10 was higher. These findings demonstrate that ulinastatin can attenuate the elevation of S100 protein levels and the incidence of POCD, most likely by the mechanism of reducing serum IL-6 and CRP levels and increasing IL-10 levels.

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