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ObjectiveTo investigate the effect of kinesin family member 15 （KIF15） on the proliferation of hepatocellular carcinoma （HCC） cells and its mechanism of action. MethodsTCGA and GEPIA datasets were analyzed to determine the expression of KIF15 in HCC and its effect on tumor stage and survival. Quantitative real-time PCR and Western blot were used to measure the expression level of KIF15 in human-derived HCC cell lines （HepG2， Hep3B， MHCC-97H， and LM3） and human normal liver cell line L02 cultured in vitro， and Hep3B and HepG2 were selected for subsequent studies. CCK-8 assay， plate colony formation assay， and EdU staining were performed for Hep3B cells transfected with shRNA-NC or shRNA-KIF15 and HepG2 cells transfected with LV-vector or LV-KIF15 to evaluate the viability and proliferative capacity of these cells. GSEA was used to analyze the potential signaling pathways associated with KIF15 in HCC， and Western blot was used for detection. The independent-samples t test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsThe analysis of TCGA and GEPIA datasets showed that in HCC patients， the expression of KIF15 in HCC tissue was significantly higher than that in normal tissue， and the HCC patients with high KIF15 expression tended to have a poorer prognosis. Compared with sh-NC-Hep3B， sh3-Hep3B showed significant reductions in the mRNA and protein levels of KIF15 （P<0.05）， cell viability， clone formation number， and EdU positive rate （all P<0.05）. Compared with vector-HepG2， LV-KIF15-HepG2 showed significant increases in the mRNA and protein levels of KIF15 （P<0.05）， cell viability， clone formation number， and EdU positive rate （all P<0.05）. Subcutaneous tumor assay showed that compared with sh-NC-Hep3B， sh3-Hep3B showed reductions in tumor volume and tumor weight， as well as a significant reduction in the immunohistochemical score of Ki67 and a significant increase in the immunohistochemical score of TUNEL （P<0.05）. GSEA analysis showed that the PI3K/AKT/mTOR pathway was positively correlated with KIF15 in HCC （NES=1.59， P<0.001）. Western blot showed that LY294002 could inhibit the PI3K/AKT/mTOR pathway upregulated in LV-KIF15-HepG2， and compared with LV-KIF15-HepG2， LY294002+LV-KIF15-HepG2 showed significant reductions in cell viability， clone formation number， and EdU positive rate （all P<0.05）. ConclusionKIF15 enhances the viability and proliferative capacity of HCC cells by upregulating the PI3K/AKT/mTOR signaling pathway.
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Neoplasms immunotherapy has made a major breakthrough in the clinical practice of refractory tumor. However, there are still individual differences in treatment results and drug resistance in clinical application. Gastrointestinal microbiome is gradually recognized as an immunoregulatory factor in recent years, and more and more studies have focused on its influences on the efficacy of tumor immunotherapy. Targeting gastrointestinal microbiota to improve the response of tumor patients to immunotherapy has potential clinical application value.
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Since there is a lack of obvious clinical symptoms in the early stage of hepatocellular carcinoma (HCC), most patients have progressed to the advanced stage at the time of confirmed diagnosis. There are limited treatment options for HCC patients who miss the opportunity for surgery, so it is of great importance to find new therapeutic targets. Tumor-associated macrophages (TAMs) are a group of macrophages existing in the tumor immune microenvironment and affect the malignant behaviors of HCC cells and the state of immune escape within the tumor. This article introduces the origin and classification of TAM, summarizes the role and mechanism of TAMs in vascular proliferation, invasion and metastasis, formation and maintenance of stemness, and anti-tumor immunity in HCC, and briefly describes the current research advances in therapeutic targets for TAM, and it is pointed out that targeting TAM may be a promising direction for clinical treatment.
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Objective To investigate the safety and therapeutic effects of the novel bioartificial liver (BAL) combined with liver transplantation in patients with liver failure.Method Twenty-two patients with liver failure were admitted.Ten of them were treated with the novel BAL 24 h before liver transplantation,while the rest 12 served as controls and received liver transplantation only.The clinical signs and symptoms,liver function,ammonia,coagulation function and complete blood count were evaluated before,during and after the treatment.Levels of xenoantibodies (IgG and IgM) were detected by ELISA kit.Titers of complement were quantified by CH50 kit.DNA in the collected PBMCs was extracted for PCR with PERV specific primers and the porcine specific primer Sus scrofa cytochrome B.The RT activity was detected as well.The operation related information was recorded,such as operation success rate,operative time,cold ischemia time,bleeding volume in operation and liver function.Result All treatment procedures were completed successfully without any adverse reaction.In the BAL group,the clinical symptoms such as acratia,anorexia and abdominal distension were improved,as well as the stage of hepatic encephalopathy and the results of experimental tests such as liver function,ammonia,and coagulation function.No PERV infection and no obvious changes of the IgG,IgM and CH50 levels were detected in patients plasma.All patients were successfully bridged to modified pig-back liver transplantation and recovered.There were no differences in operative time and cold ischemia time (P＞0.05).However,bleeding volume was different in these two groups (P＜0.05).The liver function was improved significantly in BAL group than the control group after liver transplantation (P＜0.01).Conclusion The novel BAL could improve the internal environment of patients with liver failure,and enhance the safety and efficiency of liver transplantation.The novel BAL combined with liver transplantation could be an effective therapy for patients with liver failure.
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The lack of organ donors is a major obstacle against the application of liver transplantation.Recently,how to expand the source of liver donors has become a focus of transplantation research.The use of marginal donor may help solve current dilemma between the increasing waiting recipients and the relatively few donors.However,marginal donors always comes with elevated risk of primary nonfunction,initial poor function,delayed graft function loss and infection.Research on risk factors and complication preventing strategies of marginal donor transplantation is important in improving our understanding of liver transplantation.In the present article,we summarized recent progress in the research of marginal donors.And based on the experience from our center,we believe that the use of marginal donors in liver transplantation may help improve the situation of donor shortage,and isehemia-reperfusion injury remains the core topic of marginal donor transplantation and represents the direction of future study.
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As an essential technique involved in complicated liver surgery,portal vein reconstruction results in eradication of macro- or microscopic tumor residual on surgical margins when combined with precise hepatectomy,improving both the living quality and the survival rate of patients.The application of this reconstruction technique needs precise evaluation of pre-operational image data,clearly dissection of portal vessels and tremendous amount of collaborative effort by the surgery team. Other techniques performed during the surgical procedure include intra-operative ultrasound scan,revitalizing the cryopreserved vessels,and angioplasty.
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Liver failure is a dreaded and often fatal complication that sometimes follows partial hepatectomy.This article reviews the pathophysiology, risk factors and treatment of post-resectional liver failure (PLF). An inadequate quantity or quality of residual liver mass are the key event in its pathogenesis. The major risk factors are small remnant liver volume (RLV), excessive blood loss or transfusion, ICGR15 of greater than 20%, and F4/F3 liver cirrhosis. It is essential to identify these risk factors during the pre-operative assessment. Preventive measures should be applied whenever possible as options of curative treatment for PLF are limited. Artificial liver and/or liver transplantation are the important treatment alternatives for hepatic failure after hepatectomy.
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Studies in recent years revel that there is a close relationship between gastrin/cholecystokinin-2 receptors (GAS/CCK-2R) and pancreatic cancer. CCK-2R is widely distributed in human body, but not in normal exocrine pancreas. However, CCK-2R is abnormally expressed in pancreatic carcinoma. The abnormal expression of CCK-2R in pancreatic tissues leads to the abnormal protein expression and activation, changes in acinar cells' morphology and phenotype and an increase in the sensitivity to carcinogenic substances. And some GAS/CCK-2R antagonists can be used for the early and late treatment of pancreatic cancer.
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The hypothesis that tumor comes from stem cells has been demonstrated in various human tumors.Cancer is not only a genetic disease but also a stem cell disease. It is a key to regeneration, mutations and recurrence of tumors that gene mutations affect stem cells, and then stem cells mutate to cancer stem cells. In an effort to review the evidence that liver cancer stem cells exist, two fundamental questions must be addressed. First, do hepatocellular carcinomas(HCC)arise from liver stem cells? Second, do HCCs contain cells that possess properties of cancer stem cells?More recently, there is a hypothesis that HCC arise from maturation arrest of liver stem cells. Analysis of the cells in HCC supports the presence of cells with stem-cell properties(ie, immortality, transplantability, and resistance to therapy). However, definitive markers for these putative cancer stem cells have not yet been found and a liver cancer stem cell has not been isolated.
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Objective To study the expression of gastrin receptor in 4 HCC cell lines and tis-sues and their relation to clinieopathological features. Methods Immunohistochemical staining of GR was performed for the 4 HCC cell lines and the paraffin sections of 25 HCC cases. The relationship be-tween the GR expression in HCC sections and the clinicopatho[ogical parameters were analyzed. Results Positive staining for GR in the 3 HCC SMMC-7721>HepG2>QGY-7701 cell lines and HCC tissues was observed. The expression rate of gastrin receptor was 56 % (14/25). However, there was no association between expression of GR and elinieopathologieal features such as age, gender and clini-cal stage etc except for tumor thrombosis. Concision GR exists in the HCC. Futher study is needed to identify whether GR is a applicable target for endocrine therapy in HCC.
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Objective To determine the serum gastrin level, the expression of gastrin in colorectal carcinoma cells and observe the ultrastructure of gastrin secretory granule in colorectal carcinoma cells,in order to explore the relationship between gastrin and clinical behavior of colorectal carcinoma. Methods The serum gastrin and gastrin expression in colorectal carcinoma tissues of the 53 cases were examined by using radio-immunity analysis(RIA), immunohistochemistry and immunoelectron microscopic technique. Results Compared with control group,the preoperative level of serum gastrin in colorectal group was significantly increased, especially in well-differentiation adenocarcinoma . In the tissue of colorectal carcinoma, the gastrin expression rate was 56.6%. The expression rate of well-differentiated adenocaroinoma was higher than that in moderate and poor differentiation adenocarcinoma. Immunoelectron microscopy showed that the granules of protein A-gold (PAG) could be seen in different electro- density secretion granules in carcinoma cells, in intercellular space and on the surface of membrane of microvillus.Conclusions The level of serum gastrin and the expression of gastrin in cancer tissues in colorectal carcinoma patients are increased. The colorectal carcinoma cells may synthesize and secrete gastrin themselves, which may be correlated with clinical behavior of colorectal carcinoma.