Jing Jia

Background. Preoperative serum level of carcinoembryonic antigen (pCEA) is generally recognized as a prognostic factor for colorectal cancer (CRC), but the stage-specific role of pCEA in colorectal cancer remains unclear. Objective. We investigated the prognostic significance of pCEA levels in different tumor stages of nonmetastatic CRC patients. Methods. Six hundred and fifteen CRC patients at stage I–III were retrospectively analyzed. All of them received curative tumor resection. The X-tile program was used to generate stage-specific cutoff values of pCEA for all patients and two subpopulations (lymph node-positive or -negative). The prognostic significance of pCEA was assessed using Kaplan–Meier analysis and Cox proportional hazards regression analysis. A nomogram model that combined pCEA score and clinical feature indexes was established and evaluated. Results. Two cutoff values were identified in the study population. At a cutoff value of 4.9 ng/mL, a significantly higher 5-year overall survival (OS) rate (82.16%) was observed in the pCEA-low group ( ) in the subpopulation of lymph node metastasis (stage III) patients, and the relative survival rates in the pCEA-low (≤4.9 ng/mL), pCEA-medium (4.9–27.2 ng/mL), and pCEA-high (≥27.2 ng/mL) groups were 73.4%, 60.5%, and 24.8%, respectively ( ). However, no such effect was observed in the lymph node nonmetastasis (stage I and II) subgroup. The established nomogram showed acceptable predictive power of the 5-year OS rate (C-index: 0.612) in lymph node-positive CRC patients, with an area under the curve value of 0.772, as assessed by ROC curve analysis. Conclusions. Pretreatment serum CEA levels had different prognostic significance based on the lymph node metastasis status. Among stage III CRC patients, pCEA was an independent prognostic factor. Five-year OS rates could be predicted according to the individual pCEA level at the different cutoff values.

Background: Gastric cancer (GC) is one of the most prevalent and deadly malignancies worldwide. Accumulating reports have indicated the participation of long non-coding RNAs (lncRNAs) in the onset and progression of GC. Methods: GSE109476 data was utilized to screen out lncRNAs dysregulated in GC. Gene expressions were determined by qRT-PCR and western blot. Both in vitro and in vivo experiments were carried out to assess the function of HOXC-AS1 in GC. The association between genes was verified via RIP, ChIP, CoIP, RNA pull down and luciferase reporter assays, as appropriate. Results: HOXC-AS1 was discovered to be upregulated in GC and located both in cytoplasm and in nucleus in GC cells. Functionally, inhibition of HOXC-AS1 restrained GC cell growth and metastasis both in vitro and in vivo. Moreover, HOXC-AS1 was proved to be trans-activated by c-MYC in GC. In return, HOXC-AS1 positively regulated MYC expression in GC through targeting miR-590-3p/MYC axis in cytoplasm and modulating BRG1/β-catenin complex-activated MYC transcription in nucleus. Furthermore, the rescue assays verified that MYC mediated HOXC-AS1-affected GC progression. Conclusion: Our research illustrated a feedback loop of HOXC-AS1-MYC in aggravating GC cell growth and metastasis, highlighting HOXC-AS1 as a promising target for GC diagnosis and treatment.

Background Choledocholithiasis can be managed by transcystic (TC) and transduct (TD) stone extraction or using cholangioscopy through the left hepatic duct orifice (LHD). Objective The aim of this study is to evaluate the safety and effectiveness of common bile duct exploration through the TC approach, TD approach, and LHD approach for choledocholithiasis, with a specific emphasis on the TC and LHD approaches versus the TD approach. Methods Between January 2011 and June 2014, a total of 172 choledocholithiasis patients accompanied by cholecystitis and/or left intrahepatic gallstones were scheduled for laparoscopic or open common bile duct (CBD) exploration using cholangioscopy through the CBD (TD group: n = 72), cystic duct (TC group: n = 63), or LHD orifice (LHD group: n = 37). T-tube insertion was performed in selected patients. Patients were regularly followed up at bimonthly intervals or more frequently in presence of any symptom. Primary outcomes measures included overall operative time, length of hospital stay, and postoperative bile leaks. Results Successful bile duct clearance was 100 % in the TD group, 93.6 % in the TC group, and 90.9 % in the LHD group. Sixteen cases in the TD group had T-tube placement in contrast to no cases in the TC and LHD groups. There were more bile leaks after TD stone extraction (12.5 %) than TC (3.2 %) and LHD stone extraction (0 %), which prolonged hospitalization in the TD group more than in the TC and LHD groups. For choledocholithiasis patients accompanied by cholecystitis, 2 groups (TC and TD groups) were comparable in operative time. However, for choledocholithiasis patients accompanied by left intrahepatic gallstones, the LHD group had a significantly shorter operative time than the TD group (121.1 ± 16.9 minutes vs. 149.3 ± 42.8 minutes, p < 0.05). Conclusion The TD group had a higher stone clearance rate but was associated with a higher risk of bile leaks. TC and LHD stone extraction, which seems to be the more effective approach with lower complication rates, is an accessible technique that simplifies the operation procedure by avoiding choledochotomy and subsequent T-tube insertion.

Krüppel-like factor 5 (KLF5) is frequently deleted and inactivated in prostate cancer, and exerts tumor-suppressing function in prostate cancer cells. However, the function of KLF5 in the apoptosis of prostate cancer cells remains unclear. In the present study, the effect of KLF5 on phorbol 12-myristate 13-acetate (PMA)-induced apoptosis was investigated in prostate cancer LNCaP cells. It was demonstrated that PMA induced the expression of KLF5 at the mRNA and protein level. To identify whether KLF5 regulates the activity of the downstream pathway, stable KLF5 knockdown or overexpression cell lines were constructed with lentivirus harboring shRNA targeting KLF5 or full-length KLF5 in LNCaP cells. Knockdown of KLF5 significantly decreased PMA-induced apoptosis, while cell apoptosis was significantly increased following KLF5 overexpression compared with the corresponding control groups. Consistently, expression of cleaved poly(ADP-ribose) polymerase and caspase-3 induced by PMA was decreased following KLF5 knockdown and increased following KLF5 overexpression. Using the control medium from cells treated with PMA, it was demonstrated that KLF5 is required for the control medium to induce apoptosis. c-Jun N-terminal kinase (JNK) activity is essential for the apoptosis induced by PMA. It was revealed that knockdown of KLF5 decreased, while overexpression of KLF5 increased the phosphorylation of JNK induced by PMA and control medium treatment. Furthermore, inhibition of tumor necrosis factor α (TNFα) decreased KLF5 expression and significantly decreased cell apoptosis induced by PMA, and control medium. This data indicates that KLF5 is essential for the apoptosis induced by PMA in LNCaP prostate cancer cells. Furthermore, KLF5 is essential for activity of the autocrine factor TNFα, which is secreted by cells treated with PMA and mediates the function of PMA-induced apoptosis through regulating the activity of JNK signaling pathway. These results provide novel insights into the complexity of the signaling pathways regulating apoptosis in prostate cancer cells, which could aid in the development of novel treatments for patients with prostate cancer.

Tyroserleutide (YSL), extracted from spleen of pigs, is a tripeptide that has shown therapeutic efficacy in an experimental BEL-7402 human hepatocarcinoma model. The hollow fiber assay (HFA) is a solid tumor model for large-scale screening of potential anticancer compounds that minimizes expenditures of materials, time, and money. Tumor cells are cultivated within biocompatible, semipermeable hollow fibers, which are implanted in immunosuppressed mice. In this study, the HFA was used to investigate the therapeutic efficacy of YSL for human hepatocarcinoma. In vitro effects of YSL on human hepatocarcinoma cell lines BEL-7402, SMMC-7721, Hep3B, HepG2, and SK-HEP-1 were assayed by the MTS method. In vivo effects of YSL on the five human hepatocarcinoma cell lines were assayed by HFA. Mice implanted with tumor cells in hollow fibers were treated with YSL, and the effects of YSL on tumor cell populations were assessed by MTT assay. YSL significantly inhibited the proliferation of the five human hepatocarcinoma, both in vitro and in vivo (P < 0.05). The HFA is a rapid, accurate, and economical method for evaluating the inhibitory effects of drugs on different tumor cells in vivo. These results support the clinical application of YSL for treatment of human hepatocarcinoma.