Intra-tumor injection of H101,a recombinant adenovirus,in combination with chemotherapy in patients with advanced cancers:A pilot phase Ⅱ clinical trial

AIM: HI01, an EIB 55 kD gene deleted adenovirus, has been shown to possess oncolysis activity experimentally and proved to be safe in preliminary phase I study. The current study was designed to evaluate its anti-tumor activity and toxicity in combination with chemotherapy in patients with late stage cancers.METHODS: H101 5.0×10^11 virus particles were given by intra-tumor injection daily for five consecutive days at every three-week cycle, combined with routine chemotherapy,to one of the tumor lesions of 50 patients with different malignant tumors. Tumor lesions without H101 injection in the same individuals were used as controls. The efficacy and toxicity were recorded.RESULTS: Forty-six patients were evaluable with a 30.4% response rate. H101 injection in combination with chemotherapy induced three complete response (CR) and 11 partial response (PR), giving an overall response rate of 28.0% (14/50) among intention-to-treat patients. The response rate for the control lesions was 13.0%, including one case with CR and five cases with PR, which was significantly lower than that for the injected lesions (P<0.05).Main side effects were fever (30.2%) and pain at the injected sites (26.9%). Grade 1 hepatic dysfunction was found in four patients, grade 2 in one patient, and grade 4 in one patient. Hematological toxicity (grade 4) was found in four patients.CONCLUSION: Intra-tumor injection of the genetically engineered adenovirus H101 exhibits potential anti-tumor activity to refractory malignant tumors in combination with chemotherapy. Low toxicity and good tolerance of patients to H101were observed.

Relationship between encephalopathy and portal vein-vena cava shunt:Value of computed tomography during arterial portography

AIM: TO assess the value of computed tomography during arterial portography (CTAP) in portal vein-vena cava shunt,and analysis of the episode risk in encephalopathy.METHODS: Twenty-nine patients with portal-systemic encephalopathy due to portal hypertension were classified by West Haven method into grade Ⅰ(29 cases), gradeⅡ(16 cases), grade Ⅲ(10 cases), grade Ⅳ( 4 cases). All the patients were scanned by spiraI-CT. Plane scans, artery phase and portal vein phase enhancement scans were performed, and the source images were thinly reconstructed to 1.25 mm. We reconstructed the celiac trunk, portal vein,inferior vena cava and their branches and subjected them to three-dimensional vessel analysis by volume rendering(VR) technique and multiplanar volume reconstruction (MPVR) technique. The blood vessel reconstruction technique was used to evaluate the scope and extent of portal vein-vena cava shunt, portal vein emboli and the fistula of hepatic artery- portal vein. The relationship between the episode risk of portal-systemic encephalopathy and the scope and extent of portal vein-vena cava shunt,portal vein emboli and fistula of hepatic artery- portal vein was studied.RESULTS: The three-dimensional vessel reconstruction technique of spiraI-CT could display celiac trunk, portal vein,inferior vena cava and their branches at any planes and angles and the scope and extent of portal vein-vena cavashunt, portal vein emboli and the fistula of hepatic artery- portal vein. In twenty-nine patients with portal-systemicencephalopathy, grade Ⅰ accounted for 89.7% esophageal varices, 86.2% paragastric varices; grade Ⅱ accounted for 68.75% cirsomphalos, 56.25% paraesophageal varices,62.5% retroperitoneal varices and 81.25% dilated azygos vein; grade Ⅲ accounted for 80% cirsomphalos, 60%paraesophageal varices, 70% retroperitoneal varices, 90% dilated azygos vein, and part of the patients in grades Ⅱand Ⅲ had portal vein emboli and fistula of hepatic arteryportal vein; grade Ⅳ accounted for 75% dilated left renal vein, 50% paragallbladder varices, all the patients had fistula of hepatic artery- portal vein.CONCLUSION: The three-dimensional vessel reconstruction technique of spiraI-CT can clearly display celiac trunk, portal vein, inferior vena cava and their branches at any planes and angles and the scope and extent of portal vein-vena cava shunt. The technique is valuable for evaluating the episode risk in portal-systemic encephalopathy.

Cell apoptosis and regeneration of hepatocellular carcinoma after transarterial chemoembolization

AIM: To evaluate whether cell apoptosis and regeneration were existed in normal liver cells adjacent to carcinoma after transarterial chemoembolization (TACE).METHODS: Fifty rabbits with hepatic carcinoma were divided into 5 groups at random: group A (control group),groups B and C (TACE treatment groups), groups D and E (partial hepatectomy groups). There were 10 rabbits in each group. Rabbits in groups B-E were treated by transartedal chemoembolization (TACE) and partial hepatectomy (PH) respectively. The changes of S-phase cell fraction (SPF),proliferation index (PI) and cell apoptosis in the normal liver tissue were determined with flow cytometry (FCM) after operations on the first and third days. We determined the mitosis index (MI) with histo-pathological method and the apoptosis index (AI) with TUNEL method at the same time.RESULTS: Twenty-four hours after operations, compared with control group, the rabbits in TACE group had much higher index of SPF, PI and MI (MI: t=-4.89, P<0.001; SPF:t=-5.27, P<0.001; PI: ~4.87, P<0.001). Moreover, the proliferation of liver cells in TACE group was much weaker than that of the cells treated by partial hepatectomy, and the differences were significant (MI: t=7.02, P<0.001; SPF:t=-4.06, P<0.001; PI: t=2.70, P<0.05). Seventy-two h after operations, FCM showed a small sub-G1 peak in TACE group and PH group, compared with the control group, but there was no difference between them (t=0.41, P>0.05).TACE showed that AI in the treated rabbits was higher than that in control group (t=-3.07, P<0.05), and there were no differences between TACE group and PH group, either(t=0.93, P>0.05).CONCLUSION: Cell apoptosis and regeneration exist in rabbit liver tissues after TACE in some degree, which may be associated with the selective embolization of iodised oil, chemotherapeutic drug and free radical damage.

Synthesis and Nonlinear Optical Property of a Polyphosphazene with High Glass Transition Temperature

A new polyphosphazene containing binaphtholyl and indole azo chromophores as side chains with high glass transition temperature ( Tg ) was synthesized by a post-functional method. The polymer was well characterized. Its Tg was tested to be 168℃, and the poled film of P2 reveals a resonant d33 value of 20 pm/V by second harmonic generation ( SHG ) measurements.