Irathérapie génique anticancéreuse utilisant le NIS : une approche très prometteuse

The symporter Na/iodine (NIS) is a recently discovered membrane protein, recognized to be at the origin of accumulation of iodine in the thyroid, salivary glands, stomach and mammary glands during lactation. If its intrinsic property served as the basis for nuclear imaging and radiotherapy metabolic of differentiated thyroid cancers and their metastases, the cloning of its gene provides a powerful strategy for cytoreductive gene therapy, based on the targeted transfer of this last one in all types of cancer cells. Its expression gives the ability to these cells to accumulate iodine. The aim is to benefit from the advantages of radioiodine therapy (efficiency, reduced side effects) and to optimize the management of thyroid cancer. This approach offers an attractive therapeutic alternative for non-thyroidal cancers, especially in the context of a multimodal approach. Techniques and equipments necessary for the first clinical trials are already existing in the departments of nuclear medicine. The perspectives of clinical application, however, require a better knowledge of the regulation of expression and functionality of NIS. After a review of the biology of NIS, our work aims to recount the results of different tests that have demonstrated the benefits of this approach, its limitations and prospects for its improvement.     

Tumeur du scalp : mode révélateur rare de carcinome vésiculaire thyroïdien

Cutaneous metastases of thyroid follicular carcinoma are rare. A scalp metastasis revealing a thyroid cancer is exceptional. We report the case of a 70 year-old women who presented with a scalp tumor progressively increased. Morphological imaging disclosed an important cutaneous tumor in occipital region with osteolysis. Surgical resection of this tumor was performed and pathology identified a cutaneous metastasis of a thyroid follicular cancer. This case report illustrates a rare presenting sign of thyroid follicular cancer. Cutaneous metastases coexists with other metastases (bone or lung) and means and ominous prognostic factor for the evolution of thyroid follicular cancer.     

Introduction à l’étude du site de Longgupo

The site of Longgupo, discovered in 1984, is located south of the crossing of the Three Gorges of the Yangtze, in the eastern part of Chongqing Province. Situated on the limestone slope of the Miaoyu Valley, three excavation campaigns have been carried out since 1985. The first two seasons took place from 1985–1988 and 1997–1998, directed by W.B. Huang and the last campaign from 2003–2006 by E. Boëda and Y.M. Hou. After the first two campaigns, the presence of several bones, with an estimated age of 1.9 My, notably including a mandible fragment attributed to a hominid² and the discovery of more than 20 lithic artifacts incited not only great interest in the scientific community, but controversy as well since these data contradicted diffusion models of the first hominids out of Africa. Paleoanthropological data often being privileged over other data, including lithic artifacts, the anthropic nature of the site was contested. Yet the few artifacts from the initial excavations irrefutably demonstrate their manufacture by humans, in particular those in exogenous stone. To definitively re-establish the authenticity of this site by applying the latest investigative methods, a new Franco-Chinese campaign was organized. The objective of the 2003–2006 field seasons focused on understanding and analysis of the archaeological data in their geomorphological and stratigraphic contexts.     

Étude préliminaire des industries archaïques de faciès Oldowayen du site de Hummal (El Kowm, Syrie centrale)

The spring site of Hummal is located in Central Syria, near the village of El Kowm between the Euphrates basin and the desert steppe stretching from Palmyra to Deir-ez-Zor. In 1966 the well was noted in a survey as Bir Onusi and a short preliminary study was carried out at the beginning of the 1980s. Since 1997, the Institute for Prehistory and Archaeological Science of the University of Basel has undertaken a complete interdisciplinary research program of this major site under the direction of J.M Le Tensorer, supported by the Swiss National Science Foundation and associated with the Directorate General of Antiquities and Museums of Syria under the direction of S. Muhesen. The site of Hummal is a prominent mound at an artesian spring built out of the sediments, which piled up during the whole Quaternary. Tectonic faults in the bed rock enabled the underlying water in a karstic system to flow out into a dolina, which trapped lacustrine, limnic and aeolian sediments since the Oldest Pleistocene. The impressive stratigraphy – 20 m high – comprises 23 geological units preserving a great number of archaeological levels. It covers an extremely long period of time ranging from the Oldest Palaeolithic (Oldowan) to Upper Palaeolithic (Aurignacian) over more than a million years. This impressive Old and Middle Palaeolithic sequence comprises several layers of Oldowan-like assemblage (23-16), an Acheuleo-Tayacian complex (14-13), five layers of Yabrudian (12-8) at least four levels of Hummalian (7, 6c, 6b, 6a) and a thick sediment complex with 8 Mousterian layers, each of them liable to be subdivided into several sublayers. The lithic industry in the lowest levels of the Hummal sequence, associated with abundant remains of large mammals, can be characterized by non-modified, quite fresh flakes, with, once in a while, traces of use but never bearing intentional retouches. Theses flakes are found with pebble-tools: choppers, chopping-tools, polyhedrons, bolas and core-like artifacts. This assemblage is typical in a broad sense of archaic Palaeolithic whose debitage corresponds to mode 1. From a techno-typological point of view, this industry tallies quite well with the so-called Oldowan stage. It shows remarkable similarities with the oldest assemblages at Ubeidiya but, so far, with no occurrence of bifacial knapping. If the layers 17 and 18 of Hummal relate to this period dating back to 1.6 to 1.2 million years, these levels would be the oldest ones ever found in central Syria. However, as we have no absolute dating at our disposal so far, we will remain careful in assigning a chronological time span for these layers. For this area, from a stratigraphic point of view, the Oldowan levels of Hummal occur before the Acheulean and certainly before the Acheulean sequence of El Meirah (region of El Kowm) which is itself related to the period before Matuyama-Brunhes paleomagnetic reverse. Dating of the lowest sequence of Hummal is underway. If we take into account stratigraphic and techno-typological observations, we assume that the Oldowan-like levels of the site should be older than one million years at least. The sequence of Hummal is one of the largest in the Near-East. Therefore, it can be regarded as a key-site for world prehistory.     

Apport de la fusion d’images tomoscintigraphiques avec la tomodensitométrie X ou l’imagerie par résonance magnétique en pathologie osseuse : expérience du service de médecine nucléaire de Sfax

The aim of our study was to assess the contribution of image fusion of SPECT combined with computed tomography (SPECT-CT) or magnetic resonance imaging (SPECT-MRI) in our daily practice of bone scintigraphy. Seventeen patients underwent a SPECT image fusion, SPECT-CT or MRI in addition to conventional bone scintigraphy. These acquisitions are made separately with images stored in DICOM format. The fusion was operated after a manual coregistration of the images. Results show that in 35.29% of cases, the image fusion allowed to pinpoint the exact location of increased uptake seen on the whole body scan and/or on static images. In 35.29% of cases, the fusion has confirmed a diagnosis doubtful in planar imaging. In five patients, representing 29.41% of cases, the fusion has corrected a diagnosis. In one patient (5.88% of cases), the fusion has eliminated a false positive related to increased uptake visualized on the whole body scan. In two patients (11.11% of cases), the fusion has eliminated false negative of bone scan in one case and of MRI in the other case. Finally, in nine patients (50% of cases), the fusion has influenced the therapeutic management.     

Segmentation d’images synchronisées à la respiration en TEP/TDM : étude sur fantôme

The aim of this study is to evaluate the accuracy of segmentation method by adaptive threshold in gated respiratory PET/CT and to deduce their indications and limits. Different acquisitions with phantom allow to study effect of movement, size and tumor activity compared to environment. The validity domain of these techniques, based on optimal threshold, is accurate if the tumor size is superior to 17 mm and the amplitude in a cycle is inferior or equal to 7.5 mm. For patient exams, an acquisition synchronized allows, even in the worst case, to freeze enough displacement in a cycle in which the relative amplitude is the lowest. Threshold adaptive method are validated for gated acquisitions for homogeneous tumors and not subjected to partial volume effect. If tumor size is inferior to three times the spatial resolution of the system, a more complex approach has to be employed.     

Étude du site de Longgupo – Synthèse

If the hominids are of African origin, as data support, we can hypothesize that the date of the first population diffusion must be moved back to 2.5–2.6 mya, and that the first populations in central China were oriented toward new technological options, which are only found in Africa much later. In the present state of research, it appears that we should abandon our old paradigms, which have over time become “truths”, because instead of a unifying view–monolithic–of these periods, we advocate recognition of the existence of spatial and temporal cultural otherness.     

Les associations des calpionelles du Berriasien et du Valanginien inférieur de la Tunisie septentrionale. Comparaison avec les associations du Rif externe (Maroc)

The study of ten thin sections from outcrops from Lower Cretaceous deposits and several thin sections obtained from three petroleum wells, allow us to better characterize the associations of calpionellid zones and subzones of the Berriasian and Lower Valanginian in northern Tunisia. The B and C zones, respectively, show three and two levels with calpionellid associations corresponding to B1, B2, B3 and C1, C2 subzones. In the D zone, associations of the D1 and D2 subzones were identified. The E zone has been characterized for the first time in Tunisia and in southern-Tethyan margin of North Africa, on the basis of its index specie and associated species.     

Sur un occipital néandertalien des Pradelles (Marillac-le-Franc, Charente) : étude morphométrique préliminaire

In 2001 and 2003, several occipital fragments of a single mature skull were unearthed on the site of les Pradelles (Marillac-le-Franc, Charente). The archaeological context of the deposit allowed us to provisionally assign the remains to the Neandertal taxon. A morphometric study of this piece was conducted in order to confirm its placement in this lineage. Some features observed on this specimen and commonly described among Neandertals (e.g. the presence of a suprainiac fossa) as well as dimensional data locate the les Pradelles occipital within the morphological variability of Neandertals.     

Le site de Longgupo dans son environnement géologique et géomorphologique

On a regional scale, Longgupo is found within a karstic landscape of fenglin-ouvala developed in the Triassic limestones of the Yangtze platform. After several seasons, it is now possible to define and propose a scenario for the formation of the site. During one of the intense karstification phases during the Cretaceous or early Tertiary, karstic conduits were created deep in the substratum. In concert with these deep flows and by karstic collapse, a cave was created. With the start of Himalayan uplift during the Oligocene and Miocene, the beginning of fluvial cutting was reflected by the partial erosion of the upper sandstone formations and the creation of the Miaoyu Valley. This action opened the cave, which would later be occupied by the hominid groups that interest us here. Probably at the end of the Tertiary, the cave, open at the bottom of the valley slope and facing upstream, began to be filled with alluvial deposits from the valley. The basal deposits (C III 10 of the current stratigraphic sequence, levels 20-13 of the first sequence) begin with black clays; at the Plio-Pleistocene transition, deposits become clearly alluvial, increasingly marked by reworking of surface and karstic clays and by systematically coarser contributions. During the deposition period of archaeological complexes III/III’ (previously levels 12-6), karstic collapse appears to have still been active. During the Lower Pleistocene sensu lato, the coarse nature of the deposits becomes accentuated. The material of complex II (previously levels 5-2) is a deposit that is clearly heterometric and coarse, composed at the end mainly of gravels, pebbles and more or less rounded blocks in a clayey matrix. At the conclusion of this new stage, the cave was entirely filled and, purely and simply, disappeared from the landscape. As the valley deepened during the Middle and Upper Pleistocene, the Longgupo slope underwent profound changes, the last of the limestone blocks disappeared from the slope limit and the archaeological site was protected by the coarse breccias that carpeted the slope. The main cause for the sedimentation processes at the site of Longgupo is the hydrosystem of the Miaoyu he, although injections of karstic type sensu stricto cannot be excluded. All of the arguments effectively support alluvial deposition: pebbles, an alternation of coarse and clayey beds, systematic and repeated granulometric decrease. But the stratigraphic disposition was disturbed by deformations due to gravity and karstic origins; the alluvial sediments, rendered plastic by the high proportion of clayey beds, were deformed by gravity (deformation of beds, faults, slopes) following the direction of the slope and by karstic collapse along the two limestone walls north and south of the sites (in sub-parallel faults to the south and by circular aspiration to the north). To this is added a calcitic consolidation of the upper levels that made it difficult to excavate complex C II. The stratigraphic disposition of the archaeological levels at Longgupo is now well understood. It has thus been possible to collect samples for absolute dating, to be published soon.     

Radioactivité résiduelle avant vidange des cuves de décroissance de déchets liquides : bilan annuel d’un service de médecine nucléaire hospitalier au Luxembourg

Residual radioactivity within decay tanks in an in-hospital clinical nuclear medicine unit reflects the specific typology of the concerned unit. To learn how to improve management of emptying the tanks, measures of residual radioactivity over the year 2009 have been compared to prevailing legal norms in Luxembourg. Legal norms have in no case been outpassed. A minimal residual radioactivity, below legal thresholds, has been often found (84%). It concerned ¹³¹I, ^99mTc and ¹¹¹In. This is why management of radioactive decay tanks may be continued unchanged.     

Le site des Vachons : étude de la partie gravettienne de la collection de l’IPH

This article firstly summarizes the process of study of an old collection, which had not been considered since the excavations at the site Les Vachons, started before 1914 and completed around 1939. The studied collection of J. Coiffard, both excavator and inventor of this site, includes four-fifths of the artefacts because, in 1940, he donated approximately one fifth to the Eyzies Museum. For his part, J. Bouyssonie who participated in the excavations for 3 years gave the major part of his own collection to the Archaeological Society of Charentes Angouleme where its condition makes it difficult to analyze. Despite these restrictions, based on statistical comparisons with counts many other sites, I came to the conclusion that the top three layers of Les Vachons are a confirmation of the Gravettian model, developed by B. Bosselin and F. Djindjian through their factor analysis. This model seems much better suited to the stratigraphy of Les Vachons, than all assumptions made by previous analysts in their attempt to bring the industries from the three layers in what remains from the Peyrony model.     

Intérêt du dosage de la thyroglobulinémie chez les sujets porteurs du goitre en zones de déficience iodée au Bénin

In the present study, we analyze the results of thyroid hormones and thyroglobulinemia of 162 patients with goiter living in the departments of Collines and Donga, known to be areas of iodine deficiency in Benin. These results are compared with those of 85 healthy subjects living in the same departments. This study is a cross-sectional analytical study carried out from 1st July 2009 to 30th June 2010. The population of patients consisted of seven males and 155 females. The average age was of 45.7 years. Most of the patients were suffering of simple goiter. Only six of them had thyroid nodules. The diagnosis of biological hyperthyroidism was positive for 20 patients; 16 of them had subclinical hypothyroidism and four clinical hyperthyroidism. One case of clinical hypothyroidism was found. All other 141 patients were biologically normal (euthyroidism). Seventeen of the patients (including six patients presenting a thyroid nodule) had a normal thyroglobulin rate. Hyperthyroglobulinemia was observed in all other 145 patients. These results suggest that patients with goiter in zone of iodine deficiency are biologically euthyroid with hyper-thyroglobulinemia. Thyroglobulin dosage is then recommended, especially when nodules are perceptible.     

A Middle Cambrian edrioasteroid from the Murero biota (NE Spain) with Australian affinities

A Middle Cambrian edrioasteroid belonging to the genus Cambraster is described from the Middle Cambrian Murero biota (Cadenas Ibéricas, NE Spain). Up to now, this genus was known only from Australia and France. This represents the first record of the class Edrioasteroidea in the Cambrian of Spain. Moreover, preliminary results on the diversity and biostratigraphic position of Cincta, Eocrinoidea and Edrioasteroidea from this area are reported.     

La frontière entre le Châtelperronien et l’Uluzzien : analyse comparative des typologies lithiques sur la base des dernières découvertes

The end of the Middle Paleolithic sees the appearance of “transitional” industries, which emerge at the same moment as anatomical modern humans enter Europe. All these transitional industries come from a Mousterian background and are closely connected to late Neanderthals. Among these industries we find two traditions characterized by backed blade pieces in Western Europe: the Châtelperronian and the Uluzzian. Two big conditions have been defined to allow a comparison between these industries: a chronological continuity and a geographic link. The recent data allows a new comparison.     

Les derniers Homo heidelbergensis et leurs descendants les néandertaliens : datation des sites d’Orgnac 3, du Lazaret et de Zafarraya

This article presents the dating results recently obtained on three archaeological sites in Europe. At Orgnac 3 (Ardèche, France) from where the last Homo heidelbergensis fossils are associated with the first evidence of levallois technique, two speleothem formations from the 5b–6–7^th layers were U-Th dated with MC-ICPMS, giving an age range of 319–255 ka (2σ) (MIS 8–9), while the volcanic ash-bearing second layer was dated by ⁴⁰Ar/³⁹Ar, obtaining a preliminary date of 308.2 ± 6.8 ka (2σ). The combined ESR/U-Th dating of red deer enamel teeth from Lazaret cave (Alpes-Maritimes, France) attributed ages of 120–190 ka to the Acheulean and pre-Mousterian layers (MIS 6), which is in agreement with previous TIMS U-Th dates between 108 and 44 ka on calcite samples from the overlying TRA trench (MIS 5, 4, 3). At Zafarraya (Andalousie, Espagne), a number of ¹⁴C measurements on charcoal samples as well as combined ESR/U-Th dates on Capra and Equus dental enamels assigned the Mousterian artefacts and neandertalian fossils-bearing deposits an age interval between 42 and 34 ka (MIS 3).     

Unexpected morphological and karyological changes in invasive Carpobrotus (Aizoaceae) in Provence (S-E France) compared to native South African species

Hybridization processes can lead to evolutionary changes, particularly in co-introduced congeneric plant species, such as Carpobrotus spp. which are recognized as invasive in Mediterranean climate regions. Morphological and karyological comparisons have therefore been made between native Carpobrotus edulis and C. acinaciformis in South Africa and their invasive counterparts in Provence (C. edulis and C. aff. acinaciformis). Morphological data exhibited the most significant differences in invasive C. aff. acinaciformis that forms a new phenotypic variant. Unexpected chromosomal restructuring has been highlighted for both taxa in Provence, with in particular a clear decrease in asymmetry, an increase in the intraspecific variability, and an interspecific convergence of karyotypes. These changes suggest a drift that has facilitated various crosses, and has been amplified through hybridization/introgression. Furthermore, several morphological and karyological transgressive characters have been found in the two invasive taxa. These results stress the important role and the rapidity of karyological changes in invasive processes.     

Mise en place d’une équipe d’experts en physique médicale au Luxembourg : organisation, résultats qualité et radioprotection en médecine nucléaire (2002–2011)

Implementations of the statutory UE requirements concerning ionizing radiation in the medical domain (96/29/Euratom, 13th May 1996; 97/43/Euratom, 30th June 1997) have changed quality control in medical imaging departments. In Luxembourg, the Ministry of Health and the “Union of Luxembourg Hospitals” have thus created a “Medical Physics Cell” (five Medical Physics experts). It is in charge of implementing a standardized program of Quality Assurance (QA) and radiation protection relative to patients as well as staffs, on a coordinated national basis, in all five in-hospital nuclear medicine departments of the country. The program distributes QA controls between three levels, various periodicities and degrees of expertise. It sensitizes staff and medical doctors by trainings and facilitates ISO accreditation. From 2002 to 2011, in all five in-hospital departments of nuclear medicine of a small country, image quality, radiation protection and reference values of each medical equipment were defined and implemented in a standard way. In 2011, the medical physics cell, the driving force leading to the institutionalization of the discipline within the nuclear medicine departments, is considered as a partner rather than as a control body by the teams in charge of the nuclear medicine departments.     

Perturbateurs endocriniens et troubles du comportement : non, nous n’avons pas encore tiré toutes les leçons de l’histoire du DES

Synthetic oestrogens such as diethylstilbestrol (DES) or 17-alpha-ethinylestradiol (EE) administered to pregnant women during numerous years were demonstrated as responsible of severe ravages for children. Regarding behavior disorders, works on mice or rat have shown the effects of these xeno-hormones used even at very weak dose, time of fetal exposition being crucial. Works are less numerous for humans but recent analysis of the spontaneous Hhorages cohort brings demonstrative data. Analogy between animal and man is discussed as well as the effects of bisphenol A and organophosphate pesticides.     

Consolidation par Y-epratuzumab en fractionné dans le lymphome B diffus à grandes cellules : résultats préliminaires d’une étude de phase II

Purpose

A multicenter, non-randomized, on-going phase II study, promoted by the GOELAMS aims to evaluate the efficacy and safety of fractionated administration of ⁹⁰Y-epratuzumab (two injections 7 days apart) in consolidation therapy for patients older than 60 years with diffuse large B-cell lymphoma and large tumor mass who presented a complete response (CR), unconfirmed CR (uCR) or partial response (PR) after induction therapy with six courses of R-CHOP14. We report the preliminary results on 41 of the 75 enrolled patients.

Patients and method

Toxicity was evaluated according to NCI-CTC version 3. The CR and uCR rate and the rate of conversion of PR to CR/uCR 6 weeks after injections of ⁹⁰Y-epratuzumab were evaluated using IWRC criteria.

Results

Thirty-three patients received two injections of ⁹⁰Y-epratuzumab. The toxicity of ⁹⁰Y-epratuzumab was mainly hematologic, characterized by neutropenia grade 3/4 in 81.8% of patients and thrombocytopenia grade 3/4 in 78.8% of patients, reversible. Two patients (6.1%) had grade 3/4 non-hematologic toxicity. Six weeks after injection of ⁹⁰Y-epratuzumab, 40.0% of patients improved their response and the rate of CR/RCu was 83.9%.

Conclusion

These preliminary results show significant toxicity, but mainly hematologic, expected in consolidation. The response rate is encouraging and needs to be confirmed by sufficient number of inclusions and follow-up.