Biomedical subjects

P Marini

Publications and source records attributed to P Marini.

At least 19 recordsLinked to original sources

PubMed2006

Combined treatment of colorectal tumours with agonistic TRAIL receptor antibodies HGS-ETR1 and HGS-ETR2 and radiotherapy: enhanced effects in vitro and dose-dependent growth delay in vivo.

We and others have demonstrated already that TRAIL (TNF-related apoptosis-inducing ligand) is a very promising candidate for molecular targeted anticancer therapy, especially when combined with ionizing radiation or other DNA-damaging agents. Agonist monoclonal antibodies that activate and are specific for the death signaling TRAIL receptors are an alternative method to stimulate the programmed cell death pathway. Phase 1 clinical trials have subsequently been conducted and shown a very good tolerability of these antibodies. In order to assess the efficacy of TRAIL receptor stimulation to induce cell death by this alternate method, we studied the combination of the agonistic-TRAIL receptor antibodies HGS-ETR1 and HGS-ETR2 with radiation in vitro and in vivo. Induction of apoptosis after combined treatment with TRAIL receptor antibodies HGS-ETR1 and/or HGS-ETR2 (0.01, 0.1, 1.0 mg/ml) and irradiation with 2, 5 or 10 Gy was determined by fluorescence microscopy and Western blot analysis of caspase-8 and PARP. The colorectal tumour cell lines Colo 205, HCT 116 and HCT-15 were used for in vitro experiments. Growth delay experiments were performed with combined treatment with fractionated irradiation (days 1-5 and 3 Gy single dose/day) and the receptor antibodies (intraperitonially, three different concentrations, application on days 1, 4 and 8) on Colo 205 xenograft-bearing NMRI (nu/nu) nude mice. HGS-ETR1 and HGS-ETR2 induced apoptotic cell death in a dose-dependent fashion and significantly increased cell death in combination with irradiation in vitro when compared to either irradiation or antibody treatment alone. The efficacy of the combined treatment seems to be at least partially Bax-dependent. Similar to the results from cell culture experiments, in vivo experiments demonstrated a dose-dependent delay in tumour growth after combined treatment. In vivo, in the Colo205 xenograft model, HGS-ETR2 revealed a higher activity than HGS-ETR1. This is the first study to demonstrate significant efficacy of combined treatment with the monoclonal agonistic TRAIL receptor antibodies HGS-ETR1 and HGS-ETR2 and ionising radiation in in vitro and in vivo models. We postulate that HGS-ETR1 and HGS-ETR2 will be very promising new agents in the field of molecular targeted multi-modality anticancer therapy.

Antibodies, Monoclonal↗

PubMed2005

Early-onset parkinsonism associated with PINK1 mutations: frequency, genotypes, and phenotypes.

OBJECTIVE: To assess the prevalence, nature, and associated phenotypes of PINK1 gene mutations in a large series of patients with early-onset (<50 years) parkinsonism. METHODS: The authors studied 134 patients (116 sporadic and 18 familial; 77% Italian) and 90 Italian controls. The whole PINK1 coding region was sequenced from genomic DNA; cDNA was analyzed in selected cases. RESULTS: Homozygous pathogenic mutations were identified in 4 of 90 Italian sporadic cases, including the novel Gln456Stop mutation; single heterozygous truncating or missense mutations were found in another 4 Italian sporadic cases, including two novel mutations, Pro196Leu and Gln456Stop. Pathogenic mutations were not identified in the familial cases. Novel (Gln115Leu) and known polymorphisms were identified with similar frequency in cases and controls. In cases carrying single heterozygous mutation, cDNA analysis detected no additional mutations, and revealed a major pathogenic effect at mRNA level for the mutant C1366T/Gln456Stop allele. All patients with homozygous mutations had very early disease onset, slow progression, and excellent response to l-dopa, including, in some, symmetric onset, dystonia at onset, and sleep benefit, resembling parkin-related disease. Phenotype in patients with single heterozygous mutation was similar, but onset was later. CONCLUSIONS: PINK1 homozygous mutations are a relevant cause of disease among Italian sporadic patients with early-onset parkinsonism. The role of mutations found in single heterozygous state is difficult to interpret. Our study suggests that, at least in some patients, these mutations are disease causing, in combination with additional, still unknown factors.

Adolescent↗

PubMed2004

PC-aided assessment of the thermal performances of a MW applicator for oncological hyperthermia.

The thermal performances of an MW oncological hyperthermic (OH) system have been assessed with a PC-aided procedure. Measurements were performed on a muscle-equivalent phantom. Between the applicator and the phantom a water bolus was interposed which, to simulate real OH treatments, could be connected to a forced cooling water circulation system. Direct thermal measurements of temperatures and SAR (using the 'short pulse technique') and simulation by numerical modelling were performed, both aiming at describing the 3-D thermal field inside the phantom. Accuracy and manageability of the automated procedure proved suitable for characterization and quality assurance of MW applicators in clinical hyperthermia and encourage further efforts towards the development of computerized treatment simulations in OH.

Automation↗

PubMed2003

Deficit of short-term memory in newly diagnosed untreated parkinsonian patients: reversal after L-dopa therapy.

We assessed the effect of pathology and L-dopa therapy on attention, working memory, and executive functions, in newly diagnosed Parkinson's disease patients. Twenty-one consecutive outpatients who met the criteria for de novo Parkinson's disease, and were naive for L-dopa therapy, were observed for the first time. All patients underwent clinical and neuropsychological evaluations (cognitive decline, memory, executive control). Each patient was reevaluated on standard L-dopa therapy. Serial Position Curves showed an increased primacy effect (5.18+/-2.07) and a decreased recency effect (13.35+/-5.51). These findings normalized after L-dopa therapy (3.50+/-1.72 and 16.20+/-3.09 respectively). The effect of L-dopa on working memory is discussed.

Adult↗

PubMed2002

Mitomycin C in combination with radiotherapy as a potent inhibitor of tumour cell repopulation in a human squamous cell carcinoma.

The potential of Mitomycin C in combination with fractionated irradiation to inhibit tumour cell repopulation of a fast growing squamous cell carcinoma after fractionated radiotherapy was investigated in vivo. A rapidly growing human squamous cell carcinoma (FaDu(dd)) was used for the study. For experiments, NMRI (nu/nu) mice with subcutaneously growing tumours were randomly allocated to no treatment, Mitomycin C, fractionated irradiation (ambient: 11 x 4.5 Gy in 15 days), or fractionated irradiation combined with Mitomycin C. Graded top up doses (clamped blood flow: 0-57 Gy) were given at day 16, 23, 30 or 37. End point of the study was the time to local tumour progression. Data were examined by multiple regression analysis (Cox). Mitomycin C alone resulted in a median time to local tumour progression of 23 (95% confidence limits: 17-43) days, fractionated irradiation in 31 (25-35) days and combined Mitomycin C plus fractionated irradiation in 65 (58-73) days (P=0.02). Mitomycin C decreased the relative risk of local recurrence by 94% (P<<0.001) equivalent to 31.7 Gy top up dose. Repopulation accounted for 1.33 (0.95-1.72) Gy per day top up dose after fractionated irradiation alone and for 0.68 (0.13-1.22) Gy per day after fractionated irradiation+Mitomycin C (P=0.018). Mitomycin C significantly reduces the risk of local recurrence and inhibits tumour cell repopulation in combination with fractionated irradiation in vivo in the tested tumour model.

Animals↗

PubMed2002

Management of spontaneous rupture of liver tumours.

Spontaneous ruptures of a liver tumour are often considered as a potentially life-threatening situation. The aim of the present study was to evaluate both clinical features and treatment in a subgroup of patients with ruptured liver tumours. From 1995 to 2000, 20 patients were referred to our centre for spontaneous rupture of a liver tumour associated with haemoperitoneum. Hepatocellular carcinoma (HCC) was present in 13 patients (11 men and 2 women) aged from 48 to 72 years (mean 62) and adenoma in 7 women aged from 23 to 52 years (mean 35). Although all patients experienced sudden abdominal pain and anaemia, shock at admission was present in 4 (20%) patients including 3 with HCC. In patients with HCC, severe liver insufficiency (Child-Pugh C) was present in 5 cases including the 3 shocked patients. No treatment was undertaken in 2 patients, transarterial embolization was performed in 9 cases and 5 patients underwent delayed resection. In hospital, mortality was observed in 3 (23%) patients, all of them had severe liver insufficiency. Long-term survival was observed in patients with good liver function who underwent resection. In patients with adenoma, shock at admission was observed in only 1 patient under anticoagulation treatment. Emergency resection was performed in 3 cases. A decrease of the tumour size was observed in patients who underwent delayed resection resulting in a lower rate of peri-operative transfusion. In conclusion, this study confirms that the majority of patients with ruptured liver tumours had no evidence of haemodynamic instability and therefore should be initially managed conservatively. In patients with single ruptured HCC associated with good liver function, long-term survival can be observed after liver resection. Delayed resection facilitated the operative procedure in patients with ruptured adenoma.

Aged↗

PubMed2001

Sensitization of resistant lymphoma cells to irradiation-induced apoptosis by the death ligand TRAIL.

A combination of antitumor approaches acting on different death pathways seems ideal for increasing therapeutic responses, especially when defined resistance mechanisms interfere with individual cellular processes. Apoptosis pathways triggered by ionizing radiation (XRT) and the death ligand TRAIL were analysed in Jurkat lymphoma cells. Both induced the activation of caspase-8, caspase-3, BID and mitochondrial potential loss. TRAIL induced apoptosis required caspase-8, whereas it was not essential for radiation induced apoptosis. The inhibition of mitochondrial damage by Bcl-2 abrogated XRT induced apoptosis and caspase activation, but only marginally attenuated TRAIL induced cell death. The combined treatment with TRAIL and XRT exerted additive apoptotic effects in control cells, whereas highly synergistic effects occurred in cells overexpressing Bcl-2. In addition, a strong effect of TRAIL on radiation induced clonogenic cell death was found. In conclusion, TRAIL seems to be of high potential value for a combination with ionizing radiation in tumor therapy.

Apoptosis↗

PubMed2001

Which target for DBS in Parkinson's disease? Subthalamic nucleus versus globus pallidus internus.

We selected 14 patients with advanced idiopathic Parkinson's disease (PD) and examined the clinical effects of STN DBS versus GPi DBS. Nine patients underwent bilateral STN DBS and five underwent bilateral GPi patients. All patients were followed for at least 12 months. The evaluation was performed on and off drug before surgery; on-drug/on-DBS and off-drug/on-DBS at 1, 3, 6 and 12 months after stereotactic surgery. At 1 and 3 months after surgery in off-drug/on-DBS condition, both groups showed an improvement in motor score (UPDRS III). Nevertheless, the results changed after long-term stimulation in the two groups. Chronic STN DBS is superior to GPi DBS in the amelioration of the clinical features and in the decrease of time spent in the off state. The efficacy in reduction of LID was comparable at 1 and 3 months after surgery, but the results were better in STN DBS after chronic stimulation. The L-dopa dose was reduced only in the STN group.

Electric Stimulation Therapy↗

PubMed2001

Radiation sensitivity and apoptosis in human lymphoma cells.

PURPOSE: The impact ofapoptosis on radiation-induced eradication of clonogenic tumour cells is uncertain. The aim was to analyse the relationship of different functional stages during the apoptotic process to cell death and clonogenic cell eradication. MATERIALS AND METHODS: Apoptosis in Jurkat T-cells was studied by morphology, light scatter and caspase activation. Mitochondrial integrity was determined by the mitochondrial membrane potential (delta(phi)m). Cell death was quantified using propidium iodide exclusion. Clonogenic cell death was determined using a dilution survival assay. The influence of Bcl-2 was tested using a Bcl-2 transfected Jurkat clone. RESULTS: Irradiation induced profound apoptosis within 48 h associated with caspase activation and breakdown of delta(phi)m. Inhibition of caspases abrogated the apoptotic morphology with no influence on breakdown of delta(phi)m and survival. Over-expression of Bcl-2 abrogated all hallmarks of apoptosis; delayed cell death, however, had no influence on clonogenic survival after irradiation. CONCLUSION: Based on Bcl-2 as a positional marker, radiation-induced apoptosis can be divided into two stages: the initiation/decision phase, characterized by a breakdown of the mitochondrial membrane potential, and the execution phase, characterized by caspase activation. The execution phase had no influence on survival, whereas the initiation/decision phase controls immediate survival. However, abrogation of both phases did not influence radiation sensitivity.

Amino Acid Chloromethyl Ketones↗

PubMed2001

Outcome of biliopancreatic diversion in subjects with Prader-Willi Syndrome.

BACKGROUND: In Prader-Willi Syndrome (PWS), mental retardation and compulsive hyperphagia cause early obesity, the co-morbidities of which lead to short life-expectancy, with death usually occurring in their 20s. Long-term weight loss is mandatory to lengthen the survival; therefore, the lack of compliance in voluntary food restriction requires a surgical malabsorptive approach. METHODS: 15 PWS subjects were submitted to biliopancreatic diversion (BPD) and followed (100%) for a mean period of 8.5 (4-13) years. BPD consists of a distal gastrectomy with a long Roux-en-Y reconstruction which, by delaying the meeting between food and biliopancreatic juices, causes an intestinal malabsorption. Indication for BPD was BMI > 40 or > 35 with metabolic complications. Preoperative mean age was 21 +/- 5 years, mean weight 127 +/- 26 kg, and mean Body Mass Index (BMI, kg/m2) 53 +/- 10. According to Holm's criteria, all of the subjects had a total score > or = 8. IQ assessment was performed in each subject, with a mean score of 72 +/- 10. An arbitrary lifestyle score was given to each subject. RESULTS: No perioperative complications were observed. Percent excess weight loss (%EWL) was 59 +/- 15 at 2 years and 56 +/- 16 at 3 years, and then progressive regain occurred; at 5 years %EWL was 46 +/- 22 and at 10 years 40 +/- 27. Spearman rank test failed to demonstrate any correlation between weight loss at 5 years and patient data, except with lifestyle score (Spearman r = 0.8548, p < .0001). Current mean age is 31 +/- 7 years. CONCLUSION: BPD has to be considered for its value in prolonging and qualitatively improving the PWS patient's life.

Adult↗

PubMed2001

[Measures of specific absorption rate (SAR) in microwave hyperthermic oncology and the influence of the dynamic bolus on clinical practice].

AIM: The bolus (silicon + deionized water) is used in order to achieve a good electromagnetic match between the biological tissue and the applicator surface and to locally modify the skin temperature, to regulate it based on the patient's sensitivity. Therefore, it is very important to know the electromagnetic power deposition and how the bolus can induce a variation in the thermal map, both superficially and deeply. The aim of this study is to evaluate the applicator characteristics in the same conditions as those indicated by the ESHO guidelines for clinical practice and to investigate the penetration depth in the absence and in the presence of a very effective circulating bolus. The first condition is used by the manufacturer to characterize MW applicator while the second condition is used by medical equipes delivering HT treatments. MATERIAL AND METHODS: The specific absorption rate (SAR) generated by a microwave planar applicator (H2, CFMA, Istok,Russia) operating at 433 MHz connected with the hyperthermic equipment ALBA (Restek, Italy) was studied in a muscle-equivalent polyacrilamide phantom. IsoSAR lines were detected on a liquid crystal sheet with a video camera. Images analysis was performed using the graphic software Paint Shop Pro 6. This method allows to evaluate PD in the phantom under the plane of MW applicator. The hyperthermic equipment ALBA is used in the Radiotherapy Unit of the Mauriziano Umberto I Hospital in Turin for both oncologic and psychiatric treatments. RESULTS AND DISCUSSION: The actual pattern of measured SAR mainly depends on the applicator and the phantom characteristics, but also the thickness and the efficiency of the bolus inserted between the applicator and the patient's skin have been shown to affect the results. In this study the penetration depth was measured on 5 applicator sections both with non circulating bolus (static) and with circulating bolus (dynamic). The penetration depth is reduced with the dynamic bolus with respect to the static bolus in all sections, and specifically: in section I it is reduced from 19.46 +/- 1.49 mm to 17.22 +/- 0.71 mm; in section II from 38.17 +/- 4.77 mm to 26.91 +/- 1.48 mm; in section III from 39.81 +/- 3.24 mm to 30.38+/- 4.56 mm; in section IV from 42.12 +/- 1.67 mm to 33.11 +/- 1.89 mm; and finally in section V from 39.83 +/- 4.14 mm to 31.064 +/- 1.57 mm. The above reduction ranges between 11.5 and 29 % with an average value of 21.64 % Our results suggest that different conditions at the interface between bolus and phantom resulting from the use of a dynamic or static bolus produce considerable changes on the heated volume dimension and on the SAR local pattern. The effect of the convective heat losses due to the circulating bolus' assessed by our measurements is not negligible and should be taken into account when evaluating the SAR distribution before clinical treatments. CONCLUSIONS: To disregard the heat losses due to a circulating bolus in MW applicator characterization can severely affect the SAR estimation. This may have serious consequences on clinical applications, since the temperature in the heated lesion can be lower than expected, and the clinical effectiveness of the therapeutical session can be therefore severely reduced. Since at the moment inexpensive and accurate non-invasive temperature monitoring systems are not available, a sound knowledge of the PD of the MW applicator is of primary importance for clinical applications and for a treatment plan allowing to deliver customized treatment to each patient.

Absorption↗

PubMed2000

Differential role of caspase-8 and BID activation during radiation- and CD95-induced apoptosis.

Activation of the CD95 death receptor as well as ionizing radiation induces apoptotic cell death in human lymphoma cells. The activation of caspases is a hallmark of apoptosis induction irrespective of the apoptotic trigger. In contrast to death receptor signaling, the exact mechanisms of radiation-induced caspase activation are not well understood. We provide evidence that both, radiation and CD95 stimulation, induce the rapid activation of caspase-8 and BID followed by apoptosis in Jurkat T-cells. To analyse the relative position of caspase-8 within the apoptotic cascade we studied caspase activation and apoptosis in Jurkat cells overexpressing Bcl-2 or Bcl-xL. Caspase-8 activation, pro-apoptotic BID cleavage and apoptosis in response to radiation were abrogated in these cells, while the responses to CD95 stimulation were only partially attenuated by overexpression of Bcl-2 family members. In parallel, the breakdown of the mitochondrial transmembrane potential (DeltaPsim) in response to radiation was inhibited by overexpression of Bcl-2/Bcl-xL Jurkat cells genetically deficient for caspase-8 were found to be completely resistant towards CD95. However, radiation-induced apoptotic responses in caspase-8-negative cells displayed only a modest reduction. We conclude that ionizing radiation activates caspase-8 and BID downstream of mitochondrial damage suggesting that, in contrast to CD95, both events function as executioners rather than initiators of the apoptotic process.

Apoptosis↗

PubMed2000

Risperidone in idiopathic and symptomatic dystonia: preliminary experience.

Risperidone is a heterocyclic neuroleptic with prominent antiserotoninergic (5HT2) as well as antidopaminergic (D2) activity. We studied the efficacy of risperidone in the treatment of idiopathic and symptomatic dystonias in seven patients using the Fahn and Marsden rating scale for torsion dystonia before and after four weeks of treatment (2-6 mg/day). The twisting and involuntary movements with abnormal postures decreased in all the patients treated, with a statistically significant mean improvement (41%; p = 0.009, CI 95%). Our results suggest that risperidone is useful in idiopathic and symptomatic dystonia.

Adolescent↗

PubMed2000

Anterior tension-free repair of recurrent inguinal hernia under local anesthesia: a 7-year experience in a teaching hospital.

OBJECTIVE: To describe a 7-year experience with recurrent inguinal hernia repair performed mainly with tension-free mesh or plug technique under local anesthesia through the anterior approach, and to evaluate the safety and effectiveness of this method of treatment. METHODS: One hundred forty-five elective and 1 emergency herniorrhaphies for recurrent groin hernia were performed in 141 subjects (134 men and 7 women) with a mean age of 65 years (range 30-89). Concomitant medical and surgical problems were present in 73% and 8% of subjects, respectively. In 28 instances, the relapsed hernia had already been operated on once or twice for recurrence. A traditional hernioplasty had been previously performed in the vast majority of cases (136). Tension-free mesh or plug techniques through an anterior approach under local anesthesia were performed in 144 reoperations. Preperitoneal mesh repair and general or spinal anesthesia were used in all but one case when herniorrhaphy was performed during simultaneous operations. RESULTS: Mean hospital stay after surgery was 1.5 days (range 3 hours-14 days). No perioperative deaths occurred in this series. General complications were one case of acute intestinal bleeding and two cases of urinary retention. Local complications consisted of eight (5.5%) minor complications and one case of orchitis (0.7%) followed by testicular atrophy. In no instance was postoperative neuralgia or chronic pain reported. Two re-recurrences occurred. CONCLUSIONS: Given the low complication rate in this and other reported series and the absence of surgical or general complications described after preperitoneal open or laparoscopic repair and after general and spinal anesthesia, anterior mesh repair under local anesthesia seems to be a low-cost surgical technique that can be safely and effectively used even in a teaching hospital for the treatment of the majority of patients with recurrent groin hernias.

Adult↗

PubMed2000

Energy and nitrogen absorption after biliopancreatic diversion.

BACKGROUND: The strict long-term weight maintenance in good nutritional conditions observed after biliopancreatic diversion (BPD) needs to be explained. MATERIALS AND METHODS: 15 operated subjects were maintained at an isoenergetic and isonitrogenic diet as similar as possible to their usual diet. Apparent absorption (AA) of energy, fat, nitrogen and calcium was calculated subtracting the fecal content, measured directly, from the oral intake, derived from tables. The alimentary protein absorption was directly determined by I125 albumin oral administration. RESULTS: Mean AA for energy and fat was 57% and 32%, respectively; AAs were unrelated as absolute value and negatively associated as percent of the intake with the energy and fat intake. I125 intestinal absorption was 73%, while nitrogen percent AA was 57%, indicating higher than normal loss of endogenous nitrogen. Calcium AA was 551 mEq/day, 26% of the intake. A positive correlation between nitrogen and calcium AA as absolute values and alimentary intake was observed, while there was no correlation when AA were considered as per cent of the intake. CONCLUSIONS: For energy and fat, an increase in intake corresponds to an increase in percent malabsorption, so that the absolute amount absorbed tends to remain constant, accounting for the excellent weight maintenance observed following BPD. This was confirmed by a long-term hypernutrition study after BPD. On the contrary, for nitrogen and calcium, the percent absorption tends to remain constant when intake varies, so that an increase in alimentary intake results in an increased absolute amount absorbed.

Adult↗

PubMed1999

The tyrosine kinase lck is required for CD95-independent caspase-8 activation and apoptosis in response to ionizing radiation.

Induction of apoptosis is a hallmark of cytostatic drug and radiation-induced cell death in human lymphocytes and lymphoma cells. However, the mechanisms leading to apoptosis are not well understood. We provide evidence that ionizing radiation induces a rapid activation of caspase-8 (FLICE) followed by apoptosis independently of CD95 ligand/receptor interaction. The radiation induced cleavage pattern of procaspase-8 into mature caspase-8 resembled that following CD95 crosslinking and resulted in cleavage of the proapoptotic substrate BID. Overexpression of dominant-negative caspase-8 interfered with radiation-induced apoptosis. Caspase-8 activation by ionizing radiation was not observed in cells genetically defective for the Src-like tyrosine kinase Lck. Cells lacking Lck also displayed a marked resistance towards apoptosis induction upon ionizing radiation. After retransfection of Lck, caspase-8 activation and the capability to undergo apoptosis in response to ionizing radiation was restored. We conclude that radiation activates caspase-8 via an Lck-controlled pathway independently of CD95 ligand expression. This is a novel signaling event required for radiation induced apoptosis in T lymphoma cells.

Antibodies↗

PubMed1999

SiMa, a new neuroblastoma cell line combining poor prognostic cytogenetic markers with high adrenergic differentiation.

We describe the establishment and characterization of a new neuroblastoma (Nb) cell line, SiMa, carrying the major recurrent chromosome changes associated with poor prognosis Nb, including amplification of N-MYC by formation of double minutes (dmin), der(1)t(1;17)(p35;q12) and der(22)t(17;22)(q22;p13), and loss of chromosome 11, documented at both initiation and late passage. In contrast to these cytogenetic stigmata of poor prognosis, analysis of catecholamine synthesis by high pressure liquid chromatography (HPLC) measurement revealed an advanced degree of adrenergic differentiation with high rates of 3,4-Dihydroxyphenylalanine (DOPA), noradrenaline, homovanillic acid (HVA), and vanillylmandelic acid (VMA) production. Contrastingly advanced differentiation and poor prognostic genetic markers combine to render SiMa a unique instrument for investigating the pathology and therapy of Nb.

Cell Differentiation↗

PubMed1999

Ionizing radiation and the activation of caspase-8 in highly apoptosis-sensitive lymphoma cells.

PURPOSE: Ionizing radiation induces apoptosis in human lymphoma cells. However, the participating molecules and their exact order is unknown. Caspases are reported as essential cysteine proteases required for the activation and execution of programmed cell death. The activator caspase-8 is a key component of the CD95/Fas/APO-1 death receptor-triggered apoptosis pathway. Since contributing molecules for radiation-induced apoptosis and their exact order have not been analyzed in greater detail, the involvement of caspase-8 for radiation-induced apoptosis in human lymphoma cell lines was studied. MATERIALS AND METHODS: Apoptosis induction by CD95 stimulation and ionizing radiation was analyzed in eight different cell lines. In parallel, Western blotting tested activation of caspase-8. RESULTS: Activation of caspase-8 by ionizing radiation occurred in five cell lines and was associated with high apoptosis sensitivity. Caspase-8 activation and apoptosis was detectable in cells resistant to CD95 stimulation, so suggesting separate pathways for CD95 and radiation-induced caspase-8 activation. CONCLUSION: The activator caspase-8 is activated during radiation-induced cell death and, in some cases, ionizing radiation induces caspase-8 independently of the CD95 system.

Apoptosis↗