126 research outputs found

    Safety and preliminary efficacy data of a novel Casein Kinase 2 (CK2) peptide inhibitor administered intralesionally at four dose levels in patients with cervical malignancies

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Cervical cancer is now considered the second leading cause of death among women worldwide, and its incidence has reached alarming levels, especially in developing countries. Similarly, high grade squamous intraepithelial lesion (HSIL), the precursor stage for cervical cancer, represents a growing health problem among younger women as the HSIL management regimes that have been developed are not fully effective. From the etiological point of view, the presence of Human Papillomavirus (HPV) has been demonstrated to play a crucial role for developing cervical malignancies, and viral DNA has been detected in 99.7% of cervical tumors at the later stages. CIGB-300 is a novel cyclic synthetic peptide that induces apoptosis in malignant cells and elicits antitumor activity in cancer animal models. CIGB-300 impairs the Casein Kinase (CK2) phosphorylation, by targeting the substrate's phosphoaceptor domain. Based on the perspectives of CIGB-300 to treat cancer, this "first-in-human" study investigated its safety and tolerability in patients with cervical malignancies.</p> <p>Methods</p> <p>Thirty-one women with colposcopically and histologically diagnosed microinvasive or pre-invasive cervical cancer were enrolled in a dose escalating study. CIGB-300 was administered sequentially at 14, 70, 245 and 490 mg by intralesional injections during 5 consecutive days to groups of 7 – 10 patients. Toxicity was monitored daily until fifteen days after the end of treatment, when patients underwent conization. Digital colposcopy, histology, and HPV status were also evaluated.</p> <p>Results</p> <p>No maximum-tolerated dose or dose-limiting toxicity was achieved. The most frequent local events were pain, bleeding, hematoma and erythema at the injection site. The systemic adverse events were rash, facial edema, itching, hot flashes, and localized cramps. 75% of the patients experienced a significant lesion reduction at colposcopy and 19% exhibited full histological regression. HPV DNA was negative in 48% of the previously positive patients. Long term follow-up did not reveal recurrences or adverse events.</p> <p>Conclusion</p> <p>CIGB 300 was safe and well tolerated. This is the first clinical trial where a drug has been used to target the CK2 phosphoaceptor domain providing an early proof-of-principle of a possible clinical benefit.</p

    Mixed Waste Focus Area Work Conducted by

    No full text
    Over 1140 yd of radioactively contaminated soil containing toxic mercury (Hg) and several liters of mixedwaste elemental mercury were generated during a Comprehensive Environmental Response, Compensation and Liability Act (CERCLA) removal action at Brookhaven National Laboratory (BNL). The U.S. Department of Energy&apos;s (DOE) Office of Science and Technology Mixed Waste Focus Area (DOE MWFA) is sponsoring a comparison of several technologies that may be used to treat these wastes and similar wastes at BNL and other sites across the DOE complex. This report describes work conducted at BNL on the application and pilot-scale demonstration of the newly developed Sulfur Polymer Stabilization/Solidification (SPSS) process for treatment of contaminated mixed-waste soils containing high concentrations (~5000 mg/L) of mercury and liquid elemental mercury. BNL&apos;s SPSS (patent pending) process chemically stabilizes the mercury to reduce vapor pressure and leachability and physically encapsulates the waste in a solid matrix to eliminate dispersion and provide long-term durability. Two 55gallon drums of mixed-waste soil containing high concentrations of mercury and about 62 kg of radioactively contaminated elemental mercury were successfully treated. Waste loadings of 60 wt% soil were achieved without resulting in any increase in waste volume, while elemental mercury was solidified at a waste loading of 33 wt% mercury. Toxicity Characteristic Leaching Procedure (TCLP) analyses indicate the final waste form products pass current Environmental Protection Agency (EPA) allowable TCLP concentrations as well as the more stringent proposed Universal Treatment Standards. Mass balance measurements show that 99.7% of the mercury treated was successfully retained within the waste form, while ..
    corecore