Biomedical subjects

T J Liu

Publications and source records attributed to T J Liu.

At least 37 records · Page 2Linked to original sources

PubMed2000

Expression of constitutively active phosphatidylinositol 3-kinase inhibits activation of caspase 3 and apoptosis of cardiac muscle cells.

Apoptosis of cardiac muscle cells contributes to the development of cardiomyopathy. Recent studies showed that insulin-like growth factor I (IGF-I) inhibits apoptosis of cardiac muscle cells and improves myocardial function in experimental heart failure. This study was carried out to elucidate the role of phosphatidylinositol 3-kinase (PI 3-kinase) in the anti-apoptotic actions of IGF-I in cardiomyocytes and to explore whether expression of constitutively active PI 3-kinase can inhibit apoptosis in cardiomyocytes. Apoptosis of primary cardiomyocytes was induced by doxorubicin treatment and serum withdrawal. Transduction of cardiomyocytes with constitutively active PI 3-kinase specifically lead to serine phosphorylation of Akt, whereas phosphorylation of IGF-I receptor, IRS1/2 and p44/42 mitogen-activated protein kinase were not increased. In the cardiomyocytes transduced with constitutively active PI 3-kinase, activation of the pro-apoptotic caspase 3 was attenuated and fragmentation of DNA was reduced. Preincubating cells with PI 3-kinase inhibitor LY294002 was associated with loss of anti-apoptotic actions of IGF-I and PI 3-kinase. Neither IGF-I nor constitutively active PI 3-kinase lead to serine phosphorylation of Bad, suggesting that the anti-apoptotic effects of PI 3-kinase are not mediated through Bad phosphorylation in cardiac muscle cells. To determine whether activation of caspase 3 is sufficient to induce apoptosis in cardiomyocytes, an engineered TAT-caspase 3 protein was introduced to cardiomyocytes. Significant reduction of cell viability occurred in the cardiomyocytes transduced with active caspase 3, indicating that activation of caspase 3 is sufficient to cause cardiomyocyte death. These findings indicate the existence of an IGF-I receptor-PI 3-kinase-caspase 3 pathway in cardiomyocytes that plays an important role in the anti-apoptotic actions of IGF-I in heart. Moreover, these data suggest that modulation of PI 3-kinase activities may represent a potential therapeutic strategy to counteract the occurrence of apoptosis in cardiomyopathy.

Animals↗

PubMed2000

An appraisal of liver and portal vein resection for hepatocellular carcinoma with tumor thrombi extending to portal bifurcation.

BACKGROUND: The role of surgical resection for hepatocellular carcinoma with tumor thrombi involving the major portal vein is controversial because of a high operative risk and poor prognosis. Previously, a resection was performed only when the tumor thrombi were limited to the first branch of the portal vein without extension to the portal bifurcation. HYPOTHESIS: Concomitant liver and portal vein resection may be beneficial in patients with hepatocellular carcinoma with tumor thrombi extending to portal bifurcation. DESIGN: Retrospective review. SETTING: University hospital, tertiary referral center. PATIENTS: Among 368 patients with hepatocellular carcinoma who underwent a curative resection, portal vein involvement occurred in 112 patients. Fifteen of the 112 patients underwent a concomitant liver and portal vein resection owing to extension of tumor thrombi to the portal bifurcation (group 1). The remaining 97 patients did not need portal vein resection (group 2). INTERVENTION: Surgical indications, procedures, and results of pathological examination of resected specimens were assessed in patients in group 1. The clinicopathological characteristics, operative morbidity and mortality, and operative results were compared between the 2 groups. MAIN OUTCOME MEASURES: Disease-free and actuarial survival rates. RESULTS: Intramural tumor infiltration was found at the site of thrombi adhesion to the portal vein cuff in 11 of 15 patients in group 1. Owing to patient selection bias, patients in group 1 were significantly younger and had better liver function and greater resected liver weight. The operative time, postoperative hospitalization, operative blood loss, amount of blood transfusion, and operative morbidity and mortality did not differ significantly between the 2 groups. The 5-year disease-free survival rates of groups 1 and 2 were 21.6% and 20.4% (P =.19), respectively, while the actuarial survival rates were 26. 4% and 28.5% (P =.33), respectively. CONCLUSION: Liver resection with partial resection of the portal vein is justified in selected patients with hepatocellular carcinoma with tumor thrombi extending to portal bifurcation.

Carcinoma, Hepatocellular↗

PubMed2000

Surgical treatment for recurrent hepatocellular carcinoma with tumor thrombi in right atrium: using cardiopulmonary bypass and deep hypothermic circulatory arrest.

Tumor in the right atrium creates a life-threatening condition and should be removed immediately. A cirrhotic patient who had recurrent hepatocellular carcinoma (HCC) over remnant liver with tumor thrombi extending to inferior vena cava (IVC) and right atrium presented with impending congestive heart failure. The recurrent tumor and its thrombi were successfully resected en-bloc using cardiopulmonary bypass and hypothermic circulatory arrest. Although the patient's disease-free and actual survival time were only 6 months and 14 months, respectively, he was rescued from heart failure. This aggressive surgical strategy creates further possibility to treat such advanced HCC cases. Further investigations regarding adjuvant therapies in these circumstances, however, are necessary.

Adult↗

PubMed2000

Telomerase activity in head and neck tumors after introduction of wild-type p53, p21, p16, and E2F-1 genes by means of recombinant adenovirus.

BACKGROUND: Telomerase (reverse transcriptase) has been shown to play a role in the process of cellular immortalization. METHODS: Telomerase activity was determined in 11 head and neck squamous cell carcinoma (SCCHN) cell lines. The effects of wild-type p16, p21, E2F-1, and p53 genes on telomerase activity were examined by introducing the wild-type genes into two SCCHN cell lines by means of a recombinant adenovirus. RESULTS: We found elevated telomerase activity in 10 of the 11 SCCHN cell lines tested. When we infected Tu-138 and Tu-167 cell lines with wild-type p16, p21, E2F-1, and p53 genes, we found that p16 had little effect on telomerase activity. Both E2F-1 and p53 were known to induce apoptosis in SCCHN cell lines. Significantly reduced telomerase activity by p53 in both cell lines and E2F-1 in Tu-167 cells was in agreement with suppression of cell growth. Overexpression of p21 also exhibited reduction in telomerase activity. CONCLUSIONS: We conclude from this study that overexpression of E2F-1 and p53 can reverse telomerase activity in SCCHN cell lines and that telomerase activity may be involved in cancer cell immortalization.

Adenoviridae↗

PubMed2000

Selective sentinel lymph node dissection in breast cancer: experiences from Taiwan.

The significance of the sentinel lymph node (SLN) was examined in 58 Chinese breast cancer patients. The method of technetium-99m sulfur colloid injection and the intraoperative gamma probe was found to be very useful for identifying the SLN. The positive predictive value was 64.5%, and the negative predictive value was 93.2%. Findings suggest that lymph node dissection is not necessary in breast cancer patients with a negative SLN.

Adult↗

PubMed2000

Inhibition of cell growth in human glioblastoma cell lines by farnesyltransferase inhibitor SCH66336.

Ras activation occurs through stimulation of an upstream growth factor receptor such as epidermal growth factor receptor (EGFR). The ultimate effect of Ras is to induce nuclear transcription via a signaling pathway sequentially involving Raf, MAP kinase kinase (MEK), and mitogen-activated protein kinase (MAPK). To transform cells, Ras oncoproteins must be posttranslationally modified with a farnesyl group in a reaction catalyzed by farnesyl protein transferase. Farnesyltransferase inhibitors, therefore, have been proposed as potent anticancer agents. This study demonstrates the growth-inhibitory effects of farnesyltransferase inhibitor SCH66336 on human glioblastoma cell lines U-251 MG, U-251/E4 MG (a stably transfected cell line with elevated EGFR expression), and U-87 MG. As determined by (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) and viability assays, the concentration required to achieve 50% inhibition (IC50) ranged from 30 microM (single 24-h treatment) to 10 microM (5-day treatment). U-251/E4 MG with overexpression of EGFR were more sensitive than U-251 MG parental cells. These observations were also supported by soft agar analysis. Cells treated with SCH66336 underwent G2 arrest. Western blot analysis revealed a decrease in phospho-MAPK levels upon treatment with 10 microM SCH66336, whereas MAPK levels were unaffected by the drug. Interestingly, increased expression of EGFR was observed in U-251 MG and U-251/E4 MG but not in U-87 MG in the presence of the inhibitor. These results demonstrate that SCH66336 inhibits viability and anchorage-independent growth in a time- and dose-dependent manner in glioblastoma cell lines U-251 MG, U-251/E4 MG, and U-87 MG via a signal transduction pathway involving the down-regulation of phospho-MAPK. Overexpression of EGFR appears to alter cellular sensitivity to farnesyltransferase inhibitors. This may have a particularly important implication in glioblastoma, where over 50% of tumors have amplification and overexpression of EGFR.

Alkyl and Aryl Transferases↗

PubMed2000

Lymphoscintigraphy using larger colloid particles may enhance visualization of the sentinel node in breast cancer: a case report.

Lymphoscintigraphy along with a gamma-detecting probe has been applied successfully to breast cancer patients to localize the sentinel node during surgery, with a 5% false-negative rate. The authors report a case of stage II breast cancer. The sentinel node was not visualized on the initial lymphoscintigraphy with peritumoral injection of 37 MBq (1 mCi) 10 ml Tc-99m colloidal rhenium sulfide (Tc-99m ReS colloid; average particle size, 100 nm). However, the sentinel node was visualized in the left lateral view of the second lymphoscintigraphy with peritumoral injection of 37 MBq (1 mCi) 10 ml Tc-99m ReS colloid (average particle size, 500 nm). Lymphoscintigraphy using the larger colloid particles may enhance visualization of a sentinel node in breast cancer.

Adult↗

PubMed2000

Adenovirus-mediated E2F-1 gene transfer induces an apoptotic response in human gastric carcinoma cells that is enhanced by cyclin dependent kinase inhibitors.

E2F -1 is a transcription factor that regulates cell cycle progression into S-phase. Deregulation of E2F-1 activity has been associated with cellular commitment to apoptosis. Also critical in the regulation of S-phase are the actions of the cyclin dependent kinases, Cdk2 and cdc2. Inhibition of these cyclin dependent kinases has been similarly associated with disrupting orderly S-phase progression and causing subsequent apoptosis in certain cancer cells. In this study, we examine the ability of adenovirus-mediated E2F-1 overexpression to induce apoptosis in human gastric carcinoma cells. Furthermore, we investigate the effect of the cyclin dependent kinase inhibitors, olomoucine and roscovitine, on E2F-1-mediated apoptosis in human gastric carcinoma cells. AGS and SNU-1 gastric adenocarcinoma cells were infected with adenoviral vectors expressing E2F-1 (Ad5CMVE2F-1) or control viruses expressing beta-galactosidase (Ad5CMVLacZ) or lacking a transgene (Ad5). Gastric adenocarcinoma cells were then independently treated with roscovitine or olomoucine. Finally, gastric adenocarcinoma cells were infected with the various adenoviral vectors in combination with roscovitine or olomoucine. E2F-1 overexpression resulted in an 85% reduction in cell viability at 72 h compared to controls. Combining E2F-1 overexpression with roscovitine resulted in >99% reduction in cell viability by 72 h. Overexpression of E2F-1 resulted in premature S-phase entry and G2/M arrest at 24 h, followed by apoptosis by 72 h. Combining E2F-1 overexpression with roscovitine resulted in an earlier G2/M arrest, followed by a more complete, widespread apoptotic response by 24 h. Caspase 3/CPP32 activation and PARP cleavage in response to E2F-1 overexpression, alone and in combination with roscovitine, implicate the caspase cascade in E2F-1-mediated apoptosis of gastric cancer cells. Bax levels also increased in response to E2F-1 gene transfer, alone and in combination with roscovitine. E2F-1 overexpression induces widespread apoptosis in human gastric carcinoma cells. Combining E2F-1 overexpression with cyclin-dependent kinase inhibitors results in an enhanced apoptotic response, causing nearly complete gastric tumor cell death within 72 h. E2F-1 gene therapy in combination with cyclin dependent kinase inhibitors is a potentially active chemogene therapy strategy for the treatment of human gastric cancer.

Adenoviridae↗

PubMed2000

Caspase activation and changes in Bcl-2 family member protein expression associated with E2F-1-mediated apoptosis in human esophageal cancer cells.

The prognosis for patients with esophageal cancer remains poor, prompting the search for new treatment strategies. Overexpression of E2F-1 has been shown to induce apoptosis in several cancer cell types. In the present study, the effect of adenovirus-mediated E2F-1 overexpression on human esophageal cancer cell lines Yes-4 and Yes-6 was evaluated. Cells were treated by mock infection, infection with an adenoviral vector expressing beta-galactosidase (Ad5CMV-LacZ), or E2F-1 (Ad5CMVE2F-1). Western blot analysis confirmed marked overexpression of E2F-1 in Ad5CMVE2F-1-infected cells. Overexpression of E2F-1 resulted in marked growth inhibition and rapid loss of cell viability due to apoptosis, although Yes-6 cells were somewhat more resistant to E2F-1-mediated growth inhibition than Yes-4 cells. Cell cycle analysis revealed that overexpression of E2F-1 led to G2 arrest, followed by apoptotic cell death. p53 expression remained undetectable in both cell lines after E2F-1 overexpression. The apoptosis inhibitor proteins of the Bcl-2 gene family, Bcl-2, Mcl-1, and BcI-XL, decreased at 48 h after infection in Yes-4 cells, but remained unchanged in Yes-6 cells. Levels of retinoblastoma gene product (pRb) declined at 48 h after E2F-1 infection in Yes-4 cells, at which apoptosis predominated, whereas pRb expression remained constant in Yes-6 cells. Expression of p14ARF did not change after E2F-1 infection in either cell line. Involvement of caspase 3 and caspase 6 in E2F-1-mediated apoptosis was demonstrated by cleavage of caspase 3/CPP32 and poly-ADP-ribose polymerase, as well as fragmentation of the caspase 6 substrate, lamin B. These results indicate that the sensitivity of esophageal cancer cells to E2F-1-mediated apoptosis may be related to differential expression of Bcl-2 family member proteins and suggest that the adenovirus-mediated E2F-1 gene therapy may be a promising treatment strategy for the treatment of this disease.

Adenoviridae↗

PubMed2000

Induction of apoptosis in human esophageal cancer cells by sequential transfer of the wild-type p53 and E2F-1 genes: involvement of p53 accumulation via ARF-mediated MDM2 down-regulation.

Transcriptional factor E2F-1 as well as tumor suppressor p53 have been shown to cause apoptosis independently in some types of human cancer cells when overexpressed. Here we report that sequential transfer of the wild-type p53 and E2F-1 genes efficiently induces apoptosis in human esophageal cancer cells and that E2F-1 overexpression directly, activates expression of p14 (ARF), which inhibits MDM2-mediated p53 degradation, resulting in the stabilization of p53. Infection of human esophageal cancer cell lines T.Tn and TE8 with adenovirus vector-expressing E2F-1 (Ad-E2F-1) enhanced mRNA and protein expression of ARF and decreased MDM2 protein expression. Transfection of ARF plasmid decreased MDM2 protein expression, which in turn increased p53 protein expression. Infection of T.Tn and TE8 cells first with adenovirus-expressing wild-type p53 (Ad-p53) and then with Ad-E2F-1 resulted in rapid induction of apoptosis; in contrast, simultaneous infection with Ad-E2F-1 and Ad-p53 had no significant antitumor effect. As shown by Western blot analysis, infection with suboptimal concentrations of Ad-E2F-1 induced the accumulation of exogenous p53 transduced by suboptimal concentrations of Ad-p53. Moreover, Ad-E2F-1-mediated ARF expression inhibited the up-regulation of MDM2 by overexpressed p53 in TE8 cells. Thus, overexpression of ectopic E2F-1 protein may stabilize endogenous as well as ectopic p53 protein via the E2F-1/ARF/MDM2/p53 regulatory pathway and, in this way, render cells more sensitive to apoptosis, an outcome that has important implications for the treatment of human esophageal cancers.

Adenoviridae↗

PubMed2000

[Effect of dissolved oxygen on mutanolysin fermentation].

Effects of several parameters relating to dissolved oxygen(DO) on mutanolysin fermentation were studied. The experiment using shake flasks shows that the medium volume and shaker agitation speed affect the production of mutanolysin. At the same time, the agitation rate together with aeation rate has effects on DO in fermentor. Mutanolysin fermentation was affected by DO greatly. Oxygen is a key restricted factor in mutanolysin fermentation. It affects the metablism and physiological action of Streptomyces globisporus S186. Whatever the DO is excessive high or low, it won't benefit the mutanolysin production. If DO is super, S. globisporus S186 will grow luxuriantly but do not produce mutanolysin, while if DO is lower, the S. globisporus S186 won't grow well even not to produce mutanolysin. During the course of fermentation, the DO changed regularly. It is similar to many antibiotic fermentation and some amino acid fermentation. As S. globisporus S186 grow in exponential phase, DO begin to decrease rapidly from 6 h and get to the lowest point at 40 h or so. Subsequently mutanolysin starts to be produced. DO rises again from 90 h. The key technoloyg of oxygen control in the fermentation is to keep the DO at a suboptimum level. In order to get a high mutanolysin yield, during the culture in fermentor the agitation rate and aeration rate should be kept at 200 r/min and 1:0.8(V:V) respectively.

Endopeptidases↗

PubMed2000

Histopathologic analysis of sentinel lymph nodes in breast carcinoma.

BACKGROUND: Intraoperative lymphatic mapping and identification of the first draining lymph node (the sentinel lymph node) may allow some patients with breast cancer to avoid the morbidity of formal axillary clearance. The aim of this study was to determine the accuracy of sentinel lymph node (SLN) biopsy in predicting axillary nodal involvement. METHODS: From August, 1998 until July, 1999, 41 patients with clinically node-negative breast cancer underwent SLN biopsy that was immediately followed by axillary lymph node dissection. If the SLN section was found free of metastasis by routine hematoxylin and eosin staining (H&E), then an additional four sections of the SLN were cut and examined for the presence of tumor cells by H&E staining (three sections) and by cytokeratin immunohistochemical staining (IHC) (one section). If the SLN had metastatic cells and the other remaining nonsentinel axillary lymph nodes were free of metastases by routine H&E staining, then an additional three sections of the nonsentinel axillary lymph nodes were cut and examined for the presence of tumor cells by H&E staining. RESULTS: The 41 patients had a mean of 2.2 sentinel (range, 1-7) and 14.6 nonsentinel (range, 5-32) lymph nodes excised per patient. Routine H&E staining identified 13 patients (31.7%) with SLN metastases and 28 patients (68.3%) with tumor-free SLNs. Applying IHC and the additional three sections stained with H&E to these tumor-free SLNs showed one additional patient with sentinel node metastasis. The conversion rate from being a sentinel node-negative patient to a sentinel node-positive patient was 3.6% (1/28). Overall, SLN metastases were detected in 14 (34.1%) of the 41 patients. The SLNs were negative in 27 patients (65.9%), two of whom had at least one positive nonsentinel lymph node each (7.4% "skip" metastasis). Biopsy of SLNs was 92.6% accurate in predicting the absence of nonsentinel nodal metastasis (p=0.001). CONCLUSIONS: Our results suggest that formal axillary lymph node dissection may need only be performed in SLN-positive patients. Nonetheless, further experience and refinement are needed to perfect this technique.

Adult↗

PubMed1999

Adenovirus-mediated E2F-1 gene transfer efficiently induces apoptosis in melanoma cells.

BACKGROUND: E2F-1 is a transcription factor that stimulates cellular proliferation and cell cycle progression from G(1) to S-phase. Somewhat paradoxically, E2F-1 also has the properties of a tumor suppressor. Overexpression of E2F-1 has been shown to induce apoptosis in some cancer cells. In the current study, the effect of adenovirus-mediated E2F-1 gene transfer on human melanoma cell growth was investigated. METHODS: Two human melanoma cell lines, SK-MEL-28 (wild-type p53) and SK-MEL-2 (mutant p53), were treated by mock infection, infection with a control vector expressing the beta-galactosidase gene (Ad5CMV-LacZ), or infection with a vector expressing E2F-1 (Ad5CMV-E2F-1) at a multiplicity of infection of 100. Cell proliferation and viability were determined by WST-1 assay and trypan blue exclusion, respectively. Apoptosis was assessed by cell flow cytometry and confirmed by cell morphology, in situ terminal deoxynucleotidyl nick end labeling assay, and poly(ADP-ribose) polymerase cleavage assay. RESULTS: Marked overexpression of E2F-1 was evident in both cell lines 24 hours after infection with Ad5CMVE2F-1 by Western blot analysis. E2F-1 overexpression resulted in growth inhibition and rapid loss of cell viability. Overexpression of E2F-1 also resulted in premature S-phase entry and G(2) arrest at 24 hours followed by apoptotic cell death at 48 hours. After Ad5CMVE2F-1 infection, expression of Bax and Bak was unchanged, whereas Mcl-1 levels decreased markedly. In SK-MEL-28 cells, Bcl-XL levels also declined after E2F-1 expression. Bcl-2 was undetectable in SK-MEL-28 cells but was increased in SK-MEL-2 cells in response to E2F-1 overexpression. CONCLUSIONS: Adenovirus-mediated E2F-1 gene transfer efficiently induces widespread apoptosis in human melanoma cells. E2F-1 overexpression induced apoptosis in cell lines containing wild-type and mutant p53, suggesting that this effect does not require wild-type p53 function. Anti-apoptotic proteins of the Bcl-2 family, notably Mcl-1 and Bcl-XL, may be involved in mediating the response to E2F-1. These data suggest that adenovirus-mediated E2F-1 gene therapy may be effective in the treatment of melanoma.

Adenovirus E2 Proteins↗

PubMed1999

Antiangiogenesis treatment for gliomas: transfer of antisense-vascular endothelial growth factor inhibits tumor growth in vivo.

Presently, there is no effective treatment for glioblastoma, the most malignant and common brain tumor. Angiogenic factors are potentially optimal targets for therapeutic strategies because they are essential for tumor growth and progression. In this study, we sought a strategy for efficiently delivering an antisense cDNA molecule of the vascular endothelial growth factor (VEGF) to glioma cells. The recombinant adenoviral vector Ad5CMV-alphaVEGF carried the coding sequence of wild-type VEGF165 cDNA in an antisense orientation. Infection of U-87 MG malignant glioma cells with the Ad5CMV-alphaVEGF resulted in reduction of the level of the endogenous VEGF mRNA and drastically decreased the production of the targeted secretory form of the VEGF protein. Treatment of s.c. human glioma tumors established in nude mice with intralesional injection of Ad5CMV-alphaVEGF inhibited tumor growth. Taken together, these findings indicate that the efficient down-regulation of the VEGF produced by tumoral cells using antisense strategies has an antitumor effect in vivo. This is the first time that an adenoviral vector is used to transfer antisense VEGF sequence into glioma cells in an animal model, and our results suggest that this system may have clinical and therapeutic utility.

Adenoviridae↗

PubMed1999

Plate fixation of fresh displaced midshaft clavicle fractures.

From 1992-1994, we operated on 251 fresh completely displaced mid-third clavicle fractures in adults; 232 were followed up. The fractures were plated with a Mizuho C-type plate or an AO/ASIF 3.5 mm reconstruction plate. Comminuted fragments were reduced and wired (133 cases). There were 150 men and 82 women; the median age was 37.3 years (range 18-79). The mean follow-up was 4.4 years (range 3.0-5.9). The mean time to radiographic union was 10 weeks. Seven patients (3%) developed nonunion. Healing with angulation occurred in 14 patients. Deep infection developed in one patient, and superficial infection in four cases; 21 patients reported soreness with changes in the weather and activity; 28 patients had residual skin numbness caudal to the incision. No patient had shoulder droop, and none had impairment of range of motion or shoulder strength. None developed new or late neurovascular impairment; 171 patients eventually had the hardware removed at an average 401 days post operatively. Overall, 94% were satisfied with the procedure. For completely displaced clavicle fractures in adults, plating is a reliable procedure.

Adolescent↗

PubMed1999

Mesohepatectomy for centrally located hepatocellular carcinoma: an appraisal of a rare procedure.

BACKGROUND: For centrally located hepatocellular carcinoma (HCC), extended major hepatectomy is usually recommended, but the risk of postoperative liver failure is high when liver function is not sound. Mesohepatectomy (en bloc resection of Goldsmith and Woodburne's left medial and right anterior segments or Couinaud's segments IV, V, and VIII) is a rare procedure, so its role in treating HCC is unclear. STUDY DESIGN: We retrospectively reviewed 364 patients who underwent a curative resection for HCC. Among them, 15 patients were treated by mesohepatectomy. Their nontumorous liver revealed cirrhosis in 11 and chronic hepatitis in 4. The mean tumor diameter was 12.8 cm. In 10 of the 15 patients, HCC also invaded adjacent organs. The operative results of another 25 patients with different disease extent who underwent extended major hepatectomy were compared. RESULTS: The hepatic inflow occlusion time for mesohepatectomy was longer than for extended hepatectomy (p = 0.01). The mean operative blood loss, amount of blood transfusion, operating time, and postoperative hospital stay in the mesohepatectomy group were 2,450 mL, 1,100 mL, 7.9 hours, and 14.9 days, respectively. In the extended-hepatectomy group, the values were 1,863mL, 768mL, 5.8 hours, and 16.8 days, respectively (all p>0.05 compared with mesohepatectomy). No patient died after mesohepatectomy, but after extended hepatectomy there was one death from liver failure. The Union Internationale contre le cancer (UICC) TNM stages of patients who underwent mesohepatectomy were as follows: stage II in 1, stage III in 4, and stage IVA in 10. All patients who underwent extended hepatectomy presented with stage IVA disease. The 6-year disease-free and actuarial survival rates after mesohepatectomy were 21% and 30%, respectively. The 6-year disease-free survival rate after extended hepatectomy was 9% (p = 0.11 compared with mesohepatectomy). CONCLUSION: Although mesohepatectomy is time-consuming, it is justified for selected patients with centrally located large HCC in a diseased liver.

Adult↗

PubMed1999

Video microscopy of tumor metastasis: using the green fluorescent protein (GFP) gene as a cancer-cell-labeling system.

Video microscopy allows dynamic observation of cancer-cell activity in the microcirculation of live animals. However, observation of cancer invasion and metastasis in situ has never been successful because of the lack of a technique for labeling cancer cells. We report here our success with video microscopy of cancer-cell activity, detection of remote metastases and cancer cells endogenously generated using the green fluorescent protein (GFP) gene as a cell-labeling system in live animals. As a cell-labeling system, GFP is stable, efficient, and nontoxic, and it is passed on to subsequent generations of cells. This pilot experiment has demonstrated the feasibility of direct observation and documentation of tumor growth and tumor invasion as well as the metastatic activities of cancer cells in live animals.

Animals↗

PubMed1999

The adsorption protein genes of Xanthomonas campestris filamentous phages determining host specificity.

Gene III (gIII) of phiLf, a filamentous phage specifically infecting Xanthomonas campestris pv. campestris, was previously shown to encode a virion-associated protein (pIII) required for phage adsorption. In this study, the transcription start site for the gene and the N-terminal sequence of the protein were determined, resulting in the revision of the translation initiation site from the one previously predicted for this gene. For comparative study, the gIII of phiXv, a filamentous phage specifically infecting X. campestris pv. vesicatoria, was cloned and sequenced. The deduced amino acid sequences of these two pIIIs exhibit a high degree of identity in their C-terminal halves and possess the structural features typical of the adsorption proteins of filamentous phages: a signal sequence in the N terminus, a long glycine-rich region near the center, and a hydrophobic membrane anchorage domain in the C terminus. The regions between gIII and the upstream gVIII, 128 nucleotides in both phages, are larger than those of other filamentous phages. A hybrid phage of phiXv, consisting of the phiLf pIII and all the other components derived from phiXv, was able to infect X. campestris pv. campestris but not X. campestris pv. vesicatoria, indicating that gIII is the gene specifying host specificity and demonstrating the interchangeability of the pIIIs.

Amino Acid Sequence↗