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Biomedical subjects

Wen Gao

Publications and source records attributed to Wen Gao.

At least 19 recordsLinked to original sources

Developing Highly Effective Nanoparticle mRNA Therapeutic for Pediatric Acute Respiratory Distress Syndrome.

Sepsis-induced pediatric acute lung injury (ALI) and pediatric acute respiratory distress syndrome (PARDS) are life-threatening conditions with high mortality rates and no current cure. Most ALI/ARDS studies focus on adults, albeit the pediatric population has unique challenges often underrepresented. ALI/PARDS severely impacts pulmonary endothelial cells (ECs), causing endothelial dysfunction and vascular leakage. FOXF1 is a transcription factor critical for lung repair after injury, representing a viable target for ALI/PARDS. This study developed and tested a novel nanoparticle system for precise delivery of FOXF1 mRNA into lung ECs to reduce endothelial damage and improve lung function in mouse model of PARDS. Systemic inflammatory response was induced in neonatal mice after intraperitoneal administration of lipopolysaccharide (LPS). Specifically designed nanoparticles (NP) were used to intravenously deliver stabilized FOXF1 mRNA (FOXF1 NP) after LPS injury to restore FOXF1 expression in injured lung endothelial cells. FOXF1 NP selectively targeted pulmonary ECs without affecting other cell types or organs. FOXF1 NP treatment reduced vascular leakage, enhanced endothelial barrier function, and improved survival of neonatal mice after injury. FOXF1 NP decreased EC apoptosis by restoring the expression of BCL2, an anti-apoptotic FOXF1 target gene. Nanoparticle-based rescue of lung ECs has promise for future treatments of human ALI/PARDS.

endothelial cells↗

IndexToolkit: an open source toolbox to index protein databases for high-throughput proteomics.

UNLABELLED: A software package, IndexToolkit, aimed at overcoming the disadvantage of FASTA-format databases for frequent searching, is developed to utilize an indexing strategy to substantially accelerate sequence queries. IndexToolkit includes user-friendly tools and an Application Programming Interface (API) to facilitate indexing, storage and retrieval of protein sequence databases. As open source, it provides a sequence-retrieval developing framework, which is easily extensible for high-speed-request proteomic applications, such as database searching or modification discovering. We applied IndexToolkit to database searching engine pFind to demonstrate its effect. Experimental studies show that IndexToolkit is able to support significantly faster searches of protein database. AVAILABILITY: The IndexToolkit is free to use under the open source GNU GPL license. The source code and the compiled binary can be freely accessed through the website http://pfind.jdl.ac.cn/IndexToolkit. In this website, the more detailed information including screenshots and documentations for users and developers is also available.

Database Management Systems↗

[Survival and prognostic analysis of radiofrequency ablation of hepatocellular carcinoma].

OBJECTIVE: To assess the survival of radiofrequency ablation (RFA) and investigate the prognostic factors affecting overall survival, local recurrence-free survival and disease-free survival in hepatocellular carcinoma (HCC). METHODS: A total of 192 HCC patients underwent RFA treatment in our department and were enrolled into this study. Among them, 151 patients were males and 41 were females (mean age, 59.2 years, range, 24 - 87 years old). The average tumor size was (3.9 +/- 1.3) cm (range, 1.2 - 8.0 cm). Of these 192 HCC patients, their Child-Pugh grade of A, B and C were 106, 77 and 9, respectively. According to UICC-TNM system, 57, 85, 44 and 6 patients were in stage I, II, III and IV respectively. Kaplan-Meier model and log-rank test were used in univariate analysis and COX regression model was used in multivariate analysis to identify prognostic factors for survival. RESULTS: The 1-, 2-, 3- and 4-year overall survival were 84.9%, 69.1%, 60.4% and 52.8%, respectively. Local recurrence-free survival were 75.1%, 53.8%, 43.9% and 40.8%, respectively. Disease-free survival were 64.3%, 43.2%, 37.1% and 25.0%, respectively. The following factors were identified as independent prognostic factors for survival by multivariate model: (1) Overall survival: Child-Pugh classification, standard treatment protocol and UICC-TNM staging. (2) Local recurrence-free survival: Child-Pugh classification and UICC-TNM staging. (3) Disease-free survival: UICC-TNM staging, Child-Pugh classification and daughter lesion. Among these, both Child-Pugh classification and UICC-TNM staging were independent prognostic factors for three kinds of survivals. CONCLUSIONS: Degree of tumor progress (UICC-TNM stage, daughter lesion), treatment method (applying of standard treatment protocol) and patients' liver function are the most important factors for survival after RFA. So application of proper treatment strategy before, during and after RFA should be required to improve survival.

Adult↗

Effect of phosphorylation of myelin basic protein by MAPK on its interactions with actin and actin binding to a lipid membrane in vitro.

Myelin basic protein (MBP) binds to negatively charged lipids on the cytosolic surface of oligodendrocyte membranes and is most likely responsible for adhesion of these surfaces in the multilayered myelin sheath. It can also polymerize actin, bundle F-actin filaments, and bind actin filaments to lipid bilayers through electrostatic interactions. MBP consists of a number of posttranslationally modified isomers of varying charge, some resulting from phosphorylation at several sites by different kinases, including mitogen-activated protein kinase (MAPK). Phosphorylation of MBP in oligodendrocytes occurs in response to various extracellular stimuli. Phosphorylation/dephosphorylation of MBP also occurs in the myelin sheath in response to electrical activity in the brain. Here we investigate the effect of phosphorylation of MBP on its interaction with actin in vitro by phosphorylating the most highly charged unmodified isomer, C1, at two sites with MAPK. Phosphorylation decreased the ability of MBP to polymerize actin and to bundle actin filaments but had no effect on the dissociation constant of the MBP-actin complex or on the ability of Ca2+-calmodulin to dissociate the complex. The most significant effect of phosphorylation on the MBP-actin complex was a dramatic reduction in its ability to bind to negatively charged lipid bilayers. The effect was much greater than that reported earlier for another charge isomer of MBP, C8, in which six arginines were deiminated to citrulline, resulting in a reduction of net positive charge of 6. These results indicate that although average electrostatic forces are the primary determinant of the interaction of MBP with actin, phosphorylation may have an additional effect due to a site-specific electrostatic effect or to a conformational change. Thus, phosphorylation of MBP, which occurs in response to various extracellular signals in both myelin and oligodendrocytes, attenuates the ability of MBP to polymerize and bundle actin and to bind it to a negatively charged membrane.

Actins↗

Treatment strategy to optimize radiofrequency ablation for liver malignancies.

PURPOSE: The purposes of this study were to investigate a treatment strategy to increase liver tumor necrosis and minimize complications with ultrasound-guided percutaneous radiofrequency (RF) ablation and to evaluate its therapeutic efficacy. MATERIALS AND METHODS: A total of 332 patients with 503 liver malignancies underwent RF ablation according to a mathematical protocol with adjunctive measures. In the 332 patients, 205 had 308 hepatocellular carcinomas (HCCs) with a mean largest diameter of 4.1 cm and 127 had 195 metastatic liver carcinomas (MLCs) with a mean largest diameter of 3.9 cm. In patients with HCC, 60 (29.3%) had stage I/II disease and 145 (70.7%) had stage III/IV disease. Depending on tumor size, shape, and location, a defined treatment strategy was adopted that consisted of a mathematical protocol, an individualized protocol, and adjunctive measures. The mathematical protocol was followed for tumors larger than 3.5 cm. The individualized protocol was used for tumors located adjacent to the diaphragm, gastrointestinal tract, or gallbladder. Some adjunctive measures such as supplementary fine needle localization, local saline solution injection, and feeding vessel ablation were used to deal with different features of these liver tumors. Patients were followed regularly to assess treatment efficiency, and the tumor was considered to have early complete necrosis if no viability was found on enhanced computed tomography 1 month after RF ablation. RESULTS: In this series, the early necrosis rates were 95.8% for HCC (295 of 308 tumors), 94.9% for MLC (185 of 195 tumors), 91.3% for tumors larger than 3.5 cm (189 of 207 tumors), 90.7% for tumors near the gastrointestinal tract (49 of 54 tumors), 91.5% for tumors near the diaphragm (86 of 94 tumors), and 90.6% for tumors near the gallbladder (48 of 53 tumors). The local recurrence rates were 10.7% for HCC (33 of 308 tumors) and 14.9% for MLC (29 of 195 tumors). The 1-, 2-, and 3-year overall survival rates were 89.6%, 69.4%, and 59.6%, respectively, for HCC and 80.3%, 52.8%, and 30.9%, respectively, for MLC. The 1-, 2-, and 3-year survival rates in 60 patients with stage I/II HCC were 93.7%, 87.1%, and 76.2%, respectively. The incidence of major complications was 1.4% (eight of 574 sessions), which included of three hemorrhages, four injuries to adjacent structures, and one case of needle tract seeding. CONCLUSION: In RF ablation of hepatic tumors, application of a proper protocol and adjunctive measures play important roles in improving tumor necrosis rate and minimizing potential complications.

Adult↗

Radiofrequency ablation of recurrent hepatocellular carcinoma after hepatectomy: therapeutic efficacy on early- and late-phase recurrence.

OBJECTIVE: Our objective was to assess the efficacy and safety of radiofrequency ablation of recurrent hepatocellular carcinoma (HCC) after hepatectomy and to compare the effects on early- and late-phase recurrence. SUBJECTS AND METHODS: We studied 41 patients with 76 recurrent HCC tumors (diameter range, 2.0-6.6 cm; mean, 3.8 +/- 1.3 [SD] cm) after hepatectomy who underwent sonography-guided percutaneous radiofrequency ablation in our hospital (recurrent-HCC group). The interval between surgery and recurrence ranged from 1 to 96 months (mean, 24.5 months). These patients were divided into an early-recurrence group (20 patients with 41 recurrent HCC tumors) and a late-recurrence group (21 patients with 35 recurrent HCC tumors). Early recurrence was defined as that occurring within 1 year after surgery, and late recurrence was defined as that occurring after 1 year. Another 116 patients with 172 primary HCC tumors (diameter range, 1.2-7.0 cm; mean, 3.9 +/- 1.1 cm) treated by radiofrequency ablation were regarded as a control group. No other therapies were given before radiofrequency ablation in any group. Regular follow-up with enhanced CT was performed to evaluate the treatment results. Ablation was considered successful if no contrast enhancement was detected in the treated area on 1-month CT scans. Indexes including ablation success rate, local recurrence rate, distant recurrence rate, and survival were obtained for analysis and comparison. RESULTS: The ablation success rate, local recurrence rate, distant recurrence rate, and mean overall survival time of the recurrent-HCC group were 93.4% (71/76 tumors), 9.2% (7/76 tumors), 36.6% (15/41 patients), and 30.9 +/- 3.7 months, respectively. The incidence of distant recurrence in the early-recurrence group was significantly higher than that in the late-recurrence group (55.0% vs 19.0%, p = 0.017). The early-recurrence group had a shorter overall survival than did the late-recurrence group (mean overall survival, 16.4 +/- 2.4 vs 42.9 +/- 4.4 months, p < 0.001) or the control group (16.4 +/- 2.4 vs 45.9 +/- 2.5 months, p < 0.001). The survival time of the late-recurrence group was similar to that of the control group (42.9 +/- 4.4 vs 45.9 +/- 2.5 months, p > 0.05). Serious hemorrhage after radiofrequency ablation occurred in one patient in the late-recurrence group and was controlled with conservative treatment. CONCLUSION: Radiofrequency ablation is generally effective and safe in treating recurrent HCC after hepatectomy and is more effective in late recurrence than in early recurrence.

Adult↗

[The effect of cyclophosphamide, thalidomide and dexamethasone combination therapy in relapsed/refractory multiple myeloma].

OBJECTIVE: To investigate the effect of the combination of thalidomide, cyclophosphamide and dexamethasone for the treatment of relapsed/refractory multiple myeloma. METHODS: 20 relapsed/refractory multiple myeloma patients received thalidomide (200 mg/d), cyclophosphamide (300 mg.m(-2).d(-1), d1-4, every 4 weeks) and pulsed dexamethasone (20-40 mg/d, d1-4, every 4 weeks). RESULTS: After 3 cycles of therapy, 9 cases obtained partial remission (PR), 4 had minimal responses (MR), 5 were of no change and 2 had progressive disease. After 6 cycles of therapy, 13 patients achieved PR and 5 had MR. CONCLUSION: The combination of thalidomide, cyclophosphamide and dexamethasone is a promising treatment regime for relapsed/refractory multiple myeloma.

Aged↗

[Evaluation of the ultrasonographic features of axillary lymph node metastasis in breast cancer].

OBJECTIVE: To analyze the ultrasonographic features of axillary lymph node metastasis in breast cancer patients, and to evaluate the accuracy of these features by Receiver Operating Characteristic (ROC) curve. METHODS: Ultrasonography was carried out in 113 patients (mean age 56.5 yr, range 29 - 77 yr). The ultrasonographic features of the primary tumor and the axillary lymph node were observed. Univariate analysis was performed by Chi-squared test and Fisher exact test, and multivariate analysis to determine independent significant individual variables by multiple logistic regression analysis. ROC curve analysis was done to determine the sensitivity and specificity of individual and combined ultrasonographic features in distinguishing metastatic lymph node from the normal one. RESULTS: The primary tumor size, abundance of blood supply in the primary tumor, longitudinal-transverse diameter ratio, cortex-hilum thickness ratio (on the longitudinal section), abnormal cortex thickness, distribution of intra-nodal vascularity of axillary lymph nodes were found to be statistically significant factors by univariate analysis. The primary tumor size, longitudinal-transverse ratio and cortex-hilum thickness ratio of lymph node were proved to be significant independent predictors of axillary lymph node metastasis by logistic regression analysis. Through ROC analysis, the combination of these independent ultrasonographic feature predictors was found to contribute significantly in differentiating metastatic lymph node from the normal with a sensitivity of 88.6% and specificity of 84.5%. CONCLUSION: Axillary ultrasonography is helpful in staging the axillary lymph node in breast cancer patient. The primary tumor size, longitudinal-transverse diameter ratio and cortex-hilum thickness ratio of lymph node are the main features to determine whether metastatic involvement is present or not.

Adult↗

[Detection of micrometastasis in mediastinal lymph nodes in operable non-small cell lung cancers].

OBJECTIVE: Using the LUNX-mRNA as a marker and RT-PCR technique to assess mediastinal lymph nodes in patients with operable NSCLC, to evaluate at gene level the feasibility of this method in detection of micrometastasis in NSCLC and the necessity of systematic mediastinal lymphadenectomy during surgery. METHODS: Twenty patients with operable NSCLC were involved in this study. The mediastinal lymph nodes were taken during operation. RT-PCR assay was carried out to detect the LUNX-mRNA. Ten cases with benign lung disease were assayed by the same method as control. RESULTS: Seventy one mediastinal lymph nodes were obtained from 20 patients, 8 (11.3%) of which showed histologically metastasis with HE staining, while 23 (32.4%) were LUNX-mRNA positive by RT-PCR, P < 0.001. Micrometastasis was detected in 25.4% of all lymph nodes. LUNX-mRNA was found to be positive in 23.6% of lymph nodes from 15 patients with stage I A-II B NSCLC compared with 62.5% from 5 patients with stage III NSCLC, with a significant difference (P = 0.003). CONCLUSION: About 25.4% of mediastinal lymph nodes are with micrometastasis in patients with operable NSCLC. Systematic mediastinal lymphadenectomy is necessary to deal with the regional lymph nodes during surgery.

Adult↗

[Clinicopathologic study of cryptogenic organizing pneumonia].

OBJECTIVE: To study the clinicopathologic features and differential diagnosis of cryptogenic organizing pneumonia (COP). METHODS: The clinical, radiologic and pathologic features of 11 patients with COP confirmed by open or video-assisted thoracoscopic (VATS) lung biopsy were analyzed. Treatment information and follow-up data were also obtained. RESULTS: COP usually affected female patients over 40 years of age. Clinical presentations included cough, sputum and exertional dyspnea. High-resolution computerized tomography showed scattered speckled, patchy and trabecular shadows over both lung fields. Honeycomb changes were not found. Histologically, polypoid growths of granulation tissue were noted within respiratory bronchioles, small airways and alveolar spaces. These lesions had a patchy and peribronchiolar distribution and were uniform in appearance. The overall response rate to glucocorticoid was 81.8% (P < 0.01). The duration of follow up ranged from 6 to 134 months. Apart from one patient who developed aggravation of symptoms, the disease pursued a relatively stable clinical course. CONCLUSIONS: In general, COP responds well to glucocorticoid therapy. Open or VATS lung biopsy is important for arriving at a definitive diagnosis, especially for those cases presenting with atypical clinical and radiographic manifestations. Multiple biopsies with larger samples are preferred in order to avoid misdiagnosis.

Adult↗

[Surgical treatment of multi-drug resistant pulmonary tuberculosis in 188 cases].

OBJECTIVE: Multi-drug resistant pulmonary tuberculosis (MDR-PTB) is a major cause of morbidity and mortality throughout the world currently. Optimal therapy for patients infected with MDR-PTB often requires surgical intervention to eradicate the infection. METHODS: During a 15-year period from 1990 to 2005, of the 906 cases receiving surgical treatment for pulmonary tuberculosis in Shanghai Pulmonary Disease Hospital, 188 patients with MDR-PTB underwent 200 surgical procedures. All the patients of MDR-PTB had received individualized multiple-drug chemotherapy at least 2 - 3 months before surgery, as determined by drug susceptibility studies. Of the surgical procedures, 85 lobectomies, 48 pneumonectomies and other complicated surgical techniques were performed respectively. Twelve patients underwent repeated operation. Muscle flaps and omentum in some cases were used to avoid residual space and bronchial stump problems. RESULTS: Operative mortality was 0.5% (1/200). Postoperative mortality was 3.2% (6/187). Significant morbidity was 13.9% (26/187). All of the patients had positive sputum at the time of surgery. After the operation, the sputum remained positive in only 2 patients. Mean length of follow-up was 6.7 years (range 3 - 180 months). All of the patients after surgery continued their individualized multiple-drug chemotherapy for 3 - 18 months. CONCLUSION: Surgery remains an important adjunct to medical therapy for the treatment of MDR-PTB. Surgical treatment should be considered for localized diseases, persistent sputum positivity, or intolerance of medical therapy.

Adolescent↗

An SVM scorer for more sensitive and reliable peptide identification via tandem mass spectrometry.

Tandem mass spectrometry (MS/MS) has become increasingly important and indispensable in high-throughput proteomics for identifying complex protein mixtures. Database searching is the standard method to accomplish this purpose. A key sub-routine, peptide identification, is used to generate a list of candidate peptides from a protein database according to an experimental MS/MS spectrum, and then validate these candidate peptides for protein identification. Although currently there are many algorithms for peptide identification, most of them either lack an effective validation module or only validate the first-ranked peptide, thus leading to a low identification reliability or sensitivity. This paper proposes a new algorithm, named pepReap, to overcome the above drawbacks. It consists of a two-layered scoring scheme based on machine learning. The first layer is a rough scoring function which uses some simple and heuristic factors to measure the degree of the matches between an experimental MS/MS spectrum and the candidate peptides; thus a ranked list of candidate peptides is generated at a relatively low computational cost. The second layer is a fine scoring function which re-ranks the candidate peptides generated in the first layer and determines which one among them is the true positive. The fine scoring function was designed based on support vector machines (SVMs) using more comprehensive factors, such as the correlations between ions, the mass matching errors of fragment and peptide ions, etc. Consequently, the SVM classifier serves as not only a scorer but also a validation module. Experimental comparison with the popular SEQUEST algorithm coupled with threshold validation criteria on a reported dataset demonstrates that the pepReap algorithm achieves higher performance in terms of identification sensitivity with comparable precision.

Algorithms↗

[Application of contrast-enhanced ultrasonography in selecting indication of radiofrequency ablation among hepatocellular carcinoma patients].

OBJECTIVE: To evaluate the clinical value of contrast-enhanced ultrasound (CEUS) in selection of the patients with hepatocellular carcinoma (HCC) indicated to radiofrequency ablation (RFA). METHODS: 164 patients with HCC, 121 males and 43 females, aged 52.4 (38-72), who asked for RFA were randomly divided into 2 groups: 81 patients undergoing CEUS before RFA (CEUS Group), and 83 patients not undergoing CEUS before RFA (Control Group). There were not significant differences in the TNM staging, liver function Child-Pugh classing, and average tumor size between the 2 groups. Follow-up by conventional ultrasonography, enhanced CT and/or enhanced ultrasonography was conducted for 6-36 months. RESULTS: Nine of the 81 patients in CEUS Group (11.8%) were determined by CEUS as unsuitable for RFA; 5 of the 9 patients had more than 5 lesions, 2 of the 9 patients had lesions > 8 cm in diameter, and the tumor had invaded 2 large vessels or intestine in 2 of the 9 patients. The other 72 patients in CEUS Group, with 101 lesions, underwent RFA after CEUS. CEUS discovered 12 lesions < or = 1.7 cm that had not been discovered by conventional ultrasonography and CT in 8 patients, 3 of which were patients with cirrhosis undergoing follow-up, and 2 of which were HCC patients undergoing follow-up after treatment. Of these 8 patients, 3 had 7 newly discovered satellite lesions around the main lesions. The successful rates of CEUS Group and Control Group were 95.0% and 89.6% respectively (P > 0.05). The distant recurrence rate of Control Group was 22.9%, significantly higher than that of CEUS Group (9.7%, P < 0.05). CONCLUSION: Helping find minute tumors, CEUS is useful in selecting HCC patients suitable for RFA, thus decreasing the intrahepatic recurrence after RFA.

Adult↗

[Long term (5 years) outcome of radiofrequency ablation for hepatocellular carcinoma in 256 cases].

A total of 267 patients with hepatocellular carcinoma underwent ultrasound-guided radiofrequency ablation (RFA) in Peking University School of Oncology between 1999 and 2005 (421 RFA sessions). Among them, 254 patients were candidates for RFA treatment and the selective criteria were: (1) the greatest diameter of tumor 5 cm, respectively. According to tumor size, shape and location, we adopted a defined treatment strategy, which consisted of a mathematical protocol, an individualized protocol and adjunctive measures. And several methods were also used to prevent and deal with complications in tumors with different features. In this series the tumor complete necrosis rate (CR)was 95.2% (356/374 tumors). It was higher in 3.5 cm tumors with a CR of 91.3% (156/171 tumors). CR were 95.6% (44/46 tumors) for tumors near the gallbladder, 92.9%(79/85 tumors) for tumors near the diaphragm, 90.9%(40/44 tumors) for tumors near the gastrointestinal tract, 91.2% (31/34 tumors) for tumors near large vessel. In a follow-up period of 2-69 months, the local recurrence rates were 11.7% for HCC and 12.5% for recurrent HCC. The incidence of complications was 2.4% (10/409 sessions), including intraperitoneal hemorrhage (n=2), biliary duct stricture (n=1), hemothorax (n=1), bowel perforation (n=1) and needle tract seeding (n=5). Of these cases, only 3 required operation and the mortality related to RFA was zero in this series. We used Kaplain-Meier method and log-rank test to estimate and compare the survival rate. The 1-, 3-, and 5-year survival rates after RFA were 83.3%, 66.9%, 41.2%, respectively for all HCC patients and 74.6%, 41.3%, 33.6%, respectively for recurrent HCC. Survivals based on TNM stage, Child-Pugh grade, tumor number and tumor size are shown in Table 1. In conclusion, RFA with standard protocol has evolved as a minimally invasive local treatment that could achieve satisfactory outcomes for small liver tumors, and has become an effective and relatively safe alternative for the treatment of advanced tumors and recurrent tumors, which are not suitable for traditional therapy. RFA has broaded the treatment threshold for hepatic malignancies and might become one of the regular treatment methods in focal liver tumor and find wide application.

Adult↗

Treatment efficacy of radiofrequency ablation of 338 patients with hepatic malignant tumor and the relevant complications.

AIM: To investigate the treatment efficacy of radiofrequency ablation (RFA) of hepatic malignant tumor and the relevant complications. METHODS: A total of 338 patients with 763 hepatic tumors underwent ultrasound-guided RFA (565 procedures). There were 204 cases of hepatic cellular carcinoma (HCC) with 430 tumors, the mean largest diameter was 4.0 cm. Of them, 48 patients (23.5%) were in stages I-II (UICC Systems) and 156 (76.5%) in stages III-IV There were 134 cases of metastatic liver carcinoma (MLC), with 333 metastases in the liver, the mean diameter was 4.1 cm, the liver metastases of 96 patients (71.6%) came from gastrointestinal tract. Ninety-three percent of the 338 patients were treated using the relatively standard protocol. Crucial attention must be paid to monitor the abnormal changes in ultrasound images as well as the vital signs of the patients to find the possible hemorrhage and peripheral structures injury in time. The tumors were considered as ablated completely, if no viability was found on enhanced CT within 24 h or at 1 mo after RFA. These patients were followed up for 3-57 mo. RESULTS: The ablation success rate was 93.3% (401/430 tumors) for HCC and was 96.7% (322/333 tumors) for MLC. The local recurrence rate for HCC and MLC was 7.9% (34/430 tumors) and 10.5% (35/333 tumors), respectively. A total of 137 patients (40.5%) underwent 2-11 times of repeated ablations because of tumor recurrence or metastasis. The 1st, 2nd, and 3rd year survival rate was 84.6%, 66.6%, and 63.1%, respectively; the survival rate from 48 patients of I-II stage HCC was 93.7%, 80.4%, and 80.4%, respectively. The major complication rate in this study was 2.5% (14 of 565 procedures), which consisted of 5 hemorrhages, 1 colon perforation, 5 injuries of adjacent structures, 2 bile leakages, and 1 skin burn. CONCLUSION: RFA, as a minimally invasive local treatment, has become an effective and relatively safe alternative for the patients of hepatic malignant tumor, even of advanced liver tumor, tumor recurrence, and liver metastases. Knowledge about possible complications and their control may increase the treatment efficacy and help to promote the use of RFA technique.

Adult↗

[Intraperitoneal hemorrhage during and after percutaneous radiofrequency ablation of hepatic tumors: reasons and management].

BACKGROUND: Intraperitoneal hemorrhage is one of the most common complications of radiofrequency (RF) ablation of hepatic tumors. This study was designed to investigate the reason and management of intraperitoneal hemorrhage occurred during or after percutaneous RF ablation of hepatic tumors. METHODS: Three hundred and fifty-six patients with hepatic tumors have been treated at 592 procedures of ultrasound guided RF ablation. Intraperitoneal hemorrhage occurred in 5 patients (0.8%). The reasons and management of intraperitoneal hemorrhage in these 5 cases were retrospectively analyzed. RESULTS: Two patients with liver metastasis and one hepatocellular carcinoma (HCC) patient suffered from hemorrhage during the RF treatment. Two patients with recurrent HCC after surgery developed hemorrhage 20 minutes or 4 hours after RF treatment. One case of hemorrhage was due to the inappropriate electrode positioning induced liver laceration while treating a 1 cm liver metastasis near the liver capsule. One was due to the injury of a small vessel by the RF needle in another liver metastasis patient. Three cases were due to tumor rupture with two cases induced by cough or position change after treating large protruding HCC lesions. Four (80%) of the 5 cases of hemorrhage were rapidly identified by ultrasound. The causes and sites of bleeding during the RF treatment in three cases were confirmed through ultrasound, which were successfully treated using RF coagulation to achieve hemostasis of the bleeding site. Two patients with post-ablation hemorrhage recovered in one hour and 24 hours, respectively after given blood transfusion and other conservative measures. No surgical intervention was required. Two patients died of wide spread metastasis 23 - 36 months afterwards and the other three patients have lived for 18 - 25 months to date. CONCLUSIONS: It is important to perform close monitoring during and after RF ablation in order to identify intraperitoneal hemorrhage in time. RF ablation of the bleeding sites was a simple and effective management when the bleeding site could be confirmed by ultrasound. The hemorrhage due to the rupture of large and protruding liver tumors could be serious and should be considered as contraindication for RF treatment.

Adult↗

Carnitine/xenobiotics transporters in the human mammary gland epithelia, MCF12A.

The barrier function of the human mammary gland collapses if challenged with cationic drugs, causing their accumulation in milk. However, underlying molecular mechanisms are not well understood. To gain insight into the mechanism, we characterized transport of organic cations in the MCF12A human mammary gland epithelial cells, using carnitine and tetraethylammonium (TEA) as representative nutrient and xenobiotics probes, respectively. Our results show that the mammary gland cells express mRNA and proteins of human (h) novel organic cation transporters (OCTN) 1 and hOCTN2 (a Na+-dependent carnitine carrier with Na+-independent xenobiotics transport function), which belong to the solute carrier superfamily (SLC) of transporters. Other SLC OCTs such as hOCT1 and extraneuronal monoamine transporter (EMT)/hOCT3 are also expressed at mRNA levels, but hOCT2 was undetectable. We further showed mRNA expression of ATB0+ (an amino acid transporter with a Na+/Cl(-)-dependent carnitine transport activity), and Fly-like putative transporter 2/OCT6 (a splice variant of carnitine transporter 2: a testis-specific Na+-dependent carnitine transporter). TEA uptake was pH dependent. Carnitine uptake was dependent on Na+, and partly on Cl-, compatible with hOCTN2 and ATB0+ function. Modeling analyses predicted multiplicity of the uptake mechanisms with the high-affinity systems characterized by K(m) of 5.1 microM for carnitine and 1.6 mM for TEA, apparently similar to the reported hOCTN2 parameter for carnitine, and that of EMT/hOCT3 for TEA. Verapamil, cimetidine, carbamazepine, quinidine, and desipramine inhibited the carnitine uptake but required supratherapeutic concentrations, suggesting robustness of the carnitine uptake systems against xenobiotic challenge. Our findings suggest functional roles of a network of multiple SLC organic cation/nutrient transporters in human mammary gland drug transfer.

Carnitine↗