Effect of Antisense Oligodeoxynucleotide of Vascular Endothelial Growth Factor C on Lymphangiogenesis and Angiogenesis of Pancreatic Cancer

In order to investigate the effect of antisense oligonucleotide (ASODN) of vascular en-dothelial growth factor C (VEGF-C) on lymphangiogenesis and angiogenesis of pancreatic cancer, antisense and scamble-sense oligonucleotide of VEGF-C were constructed, and the model of nude mice with orthotopically xenografted human pancreatic cancer cells (Panc-1) was established. Thirty nude mice were randomly divided into 3 groups: PBS control group (group A), scramble-sense con-trol group (group B) and antisense group (group C). All nude mice were treated once every 2 days as 3 times per week, for 3 weeks (oligonucleotide 10 mg/kg every time). After treatments were com-pleted, ELISA method was used to examine the concentration of VEGF-C in plasma and immunohis-tochemical method to examine microvessel density (MVD), lymphtic vessel density (LVD) of pan-creatic cancer. The results showed that the expression of VEGF-C was inhibited significantly in group C. The concentrations were 237.5±41.5, 221.5±52.3 and 108.6±14.9 pg/mL in groups A, B and C re-spectively (P<0.01). LVD in groups A, B and C was 13.8±2.1, 12.4±1.9 and 4.2±1.6 respectively (P<0.01). MVD in groups A, B and C was 27.5±8.7, 25.9±4.2 and 19.4±5.6 respectively with no sig-nificant difference among the groups (P>0.05). It was suggested that VEGF-C ASODN decreased the expression levels of VEGF-C in nude mice with orthotopically xenografted human pancreatic cancer, and it could inhibit lymphangiogenesis, but had no significant effect on angiogenesis.     

Increased Expression of PI-3K in Asthmatic Rat T Lymphocytes

In order to explore the expression of PI-3K in T lymphocytes of asthmatic rats and the relationship between PI-3K and activation of T lymphocytes, 24 Wistar rats were randomly divided into 4 groups: normal control group, asthmatic one-week group, asthmatic two-week group and asth-matic four-week group. T cells were purified from blood of each rat and the expression of PI-3K was observed by immunocytochemical fluorescence staining, the semiquantitative fluorescence intensity was measured by HPIAS-2000 analytic software, and the expression of IL-4 in supernatants was de-tected by ELISA. The results showed that the fluorescence intensity of T lymphocytes in asthmatic groups was significantly higher than that in normal control (P<0.001), indicating that the expression of PI-3K in T lymphocytes of asthmatic rats was significantly higher than that in those of normal controls, and the difference between acute and chronic stage asthmatic groups was significant (P<0.05). The expression levels of IL-4 protein in supernatants of asthmatic T lymphocytes were sig-nificantly higher than those in the normal controls (P<0.05). There was a significant positive correla-tion between the expression of PI-3K in T lymphocytes and the IL-4 protein expression in super-natants (r=0.583, P<0.01). It was suggested that PI-3K signal pathway may participate in the proc-esses of activation and other cytological effects of asthmatic T lymphocytes, thus may play an impor-tant roles in the pathogenesis of asthma.     

Enhanced Response of Acute Monocytic Leukemia Cells to Low-dose Cytarabine by 1,25-dihydroxyvitamin D3

Low-dose cytarabine combined with differentiating or DNA hypomethylating agents, such as vitamin D compounds, is a potential regimen to treat acute myeloid leukemia (AML) patients who are unfit for high-intensity chemotherapy. The present study aimed to determine which subset of AML would be most responsive to low-dose cytarabine with the differentiating agent 1,25-dihydroxyvitamin D3 (1,25-D3). Here, firstly, cBioPortal database was used and we found out that vitamin D receptor (VDR) was highly expressed in acute monocytic leukemia (M5) and high VDR expression was associated with a poor survival of AML patients. Then, we confirmed that 1,25-D3 at clinical available concentration could induce more significant differentiation in acute monocytic leukemia cell lines (U937, MOLM-13, THP-1) and blasts from M5 patients than in non-monocytic cell lines (KGla and K562) and blasts from M2 patient. Finally, it was shown that the combination of 1,25-D3 and low-dose cytarabine further increased the differentiating rate, growth inhibition and G0/G1 arrest, while mild changes were found in the apoptosis in acute monocytic leukemia cell lines. Our study demonstrates that the enhanced response of acute monocytic leukemia cells to low-dose cytarabine by 1,25-D3 might indicate a novel therapeutic direction for patients with acute monocytic leukemia, especially for elderly and frail ones.     

Inhibitory activity of nuclear factor-κB potentiates cisplatin-induced apoptosis in A549 cells

Whether inhibiting the activity of nuclear factor （NF）-κB potentiates cisplatin-induced apoptosis in non-small cell lung cell line A549 cells was investigated. The recombinant plasmid pcDNA3.1（＋）/IκBα expressing IκBα was constructed. The in vitro cultured A549 cells were transfected with pcDNA3.1 （＋）/IκBα alone, or pcDNA3.1（＋）/IκBα combined with cisplatin. The mitochondrial membrane potential （△ψm） was determined by rhodamine 123, the activity of caspase-3 was tested by colorimetric assay, and cell apoptosis was detected by flow cytometry with the annexin V/propidium iodide assay. The results showed that the activity of NF-κB in A549 cells was inhibited by transfecting pcDNA3.1（＋）/IκBα. Transfection of pcDNA3.1（＋）/IκBα alone did not promote apoptosis. Treatment of cisplatin alone had a little effect on cell apoptosis. Transfection of pcDNA3.1（＋）/IκBα combined with cisplatin treatment significantly induced apoptosis of A549 ceils. It was concluded that inhibiting the activity of NF-κB potentiated cisplatin-induced apoptosis of A549 cells.     

Postoperative Liver Dysfunction and Future Remnant Liver: Where Is the Limit?

Background The future remnant liver (FRL) limit for safe major hepatectomy with low risk of postoperative liver failure has not yet been well defined. Methods Between April 2000 and September 2004, every patient scheduled for major hepatectomy in our institution underwent CT-volumetry of FRL. Patients with FRL <25% underwent portal vein embolization (PVE). Exclusion criteria were PVE, associated vascular resection and liver cirrhosis. The FRL was correlated with short-term results in patients with normal liver (group A) and those with impaired liver function secondary to neoadjuvant chemotherapy or cholestasis (bilirubin >2 mg/100 ml) (group B). Liver dysfunction was defined as both PT <50% and serum bilirubin level >5 mg/100 ml for three or more consecutive days. Results A total of 119 patients were analyzed, 72 in group A and 47 in group B. The FRL value was the only significant risk factor for postoperative liver dysfunction in the univariate and multivariate analysis (p = 0.009). The FRL did not correlate with postoperative mortality and morbidity. Bilirubin and prothrombin time (PT) on days 3 and 7 were significantly correlated to FRL in both groups. In group A, patients with postoperative liver dysfunction had a FRL<30% (3 versus 0; p = 0.005). According to receiving operator characteristic (ROC) curve analysis, a FRL value of 26.5% predicted postoperative liver dysfunction with 66.7% sensitivity, 97.1% specificity, 50% positive predictive value (PPV), and 98.5% negative predictive value (NPV). In group B, patients with postoperative liver dysfunction had a FRL <35% (4 versus 0; p = 0.027). According to ROC curve analysis, a FRL value of 31.05% predicted postoperative liver dysfunction with 75% sensitivity, 79.1% specificity, 25% PPV, and 97.1% NPV. Conclusions Hepatectomy can be considered safe when FRL is >26.5% in patients with healthy liver and >31% in patients with impaired liver function.     

The Emerging Role of Robotics in Adrenal Surgery

Robotic surgery is being performed more frequently for a variety of urologic procedures. Since the first robotic adrenalectomy less than a decade ago, this modality has gained increased acceptance in the urologic community and has been employed with increased frequency in minimally invasive centers. This review evaluates the current literature on robotic adrenalectomy, its indications, as well as its advantages and limitations compared with other forms of surgical management of adrenal pathology.