Short-term outcomes and prognosis of laparoscopy-assisted total gastrectomy in elderly patients with stomach cancer.

BACKGROUND: The aim of this study was to evaluate the short-term outcomes and prognosis of laparoscopy-assisted total gastrectomy (LTG) in elderly patients with gastric cancer. METHODS: The clinical data of 275 patients aged over 65 years undergoing open total gastrectomy (OTG, n = 184) or laparoscopy-assisted total gastrectomy (LTG, n = 91) were reviewed from January 2015 to August 2017 at the First Affiliated Hospital of the University of Science and Technology of China. Short-term outcomes were compared between the two groups, and risk factors for postoperative complications were explored. In addition, the 2-year overall survival (OS) and disease-free survival (DFS) were investigated for both groups. RESULTS: Except for the ASA score (P = 0.01), there was no significant difference regarding patient baselines between the two groups. Patients in the LTG group had a longer operative time (P < 0.001), less intraoperative blood loss (P = 0.004), a shorter time of resumption to a semi-liquid diet (P < 0.001) and a shorter postoperative hospital stay (P = 0.001). The incidence of pulmonary complications was significantly lower in the LTG group than in the OTG group (4.4% vs. 13%, P = 0.026). The number of lymph nodes harvested in the LTG group was higher than that in the OTG group (20.7 ± 7.4 vs. 17.5 ± 6.9, P = 0.001), and the proportion of patients with TNM stage III gastric cancer was higher in the LTG group than in the OTG group (P = 0.035). There was no significant difference in the 2-year OS rate or 2-year DFS rate between the two groups (P = 0.057 and P = 0.344). Sex, age, preoperative comorbidity, intraoperative blood loss, and TNM stage were identified as independent prognostic factors for postoperative survival. CONCLUSION: Comparing with OTG, LTG is feasible and contributes to less surgical trauma and a faster recovery after total gastrectomy. In addition, LTG contributes to a lower risk of postoperative pulmonary complications. Regarding oncological results, LTG is more effective for lymph node dissection and has a comparable long-term prognosis as OTG.

MicroRNA-585 suppresses tumor proliferation and migration in gastric cancer by directly targeting MAPK1.

Increasing evidence reveals that microRNA contributes to the development and progression of gastric cancer (GC), but the roles of miR-585 in GC remain unclear. In this study, we confirmed that miR-585 was down-regulated in GC tissues and cell lines and that miR-585 expression was related to extent of invasion, TNM stage, lymph node invasion and poor prognosis. Our results showed that miR-585 inhibits the proliferation and migration of GC, and MAPK1 is a direct and functional target of miR-585. Our study sheds light on the role of miR-585 as a suppressor for tumor growth and metastasis and raises the intriguing possibility that miR-585 may serve as a new potential marker for monitoring and treating GC.

6-C-methyl flavonoids isolated from Pinus densata inhibit the proliferation and promote the apoptosis of the HL-60 human promyelocytic leukaemia cell line.

Three structurally related 6-C-methyl flavonoids isolated from Pinus densata, including 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone (PD1), 5,7,4'-trihydroxy-3,8-dimethoxy-6-C-methylflavone (PD2), and 5,7,4'-trihydroxy-3-methoxy-6-C-methylflavone (PD3), were tested for their ability to inhibit the proliferation and promote the apoptosis of the HL-60 human leukaemia cell line. Cytotoxicity assays in the HL-60 human cancer cell line demonstrated that 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone exhibited the most potent cytotoxicity of the three structurally related 6-C-methyl flavonoids. 5,4'-Dihydroxy-3,7,8-trimethoxy-6-C-methylflavone inhibited the proliferation of HL-60 cells in a dose-dependent manner with an IC50 of 7.91 µM (48 h treatment). Furthermore, 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone-induced apoptosis was associated with mitochondrial membrane disruption and cytochome c release. Flow cytometry analyses revealed an increase in the hypodiploid population in 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone-treated HL-60 cells. Treatment with a concentration of 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone that induced apoptosis activated caspase-3 but did not activate caspase-1. A caspase-3 inhibitor (Ac-DEVD-CHO), but not a caspase-1 inhibitor (Ac-YVAD-CHO), reversed the cytotoxic effects of 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone in HL-60 cells. These data demonstrated that 5,4'-dihydroxy-3,7,8-trimethoxy-6-C-methylflavone effectively induced the apoptosis of HL-60 cells and exhibited significant anticancer activity via the mitochondrial caspase-3-dependent apoptosis pathway.

Alkaloids from Cephalotaxus lanceolata and their cytotoxicities.

A phytochemical investigation of the branches and leaves of Cephalotaxus lanceolata resulted in the isolation of three new cephalotaxus alkaloids, cephalancetines A, B, and D (1, 2, and 4, resp.), together with ten known alkaloids, 3 and 5-13. The structures of the alkaloids were elucidated on the basis of spectroscopic analyses, including 1D- and 2D-NMR, and HR-ESI-MS, and single-crystal X-ray diffraction. All isolated compounds were tested for their cytotoxicities against four human tumor cell lines, A549, HCT116, SK-BR-3, and HepG2. Compounds 12 and 13 showed remarkable activities against A549, HCT116, and HepG2 cell lines.

Marked paper: Type 2 diabetes mellitus indicates increased postoperative complications and poor prognosis in colorectal cancer patients receiving curative surgery.

Purpose: This study aimed to evaluate the impact of type 2 diabetes mellitus (T2DM) on the short-term outcomes and long-term survival of patients with colorectal cancer (CRC) who underwent curative resection. Methods: This study retrospectively included 136 patients (T2DM group) with resectable CRC and T2DM from Jan 2013 to Dec 2017. Propensity score-matched control group consisting of 136 patients (non-T2DM group) were selected from 1143 CRC patients without T2DM. The short-term outcomes and prognosis were compared between the T2DM and non-T2DM group. Results: A total of 272 patients (136 patients for each group) were included in this study. Patients in T2DM group had higher body mass index (BMI), higher proportion of hypertension and cerebrovascular diseases (P<0.05). T2DM group had more overall complications (P=0.001), more major complications (P=0.003) and higher risk of reoperation (P=0.007) when compared with non-T2DM patients. T2DM patients had longer hospitalization time than non-T2DM (20.7 ± 10.2 vs. 17.5 ± 6.2, P=0.002). As for the prognosis, T2DM patients had worse 5-year overall survival (OS) (P=0.024) and 5-year disease-free survival (DFS) (P=0.019) in all stage. Moreover, T2DM and TNM stage were the independent predictors of OS and DFS for CRC patients. Conclusions: T2DM increases overall complications and major complications, and prolongs the hospitalization time after CRC surgery. In addition, T2DM indicates the poor prognosis of CRC patients. A prospective study with large sample size is required to confirm our findings.

New alkaloids from Lycopodium japonicum.

Three new alkaloids (1-3), together with ten known alkaloids, were isolated from the ethanolic extract of the whole plants of Lycopodium japonicum THUNB. Their structures were elucidated on the basis of spectroscopic analysis, including MS and NMR methods. All alkaloids isolated were assayed for cytotoxic activity against four human cancer cell lines and acetylcholinesterase (AChE) inhibitory activity. No alkaloid showed either cytotoxic activity against four human cancer cell lines or AChE inhibitory activity.

Long non-coding RNA BX357664 inhibits gastric cancer progression by sponging miR-183a-3p to regulate the PTEN expression and PI3K/AKT pathway.

Lately, long non-coding RNA (lncRNA) is recognized as a key regulator of gastric cancer (GC) which has aroused great interest in the fields of medicine, toxicology, and functional food. Studies related to LncRNA expression microarray data indicate that BX357664 is down-regulated in GC specimens. However, the expression pattern and molecular mechanism of BX357664 in GC have not been studied so far. The purpose of this study was to investigate the expression of lncRNA BX357664 in GC and its function in GC cell lines. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the level of BX357664 in 50 pairs of cancer tissues and adjacent non-cancer tissues collected from GC patients. It was found that BX357664 level was lowered in cancer specimens than adjacent non-cancer tissues and correlated with tumor size and TNM stage. Also, we used cell counting kit 8 (CCK8), cell clone formation assay and transwell assay, which affirmed that up-regulation of BX357664 inhibited the proliferation, migration, and invasion of GC cells, but promoted apoptosis. In the dual-luciferase report analysis, BX357664 acted as a miR-183-3p ceRNA to target and regulate the expression of PTEN and affect the PI3K/AKT pathway. These results indicate that BX357664 can inhibit the proliferation and metastasis of GC through the miR-183-3p/PTEN/PI3K/AKT pathway, which may serve as potential targets for the treatment of GC in the future.

Circular RNA circ_0006282 Contributes to the Progression of Gastric Cancer by Sponging miR-155 to Upregulate the Expression of FBXO22.

BACKGROUND: There is increasing evidence that circular RNAs (circRNAs) play an important role in human cancers. As a newly identified human circular RNA, circ_0006282 is abnormally expressed in several types of cancers and promotes the development of cancers. However, the expression and function of circ_0006282 in gastric cancer (GC) remain unclear. METHODS: The expression of circ_0006282 in cancer tissues and adjacent non-cancer tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR) method, and the relationship between circ_0006282 expression and clinicopathological parameters was analyzed. After knockdown of circ_0006282 by RNA interference in GC cells, CCK-8 assay, colony formation and transwell assays were conducted to examine the effects of circ_0006282 on GC cells. The influence of circ_0006282 on tumor growth in vivo was assessed in a xenograft model. Furthermore, regulatory relationship between circ_0006282, miR-155 and FBXO22 was detected by luciferase assay, qRT-PCR and Western blot. RESULTS: The expression of circ_0006282 in GC tissues was significantly higher than its adjacent non-cancer tissues and over-expression of circ_0006282 was associated with tumor size, lymph nodes metastasis and TNM stage, but no obvious links with other pathological parameters. Knockdown of circ_0006282 inhibited the proliferation and metastasis ability of GC cells in vitro and suppressed the tumor growth in vivo. Furthermore, mechanistic investigations suggested that circ_0006282 served as a competing endogenous RNA (ceRNA) of miR-155. Moreover, FBXO22 was identified as the functional target of miR-155 and down-expression of circ_0006282 inhibited FBXO22 expression. Rescue assays also demonstrated that the oncogenic function of circ_0006282 is partly attributed to its regulation on miR-155/FBXO22 axis. CONCLUSION: Our findings indicated that over-expression of circ_0006282 down­regulated miR-155 to activate the expression of FBXO22, thus promoting proliferation and metastasis of GC cells, which provides a promising therapeutic target for GC treatment.

Calcium-sensing receptor promotes tumor proliferation and migration in human intrahepatic cholangiocarcinoma by targeting ERK signaling pathway.

The Calcium-sensing receptor (CaSR) is functionally expressed in the biliary epithelial cells and it has been verified to possess various regulatory functions in several different forms of human cancers. But its pathological role in human intrahepatic cholangiocarcinoma (ICC) development remains obscure. Here, we confirmed that CaSR expression was up-regulated in ICC tumor specimens and cell lines, which was positively correlated with number of tumors, lymph node metastasis and poor prognosis of ICC patients. CaSR activation induced by CaCl2 or Calindol (a selective CaSR agonist) markedly facilitated cell proliferation and migration in ICC cells, while knockdown of CaSR or NPS2143 treatment (a CaSR antagonist) dramatically suppressed the above effects. We also demonstrated that alteration of CaSR activity mediated tumorigenesis and growth of ICC in vivo. Mechanistically, CaSR activation could promote cell cycle progression and induce an upregulation of MMP-2 and MMP-9 expression partly via the simulation of ERK1/2 signaling pathway. And further inhibition of ERK pathway significantly suppressed ICC cell viability and migration capacity. Together, our findings shed novel light on the role of CaSR as an oncogene in ICC progression and indicated that modulation of CaSR might serve as a preventive or therapeutic strategy for ICC.

[Effect of anastomotic reinforcing sutures on the incidence of anastomotic leakage after laparoscopic radical resection of rectal cancer: a prospective randomized controlled trial].

OBJECTIVE: To investigate the effect of anastomotic reinforcing sutures on the incidence of anastomotic leakage after laparoscopic radical resection of rectal cancer. METHODS: In this study, 300 patients diagnosed with rectal cancer, scheduled to undergo laparoscopic anterior resection at the Department of Gastrointestinal Surgery of Anhui Provincial Hospital, between September 2014 and December 2016, were prospectively enrolled. Patients were randomly assigned to undergo laparoscopic rectal resection with (reinforcing group, n=150) or without (control group, n=150) anastomotic reinforcing sutures. The laparoscopic total mesorectal excision was followed for all patients. In the reinforcing group, 4-0 absorbable sutures were used to reinforce the 2-4 needles used for the 2 cross-cutting lines that formed the stapler. Concurrent obstructions; the need for hemorrhagic emergency surgery, preventive ileostomy, Hartmann operation, abdominoperineal resection, or open surgery; and the presence of unresectable cancer were all reasons for excluding patients from the study. Univariate and multivariate analyses were performed on the clinical data collected for the two groups. According to the multivariate analysis results, patients were further divided into high-risk(≥2 high risk factors) and low-risk (≤1 high risk factor) groups, and were stratified to analyze the relationship between reinforcing suture use and the incidence of anastomotic leakage. This trial, approved by the Ethics Committee of Anhui Provincial Hospital, was registered as NCT02830633. RESULTS: A total of 291 patients were included in the study, namely 145 in the reinforcing group and 146 in the control group. There were no significant differences between the two groups with respect to their general data or intra-operative conditions(all P>0.05). The overall incidence of anastomotic leakage was 7.6%(22/291); 3.4%(5/145) in the reinforcing group and 11.6% (17/146) in the control group(χ2=6.992, P=0.008). Multivariate analyses showed that the lack of reinforcing sutures was an independent risk factor for anastomotic leakage (OR=2.75; 95%CI, 1.72-5.48; P=0.014). Other independent risk factors included NRS2002 score ≥3 points, tumor diameter ≥4 cm, and tumor to anal margin distance <5 cm. There were 80 patients in the high-risk group and 211 in the low-risk group, based on the aforementioned 3 risk factors. The incidence of anastomotic leakage was 27.1%(13/48) among the control patients in the high-risk group, but only 6.2% (2/32) among high-risk patients receiving reinforcing anastomotic sutures(χ2=5.470, P=0.019). In the low-risk group, the incidence of anastomotic leakage was 2.7%(3/113) among patients receiving reinforcing anastomotic sutures, and 4.1%(4/98) among those not receiving reinforcing sutures. No significant difference was observed (χ2=0.333, P=0.564). CONCLUSION: Anastomotic reinforcing sutures for the prevention of anastomotic leakage after laparoscopic radical resection of rectal cancer is convenient and effective, particularly for patients with multiple risk factors.

Circular RNA hsa_circ_0000745 may serve as a diagnostic marker for gastric cancer.

AIM: To determine whether circular RNAs (circRNAs) are involved in pathological processes of gastric cancer (GC). METHODS: Three circRNAs with differential expression in GC and colorectal cancer were randomly selected for validation by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), using 20 pairs of gastric tissues and normal tissues. Based on the predicted circRNA-miRNA network, we then focused on hsa_circ_0000745, which was found to be down-regulated in 20 GC tissues compared with normal tissues. The hsa_circ_0000745 levels were further analyzed by qRT-PCR in 60 GC tissues and paired adjacent non-tumor tissues, as well as 60 plasma samples from GC patients and 60 plasma samples from healthy controls. The associations between the levels of hsa_circ_0000745 and the clinicopathological features of GC patients were statistically assessed. A receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of hsa_circ_0000745 in GC. RESULTS: Hsa_circ_0000745 was down-regulated in GC tissues vs non-tumorous tissues (P < 0.001) and in plasma samples from patients with GC vs healthy controls (P < 0.001). The expression level of hsa_circ_0000745 in GC tissues correlated with tumor differentiation, while the expression level in plasma correlated with tumor-node-metastasis stage. The area under the ROC curve (AUC) of hsa_circ_0000745 in plasma was 0.683, suggesting good diagnostic value. Plasma hsa_circ_0000745 level combined with carcinoembryogenic antigen (CEA) level increased the AUC to 0.775. CONCLUSION: Hsa_circ_0000745 plays an important role in GC and its expression level in plasma in combination with CEA level is a promising diagnostic marker for this malignancy.

Pseudolaridimers A and B, hetero-cycloartane-labdane Diels-Alder adducts from the cone of Pseudolarix amabilis.

Pseudolaridimers A (1) and B (2), two unprecedented heterodimers formed via a [4 + 2] Diels-Alder cycloaddition between a cycloartane triterpenoid unit and a labdane diterpenoid unit, were isolated from the cones of Pseudolarix amabilis. Their structures were established by extensive analysis of HRESIMS and NMR spectra. The absolute configuration of 1 was determined by single crystal X-ray diffraction (CuK(α)) of its methyl esterified derivative. Pseudolaridimer A (1) showed strong cytotoxicity against HCT116, ZR-75-30, and HL-60 human tumor cell lines, with IC(50) values 9.62, 7.84, 8.29 µg/mL, respectively. Pseudolaridimer B (2) only exhibited potent inhibition against the HL-60 cell line with an IC(50) value of 7.50 µg/mL.