Cancer Cell Research (Online ISSN: 2161-2609)

Cancer Cell Research 2019 6(24) 628-637; published online  28 October 2019

Abstract: Macrophage colony stimulating factor (M-CSF or CSF1) may accelerate microglial activation through targeting CSF1 receptor (CSF1R), and DNAX-activating protein of 12kDa (DAP12) is suggested to be the downstream of CSF1R. Brain-derived neurotropic factor (BDNF), the key cytokine in the development of hyperalgesia, is reported to be released from activated microglia. We attempted to investigate the mechanisms of CSF1/CSF1R signaling induced BDNF release in microglia. Rat microglia was treated with CSF1. Iba1, iNOS, Arg1, DAP12 and P2 purinoceptors expressions were detected. DAP12 siRNA was transfected with microglia to investigate the expression of purinoceptors. BDNF protein level of the culture medium and cell lysates was measured by ELISA kit. CSF1 promoted a M2 phenotype polarization of microglia and increased P2X4R expression in microglia. BDNF mRNA and protein level was also increased in CSF1 treated microglia, but the secretion of BDNF was depended on activation of ATP/P2X4R pathway. DAP12, the downstream of CSF1R, was responsible for CSF1 induced P2X4R upregulation. These data indicated that CSF1/CSF1R/DAP12 signaling regulated the synthesis of P2X4R and BDNF. And ATP/P2X4R pathway was responsible for BDNF secretion. These contributes may lead to explicit CSF1 induced BDNF release in vitro.

Cancer Cell Research 2019 6(24) 638-643; published online  28 October 2019

Abstract: To compare the safety and recent clinical efficacy of total laparoscopic distal gastrectomy (TLDG) with laparoscopic assisted distal gastrectomy (LADG), and to explore the advantages of TLDG, prospective clinical study methods were used to design gastric cancer patients treated with gastrointestinal surgery in the Affiliated Hospital of Qingdao University from March 2018 to October 2018, total of 60 patients were included in the study, including 30 in the TLDG group and 30 in the LADG group. The cases were divided into TLDG group and LADG group by random number table. The intraoperative and postoperative conditions of the two groups were compared and analyzed to measure the therapeutic effect. The operation time and number of lymph nodes dissected in the TLDG group were higher than those in the LADG group (P>0.05). There was no statistical difference in the distance of the upper cutting edge (P>0.05). The incision length was significantly smaller than that of the LADG group (P<0.05). The first anal exhaust time was earlier than LADG group (P<0.05). The postoperative hospitalization time was shorter than that of the LADG group (P<0.05). The hospitalization cost was slightly higher than that of the LADG group, but the difference was not statistically significant (P>0.05). The white blood cell count on the first day after the operation and the c-reactive protein on the first and third day after the operation were all smaller than the LADG group (P<0.05). VAS pain scores of postoperative patients: all the scores on the first, third and fifth days after the operation were smaller than those in the LADG group (P<0.05). The total amount of postoperative analgesic was lower than that of the LADG group (P<0.05). One case of incision infection and one case of postoperative intestinal obstruction occurred in the LADG group. Gastroparesis occurred in 1 case of TLDG group. Total laparoscopic radical gastrectomy for distal gastric cancer is safe and feasible, and has more advantages than laparoscopic-assisted radical gastrectomy for distal gastric cancer, which is worthy of clinical promotion and application.

Cancer Cell Research 2019 6(24) 644-649; published online  28 October 2019

Abstract: Circulating tumor cells (CTCs) are cells released from primary tumor into bloodstream that associated with tumor metastatic and recurrence. Many studies reveal that circulating tumor cells are thought to play an important role in the poor prognosis of patient with hepatocellular cancer (HCC). HCC is a serious health problem worldwide especially in China due to worse prognosis, high incidence and high mortality. It is an urgent task to identify potentially markers for early diagnosis, surgical treatment, improve management of patients and provide personalized therapy. There are many encouraging studies indicate that CTCs has a great potential use as diagnosis markers for patient with HCC. In this review, we are focus on the advances in studies of HCC CTCs, including the detection of CTCs, the clinical implications, the biological characteristic of HCC CTCs and future perspectives.

Cancer Cell Research 2019 6(24) 650-658; published online  28 October 2019

Abstract: A combination of fibrinogen (FBG), platelet (PLT), neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) (abbreviated as CO-NPF) has been recently evaluated as a marker for prognostication in lung cancer. While previous study on CO-NPF has evaluated in lung adenosquamous patients, the combination of these four markers has not been evaluated in advanced lung adenocarcinoma yet. In this study, we investigated the significance of CO-NPF in predicting the survival of patients with advanced lung adenocarcinoma. 225 patients with pathologically diagnosed lung adenocarcinoma were enrolled. The cutoff values for FBG, PLT, NLR and PLR were defined by receiver operating characteristic (ROC). The CO-NPF was calculated as the combination of FBG, PLT, NLR and PLR based on these cutoff values. Kaplan-Meier analysis and Cox proportional hazard models were used to assess the prognostic value of CO-NPF. Kaplan-Meier analysis reveals that CO-NFP was associated with poorer progressive free survival (PFS) [hazard ratio (HR), 0.657; 95% confidence interval (CI), 0.501-0.862; P=0.002] and overall survival (OS) (HR, 0.701; 95% CI, 0.523-0.938; P=0.016). Cox proportional hazard models further reveals CO-NFP as an independent prognostic factor for PFS (HR, 0.665; 95% CI, 0.504-0.876; P=0.004) and OS (HR, 0.672; 95% CI, 0.495-0.914; P=0.011). CO-NPF can serve as a useful biomarker to predict recurrence and death for patients with advanced lung adenocarcinoma.

Cancer Cell Research 2019 6(24) 659-665; published online  28 October 2019

Abstract: To evaluate the potential value of the plasma level of receptor- interacting protein kinase 3 (RIPK3), a key protein involved in the activation of necroptosis, as a biomarker for the differential diagnosis of lung cancer in patients with lung lesions detected by chest computed tomography. The subjects of this study were divided into 3 groups: lung cancer (n = 30), benign disease (n = 13), and healthy controls (n = 33). The measurement of plasma RIPK3 was performed by enzyme-linked immunosorbent assay. The plasma RIPK3 level in patients with lung cancer (1467.4 ± 347.4 pg/ml) was significantly higher than that in patients with benign disease (1219.8 ± 156.4 pg/ml) and healthy controls (746.2 ± 255.3 pg/ml). Besides, plasma RIPK3 levels that were greater than 970.06 pg/ml provided 96.7% sensitivity and 84.8% specificity for lung cancer. Our results show that plasma RIPK3 levels are higher in lung cancer patients. We suggest that plasma RIPK3 level could be used as an auxiliary tool for distinguishing lung cancer from benign lesions and healthy lungs.