Radiofrequency ablation,heat shock protein 70 and potential anti-tumor immunity in hepatic and pancreatic cancers:a minireview

BACKGROUND: Radiofrequency ablation (RFA) is a minimally invasive surgical procedure which has widespread popularity in the treatment of hepatic and pancreatic cancers. Increased evidence indicates that RFA stimulates anti-tumor immunity, possibly through the induction heat shock protein 70 (HSP70) expression. HSP70 has the capacity to affect the immunogenicity of tumor cells, to chaperone antigenic peptides and deliver these into antigen presentation pathways within antigen-presenting cells, and to activate and regulate innate and adaptive immunity, which makes it useful in immunotherapeutic strategies for the treatment of cancers. DATA SOURCES: An English-language literature search was conducted using MEDLINE (1991-2010) on anti-tumor immunity, heat shock protein 70, radiofrequency ablation, hepatic cancer, pancreatic cancer, and other related subjects. RESULTS: RFA has an increasing application in the surgical treatment of hepatic and pancreatic cancers. Increased evidence indicates that RFA can induce the expression of HSP70 which possesses properties that enable it to influence a variety of immunological processes. Tumor-derived HSP70 is regarded as a potent adjuvant facilitating presentation of tumor antigens and induction of anti-tumor immunity. CONCLUSIONS: This review addresses the potential association of RFA, HSP70, and anti-tumor immunity in treatment of hepatic and pancreatic cancers. To establish direct evidence of a potential association of RFA, HSP70, and anti-tumor immunity in hepatic and pancreatic cancers, further investigations should be conducted.

Novel functional proteins interact with midkine in hepatic cancer cells

BACKGROUND: Midkine is a heparin-binding growth factor that promotes the proliferation, survival, migration and differentiation of various target cells. Midkine plays an important role in tumorigenesis and tumor progression, and is overexpressed in many human malignant tumors. Patients with high tumor midkine expression frequently have a worse prognosis than those with low expression. The present study was designed to investigate the interaction network of midkine in hepatic cancer cells, and to elucidate its role in hepatocellular carcinoma. METHODS: DNA encoding full-length midkine was cloned into pDBLeu vector to serve as bait in yeast two-hybrid screening to identify interacting proteins. Candidate proteins were examined on SC-Leu-Trp-His+3-AT (20 mmol/L) plates and assayed for X-gal activity, then sequenced and classified according to the GenBank. Finally, identified proteins were expressed by the in vitro expression system pCMVTnT, and protein interactions were confirmed by co-immunoprecipitation. RESULTS: Using the yeast two-hybrid system, we found 6 proteins that interacted with midkine: NK-kappa-B inhibitor alpha (I-κ-B-α), Dvl-binding protein naked cuticle 2, granulin, latent active TGF-β binding protein 3, latent active TGF-β binding protein 4, and phospholipid scramblase 1. In vitro co-immunoprecipitation demonstrated that all identified proteins directly interacted with midkine.CONCLUSION: The identification of midkine-interacting proteins in hepatic cancer cells indicates that midkine is a multifunctional factor that may participate in cell migration, differentiation, and proliferation, and is also associated with the multicellular response feedback during the development of hepatocellular carcinoma.

SIMULTANEOUS OVER-EXPRESSION OF INSULIN-LIKE GROWTH FACTOR- Ⅱ (IGF- Ⅱ ) AND IGF- Ⅱ RECEPTOR(IGF- Ⅱ R) GENES IN HUMAN PRIMARY CANCER-IMPLICATION OF AUTOCRINE AND PARACRINE MECHANISM IN AUTONOMOUS GROWTH OF HEPATIC CANCER

This is first report about the simultaneous over-expression of both Insulin-like growth factor (IGF- I ) and its receptor (IGF- I R) at mRNA level in human primary hepatic Cancer (PHC). In 10 PHC samples from China, IGF-I and IGF- I R were both over-expressed, whereas only a background signal was detected in normal liver. In 5 pairs of PHC and its non- tumorous adjacent liver tissues from South Africa, IGF- I and IGF- I R were also over-expressed in PHC. mRNA expression of IGF- I in all 5 cases and IGF- I R in 4 of 5 cases were higher in cancer than non- tumorous adjacent liver tissues. These results strongly implicate that an autocrine and/ or paracrine mechanism might be Involved in formation and progression of PHC.

Hemodynamic changes in hepatic cancer before and after cluster electrode radio-frequency ablation

Objective: To evaluate the hemodynamic changes of hepatic artery (HA), portal vein (PV) and tumors in hepatic cancer patients treated by cluster electrode radio-frequency ablation with the aid of color Doppler flow imaging (CDFI). Methods: The hemodynamic changes of HA, PV and 42 tumors in 30 cases of hepatic cancer were investi- gated by CDFI one week before and after cluster e- lectrode radio-frequency ablation. Results: One week after radio-frequency ablation, the velocity of HA decreased (P<0.05), but the dia- meter and velocity of PV unchanged. Before radio- frequency ablation, blood signals were observed in 35 cancer nodes (83.0 % of all 42 nodes). After radio- frequency ablation, blood signals were reduced in 15 nodes and disappeared in 14 nodes. Early investiga- tion implied that the decrease of blood supply was parallel with the reduction of node size. However, the outcome in case of huge nodes with double blood supply was not as promising as those small nodes. Conclusion: CDFI is useful to assess blood supply in ablation of hepatic cancer by using cluster electrode radio-frequency therapy.

Hepatitis B virus envelope as a targeting gene transfer vector for hepatic cancer cells

Objective： The aim of the study was to observe the transfection efficacy of hepatitis B virus envelope （HBVE） and evaluate its ability as a gene transfer vector for liver cancer cells. Methods： To obtain HBVE, the supematant fluid of HepG 2.2.15 cells was mixed with a PEG8000 solution for concentration and was inactivated by β-propiolactone. The acquired HBVE was used to pack plRES2-EGFP to test its package ability. Then, we examined its quantity and quality with ELISA, PCR, SDS-PAGE and electron microscopy. The plRES2-EGFP was packed with HBVE and obtained the product HBVE-GFP. The plRES2-EGFP was packed with liposome and obtained the product liposome-GFP. HBVE-GFP and liposome-GFP were used to transfer HepG 2 cells to study the transfection efficiency. HBVE-GFP was used to transfer HepG 2, A549, HeLa and FB cells to study the targeting ability. The green fluorescent protein （GFP） expression was observed under a fluorescent microscope. The rate of GFP positive cells was determined by flow cytometry. Results： 1. The acquired HBVE could retain the surface protein HBsAg ＋ pre S1 ＋ pre S2 and had no virus DNA. It had good package ability for plRES2-EGFP. 2. Transfection efficiency： The GFP could be observed in both the liposome group and HBVE group under the fluorescent microscope. But the HBVE group had a higher fluorescent intensity than liposome group. The transfection rate of liposome group was 49.97% ＋ 2.37% while the HBVE group was 70.65% ＋ 3.15% and the fluorescent intensity of the HBVE group was 3-4 times （P = 0.000） for liposome group with the determination of flow cytometry. 3. Targeting ability： The GFP could be observed in the four groups under the fluorescent microscope. The HepG 2 group had the highest fluorescent intensity among the four groups. The transfection rate of HepG 2 group was 71.35% ＋ 0.03% which was highly expressed than other groups （P = 0.000） and the fluorescent intensity of the HepG 2 group was 2-3 times （P = 0.000） for the other 3 groups with the determination of flow cytometry. Conclusion： HBVE can be constructed successfully with the methods of PEG8000 and β-propiolactone from the supernatant fluid of HepG 22.15 cells. The HBVE can be a candidate gene transfer vector for liver cancer cells.

CT arterial portography and CT hepatic arteriography in detection of micro liver cancer

AIM To recognize the characteristic findings of micrQliver cancer (MLC) and to evaluate the effect of CT arterial portography (CTAP) and CT hepatic arteriography (CTHA) in diagnosis of MLC. METHODS Between April 1996 to December 1998, CTAP and CTHA were performed in 12patients with MLC, which were not detect ed byconventional CT examinations. After CTHA, 3 mL-- 5 mL mixture of lipiodol, doxorubic in andmitomycin C were injected into hepatic arterythrough the catheter, and then followed up by CTthree or four weeks later (Lipiodol CT LP-CT).RESULTS A total of 22 micro--tumors (0 .2 cm 0.6 cm in diameter ) were detected in 12patients, which manifested as small perfusiondefects in CTAP and small round enhancement inCTHA. The rate of detectability of CTAP andCTHA was 68.2% (15/ 22) and 77.3% (17/ 22)respectively, and the rate of the simultaneoususe of both procedures reached 86. 4% (19/ 22 ).All micro--tumors were demonstrated as punctatelipiodol deposit fool in LP--CT. After LP--CT, theelevated serum level of Q-fetoprotein (AFP)dropped to the normal level in all patients.CONCLUSION The CTAP and CTHA are the mostsensitive imaging methods for detecting microIiver cancer. Confirmed by the change of theelevated serum AFP level and lipiodol depositfool in LP-CT, small perfusion defects in CTAPand punctate enhancement in CTHA may suggestmicro--liver cancer.

Meta-analysis of transarterial chemoembolization combined with cryoablation vs transarterial chemoembolization alone for≥5 cm hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)ranks sixth globally in cancer incidence and third in mortality rates.Unfortunately,over 70% of HCC patients forego the opportunity for curative surgery or liver transplantation due to inadequate physical examinations,poor physical condition,and limited organ availability upon diagnosis.Clinical guidelines endorse transarterial chemoembolization(TACE)as the frontline treatment for intermediate to advanced-stage HCC.Cryoablation(CRA)is an emerging local ablative therapy increasingly used in HCC management.Recent studies suggest that combining CRA with TACE offers complementary and synergistic effects,potentially improving long-term survival rates.However,the superiority of combined TACE+CRA therapy over TACE alone for HCC lesions equal to or exceeding 5 cm requires further investigation.AIM To compare the efficacy and safety of TACE combined with CRA vs TACE alone in the treatment of HCC with a diameter of≥5 cm.METHODS PubMed,EMBASE,Cochrane Library,CNKI,Wanfang,and VIP databases were searched to retrieve all relevant studies on TACE and CRA up to July 2022.Meta-analysis was performed using RevMan 5.3 software.RESULTS After screening according to the inclusion and exclusion criteria,6 articles were included,including 2 randomized controlled trials and 4 nonrandomized controlled trials,with a total of 575 patients included in the meta-analysis.The results showed that the objective response rate[odds ratio(OR)=2.56,95%confidence interval(CI):1.66-3.96,P<0.0001],disease control rate(OR=3.03,95%CI:1.88-4.89,P<0.00001),1-year survival rate(OR=3.79,95%CI:2.50-5.76,P<0.00001),2-year survival rate(OR=2.34,95%CI:1.43-3.85,P=0.0008),and 3-year survival rate(OR=3.34,95%CI:1.61-6.94,P=0.001)were all superior to those of the control group;the postoperative decrease in alpha-fetoprotein value(OR=295.53,95%CI:250.22-340.85,P<0.0001),the postoperative increase in CD4 value(OR=10.59,95%CI:8.78-12.40,P<0.00001),and the postoperative decrease in CD8 value(OR=6.47,95%CI:4.44-8.50,P<0.00001)were also significantly higher than those in the TACE-alone treatment group.CONCLUSION Compared with TACE-alone treatment,TACE+CRA combined treatment not only improves the immune function of HCC patients with a diameter of≥5 cm,but also enhances the therapeutic efficacy and long-term survival rate,without increasing the risk of complications.Therefore,TACE+CRA combined treatment may be a more recommended treatment for patients with HCC with a diameter of≥5 cm.

Protective effect of antioxidant on renal damage caused by Doxorubicin chemotherapy in mice with hepatic cancer

Objective:To investigate the protective effects and mechanism of antioxidant TBHQ on renal damage caused by doxorubicin chemotherapy in mice with hepatic cancer.Methods:Cell H22 of mice with hepatic cancer which was subcultured for three times was subcutaneously transplanted to the groin of right lower limb of 45 SPF Kunming mice to establish the transplanted tumor model.The doxorubicin chemotherapy group and antioxidant intervention group received intraperitoneal injection of ADM(1 mg/kg·0.2 mL/2d).The model control group received normal saline(NS) of the same volume at the same time.1%TBHQ was added into the diet of mice of the antioxidant intervention group.Seven weeks later,morning urines and peripheral blood were randomly collected to detect UAIb,UCr,BUN,Scr and UAlb/Cr levels.All mice were beheaded.The renal tissues were made into homogenate,and SOD,T-AOC and MDA content in tissues were detected followed by cell lysis.All data were processed using SPSS 19.0.Results:The UAlb/Cr,BUN.Scr and MDA of doxorubicin chemotherapy group were significantly higher those of model control group and the activities of SOD,T-AOC in doxorubicin chemotherapy group were lower than those of model control group(P<0.01).The UAlb/Cr,BUN,Scr and MDA of antioxidant intervention group were lower than those of doxorubicin chemotherapy group and the activities of SOD,T-AOC of antioxidant intervention group were higher than those of doxorubicin chemotherapy group doxorubicin chemotherapy group(P<0.05).The BUN of model control group was higher than that of blank group,and T-AOC was lower than that of blank group,and difference was statistically significant(P<0.05).Conclusions:Doxorubicin chemotherapy could lead to abnormal antioxidant capacity and renal function of tumor-bearing mice with hepatic cancer.TBHQ antioxidant intervention could effectively improve the antioxidant capacity of renal tissue and reduce the renal damage caused by doxorubicin to some extent.

DUCK HEPATITIS B VIRUS DNA WITHIN HEPATIC MULTICENTRIC CANCER AND/OR METASTATIC CANCER

Duck hepatitis B vims (DHBV) DNA was detected in different tumorous nodules of ducks with hepatic multicentric cancer or intrahepatic metastasis by Southern blot technique. Among 7 ducks with hepatocellular carcinoma of multiple tumor nodules, the hybridization pattern of Integrated DHBV DNA In different tumorous nodules was identical in 3 cases and different in 2 cases. One case showed a similar hybridization pattern in two tumorous nodules and other one was negative tor DHBV DNA. Integrated DHBV DNA was also identified in a metastatic lung cancer of ducks with hepatocellular carcinoma. The hybridization pattern of metastasis of lungs was as the some as that in primary hepatocellular carcinoma. The same discrete hybridization bands In the different tumorous nodules indicate that these nodules might arise from one transformed cell. The different hybridization patterns In various tumorous nodules show that these tumorous nodules might arise from various transformed cells. The results suggest that the hybridization pattern of different nodules of hepatocellular carcinoma with viral DNA probe could make a cell clone origin marker of tumor nodule to differentiate hepatic multlcentric cancer from Intrahepatic metastatic cancer.

Studies of Selective Arterial Perfusion plus Chemoembolization on Hepatic Metastasis from Rectal Cancer

OBJECTIVE To develop an effectual method for treating hepatic metas-tasis from rectal cancer. METHODS A randomized control study of celiac artery perfusion plus transcatheter hepatic arterial chemoembolization (TACE) (observation group) and intravenous chemotherapy (control group) for 99 cases with hepatic me-tastasis from rectal cancer was performed. The perfusion was repeated once at 4 weeks after the first treatment of 52 cases in the observation group, and it was subsequently repeated at an interval of 2 or 3 months. Using intrave-nous administration, the perfusion was repeated once every 3 weeks with 47 cases in the control group. RESULTS Three months after treatment, the patients in the observation group who showed a relief or elimination of a former superior abdominal pain amounted to 70.6%, and those with a diminution of their intrahepatic mass reached 55.8%. In the control group, the patients with a relief or disappear-ance of hepatalgia reached 20%, and those with a diminution of their intrahe-patic mass reached 10.6%. The 1, 2 and 3-year survival rates were 80.8%, 46.2% and 25.0% in the cases of the observation group and 61.7%, 19.1% and 4.3% in the control group, respectively. CONCLUSION For the patients who failed to receive a surgical opera-tion on their hepatic metastasis from rectal cancer, celiac artery perfusion plus TACE is a more effective regimen for improvement of the clinical symp-toms and extension of the survival time, compared to intravenous chemo-therapy, and is a better choice for palliative therapy.

EXPERIMENTAL PRIMARY LIVER CANCER IN TREE SHREWS EXPOSED TO HUMAN HEPATITIS B VIRUS AND AFLATOXIN B_(1)

On the basis of the successful establishment of an animal model in tree shrews experimentally in fected with human hepatitis B virus (HHBV), a study on the hepatocarcinogenic effects of HHBV and aflatoxin B1 (AFB1) by using this animal model was conducted through a lifelong experiment. Among 41 tree shrews exposed to AFB1, 17 were experimentally infected by HHBV and 24 were uninfected. After 158 weeks, significant difference of primary liver cancer (PLC) incidence was present between the HHBV infected (52.94%) and uninfected (12.5%) groups (p<0.05). No difference was found between these two groups in the amount of AFB4 ingestion. Moreover, 1/9 of the tree shrews infected only by HHBV but not exposed to AFB4 developed PLC. No PLC was found in 6 tree shrews that had neither been infected with HHBV nor been exposed to AFB4. These results suggest the possible etiologic relationship between HHBV infection and PLC, as well as the synergetic effects of HHBV and AFB4 during PLC development.

Studies on the Mechanism of Arsenic Trioxide-Induced Apoptosis in HepG_2 Human Hepatocellular Carcinoma Cells

OBJECTIVE To study the anti-tumor effect of arsenic trioxide on the HepG2 human hepatocellular carcinoma cell line, and to explore its mechanism of action. METHODS The MTT assay was used to determine the inhibitory effect of As2O3 on HepG2 cells at various As2O3 concentrations. The expression of p-JNK, caspase-3 and PARP was detected by Western blots. RESULTS As2O3 markedly inhibited the growth of the HepG2 cells and induced apoptosis. The results of Western blot analysis showed that the As2O3-induced apoptosis was accompanied by caspase-3 and PARP activation. p-JNK was detected at 10 min following As2O3 treatment, and preceded to peak at 20 min, and decreased by 30 min. The total protein content did not obviously change. The activation of JNK occurred prior to cell apoptosis. SP600125, a JNK inhibitor, suppressed the As2O3-induced activation of caspase-3 and PARP cleavage. CONCLUSION As2O3 inhibits the proliferation of human HepG2 hepatocellular carcinoma cells by inducing apoptosis in vitro. As2O3-induced apoptosis is accessed through the caspase-3 pathway. The JNK signal-transduction pathway and caspase-3 are involved upstream in the As2O3 induced HepG2 apoptotic response.

Dihydromyricetin inhibits migration and invasion of hepatoma cells through regulation of MMP-9 expression

AIM: To investigate the effects of dihydromyricetin (DHM) on the migration and invasion of human hepatic cancer cells.

Endothelial precursor cells promote angiogenesis in hepatocellular carcinoma

AIM:To investigate the role of bone marrow-derived endothelial progenitor cells(EPCs) in the angiogenesis of hepatocellular carcinoma(HCC).METHODS:The bone marrow of HCC mice was reconstructed by transplanting green fluorescent protein(GFP) + bone marrow cells.The concentration of circulating EPCs was determined by colony-forming assays and fluorescence-activated cell sorting.Serum and tissue levels of vascular endothelial growth factor(VEGF) and colony-stimulating factor(CSF) were quantified by enzyme-linked immunosorbent assay.The distribution of EPCs in tumor and tumor-free tissues was detected by immunohistochemistry and real-time polymerase chain reaction.The incorporation of EPCs into hepatic vessels was examined by immunofluorescence and immunohistochemistry.The proportion of EPCs in vessels was then calculated.RESULTS:The HCC model was successful established.The flow cytometry analysis showed the mean percentage of CD133CD34 and CD133VEGFR2 double positive cells in HCC mice was 0.45% ± 0.16% and 0.20% ± 0.09% respectively.These values are much higher than in the sham-operation group(0.11% ± 0.13%,0.05% ± 0.11%,n = 9) at 14 d after modeling.At 21 d,the mean percentage of circulating CD133CD34 and CD133VEGFR2 cells is 0.23% ± 0.19%,0.25% ± 0.15% in HCC model vs 0.05% ± 0.04%,0.12% ± 0.11% in control.Compared to the transient increase observed in controls,the higher level of circulating EPCs were induced by HCC.In addition,the level of serum VEGF and CSF increased gradually in HCC,reaching its peak 14 d after modeling,then slowly decreased.Consecutive sections stained for the CD133 and CD34 antigens showed that the CD133+ and CD34+ VEGFR2 cells were mostly recruited to HCC tissue and concentrated in tumor microvessels.Under fluorescence microscopy,the bone-marrow(BM)-derived cells labeled with GFP were concentrated in the same area.The relative levels of CD133 and CD34 gene expression were elevated in tumors,around 5.0 and 3.8 times that of the tumor free area.In frozen liver sections from HCC mice,cells co-expressing CD133 and VEGFR2 were identified by immunohistochemical staining using anti-CD133 and VEGFR2 antibodies.In tumor tissue,the double-positive cells were incorporated into vessel walls.In immunofluorescent staining.These CD31 and GFP double positive cells are direct evidence that tumor vascular endothelial cells(VECs) come partly from BM-derived EPCs.The proportion of GFP CD31 double positive VECs(out of all VECs) on day 21 was around 35.3% ± 21.2%.This is much higher than the value recorded on day 7 group(17.1% ± 8.9%).The expression of intercellular adhesion molecule 1,vascular adhesion molecule 1,and VEGF was higher in tumor areas than in tumor-free tissues.CONCLUSION:Mobilized EPCs were found to participate in tumor vasculogenesis of HCC.Inhibiting EPC mobilization or recruitment to tumor tissue may be an efficient strategy for treating HCC.

Nanotheranostics:A powerful next-generation solution to tackle hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is an epidemic burden and remains highly prevalent worldwide.The significant mortality rates of HCC are largely due to the tendency of late diagnosis and the multifaceted,complex nature of treatment.Meanwhile,current therapeutic modalities such as liver resection and transplantation are only effective for resolving early-stage HCC.Hence,alt-ernative approaches are required to improve detection and enhance the efficacy of current treatment options.Nanotheranostic platforms,which utilize biocompatible nanoparticles to perform both diagnostics and targeted delivery,has been considered a potential approach for cancer management in the past few decades.Advancement of nanomaterials and biomedical engineering techniques has led to rapid expansion of the nanotheranostics field,allowing for more sensitive and specific diagnosis,real-time monitoring of drug delivery,and enhanced treatment efficacies across various malignancies.The focus of this review is on the applications of nanotheranostics for HCC.The review first explores the current epidemiology and the commonly encountered obstacles in HCC diagnosis and treatment.It then presents the current technological and functional advancements in nanotheranostic technology for cancer in general,and then specifically explores the use of nanotheranostic modalities as a promising option to address the key challenges present in HCC management.

Incidental gallbladder cancer during laparoscopic cholecystectomy:Managing an unexpected finding

AIM:To evaluate the impact of incidental gallbladder cancer on surgical experience.METHODS:Between 1998 and 2008 all cases of cholecystectomy at two divisions of general surgery,one university based and one at a public hospital,were retrospectively reviewed.Gallbladder pathology was diagnosed by history,physical examination,and laboratory and imaging studies [ultrasonography and computed tomography(CT)].Patients with gallbladder cancer(GBC) were further analyzed for demographic data,and type of operation,surgical morbidity and mortality,histopathological classification,and survival.Incidental GBC was compared with suspected or preoperatively diagnosed GBC.The primary endpoint was diseasefree survival(DFS).The secondary endpoint was the difference in DFS between patients previously treated with laparoscopic cholecystectomy and those who had oncological resection as first intervention.RESULTS:Nineteen patients(11 women and eight men) were found to have GBC.The male to female ratio was 1:1.4 and the mean age was 68 years(range:45-82 years).Preoperative diagnosis was made in 10 cases,and eight were diagnosed postoperatively.One was suspected intraoperatively and confirmed by frozen sections.The ratio between incidental and nonincidental cases was 9/19.The tumor node metastasis stage was:pTis(1),pT1a(2),pT1b(4),pT2(6),pT3(4),pT4(2);five cases with stageⅠa(T1 a-b);two with stageⅠb(T2 N0);one with stage Ⅱa(T3 N0);six with stage Ⅱb(T1-T3 N1);two with stage Ⅲ(T4 Nx Nx);and one with stage Ⅳ(Tx Nx Mx).Eighty-eight percent of the incidental cases were discovered at an early stage(≤Ⅱ).Preoperative diagnosis of the 19 patients with GBC was:GBC with liver invasion diagnosed by preoperative CT(nine cases),gallbladder abscess perforated into hepatic parenchyma and involving the transversal mesocolon and hepatic hilum(one case),porcelain gallbladder(one case),gallbladder adenoma(one case),and chronic cholelithiasis(eight cases).Every case,except one,with a T1b or more advanced invasion underwent Ⅳb + Ⅴ wedge liver resection and pericholedochic/hepatoduodenal lymphadenectomy.One patient with stage T1b GBC refused further surgery.Cases with Tis and T1a involvement were treated with cholecystectomy alone.One incidental case was diagnosed by intraoperative frozen section and treated with cholecystectomy alone.Six of the nine patients with incidental diagnosis reached 5-year DFS.One patient reached 38 mo survival despite a port-site recurrence 2 years after original surgery.Cases with non incidental diagnosis were more locally advanced and only two patients experienced 5-year DFS.CONCLUSION:Laparoscopic cholecystectomy does not affect survival if implemented properly.Reoperation should have two objectives:R0 resection and clearance of the lymph nodes.

Surgery for oligometastasis of pancreatic cancer

The incidence of pancreatic adenocarcinoma（PDAC） has steadily increased over the past several decades. The majority of PDAC patients will present with distant metastases, limiting surgical management in this population. Hepatectomy and pulmonary metastasectomy（PM） has been well established for colorectal cancer patients with isolated, resectable hepatic or pulmonary metastatic disease. Recent advancements in effective systemic therapy for PDAC have led to the selection of certain patients where metastectomy may be potentially indicated. However, the indication for resection of oligometastases in PDAC is not well defined. This review will discuss the current literature on the surgical management of metastatic disease for PDAC with a specific focus on surgical resection for isolated hepatic and pulmonary metastases.

Target gene prediction and functional analysis of miRNAs differently expressed in colon cancer primary tumors to metastases formed in the liver

Background:Colon cancer is one of the main tumor-related causes of death worldwide and now surgical resection is still the most effective method for the treatment of colon cancer.However,many colon cancers currently lose the opportunity for surgical treatment because of liver metastases.The possible molecular mechanism of liver metastasis of colon cancer can provide ideas for the prevention and treatment of liver metastasis colon cancer.Several studies have recently indicated the regulatory effects of microRNAs(miRNAs)in cancer metastasis.Bioinformatics methods were used to analyze the differentially expressed miRNAs in primary colon cancer tissues and liver metastases.Then the target genes of differentially expressed miRNAs were predicted.By analyzing the biological processes and signaling pathways that the target gene may participate in,we infer the possible molecular mechanisms of liver metastasis of colon cancer and the effects of target genes on prognosis of patients were explored.Methods:The chip data GSE98406 was selected and differentially expressed miRNAs between primary colon cancer and liver metastatic colon cancer were explored by Morpheus.TargetScan and miRanda were used to predict target genes of differentially expressed miRNAs.The gene oncology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to analyze the biological processes and possible signaling pathways the target genes involved in.Protein-ptotein interaction analysis was performed by String and Cyotscape,the interactions among target genes and hub genes were analyzed.Finally,we explored the effects of differentially expressed miRNAs and their target genes on the prognosis of colon cancer patients.Results:Two differentially expressed miRNAs were screened out,of which miR-122 was upregulated more than 2 folds and miR-143 was downregulated more than twofold in liver metastatic colon cancer.Target genes of miR-122 and miR-143 were mainly involved in energy metabolism.The major signaling pathways involved are epithelial-mesenchymal transition pathways.Ten hub genes were selected by protein interaction analysis.Among them,KRAS,CDK1,CREB1,CS,PC,RAB7A,and CANX were highly expressed in tumor tissues,and CALM1 and MAPK7 were lowly expressed in tumor tissues.The results showed that reduced expression of CS and PC reduced survival of patients with colon cancer.However,the impact of miR-122 and mi-143 on the prognosis of patients with colon cancer is not clear.Conclusion:Differentially expressed miRNAs mainly affect the expression of target genes involved in energy metabolism and cellular transformation in colon cancer.Intracellular metabolic activity is the center of cellular activity,the treatment of metabolic processes in tumor cells may be a new idea for the treatment of tumors.

Screening of QHF formula for effective ingredients from Chinese herbs and its anti-hepatic cell cancer effect in combination with chemotherapy

Background Recent studies have shown that effective ingredients of Chinese herbs are used more and more widely in the treatment or co-treatment of cancers, however, they are usually used separately and there has been limited research about joint application of Chinese herbs in multi-modal treatment. The aim of this study was to screen a QHF （Q： Qingrejiedu, H： Huoxuehuayu and F： Fuzhengguben） formula for effective ingredients from Chinese medicines and assess its anti-hepatic cell cancer （HCC） effect in combination with chemotherapy.Methods Six effective ingredients from Chinese medicine were selected based on the previous literature and used in the study. The QHF formula and the best ratio of ingredients were evaluated in H22 mouse （KM） models with solid tumors and ascites tumors by uniform design and monitoring inhibition of tumor growth and survival. We then observed the anti-hepatic cell cancer （HCC） effect of QHF when combined with cisplatin （DDP） in H22 mouse （Balb/c） models with solid tumors and ascites tumors. Evaluating of the therapeutic effect included the general condition of the mice, inhibition of tumor growth, survival, changes in body weight, thymus index, spleen index and WBC counts.Results The optimal QHF dose ratio for anti-hepatic cell cancer treatment was： 800 mg/kg Cinobufotalin, 14 mg/kg Ginsenosides Rg3, 5.5 mg/kg PNS and 100 mg/kg Lentinan. Treatment was more efficient in inhibiting the growth of transplanted tumors in H22 mice when using the QHF formula （55.91%） than using Cinobufotalin （33.25%）, Ginsenosides Rg3 （35.11%）, PNS （27.12%） or Lentinan （4.97%） separately. QHF also prolonged the life of H22 ascites hepatic cancer mice more efficiently （38.13%） than Cinobufotalin （25.00%）, Ginsenosides Rg3 （27.27%）, PNS （23.30%） or Lentinan （24.43%）. QHF combined with DDP could reduce DDP-induced leucopenia, spleen and thymus atrophy and other toxic reactions. Combining QHF with DDP the tumor growth inhibition reached 82.54% with a 66.83% increase in survival. Conclusions QHF is more efficient in anti-hepatic cell caner treatment than the single drugs that constitute the formula. QHF combined with DDP can attenuate tumor growth and suppresses the DDP-induced toxic reactions.

Sialic acid-engineered mesoporous polydopamine nanoparticles loaded with SPIO and Fe3+as a novel theranostic agent for T1/T2 dual-mode MRI-guided combined chemo-photothermal treatment of hepatic cancer

diagnostic and therapeutic capability are highly needed for the treatment of hepatic cancer.Herein,we aimed to develop a novel mesoporous polydopamine(MPDA)-based theranostic agent for T1/T2 dual magnetic resonance imaging(MRI)-guided cancer chemo-photothermal therapy.Superparamagnetic iron oxide(SPIO)-loaded MPDA NPs(MPDA@SPIO)was firstly prepared,followed by modifying with a targeted molecule of sialic acid(SA)and chelating with Fe^(3+)(SA-MPDA@SPIO/Fe^(3+) NPs).After that,doxorubicin(DOX)-loaded SA-MPDA@SPIO/Fe^(3+) NPs(SA-MPDA@SPIO/DOX/Fe^(3+))was prepared for tumor theranostics.The prepared SAPEG-MPDA@SPIO/Fe^(3+) NPs were water-dispersible and biocompatible as evidenced by MTT assay.In vitro photothermal and relaxivity property suggested that the novel theranostic agent possessed excellent photothermal conversion capability and photostability,with relaxivity of being r1=4.29 mM1s1 and r2=105.53 mM1s1,respectively.SAPEG-MPDA@SPIO/Fe^(3+) NPs could effectively encapsulate the DOX,showing dual pH-and thermal-triggered drug release behavior.In vitro and in vivo studies revealed that SA-MPDA@SPIO/DOX/Fe^(3+) NPs could effectively target to the hepatic tumor tissue,which was possibly due to the specific interaction between SA and the overexpressed E-selectin.This behavior also endowed SA-MPDA@SPIO/DOX/Fe^(3+)NPs with a more precise T1-T2 dual mode contrast imaging effect than the one without SA modification.In addition,SAPEG-MPDA@SPIO/DOX/Fe^(3+) NPs displayed a superior therapeutic effect,which was due to its active targeting ability and combined effects of chemotherapy and photothermal therapy.These results demonstrated that SAPEG-MPDA@SPIO/DOX/Fe^(3+) NPs is an effective targeted nanoplatform for tumor theranostics,having potential value in the effective treatment of hepatic cancer.