The mutagenicity and DNA-modifying effect of haloalkanes.
Explore the source record for details and available documents.
Chromosomes, Bacterial↗
Biomedical subjects
H Brem
Publications and source records attributed to H Brem.
Treatment of melanoma metastases in the brain.
Melanoma is prone to spread to the brain and is the third most common source of intracranial metastasis. Patients usually present with signs and symptoms of increased intracranial pressure, a new focal neurologic deficit, or seizures. Contrasted magnetic resonance imaging (MRI) is the single most valuable imaging modality. Surgical therapy is the appropriate choice for single lesions that are accessible, especially if they are causing significant mass effect or are located in the posterior fossa. Patients with several intracranial metastases who undergo resection of all lesions may have a similar prognosis to those with single resected lesion. Stereotactic radiosurgery appears to provide good local control of small lesions. External beam radiotherapy may provide some benefit to patients, and is often used in conjunction with surgery or stereotactic radiosurgery. To date, chemotherapy has been limited because of chemo-resistance and drug delivery issues. Future directions for treatment may include local sustained delivery of either chemotherapy or immunoregulatory molecules.
Antineoplastic Agents↗
New directions in CNS drug delivery.
This commentary expands on the above article in 2 ways. First, it provides more recent information on polymer-based drug delivery systems. Second, it discusses experimental systems that may be clinically viable in the future such as prodrugs, cell-polymer transplants and gene transplants.
Brain Diseases↗
Local anti-angiogenic brain tumor therapies.
The critical role of angiogenesis in the growth of solid tumors, including neoplasms of the central nervous system, has provided the impetus for research leading to the discovery of inhibitors of tumor neovascularization. The therapeutic potential of systemically administered antiangiogenic drugs for brain tumors, however, is limited by a variety of anatomic and physiologic barriers to drug delivery. Implantable controlled-release polymers for local drug administration directly into the tumor parenchyma have therefore been developed to achieve therapeutic concentrations of these drugs within the brain while minimizing systemic toxicity. With use of these polymers, successful antiangiogenic therapy for treatment of experimental intracranial malignancies has been achieved. This has been demonstrated with a variety of otherwise unrelated drugs -- including the angiostatic steroids, tetracycline derivatives, and amiloride -- which modulate collagenase activity, and thus, basement membrane and interstitial matrix metabolism. Controlled-release polymers provide a clinically practicable method of achieving sustained antiangiogenic therapy which can be readily used in combination with other treatment modalities such as cytoreductive surgery, radiation, and cytotoxic chemotherapy.
Amiloride↗
Intracranial paracrine interleukin-2 therapy stimulates prolonged antitumor immunity that extends outside the central nervous system.
To explore the potential efficacy of local cytokine delivery against tumors in the central nervous system (CNS), C57BL6 mice were simultaneously given intracranial injections of tumor challenge and of irradiated B16F10 melanoma cells transduced to secrete interleukin-2 (IL-2). Intracranial IL-2 therapy generated antitumor responses capable of extending the survival of animals that received simultaneous intracranial tumor challenge either locally or at distant sites in the brain. Nontransduced melanoma cells had little effect. Animals that survived intracranial IL-2 therapy and tumor challenge showed prolonged survival compared with controls when challenged with a second tumor dose 70 days after initial treatment. In addition, animals that rejected intracranial tumors were also protected from tumor growth upon rechallenge at sites outside the CNS (i.e., subcutaneous tumor challenge). Conversely, identical or 10-fold larger doses of IL-2-transduced cells administered by subcutaneous injection failed to generate protection against intracranial tumor challenges. Elimination of T-cell and natural killer (NK) subsets using gene knockout mice and antibody-depletion techniques demonstrated that NK cells were most important for the initial antitumor response, whereas CD4+ T-cells were not necessary. These studies demonstrate that local IL-2 therapy in the brain not only generates an immediate local antitumor immune response, but also establishes long-term immunologic memory capable of eliminating subsequent tumor challenges within and outside of the CNS. Furthermore, the antitumor response to paracrine IL-2 in the brain differed significantly from that in the flank, suggesting that the intrinsic CNS cells involved in initiating immunity within the brain have different cytokine requirements from their peripheral counterparts.
Adjuvants, Immunologic↗
Developing new methods for the treatment of malignant brain tumours: local delivery of anti-neoplastic agents using biodegradable polymers.
Controlled delivery of chemotherapeutic agents by biodegradable polymers is a new strategy that has been added to the arsenal available for the treatment of malignant neoplasms. This approach is particularly suitable for the management of brain tumours because of the constraints imposed by the blood brain barrier (BBB). The use of polymers for local drug delivery minimises systemic toxicity, while achieving prolonged elevation of intratumoural drug concentrations that results in improved efficacy. In addition, this strategy broadens the spectrum of drugs available for the treatment of neoplasms in the central nervous system to include agents whose efficacy is significantly limited by systemic toxicity or inability to penetrate the BBB. In this review, we discuss the rationale and background for the use of this novel approach. We also summarise the clinical trials and laboratory investigations leading to the development of local delivery of anti-neoplastic agents from biodegradable polymers for the treatment of malignant gliomas.
Animals↗