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Tumor Treatment (tumor + treatment)
Selected AbstractsTherapy with Cell Encapsulation for Substitution of Organ Function and Tumor Treatment (Adv. Eng.ADVANCED ENGINEERING MATERIALS, Issue 8 2009Mater. The cover shows life and dead assay demonstrating living cells within a cellulose sulfate capsule. More information can be found in the article by J. M. Lohr et al. on page B129. [source] Therapy with Cell Encapsulation for Substitution of Organ Function and Tumor Treatment,ADVANCED ENGINEERING MATERIALS, Issue 8 2009J. Matthias Löhr Cell encapsulation represents an innovative technique. However, clinical applications are sparse. Most experiments and clinical studies have been performed with either alginate or cellulose sulfate capsules, containing several cell lines and a broad variety of applications, ranging all the way from substitution for impaired organ function and release of cytokines or growth factors to gene-directed enzyme prodrug therapy. A few clinical studies have been conducted and/or are under way. [source] Role of Complement Anaphylatoxin C3a in Photodynamic Therapy-elicited Engagement of Host Neutrophils and Other Immune CellsPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2006Ivana Cecic ABSTRACT Tumor treatment by photodynamic therapy (PDT) provokes a host-protective inflammatory and acute-phase response and an immune reaction. Neutrophilia manifested in this context is driven by multiple mediators of neutrophil chemotaxis orchestrated by an activated complement system. Mouse FsaR fibrosarcoma was used in this study to further investigate neutrophilia induced by Photofrin-based PDT. The complement anaphylatoxin C3a was identified as a major chemo-attractant in the advanced phase of PDT-induced neutrophilia, because injecting mice with antibodies blocking its receptor C3aR significantly inhibited the increase in neutrophil levels 8 h after PDT. At the same time point, an increased C3aR expression was detected in neutrophils, monocytes and B lymphocytes in the blood of host mice. Peritoneal macro-phages and mast cells harvested from treatment-naive mice exhibited elevated C3aR expression after coincubation in vitro for 8 h with PDT-treated FsaR cells. Thus, C3a emerges as one of the key effector molecules engaged in PDT-induced host response. [source] Proposing magnetic nanoparticle hyperthermia in low-field MRICONCEPTS IN MAGNETIC RESONANCE, Issue 1 2010Pádraig Cantillon-Murphy Abstract This work examines feasibility, practical advantages, and disadvantages of a combined MRI/magnetic particle hyperthermia (MPH) system for cancerous tumor treatment in low perfusion tissue. Although combined MRI/hyperthermia systems have been proposed and constructed, the current proposal differs because the hyperthermia system would be specifically designed to interact with the magnetic nanoparticles injected at the tumor site. The proposal exploits the physical similarities between the magnetic nanoparticles currently employed for MPH and those used as superparamagnetic iron oxide (SPIO) contrast agents in MR imaging. The proposal involves the addition of a rotating magnetic field RF hyperthermia source perpendicular to the MRI B0 field which operates in a similar manner to the MRI RF excitation field, B1, but at significantly higher frequency and field strength such that the magnetic nanoparticles are forced to rotate in its presence. This rotation is the source of increases in temperature which are of therapeutic benefit in cancer therapy. For rotating magnetic fields with amplitudes much smaller than B0, the nanoparticles' suspension magnetization rapidly saturates with increasing B0. Therefore, the proposal is best suited to low-field MRI systems when magnetic saturation is incomplete. In addition, careful design of the RF hyperthermia source is required to ensure no physical or RF interference with the B1 field used for MRI excitation. Notwithstanding these caveats, the authors have shown that localized steady-state temperature rises in small spherical tumors of up to 10°C are conceivable with careful selection of the nanoparticle radius and concentration, RF hyperthermia field amplitude and frequency. © 2010 Wiley Periodicals, Inc. Concepts Magn Reson Part A 36A: 36,47, 2010. [source] Loco-regional treatment of hepatocellular carcinoma,HEPATOLOGY, Issue 2 2010Riccardo Lencioni Loco-regional treatments play a key role in the management of hepatocellular carcinoma (HCC). Image-guided tumor ablation is recommended in patients with early-stage HCC when surgical options are precluded. Radiofrequency ablation has shown superior anticancer effects and greater survival benefit with respect to the seminal percutaneous technique, ethanol injection, in meta-analyses of randomized controlled trials, and is currently established as the standard method for local tumor treatment. Novel thermal and nonthermal techniques for tumor ablation,including microwave ablation, irreversible electroporation, and light-activated drug therapy,seem to have potential to overcome the limitations of radiofrequency ablation and warrant further clinical investigation. Transcatheter arterial chemoembolization (TACE) is the standard of care for patients with asymptomatic, noninvasive multinodular tumors at the intermediate stage. The recent introduction of embolic microspheres that have the ability to release the drug in a controlled and sustained fashion has been shown to significantly increase safety and efficacy of TACE with respect to conventional, lipiodol-based regimens. The available data for radioembolization with yttrium-90 suggests that this is a potential new option for patients with HCC, which should be investigated in the setting of randomized controlled trials. Despite the advances and refinements in loco-regional approaches, the long-term survival outcomes of patients managed with interventional techniques are not fully satisfactory, mainly because of the high rates of tumor recurrence. The recent addition of molecular targeted drugs with antiangiogenic and antiproliferative properties to the therapeutic armamentarium for HCC has prompted the design of clinical trials aimed at investigating the synergies between loco-regional and systemic treatments. The outcomes of these trials are eagerly awaited, because they have the potential to revolutionize the treatment of HCC. (HEPATOLOGY 2010;) [source] Microparticulate formulations for the controlled release of interleukin-2JOURNAL OF PHARMACEUTICAL SCIENCES, Issue 5 2004Tommy T. Thomas Abstract Interleukin 2 (IL-2) is a pleotropic growth factor essential to immune system function. Current methods of administration are limited by the necessity of hospitalization as well as dose-limiting toxicities and side effects. There is also the issue of low therapeutic concentrations at the desired site of action; for instance, in the case of solid tumor treatment. Here we describe the design of controlled-release vehicles for the local administration of IL-2 based on single (SE) and double emulsion (DE) poly(lactic- co -glycolic acid) (PLGA) systems and a newly developed class of spray-dried lipid,protein,sugar systems composed of L -,-dipalmitoylphosphatidylcholine (DPPC) and 0.2% Eudragit E 100. All three systems demonstrated the release of therapeutic drug quantities. Totals of 2.0, 0.5, and 2.8 ,g of IL-2 (per mg of solid) were encapsulated in the SE, DE, and spray-dried formulations, respectively. The SE and DE released of 30 and 15% of the encapsulated protein, respectively, with delivery of biologically active IL-2 during the first 5 to 10 days. The lipid,protein,sugar-based system demonstrated extended sustained release of biologically active IL-2 for a period of 4 months. These systems provide a potential framework for long-term loco-regional immunotherapeutic treatment regimens. © 2004 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1100,1109, 2004 [source] Clinically relevant radioresistant cells efficiently repair DNA double-strand breaks induced by X-raysCANCER SCIENCE, Issue 4 2009Yoshikazu Kuwahara Radiotherapy is one of the major therapeutic modalities for eradicating malignant tumors. However, the existence of radioresistant cells remains one of the most critical obstacles in radiotherapy and radiochemotherapy. Standard radiotherapy for tumor treatment consists of approximately 2 Gy once a day, 5 days a week, over a period of 5,8 weeks. To understand the characteristics of radioresistant cells and to develop more effective radiotherapy, we established a novel radioresistant cell line, HepG2-8960-R with clinical relevance from parental HepG2 cells by long-term fractionated exposure to 2 Gy of X-rays. HepG2-8960-R cells continued to proliferate with daily exposure to 2 Gy X-rays for more than 30 days, while all parental HepG2 cells ceased. After exposure to fractionated 2 Gy X-rays, induction frequencies of micronuclei and remaining foci of ,-H2AX in HepG2-8960-R were less than those in HepG2. Flow cytometric analysis revealed that the proportion of cells in S- and G2/M-phase of the cell cycle was higher in HepG2-8960-R than in HepG2. These suggest that the response of clinically relevant radioresistant (CRR) cells to fractionated radiation is not merely an accumulated response to each fractionated radiation. This is the first report on the establishment of a CRR cell line from an isogenic parental cell line. (Cancer Sci 2009; 100: 747,752) [source] A Novel Class of Antitumor Prodrug, 1-(2,-Oxopropyl)-5-fluorouracil (OFU001), That Releases 5-Fluorouracil upon Hypoxic IrradiationCANCER SCIENCE, Issue 4 2000Yuta Shibamoto We have been developing prodrugs of anticancer agents such as 5-fluorouracil (5-FU) that are activated by irradiation under hypoxic conditions via one-electron reduction. Among them, OFU001 [1-(2,-oxopropyl)-5-fluorouracil] is a prototype radiation-activated prodrug. In this study, we investigated the radiation chemical reactivity and the biological effects of OFU001. This prodrug is presumed to release 5-FU through incorporation of hydrated electrons into the antibonding ,* orbital of the C(1,)-N(1) bond. Hydrated electrons are active species derived from radiolysis of water, but are readily deactivated by O2 into superoxide anion radicals () under conditions of aerobic irradiation. Therefore, 5-FU release occurs highly specifically upon irradiation under hypoxic conditions. OFU001 dissolved in phosphate buffer released 5-FU with a G -value (mol number of molecules that are decomposed or produced by 1 J of absorbed radiation energy) of 1.9×10,7 mol/ J following hypoxic irradiation, while the G -value for 5-FU release was 1.0×10,8 mol/J following aerobic irradiation. However, the G -values for decomposition of OFU001 were almost the same, i.e., 3.4×10,7 mol/J following hypoxic irradiation and 2.5×10,7 mol/J following aerobic irradiation. When hypoxically irradiated (7.5,30 Gy) OFU001 was added to murine SCCVII cells for 1,24 h, a significant cell-killing effect was observed. The degree of this cytotoxicity was consistent with that of authentic 5-FU at the corresponding concentrations. On the other hand, cytotoxicity was minimal when the cells were treated with aerobically irradiated or unirradiated OFU001. This compound had no radiosensitizing effect against SCCVII cells under either aerobic or hypoxic conditions when the drug was removed immediately after irradiation. Since hypoxia is generally most marked in tumors and irradiation is applied at the tumor site, this concept of prodrug design appears to be potentially useful for selective tumor treatment with minimal adverse effects of anticancer agents. [source] Melanoma stem cells: targets for successful therapy?JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT, Issue 7 2008Roland Houben Summary Increasing evidence suggests that cancer is a disease in which the persistence of the tumor relies on a small population of tumor-initiating cells, the so called tumor stem cells (TSC). Only these cells are capable of self-renewal and thereby possess the ability for unlimited proliferation. One reason for the inability of conventional tumor treatments to achieve long-term cures seems to be that TSC are resistant to many therapeutic approaches. A detailed characterization of TSC should have a substantial impact on the optimization of therapeutic protocols. While TSC in hematopoietic malignancies have been most intensively studied, subpopulations with stem cell properties have been identified in some solid tumors including breast carcinomas, gliomas and melanomas. In case of melanoma, however, a clear-cut molecular characterization is still pending. Considerable research is needed to establish standard procedures for the isolation of melanoma stem cells to facilitate determining how these cells, critical for tumor persistence and progression, can be effectively eliminated. A pressing question is if melanoma stem cells are in principle sensitive to immunotherapy. [source] | ||||||||||