Gene therapy for primary and metastatic pancreatic cancer with intraperitoneal retroviral vector bearing the wild-type p53 gene

BACKGROUND: Metastatic pancreatic cancer is uniformly fatal because no effective chemotherapy is available. Mutations in the p53 tumor suppressor gene are found in up to 70% of pancreatic adenocarcinomas. We examined the efficacy of a retroviral vector containing the wild-type p53 gene on metastatic pancreatic cancer in a nude mouse model. METHODS: Bxpc3 human pancreatic cancer cells were transduced with either a retroviral p53 vector or an LXSN empty vector. Cells were examined for incorporation of tritiated thymidine to determine the effect of p53 retroviral transduction on DNA synthesis, and a TACS2 assay for apoptosis was performed. The functional activity of p53 in transduced cells was assessed by Western blot analysis with an antibody to WAF1/p21. In vivo effects of intraperitoneal injections of the p53 vector were examined in a nude mouse model of peritoneal carcinomatosis. RESULTS: Cells treated with the p53 vector exhibited a 59% to 85.5% reduction in cell number compared with the control cells (P < .05). p53-treated cells demonstrated decreased incorporation of tritiated thymidine (12.7% +/- 0.7% vs 17.5% +/- 1.4%; P = .002), increased staining for apoptosis, and increased expression of the WAF1/p21 protein. Treatment of nude mice with the retroviral p53 vector resulted in a significant inhibition of growth of the primary pancreatic tumor, as well as the peritoneal tumor deposits, compared with the LXSN control vector. CONCLUSIONS: Intraperitoneal delivery of a retroviral p53 vector may provide a novel treatment approach for peritoneal carcinomatosis from pancreatic cancer.     

Development of systemic immunologic responses against hepatic metastases during gene therapy for peritoneal carcinomatosis with retroviral HS-tk and ganciclovir

Gene therapy with retroviral mediated gene transfer of the herpes simplex thymidine kinase (HS-tk) gene into a tumor mass confers sensitivity of the tumor cells to ganciclovir (GCV). Tumor-specific immunologic responses may develop following treatment of the primary tumor with retroviral HS-tk and GCV. In the present study we assessed whether GCV treatment of HS-tk transduced colon cancer (TK+) implanted in the peritoneal cavity induced a systemic antitumor response that would inhibit growth of a second wild-type (TK-) tumor implanted in the liver. DHDK12 rat colon cancer cells were transduced in vitro with the retroviral HS-tk vector and established as a permanent cell line (TK+ cells). TK+ or TK- DHDK12 cells (6x10(6) cells) were injected intraperitoneally on day 0 into BD-IX rats. On day 10, TK- cells (3x10(6) cells) were injected into the liver in all the groups. The animals were then treated with GCV (150 mg/kg) for 13 days. TK+ peritoneal tumors underwent significant regression during therapy with GCV (0.05+/-0.004 g; n=7) compared to wild-type (TK-) tumors (2.2+/-0.7g; n=6) (P<0.05). The volume of TK- tumors in the liver was significantly lower in GCV-treated rats with TK+ peritoneal tumors (12.5+/-8.3 mm3) compared to rats with TK- peritoneal tumors (96.7+/-18.1 mm3) (P<0.05). Histology of the liver tumors in the TK+ groups showed a dense monocytic infiltrate with fibrosis and only occasional viable tumor cells. Gene therapy with retroviral HS-tk vectors may provide a novel approach to treatment of gastrointestinal cancer by both direct cytotoxicity and an indirect mechanism that may include enhanced immuno logic responses against disseminated disease.     

Postpolarizer mismatch effects in waveguide radiating systems

Postpolarizer impedance mismatch effects are known to have a degrading influence on the performance of a circularly polarized waveguide radiating system. These effects are analyzed in this paper     

Intravital microscopical studies of the tubular urine flow in the conscious rat

A case of severe lesion of the hand is reported in which the circulation of the thumb was restored by using a vein graft. The operative procedure and postoperative management are described. The periods of arterial insufficiency in the thumb, likely due to spasms, are discussed.     

First-principles investigation of elastic and electronic properties of double transition metal carbide MXenes

We use first-principles-based density functional theory (DFT) calculations to investigate the structural, elastic, and electronic properties of various pristine and oxygen (O)-functionalized double transition metal (DTM) MXenes with general formulas of M₂′M′′C₂ and M₂′M′′C₂O₂, where M′ = Mo, Cr and M′′ = Ti, V, Nb, Ta. The dynamic stability of the DTM MXenes are assessed and elastic stiffness constants (C_ij) are used to investigate the mechanical stability and properties of the compositions. The calculated elastic properties of the pristine Mo-based MXenes are found to be superior compared to Cr-based compounds. Furthermore, the O-functionalized MXenes exhibit improved in-plane elastic constants, Young's moduli, and shear moduli compared to their pristine counterpart. We observe that the hybridization of the energy states results in stronger covalent interactions as such increased elastic properties for the M₂′M′′C₂O₂ MXenes. Ashby plot clearly demonstrates superior materials properties of O-functionalized Mo-based DTM MXenes compared to other commonly known two-dimensional materials. All the MXenes exhibit metallic character evident from the density of states (DOS) calculations. Additionally, the work functions are studied and the calculated values are higher in the case of O-functionalized MXenes. Overall, this work will be a guide for future investigations on the mechanical properties of DTM MXenes for their targeted applications in structural nanocomposites.     

Close-packed noncircular nanodevice pattern generation by self-limiting ion-mill process

We describe a self-limiting, low-energy argon-ion-milling process that enables noncircular device patterns, such as squares or hexagons, to be formed using precursor arrays of uniform circular openings in poly(methyl methacrylate) defined using electron beam lithography. The proposed patterning technique is of particular interest for bit-patterned magnetic recording medium fabrication, where square magnetic bits result in improved recording system performance. Bit-patterned magnetic medium is among the primary candidates for the next generation magnetic recording technologies and is expected to extend the areal bit density limits far beyond 1 Tbit/in(2). The proposed patterning technology can be applied either for direct medium prototyping or for manufacturing of nanoimprint lithography templates or ion beam lithography stencil masks that can be utilized in mass production.     

A feasibility study of an integrated process for solid waste utilization

ABSTRACT

Pre-combustion coal cleaning and post-combustion flue gas desulfunzation (FGD) using lime or limestone are often used to reduce sulfur dioxide (SO₂) emission from high-sulfur coal combustion. These processes generate voluminous pyrite and gypsum solid wastes that are usually landfilled, occupying thousands of acres of land and creating serious land and water pollution problems due to the release of acids and toxic substances. An integrated thermochemical process has been developed for the combined utilization of gypsum and pyrite wastes by converting them into useful products including lime, sulfur, and direct reduced iron (DRI). The thermochemical reactions involved in the process were studied using thermogravimetric analysis (TGA) for reaction kinetics and X-ray diffraction (XRD) technique for product characterization. Reaction rate constant and activation energy were determined for individual reactions. Process variables studied included reaction temperature, time, reactant composition, and the purity of reactants.     

Improvement of Plasma Performance with Lithium Wall Conditioning in Aditya Tokamak

Lithiumization of the vacuum vessel wall of the Aditya tokamak using a lithium rod exposed to glow discharge cleaning plasma has been done to understand its effect on plasma performance. After the Li-coating, an increment of ～100 eV in plasma electron temperature has been observed in most of the discharges compared to discharges without Li coating, and the shot reproducibility is considerably improved. Detailed studies of impurity behaviour and hydrogen recycling are made in the Li coated discharges by observing spectral lines of hydrogen, carbon, and oxygen in the visible region using optical fiber, an interference filter, and PMT based systems. A large reduction in O I signal (up to ～ 40% to 50%) and a 20% to 30% decrease of H α signal indicate significant reduction of wall recycling. Furthermore, VUV emissions from O V and Fe XV monitored by a grazing incidence monochromator also show the reduction. Lower Fe XV emission indicates the declined impurity penetration to the core plasma in the Li coated discharges. Significant increase of the particle and energy confinement times and the reduction of Z eff of the plasma certainly indicate the improved plasma parameters in the Aditya tokamak after lithium wall conditioning.