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Tumor-associated mesenchymal stem cells (MSCs) play a critical role in the growth and metastasis of hepatocellular carcinoma (HCC). However, the mechanism underlying the crosstalk between MSCs and HCC cells is not completely understood. Here, HCC cells were treated with or without conditioned medium of MSCs (CM-MSC), and examined for differential expression of long non-coding RNAs (lncRNAs). Knockdown and overexpression experiments were conducted to explore the function of the lncRNA DNM3OS in MSC-induced HCC growth and metastasis. CM-MSC treatment led to a concentration-dependent induction of DNM3OS in HCC cells. DNM3OS was significantly upregulated in HCC compared to adjacent liver tissues. High DNM3OS expression was associated with TNM stage, vascular invasion, and poor prognosis of HCC patients. Silencing of DNM3OS inhibited HCC cell proliferation and invasion in vitro and tumorigenesis and metastasis in vivo. Overexpression of DNM3OS enhanced HCC cell proliferation, invasion, and metastasis. Biochemically, DNM3OS was mainly localized in the nucleus and physically interacted with KDM6B. The association of DNM3OS with KDM6B induced the expression of TIAM1 through reduction of H3K27me3 at the TIAM1 promoter. TIAM1 overexpression restored the proliferation and invasion of DNM3OS-depleted HCC cells. Our data delineate a mechanism by which MSCs accelerate HCC growth and metastasis through a DNM3OS/KDM6B/TIAM1 axis.

The present study compared the expression levels of limb-bud and heart (LBH) between gastric intestinal-type adenocarcinoma (GITA) and healthy gastric tissues; with the aim of investigating the possible effect of LBH on the prognosis of patients with GITA and to analyze the associated signaling pathways in GITA. Three Oncomine gastric datasets were utilized for the preliminary prediction of the expression levels of LBH mRNA in GITA and healthy gastric tissues. Gene expression and corresponding clinical data of 163 patients with GITA were downloaded from The Cancer Genome Atlas. Wilcoxon signed rank-sum test was used to distinguish the clinical value of LBH expression in the various clinicopathological features. Subsequently, Kaplan-Meier univariate and Cox multivariate survival analyses were performed to determine the prognostic significance of LBH expression in patients with GITA. Function enrichment analysis was conducted for the co-expression gene of LBH, defined as correlation coefficient r>0.06 and P

BACKGROUND Sorafenib, a multiple-target-point kinase inhibitor, has been used as a standard treatment for advanced liver cancer and has shown therapeutic benefits. However, resistance often occurs, prompting the need for identification of synergizing agents. Celastrol is a major active ingredient of Tripterygium wilfordii, which can increase the antitumor effect of traditional antitumor drugs. This work focused on the sensitization of liver cancers in use of celastrol combined with sorafenib. MATERIAL AND METHODS The IC50 values of sorafenib and celastrol on cancer cells were determined through MTT assays. The effects of sorafenib on AKT signaling and VEGF levels in sorafenib-treated cancer cells were analyzed by Western blotting and ELISA, respectively. After combined treatment with celastrol and sorafenib, the survival rate of tumor cells was determined by MTT and clonogenic assays, and the apoptosis rate was also determined by flow cytometry. In addition, the in vivo antitumor activity of celastrol combined with sorafenib was evaluated in Hepa1-6 tumor-bearing mice. RESULTS Sorafenib treatment induced the compensatory activation of the AKT pathway and autocrine VEGF in hepatoma cells, which could be reversed by celastrol. Furthermore, celastrol enhanced the growth inhibition and apoptosis induction of cancer cells by sorafenib both in vitro and in vivo and reduced the dosage of sorafenib needed. CONCLUSIONS Celastrol enhances the antitumor activity of sorafenib in HCC tumor cells by suppressing the AKT pathway and VEGF autocrine system.

Background To find the relationship between prostaglandin E receptor 2 (EP2) and epidermal growth factor receptor (EGFR) in esophageal squamous cell carcinoma (ESCC) patients with regional lymph nodes metastasis (pN+) who had undergone curative resection, and to analyze them in the role of judging prognosis. Methods Sixty-three patients with ESCC who underwent attempted curative esophagectomy with lymph node metastasis were collected. Immunohistochemistry (IHC) was used to analyse the expression of EP2 and EGFR in tumor tissues. We analyzed the relationship between the two markers. Furthermore, we analyzed the role of EP2 and EGFR in disease-free survival (DFS) and overall survival (OS). Results The expression rate of EP2 and EGFR in this study were 73.0%, 85.7%, respectively. And the EP2 status was closely related with the expression of EGFR in tumor tissues (χ2=0.260, P=0.011). The patients with EP2 or EGFR positive expression had a shorter DFS and OS than the negative group. Further analysis found EGFR is an important prognostic factor for DFS and OS (P0.05). Conclusions The expression of EP2 and EGFR were high in tumor tissues of (pN+) ESCC, and they are playing a key role in the prognosis of ESCC patients with local lymph node metastases.

The present study aimed to analyze the clinical characteristics and prognosis-related factors of non-small cell lung cancer (NSCLC) patients with bone metastases at the time of diagnosis. A total of 46 NSCLC patients with skeletal metastases at the time of diagnosis from Anhui Provincial Hospital and Anhui Provincial Cancer Hospital Affiliated to Anhui Medical University (Hefei, China) between February 2010 and February 2012 were investigated retrospectively. The median age was 58 years, with a range of 40–80 years, the ratio of males and females was 2:1, and adenocarcinoma and squamous cell carcinoma accounted for 71.7 and 28.3% of cases, respectively. Furthermore, 84.8% of patients exhibited multiple skeletal metastases at more than two sites and 54.3% of patients experienced skeletal-related events at the time of diagnosis. The median overall survival (OS) time of the patients was 237 days, and Kaplan-Meier analysis demonstrated that patients with adenocarcinoma (P=0.002), single bone metastases (P=0.023), an Eastern Cooperative Oncology Group performance status of 0–1 (P

Objective: The immune makers including CD4+CD25+ T cells, natural killer cells, and T cells subgroup were retrospectively analyzed to find the relationship between apatinib and the immune system in the patients treated with apatinib. Method: Forty-two patients with advanced malignant tumors orally took apatinib as treatment and 16 patients with the same situation did not take apatinib as a control group. These patients were all included in the study, and they orally received apatinib 500 mg daily as monotherapy or combination. The treatment was continued until disease progression or intolerable toxicity. CD4+CD25+ T cells, natural killer cells, and T cells subgroup were detected before and 1 month after therapy for all the patients. The relationship between the changing number of immune cells and progression-free survival was analyzed in this study. Result: For the apatinib group, the rate of CD4+CD25+ T cells significantly increased ( P = .048). The median progression-free survival was 3.25 months for the 42 patients. The median progression-free survival in the patients with the rate of CD4+CD25+ T cells increased and decreased was 5.8 months and 2.9 months, respectively ( P = .012). Multivariate analysis found the increased rate of CD4+CD25+ T cells was an independent prognostic factor for a longer progression-free survival. The rate of natural killer cells and T cells subgroup did not change much after apatinib therapy, and they were not independent prognostic factors for progression-free survival. Conclusion: The rate of CD4+CD25+ T cells is very important in patients with apatinib treatment. The changing number of CD4+CD25+ T cells may be a good indicator for apatinib prognosis. Natural killer cells and T cells subgroup did not change much after apatinib, and they were not independent prognostic factors for progression-free survival.

To investigate the surgical approach, feasibility and surgical outcomes of laparascopic distal gastrectomy D2(LDGD2).Fifty-four patients who underwent LDGD2 were examined in terms of pathologic findings, operative outcomes, and complications. A simple and effective surgical procedure was as follows: gastrocolic ligament--transverse mesocolon anterior lobe--pancreatic capsule--4sb--4d--6--14v, 8a--12a--9--7--11p, 1--3--5--lesser omental bursa. Efficacy and feasibility of this procedure was analyzed.The mean operative time was (236±51) minutes, the mean number of lymph nodes was(18±5), the mean positive lymph nodes were 0-14, the mean blood loss was(217±65) ml, and postoperative mean hospital stay was(15±4) days.LDGD2 for lower and lower-middle gastric cancer is feasible and safe, and can meet the oncological demand.

To explore effective method to avoid iatrogenic bile duct injury during laparoscopic cholecystectomy (LC).10 492 patients underwent LC from May 1996 to May 2006, 8566 of them were treated by the method to identify the cystic duct, common hepatic duct, and common bile duct during LC (tri-duct method group), and the left 1926 cases whose cystic duct failed to be exposed easily were treated with the method to identify at least two of the 4 structures (cystic lymph node, Hartmann's pouch, cystic artery, and emptiness of cystic triangle) so as to help identify the cystic duct (tri-duct plus tri-structure group). The operating time, amount of blood loss, open conversion rate, and morbidity were compared between these 2 groups.No cases of bile leakage or jaundice because of accidental injury of bile duct were found. The operating time of the tri-duct plus tri-structure group was (28 +/- 12) (15 - 52) min, significantly shorter than that of the tri-duct group [(38 +/- 16) (15 - 92) min, P0.05]. The open conversion rate of the tri-duct plus tri-structure group was 1.8%, significantly lower than that of the tri-duct group (8.7%, P0.05). There were no significant difference in the amount of blood loss and morbidity between the two groups (both P0.05).The tri-structure method can not only confirm the cystic duct correctly, thus preventing iatrogenic bile duct injury, but also shorten the operating time and reduce the open conversion ratio during LC.