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G Stoter

Publications and source records attributed to G Stoter.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effective cross-over to granisetron after failure to ondansetron, a randomized double blind study in patients failing ondansetron plus dexamethasone during the first 24 hours following highly emetogenic chemotherapy.

In view of the similarity in chemical structure of the available 5HT(3)-receptor antagonists it is assumed, whilst these agents all act at the same receptor, that failure to one agent would predict subsequent failure to all 5HT(3)-receptor antagonists. We conducted a randomized double blind trial of granisetron 3 mg plus dexamethasone 10 mg versus continued treatment with ondansetron 8 mg plus dexamethasone 10 mg in patients with protection failure on ondansetron 8 mg plus dexamethasone 10 mg during the first 24 hours following highly emetogenic chemotherapy. Of 40 eligible patients, 21 received ondansetron + dexamethasone and 19 received granisetron + dexamethasone. We found a significant benefit from crossing-over to granisetron after failure on ondansetron. Of the 19 patients who crossed over to granisetron, 9 patients obtained complete protection, whereas this was observed in 1 of the 21 patients continuing ondansetron, P = 0.005. These results indicate that there is no complete cross-resistance between 5HT(3)-receptor antagonists, and that patients who have acute protection failure on one 5HT(3)-receptor antagonist should be offered cross-over to another 5HT(3)-receptor antagonist.

Adult↗
PubMed2001

SKY1 is involved in cisplatin-induced cell kill in Saccharomyces cerevisiae, and inactivation of its human homologue, SRPK1, induces cisplatin resistance in a human ovarian carcinoma cell line.

The therapeutic potential of cisplatin, one of the most active and widely used anticancer drugs, is severely limited by the occurrence of cellular resistance. In this study, using budding yeast Saccharomyces cerevisiae as a model organism to identify novel drug resistance genes, we found that disruption of the yeast gene SKY1 (serine/arginine-rich protein-specific kinase from budding yeast) by either transposon insertion or one-step gene replacement conferred cellular resistance to cisplatin. Heterologous expression of the human SKY1 homologue SRPK1 (serine/arginine-rich protein-specific kinase) in SKY1 deletion mutant yeast cells restored cisplatin sensitivity, suggesting that SRPK1 is a cisplatin sensitivity gene, the inactivation of which could lead to cisplatin resistance. Subsequently, we investigated the role of SRPK1 in cisplatin sensitivity and resistance in human ovarian carcinoma A2780 cells using antisense oligodeoxynucleotides. Treatment of A2780 cells with antisense oligodeoxynucleotides directed against the translation initiation site of SRPK1 led to down-regulation of SRPK1 protein and conferred a 4-fold resistance to cisplatin. The human SRPK1 gene has not been associated with drug resistance before. Our new findings strongly suggest that SRPK1 is involved in cisplatin-induced cell kill and indicate that SRPK1 might potentially be of importance for studying clinical drug resistance.

Antineoplastic Agents↗
PubMed2001

Body-surface area-based dosing does not increase accuracy of predicting cisplatin exposure.

PURPOSE: Most anticancer drugs are dosed based on body-surface area (BSA) to reduce interindividual variability of drug effects. We evaluated the relevance of this concept for cisplatin by analyzing cisplatin pharmacokinetics obtained in prospective studies in a large patient population. PATIENTS AND METHODS: Data were obtained from 268 adult patients (163 males/105 females; median age, 54 years [range, 21 to 74 years]) with advanced solid tumors treated in phase I/II trials with cisplatin monotherapy or combination chemotherapy with etoposide, irinotecan, topotecan, or docetaxel. Cisplatin was administered either weekly (n = 93) or once every 3 weeks (n = 175) at dose levels of 50 to 100 mg/m(2) (3-hour infusion). Analysis of 485 complete courses was based on measurement of total and non-protein-bound cisplatin in plasma by atomic absorption spectrometry. RESULTS: No pharmacokinetic interaction was found between cisplatin and the anticancer drugs used in combination therapies. A linear correlation was observed between area under the curves of unbound and total cisplatin (r = 0.63). The mean plasma clearance of unbound cisplatin (CL(free)) was 57.1 +/- 14.7 L/h (range, 31.0 to 116 L/h), with an interpatient variability of 25.6%. BSA varied between 1.43 and 2.40 m(2) (mean, 1.86 +/- 0.19 m(2)), with an interpatient variability of 10.4%. When CL(free) was corrected for BSA, interindividual variability remained in the same order (23.6 v 25.6%). Only a weak correlation was found between CL(free) and BSA (r = 0.42). Intrapatient variability in CL(free), calculated from 90 patients was 12.1% +/- 7.8% (range, 0.30% to 32.7%). CONCLUSION: In view of the high interpatient variability in CL(free) relative to variation in observed BSA, no rationale for continuing BSA-based dosing was found. We recommend fixed-dosing regimens for cisplatin.

Adult↗
PubMed2001

[Treatment of metastatic testicular carcinoma according to prognosis; new development].

The majority of patients with a metastatic germ cell tumour can be successfully treated with a combination chemotherapy containing cisplatin. For more than a decade the combination of cisplatin, etoposide and bleomycin (BEP) has been the gold standard of treatment. In both the United States and Europe, a number of studies have been carried out, with the purpose of reducing the toxicity of the treatment for patients with a good prognosis as well as improving the treatment result for patients with intermediate or unfavourable prognostic characteristics, by intensifying the chemotherapy regimen or by adding new cytotoxic agents. The standard treatment for patients with a good prognosis consists at present of three BEP cycles, which can be administered in a shortened schedule of three days per cycle. Bleomycin is essential for the success of the therapy and cisplatin cannot be replaced by carboplatin. Efforts to increase the dose of cisplatin per cycle, reduce the interval between cycles, the addition of ifosfamide and sequential/alternating therapy do not provide any additional benefit compared to the standard treatment with BEP.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

Pharmacokinetic modeling of paclitaxel encapsulation in Cremophor EL micelles.

Nonlinear disposition of paclitaxel (Taxol) in cancer patients has been described in several studies, but the underlying mechanism is still a matter of speculation. Previously, we have shown in vitro that the paclitaxel formulation vehicle, Cremophor EL (CrEL), alters the blood distribution of paclitaxel as a result of entrapment of the compound in circulating CrEL micelles, thereby reducing the free drug fraction available for cellular partitioning. Based on these findings, we prospectively re-evaluated the linearity of paclitaxel disposition in patients using whole blood and plasma analysis, and sought to define a new pharmacokinetic model to describe the data. Seven patients with solid tumors were treated with paclitaxel infused over 3 h, each at consecutive 3-weekly dose levels of 225, 175 and 135 mg/m2 (CrEL dose level, 18.8, 14.6, and 11.3 ml/m2, respectively). Patient samples were collected up to 24 h after the start of infusion, and analyzed by high-performance liquid chromatography. Paclitaxel peak levels and areas under the curve in whole blood increased linearly with dose, whereas plasma levels showed substantial deviation from linearity. This was shown to be caused by a CrEL concentration-dependent decrease in paclitaxel uptake in blood cells, as reflected by the blood:plasma concentration ratios which altered significantly from 0.83 +/- 0.11 (at 135 mg/m2) to 0.68 +/- 0.07 (at 225 mg/m2). It is concluded that the nonlinear disposition of paclitaxel is related to paclitaxel dose-related levels of the formulation vehicle CrEL, leading to a disproportionate drug accumulation in the plasma fraction. The pharmacokinetic model developed accurately described the data, and will help guide future development and refinement of clinical protocols, especially in defining the exposure measure best linked to paclitaxel effects and toxicities.

Adult↗
PubMed2001

Interleukin 12 induces activation of fibrinolysis and coagulation in humans.

Interleukin 12 (IL-12) has potential efficacy in malignant, infectious and allergic diseases. Its side-effects include activation of coagulation and fibrinolysis, as documented in chimpanzees. We assessed the coagulative and fibrinolytic response in 18 patients with renal cell carcinoma after subcutaneous injection of 0.5 microg/kg recombinant human IL-12. IL-12 induced a fibrinolytic response in 17 patients (94%): plasmin-alpha2-anti-plasmin complexes (PAPc) increased from 11.8 +/- 6.6 nmol/l (mean +/- SD) to a maximum of 18.8 +/- 7.4 nmol/l at 72 h. Baseline levels of tissue plasminogen activator (tPA) and plasminogen-activator inhibitor-I (PAI) were elevated in eight and 14 patients respectively. tPA increased from 12.6 +/- 5.2 ng/ml to a maximum of 19.0 +/- 6.7 ng/ml at 72 h. PAI decreased from 111 +/- 69 ng/ml to a minimum of 65 +/- 53 ng/ml at 8 h, thereafter remaining below baseline. Elevation of PAPc correlated with elevation of tPA and reduction of PAI. A coagulative response occurred in nine patients (50%): thrombin-anti-thrombin III complexes increased from 29 +/- 53 ng/ml to a maximum of 460 +/- 322 ng/ml at 12 h. Patients with and without a coagulative response had similar levels of recombinant human IL-12, interferon-gamma or tumour necrosis factor-alpha. We conclude that IL-12 can activate both fibrinolysis and coagulation in a significant proportion of patients with cancer. The time-frame and sequence of these activation processes differ from those known for other cytokines.

Adult↗
PubMed2001

Phase II study of the combination cisplatin, etoposide, 5-fluorouracil and folinic acid in patients with advanced squamous cell carcinoma of the esophagus.

The objective of this study was to determine the toxicity and the efficacy of the combination of cisplatin, etoposide, 5-fluorouracil (5-FU) and folinic acid in the treatment of patients with advanced squamous cell carcinoma of the esophagus. Patients received cisplatin 80 mg/m(2) i.v. on day 1, etoposide 125 mg/m(2) i.v. on day 1 and etoposide 200 mg/m(2) p.o. on days 3 and 5, 5-FU 375 mg/m(2)/day continuously i.v. combined with folinic acid 30 mg p.o. 6 times per day on days 1--4. Courses were repeated every 4 weeks until progression or up to a maximum of 6 courses. Patients were evaluated for response after every two courses. Sixty-nine patients received a total of 291 courses (median 4, range 1--6). The hematological toxicity consisted of leukocytopenia grade 3 or 4 in 17 and 16% of patients, respectively. Leukocytopenic fever was seen in 19% of patients. Thrombocytopenia grade 3 or 4 was seen in 13 and 7% of patients, respectively. Non-hematological toxicity consisted of nausea/vomiting grade 3 in 32%, diarrhea grade 3 in 6% and mucositis grade 3 or 4 in 23% of patients. The overall response rate was 34% (complete response 4%, partial response 30%) and the median time to progression was 7 months in 13 patients who received no additional treatment. The median survival for all patients was 9.5 months with a 1-year survival rate of 36%. Ten patients with initially locally unresectable disease (N=2) or celiac or supraclavicular lymph node metastases (N=8) who received additional treatment (esophageal resection in seven patients and radiotherapy in three patients) after they had responded to chemotherapy had a 3-year survival of 50%. We conclude that the combination cisplatin and etoposide combined with 5-FU and folinic acid is a safe and active regimen for patients with advanced squamous cell carcinoma of the esophagus. Mucositis is the most prevalent toxicity.

Adult↗
PubMed2001

Clinical pharmacokinetics and metabolism of irinotecan (CPT-11).

CPT-11 belongs to the class of topoisomerase I inhibitors, and it acts as a prodrug of SN-38, which is approximately 100-1000-fold more cytotoxic than the parent drug. CPT-11 has shown a broad spectrum of antitumor activity in preclinical models as well as clinically, with responses observed in various disease types including colorectal, lung, cervical, and ovarian cancer. The pharmacokinetics and metabolism of CPT-11 are extremely complex and have been the subject of intensive investigation in recent years. Both CPT-11 and SN-38 are known in an active lactone form and an inactive carboxylate form, between which an equilibrium exists that depends on the pH and the presence of binding proteins. CPT-11 is subject to extensive metabolic conversion by various enzyme systems, including esterases to form SN-38, UGT1A1 mediating glucuronidation of SN-38, as well as CYP3A4, which forms several pharmacologically inactive oxidation products. Elimination routes of CPT-11 also depend on the presence of drug-transporting proteins, notably P-glycoprotein and canalicular multispecific organic anion transporter, present on the bile canalicular membrane. The various processes mediating drug elimination, either through metabolic breakdown or excretion, likely impact substantially on interindividual variability in drug handling. Strategies to individualize CPT-11 administration schedules based on patient differences in enzyme or protein expression or by coadministration of specific agents modulating side effects are under way and may ultimately lead to more selective chemotherapeutic use of this agent.

Antineoplastic Agents, Phytogenic↗
PubMed2000

A genome-wide screening in Saccharomyces cerevisiae for genes that confer resistance to the anticancer agent cisplatin.

Cisplatin is a potent DNA-damaging agent that has demonstrated anticancer activities against several tumors. However, manifestation of cellular resistance is a major obstacle in anticancer therapy that severely limits the curative potential of cisplatin. Therefore, understanding the molecular basis of cisplatin resistance could significantly improve the clinical efficacy of this anticancer agent. Here, we employed Saccharomyces cerevisiae as a model organism to study cisplatin resistance mechanisms and describe a one-step cisplatin selection to identify and characterize novel cisplatin resistance genes. Screening a multicopy yeast genomic library enabled us to isolate several yeast clones for which we could confirm that the cisplatin resistance phenotype was linked to the introduced fragment. In a first attempt, a number of open reading frames could be identified. Among these genes, PDE2 and ZDS2 were repeatedly identified as genes whose overexpression confers cellular resistance to cisplatin. PDE2, encoding cAMP-phosphodiesterase 2, is of particular interest because the overexpression of this yeast gene is known to induce cisplatin resistance in mammalian cells as well, providing proof of the principle of our experimental approach. In addition, the identification of PDE2 shows that our yeast screening system can directly be informative for drug resistance in mammalian cells.

Chromosome Mapping↗
PubMed2000

Liposomal lurtotecan (NX211): determination of total drug levels in human plasma and urine by reversed-phase high-performance liquid chromatography.

Lurtotecan (GI147211; LRT) is a semisynthetic and water-soluble analogue of the topoisomerase I inhibitor camptothecin. To determine whether the therapeutic efficacy of LRT in patients could be improved, the drug was encapsulated in liposomes (NX211; Gilead Sciences). In order to allow accurate description of the pharmacokinetic behavior of NX211 in cancer patients, we have developed sensitive RP-HPLC assays with fluorescence detection (lambdaex=378 nm; lambdaem=420 nm) for the determination of total LRT levels in human plasma and urine. Sample pretreatment involved deproteinization with 10% (w/v) aqueous perchloric acid-acetonitrile (2:1, v/v), and chromatographic separations were achieved on an Inertsil-ODS 80A analytical column. The lower limit of quantitation (LLQ) was established at 1.00 ng/ml in plasma (200-microl sample) and at 100 ng/ml in urine (200 microl of 40-fold diluted sample). The within-run and between-run precisions were <7.5%. LRT concentrations in urine of <100 ng/ml were determined by a modified procedure comprising a single solvent extraction with n-butanol-diethyl ether (3:4, v/v). In this assay, the fluorescence signal of LRT was increased 14-fold prior to detection by post-column exposure to UV light (254 nm) in a photochemical reaction unit. The LLQ of this assay was 0.500 ng/ml (150-microl sample) and the within-run and between-run precisions were <10%.

Acetonitriles↗
PubMed2000

Interferon-alpha induced Raynaud's syndrome.

The cytokine interferon-alpha (IFN-alpha) is increasingly prescribed for a number of indications, especially viral hepatitis and several malignancies. Two patients are described who developed Raynaud's syndrome during treatment with IFN-alpha as adjuvant therapy for high-risk melanoma. With a review of the available literature the symptomatology, possible pathophysiologic mechanisms and treatment options are discussed.

Adult↗
PubMed2000

Intrapleural administration of tumour necrosis factor-alpha (TNFalpha) in patients with mesothelioma: cytokine patterns and acute-phase protein response.

BACKGROUND: Tumour necrosis factor-alpha (TNFalpha) has been found to be very effective in the isolated limb perfusion setting for advanced extremity tumours. In a phase I study of intrapleural administration of TNFalpha 5 patients were followed for inflammatory response patterns. PATIENTS AND METHODS: Malignant mesothelioma patients were treated with repeated intrapleural administration of 0. 1-0.2 mg recombinant TNFalpha. Samples of serum and pleural fluid were taken at different time-points before and after TNFalpha-administration. Levels of TNFalpha, interleukin-6 (IL-6), interleukin-8 (IL-8), C-reactive protein (CRP) and secretory phospholipase A2 (sPLA2) were measured using enzyme-linked immunosorbent assays (ELISAs). Alpha 1-acid glycoprotein (alpha1-AG) was measured by nephelometry. RESULTS: In pleural fluid TNFalpha and IL-8 reached peak levels, up to 50-700 ng mL-1 and 6-60 ng mL-1, respectively, 24 h after administration of TNFalpha. IL-6 (peak levels up to 250 ng mL-1) and sPLA2 peaked after 48 h. A slower and less dramatic pattern was observed for the levels of CRP and alpha1-AG. In serum no detectable levels of TNFalpha and no IL-8 were observed, whereas serum levels of IL-6, sPLA2 and CRP showed a clear increase after intrapleural administration of TNFalpha. Cytokines and acute-phase proteins showed the same pattern during subsequent cycles even up to 12 cycles. Tumour regression was not observed. CONCLUSIONS: In the setting of a phase I study of repetitive intrapleural administration of TNFalpha in mesothelioma patients, we studied the characteristics of the inflammatory response. Intrapleural administration was followed by a clear inflammatory response locoregionally. In spite of TNFalpha peak levels as high as 700 ng mL-1 systemic levels were never detectable. The secondary cytokine response led to very high intrapleural IL-6 and IL-8 levels. Systemically IL-8 levels were never detectable whereas high IL-6 levels were induced systemically initially, with a decreased response to each intrapleural TNFalpha administration over time. The acute-phase response in contrast remained remarkably constant throughout the course of repeated intrapleural administrations of TNFalpha. Intrapleural administration of TNFalpha is well tolerated but associated with inconsistent and rather moderate impact on production of pleural fluid. This can be achieved by other simpler and cheaper treatment, thus we see no justification for further studies.

Acute-Phase Proteins↗
PubMed2000

Farnesyl transferase inhibitors: current developments and future perspectives.

Ras oncogenes play an important role in carcinogenesis and are frequently found in various human tumour types. Cellular activity of Ras oncoprotein, regulated through the enzyme farnesyl transferase, is crucial in the process of ras -dependent carcinogenesis, and therefore, specific inhibition of this enzyme is an attractive goal in anticancer treatment. Specific inhibitors of farnesyl transferase have been developed in recent years, many of them showing in vitro and in vivo growth inhibitory or cytostatic activity. Recently, results of the first clinical studies with various farnesyl transferase inhibitors have been presented. In the design of phase I and II studies, either single-agent or combination studies, new endpoints have to be defined in order to properly assess feasibility, antitumour activity and clinical valuability.

Alkyl and Aryl Transferases↗
PubMed2000

Role of intestinal P-glycoprotein in the plasma and fecal disposition of docetaxel in humans.

Multidrug resistance (MDR)-1-P-glycoprotein (P-gp) is a drug-transporting protein that is abundantly present in biliary ductal cells and epithelial cells lining the gastrointestinal tract. Here, we have determined the role of P-gp in the metabolic disposition of the antineoplastic agent docetaxel (Taxotere) in humans. Pharmacokinetic profiles were evaluated in five cancer patients receiving treatment cycles with docetaxel alone (100 mg/m2 i.v. over a 1-h period) and in combination with a new potent inhibitor of P-gp activity, R101933 (200-300 mg b.i.d.). The terminal disposition half-life and total plasma clearance of docetaxel were not altered by treatment with oral R101933 (P > or = 0.27). The cumulative fecal excretion of docetaxel, however, was markedly reduced from 8.47 +/- 2.14% (mean +/- SD) of the dose with the single agent to less than 0.5% in the presence of R101933 (P = 0.0016). Levels of the major cytochrome P450 3A4-mediated metabolites of docetaxel in feces were significantly increased after combination treatment with R101933 (P = 0.010), indicating very prominent and efficient detoxification of reabsorbed docetaxel into hydroxylated compounds before reaching the systemic circulation. It is concluded that intestinal P-gp plays a principal role in the fecal elimination of docetaxel by modulating reabsorption of the drug after hepatobiliary secretion. In addition, the results indicate that inhibition of P-gp activity in normal tissues by effective modulators, and the physiological and pharmacological consequences of this treatment, cannot be predicted based on plasma drug monitoring alone.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Determination of 5-fluorouracil in microvolumes of human plasma by solvent extraction and high-performance liquid chromatography.

In the present study, a new reversed-phase HPLC method has been developed and validated for the quantitative determination of 5-fluorouracil (5-FU) in human plasma using only 100-microl samples. The sample extraction and clean-up procedure involved a simple liquid-liquid extraction after addition of 5-chlorouracil (5-CU), used as internal standard, with 5 ml ethyl acetate. Chromatographic separations were performed on an Inertsil ODS-3 column (250x4.6 mm ID; 5 microM particle size), eluted with a mobile phase composed of acidified water (pH 2.0). The column effluent was monitored by UV absorption measurement at a wavelength of 266 nm. The calibration curves were constructed over a range of 0.20-50.0 microM and were fitted by weighted (1/x) linear regression analysis using the ratio of peak heights of 5-FU and 5-CU versus concentrations of the nominal standards. Extraction recoveries over the total range averaged 92 and 93% for 5-FU and 5-CU, respectively. The lower limit of quantitation was established at 0.20 microM (approximately 26 ng/ml), with within-run and between-run precisions of 4.2 and 7.0%, respectively, and an average accuracy of 109.3%. The within-run and between-run precisions at four tested concentrations analyzed in quintuplicate over a time period of four days were < 1.4 and < 4.4%, respectively. The accuracy at the tested concentrations ranged from 98.4 to 102.3%. Compared to previously described validated analytical methods for 5-FU, our present assay provides equivalent to superior sensitivity, using only microvolumes of sample.

Antimetabolites, Antineoplastic↗
PubMed1999

Liquid chromatographic analysis and preliminary pharmacokinetics of methotrexate in cancer patients co-treated with docetaxel.

A new HPLC method has been developed for the quantitative determination of methotrexate (MTX) and its 7-hydroxyl metabolite in human plasma. Samples were purified by protein precipitation with acetone and methanol, and a sample clean-up with a mixture of n-butanol and diethyl ether. The analytes were separated on an RP Inertsil ODS-80A column and eluted in a solvent system containing 5% (v/v) tetrahydrofuran in water (pH 2.0). UV absorption measurement was performed at 313 nm, and the detector response was linear in a concentration range of 10-10,000 ng/ml. The lower limit of quantitation of MTX was 10 ng/ml using 1 ml sample aliquots. Values for accuracy and (within-run and between-run) precision were between 95.5-111% and 3.69-11.0%, respectively, at four concentrations analyzed in quintuplicate on four separate occasions. The assay was applied to study the effects of docetaxel co-administration on the pharmacokinetics and metabolism of MTX in cancer patients.

Acetone↗
PubMed1999

Distinct p53-independent apoptotic cell death signalling pathways in testicular germ cell tumour cell lines.

The induction of apoptosis by diverse apoptotic stimuli was studied in a panel of 6 testicular germ cell tumour (TGCT) cell lines with defined p53 status. Although the sensitivity to a particular stimulus varied considerably among the TGCT cell lines, the differences in response were not associated with the presence of functional p53. Mutant (mt) p53-expressing NCCIT and S2 (no p53 protein) were both readily triggered into apoptosis by cisplatin and doxorubicin, while wild-type(wt)-p53-transactivation-competent 2102 EP cells failed to undergo drug-induced apoptosis. Moreover, transactivation-deficient NCCIT cells and wtp53-expressing NT2 cells were equally sensitive to cisplatin, doxorubicin, gamma radiation, and cell-permeable C2-ceramide. Our p53 data suggest that, at least in this panel of non-isogeneic TGCT cell lines, hypersensitivity to therapeutic agents is not associated with p53 status. Next, we examined the impact of p53 inactivation on apoptosis induction in isogeneic NT2 sublines expressing human papillomavirus E6 protein. Evidently, abrogation of p53 function did not affect the hypersensitivity to apoptotic stimuli. We noted that drug-sensitive S2 cells were highly resistant to radiation-induced apoptosis, indicating distinct signalling pathways for chemotherapy and irradiation. The impaired radiation-induced apoptotic pathway in S2 and 2102 EP could not be restored by addition of cell-permeable C2-ceramide, suggesting that the blockade is downstream of ceramide generation. Ligation of Fas/APO-1/CD95 by anti-Fas effectively induced apoptosis in Fas-antigen expressing S2, 2102 EP and 833 KE. The efficient Fas-mediated activation of apoptosis in drug-, radiation-, and ceramide-resistant 2102 EP cells further suggests that diverse apoptosis-inducing factors may use distinct signalling pathways. In summary, we demonstrated the presence of distinct p53-independent apoptotic pathways in TGCT cells.

Apoptosis↗