Fusion to the Lysosome Targeting Signal of the Invariant Chain Alters the Processing and Enhances the Immunogenicity of HIV-1 Reverse Transcriptase.

Intracellular processing of the antigen encoded by a DNA vaccine is one of the key steps in generating an immune response. Immunization with DNA constructs targeted to the endosomal-lysosomal compartments and to the MHC class II pathway can elicit a strong immune response. Herein, the weakly immunogenic reverse transcriptase of HIV-1 was fused to the minimal lysosomal targeting motif of the human MHC class II invariant chain. The motif fused to the N-terminus shifted the enzyme intracellular localization and accelerated its degradation. Degradation of the chimeric protein occurred predominantly in the lysosomal compartment. BALB/c mice immunized with the plasmid encoding the chimeric protein demonstrated an enhanced immune response, in the form of an increased antigen-specific production of Th1 cytokines, INF-γ and IL-2, by mouse splenocytes. Moreover, the majority of the splenocytes secreted both cytokines; i.e., were polyfunctional. These findings suggest that retargeting of the antigen to the lysosomes enhances the immune response to DNA vaccine candidates with low intrinsic immunogenicity.

[Direct results of endovascular prosthetics of aneurysms of the infrarenal part of the aorta in patients with a severe concomitant pathology].

From May 2007 to March 2009 under observation there were 58 patients aged from 52 to 79 years (mean age 68) with the diagnosis of abdominal aortic aneurysm (AAA). Selection of patients for endoprosthesis was performed by the data of spiral computed aortography. The endovascular exclusion ofAAA from blood flow was performed in 15 patients. All the patients had high risk of surgery because of multiple concomitant pathologies. In 14 (93%) patients bifurcational and in 1 patient aortofemoral unilateral prostheses of AAA were made with the application of femoro-femoral bypass. All implantations were technically successful without complications. Shorter time of operation, less intraoperative blood loss, shorter tine of staying in hospital and time of rehabilitation were found to be 1.5-3 times as compared with classical surgical intervention. Implantation of bifurcational stent-graph seems to be the method of choice in treatment of AAA patients with severe concomitant pathology.

[Influence of immunological parameters on the effectiveness of systemic and loco-regional immunotherapy in disseminated renal carcinoma].

Survival was assessed among patients with disseminated renal carcinoma from different prognostic groups as established by MSKCC protocol. Multivariate evaluation pointed to prognostic value of IL-6 (spontaneous and induced production), IL-8 (spontaneous and induced production),TNF-alpha (spontaneous production), IFN-gamma (induced production), TNK-cells (CD3+CD16+CD56+), and T-regulatory cells (CD4+CD25+Treg). It was demonstrated that additional criteria may be used to evaluate prognosis.

[Methods of correcting hepatic arterial blood supply for subsequent implantation of the "port-catheter" infusion system].

The study was undertaken to investigate the feasibility of using surgical and roentgenoendovascular redistribution of the hepatic arterial blood flow for adequate implantation of the "port-catheter" infusion system. Between December 2001 and March 2008, we performed surgical (n = 25) or transcutaneous (n = 22) implantations of the infusion systems for carrying out regional chemotherapy in a total of forty-seven patients presenting with hepatic metastases of colorectal carcinoma. Anatomical variants of the hepatic arteries were observed in eleven cases. The blood stream was corrected by means of either transcatheter embolization (n = 7), ligation (n = 2), or transposition (n = 2) of the aberrant arteries. No complications were encountered. In all the cases, the "port-catheter" system was implanted successfully, with adequate hepatic perfusion achieved. Both transcatheter embolization and surgical reconstruction turned out to be efficient methods in correction of the blood flow in various anatomical structures of the hepatic arteries, thus favourably contributing to increased efficacy of regional chemotherapy.

[Modern diagnostic technologies in determination of the strategy of treatment of patients with obliterating atherosclerosis of the lower artery vessels].

The authors analyzed results of surgical treatment of 332 patients in whom 410 reconstructive operations were performed on the lower extremity arteries. During 12 months after operation on the aorto-femoral segment with high peripheral vascular resistance reocclusions were noted in 61% of the cases, with normal resistance--in 11.8%, after operation on the femoro-popliteal segment--in 77.1% and 28.3% respectively. According to the findings of computed tomography and magnetic resonance imaging, densitometry the indices were established allowing prognosis of high peripheral resistance in the lower extremity arteries at the preoperative stage. Such indices are considered to be indications to femoro-profundoplasty on the aortofemoral segments or arterio-venous fistula on the femoro-popliteal segment. Such effectively fulfilled interventions could reduce the frequency of reocclusions to 3.1% on the aorto-femoral segment and to 11.8% on the femoro-popliteal segment.

[Combined treatment for malignant tumors using focal ethanol injections].

The potential of focal ethanol injection therapy (FEIT) as a component of combined treatment for malignant tumors was investigated. Thirty-four patients with inoperable primary and recurrent liver cancer received 72 FEIT procedures at the Institute's Clinic - 16 males (47%) and 18 females (53%), aged 35-80, (average 57), (1991-2004). Forty-three metastatic foci - colorectal carcinoma (23), non-colorectal carcinoma (20) and hepatocellular carcinoma (11) - were detected. Size of metastatic foci ranged 3.2-27.8 cm3 (average 15.4+/-6.4 cm3), while those of hepatocellular carcinoma - 156.7-982.4 cm3, (average 492.4+/-136.8 cm3). All patients received regional endovascular chemotherapy, without any life-threatening complications. Reduction in focal size after FEIT for hepatocellular carcinoma ranged 490.2+/-136.8 - 41.8+/-14 cm3. One-, three- and five-year survival was 100, 80 and 60%, respectively. In cases of hepatocellular carcinoma, ethanol-treated foci shrank by 88.4% - from 15.5+/-1.6 to 1.8 +/- 0.3 cm3 (p<0.05). One-, and three-year survival rates were 83 and 14%, respectively. After ethanol ablation, size of metastatic foci fell by 79%, from 13.9+/-4.3 to 2.9+/-2.4 cm3 (p<0.05). One- and three-year survival rates were 91 and 13%, respectively.