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At least 973 records · Page 54Linked to original sources
PubMed2002

Microencapsulated, CYP2B1-transfected cells activating ifosfamide at the site of the tumor: the magic bullets of the 21st century.

BACKGROUND: Conventional chemotherapy of pancreatic carcinoma is only marginally effective. This is in part due to the severity of side effects following systemic administration of the cytostatic drug. The aim was to create a therapeutic tool allowing the targeting of the conversion site of a cytotoxic prodrug to the site of the tumor. This was realized by transfection of the CYP2B1 gene, the major ifosfamide-converting P450 enzyme, in cells with subsequent microencapsulation and administration of these microcapsules to or into the tumor. The enzyme activity (resorufin assay) remained stable for weeks in vitro and in vivo within the microencapsulated CYP2B1-expressing cells. We demonstrated a significant antitumor effect of the intratumorally injected capsules against xenotransplanted human pancreatic carcinomas in the nude mouse. Angiographic experiments in the pig confirmed the feasibility of an intraarterial placement of the capsules into the pancreas. A clinical protocol was established and approved. PATIENTS, MATERIAL AND METHODS: L293 cells were transfected with the CYP2B1 gene, microencapsulated (diameter 0.7 mm) under GCP conditions and packed sterile. Patients with confirmed inoperable adenocarcinoma of the pancreas underwent angiography, and capsules were injected into a vessel leading into the tumor. The patients were monitored for 48 h to exclude allergic reactions or pancreatitis. A day later, ifosfamide was administered for three consecutive days to be repeated on days 21-23. The patients were followed up for 5 months. RESULTS: A total of 17 patients were enrolled. The patients tolerated the procedure without any complications. No allergic reactions or pancreatitis were encountered. Chemotherapy was uneventful. All patients had stable disease, and two patients a partial remission. The median survival was 44 weeks which compared favorably with that of a historical control group (22 weeks). CONCLUSIONS: The intraarterial administration of microcapsules for targeted chemotherapy was well tolerated. Control of local tumor growth was achieved.

Animals↗
PubMed1992

Magic bullets.

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Chronic Disease↗
PubMed1976

The sequence of ppGpp and pppGpp in the reaction scheme for magic spot synthesis.

The kinetics of ppGpp (guanosine 5'-diphosphate, 3'-diphosphate) ahd pppGpp (guanosine 5'-triphosphate, 3'-diphosphate) synthesis, at the onset of amino acid starvation, and of their decay after inhibiting synthesis, were analysed in Escherichia coli. The pentaphosphate, but not ppGpp, is the first product of the stringent response to amino acid starvation. The pentaphosphate is rapidly converted with first order kinetics (t 1/2 = 6 s) to ppGpp which is broken down less rapidly (t 1/2 = 20 s).

Amino Acids↗
PubMed1988

Chloramphenicol: magic bullet or double-edge sword?

The genetic and genotoxic potentials of chloramphenicol are reviewed and analyzed. Although this widely used antimicrobial agent appears to cause chromosomal effects in somatic cells, in view of the consistent absence of other genetic effects, these cytogenetic abnormalities are ascribed to non-genotoxic causes. It is pointed out that despite its widespread use in human medicine, chloramphenicol has not been systematically tested for genotoxicity.

Animals↗