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2.
Onco Targets Ther ; 12: 309-317, 2019.
Article in English | MEDLINE | ID: mdl-30643429

ABSTRACT

OBJECTIVE: Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of cells derived from bone marrow, which has a significant ability in inhibition of immune cell response. In this study, the role of miR-6991-3p in regulating function of MDSCs was investigated. METHODS: MDSCs were isolated from different tissues of the control and hepatoma-bearing mice, and then expression of miR-6991-3p was detected with qPCR. Then, the miR-6991-3p mimic and inhibitor were respectively transfected into MDSCs, and behaviors of MDSCs were evaluated, including expansion, apoptosis, and production of inflammatory factors. Furthermore, we explored the underlying mechanism from which miR-6991-3p regulated MDSC functions. RESULTS: Expression miR-6991-3p was markedly decreased in the MDSCs derived from spleen and further decreased in the MDSCs derived from the tumor tissue. MiR-6991-3p mimic transfection suppressed expansion and promoted apoptosis of MDSCs, accompanied by a significant decrease in the production of IL-6 and GM-CSF that are identified as stimulators in MDSC expansion. In contrast, miR-6991-3p inhibitor transfection displayed the opposite effect. miR-6991-3p bound with and negatively regulated expression of LGALS9, a newly identified immune checkpoint gene and activator of STAT3, suppressing production of multiple factors that were customarily used to characterize the activation of MDSCs. MiR-6991-3p-accommodated MDSCs displayed less suppression on T cells, while miR-6991-3p inhibitor enhanced the suppression of MDSCs on T cells. CONCLUSION: MiR-6991-3p is identified as a novel suppressor in the expansion and activation of myeloid-derived suppressor cells, which may be regarded as a promising target for modulating the function of MDSCs.

3.
RSC Adv ; 8(72): 41415-41421, 2018 Dec 07.
Article in English | MEDLINE | ID: mdl-35559288

ABSTRACT

HOXB5, a member of the HOX gene family, is a developmental gene which encodes homeoproteins and is known to be a crucial player in development of enteric nervous systems. Recently, HOXB5 was reported to be associated with cancer progression. However, the specific effect of HOXB5 in hepatocellular carcinoma (HCC) remains unclear. In this study, we demonstrated the important role of HOXB5 in HCC. We showed that HOXB5 was up-regulated in HCC tissues and cell lines. Furthermore, down-regulation of HOXB5 inhibited TGF-ß-induced HCC cell migration and invasion in vitro and suppressed tumor metastasis in vivo. We also found that the PI3K/Akt pathway partly accounted for the mechanisms underlying the inhibitory effect of HOXB5 down-regulation on TGF-ß-induced HCC progression. Taken together, these findings demonstrated that down-regulation of HOXB5 inhibits TGF-ß-induced migration and invasion in HCC cells via inactivation of the PI3K/Akt pathway. Thus, HOXB5 may be a novel therapeutic target for HCC treatment.

4.
Exp Mol Med ; 49(9): e383, 2017 09 29.
Article in English | MEDLINE | ID: mdl-28960212

ABSTRACT

The primary purpose of this study was to explore the short-term efficacy of different cisplatin and fluorouracil-based chemotherapy regimens in the treatment of patients with esophagogastric junctional adenocarcinoma (EGJA) using a network meta-analysis (NMA). Randomized controlled trials (RCTs) related to chemotherapy regimens based on cisplatin and fluorouracil for EGJA were included from the PubMed, EMBASE and Cochrane Library electronic databases (from inception to June 2016). Direct and indirect evidence were combined to calculate the pooled odds ratio (OR) and its 95% confidence interval (95% CI) as well as to draw the surface under the cumulative ranking (SUCRA) curves. This NMA finally enrolled ten eligible RCTs with the following five regimens: cisplatin plus fluorouracil (cisplatin+fluorouracil), cisplatin+fluorouracil-based chemotherapy (cisplatin+fluorouracil+docetaxel/epirubicin/irinotecan), fluorouracil-based chemotherapy (fluorouracil+docetaxel/doxorubicin/methotrexate/irinotecan), cisplatin-based chemotherapy (cisplatin+docetaxel/epirubicin/irinotecan/capecitabine/s-1) and other drug-based chemotherapy (docetaxel/irinotecan/capecitabine). These results revealed that compared with a cisplatin+ fluorouracil-based chemotherapy regimen, the fluorouracil-based chemotherapy regimen had a lower overall response rate (ORR) and partial response (PR) for EGJA patients (ORR: OR=0.43, 95% CI=0.22-0.86; PR: OR=0.46, 95% CI=0.23-0.91). Cluster analyses suggested that the cisplatin+fluorouracil-based chemotherapy regimen had the best short-term efficacy for EGJA in terms of the complete response (CR), PR, ORR, stable disease (SD) and progression disease (PD). Our results indicated that cisplatin+fluorouracil-based chemotherapy regimens may have the best short-term efficacy in the treatment of EGJA.


Subject(s)
Adenocarcinoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Esophageal Neoplasms/drug therapy , Esophagogastric Junction/pathology , Stomach Neoplasms/drug therapy , Adenocarcinoma/diagnosis , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/administration & dosage , Cluster Analysis , Disease Progression , Esophageal Neoplasms/diagnosis , Fluorouracil/administration & dosage , Humans , Network Meta-Analysis , Odds Ratio , Publication Bias , Stomach Neoplasms/diagnosis , Time Factors , Treatment Outcome
5.
Zhongguo Gu Shang ; 25(8): 670-3, 2012 Aug.
Article in Chinese | MEDLINE | ID: mdl-25058961

ABSTRACT

OBJECTIVE: To compare therapeutic effects between surgical and conservative treatment for postoperative lumbar discitis. METHODS: From January 2004 to January 2009, 41 patients (17 males and 24 females ranging the age from 37 to 68 years with an average of 53.6 years) with postoperative lumbar discitis were retrospectively studied and divided into two groups. There were 19 patients in operation group, 22 patients in conservative group. Clinical data and features,image data, laboratory examinations, antibiotics utilization, hospital stays and sequelae were recorded and analyzed. Visual analogue scales system (VAS) and Oswestry disability index (ODI) were applied to evaluate therapeutic effects. RESULTS: All patients were followed up over 2 years. Imaging revealed good bone fusion and no occurrence of discitis. VAS score and ODI at 1 month, 1 year and 2 years were significantly improved after treatment (P < 0.01). While VAS and ODI in operation group at 1 month were improved more than that of conservative group (P < 0.01), and there was no significant difference between two groups at 1 year and 2 years (P > 0.01). CONCLUSION: Surgical and conservative treatment for postoperative lumbar discitis is effective. Surgical treatment is superior to conservative treatment in a short time, while conservative treatment can achieve long-term satisfactory curative effects.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Discitis/drug therapy , Discitis/surgery , Lumbar Vertebrae/drug effects , Lumbar Vertebrae/surgery , Postoperative Complications/drug therapy , Postoperative Complications/surgery , Adult , Aged , Anti-Bacterial Agents/pharmacology , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome
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