Adjuvant low-dose interferon α2a with or without dacarbazine compared with surgery alone: a prospective-randomized phase III DeCOG trial in melanoma patients with regional lymph node metastasis

Background: More than half of patients with melanoma that has spread to regional lymph nodes develop recurrent disease within the first 3 years after surgery. The aim of the study was to improve disease-free survival (DFS) and overall survival (OS) with interferon (IFN) α2a with or without dacarbazine (DTIC) compared with observation alone. Patients and methods: A total of 444 patients from 42 centers of the German Dermatologic Cooperative Oncology Group who had received a complete lymph node dissection for pathologically proven regional node involvement were randomized to receive either 3 MU s.c. of IFNα2a three times a week for 2 years (Arm A) or combined treatment with same doses of IFNα2a plus DTIC 850 mg/m2 every 4-8 weeks for 2 years (Arm B) or to observation alone (Arm C). Treatment was discontinued at first sign of relapse. Results: A total of 441 patients were eligible for intention-to-treat analysis. Kaplan-Meier 4-year OS rate of those who had received IFNα2a was 59%. For those with surgery alone, survival was 42% (A versus C, P = 0.0045). No improvement of survival was found for the combined treatment Arm B with 45% survival rate (B versus C, P = 0.76). Similarly, DFS rates showed significant benefit for Arm A, and not for Arm B. Multivariate Cox model confirmed that Arm A has an impact on OS (P = 0.005) but not Arm B (P = 0.34). Conclusions: 3 MU interferon α2a given s.c. three times a week for 2 years significantly improved OS and DFS in patients with melanoma that had spread to the regional lymph nodes. Interestingly, the addition of DTIC reversed the beneficial effect of adjuvant interferon α2a therap

Reaction paths of phosphine dissociation on silicon (001)

Using density functional theory and guided by extensive scanning tunneling microscopy (STM) image data, we formulate a detailed mechanism for the dissociation of phosphine (PH3) molecules on the Si(001) surface at room temperature. We distinguish between a main sequence of dissociation that involves PH2+H, PH+2H, and P+3H as observable intermediates, and a secondary sequence that gives rise to PH+H, P+2H, and isolated phosphorus adatoms. The latter sequence arises because PH2 fragments are surprisingly mobile on Si(001) and can diffuse away from the third hydrogen atom that makes up the PH3 stoichiometry. Our calculated activation energies describe the competition between diffusion and dissociation pathways and hence provide a comprehensive model for the numerous adsorbate species observed in STM experiments

Local therapy of cancer with free IL-2

This is a position paper about the therapeutic effects of locally applied free IL-2 in the treatment of cancer. Local therapy: IL-2 therapy of cancer was originally introduced as a systemic therapy. This therapy led to about 20% objective responses. Systemic therapy however was very toxic due to the vascular leakage syndrome. Nevertheless, this treatment was a break-through in cancer immunotherapy and stimulated some interesting questions: Supposing that the mechanism of IL-2 treatment is both proliferation and tumoricidal activity of the tumor infiltrating cells, then locally applied IL-2 should result in a much higher local IL-2 concentration than systemic IL-2 application. Consequently a greater beneficial effect could be expected after local IL-2 application (peritumoral = juxtatumoral, intratumoral, intra-arterial, intracavitary, or intratracheal = inhalation). Free IL-2: Many groups have tried to prepare a more effective IL-2 formulation than free IL-2. Examples are slow release systems, insertion of the IL-2 gene into a tumor cell causing prolonged IL-2 release. However, logistically free IL-2 is much easier to apply; hence we concentrated in this review and in most of our experiments on the use of free IL-2. Local therapy with free IL-2 may be effective against transplanted tumors in experimental animals, and against various spontaneous carcinomas, sarcomas, and melanoma in veterinary and human cancer patients. It may induce rejection of very large, metastasized tumor loads, for instance advanced clinical tumors. The effects of even a single IL-2 application may be impressive. Not each tumor or tumor type is sensitive to local IL-2 application. For instance transplanted EL4 lymphoma or TLX9 lymphoma were not sensitive in our hands. Also the extent of sensitivity differs: In Bovine Ocular Squamous Cell Carcinoma (BOSCC) often a complete regression is obtained, whereas with the Bovine Vulval Papilloma and Carcinoma Complex (BVPCC) mainly stable disease is attained. Analysis of the results of local IL-2 therapy in 288 cases of cancer in human patients shows that there were 27% Complete Regressions (CR), 23% Partial Regressions (PR), 18% Stable Disease (SD), and 32% Progressive Disease (PD). In all tumors analyzed, local IL-2 therapy was more effective than systemic IL-2 treatment. Intratumoral IL-2 applications are more effective than peritumoral application or application at a distant site. Tumor regression induced by intratumoral IL-2 application may be a fast process (requiring about a week) in the case of a highly vascular tumor since IL-2 induces vascular leakage/edema and consequently massive tumor necrosis. The latter then stimulates an immune response. In less vascular tumors or less vascular tumor sites, regression may require 9–20 months; this regression is mainly caused by a cytotoxic leukocyte reaction. Hence the disadvantageous vascular leakage syndrome complicating systemic treatment is however advantageous in local treatment, since local edema may initiate tumor necrosis. Thus the therapeutic effect of local IL-2 treatment is not primarily based on tumor immunity, but tumor immunity seems to be useful as a secondary component of the IL-2 induced local processes. If local IL-2 is combined with surgery, radiotherapy or local chemotherapy the therapeutic effect is usually greater than with either therapy alone. Hence local free IL-2 application can be recommended as an addition to standard treatment protocols. Local treatment with free IL-2 is straightforward and can readily be applied even during surgical interventions. Local IL-2 treatment is usually without serious side effects and besides minor complaints it is generally well supported. Only small quantities of IL-2 are required. Hence the therapy is relatively cheap. A single IL-2 application of 4.5 million U IL-2 costs about 70 Euros. Thus combined local treatment may offer an alternative in those circumstances when more expensive forms of treatment are not available, for instance in resource poor countries

Clean and metal-doped bundles of boron-carbide nanotubes: a density functional study

Carbon nanotubes and many types of inorganic nanotubes can be produced in the form of hexagonal arrays or bundles. In this paper, we discuss results of ab initio density functional theory calculations on the stability, and atomic and electronic structure, of bundles of narrow, clean, and Li- and Cu-doped, boron-carbide nanotubes related to LiBC and CuBC layered compounds. We find that covalent bonding arises between neighboring tubes in the bundles which results in the formation of complex structures. We show that a high concentration of dopant Li atoms in the bundles can be achieved by a combination of in-tube and interstitial doping. A high concentration of Li atoms involving only in-tube doping is energetically unfavorable due to repulsive interaction between the Li atoms. By contrast, increased doping with Cu atoms can produce a metallic wirelike structure along the longitudinal axis of each tube within the bundle

Structure and energetics of hydrogenated and dehydrogenated carbon tori

It is shown that large-diameter, finite and extended, hydrogenated, single-walled carbon nanotubes are energetically and structurally unstable. The instability of short, large-diameter, finite hydrogenated tubes leads to the formation of hydrogenated circular carbon tori of small tubular cross-section. It is also shown that carbon toroidal structures, formed by desorption of hydrogen from the hydrogenated tori, are more energetically stable than the corresponding open-ended, finite single-walled carbon nanotubes

Small-radius clean and metal-doped boron carbide nanotubes: a density functional study

We present the results of ab initio density functional theory calculations of the atomic and electronic structure of small radius boron carbide nanotubes, and the effects of doping these tubes with Li and Cu atoms. We have found that undoped narrow tubes are more energetically favorable than the corresponding boron carbide strips. The effects of doping on the atomic and electronic structure of these tubes have been found to be dependent on the size and symmetry of the tubes, and the type of dopant atoms

Atomic and electronic structure of the Si(001)-Rb chemisorption system at 0.5 and 1.0 monolayer coverage

The atomic and electronic structure of the Si(001)-Rb chemisorption system at 0.5 and 1.0 monolayer coverage has been investigated using the plane wave, pseudopotential density functional method contained in the VASP code. The atomic and electronic structures of the Rb chemisorption system at 0.5 monolayer coverage are found to be very similar to the Li chemisorption system at the same coverage. The minimum energy structure determined for the Si(001)-Rb chemisorption system at 1.0 NIL coverage has been found to be in good agreement with the x-ray standing-wave (XSW) field data. The predicted occupied and unoccupied electronic surface state bands have also been shown to be in excellent agreement with the ARUPS and IPES results. The calculations suggest that the bonding between the Rb adatoms and the Si substrate atoms is neither purely ionic nor covalent. No evidence has been found in support of strong Rb-Rb interactions and the formation of a metallic overlayer