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Biomedical subjects

T J Liu

Publications and source records attributed to T J Liu.

At least 55 records · Page 3Linked to original sources

Liver resection for hepatocellular carcinoma in octogenarians.

BACKGROUND: Liver resection is risky in patients aged > or = 80 years. Because of short life expectancies and improved nonoperative modalities, the role of liver resection in octogenarians with hepatocellular carcinoma (HCC) is unclear. METHODS: A retrospective review of the operative results of 260 patients with HCC between 1991 and 1997 was performed. According to the age at the time of operation, these patients were divided into 2 groups. Group 1 comprised 21 patients aged > or = 80 years, and group 2 comprised the other 239 younger patients. The backgrounds, pathologic features of the tumor, and operative results of the patients were compared. RESULTS: Octogenarians had a higher incidence of associated medical diseases, a higher incidence of negative serum hepatitis B surface antigen, a lower alpha-fetoprotein level, and a higher indocyanine green retention rate. Although octogenarians had a longer postoperative hospital stay, there were no significant differences between the 2 groups regarding operative morbidity and mortality. The 5-year disease-free and actuarial survival rates for octogenarians and younger patients were 50.6% and 35.3% (P = .15) and 40.9% and 59.3% (P = .46), respectively. CONCLUSION: Under meticulous preoperative assessments and postoperative care, liver resection for HCC is justified in selected octogenarians, with short- and long-term results comparable to those of younger patients.

Actuarial Analysis↗

Adenovirus-mediated E2F-1 gene transfer inhibits MDM2 expression and efficiently induces apoptosis in MDM2-overexpressing tumor cells.

The oncoprotein MDM2 binds and inactivates p53. MDM2 also binds to the tumor suppressor pRB, as well as E2F-1. E2F-1 is a transcription factor that regulates S phase entry and has been shown to cause apoptosis in some cell types when overexpressed. To investigate the effect of adenovirus-mediated E2F-1 overexpression, MDM2-overexpressing tumor cell lines were treated by mock infection, infection with an adenoviral vector expressing beta galactosidase, or E2F-1 (Ad5CMV-E2F-1). Western blot analysis confirmed significant overexpression of E2F-1 in Ad5CMV-E2F-1-infected cells. E2F-1 overexpression resulted in marked growth inhibition and rapid loss of cell viability. Ad5CMV-E2F-1 infection resulted in early S phase entry, followed by apoptotic cell death. E2F-1 overexpression was associated with a marked decrease in MDM2 levels and no evidence of increased Bax levels, whereas p53 and Bcl-2 levels remained undetectable. Cleavage of poly-ADP-ribose polymerase and caspase 3/CPP32 implicated activation of the caspase cascade in E2F-1-mediated apoptosis. These results indicate that adenovirus-mediated E2F-1 overexpression in MDM2-overexpressing tumor cells results in decreased MDM2 expression and widespread apoptosis. Because MDM2-overexpressing tumors are often resistant to p53 gene therapy, adenovirus-mediated E2F-1 gene therapy may be a promising alternative strategy.

Adenoviridae↗

Treatment of cerebral palsy with botulinum toxin: evaluation with gross motor function measure.

The objective of this study was to investigate the effects of botulinum toxin A (BTA) injection in reducing muscular spasticity and improving locomotor function in children with cerebral palsy. Thirty-eight children with spastic cerebral palsy who were undergoing regular physical therapy were enrolled. Twenty-eight of these received BTA injection at the hip adductors and/or gastrocnemius, while the other 10, whose parents refused the BTA treatment protocol, served as the comparison group. The main outcome measures were: improvements in the severity of spasticity, walking distance, gross motor function (as assessed with the Gross Motor Function Measure, GMFM), and gait pattern (as assessed with the Physician Rating Scale, PRS), all measured 6 and 12 weeks after the start of BTA treatment. The severity of spasticity and walking distance at baseline did not differ significantly between the two groups. However, the severity of spasticity improved markedly in the BTA group, from 2.7 to 1.5 (Modified Ashworth Scale) at the hip adductor, and from 2.9 to 1.9 at the gastrocnemius at the 6-week follow-up. The walking distance improved from 46.17 m to 55.32 m at the 6-week follow-up, and to 66.6 m at the 12-week follow-up in the BTA group. Marked improvements in the quality of several gross motor functions were also noted in the BTA group. The improvements in spasticity, walking distance, and gross motor function were significantly greater in the BTA group than in the comparison group. The improvements in gait pattern did not differ significantly between the BTA and comparison groups. The findings of this study show BTA injection to be an effective treatment for reducing spasticity and improving gross motor function in children with spastic cerebral palsy. GMFM provides objective evidence regarding functional improvement after treatment in this patient population.

Anti-Dyskinesia Agents↗

Purification and expression of the gene III protein from filamentous phage phi Lf.

The gene III protein (pIII) from phi Lf, a filamentous phage of Xanthomonas campestris pv.campestris, was purified by gel filtration with FPLC. The gIII coding region was amplified by PCR, which was then cloned into pUC18 and expressed in Escherichia coli. The size of both pIII, purified from phage particle and expressed in E. coli, is similar to the value deduced from the nucleotide sequence as shown by Western blot analysis. This is different from the case in Ff phages (f1, fd, and M13), in which the size of pIII observed in SDS-polyacrylamide gel electrophoresis is substantially larger than the deduced value. Upon infection of X. c. pv. vesicatoria carrying cloned phi Lf gIII with phi Xv, a filamentous phage of pv. vesicatoria, the progeny particles in supernatant were able to infect both pv. campestris carrying cloned phi Lf gIII and pv. vesicatoria, indicating that a mixture of authentic phi Xv and chimeric phage consisting of phi Xv DNA and phi Lf pIII was produced. These results suggest pIII to be the adsorption protein required for host recognition.

Bacteriophages↗

In vitro growth suppression by adenoviral transduction of p21 and p16 in squamous cell carcinoma of the head and neck: a research model for combination gene therapy.

OBJECTIVES: To determine the duration of expression of the cell cycle regulators p21 and p16 and the effect of these 2 genes both alone and in combination on the growth of squamous cell carcinoma of the head and neck cell lines in vitro. EXPERIMENTAL METHODS AND DESIGN: Cells were transduced via an adenoviral vector with p21 (Ad5CMV-p21), p16 (Ad5CMV-p16), or both. Western blotting was performed to determine duration of expression of the protein products of the transduced p21 and p16 genes. In vitro growth assays and cell cycle analyses were performed on transduced cells. RESULTS: Transduced gene products were detected up to day 12 after infection. Western blotting showed high levels of p21 and p16 in transduced cells. Growth suppression was observed in squamous cell carcinoma of the head and neck cell lines transduced with Ad5CMV-p21, Ad5CMV-p16, or both, but the combination of p21 and p16 did not achieve significantly greater growth suppression than that seen in cells transduced with Ad5CMV-p16 alone. Cell cycle analysis demonstrated that the percentage of cells arrested at G1 stage in the cells transduced with Ad5CMV-p16 was similar to that in the cells transduced with both Ad5CMV-p21 and Ad5CMV-p16. No significant in vivo growth suppression was observed in tumor nodules treated with Ad5CMV-p16. CONCLUSIONS: Although p21 and p16 are believed to function as cell cycle regulators of cyclin-dependent kinases, we observed no additive or synergistic effect when using them in combination. The expression of transduced p21 and p16 gene products up to days 9 and 12, respectively, was consistent with the growth suppression and cell cycle arrest observed. This work provides information on the previously uncharacterized duration of p21 and p16 transgene product expression and also lends insight into the interaction of these 2 cell cycle regulators in squamous cell carcinoma of the head and neck.

Adenoviruses, Human↗

Prediction and limitation of hepatic tumor resection without blood transfusion in cirrhotic patients.

BACKGROUND: The need for blood transfusion in cirrhotic liver resection is difficult to determine because of inaccurate estimation of operative blood loss. Moreover, blood transfusion is detrimental to cirrhotic patients. OBJECTIVE: To investigate the predictors and limitations of hepatectomy without blood transfusion for cirrhotic patients. DESIGN: Retrospective study. SETTING: University hospital, a tertiary referral center. PATIENTS: A consecutive 163 cirrhotic patients underwent resection for liver tumor(s) under a policy of restrictive blood transfusion. INTERVENTIONS: Estimated blood losses and clinicopathological features of patients who received and those who did not receive a blood transfusion were compared. MAIN OUTCOME MEASURES: Estimated operative blood losses, preoperative assessments, and operative procedures. RESULTS: There were 48 patients in the group who received a blood transfusion, with 1275 +/- 650 mL (mean +/- SE) of blood transfused, and 115 patients in the group who did not receive a blood transfusion. From discriminant analysis, the cutoff value of estimated blood loss for blood transfusion was 1685 mL. Tumor size and site of hepatectomy were found to be independent variables influencing blood transfusion under logistic regression analysis. CONCLUSIONS: Most cirrhotic patients tolerate hepatectomy without blood transfusion when the estimated operative blood loss is less than 1600 mL. Hepatectomy can be performed in cirrhotic patients without blood transfusion if the tumor is small (<5 cm), and/or the resection area is confined to Couinaud segments II, III, and VI. In this study, the largest amount of estimated blood loss in cirrhotic liver resection without blood transfusion was 2350 mL, but the uppermost limit remains to be determined.

Adult↗

A simple and sensitive method for detecting adenovirus in serum and urine.

A method to detect shed virus in patients' serum and urine was developed following Ad5CMV-p53 gene transfer via direct tumor injections. The procedure differs from those reported previously in that it first uses polyethylene glycol to precipitate adenoviral particles from patient serum or urine. Adenoviral DNA is then extracted following proteinase K digestion. Finally, polymerase chain reaction (PCR) amplification followed by Southern blot transfer are employed to enhance the limit of detection to less than ten viral particles. The detection limit in a 0.25-ml sample is five viral particles in serum and one viral particle in urine. This procedure is sensitive, reproducible, and can be completed in less than 2 days.

Adenoviruses, Human↗

Overexpression of E2F-1 in glioma triggers apoptosis and suppresses tumor growth in vitro and in vivo.

The transfer of apoptosis genes to tumors is one of the most promising strategies for cancer gene therapy. We have shown that massive apoptosis occurs when wild-type p53 expression is induced in glioma cells carrying a p53 gene mutation. However, adenovirus-mediated p53 gene transfer is ineffective in causing apoptosis in glioma cells that retain a wild-type p53 genotype. We evaluated the effect of E2F-1 overexpression on the growth of gliomas in vitro and in vivo. In the in vitro study, the adenovirus-mediated transfer of exogenous E2F-1 protein precipitated generalized apoptosis in gliomas. The treatment with Ad5CMV-E2F-1 of nude mice carrying subcutaneous gliomas arrested tumor growth. Our results indicate that E2F-1 has anti-glioma activity in vitro and in vivo.

Adenoviruses, Human↗

Prospective randomized trial of systemic antibiotics in patients undergoing liver resection.

BACKGROUND: Systemic antibiotics are administered frequently after hepatectomy to prevent infective complications, but their effectiveness is uncertain. METHODS: A total of 127 patients with liver tumours were prospectively randomized into two groups after hepatectomy: in group 1 (62 patients) no antibiotics were given until the appearance of infective complications; in group 2 (65 patients) intravenous cephazolin 1 g every 6 h and gentamicin 80 mg every 8 h were given for 7 days. On the day before surgery all patients received bowel preparation by clear liquid diet and oral antibiotics (neomycin 1 g and erythromycin 1 g, given together in three doses). RESULTS: The infective complication rate was 23 per cent in both groups (P = 0.95). The hospital costs were higher in group 2 (P < 0.001). Of the group 1 patients, 51 (82 per cent) did not require antibiotic treatment. No patient in either group died after hepatectomy. CONCLUSION: Postoperative systemic antibiotics cannot prevent infective complications, and their routine use after hepatectomy is unnecessary and costly. The use of antibiotics should be delayed until infective complications and persistent septic symptoms occur.

Antibiotic Prophylaxis↗

Adenovirus-mediated p53 gene transfer in patients with advanced recurrent head and neck squamous cell carcinoma.

PURPOSE: Standard therapies of head and neck squamous cell carcinoma (HNSCC) often cause profound morbidity and have not significantly improved survival over the last 30 years. Preclinical studies showed that adenoviral vector delivery of the wild-type p53 gene reduced tumor growth in mouse xenograft models. Our purpose was to ascertain the safety and therapeutic potential of adenoviral (Ad)-p53 in advanced HNSCC. PATIENTS AND METHODS: Patients with incurable recurrent local or regionally metastatic HNSCC received multiple intratumoral injections of Ad-p53, either with or without tumor resection. Patients were monitored for adverse events and antiadenoviral antibodies, tumors were monitored for response and p53 expression, and body fluids were analyzed for Ad-p53. RESULTS: Tumors of 33 patients were injected with doses of up to 1 x 10(11) plaque-forming units (pfu). No dose-limiting toxicity or serious adverse events were noted. p53 expression was detected in tumor biopsies despite antibody responses after Ad-p53 injections. Clinical efficacy could be evaluated in 17 patients with nonresectable tumors: two patients showed objective tumor regressions of greater than 50%, six patients showed stable disease for up to 3.5 months, and nine patients showed progressive disease. One resectable patient was considered a complete pathologic response. Ad-p53 was detected in blood and urine in a dose-dependent fashion, and in sputum. CONCLUSION: Patients were safely injected intratumorally with Ad-p53. Objective antitumor activity was detected in several patients. The infectious Ad-p53 in body fluids was asymptomatic, and suggests that systemic or regional treatment may be tolerable. These results suggest the further investigation of Ad-p53 as a therapeutic agent for patients with HNSCC.

Adenoviridae↗

Suppression of human glioma growth by adenovirus-mediated Rb gene transfer.

OBJECTIVE: This study was conducted to obtain evidence that restoration of the retinoblastoma protein function may have therapeutic application for gliomas. BACKGROUND: The development of glioblastoma multiforme involves progressive inactivation of several tumor suppressor genes. Abnormalities of the retinoblastoma tumor suppressor gene are found in the majority of cancers, including at least 30% of malignant gliomas. No final evidence has been produced about the role of Rb in suppressing glioma growth. METHODS: To address this question, the Ad5CMV-Rb adenovirus carrying a 3.2-kb cDNA of the Rb gene was constructed. Expression of the exogenous protein was assessed by immunoblot and immunohistochemistry analyses. Growth curve assays were used to evaluate the effect of the Rb protein on glioma cell growth. Flow-cytometry analyses were used to analyze the phenotype of the cell cycle after the transfer of Rb. Human glioma xenografts implanted subcutaneously in nude mice were used for the tumorigenicity assay. RESULTS: After the transfer of Rb, 80% of the treated cells expressed high levels of the retinoblastoma protein for at least 7 days. Within 5 days of treatment, the cells lost the neoplastic morphology and showed marked growth suppression. The majority of the Rb-expressing cells were arrested in the G1 phase of the cell cycle. In addition, the restoration of the retinoblastoma activity rendered the human glioma cells unable to form tumors in nude mice. CONCLUSIONS: These findings provide direct evidence that inactivation of the retinoblastoma protein is a critical event in gliomas, and suggest that the restoration of wild-type retinoblastoma activity in these tumors may have therapeutic utility.

Adenoviridae↗

beta-Lapachone induced cell death in human hepatoma (HepA2) cells.

In present study we studied the cytotoxic effects of beta-lapachone, a potent anticancer drug, on the human hepatoma cell line (HepA2) under serum-free condition. Most cells died after 2 microM beta-lapachone addition at 48 hours. No apoptotic characteristics of DNA ladder was documented by agarose DNA electrophoresis. The blockage of cell cycle at S phase and unscheduled DNA synthesis were demonstrated by flow cytometric analysis and anti-bromodeoxyuridine immunocytochemistry. Ultrastructural observation showed that the swollen mitochondria, dilatation and vesiculation of rER and proliferation of peroxisome-like granules appeared within the cytoplasm of HepA2 cells following drug treatment. Using enzyme cytochemistry, both peroxidase and acid phosphatase activities but not catalase activity were localised in these peroxisome-like granules. Therefore, these results suggested that (a) beta-lapachone has a novel cytotoxic effect on human hepatoma cell; (2) beta-lapachone induces the interruption of the cell cycle and unscheduled DNA synthesis in HepA2 cells; and (3) beta-lapachone promotes the proliferation of peroxisome-like granules containing peroxidase and acid phosphatase activities without evidence of catalase activity in hepatoma cell line.

Antibiotics, Antineoplastic↗

Hepatic resection for bilobar multicentric hepatocellular carcinoma: is it justified?

BACKGROUND: Hepatic resection for multiple hepatocellular carcinomas (HCCs) involving both lobes of the liver is rarely recommended because of high operative risks and low radicality. Thus the justification of hepatic resection for bilobar multicentric HCC remains undefined. METHODS: Two hundred eleven patients with HCC, who underwent curative hepatic resection, were studied retrospectively. The patients were divided into two groups. Group A consisted of 39 patients with bilobar (both sides of Cantlie's line) multicentric HCCs. Group B consisted of 172 patients with HCC with solitary or unilobar lesions. The backgrounds and resectional results of patients in groups A and B were compared. RESULTS: Patients in group A usually required multiple separate liver resections and a longer operative time. However, the operative blood loss, amount of blood transfused, and operative morbidity and mortality rates were not significantly different. Patients in group A showed higher incidences of associated satellite nodules, microscopic vascular invasion, and a lack of capsules. The 6-year disease-free and actuarial survival rates of patients in groups A and B were 30.5% and 41.8% (p = 0.17) and 42.9% and 51.4% (p = 0.12), respectively. For patients in group A the presence of satellite nodules in any resected tumor was the only independent unfavorable feature that influenced the actuarial survival rate after multivariate analysis. CONCLUSIONS: Liver resection is justified for bilobar multicentric HCCs in selected patients, if the tumors can be totally resected. Postoperative adjuvant therapies should be considered when satellite nodules are present in any resected tumor.

Adult↗

Combination E2F-1 and p53 gene transfer does not enhance growth inhibition in human squamous cell carcinoma of the head and neck.

Ample data exist contending that wild-type p53 and E2F-1 cooperate to mediate apoptosis, that E2F-1-mediated apoptosis is p53 dependent in some situations, and that E2F-1 can induce accumulation of p53 in mammalian cells. These data support the investigation of the biological consequences of combined wild-typep53 and E2F-1 overexpression in human squamous cell carcinoma of the head and neck (SCCHN) for the purpose of developing apoptosis-inducing molecular intervention strategies for the management of this devastating disease. The recombinant adenovirus (Ad) vectors Ad-p53 and Ad-E2F-1 were used for wild-type p53 and E2F-1 gene transfers, respectively, into SCCHN cell lines TU138 and TU167. SCCHN cells transduced with either p53, E2F-1, or both underwent in vitro growth analysis, which revealed that simultaneous p53 and E2F-1 gene transfer did not result in enhanced growth inhibition. To explain our growth assay findings on the basis of potential negative molecular interactions between E2F-1 and p53, Western and Northern blotting analyses were performed to investigate the differential expression of the downstream p53-transactivated genes, p21Waf1 and BAX, under various p53 and E2F-1 gene transfer conditions. Whereas Western immunoblotting demonstrated that E2F-1 antagonized p53 induction of p21Waf1 and BAX, Northern blotting revealed that this interference was pretranslationally regulated and p53 dependent. Coimmunoprecipitation assay confirmed that the wild-type p53 and E2F-1 gene products formed protein-protein complexes in our cell lines. Our in vitro data demonstrated that in SCCHN, E2F-1 interferes with induction of p53-transactivated genes, probably through the formation of protein-protein complexes. Simultaneous p53 and E2F-1 gene transfer is not therapeutically advantageous in this in vitro model of SCCHN.

Apoptosis↗

Bystander effect in the adenovirus-mediated wild-type p53 gene therapy model of human squamous cell carcinoma of the head and neck.

In models of human lung and head and neck cancer, there have been anecdotal reports of a bystander effect in wild-type p53 gene therapy, an apoptosis-inducing molecular intervention strategy. These reports do not definitively demonstrate the presence of a bystander effect, nor do they elucidate requirements for or characteristics of this phenomenon. We have investigated human squamous cell carcinoma of the head and neck for the presence and requirements of a bystander effect after wild-type p53 gene transduction. Recombinant adenovirus, Ad-p53, was used for wild-type p53 gene transfers. To investigate the role of intercellular contact between p53-transduced and nontransduced cells in mediating a growth inhibitory (bystander) effect on nontransduced cells, coculturing experiments were conducted on human squamous cell carcinoma of the head and neck cell lines TU138 and TU167. For TU138, 29% growth inhibition of nontransduced cells was demonstrated 3 days after p53-transduced and nontransduced cells were cocultured with intercellular contact. This growth inhibition was abolished when cells were cocultured without intercellular contact. TU167 did not demonstrate a bystander effect under any coculturing condition. Supernatant from Ad-p53-infected TU138 and TU167 cells demonstrated no growth-inhibitory effect on respective nontransduced cells. The bystander effect in the adenovirus-mediated wild-type p53 gene therapy model of squamous cell carcinoma of the head and neck, when present, requires intercellular contact. Possible mechanisms of the observed in vitro bystander effect are discussed.

Adenoviridae↗

Heart rate variability as an assessment of acute rejection after heart transplantation.

BACKGROUND: Orthotopic heart transplantation is currently a widely accepted treatment for end-stage heart disease. Early detection and adequate therapy of acute rejection increases the survival rate. Currently, the most reliable technique for the detection of acute cardiac rejection (ACR) is endomyocardial biopsy (EMB), which is an invasive procedure with some intrinsic problems. The purpose of this study was to assess heart rate variability (HRV) as a noninvasive procedure for frequent monitoring of ACR. METHODS: Six consecutive orthotopic cardiac transplant recipients were prospectively recruited into this study. The follow-up periods ranged from seven to 359 days (median; 146 days). A precordial electrocardiograph (ECG) of 288 seconds was recorded at 5:00 PM before the patient underwent EMB. The results from the frequency domain analysis of the ECG signals were evaluated to correlate with the findings from EMB. RESULTS: Of 48 EMBs, 42 (87.5%) showed no evidence of rejection, four showed mild focal ACR (EMB grade 1A), one mild diffuse ACR (1B) and one moderate plurifocal ACR (3A). There was no moderate focal ACR (2), severe diffuse ACR (3B) or severe ACR (4). Correlation between ACR (3A) and a significant increase in HRV with a corresponding 'broad-band' or bell-shaped pattern on the power spectrum was noted. CONCLUSIONS: Our study in consecutive cardiac transplant recipients indicates that the changes in HRV provide clinicians with a new concept for heart transplant monitoring. Further study is needed to verify clinical utility.

Acute Disease↗

Adenovirus-mediated overexpression of the transcription factor E2F-1 induces apoptosis in human breast and ovarian carcinoma cell lines and does not require p53.

Apoptosis is a mode of cell death that is carefully regulated based on cellular and environmental signals. The ability to modulate the individual cellular machinery and thereby to promote apoptosis is an important strategy in cancer therapy. It has previously been shown that overexpression of the transcription factor E2F-1 can induce apoptosis in quiescent rat embryo fibroblasts. This effect has been reported to occur in a p53-dependent manner. To investigate whether overexpression of E2F-1 could also induce apoptosis in human cancer cells, a recombinant adenovirus vector containing the transgene E2F-1 under control of the cytomegalovirus promoter (Ad5CMVE2F) was used to induce high levels of the E2F-1 protein in human breast and ovarian carcinoma cell lines. Significant morphological changes occurred in four of the five cell lines within 48 h of transduction with the Ad5CMVE2F. These changes were consistent with apoptosis, which was confirmed further by DNA fragmentation assay and fluorescence-activated cell sorting analysis. On the basis of these assays, which show that apoptosis occurred in those cell lines with mutations in the p53 gene, we suggest that the induction of E2F-1-mediated apoptosis does not require wild-type p53 when E2F-1 is overexpressed using an adenovirus-based strategy.

Adenoviridae↗

Identification of gene VI of filamentous phage phi Lf coding for a 10-kDa minor coat protein.

ORF95 in the filamentous phage phi Lf genome, locating behind gIII, was identified to be the gene (gVI) coding for minor coat protein pVI (95 amino acids, 10,245 dal). It was shown to be virion associated by Western blot analysis of chloroform-treated phage particles. Computer analysis predicted two transmembrane regions for this protein. Since no signal peptide was suggested and the size estimated by SDS-polyacrylamide gel electrophoresis matches that deduced from nucleotide sequence, it appears to be incorporated into the phage particle as its primary translational product. After completion of this study, eight genes organizing into an order of gVII-gX-gV-gVII-gIX-gIII-gIII-gVI have been identified for phi Lf.

Amino Acid Sequence↗