Biomedical subjects

A Gouyette

Publications and source records attributed to A Gouyette.

At least 19 recordsLinked to original sources

PubMed2003

Vancomycin encapsulation in biodegradable poly(epsilon-caprolactone) microparticles for bone implantation. Influence of the formulation process on size, drug loading, in vitro release and cytocompatibility.

Vancomycin encapsulation in biodegradable poly(epsilon-caprolactone) microparticles (200 microm mean diameter) was most efficient with a simple emulsion technique that dispersed 122.5 mg/g of polymer. Scanning electron micrographs showed smooth or pitted particles. Dissolution studies were correlated with microparticle morphology, indicating higher release with pitted particles when vancomycin was encapsulated in a dissolved state. The cytocompatibility of these poly(epsilon-caprolactone) microparticles was demonstrated by a direct contact cytotoxic assay. This material can be considered as an efficient drug delivery system for bone implantation.

Absorbable Implants↗

PubMed2000

Synthesis, spectroscopy, and cytotoxicity of glycosylated acetogenin derivatives as promising molecules for cancer therapy.

Several glycosyl derivatives of squamocin (1) have been synthesized by glycosylation under Lewis acid catalysis with two different 1-O-acetyl sugars. Separation of these compounds has been achieved by HPLC and centrifugal partition chromatography (CPC). A detailed NMR, ESIMS, and LSIMS study allowed complete structural elucidations. The cytotoxic activity of the glycosyl derivatives was investigated and compared with that of squamocin and dihydrosquamocin against human epidermoid carcinoma cells (KB), African green monkey (Cercopithecus aethiops) kidney epithelial cells (VERO), and mouse lymphocytic leukemia cells (L1210). The antiproliferative effects of some derivatives were studied on cell cycles in mouse lymphocytic leukemia cells (L1210).

Animals↗

PubMed2000

Transactivation of the metallothionein promoter in cisplatin-resistant cancer cells: a specific gene therapy strategy.

BACKGROUND: Cisplatin (cis-diamminedichloroplatinum) is one of the most active agents against a broad range of malignancies, including ovarian cancer. Cisplatin resistance appears to be associated with several molecular alterations, including overexpression of metallothionein, a metal-binding protein. In the present study, we attempted to take advantage of metallothionein overexpression to overcome cisplatin resistance. METHODS: Using a virus-free system (liposomes), we sought to express the suicide gene, thymidine kinase (TK), driven by the promoter of the human metallothionein IIa (hMTIIa) gene using the pMT-TK plasmid. We used cisplatin-resistant human ovarian carcinoma cells as a model. RESULTS: We first analyzed metallothionein expression using a ribonuclease protection assay. In comparison to parental cells, the cisplatin-resistant cells were found to have increased expression of metallothionein messenger RNA (mRNA). Metallothionein overexpression in these cells was not associated with an increased copy number of the hMTIIa gene or with different transfection efficiencies. Furthermore, we showed by reverse transcription-polymerase chain reaction analysis that transfection of the pMT-TK plasmid results in a 56-fold higher expression of thymidine kinase mRNA in cisplatin-resistant cells compared with parental cells, consistent with increased metallothionein promoter-mediated transactivation in the cisplatin-resistant cells. Transfection of resistant cells with pMT-TK or a control plasmid (pCD3-TK) resulted in a marked sensitization to ganciclovir, with a 50% cell growth-inhibitory concentration (IC(50)) of 20 microg/mL and 9 microg/mL, respectively. Transfections of the cisplatin-sensitive cells resulted in no sensitization to ganciclovir with pMT-TK (IC(50) 200 microg/mL) and a high sensitization with pCD3-TK (IC(50) = 6 microg/mL). CONCLUSION: These studies suggest that pMT-TK gene therapy may provide an alternative treatment for cisplatin-refractory ovarian tumors.

Cisplatin↗

PubMed2000

Synthesis and antitumour activity of a new series of nitrosoureido sugars.

New nitrosoureido derivatives of di- or tri-deoxy-sugars have been synthesized. Very potent antitumour activity against L1210 leukaemia was exhibited by the compounds derived from methyl 3-amino-3, 4-dideoxy-beta- and alpha- and 4-amino-2,4-dideoxy-beta- and alpha-D-arabino-hexopyranosides, 24, 26, 28 and 29, respectively. In further evaluation against B16 melanocarcinoma bearing mice, only compounds 24 and 26 displayed significant activity. Owing to its lower acute toxicity, methyl 3-[3-(2-chloroethyl)-3-nitrosoureido]-3, 4-dideoxy-beta-D-arabino-hexopyranoside 24 appeared as the best candidate for preclinical studies.

Animals↗

PubMed2000

Inhibition of glioma cells in vitro and in vivo using a recombinant adenoviral vector containing an astrocyte-specific promoter.

Gene therapy using the herpes simplex virus thymidine kinase (HSV-TK) gene in combination with the drug ganciclovir (GCV) is a promising approach for the treatment of cancer-inducing gliomas, a tumor with a poor prognosis. In an attempt to limit the toxic effects on normal tissues, we constructed a recombinant adenoviral vector, Adgfa2TK, in which the HSV-TK gene is driven by the promoter for the gene encoding glial fibrillary acidic protein, an intermediate filament protein expressed primarily in astrocytes. Infection by Adgfa2TK of a glial cell line (C6) and a non-glial cell line (MDA-MB-231) revealed markedly increased expression of HSV-TK in glial cells as determined by Western blot. In comparison, high HSV-TK protein levels were produced in both cell lines after infection with a control virus, AdCMVTK, in which the constitutive cytomegalovirus viral promoter was used to direct HSV-TK expression. Infection of two glial cell lines (C6, U251) and two non-glial cell lines (HepG2, MDA-MB-231) with Adgfa2TK followed by GCV treatment revealed high toxicity in glial cell lines (50% growth inhibitory concentration: <2 microg/mL of GCV) with little or no toxicity (50% growth inhibitory concentration: >75 microg/mL) in the non-glial cell lines. In vivo, injection of Adgfa2TK into C6 tumors grown in nude mice followed by intraperitoneal GCV treatment significantly repressed tumor growth compared with the controls. Adgfa2TK may be useful for directing expression of the HSV-TK gene to gliomas.

Adenoviridae↗

PubMed2000

Metabolism of irinotecan (CPT-11) by CYP3A4 and CYP3A5 in humans.

7-Ethyl-10[4-(1-piperidino)-1-piperidino] carbonyloxy-camptothecin (CPT-11), a DNA topoisomerase I inhibitor, undergoes several metabolic pathways to generate conjugated and unconjugated derivatives that could be excreted from the body. The objective of this study was to determine the oxidative metabolites of CPT-11 recovered in human urine samples and to identify cytochrome P450 (CYP) involved in their formation. In addition to the already known metabolites of CPT-11 [SN-38, SN-38-G, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]carbonyloxycamptothecin (APC), and 7-ethyl-10-(4-amino-1-piperidino) carbonyloxycamptothecin (NPC)], we isolated three oxidized metabolites from the urine of two children and two adults given CPT-11. M1 and M2 (molecular weight, 602) were hydroxylated, respectively, on the CPT moiety and on the terminal piperidine ring of CPT-11. M3 had a molecular mass of 602, but its urine concentration in patients was too low to establish its chemical structure by liquid chromatography/mass spectrometry. In vitro incubations with cells expressing CYP2C8, CYP2C9, CYP1A1, CYP1A2, or CYP3A7 did not produce any detectable metabolites. Only CYP3A4 produced both APC and NPC, resulting from the oxidation of the piperidinylpiperidine side chain of CPT-11 along with metabolite M2. The metabolism of CPT-11 by CYP3A5 was markedly different because neither APC or NPC nor M2 was produced, whereas only one new metabolite, M4 (molecular weight, 558), was generated by de-ethylation of the CPT moiety. No previous study has reported the presence of the M4 metabolite. Production of APC, NPC, M2, and M4 was prevented by ketoconazole, a specific CYP3A inhibitor. The parameters of CPT-11 biotransformation into M2 and M4 were examined using cell lines expressing, respectively, with CYP3A4 and CYP3A5, indicating that CPT-11 is preferentially metabolized by CYP3A4. In conclusion, CYP3A plays a major role in the metabolism of CPT-11, with some differences of the metabolic profile exhibited by 3A4 and 3A5.

Adolescent↗

PubMed1999

Busulphan is active against neuroblastoma and medulloblastoma xenografts in athymic mice at clinically achievable plasma drug concentrations.

High-dose busulphan-containing chemotherapy regimens have shown high response rates in children with relapsed or refractory neuroblastoma, Ewing's sarcoma and medulloblastoma. However, the anti-tumour activity of busulfan as a single agent remains to be defined, and this was evaluated in athymic mice bearing advanced stage subcutaneous paediatric solid tumour xenografts. Because busulphan is highly insoluble in water, the use of several vehicles for enteral and parenteral administration was first investigated in terms of pharmacokinetics and toxicity. The highest bioavailability was obtained with busulphan in DMSO administered i.p. When busulphan was suspended in carboxymethylcellulose and given orally or i.p., the bioavailability was poor. Then, in the therapeutic experiments, busulphan in DMSO was administered i.p. on days 0 and 4. At the maximum tolerated total dose (50 mg kg(-1)), busulphan induced a significant tumour growth delay, ranging from 12 to 34 days in the three neuroblastomas evaluated and in one out of three medulloblastomas. At a dose level above the maximum tolerated dose, busulphan induced complete and partial tumour regressions. Busulphan was inactive in a peripheral primitive neuroectodermal tumour (PNET) xenograft. When busulphan pharmacokinetics in mice and humans were considered, the estimated systemic exposure at the therapeutically active dose in mice (113 microg h ml(-1)) was close to the mean total systemic exposure in children receiving high-dose busulphan (102.4 microg h ml(-1)). In conclusion, busulphan displayed a significant anti-tumour activity in neuroblastoma and medulloblastoma xenografts at plasma drug concentrations which can be achieved clinically in children receiving high-dose busulphan-containing regimens.

Administration, Oral↗

PubMed1999

Development of a "continuous-flow adhesion cell" for the assessment of hydrogel adhesion.

The purpose of this study was to develop an in vitro perfusion technique or "continuous-flow adhesion cell" model to predict the in vivo performances of different mucoadhesive drug delivery systems based on hydrogels. Two studies were performed, either using a rabbit small intestine or a polyethylene surface; the adhesion of four gels--two poly(acrylic acid)s (PAAs) (carbomer [CM] and polycarbophil [PC]), an ethyleneoxide-propyleneoxide block copolymer (Poloxamer 407 [PM]), and a polysaccharide (scleroglucane [SG])--were evaluated. In this respect, scleroglucane was used as a control. The adhesiveness of the different gels for both supports is in accordance with that described in the literature, that is, polycarbophil adhered more strongly than carbomer, which itself adhered more strongly than poloxamer. This study proved that the gels adhere more strongly to the polyethylene tube than to the rabbit small intestine, thus indicating that evidence for adhesion properties does not need any presence of mucus. Therefore, our in vitro model could be a good method, more precise and more simple than an ex vivo technique, to predict the bioadhesion of gelified devices.

Adhesiveness↗

PubMed1999

Pharmacokinetics and tolerability of intravenous trecovirsen (GEM 91), an antisense phosphorothioate oligonucleotide, in HIV-positive subjects.

Trecovirsen, a 25-mer antisense phosphorothioate oligonucleotide targeted at the gag site of the HIV gene, was administered to HIV-positive volunteers as an i.v. infusion. Single doses ranged from 0.1 to 2.5 mg/kg in an ascending escalation in cohorts of 6 to 12 subjects. Plasma trecovirsen concentrations and pharmacokinetic parameters could be assessed at doses > or = 0.3 mg/kg. Peak plasma concentrations and AUC values increased disproportionately with increasing dose while elimination half-life increased and plasma clearance decreased, indicating a saturable process over this dose range. The only significant adverse event observed was an isolated, transitory increase in activated partial thromboplastin time at doses > or = 2.0 mg/kg that was related to plasma trecovirsen concentrations and is attributed to the polyanionic character of the molecule. Thus, trecovirsen administration was well tolerated in single i.v. doses up to 2.5 mg/kg.

Adult↗

PubMed1998

Selective killing of glioma cell lines using an astrocyte-specific expression of the herpes simplex virus-thymidine kinase gene.

Gene therapy using the herpes simplex virus thymidine kinase gene (HSV-TK) is a promising new approach for the treatment of gliomas, a tumor type with a poor prognosis. To limit the toxic effects of this procedure, it is desirable to restrict expression of the HSV-TK gene to the target cells. This can be accomplished by use of the promoter of the glial fibrillary acidic protein gene, an intermediate filament protein expressed primarily in astrocytes. A plasmid containing the HSV-TK gene, driven by the human glial fibrillary acidic protein promoter gfa2, was lipofected into glioma cell lines and into an ovarian cancer cell line. Treatment with ganciclovir showed efficient killing of glioma cells, with no effect on the ovarian cells. Thus, the gfa2 promoter is a promising candidate for directing expression of toxic genes to gliomas.

Astrocytes↗

PubMed1998

Preclinical development of camptothecin derivatives and clinical trials in pediatric oncology.

Although the prognosis of childhood cancers has dramatically improved over the last three decades, new active drugs are needed. Camptothecins represent a very attractive new class of anticancer drugs to develop in paediatric oncology. The preclinical and clinical development of two of these DNA-topoisomerase I inhibitors, i.e. topotecan and irinotecan, is ongoing in paediatric malignancies. Here we review the currently available results of this evaluation. Topotecan proved to be active against several paediatric tumour xenografts. In paediatric phase I studies exploring several administration schedules, myelosuppression was dose-limiting. The preliminary results of topotecan evaluation in phase II study showed antitumour activity in neuroblastoma (response rate: 15% at relapse and 37% in newly diagnosed patients with disseminated disease) and in metastatic rhabdomyosarcoma (40% in untreated patients). Topotecan-containing drug combinations are currently investigated. Irinotecan displayed a broad spectrum of activity in paediatric solid tumour xenografts, including rhabdo-myosarcoma, neuroblastoma, peripheral primitive neuroectodermal tumour, medulloblastoma, ependymoma, malignant glioma and juvenile colon cancer. For several of these histology types, tumour-free survivors have been observed among animals bearing an advanced-stage tumour at time of treatment. The clinical evaluation of irinotecan in children is ongoing. Irinotecan undergoes a complex in vivo biotransformation involving several enzyme systems, such as carboxylesterase, UDPGT and cytochrome P450, in children as well as in adults. Preclinical studies of both drugs have shown that their activity was schedule-dependent. The optimal schedule of administration is an issue that needs to be addressed in children. In conclusion, the preliminary results of the paediatric evaluation of camptothecin derivatives show very encouraging results in childhood malignancies. The potential place of camptothecins in the treatment of paediatric malignant tumours is discussed.

Animals↗

PubMed1998

Activity of fotemustine in medulloblastoma and malignant glioma xenografts in relation to O6-alkylguanine-DNA alkyltransferase and alkylpurine-DNA N-glycosylase activity.

Fotemustine is a chloroethylnitrosourea with antitumor activity in disseminated melanoma and adult primary brain tumors. Because new drugs are required for the treatment of medulloblastoma in children, we evaluated the preclinical antitumor activity of fotemustine in four s.c. medulloblastoma xenografts, in comparison with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Both drugs were administered as a single i.p. injection to nude mice bearing advanced-stage tumor. Fotemustine displayed significant antitumor activity in three of four medulloblastoma xenografts; two, IGRM34 and IGRM57, were highly sensitive, with 37 and 100% tumor-free survivors, respectively, more than 120 days after treatment at the highest nontoxic dose (50 mg/kg). Fotemustine was also highly active in a malignant glioma xenograft (IGRG88; five of six tumor-free survivors on day 177). Fotemustine proved to be significantly more active than BCNU in IGRM34 and the glioma xenograft IGRG88. The DNA repair protein O6-alkylguanine-DNA alkyltransferase (ATase) was detected in all tumor xenografts, ranging in activity from 6 to 892 fmol/mg protein. The high in vivo sensitivity to fotemustine and BCNU observed in three xenografts was clearly associated with a low ATase activity (> 20 fmol/mg), whereas the two poorly sensitive or refractory medulloblastoma xenografts showed high ATase activity (> 500 fmol/mg). Alkylpurine-DNA N-glycosylase activity was detected in all tumor xenografts but at levels ranging only from 513 to 1105 fmol/mg/h; no consistent relationship was found between alkylpurine-DNA N-glycosylase activity and the in vivo sensitivity to the two chloroethylnitrosoureas. The improved activity and tolerance of fotemustine in comparison with BCNU in pediatric medulloblastoma xenografts strongly support the clinical development of this agent in children with brain tumors, in which ATase should be examined as a potential prognostic indicator.

Animals↗

PubMed1997

Potent therapeutic activity of irinotecan (CPT-11) and its schedule dependency in medulloblastoma xenografts in nude mice.

The anti-tumor activity of irinotecan (CPT-11), a DNA-topoisomerase 1 inhibitor, was evaluated in 5 advanced stage subcutaneous medulloblastoma xenografts in nude mice, using different schedules of administration. With a 5-day schedule, the highest i.v. dose tested (40 mg kg-1 day-1) induced complete regressions in all xenografts but 1, and delays in tumor growth always exceeded 30 days. Two xenografts, IGRM11 and IGRM33, were highly sensitive, and animals survived tumor-free beyond 120 days after treatment. CPT-11 clearly retained its anti-tumor activity at a lower dosage (27 mg kg-1 day-1). CPT-11 was significantly more active than cyclophosphamide, thiotepa and etoposide against the 3 xenografts evaluated. To study the schedule dependency of its anti-tumor activity, CPT-11 was given i.v. at the same total doses over the same period (33 days) using either a protracted or a sequential schedule in IGRM34-bearing mice. With a dose of 10 mg kg-1 day-1 given on days 0-4, days 7-11, days 21-25 and days 28-32 (total dose, 200 mg kg-1), 3 of 6 animals were tumor free on day 378. The same total dose given with a sequential schedule, i.e., 20 mg kg-1 day-1 on days 0-4 and days 28-32, failed to induce complete regression. The plasma pharmacokinetics of CPT-11 and SN-38 were studied in IGRM34-bearing animals after a single i.v. dose of 10 and 40 mg kg-1. The plasma clearance rate of CPT-11 was dose dependent. The ratio between the SN-38 and CPT-11 area under the curve in plasma was 0.4-0.65, i.e., significantly higher than that observed in humans at the maximum tolerated dose (0.01-0.05). Conversely, this ratio was 10-fold lower in tumor than in plasma. Clinical development of irinotecan is warranted in pediatric malignancies.

Animals↗

PubMed1997

DNA-topoisomerase I, a new target for the treatment of neuroblastoma.

DNA-topoisomerase I is the nuclear target of new anticancer drugs, namely camptothecin and its derivatives. In order to establish the rational basis for their clinical development in paediatric oncology, the antitumour activity of irinotecan (CPT-11) and topotecan, two camptothecin water-soluble derivatives, was studied in nude mice bearing neuroblastoma xenografts. The panel was composed of 4 previously established subcutaneous xenograft lines (IGR-N835, IGR-N91, IGR-NB3, IGR-NB8) that exhibited the common biological markers of poor prognosis in children (MYCN amplification, 1p deletion, paradiploidy and/or MDR1 overexpression). Irinotecan and topotecan were administered i.v. or i.p. over 5 consecutive days in animals bearing tumours. Irinotecan (40 mg/kg/day) induced 20-100% complete regressions with tumour growth delays ranging from 20 to 46 days. Two out of 10 IGR-N91 bearing animals were tumour free more than 120 days after treatment with the top dose (50 mg/kg/day). Topotecan (2.7 mg/kg/day) induced 0-67% complete regressions with tumour growth delays ranging from 23 to 50 days. One out of 8 IGR-NB3 bearing mice was tumour free at the end of the experiment. The antitumour activity of both drugs was clearly sustained at a lower dose level. Topoisomerase I activity was assayed in 15 neuroblastomas, 3 ganglioneuroblastomas and 2 normal adrenal glands, using a DNA relaxation assay. Topoisomerase I activity ranged from 69 to 1304 arbitrary units/mg of protein, and was significantly higher in immature neuroblastomas than in ganglioneuroblastomas and adrenal glands. In conclusion, irinotecan and topotecan are active against neuroblastoma xenografts. Their target is expressed in patients' tumour samples. Clinical development of topoisomerase I inhibitors in children with neuroblastoma is warranted.

Adrenal Glands↗

PubMed1997

In vitro and in vivo spectrofluorometry of a water-soluble meta-(tetrahydroxyphenyl)chlorin (m-THPC) derivative.

The pharmacokinetics of a water-soluble derivative obtained from meta-(tetrahydroxyphenyl)chlorin (m-THPC) was evaluated in in vitro and in vivo studies. Cytoplasm fluorescence was measured in two cell models (L1210 and HT29) using a flow cytometer and a confocal microspectrofluorometer. Cells were incubated with the compound at several doses (0-150 micrograms ml-1 for flow cytometry) and for several time periods (0-6 h for microspectrofluorometry). For in vivo studies, nude mice were grafted with human adenocarcinoma 15 days before intraperitoneal injection of polyethylene glycol-m-THPC (PEG-m-THPC). Fluorescence was recorded through an optical fibre spectrofluorometer using the 660 nm peak for detection. In in vitro studies, the fluorescence was found to be proportional to the dose. Maximum fluorescence was recorded in L1210 cells earlier and more intensely than in HT29 cells (3 h at 202 +/- 14 counts s-1 and 5 h at 43 +/- 2.15 counts s-1 respectively). Concerning in vivo studies, maximum tumour fluorescence was observed 24 h after injection (3568 +/- 178 counts s-1). Selectivity was expressed by the calculated tumour-to-skin and tumour-to-muscle ratios. The time taken to observe the maximum ratios (2.95 +/- 0.16 for tumour-to-skin and 6.61 +/- 0.3 for tumour-to-muscle) was almost the same as the time taken to observe the maximum fluorescence in the tumour. Studies are in progress to correlate these results with photodynamic effects.

Animals↗

PubMed1997

Potential efficacy of a delta 5-aminolevulinic acid bioadhesive gel formulation for the photodynamic treatment of lesions of the gastrointestinal tract in mice.

A delta 5-aminolevulinic acid (ALA) bioadhesive gel has been developed and evaluated in an in-vivo mouse model for photodynamic treatment of gastric cancer or Barrett's oesophagus. Four gels were tested: noveon AA-1, keltrol T, lutrol and blanose. An initial in-vitro study of gel adhesion showed that noveon and keltrol had longer polyethylene transit times than lutrol and blanose. In-vivo assays indicated that protoporphyrin IX was synthesized by gastric mucosa when ALA-noveon and ALA-lutrol were used (preferable results for noveon). Keltrol was eliminated from the study after these investigations. Only ALA-noveon gel was retained for studies of the relationship between ALA dose and fluorescence. Fluorescence measurements in-vivo showed that ALA concentration and application time had an influence on protoporphyrin IX synthesis. Maximum intensity (2091 counts s-1) was found with 2 mg mL-1 ALA, and fluorescence intensities differed with application time, reaching 1805 counts s-1 after 240 min. ALA-noveon, showing good adhesion and enabling efficient diffusion of ALA at a pH < 6, was considered the best formulation for maintaining ALA stability.

Aminolevulinic Acid↗

PubMed1997

Clastogenic activity in the plasma of scleroderma patients: a biomarker of oxidative stress.

BACKGROUND: Scleroderma patients exhibit increased chromosomal instability due to circulating clastogenic plasma factors (CF). Formation and action mechanisms of CF are mediated by superoxide. In addition, previous work detected inosine triphosphate (ITP) in the plasma of 2 patients, and the enzyme adenosine deaminase (ADA) was found to be increased. OBJECTIVE: To study correlations between CF, ITP and ADA levels, CF and disease activity, as well as other biomarkers of oxidative stress. METHODS: Clastogenic activity was evaluated by means of cytogenetic methods in 48 patients and 55 healthy subjects. ITP was detected by mass spectrometry and electrospray ionisation. ADA was measured with a colorimetric assay and malondialdehyde using the Yagi method. RESULTS: Clastogenic activity was significantly increased in patients' plasma compared to controls. In 10 patients CF, ITP and ADA were studied simultaneously. All three parameters were increased in the 7 patients of subgroups 2 (skin and esophagus involvement) and 3 (skin plus multiple organ involvement). ITP was not detected in 2 patients of subgroup 1 (skin involvement only) with low ADA and CF values. CONCLUSION: ITP, the deamination product of ATP, is one of the clastogenic and superoxide generating components of CF. The formation of this deamination product of ATP is probably related to the increase in ADA. CF are biomarkers of oxidative stress and can be used for evaluation of antioxidant treatments in scleroderma.

Adenosine Deaminase↗

PubMed1997

[Value and applications of pharmacogenetics in oncology and hematology].

Pharmacogenetics could be defined as the study of genetically controlled variations in drug response. Introduction of pharmacogenetics in hematology and oncology has been done recently. With recombinant DNA technology, like restriction analysis of genomic DNA, enzymatic amplification of DNA by the polymerase chain reaction and expression of cDNAs in cell cultures, this research area has been developed during the last 10 years. In hematology and oncology, we can integrate pharmacogenetics in 3 areas. First, the concept of genetic risk of cancer and the study of drug or carcinogen metabolizing enzymes that could modulate this risk, regarding the activity of some specific enzymes; second, the use of pharmacogenetics, related to the toxicity or efficacy of anticancer drugs, allowing the identification of key enzymes involved in the biotransformation of the drug and the study of molecular aspects involved in the regulation of the activity of the enzymes; third, the implication of the study of enzymatic activities in tumoral tissues as compared to non-tumoral tissues. The following differences between the 2 tissues can be subsequently used to increase the specificity of the anticancer drugs.

Antineoplastic Agents↗