[en] IFA-514 irradiation test was performed in Halden Reactor (HBWR) in Norway to study the irradiation performance of LWR MOX fuels. The fuel specifications for this irradiation test were decided in accordance with those of BWR 8x8 fuels, and plutonium content of MOX fuels was set to be 5.8 wt.%. Six MOX fuel rods, of which parameters were pellet geometry (solid or annular) and surface roughness (grinded or as-sintered), were irradiated to the assembly average burn-up of ∼45 GWd/t, and the instrument data during irradiation, i.e. cladding elongation, fuel stack elongation, fuel center temperature, and rod inner pressure, were obtained, and subsequent post-irradiation examinations provided the following results: No remarkable corrosion and deformation was observed on the irradiated fuel rods. The averaged irradiation growth was 0.13%, no nodular corrosion was observed, and the maximum thickness of oxide layer was ∼60 μm. The FP gas release rate was ∼21%. The irradiation for three of six fuel rods irradiated in IFA-514 irradiation tests were continued to the assembly average burn-up of ∼56 GWd/t in IFA-565 irradiation tests, and the results of this irradiation test were as follows: No remarkable corrosion and deformation was observed on the irradiated fuel rods. The FP gas release behavior of LWR MOX fuels was similar to that of BWR UO₂ and ATR MOX fuels, and no difference was confirmed in the FP gas release behavior. Also FP gas release rate of annular pellets (∼13%) was lower than that of solid ones (∼16%). No remarkable difference in the effect of pellet geometry, i.e. solid and annular, on PCMI behavior was observed in any fuel rod from the instrument data of fuel stack elongation and the results of ceramography. However, the reduction of cladding diameter change in pellet geometry is expected since the cladding diameter change of annular fuel rods was less than that of solid ones. The disappearance of as-fabricated granular boundaries during irradiation is expected to cause the reduction of pellet swelling deformation. The cladding elongation was ∼0.15%, and the irradiation growth behavior was almost similar to that of BWR UO₂ and ATR MOX fuel rods. (author)

[en] The purpose of this conference was to review and discuss the research carried out at GANIL and the related activities at similar facilities around the world. The experiments performed in the first 4 years of operation of the Spiral facility as well as its future developments were largely discussed. Several sessions of the workshop were also devoted to the presentation and the discussion of the future physics opportunities with Spiral-2 and needed technical developments. The presentations have been organized into 13 topics: 1) nuclear astrophysics, 2) heavy and super-heavy nuclei, 3) multifragmentation, 4) structure and spectroscopy, 5) nuclear structure theories, 6) towards the drip-lines, 7) interdisciplinary sciences, 8) neutron-deficient nuclei, 9) gamma spectroscopy, 10) worldwide physics, 11) nuclear moments, 12) DESIR, and 13) nuclear data. This document gathers the slides of the presentations as well as the posters of the poster session

[en] SMART NPP(Nuclear Power Plant) has been developed for duel purpose, electricity generation and energy supply for seawater desalination. The objective of this project IS to design the reactor system of SMART pilot plant(SMART-P) which will be built and operated for the integrated technology verification of SMART. SMART-P is an integral reactor in which primary components of reactor coolant system are enclosed in single pressure vessel without connecting pipes. The major components installed within a vessel includes a core, twelve steam generator cassettes, a low-temperature self pressurizer, twelve control rod drives, and two main coolant pumps. SMART-P reactor system design was categorized to the reactor coe design, fluid system design, reactor mechanical design, major component design and MMIS design. Reactor safety -analysis and performance analysis were performed for developed SMART=P reactor system. Also, the preparation of safety analysis report, and the technical support for licensing acquisition are performed

[en] The present study was conducted to evaluate the potency of Nigella sativa freshly crushed seeds (0.42 g/ kg body weight) or oil (2.5 ml/kg body weight) for preventing tumor induction through exposure of rats to a common pollutant (1,4- Dioxane) as a promoter under condition of the presence of an initiator (N-nitrosodiethylamine). The antitumor effect was evaluated alone or in combination with low doses of irradiation as a route of cancer treatment. Female Swiss albino rats were administrated orally twice weekly with Nigella sativa before and during exposure of rats to the carcinogenic compounds. Animals were exposed to 3 doses of radiation (3 Gy/ dose) day after day 2 weeks before the end of the experiment. The animals were scarified after one week of radiation. Homocysteine,'glutathione, lipid peroxide, GGT activity, nitric oxide, total protein, albumin and bilirubin levels were estimated in blood after 7 and 12 months from the start of the experiment. Rats injected with the carcinogenic compounds showed marked elevation in homocysteine, GGT activity, nitric oxide, bilirubin and lipid peroxide levels accompanied by a significant decrease in glutathione, total proteins and albumin levels. Pretreatment with Nigella sativa alone or combined with γ- irradiation potentially reversed the investigated parameters. Moreover, Nigella sativa significantly suppressed the growth of the tumor and efficiently produced synergistic effect with γ-irradiation. Therefore, Nigella sativa may be a good candidate to prevent tumor induction and so, it is advicable to use freshly crushed seeds during irradiation treatment in cancer patients as they gave more effective protection than the oil extract.

[en] Carboplatin/paclitaxel is the chemotherapy of choice for advanced ovarian cancer, both in first line and in platinum-sensitive recurrence. Although a significant proportion of patients have some neurotoxicity during treatment, the long-term outcome of chemotherapy-induced neuropathy has been scantly studied. We retrospectively assessed the prevalence of residual neuropathy in a cohort of patients in clinical remission after first-line carboplatin/paclitaxel for advanced ovarian cancer. 120 patients have been included in this study (101 participating in a multicentre phase III trial evaluating the efficacy of consolidation treatment with topotecan, and 19 treated at the National Cancer Institute of Naples after the end of the trial). All patients received carboplatin (AUC 5) plus paclitaxel (175 mg/m²) every 3 weeks for 6 cycles, completing treatment between 1998 and 2003. Data were collected between May and September 2004. Residual sensory and motor neurotoxicity were coded according to the National Cancer Institute – Common Toxicity Criteria. 55 patients (46%) did not experience any grade of neurological toxicity during chemotherapy and of these none had signs of neuropathy during follow-up. The other 65 patients (54%) had chemotherapy-induced neurotoxicity during treatment and follow-up data are available for 60 of them. Fourteen out of 60 patients (23%) referred residual neuropathy at the most recent follow-up visit, after a median follow up of 18 months (range, 7–58 months): 12 patients had grade 1 and 2 patients grade 2 peripheral sensory neuropathy; 3 patients also had grade 1 motor neuropathy. The remaining 46/60 patients (77%) had no residual neuropathy at the moment of interview: recovery from neurotoxicity had occurred in the first 2 months after the end of chemotherapy in 22 (37%), between 2 and 6 months in 15 (25%), or after more than 6 months in 9 patients (15%). Considering all 120 treated patients, there was a 15% probability of persistent neurological toxicity 6 months after the end of chemotherapy. A significant proportion of patients with advanced ovarian cancer treated with first-line carboplatin/paclitaxel suffer long-term residual neuropathy. This issue should be carefully taken into account before considering re-treatment with the same agents in sensitive recurrent disease

[en] The anticancer drug Ukrain (NSC-631570) which has been specified by the manufacturer as semisynthetic derivative of the Chelidonium majus L. alkaloid chelidonine and the alkylans thiotepa was reported to exert selective cytotoxic effects on human tumour cell lines in vitro. Few clinical trials suggest beneficial effects in the treatment of human cancer. Aim of the present study was to elucidate the importance of apoptosis induction for the antineoplastic activity of Ukrain, to define the molecular mechanism of its cytotoxic effects and to identify its active constituents by mass spectrometry. Apoptosis induction was analysed in a Jurkat T-lymphoma cell model by fluorescence microscopy (chromatin condensation and nuclear fragmentation), flow cytometry (cellular shrinkage, depolarisation of the mitochondrial membrane potential, caspase-activation) and Western blot analysis (caspase-activation). Composition of Ukrain was analysed by mass spectrometry and LC-MS coupling. Ukrain turned out to be a potent inducer of apoptosis. Mechanistic analyses revealed that Ukrain induced depolarisation of the mitochondrial membrane potential and activation of caspases. Lack of caspase-8, expression of cFLIP-L and resistance to death receptor ligand-induced apoptosis failed to inhibit Ukrain-induced apoptosis while lack of FADD caused a delay but not abrogation of Ukrain-induced apoptosis pointing to a death receptor independent signalling pathway. In contrast, the broad spectrum caspase-inhibitor zVAD-fmk blocked Ukrain-induced cell death. Moreover, over-expression of Bcl-2 or Bcl-x_L and expression of dominant negative caspase-9 partially reduced Ukrain-induced apoptosis pointing to Bcl-2 controlled mitochondrial signalling events. However, mass spectrometric analysis of Ukrain failed to detect the suggested trimeric chelidonine thiophosphortriamide or putative dimeric or monomeric chelidonine thiophosphortriamide intermediates from chemical synthesis. Instead, the Chelidonium majus L. alkaloids chelidonine, sanguinarine, chelerythrine, protopine and allocryptopine were identified as major components of Ukrain. Apart from sanguinarine and chelerythrine, chelidonine turned out to be a potent inducer of apoptosis triggering cell death at concentrations of 0.001 mM, while protopine and allocryptopine were less effective. Similar to Ukrain, apoptosis signalling of chelidonine involved Bcl-2 controlled mitochondrial alterations and caspase-activation. The potent proapoptotic effects of Ukrain are not due to the suggested 'Ukrain-molecule' but to the cytotoxic efficacy of Chelidonium majus L. alkaloids including chelidonine

[en] CEA is a tumor-associated antigen abundantly expressed on several cancer types, including those naturally refractory to chemotherapy. The selection and characterization of human anti-CEA single-chain antibody fragments (scFv) is a first step toward the construction of new anticancer monoclonal antibodies designed for optimal blood clearance and tumor penetration. The human MA39 scFv, selected for its ability to recognize a CEA epitope expressed on human colon carcinomas, was first isolated from a large semi-synthetic ETH-2 antibody phage library, panned on human purified CEA protein. Subsequently, by in vitro mutagenesis of a gene encoding for the scFv MA39, a new library was established, and new scFv antibodies with improved affinity towards the CEA cognate epitope were selected and characterized. The scFv MA39 antibody was affinity-maturated by in vitro mutagenesis and the new scFv clone, E8, was isolated, typed for CEA family member recognition and its CEACAM1, 3 and 5 shared epitope characterized for expression in a large panel of human normal and tumor tissues and cells. The binding affinity of the scFv E8 is in a range for efficient, in vivo, antigen capture in tumor cells expressing a shared epitope of the CEACAM1, 3 and 5 proteins. This new immunoreagent meets all criteria for a potential anticancer compound: it is human, hence poorly or not at all immunogenic, and it binds selectively and with good affinity to the CEA epitope expressed by metastatic melanoma and colon and lung carcinomas. Furthermore, its small molecular size should provide for efficient tissue penetration, yet give rapid plasma clearance

[en] Isotope-coded affinity tag (ICAT) tandem mass spectrometry (MS) allows for qualitative and quantitative analysis of paired protein samples. We sought to determine whether ICAT technology could quantify and identify differential expression of tumor-specific proteins in nipple aspirate fluid (NAF) from the tumor-bearing and contralateral disease-free breasts of patients with unilateral early-stage breast cancer. Paired NAF samples from 18 women with stage I or II unilateral invasive breast carcinoma and 4 healthy volunteers were analyzed using ICAT labeling, sodium dodecyl sulfate-polyacrylamide gel (SDS-PAGE), liquid chromatography, and MS. Proteins were identified by sequence database analysis. Western blot analysis of NAF from an independent sample set from 12 women (8 with early-stage breast cancer and 4 healthy volunteers) was also performed. 353 peptides were identified from tandem mass spectra and matched to peptide sequences in the National Center for Biotechnology Information database. Equal numbers of peptides were up- versus down-regulated. Alpha2HS-glycoprotein [Heavy:Light (H:L) ratio 0.63] was underexpressed in NAF from tumor-bearing breasts, while lipophilin B (H:L ratio 1.42), beta-globin (H:L ratio 1.98), hemopexin (H:L ratio 1.73), and vitamin D-binding protein precursor (H:L ratio 1.82) were overexpressed. Western blot analysis of pooled samples of NAF from healthy volunteers versus NAF from women with breast cancer confirmed the overexpression of vitamin D-binding protein in tumor-bearing breasts. ICAT tandem MS was able to identify and quantify differences in specific protein expression between NAF samples from tumor-bearing and disease-free breasts. Proteomic screening techniques using ICAT and NAF may be used to find markers for diagnosis of breast cancer

[en] Germline mutations in RET are responsible for multiple endocrine neoplasia type 2 (MEN2), an autosomal dominantly inherited cancer syndrome that is characterized by medullary thyroid carcinoma (MTC), pheochromocytoma, and parathyroid hyperplasia/adenoma. Recent studies suggest a 'second hit' mechanism resulting in amplification of mutant RET. Somatic VHL gene alterations are implicated in the pathogenesis of MEN2 pheochromocytomas. We hypothesized that somatic VHL gene alterations are also important in the pathogenesis of MEN2-associated MTC. We analyzed 6 MTCs and 1 C-cell hyperplasia (CCH) specimen from 7 patients with MEN2A and RET germline mutations in codons 609, 618, 620, or 634, using microdissection, microsatellite analysis, phosphorimage densitometry, and VHL mutation analysis. First, we searched for allelic imbalance between mutant and wild-type RET by using the polymorphic markers D10S677, D10S1239, and RET on thyroid tissue from these patients. Evidence for RET amplification by this technique could be demonstrated in 3 of 6 MTCs. We then performed LOH analysis using D3S1038 and D3S1110 which map to the VHL gene locus at 3p25/26. VHL gene deletion was present in 3 MTCs. These 3 MTCs also had an allelic imbalance between mutant and wild-type RET. Mutation analysis of the VHL gene showed a somatic frameshift mutation in 1 MTC that also demonstrated LOH at 3p25/26. In the 2 other MTCs with allelic imbalance of RET and somatic VHL gene deletion, no somatic VHL mutation could be detected. The CCH specimen did neither reveal RET imbalance nor somatic VHL gene alterations. These data suggest that a RET germline mutation is necessary for development of CCH, that allelic imbalance between mutant and wild-type RET may set off tumorigenesis, and that somatic VHL gene alterations may not play a major role in tumorigenesis of MEN2A-associated MTC

[en] In previous analyses we identified therapy-induced upregulation of the CDK inhibitor p21^CIP/WAF-1 and consequently decreased tumor cell proliferation or loss of Bax as adverse factors for survival in rectal cancer treated with radiochemotherapy. Here, we address the individual role of p53 and its transcriptional targets, p21^CIP/WAF-1 and Bax, on apoptosis induced by individual components of multimodal anticancer therapy, i.e. 5-fluorouracil (5-FU), ionising γ-radiation (IR) and heat shock/hyperthermia. We analysed tumor samples 66 patients with rectal carcinoma treated by a neoadjuvant approach with radiochemotherapy ± heat shock/hyperthermia for the expression and mutation of p53 and the expression of p21^CIP/WAF-1 and Bax. These data were correlated with the tumor response. The functional relevance of p53, p21^CIP/WAF-1 and Bax was investigated in isogeneic HCT116 cell mutants treated with 5-FU, IR and heat shock. Rectal carcinoma patients who received an optimal heat shock treatment showed a response that correlated well with Bax expression (p = 0.018). Local tumor response in the whole cohort was linked to expression of p21^CIP/WAF-1 (p < 0.05), but not p53 expression or mutation. This dichotomy of p53 pathway components regulating response to therapy was confirmed in vitro. In isogeneic HCT116 cell mutants, loss of Bax but not p53 or p21^CIP/WAF-1 resulted in resistance against heat shock. In contrast, loss of p21^CIP/WAF-1 or, to a lesser extent, p53 sensitized predominantly for 5-FU and IR. These data establish a different impact of p53 pathway components on treatment responses. While chemotherapy and IR depend primarily on cell cycle control and p21, heat shock depends primarily on Bax. In contrast, p53 status poorly correlates with response. These analyses therefore provide a rational approach for dissecting the mode of action of single treatment modalities that may be employed to circumvent clinically relevant resistance mechanisms in rectal cancer