Immune cell dynamics and the impact on the efficiency of transvascular antitumor interventional therapies in hepatocellular carcinoma patients.

Objective: This study investigates the impact of transvascular antitumor interventional therapies on immune cell dynamics and its correlation with disease control and progression-free survival (PFS) in hepatocellular carcinoma (HCC) patients. Methods: A single-center observational case-control study was conducted with 119 HCC patients. Transvascular antitumor interventional therapy were administered based on patient-specific evaluations. Peripheral blood samples were collected before and within 28 days after the first treatment to analyze lymphocyte subsets and other immune cells. Results: Higher counts of total white blood cells (WBCs), lymphocytes, monocytes, and basophils were significantly associated with disease control rate. Subgroup analysis revealed that abnormal BMI, diabetes, infection, and multiple lesions were significantly associated with T cell abnormalities. Age, abnormal BMI, hypertension, and abnormal AFP were linked to total T cell abnormalities. NK cells, B cells, Th cells, Tc/Ts cells, and CD4/CD8 ratios did not show significant differences in PFS probabilities. Conclusion: Higher counts of WBCs, lymphocytes, monocytes, and basophils, play a crucial role in the effectiveness of HCC interventional therapy.

Application of combined ablation and immunotherapy in NSCLC and liver cancer: Current status and future prospects.

This review examines combining tumor ablation therapy with immunotherapy for respiratory and digestive system tumors, particularly NSCLC and liver cancer. Despite advancements in traditional methods, they face limitations in advanced-stage tumors. Ablation techniques like RFA, MWA, and cryoablation offer minimally invasive options, while immune checkpoint inhibitors enhance the immune system's tumor-fighting ability. This review highlights their synergistic effects, clinical outcomes, and future research directions, including optimizing protocols, exploring new combinations, uncovering molecular mechanisms, advancing precision medicine, and improving accessibility. Combined therapy is expected to improve efficacy and patient outcomes significantly.

Abnormal metabolism in hepatic stellate cells: Pandora's box of MAFLD related hepatocellular carcinoma.

Metabolic associated fatty liver disease (MAFLD) is a significant risk factor for the development of hepatocellular carcinoma (HCC). Hepatic stellate cells (HSCs), as key mediators in liver injury response, are believed to play a crucial role in the repair process of liver injury. However, in MAFLD patients, the normal metabolic and immunoregulatory mechanisms of HSCs become disrupted, leading to disturbances in the local microenvironment. Abnormally activated HSCs are heavily involved in the initiation and progression of HCC. The metabolic disorders and abnormal activation of HSCs not only initiate liver fibrosis but also contribute to carcinogenesis. In this review, we provide an overview of recent research progress on the relationship between the abnormal metabolism of HSCs and the local immune system in the liver, elucidating the mechanisms of immune imbalance caused by abnormally activated HSCs in MAFLD patients. Based on this understanding, we discuss the potential and challenges of metabolic-based and immunology-based mechanisms in the treatment of MAFLD-related HCC, with a specific focus on the role of HSCs in HCC progression and their potential as targets for anti-cancer therapy. This review aims to enhance researchers' understanding of the importance of HSCs in maintaining normal liver function and highlights the significance of HSCs in the progression of MAFLD-related HCC.

Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma (CHANCE001).

There is considerable potential for integrating transarterial chemoembolization (TACE), programmed death-(ligand)1 (PD-[L]1) inhibitors, and molecular targeted treatments (MTT) in hepatocellular carcinoma (HCC). It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations. In this nationwide, retrospective, cohort study, 826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT (combination group, n = 376) or TACE monotherapy (monotherapy group, n = 450) were included from January 2018 to May 2021. The primary endpoint was progression-free survival (PFS) according to modified RECIST. The secondary outcomes included overall survival (OS), objective response rate (ORR), and safety. We performed propensity score matching approaches to reduce bias between two groups. After matching, 228 pairs were included with a predominantly advanced disease population. Median PFS in combination group was 9.5 months (95% confidence interval [CI], 8.4-11.0) versus 8.0 months (95% CI, 6.6-9.5) (adjusted hazard ratio [HR], 0.70, P = 0.002). OS and ORR were also significantly higher in combination group (median OS, 19.2 [16.1-27.3] vs. 15.7 months [13.0-20.2]; adjusted HR, 0.63, P = 0.001; ORR, 60.1% vs. 32.0%; P < 0.001). Grade 3/4 adverse events were observed at a rate of 15.8% and 7.5% in combination and monotherapy groups, respectively. Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS, OS, and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice, with an acceptable safety profile.

A systematic review and meta-analysis comparing tumor progression and complications between radiofrequency ablation and thyroidectomy for papillary thyroid carcinoma.

Background: Papillary thyroid cancer (PTC) is the most frequent thyroid cancers worldwide. The efficacy and acceptability of radiofrequency ablation (RFA) in the treatment of PTC have been intensively studied. The aim of this study is to focus on extra detailed that may influent for PTC or papillary thyroid microcarcinoma (PTMC). Materials and methods: We identified a total of 1,987 records of a primary literature searched in PubMed, Embase, Cochrane Library, and Google Scholar by key words, from 2000 to 2022. The outcome of studies included complication, costs, and local tumor progression. After scrutiny screening and full-text assessment, six studies were included in the systematic review. Heterogeneity was estimated using I2, and the quality of evidence was assessed for each outcome using the GRADE guidelines. Results: Our review enrolled 1,708 patients reported in six articles in the final analysis. There were 397 men and 1,311 women in the analysis. Two of these studies involved PTC and four focused on PTMC. There were 859 patients in the RFA group and 849 patients in the thyroidectomy group. By contrast, the tumor progression of RFA group was as same as that surgical groups [odds ratio, 1.31; 95% CI, 0.52-3.29; heterogeneity (I2 statistic), 0%, p = 0.85]. The risk of complication rates was significantly lower in the RFA group than that in the surgical group [odds ratio, 0.18; 95% CI, 0.09-0.35; heterogeneity (I2 statistic), 40%, p = 0.14]. Conclusions: RFA is a safe procedure with a certain outcome for PTC. RFA can achieve a good efficacy and has a lower risk of major complications.

Transarterial chemoembolization combined with metformin improves the prognosis of hepatocellular carcinoma patients with type 2 diabetes.

Objective: The study aims to investigate the effect of metformin on Hepatocellular carcinoma (HCC) patients with type 2 diabetes mellitus (T2DM) who received transarterial chemoembolization (TACE) for the first time. Methods: From January 2016 to December 2019, T2DM patients diagnosed with HCC in Shandong Cancer Hospital and treated with TACE were included in this retrospective study. Overall survival (OS) and Progression-free survival (PFS) were compared between patients treated with metformin and other antidiabetics. Univariate and multivariate Cox regression models were used to evaluate the independent risk factors associated with OS and PFS. And sub-analysis was performed to investigate whether metformin could give a survival advantage in each Barcelona Clinic Liver Cancer (BCLC) stage of HCC. Propensity score matched (PSM) analyses based on patient and tumor characteristics were also conducted. Results: A total of 123 HCC patients with T2DM underwent TACE, of which 50 (40.65%) received treatment with metformin. For the whole cohort, the median OS (42 vs 32 months, p=0.054) and PFS (12 vs 7 months, P=0.0016) were longer in the metformin group than that in the non-metformin group. Multi-analysis revealed that BCLC stage, BMI (Body Mass Index), and metformin use were independent predictors of OS. Metformin use was independently associated with recurrence. After PSM, 39 matched pairs were identified. The use of metformin was associated with a numerically longer m OS (43 vs 35 months, P=0.183) than the use of other anti-diabetics. And the difference in median PFS (13 vs 7 months, p=0.018) between the metformin group and non-metformin group remained significant. Conclusion: The combination of transarterial chemoembolization and metformin may be associated with better OS and PFS in HCC patients with T2DM.

Overweight with HBV infection limited the efficacy of TACE in hepatocellular carcinoma by inhibiting the upregulated HMGB1.

BACKGROUND: Transarterial chemoembolization (TACE) is an effective treatment for patients with hepatocellular carcinoma (HCC). However, the impact of hepatitis B viral (HBV) infection and body mass index (BMI) on TACE is controversial. The present study aimed to compare the influence of HBV and high BMI on TACE outcomes in advanced HCC. METHODS: Based on HBV infection history and BMI, patients were assigned to different subgroups. Blood samples were collected and analyzed by an enzyme-linked immunosorbent assay (ELISA) kit. The primary endpoint was progression-free survival (PFS) and the overall survival (OS) in the population. RESULTS: Compared to overweight combined HBV patients who received TACE, people with normal weight or no viral infection had significantly better OS and PFS. Sex, age, portal vein tumor thrombus, BCLC, ECOG, and tumor diameter are the main risk factors affecting PFS and OS. Except for the postoperative fever, no significant difference was detected in adverse reactions. Irrespective of TACE, the average expression of HMGB1 in hepatitis or obesity patients was higher than that in normal individuals and did not show upregulation after TACE. Patients without overweight or HBV infection had a low expression of serum HMGB1 that was substantially upregulated after TACE. CONCLUSIONS: In this study, overweight combined HBV infection patients had shorter PFS and OS than other HCC patients. Thus, HBV and BMI maybe two factors affecting the efficacy of TACE via upregulated HMGB1.

Percutaneous Radiofrequency Ablation Combined With Chemotherapy Versus Chemotherapy Only for Ovarian Cancer Liver Metastasis.

PURPOSE: To compare the feasibility and efficacy of radiofrequency ablation (RFA) combined with chemotherapy and chemotherapy alone in patients with ovarian cancer liver metastasis (OCLM). METHODS: In this retrospective study, a total of 60 patients diagnosed with OCLM between May 2015 to February 2017 were included. All patients with ovarian cancer received chemotherapy and primary cytoreductive surgery before. Thirty patients underwent RFA and chemotherapy, and thirty patients only took chemotherapy. The overall survival (OS), CA-125 levels, and serum AST and ALT levels were compared between the two groups. RESULTS: In the RFA group, the 1-,2-, and 3-year OS rates after RFA were 93.3%, 80.0%, and 53.3%, respectively. Serum AST and ALT levels were both elevated after RFA (p=0.0004, p<0.0001). In the chemotherapy group, the 1-,2-, and 3-year OS rates were 79.5%, 60.1%, and 42.1%, respectively. Levels of serum AST and ALT were stable. CA-125 levels for both groups were also available. CONCLUSION: Based on our analysis of a single institution's series of patients with OCLM, RFA could be a feasibly effective option in the management of OCLM.

HMGB1, the Next Predictor of Transcatheter Arterial Chemoembolization for Liver Metastasis of Colorectal Cancer?

HMGB1 is an important mediator of inflammation during ischemia-reperfusion injury on organs. The serum expression of HMGB1 was increased significantly on the 1st day after TACE and decreased significantly which was lower on the 30th day after TACE. Tumor markers of post-DEB-TACE decreased significantly. The correlational analysis showed that patients with low HMGB1 expression had lower risks of fever and liver injury compared those with the higher expression, while the ORR is relatively worse. Patients with lower expression of HMGB1 had longer PFS, better efficacy, and higher quality of life. With the high post-expression, the low expression had lower incidence of fever and liver injury too. There was no statistical difference in the one-year survival among the different groups. The quality of life of all patients was improved significantly. The over-expression of HMGB1 in LMCRC is an adverse prognostic feature and a positive predictor of response to TACE.

Efficacy of radiofrequency ablation and microwave ablation in the treatment of thoracic cancer: A systematic review and meta-analysis.

BACKGROUND: Radiofrequency ablation and microwave ablation are frequently prescribed for thoracic cancer. However, few writers have been able to draw on any systematic research into the differences between the two ablation methods. METHODS: A literature search was carried out using Embase, PUBMED, Web of Science, Cochrane Library, and CNKI databases, with additional searches carried out manually using terms associated with thoracic cancer and thermal ablation. Then we used Google Scholar for a complementary search. Data were extracted from studies of patients that underwent radiofrequency ablation or microwave ablation, and the investigator carried out efficacy evaluation and follow up. The data obtained from the literature were summarized and analyzed using Cochrane Revman software Version 5.3 and SPSS 22.0. RESULTS: There were seven comparative studies, but no randomized studies identified for data extraction; 246 patients received radiofrequency ablation therapy and 319 controls received microwave ablation. There was no significant difference in the six-month, one-year, two-year, and three-year survival rates, and adverse reactions were found in the two treatments. For patients' long-term survival rate, the two treatments can achieve a similar survival time. CONCLUSION: In the treatment of thoracic cancer, microwave ablation can achieve the same efficacy as radiofrequency ablation.

Expert consensus on image-guided radiofrequency ablation of pulmonary tumors: 2018 edition.

Lung cancer ranks first in incidence and mortality in China. Surgery is the primary method to cure cancer, but only 20-30% of patients are eligible for curative resection. In recent years, in addition to surgery, other local therapies have been developed for patients with numerous localized primary and metastatic pulmonary tumors, including stereotactic body radiation therapy and thermal ablative therapies through percutaneously inserted applicators. Percutaneous thermal ablation of pulmonary tumors is minimally invasive, conformal, repeatable, feasible, cheap, has a shorter recovery time, and offers reduced morbidity and mortality. Radiofrequency ablation (RFA), the most commonly used thermal ablation technique, has a reported 80-90% rate of complete ablation, with the best results obtained in tumors < 3 cm in diameter. Because the clinical efficacy of RFA of pulmonary tumors has not yet been determined, this clinical guideline describes the techniques used in the treatment of localized primary and metastatic pulmonary tumors in nonsurgical candidates, including mechanism of action, devices, indications, techniques, potential complications, clinical outcomes, post-ablation surveillance, and use in combination with other therapies. In the future, the role of RFA in the treatment of localized pulmonary tumors should ultimately be determined by evidence from prospective randomized controlled trials comparing sublobar resection or stereotactic body radiation therapy.

TRAF4 promotes the growth and invasion of colon cancer through the Wnt/ß-catenin pathway.

The tumor necrosis factor receptor-associated factor 4 (TRAF4) has been linked to carcinogenesis. However, the role of TRAF4 in colon cancer is still unclear. Therefore, we investigated the role of TRAF4 in colon cancer and the underlying mechanism. In the present study, we found that TRAF4 was overexpressed in colon cancer tissues and cells, and small interfering RNA (siRNA)-mediated gene knockdown of TRAF4 significantly inhibited cell proliferation, invasion and tumorigenesis, both in vitro and in vivo, but induced apoptosis in colon cancer cells. Furthermore, siRNA-TRAF4 significantly inhibited the expression levels of ß-catenin, cyclinD1, and c-myc proteins in colon cancer cells. Taken together, these results suggest that TRAF4 promoted colon cancer cell growth and invasion by potentiating the Wnt/ß-catenin pathway, suggesting that TRAF4 may be a potential molecular target for colon cancer prevention and therapy.

Induction of apoptosis by IGFBP3 overexpression in hepatocellular carcinoma cells.

BACKGROUND: The insulin-like growth factor (IGF) system comprises a group of proteins that play key roles in regulating cell growth, differentiation, and apoptosis in a variety of cellular systems. The aim of this study was to investigate the role of insulin-like growth factor binding protein 3 (IGFBP3) in hepatocellular carcinoma. MATERIALS AND METHODS: Expression of IGF2, IGFBP3, and PTEN was analyzed by qRT-PCR. Lentivirus vectors were used to overexpress IGFBP3 in hepatocellular carcinoma cell (HCC) lines. The effect of IGFBP3 on proliferation was investigated by MTT and colony formation assays. RESULTS: Expression of IGF2, IGFBP3, and PTEN in several HCC cell lines was lower than in normal cell lines. After 5-aza-2'-deoxycytidine/trichostatin A treatment, significant demethylation of the promoter region of IGFBP3 was observed in HCC cells. Overexpression of IGFBP3 induced apoptosis and reduced colony formation in HUH7 cells. CONCLUSIONS: Expression of IGF2, IGFBP3, and PTEN in several HCC cell lines was lower than in normal cell lines. After 5-aza-2'-deoxycytidine/ trichostatin A treatment, significant demethylation of the promoter region of IGFBP3 was observed in HCC cells. Overexpression of IGFBP3 induced apoptosis and reduced colony formation in HUH7 cells.

The -842G/C polymorphisms of PIN1 contributes to cancer risk: a meta-analysis of 10 case-control studies.

BACKGROUND: Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 (PIN1) plays an important role in cancer development. The relationship between PIN1 -842G/C (rs2233678) polymorphism and cancer risk was inconclusive according to published literature. METHODOLOGY/PRINCIPAL FINDINGS: A literature search, up to February 2013, was carried out using PubMed, EMBASE and the China National Knowledge Infrastructure (CNKI) database. A total of 10 case-control studies including 4619 cases and 4661 controls contributed to the quantitative analysis. Odds ratio (OR) and 95% confidence intervals (95% CI) were used to assess the strength of association. Overall, individuals with the variant CG (OR = 0.728, 95% CI: 0.585,0.906; Pheterogeneity<0.01) and CG/CC (OR = 0.731, 95% CI: 0.602,0.888; Pheterogeneity<0.01) genotypes were associated with a significantly reduced cancer risk compared with those with wild GG genotype. Sub-group analysis revealed that the variant CG (OR = 0.635, 95% CI: 0.548,0.735; Pheterogeneity = 0.240) and CG/CC (OR = 0.645, 95% CI: 0.559,0.744, Pheterogeneity = 0.258) genotypes still showed an reduced risk of cancer in Asians; while no significant association was observed in Caucasians (CG vs.GG: OR = 0.926, 95% CI: 0.572,1.499, Pheterogeneity<0.01; CG/CC vs. GG: OR = 0.892, 95% CI: 0.589,1.353; Pheterogeneity<0.01). Furthermore, sensitivity analysis confirmed the stability of results. Begg's funnel plot and Egger's test did not reveal any publication bias. CONCLUSIONS: This meta-analysis suggests that the PIN1 -842G/C polymorphism is associated with a significantly reduced risk of cancer, especially in Asian populations.

[Inhibitory effect of silencing of HMGB1 gene expression on the invasive and metastatic abilities of MGC-803 gastric cancer cells].

OBJECTIVE: To investigate the effect of high mobility group box-1 (high mobility group box B 1, HMGB1) on the invasive and metastatic abilities of gastric cancer cell line MGC-803 and analyze the possible mechanisms. METHODS: HMGB1 gene targeting siRNA was designed and synthesized, and HMGB1 siRNA oligonucleotides were transfected into the MGC-803 cells with Lipofectamine 2000. The invasive and migratory abilities were detected by transwell assay and scratch assay. The Matrigel matrix glue adhesive ability of MGC-803 cells was evaluated by MTT assay. NF-κB activity was detected by electrophoretic mobility shift assay. The mRNA and protein levels of HMGB1 and MMP-9 were determined by RT-PCR and Western blot, respectively. RESULTS: The siRNA down-regulated the levels of HMGB1 mRNA and protein. Compared with that of the control group, the number of invasive (142.7 ± 3.4 /view vs. 303.5 ± 4.3/view) and migratory (293.7 ± 4.4/view vs. 445.5 ± 5.6/view) cells was significantly increased (P < 0.05) and the adhesive ability of MGC-803 cells to Matrigel was significantly elevated (33.4 ± 0.03% vs. 57.4 ± 4.2%, P < 0.05). In addition, silencing of HMGB1 gene significantly inhibited the activity of NF-κB and the relative expression folds of mRNA (0.2 ± 0.1 vs. 1.4 ± 0.4, P < 0.05)and protein (0.4 ± 0.1 vs. 2.3 ± 0.7, P < 0.05) of MMP-9. CONCLUSION: Silencing of HMGB1 can effectively inhibit the invasion and migration of gastric cancer cells and this effect of HMGB1 may be partly due to its regulation of NF-κB and MMP-9 expressions.

[Comparison of three methods to delineate internal gross target volume of the primary hepatocarcinoma based on four-dimensional CT simulation images].

OBJECTIVE: To compare the position and magnitude of internal target gross volume (IGTV) of primary hepatocarcinoma delineated by three methods based on four-dimensional computed tomography (4D-CT) and to investigate the relevant factors affecting the position and magnitude. METHODS: Twenty patients with primary hepatocarcinoma after transcatheter arterial chemoembolization (TACE) underwent big bore 4D-CT simulation scan of the thorax and abdomen using a real-time position management (RPM) system for simultaneous record of the respiratory signals. The CT images with respiratory signal data were reconstructed and sorted into 10 phase groups in a respiratory cycle, with 0% phase corresponding to end-inhale and 50% corresponding to end-exhale. The maximum intensity projection (MIP) image was generated. IGTVs of the tumor were delineated using the following three methods: (1) The gross tumor volume (GTV) on each of the ten respiratory phases of the 4D-CT image set was delineated and fused ten GTV to produce IGTV10; (2) The GTVs delineated separately based on 0% and 50% phase were fused to produce IGTV(IN+EX); (3) The visible tumor on the MIP image was delineated to produce IGTV(MIP). Twenty patients were divided into groups A and B based on the location of the target center,and were divided into groups C and D based on the tumor maximum diameter. The patients were divided into groups E and F based on the three-dimensional (3D) motion vector of the target center. The position of the target center, the volume of target, the degree of inclusion (DI) and the matching index (MI) were compared reciprocally between IGTV10, IGTV(IN+EX) and IGTV(MIP), and the influence of the tumor position and 3D motion vector on the related parameters were compared based on the grouping. RESULTS: The average differences between the position of the center of IGTVs on direction of X, Y and Z axes were less than 1.5 mm, and the difference was statistically not significant. The volume of IGTV10 was larger than that of IGTV(IN+EX), but the difference was not significant (t = 0.354, P = 0.725). The volume of IGTV10 was larger than that of IGTV(MIP) but the difference was not significant (t = -0.392, P = 0.697). The ratio of IGTV(IN+EX) to IGTV10 was 0.75 +/- 0.15 and the ratio of IGTV(MIP) to IGTV10 was 0.78 +/- 0.14. The DI of IGTV(IN+EX) in IGTV10 was (74.85 +/- 15.09)% and that of IGTV(MIP) in IGTV10 was (68.87 +/- 13.69)%. The MI between IGTV10 and IGTV(IN+EX), IGTV10 and IGTV(MIP) were 0.75 +/- 0.15 and 0.67 +/- 0.13, respectively. The median of ratio of IGTV(IN+EX)/ IGTV10 was 0.57 in group A versus 0.87 in group B, statistically with a significant difference between the groups A and B (Z = -3.300,P = 0.001). The median of ratio of IGTV(MIP)/IGTV10 was 0.51 in the group A and 0.72 in group B, with a significant difference between the groups A and B (Z = -3.413, P = 0.001). The median of ratio of IGTV(IN+EX)/IGTV10 was 0.79 in group C versus 0.74 in group D, with a difference not significant (Z = -0.920, P = 0.358). The median of ratio of IGTV(MIP)/IGTV10 was 0.85 in group C versus 0.80 in group D, with a non-significant difference (Z = -0.568, P = 0.570). The median of ratio of IGTV(IN+EX)/IGTV10 was 0.87 in group E versus 0.68 in group F, with a significant difference between the two groups (Z = -2.897, P = 0.004). The median of ratio of IGTV(MIP)/IGTV10 was 0.85 in the group E versus 0.81 in the group F, with a non-significant difference (Z = -0.568, P = 0.570). CONCLUSIONS: The center displacement of the IGTVs delineated separately by the three techniques based on 4D-CT images is not obvious. IGTV(IN+EX) and IGTV(MIP) can not replace IGTV10, however, IGTV(IN+EX) is more close to IGTV10 comparing with IGTV(MIP). The ratio of IGTV10 and IGTV(MIP) is correlated to the 3D motion vector of the tumor. When the tumor is situated in the upper part of the liver and with a 3D motion vector less than 9 mm, IGTV10 should be the best IGTV.

[Inhibitory effect of compound cantharides capsule on the proliferation of xenografts of human hepatocellular carcinoma HepG(2)215 in mice].

OBJECTIVE: To investigate the inhibitory effect of compound cantharides capsules on the proliferation of xenografts of human hepatocellular carcinoma HepG(2215) in mice and their mechanism of action. METHODS: One hundred healthy Balb/c mice (5-week old, male:female 1:1) were used in this study. Mouse models of human HepG(2215) hepatocarcinoma were established. The tumor-bearing mice were divided into five groups randomly. The control group A received daily intragastric administration of physiologic saline. The intervention groups B1, B2 and B3 were treated with compound cantharides capsule in a dose of 12.5 mg×kg(-1)×d(-1), 25 mg×kg(-1)×d(-1) and 37.5 mg×kg(-1)×d(-1), respectively, for 10 consecutive days. The group C had intraperitoneal injection of cyclophosphamide (25 mg×kg(-1)×d(-1)) for 10 consecutive days. The mice were sacrificed after the completion of administration. The tumors were taken out, the tumor volume was measured, the inhibitory rate of body weight was calculated, and the serum AFP concentration and the level of HBV DNA were determined. The survival of each group mice was analyzed. The levels of mRNA expression of apoptosis-related genes were assayed by quantitative RT-PCR. Apoptosis in the tumor cells was assayed with TUNEL staining. Flow cytometry was used to detect the levels of CD3(+), CD19(+), CD4(+) and CD8(+), and microvessel density (MVD) of the tumors was assessed by immunohistochemistry. RESULTS: After completion of the treatment, the inhibition rate of tumor growth of the groups B1, B2 and B3 was 29.8%, 38.7% and 48.1%, respectively, and that of the group C was 52.4%, with a significant difference among the groups (P < 0.05). The median survival time of the groups A, B1, B2, B3 and C was (30.0 ± 3.2) days, (49.0 ± 5.1) days, (50.0 ± 5.2) days, (57.5 ± 6.5) days and (49.0 ± 4.7) days, respectively. The median survival time of the group B3 was significantly longer than that of other groups (P < 0.05). The serum AFP level in the groups A, B1, B2, B3 and C was (492.7 ± 48.5) ng/ml, (281.2 ± 25.6) ng/ml, (194.3 ± 18.7) ng/ml, (170.1 ± 15.8) ng/ml and (138.7 ± 12.5) ng/ml, respectively, indicating that it was significantly inhibited in the group C. The inhibition rate of HBV DNA replication of the groups B1, B2, B3 and C was (46.0 ± 5.1)%, (65.5 ± 6.9)%, (81.3 ± 7.8)% and (19.5 ± 2.1)%, respectively, showing that compound cantharides capsules inhibited HBV DNA replication in a dose-dependent manner. The apoptosis rate of the groups A, B1, B2, B3 and C was (0.27 ± 0.03)%, (7.18 ± 2.12)%, (9.17 ± 2.42)%, (11.27 ± 3.03)% and (5.44 ± 2.45)%, respectively, and that of the group B3 was significantly higher than that of the groups A, B1, B2 and C (P < 0.05). The expression level of bax mRNA was significantly higher than that of the group C (P < 0.05). The drug could significantly decrease the bcl-2 mRNA expression level, more remarkably along with the increasing dose of cantharides, and it was significantly lower than that in the group C (P < 0.05). The levels of CD4(+), CD8(+), CD3(+) and CD19(+) were significantly higher than that in the groups A and C (P < 0.05). The value of MVD of the group B3 was significantly lower that that of groups A and C (P < 0.05). CONCLUSION: Compound cantharides capsules may inhibit the replication of HBV DNA in HepG(2215) cells, inducing apoptosis in the tumor cells, enhancing the immune function to inhibit the growth of liver cancer cells in mice, and significantly prolong the median survival time of tumor-bearing mice.

Microwave ablation: results in ex vivo and in vivo porcine livers with 2450-MHz cooled-shaft antenna.

BACKGROUND: Imaging-guided thermal ablation using different energy sources continues to gain favor as a minimally invasive technique for the treatment of primary and metastatic hepatic malignant tumors. This study aimed to evaluate the performance of microwave ablation with 2450-MHz internally cooled-shaft antenna in ex vivo and in vivo porcine livers. METHODS: All studies were animal care and ethics committee approved. Microwave ablation was performed using a noncooled or cooled-shaft antenna in 23 ex vivo (92 ablations) and eight in vivo (36 ablations) porcine livers. Diameters of the coagulation zone were observed on gross specimens. The coagulation diameters achieved in different microwave ablation parameter groups were compared. Curve estimation analysis was performed to characterize the relationship between applied power and treatment duration and coagulation diameter (including short-axis and long-axis diameter). RESULTS: Coagulation zones were elliptical and an arrowed-shaped carbonization zone around the shaft was observed in all groups. But the antenna track was also coagulated in the noncooled-shaft antenna groups. In ex vivo livers, the short-axis diameter correlated with the power output in a quadratic curve fashion (R(2) = 0.95) by fixing ablation duration to 10 minutes, and correlated with the ablation duration in a logarithmic curve fashion (R(2) = 0.98) by fixing power output to 80 W. The short-axis reached a relative plateau within 25 minutes. In in vivo livers, short-axis diameter correlated with the coagulation duration in a sigmoidal curve fashion (60 W group R(2) = 0.76, 80 W group R(2) = 0.87), with a relative plateau achieved within 10 minutes for power settings of 60 W and 80 W. CONCLUSIONS: The internally cooled microwave antenna may be advantageous to minimize collateral damage. The short-axis diameter enlargement has a plateau by fixing power output.

[Nuclear localization of insulin-like growth factor binding protein-6].

OBJECTIVE: To study the nuclear localization of insulin-like growth factor binding protein-6(IGFBP-6) in PC-3M cells. METHODS: The two fragments of the nuclear localization sequence (NLS)-deleted IGFBP-6 and the NLS-mutated IGFBP-6 were obtained by overlapping PCR, and then the fragment was inserted into a pEGFP-C1 vector. PC-3M cells were transfected with the expression constructs containing wild-type IGFBP-6 or the two mutants (pEGFP-C1-BP6 Delta NLS and pEGFP-C1-BP6-Mut), and the different distribution of the three EGFP-fusion proteins was observed by confocal laser microscope. The statistical analysis of the ratio of the nuclear fluorescence to the cytoplasmic fluorescence (Fn/c) was performed. Results Confocal microscopic images of transfected cells showed that the green fluorescence of EGFP-IGFBP-6 was concentrated mostly in the nuclei, whereas the control cells expressing EGFP showed green fluorescence distributed uniformly. The results of Fn/c from EGFP and EGFP-IGFBP-6 were significant different (P<0.05). The NLS-deleted IGFBP-6 completely eliminated nuclear accumulation of the green fluorescent signal; in contrast, nuclear accumulation was only slightly reduced for the NLS-mutated IGFBP-6; compared with wild-type IGFBP-6, both mutants were significantly different (P<0.05). Conclusions IGFBP-6 can be translocated to the nucleus in PC-3M cell that is mediated by a putative NLS sequence. Our study provides new evidence for further studies on the insulin-like growth factor-independent activity of IGFBP-6.

[Significance of telomerase expression in diagnosis and treatment of breast tumor].

BACKGROUND AND OBJECTIVE: It was reported that the activation of telomerase can turn normal cell into tumor cell. This study was designed to investigate the expression of telomerase in breast tumor and its value for early diagnosis and treatment. METHODS: Telomerase expression in 178 breast tumor specimens was detected by using PCR-ELISA immunohistochemical method. RESULTS: Positive expression rate of telomerase in primary breast carcinoma, precancerous lesion of breast, breast fiber tumor were 86.72% (111/128), 46.67% (7/15), and 26.66% (4/15), respectively. Negative expression of telomerase was shown in normal breast tissue and cystic hyperplasia tissue. Positive expression rate of telomerase in different clinical stage were 63.16% in stage I, 85.96% in stage II, 95.65% in stage III, 100% in stage IV, respectively. Positive expression rate of telomerase in the patients with and without positive axillary lymph node were 95.83% (69/72) and 75(42/56), respectively. CONCLUSION: Expression of telomerase was closely associated with clinical stages of breast cancer (P < 0.005) and metastases of axillary lymph node (P < 0.01). Special importance is that its expression was found in breast precancerous lesion, indicating its is significance in early diagnosis of breast cancer.