unidentified cachexia patients in the oncologic setting cachexia ufo s do exist

n/

Widespread Wolbachia infection in terrestrial isopods and other crustaceans

Wolbachia bacteria are obligate intracellular alpha-Proteobacteria of arthropods and nematodes. Although widespread among isopod crustaceans, they have seldom been found in non-isopod crustacean species. Here, we report Wolbachia infection in fourteen new crustacean species. Our results extend the range of Wolbachia infections in terrestrial isopods and amphipods (class Malacostraca). We report the occurrence of two different Wolbachia strains in two host species (a terrestrial isopod and an amphipod). Moreover, the discovery of Wolbachia in the goose barnacle Lepas anatifera (subclass Thecostraca) establishes Wolbachia infection in class Maxillopoda. The new bacterial strains are closely related to B-supergroup Wolbachia strains previously reported from crustacean hosts. Our results suggest that Wolbachia infection may be much more widespread in crustaceans than previously thought. The presence of related Wolbachia strains in highly divergent crustacean hosts suggests that Wolbachia endosymbionts can naturally adapt to a wide range of crustacean hosts. Given the ability of isopod Wolbachia strains to induce feminization of genetic males or cytoplasmic incompatibility, we speculate that manipulation of crustacean-borne Wolbachia bacteria might represent potential tools for controlling crustacean species of commercial interest and crustacean or insect disease vectors.This research was funded by a European Research Council Starting Grant (FP7/2007-2013 grant 260729 EndoSexDet) to RC and a Comité Mixte de Coopération Universitaire Franco-Tunisien grant to DB and FCC

The occurrence of germline BRCA1 and BRCA2 sequence alterations in Slovenian population

<p>Abstract</p> <p>Background</p> <p>The <it>BRCA1 </it>and <it>BRCA2 </it>mutation spectrum and mutation detection rates according to different family histories were investigated in 521 subjects from 322 unrelated Slovenian cancer families with breast and/or ovarian cancer.</p> <p>Methods</p> <p>The <it>BRCA1 </it>and <it>BRCA2 </it>genes were screened using DGGE, PTT, HRM, MLPA and direct sequencing.</p> <p>Results</p> <p>Eighteen different mutations were found in <it>BRCA1 </it>and 13 in <it>BRCA2 </it>gene. Mutations in one or other gene were found in 96 unrelated families. The mutation detection rates were the highest in the families with at least one breast and at least one ovarian cancer - 42% for <it>BRCA1 </it>and 8% for <it>BRCA2</it>. The mutation detection rate observed in the families with at least two breast cancers with disease onset before the age of 50 years and no ovarian cancer was 23% for <it>BRCA1 </it>and 13% for <it>BRCA2</it>. The mutation detection rate in the families with at least two breast cancers and only one with the disease onset before the age of 50 years was 11% for <it>BRCA1 </it>and 8% for <it>BRCA2</it>. In the families with at least two breast cancers, all of them with disease onset over the age of 50 years, the detection rate was 5% for <it>BRCA2 </it>and 0% for <it>BRCA1</it>.</p> <p>Conclusion</p> <p>Among the mutations detected in Slovenian population, 5 mutations in <it>BRCA1 </it>and 4 mutations in <it>BRCA2 </it>have not been described in other populations until now. The most frequent mutations in our population were c.181T > G, c.1687C > T, c.5266dupC and c.844_850dupTCATTAC in <it>BRCA1 </it>gene and c.7806-2A > G, c.5291C > G and c.3978insTGCT in <it>BRCA2 </it>gene (detected in 69% of <it>BRCA1 </it>and <it>BRCA2 </it>positive families).</p

Genomic activation of the EGFR and HER2-neu genes in a significant proportion of invasive epithelial ovarian cancers

<p>Abstract</p> <p>Background</p> <p>The status of the EGFR and HER2-neu genes has not been fully defined in ovarian cancer. An integrated analysis of both genes could help define the proportion of patients that would potentially benefit from targeted therapies.</p> <p>Methods</p> <p>We determined the tumour mutation status of the entire tyrosine kinase (TK) domain of the EGFR and HER2-neu genes in a cohort of 52 patients with invasive epithelial ovarian cancer as well as the gene copy number and protein expression of both genes in 31 of these patients by DGGE and direct sequecing, immunohistochemistry and Fluorescent in Situ Hybridisation (FISH).</p> <p>Results</p> <p>The EGFR was expressed in 59% of the cases, with a 2+/3+ staining intensity in 38%. HER2-neu expression was found in 35%, with a 2/3+ staining in 18%. No mutations were found in exons 18–24 of the TK domains of EGFR and HER2-neu. High polysomy of the EGFR gene was observed in 13% of the invasive epthelial cancers and amplification of the HER2-neu gene was found in 10% and correlated with a high expression level by immunohistochemistry.</p> <p>Mutations within the tyrosine kinase domain were not found in the entire TK domain of both genes, but have been found in very rare cases by others.</p> <p>Conclusion</p> <p>Genomic alteration of the HER2-neu and EGFR genes is frequent (25%) in ovarian cancer. EGFR/HER2-neu targeted therapies should be investigated prospectively and specifically in that subset of patients.</p

Five recurrent BRCA1/2 mutations are responsible for cancer predisposition in the majority of Slovenian breast cancer families

<p>Abstract</p> <p>Background</p> <p>Both recurrent and population specific mutations have been found in different areas of the world and more specifically in ethnically defined or isolated populations. The population of Slovenia has over several centuries undergone limited mixing with surrounding populations.</p> <p>The current study was aimed at establishing the mutation spectrum of <it>BRCA1/2 </it>in the Slovenian breast/ovarian cancer families taking advantage of a complete cancer registration database. A second objective was to determine the cancer phenotype of these families.</p> <p>Methods</p> <p>The original population database was composed of cancer patients from the Institute of Oncology Ljubljana in Slovenia which also includes current follow-up status on these patients. The inclusion criteria for the <it>BRCA1/2 </it>screening were: (i) probands with at least two first degree relatives with breast and ovarian cancer; (ii) probands with only two first degree relatives of breast cancer where one must be diagnosed less than 50 years of age; and (iii) individual patients with breast and ovarian cancer, bilateral breast cancer, breast cancer diagnosed before the age of 40 and male breast cancer without any other cancer in the family.</p> <p>Results</p> <p>Probands from 150 different families met the inclusion criteria for mutation analysis of which 145 consented to testing. A <it>BRCA1/2 </it>mutation was found in 56 (39%). Two novel large deletions covering consecutive exons of <it>BRCA1 </it>were found. Five highly recurrent specific mutations were identified (1806C>T, 300T>G, 300T>A, 5382insC in the <it>BRCA1 </it>gene and IVS16-2A>G in the <it>BRCA2 </it>gene). The IVS16-2A>G in the <it>BRCA2 </it>gene appears to be a unique founder mutation in the Slovenian population. A practical implication is that only 4 PCR fragments can be used in a first screen and reveal the cancer predisposing mutation in 67% of the <it>BRCA1/2 </it>positive families. We also observed an exceptionally high frequency of 4 different pathogenic missense mutations, all affecting one of the cryptic cysteine residues of the <it>BRCA1 </it>Ring Finger domain.</p> <p>Conclusion</p> <p>A high mutation detection rate and the frequent occurrence of a limited array of recurring mutations facilitate <it>BRCA1/2 </it>mutation screening in Slovenian families.</p

The Immune Cellular Effectors of Terrestrial Isopod Armadillidium vulgare: Meeting with Their Invaders, Wolbachia

Most of crustacean immune responses are well described for the aquatic forms whereas almost nothing is known for the isopods that evolved a terrestrial lifestyle. The latter are also infected at a high prevalence with Wolbachia, an endosymbiotic bacterium which affects the host immune system, possibly to improve its transmission. In contrast with insect models, the isopod Armadillidium vulgare is known to harbor Wolbachia inside the haemocytes.In A. vulgare we characterized three haemocyte types (TEM, flow cytometry): the hyaline and semi-granular haemocytes were phagocytes, while semi-granular and granular haemocytes performed encapsulation. They were produced in the haematopoietic organs, from central stem cells, maturing as they moved toward the edge (TEM). In infected individuals, live Wolbachia (FISH) colonized 38% of the haemocytes but with low, variable densities (6.45±0.46 Wolbachia on average). So far they were not found in hyaline haemocytes (TEM). The haematopoietic organs contained 7.6±0.7×10(3)Wolbachia, both in stem cells and differentiating cells (FISH). While infected and uninfected one-year-old individuals had the same haemocyte density, in infected animals the proportion of granular haemocytes in particular decreased by one third (flow cytometry, Pearson's test = 12 822.98, df = 2, p<0.001).The characteristics of the isopod immune system fell within the range of those known from aquatic crustaceans. The colonization of the haemocytes by Wolbachia seemed to stand from the haematopoietic organs, which may act as a reservoir to discharge Wolbachia in the haemolymph, a known route for horizontal transfer. Wolbachia infection did not affect the haemocyte density, but the quantity of granular haemocytes decreased by one third. This may account for the reduced prophenoloxidase activity observed previously in these animals