Multimodality palliative treatment of 111In-pentetreotide negative/123I-MIBG positive metastatic carcinoid - a case report

Patients with carcinoid tumours frequently present with metastatic disease. There are only a few therapeutic options for these patients, and the main goal of palliative treatment is to reduce symptoms and thus to improve quality of life. Current therapy includes surgical resection, hepatic artery embolisation, chemotherapy and somatostatin analogue treatment; however, all these options have limitations. It seems probable that therapeutic modalities based on radiopharmaceuticals may provide better therapy, not only in relation to symptom reduction but may also improve patient survival. In this case report we present a 46-year-old woman with a symptomatic carcinoid, who at the time of diagnosis had liver and abdominal lymph node metastases, the primary tumour being located in the terminal ileum. 111In-pentetreotide scanning was negative, whereas 123I-MIBG scanning showed high avidity in the tumour tissue. After right hemicolectomy, two courses of 131I-MIBG treatment were given (12.95 GBq and 12 GBq, respectively). After the second dose of 131I-MIBG temporary pancytopenia was present. Octreotide therapy was given empirically only for a short time and was stopped because of drug intolerance. The patient underwent tricuspid and pulmonary valve replacement because of her carcinoid heart disease, followed by two courses of embolisation of liver metastases. While 131I-MIBG therapy reduced the patient’s symptoms of flushing and diarrhoea, there has not yet been any effect on tumour response or 5-HIAA production. This case illustrates the multimodality and multidisciplinary approach to such patients.U chorych z rakowiakiem często występują przerzuty. W takich przypadkach istnieje niewiele opcji terapeutycznych. Głównym celem leczenia paliatywnego jest złagodzenie objawów i poprawienie jakości życia. Dostępne obecnie metody terapii obejmują chirurgiczną resekcję zmian nowotworowych, embolizację tętnicy wątrobowej, chemioterapię i stosowanie analogów somatostatyny. Jednak wszystkie te metody mają ograniczenia. Wydaje się, że stosując techniki radiofarmakologiczne można uzyskać najlepsze rezultaty, nie tylko pod względem zmniejszenia objawów, ale również wydłużenia okresu przeżycia. W niniejszej pracy autorzy opisują przypadek 46-letniej kobiety z objawowym rakowiakiem, u której w chwili rozpoznania choroby stwierdzono przerzuty do węzłów wątroby oraz brzusznych węzłów chłonnych. Guz pierwotny znajdował się w końcowym odcinku jelita krętego. W badaniu radioizotopowym z użyciem 111In-pentetreotydu nie wykazano gromadzenia radioznacznika, natomiast w scyntygrafii z użyciem 123I-MIBG stwierdzono zwiększony wychwyt znacznika przez tkanki guza. Po wykonaniu prawostronnej hemikolektomii zastosowano dwa cykle terapii 131I-MIBG (odpowiednio: 12,95 i 12 GBq). Po drugiej dawce 131I-MIBG wystąpiła okresowa pancytopenia. Zastosowano empirycznie terapię okreotydem, jednak przerwano ją po krótkim czasie z uwagi na nietolerancję leku. Chora przebyła zabieg wymiany zastawek trójdzielnej i płucnej z powodu rakowiakowej choroby serca, a następnie 2-krotną embolizację przerzutów wątrobowych. Chociaż terapia 131I-MIBG spowodowała złagodzenie objawów, napadowego przekrwienia skóry i biegunki, jednak nie zaobserwowano zmniejszenia guza ani ograniczenia produkcji 5-HIAA. Opisany przypadek jest przykładem multimodalnego i wielodyscyplinarnego leczenia rakowiaka

Highly effective liquid and solid phase extraction methods to concentrate radioiodine isotopes for radioiodination chemistry

Radioactive iodine isotopes play a pivotal role in radiopharmaceuticals. Large-scale production of multi-patient dose of radioiodinated nuclear medicines requires high concentration of radioiodine. We demonstrate that tetrabutylammonium chloride and methyltrioctylamonium chloride are effective phase transfer reagents to concentrate iodide-124, iodide-125 and iodide-131 from the corresponding commercial water solutions. The resulting concentrated radioiodide, in the presence of either phase transfer reagent, does not hamper the chemical reactivity of aqueous radioiodide in the copper (II)-mediated one-pot three-component click chemistry to produce radioiodinated iodotriazoles

Genetic differentiation among host-associated Alebra leafhoppers (Hemiptera: Cicadellidae)

The limited importance ascribed to sympatric speciation pro cesses via host race formation is partially due to the few cases of host races that have been reported among host populations. This work sheds light on the taxonomy of Alebra leafhoppers and examines the possible existence of host races among host-associated populations. The species of this genus show varying degrees of host association with deciduous trees and shrubs and, frequently, host popu lations of uncertain taxonomic status coexist and occasion ally become pests. Allozyme electrophoresis of 21 Greek populations including sympatric, local and geographically distant samples collected on 13 different plant species, show that they represent at least five species: A. albostriella Falle´n, A. viridis (Rey) (sensu Gillham), A. wahlbergi Bo Keywords: host races; leafhoppers; sympatric speciation; sibling species; allozymes; Alebra Introduction Sympatric speciation is a controversial subject in evol utionary biology (see Mayr, 1963; Futuyma and Mayer, 1980; Paterson, 1981; Via, 2001). One of the reasons for this controversy is that sympatric speciation seems to be an extremely rare phenomenon occurring only in very few groups of taxa, represented chiefly by phytophagous insects (Tauber and Tauber, 1977; Menken, 1981; Wood, 1993; Emelianov et al, 1995; Via, 1999; Finchak et al, 2000; Craig et al, 2001). The limited number of reported cases among organisms with sexual reproduction can be at least partially attributed to the fact that taxa undergoing sympatric speciation events must fulfill very restrictive biological and ecological requirements. Most sympatric speciation models demand that there is intraspecific genetic variation in traits that differentially affect the fitness of individuals that colonise new habitats or hosts (Dieckman and Doebeli, 1999; Hawthorne and Via, 2001 but see Higashi et al, 1999 and Takimoto et al, 2000). They assume that selection acting on these traits can prevent genetic exchange between populations (Bush, 1975; Tauber and Tauber, 1977; Diehl and Bush, 1989). In phytophagous insects, this means that host pref erences must be genetically determined and mating should occur on the host (Bush, 1975; Diehl and Bush, Correspondence: D Aguin-Pombo, Department of Biology, University of Madeira, Campus Universitario da Penteada, 9000 Funchal, Madeira, Portugal. E-mail: aguin uma.pt Received 12 December 2000; accepted 13 December 2001 heman and two new species. Of these, one is associated to Quercus frainetto and other is specific to Crataegus spp. Significant genetic differences among sympatric and local host populations were found only in A. albostriella, between populations on Turkey oak, beech and common alder. It is suggested that the last two of these host populations may represent different host races. The results show that both the host plant and geographical distance affect the patterns of differentiation in the genus. The formation of some spec ies seems to have been the result of allopatric speciation events while, for others, their origin can be equally explained either by sympatric or allopatric speciation.info:eu-repo/semantics/publishedVersio

Mdm2-SNP309 polymorphism in prostate cancer: no evidence for association with increased risk or histopathological tumour characteristics

The search for inherited cancer susceptibility factors is a major focus of epidemiologic cancer studies. Analyses of single-nucleotide polymorphisms (SNP) in a variety of genes revealed a correlation between a specific allele variant and cancer predisposition. Human mouse double-minute 2 protein (Mdm2) is a cellular E3 ligase capable of ubiquitination and degradation of p53. Therefore, Mdm2 is a crucial factor of cell cycle control and cell survival. The Mdm2 promoter SNP309 was shown to increase Mdm2 expression and can, thereby, inhibit the p53 pathway. This SNP was found to be associated with increased risk and early onset of various malignancies. For prostate cancer no studies are reported to date. In a case–control study we determined the distribution of the Mdm2 SNP309 in 145 male subjects with prostate cancer and in 124 male controls without any malignancy using RFLP analysis. Cases and controls showed a similar distribution of the SNP (P=0.299). Genotype distribution showed neither an association with histopathological characteristics of the tumours nor with prognosis. Age at disease onset was also not modified by the SNP. This first study of the Mdm2 SNP309 in prostate cancer patients suggests no correlation between a certain allelic variant and an increased cancer risk

On the simple random-walk models of ion-channel gate dynamics reflecting long-term memory

Several approaches to ion-channel gating modelling have been proposed. Although many models describe the dwell-time distributions correctly, they are incapable of predicting and explaining the long-term correlations between the lengths of adjacent openings and closings of a channel. In this paper we propose two simple random-walk models of the gating dynamics of voltage and Ca2+-activated potassium channels which qualitatively reproduce the dwell-time distributions, and describe the experimentally observed long-term memory quite well. Biological interpretation of both models is presented. In particular, the origin of the correlations is associated with fluctuations of channel mass density. The long-term memory effect, as measured by Hurst R/S analysis of experimental single-channel patch-clamp recordings, is close to the behaviour predicted by our models. The flexibility of the models enables their use as templates for other types of ion channel

Somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine tumours, current aspects and new perspectives

Gastroenteropancreatic neuroendocrine tumours (GEP NETs) are rare tumours that present many clinical features

Effect of polyamines on the nicotinic ACh receptor

Introduction. In recent years, interactions of various polyamines with a number of ionotropic receptors have been reported. Such interactions can be either negative (inhibition) or positive (potentiation). It is proposed that hydrophilic polyamines act as open-channel blockers and bind sites deeply in the ion channel pore. Hydrophobic polyamines are believed to act in the shallower part of the pore. There has been cause to think that polyamines with two aromatic moieties block the nicotinic acetylcholine (nACh) receptor by adopting a U-shaped conformation, that is, a conformation in which the long positively charged polyamine chain enters the ion channel while aromatic moieties interact with extracellular parts of α-subunits. Objective. Our goal was to determine whether and how changes in the structure of methoctramine (a polyamine with two aromatic moieties) affect the way in which the nACh receptor is blocked. We synthesized derivatives of methoctramine which have a less flexible structure than methoctramine itself and may be less capable of adopting a U-shaped conformation within the ion channel. Materials and method. Whole-cell ACh-induced currents were recorded from mouse i28 satellite cells expanded in culture. Recordings were performed both in the presence and in the absence of polyamines. Results. All tested polyamines applied at a concentration of 5 mM blocked ACh-induced currents. Depending on the number of protonated nitrogen atoms, polyamines decreased the current amplitude and/or increased the decay rate of the current. Conclusions. We propose two possible mechanisms to explain the action of polyamines: desensitization, and displacement of agonist molecules from their binding sites. The impact of the number of protonated nitrogen atoms is discussed