Allele loss and down-regulation of heparanase gene are associated with the progression and poor prognosis of hepatocellular carcinoma.

OBJECTIVES: The role of heparanase (HPSE) gene in cancers including hepatocellular carcinoma (HCC) is currently controversial. This study was aimed at investigating the impact of genetic alteration and expression change of HPSE on the progression and prognosis of HCC. METHODS: The HPSE gene was studied in three different aspects: (1) loss of heterozygosity (LOH) by a custom SNP microarray and DNA copy number by real-time PCR; (2) mRNA level by qRT-PCR; and (3) protein expression by immunohistochemistry. The clinical significances of allele loss and expression change of HPSE were analyzed. RESULTS: Microarray analysis showed that the average LOH frequency for 10 SNPs located within HPSE gene was 31.6%, three of which were significantly correlated with tumor grade, serum HBV-DNA level, and AFP concentration. In agreement with SNP LOH data, DNA copy number loss of HPSE was observed in 38.74% (43/111) of HCC cases. HPSE mRNA level was notably reduced in 74.1% (83/112) of tumor tissues compared with non-tumor liver tissues, which was significantly associated with DNA copy number loss, increased tumor size, and post-operative metastasis. HPSE protein level was also remarkably reduced in 66.3% (53/80) of tumor tissues, which was correlated with tumor grade. Patients with lower expression level of HPSE mRNA or protein had a significantly lower survival rate than those with higher expression. Cox regression analysis suggested that HPSE protein was an independent predictor of overall survival in HCC patients. CONCLUSIONS: The results in this study demonstrate that genetic alteration and reduction of HPSE expression are associated with tumor progression and poor prognosis of HCCs, suggesting that HPSE behaves like a tumor suppressor gene and is a potential prognostic marker for HCC patients.

[Inhibitory effects of recombinant adenovirus carrying human endostatin gene on the growth of human pancreatic carcinoma xenograft in nude mice].

OBJECTIVE: To evaluate the inhibitory effect of recombinant adenovirus carrying human endostatin gene (Ad-endo) on the growth of human pancreatic carcinoma xenograft in nude mice. METHODS: The expression of endostatin in human pancreatic carcinoma Capan-2 cells was examined by RT-PCR after infection with Ad-endo. The supernatants of Capan-2 cells were collected after 48 h of infection with Ad-endo as the conditioned medium for human umbilical vein endothelial cells (HUVECs), whose proliferation in vitro was assayed. Capan-2 cell xenografts were established to determine the antitumoral effects of Ad-endo in vivo. The intratumoral microvessel density (MVD) was evaluated using CD31 staining. RESULTS: The expression of endostatin gene was detected by PT-PCR in infected Capan-2 cells. The conditioned medium from Ad-endo-infected cells significantly inhibited HUVEC proliferation (P<0.05). Ad-endo significantly suppressed the growth of Capan-2 tumor xenografts in nude mice (P<0.05), and the MVD decreased significantly in the treated tumor (P<0.05) as compared with that in the control group. CONCLUSION: Adenovirus carrying human endostatin gene produces inhibitory effects on the growth of human pancreatic carcinoma tumors in nude mice.

[Effect of adjusting the immunosuppressants on the prognosis of the infection in the patients with liver transplantation].

OBJECTIVE: To explore the method of adjusting the immunosuppressants in serious infection after liver transplantation. METHODS: With reference to sepsis-related organ failure assessment (SOFA), 2005.1-2007.12, when the patient's score > or =15, the immunosuppressants were withdrawn, and the patients were given powerful antibiotics and the other treatments in combination. They were further divided into two groups, SOFA 15-17 (group A, 10 cases) and > or =18 (group B, 16 cases). They were compared, and also with the patients without stoppage of immunosuppressants (group C, 13 cases, 2003.3-2004.12). After withdrawing the immunosuppressant, the rejection incidence and times, the changes in SOFA score and mortality and their relationships were analyzed. RESULTS: After adjusting the immunosuppressant and with control of serious infections, rejection occurred in 9 patients, with 5 cases in group A (50.0%), 4 in B (25.0%), none in C. The differences among groups showed statistically significant difference (chi(2)=8.0, P=0.02), but no difference was seen between group A and B (chi(2)=1.70, P=0.19). When the rejection developed, the SOFA score decreased obviously (9.78+/-3.14 vs. 17.22+/-1.86, t=6.10, P=0.00). The time of rejection was (17.56+/-2.60) days after stopping the immunosuppressant. All 25 deaths were due to serious infection with multiple organ dysfunction syndrome, but not rejection. Five deaths occurred in group A (50.0%), 7 in B (43.8%), 13 in C (100.0%). Not a single patient with rejection died from infection. Proper adjustment of the immunosuppressants could decrease the mortality (chi(2)=7.60, P=0.02). CONCLUSION: SOFA score could be used to guide the adjustment of the immunosuppressants, when SOFA> or =15, the immunosuppressants could be stopped, which would not increase the rejection incidence and decrease mortality. The lower the SOFA score is, the faster the patients recuperate better, but more rejection develops. In order to adjust the immunosuppressant in time, the period with high SOFA score should be shortened.

[Impact of adaptive positive end expiratory pressure and mechanical ventilation on hemodynamics and oxygen kinetics in post-liver transplantation patients].

OBJECTIVE: To determine the impact of adaptive positive end expiratory pressure (PEEP) and mechanical ventilation on hemodynamics and oxygen kinetics in post-liver transplantation patients. METHODS: The study included 11 patients who accepted mechanical ventilation after piggyback liver transplantation. Swan-Ganz catheter and radial artery catheter were used to monitor the cardiac output (CO), mean pulmonary arterial pressure (MPAP), mean arterial blood pressure (MABP) and central venous pressure (CVP) and airway pressure. After transplantation, PEEP of 0, 5, 10 and 15 cm H(2)O (1 cm H(2)O=0.098 kPa) was instituted to support the ventilation alternately. After 30 minutes, pressure regulated volume controlled ventilation (PRVCV) and pressure controlled synchronized intermittent mandatory ventilation+pressure support ventilation (PC-SIMV+PSV) were used to support the ventilation alternately and the indexes of hemodynamics and oxygen kinetics were analyzed. RESULTS: The data showed that differences existed in peak airway pressure, mean airway pressure, CVP and MPAP when different levels of PEEP were used. These indexes were significantly higher in PEEP of 15 and 10 cm H(2)O than those in PEEP of 0 and 5 cm H(2)O.There were no differences in pH, partial pressure of carbon dioxide in arterial blood (PaCO(2)), pressure of oxygen in arterial blood (PaO(2)), arterial oxygen saturation (SaO(2)), oxygen delivery (DO(2)), oxygen consumption (VO(2)) and oxygen extraction rate (O(2)ER) at different levels of PEEP. The airway pressure was significantly lower under PRVCV pattern than those under PC-SIMV+PSV pattern [(8.78+/-1.53) cm H(2)O vs. (11.64+/-3.30) cm H(2)O, P<0.05]. There were no differences in other indexes between these two mechanical ventilation patterns. CONCLUSION: These date suggested that a low level of PEEP (5 cm H(2)O) during mechanical ventilation should be used in post-liver transplantation patients in order to decrease the influence of PEEP on systemic circulation and hepatic regurgitation. PRVCV could be a more suitable mechanical ventilation pattern for patient after liver transplantation.

[Determination of plasma and sputum substance P content in patients with chronic obstructive pulmonary disease or asthma].

OBJECTIVE: To investigate the role of substance P (SP) in chronic obstructive pulmonary disease (COPD) or asthma. METHOD: Plasma and sputum samples were obtained from 26 COPD patients and 20 asthmatic patients as well as 12 healthy subjects for measurement of SP content. RESULTS: Patients with COPD had significantly higher levels of SP in the plasma (7.9+/-2.6 pmol/L) and sputum (53.8+/-12.5 pmol/L) than the healthy subjects (3.6+/-1.7 pmol/L and 6.2+/-2.3 pmol/L, respectively, P<0.01). The asthmatic patients also had significantly higher SP levels (8.3+/-3.1 pmol/L and 46.9+/-10.2 pmol/L, respectively) than the healthy subjects, but there was no significant difference between COPD and asthmatic patients (P>0.05). CONCLUSION: SP may be involved in the airway inflammation process in COPD and asthma.

[Retrospective analysis on clinical features of 35 patients with severe acute respiratory syndrome].

OBJECTIVE: To analyze the clinical features of severe acute respiratory syndrome (SARS). METHODS: The clinical features of 35 patients with SARS in the past five months were retrospectively studied, and compared with 35 patients with community-acquired pneumonia. Consecutive blood samples from 13 patients with SARS and 10 healthy volunteers were collected. The CD+4 and CD+8 in T cell in peripheral blood were detected by flow cytometry. RESULTS: The most common symptoms included fever (in 100.0 percent of the patients), cough (74.3 percent), headache (45.7 percent), myalgia (45.7 percent) and lymphopenia (20/33). Serial chest radiographs showed progressive multi-infiltration in the lung fields. The CD+4 and CD+8 in T cell in 13 patients with SARS significantly decreased [CD+4: (16.10+/-4.31) percent vs. (38.30+/-8.52) percent, t=8.174,P<0.01; CD+8: (19.90+/-5.40) percent vs. (28.38+/-4.33) percent, t=4.055, P<0.01]. The time of bringing down the fever and the time of absorption of pathological changes in SARS patients were prolonged than those of the pneumonia patients [the time of bringing down the fever (13.92+/-8.35) days vs. (3.86+/-1.42)days, t=16.490,P=0.000;the time of absorption of pathological changes: (11.97+/-4.41) days vs. (9.21+/-4.42) days, t=3.082,P=0.003]. CONCLUSION: SARS is a serious respiratory illness, the most common symptoms are fever, cough, headache and myalgia, other common findings are lymphopenia, the CD+4 and CD+8 in T cell in peripheral blood decrease and multi-infiltrate through out the lung fields.

[Changes in interleukin-1beta in serum and bronchoalveolar lavage fluid in the patient with acute respiratory distress syndrome].

OBJECTIVE: To study the role of interleukin-1beta (IL-1beta) in the pathogenesis of acute respiratory distress syndrome (ARDS). METHODS: The bronchoalveolar lavage fluid (BALF) and serum in 13 patients with ARDS and 9 healthy controls were collected. The contents of IL-1beta were measured by enzyme-linked immunoadsorbent assay(ELISA). RESULTS: The levels of IL-1beta in BALF [(144.67+/-80.79)ng/L] and serum [(45.71+/-7.09)ng/L] in patients with ARDS were significantly higher than those in the control groups [(20.39+/-1.87)ng/L, P=0.000; (35.06+/-5.46)ng/L, P=0.001, respectively], and the levels of IL-1beta in BALF were also significantly higher than those of the serum in the patients with ARDS (P=0.000). CONCLUSION: The results indicate that IL-1beta is involved in the pathogenesis of ARDS. Early determination of IL-1beta level in BALF may be more valuable in the evaluation of disease process of ARDS.