Hypochlorite-induced oxidative stress elevates the capability of HDL in promoting breast cancer metastasis.

BACKGROUND: Previous studies suggest that oxidative stress plays an important role in the development of breast cancer. There is a significant inverse relationship between HDL and the risk and mortality of breast cancer. However, it is well known that under conditions of oxidative stress, such as breast cancer, HDL can be oxidatively modifiedand these modifications may have an effect on the functions of HDL. The purpose of this study is to determine the different effects of normal and oxidized (caused by hypochlorite-induced oxidative stress) HDL on breast cancer cell metastasis. METHODS: Human breast cancer cell lines were treated with normal and hypochlorite-oxidized HDL, and then cell metastasis potency in vivo and the abilities of migration, invasion, adhesion to HUVEC and ECM in vitro were examined. Integrin expression and PKC activity were evaluated, and PKC inhibitor and PKC siRNA was applied. RESULTS: We found hypochlorite-oxidized HDL dramatically promotes breast cancer cell pulmonary metastasis (133.4% increase at P < 0.0 l for MDA-MB-231 by mammary fat pad injection; 164.3% increase at P < 0.01 for MCF7 by tail vein injection) and hepatic metastasis (420% increase at P < 0.0 l for MDA-MB-231 by mammary fat pad injection; 1840% fold increase at P < 0.001 for MCF7 by tail vein injection) in nude mice, and stimulates higher cell invasion (85.1% increase at P < 0.00 l for MDA-MB-231; 88.8% increase at P < 0.00 l for MCF7;), TC-HUVEC adhesion (43.4% increase at P < 0.00 l for MDA-MB-231; 35.2% increase at P < 0.00 l for MCF7), and TC-ECM attachment (41.0% increase at P < 0.00 l for MDA-MB-231; 26.7% increase at P < 0.05 for MCF7) in vitro compared with normal HDL. The data also shows that the PKC pathway is involved in the abnormal actions of hypochlorite-oxidized HDL. CONCLUSIONS: Our study demonstrated that HDL under hypochlorite-induced oxidative stress stimulates breast cancer cell migration, invasion, adhesion to HUVEC and ECM, thereby promoting metastasis of breast cancer. These results suggest that HDL-based treatments should be considered for treatment of breast cancer patients.

Low temperature of radiofrequency ablation at the target sites can facilitate rapid progression of residual hepatic VX2 carcinoma.

BACKGROUND: Rapid progression of residual tumor after radiofrequency ablation (RFA) of hepatocellular carcinoma has been observed increasingly. However, its underlying mechanisms remain to be clarified. The present study was designed to determine whether low temperature of RFA at the target sites facilitates rapid progression of residual hepatic VX2 carcinoma and to clarify the possible underlying mechanisms. METHODS: The residual VX2 hepatoma model in rabbits was established by using RFA at 55, 70 and 85 degrees C. Rabbits that were implanted with VX2 hepatoma but did not receive RFA acted as a control group. The relationship between rapid progression of residual hepatic VX2 carcinoma and low temperature of RFA at the target sites was carefully evaluated. A number of potential contributing molecular factors, such as proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 9 (MMP-9), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF) and Interleukin-6 (IL-6) were measured. RESULTS: The focal tumor volume and lung metastases of RFA-treated rabbits increased significantly compared with the control group (P < 0.05), and the greatest changes were seen in the 55 degrees C group (P < 0.05). Expression of PCNA, MMP-9, VEGF, HGF and IL-6 in tumor tissues increased significantly in the RFA-treated groups compared with the control group, and of the increases were greatest in the 55 degrees C group (P < 0.05). These results were consistent with gross pathological observation. Tumor re-inoculation experiments confirmed that low temperature of RFA at the target sites facilitated rapid progression of residual hepatic VX2 carcinoma. CONCLUSIONS: Insufficient RFA that is caused by low temperature at the target sites could be an important cause of rapid progression of residual hepatic VX2 carcinoma. Residual hepatic VX2 carcinoma could facilitate its rapid progression through inducing overexpression of several molecular factors, such as PCNA, MMP-9, VEGF, HGF and IL-6.

Heme is involved in the systemic inflammatory response following radiofrequency ablation of hepatic hemangiomas.

OBJECTIVE: Radiofrequency ablation (RFA) is an effective and minimally invasive treatment for managing hepatic hemangiomas. Systemic inflammatory response syndrome (SIRS) often occurs with hemoglobinuria, and its underlying pathophysiological mechanism is unknown. Heme can trigger inflammation by inducing the generation of reactive oxygen species (ROS) and the production of inflammatory mediators. We therefore investigated whether circulating heme is involved in SIRS following RFA of hepatic hemangiomas. METHODS: We enrolled 65 patients with hepatic hemangioma who underwent RFA. Serum concentrations of free heme, ROS, and tumor necrosis factor α (TNF-α) were measured after RFA. Univariate analysis and a multivariate binary logistic regression model were used to evaluate the contribution of 17 risk factors for SIRS after RFA. RESULTS: Fifty-nine (59/65, 90.8%) patients developed hemoglobinuria, among which 25 (25/59, 42.4%) experienced SIRS shortly after RFA. In the SIRS group, the serum concentrations of heme, ROS, and TNF-α were immediately elevated after RFA compared with baseline and slowly regained their normal levels 3 days after RFA. Moreover, the concentrations of circulating heme significantly correlated with those of ROS (r = 0.805, P < 0.001) and TNF-α (r = 0.797, P < 0.001). Multivariate analysis showed that the volume of hemangioma [odds ratio (OR) = 1.293, P = 0.031], time of ablation (OR = 1.194, P = 0.029) as well as the concentrations of heme (OR = 1.430, P = 0.017), ROS (OR = 1.251, P = 0.031), and TNF-α (OR = 1.309, P = 0.032) were significantly associated with SIRS. CONCLUSION: Circulating heme was associated with the induction of ROS and the production of TNF-α, which may contribute to the induction of SIRS following RFA of hepatic hemangiomas.

Resection as first-line therapy for large hepatic sclerosing hemangioma: a case report.

Hepatic sclerosing hemangioma is a rare benign disease that occurs in association with hepatic cavernous hemangioma degeneration and sclerosis. Recent studies have shown that radiofrequency (RF) ablation is an alternative treatment for hepatic cavernous hemangiomas, even for large hemangiomas (≥10 cm). However, RF ablation might not be suitable to treat large sclerosing hemangiomas. We herein report the successful surgical removal of a large hepatic sclerosing hemangioma after RF ablation treatment failure in a 65-year-old man. In conclusion, we suggest that resection should be chosen as a first-line therapy for the disease.

miR-152-3p Modulates hepatic carcinogenesis by targeting cyclin-dependent kinase 8.

BACKGROUND: Cyclin-dependent kinase 8 (CDK8) as a Mediator complex-associated transcriptional regulator has been shown to play important role in the initiation and progression of various cancers. The present study aimed to explore miR-152-3p-modulated post-transcriptional repression of CDK8 in hepatic carcinogenesis. METHODS: Eighty-nine pairs of hepatocellular carcinoma (HCC) and adjacent non-tumor tissues were collected for molecular biological analysis. Cell viability and apoptosis assays were detected using CCK8 and Annexin V-fluorescein isothiocyanate/propidium iodide (Annexinv-FITC) double staining, respectively. Bioinformatics algorithms and luciferase reporter assay were performed to validate CDK8 as a direct target of miR-152-3p. Gene and protein expression levels were monitored using RT-qPCR, western blotting or immunohistochemical (IHC) staining. RESULTS: CDK8 expression levels were up-regulated and miR-152-3p was down-regulated in HCC tissues. The correlation analysis had documented a significant negative correlation between miR-152-3p and CDK8 in the HCC tissues. Both CDK8 and miR-152-3p could serve as the independent prognostic factors for predicting the OS and DFS in HCC patients. Bioinformatics and experimental measurement revealed that CDK8 was a direct target of miR-152-3p. After co-transfection with the miR-152-3p mimics and the CDK8 overexpressed plasmids, the anti-proliferative and pro-apoptotic roles of miR-152-3p were restricted by CDK8. CONCLUSION: The present results obtained forcefully proved that miR-152-3p exhibited an antineoplastic activity via targeting CDK8 and might be served as a potential therapeutic target for the treatment of HCC.

Insufficient radiofrequency ablation-induced autophagy contributes to the rapid progression of residual hepatocellular carcinoma through the HIF-1α/BNIP3 signaling pathway.

Currently speaking, it is noted that radiofrequency ablation (RFA) has been the most widely used treatment for hepatocellular carcinoma (HCC) occurring in patients. However, accumulating evidence has demonstrated that the incidence of insufficient RFA (IRFA) may result in the identified rapid progression of residual HCC in the patient, which can greatly hinder the effectiveness and patient reported benefits of utilizing this technique. Although many efforts have been proposed, the underlying mechanisms triggering the rapid progression of residual HCC after IRFA have not yet been fully clarified through current research literature reviews. It was shown in this study that cell proliferation, migration and invasion of residual HepG2 and SMMC7721 cells were significantly increased after the IRFA was simulated in vitro. In other words, it is noted that IRFA could do this by enhancing the image of autophagy of the residual HCC cell via the HIF-1α/BNIP3 pathway. Consequently, the down-regulation of BNIP3 may result in the inhibition of the residual HCC cell progression and autophagy after IRFA. Our present study results suggest that IRFA could promote residual HCC cell progression in vitro by enhancing autophagy via the HIF-1α/BNIP3 pathway. For this reason, it is noted that the targeting of the BNIP3 may be useful in preventing the rapid growth and metastasis of residual HCC after IRFA. [BMB Reports 2019; 52(4): 277-282].

A Severe Complication of Myocardial Dysfunction Post Radiofrequency Ablation Treatment of Huge Hepatic Hemangioma: A Case Report and Literature Review.

In recent years, radiofrequency (RF) ablation has been increasingly used for treating hepatic hemangiomas attributing to its unique advantages, such as minimal invasiveness, definite efficacy, high safety, fast recovery, and wide applicability. However, complications related to RF ablation had been frequently reported, especially while being used for treating huge hemangioma (≥10 cm). Cautious measures had been taken to prevent the incidence of ablation-induced complications, but still unexpected complications occurred. Herein we reported a case of severe myocardial dysfunction along with systemic inflammatory response syndrome occurring immediately post RF ablation of a 10.7 cm hemangioma. This serious complication was effectively managed by supportive care with the full recovery in a short period of time.

Percutaneous extrapulmonary radiofrequency ablation for tumors in the hepatic dome.

BACKGROUND/AIMS: This study aims to assess the feasibility of one lung ventilation and computed tomography-guided extrapulmonary percutaneous radiofrequency ablation for tumors in the hepatic dome. METHODOLOGY: Eleven patients (10 men, 1 women; age range, 34-84 years) with 12 tumors in the hepatic dome were enrolled in the study after institutional review board approval and informed consent had been obtained. A 35F or 37F left-sided double-lumen endotracheal tube was intubated after general anesthesia was induced. The right lung is permitted to collapse, with selective left lungs ventilation. With CT monitoring, the RF electrode was inserted through the empty pleural space to the targeted tumor and radiofrequency ablation procedures were performed. RESULTS: The median operative time was 122 minutes. The median one lung ventilation time was 134 minutes. The procedures of one lung ventilation and percutaneous radiofrequency ablation were successfully performed. There was no bronchial intubation, one lung ventilation and percutaneous radiofrequency ablation related complications, excluding minor pleural effusions recovering without thoracentesis in 2 patients. Complete tumor necrosis was achieved in 10 patients (90.9%). CONCLUSIONS: One lung ventilation and computed tomography guided percutaneous extrapulmonary radiofrequency ablation for tumors in the hepatic dome appears to be useful and safe.

[Percutaneous radiofrequency ablation therapy with left single lung ventilation for liver carcinoma in the hepatic dome].

OBJECTIVE: To evaluate the advantages of percutaneous radiofrequency ablation (PRFA) therapy with contralateral single lung ventilation (SLV) for liver carcinoma in the hepatic dome (LCHD). METHODS: The clinical data of 10 patients (the SLV group) with LCHD consecutively treated from January to December 2006 were retrospectively analyzed. And another 10 cases (the control group) with LCHD treated from January 2004 to December 2005 were selected with a strict inclusion criterion for compared test according to rules of same diagnosis, similar tumor bulk and site, same sex, similar age and liver function. The patients' ages and tumor diameters of the 2 groups were compared with t-test and the rates of complications and incomplete tumor ablation were compared with chi2-test. RESULTS: There was no statistical difference in ages and tumor diameters between the 2 groups (P > 0.05). The average number of radiofrequency ablation needle punctures in the SLV group was significantly less than the control group (3.4 +/- 0.4 vs. 6.1 +/- 0.8, P < 0.01). There was no bronchial intubation related complications like hypoxemia, atelectasis, lung infection and no puncture related complications like pneumothorax, hemothorax, hemoperitoneum and bile leakage in the SLV group. Two cases in the control group had complications including pneumothorax (n = 1) and pleural effusion (n = 1). There was no mortality in the 2 groups. Though the rate of incomplete tumor necrosis in the SLV group was not statistically lower than that in the control group (10% vs. 40%), the occurrence rate of the undesirable event (complication and incomplete tumor necrosis) of the SLV group was significantly lower than that of the control group (10% vs. 60%, P < 0.05). The durations and costs of operating procedure were not significantly different between the 2 groups. CONCLUSION: Left SLV makes PRFA for LCHD more efficient, effective and safe.

Radiofrequency ablation for hepatic hemangiomas: A consensus from a Chinese panel of experts.

Recent studies have shown that radiofrequency (RF) ablation therapy is a safe, feasible, and effective procedure for hepatic hemangiomas, even huge hepatic hemangiomas. RF ablation has the following advantages in the treatment of hepatic hemangiomas: minimal invasiveness, definite efficacy, high safety, fast recovery, relatively simple operation, and wide applicability. It is necessary to formulate a widely accepted consensus among the experts in China who have extensive expertise and experience in the treatment of hepatic hemangiomas using RF ablation, which is important to standardize the application of RF ablation for the management of hepatic hemangiomas, regarding the selection of patients with suitable indications to receive RF ablation treatment, the technical details of the techniques, therapeutic effect evaluations, management of complications, etc. A final consensus by a Chinese panel of experts who have the expertise of using RF ablation to treat hepatic hemangiomas was reached by means of literature review, comprehensive discussion, and draft approval.

Feasibility of radiofrequency ablation as an alternative to surgical intervention in patients with huge multiloculated pyogenic liver abscesses: A retrospective cohort study.

This retrospective cohort study investigated the feasibility of radiofrequency (RF) ablation as an alternative to surgical intervention in patients with huge multiloculated pyogenic liver abscesses (PLAs).From August 2010 to April 2016, 83 patients with PLA were admitted to Beijing Chao-Yang Hospital, China. Four of these patients had huge multiloculated PLAs and underwent RF ablation plus antibiotics. The inclusion criteria for RF ablation were as follows: multiloculated PLA confirmed by computed tomography (CT) or magnetic resonance imaging (MRI), widest diameter of the PLA ≥5 cm, failure to respond to or not suitable to treatment with percutaneous drainage (PD), and patient refusal of surgery. The safety and effectiveness of RF ablation were initially assessed. All patients were commenced on antibiotics on admission to our hospital. CT-guided percutaneous catheter drainage was attempted in one patient but was unsuccessful. The main organism isolated from cultures of these patients' blood or abscess samples was Klebsiella pneumoniae (3/4). RF ablation was performed as soon as eligibility according to the above criteria was established.RF ablation was technically successful in all 4 study patients, all PLAs being completely eradicated. The median duration of fever after RF ablation was 4.5 days. No abscesses recurred; thus, this strategy for managing PLA was 100% successful (4/4). No procedure-related deaths or major complications occurred. One patient had an asymptomatic right pleural effusion that resolved with conservative treatment including albumin infusion and diuretics.Our preliminary data indicate that RF ablation is a safe, feasible, and effective treatment for huge multiloculated PLAs. It should be considered as an alternative treatment for patients who fail to respond to or not suitable for PD plus antibiotics and refuse surgical intervention.

Repeated Radiofrequency Ablation Combined With Ablated Lesion Elimination and Transarterial Chemoembolization Improves the Outcome of Solitary Huge Hepatocellular Carcinomas 10 m or Larger.

This study investigated the effectiveness of a new strategy, repeated radiofrequency (RF) ablation combined with ablated lesion elimination following transarterial chemoembolization (TACE)/transarterial embolization (TAE), for solitary huge hepatocellular carcinoma (SHHCC) 10 cm or larger. From July 2008 to October 2015, 39 consecutive patients with SHHCC were screened. Of these, 12 were treated with TACE/TAE and repeated RF ablation (TACE/TAE + RF ablation group) and the remaining 27 patients were treated with the aforementioned new strategy (new strategy group). Local tumor progression (LTP)-free survival, intrahepatic distant recurrence (IDR)-free survival, and overall survival (OS) rates were obtained using the Kaplan-Meier method. Univariate and multivariate analyses were performed on several clinicopathological variables to identify factors affecting long-term outcome and intrahepatic recurrence. Correlation analysis was also performed. The 1-, 2-, and 3-year LTP-free survival rates and OS rates were significantly higher in the new strategy group than in the TACE/TAE + RF ablation group (82.9% vs 58.3%, 73.9% vs 29.2%, 18.5% vs 9.7%, P = 0.002; 92.0% vs 75.0%, 84.0% vs 33.3%, 32.7% vs 16.7%, P = 0.025). However, there was no significant difference between the 2 groups in the 1-, 2-, and 3-year IDR-free survival rates (P = 0.108). Using univariate analysis, alpha-fetoprotein (AFP > 200 ng/mL), ablative margin (AM > 1.0 cm), and well-differentiated cells were found to be significant factors for predicting LTP, IDR, and OS. Surgical elimination was found to be a significant factor only for predicting OS. In multivariate analyses, AFP (>200 ng/mL), AM (>1.0 cm), and well-differentiated cells were found to be significant independent factors linked to LTP, IDR, and OS. Correlation analysis indicated that AM > 1.0 cm was strongly associated with surgical elimination (P < 0.001, correlation coefficient = 0.877). For patients with SHHCC who were initially excluded from surgery, the new strategy including repeated RF ablation combined with ablated lesion elimination following TACE/TAE should now be considered as an alternative treatment.

Laparoscopic Radiofrequency Ablation for Large Subcapsular Hepatic Hemangiomas: Technical and Clinical Outcomes.

OBJECTIVES: The aim of this study was to evaluate the technical and clinical outcomes of using laparoscopic radiofrequency (RF) ablation for treating large subcapsular hepatic hemangiomas. METHODS: We retrospectively reviewed our sequential experience of treating 124 large subcapsular hepatic hemangiomas in 121 patients with laparoscopic RF ablation. RESULTS: The mean diameter of the 124 hemangiomas was 9.1 ± 3.2 cm (5.0-16.0 cm). RF ablation was performed successfully in all patients. There were 55 complications related to the ablation in 26 patients, including 5 of 69 (7.3%) patients with hemangioma <10 cm and 21 of 52 (40.4%) patients with hemangiomas ≥10 cm (P < 0.001). No injuries to abdominal viscera occurred in all the 121 patients. According to the Dindo-Clavien classification, all the complications were minor in 26 patients (Grade I). Out of 124 hepatic hemangiomas, 118 (95.2%) were completely ablated, including 70 of 72 (97.2%) lesions < 10 cm and 48 of 52 (92.3%) lesions ≥ 10 cm (P = 0.236). CONCLUSION: Laparoscopic RF ablation therapy is a safe, feasible and effective procedure for large subcapsular hepatic hemangiomas, even in the hepatic hemangiomas ≥ 10 cm. Its use avoids thermal injury to the abdominal viscera.

iTRAQ-based quantitative proteomic analysis of Pseudomonas aeruginosa SJTD-1: A global response to n-octadecane induced stress.

N-octadecane, the shortest solid-state alkane, was efficiently consumed by Pseudomonas aeruginosa SJTD-1. To reveal its mechanism, the iTRAQ-LC-MS/MS strategy was applied for quantification of proteins in response to alkane. As a result, 383 alkane-responsive proteins were identified and these proteins could be linked to multiple biochemical pathways. Above all, the level of alkane hydroxylase AlkB2 has been significantly higher in alkane condition. Also, the presence of a putative novel AlmA-like monooxygenase and its role on alkane hydroxylation were firstly proposed in Pseudomonas. In addition, other proteins for chemotaxic, ß-oxidation, glyoxylate bypass, alkane uptake, cross membrane transport, enzymatic steps and the carbon flow may have important roles in the cellular response to alkane. Most of those differently expressed proteins were functionally mapped into pathways of alkane degradation or metabolism thereof. In this sense, findings in this study provide critical clues to reveal biodegradation of long chain n-alkanes and rationally be important for potent biocatalyst for bioremediation in future. BIOLOGICAL SIGNIFICANCE: We use iTRAQ strategy firstly to compare the proteomes of Pseudomonas SJTD-1 degrading alkane. Changes in protein clearly provide a comprehensive overview on alkane hydroxylation of SJTD-1, including those proteins for chemotaxis, alkane uptake, cross membrane transport, enzymatic steps and the carbon flow. AlkB2 and a putative novel AlmA-like monooxygenase have been highlighted for their outstanding contribution to alkane use. We found that several chemotaxic proteins were altered in abundance in alkane-grown cells. These results may be helpful for understanding alkane use for Pseudomonas.

Radiofrequency ablation for single hepatocellular carcinoma 3 cm or less as first-line treatment.

AIM: To evaluate long-term outcomes of radiofrequency (RF) ablation as first-line therapy for single hepatocellular carcinoma (HCC) ≤ 3 cm and to determine survival and prognostic factors. METHODS: We included all 184 patients who underwent RF ablation as a first-line treatment for single HCC ≤ 3 cm between April 2005 and December 2013. According to the criteria of Livraghi, the 184 patients were divided into two groups: those suitable for surgical resection (84 cases) and those unsuitable for surgical resection (100 cases). The primary endpoints were the overall survival (OS) rate and safety; the secondary endpoints were primary technique effectiveness and recurrence rate. RESULTS: There were 19 (10.3%) cases of ablation related minor complications. The complete tumor ablation rate after one RF session was 97.8% (180/184). The rate of local tumor progression, extrahepatic metastases and intrahepatic distant recurrence were 4.9% (9/184), 9.8% (18/184) and 37.5% (69/184), respectively. In the 184 patients, the 1-, 3-, and 5-year OS rates were 99.5%, 81.0%, and 62.5%, respectively. The 1-, 3-, and 5-year OS rates were 100%, 86.9%, and 71.4%, respectively, in those suitable for surgical resection and 99.0%, 76.0%, and 55.0%, respectively, in those unsuitable for surgical resection (P = 0.021). On univariate and multivariate analyses, poorer OS was associated with Child-Pugh B class and portal hypertension (P < 0.05). CONCLUSION: RF ablation is a safe and effective treatment for single HCC ≤ 3 cm. The OS rate of patients suitable for surgical resection was similar to those reported in surgical series.

Radiofrequency ablation and percutaneous permanent iodine-125 implantation as salvage therapy for giant recurrent sclerosing epithelioid fibrosarcoma of the chest wall: A case report.

Sclerosing epithelioid fibrosarcoma (SEF) is a rare soft-tissue sarcoma for which there is no standardized treatment regimen available. The current treatment options for SEF are resection, radiation and chemotherapy. Surgical resection remains the mainstay of therapy for SEF. However, SEF is an aggressive tumor that is prone to repeated local recurrence if not widely excised. Radiation and chemotherapy are less commonly used due to the insensitivity of SEF to these therapies. The treatment of recurrent SEF is even more challenging. The present study describes a patient who presented with a giant recurrent SEF arising from the chest wall that was accompanied by emergent bleeding. The patient was a 70-year-old male who had multiple comorbid diseases, including hypertension and chronic cardiac dysfunction. A computed tomography (CT) scan indicated the involvement of the sternum and anterior mediastinum. However, the patient refused any further surgery. Subsequent to careful discussion and consideration, radiofrequency (RF) ablation and percutaneous iodine-125 implantation was administered. The emergent bleeding was successfully stopped and the tumor was eliminated using RF ablation. Percutaneous iodine-125 implantation under CT guidance established effective control on the growth of the tumor involving the mediastinum. Despite this, the tumor recurred 6 months after treatment. The patient refused any further treatment and was discharged. In conclusion, RF ablation and percutaneous permanent iodine-125 implantation is a feasible and safe salvage therapy for patients with recurrent SEF of the chest wall.