Prognostic Significance of New Immunohistochemical Markers in Refractory Classical Hodgkin Lymphoma: A Study of 59 Cases

Although most classical Hodgkin lymphoma patients are cured, a significant minority fail after primary therapy and may die as result of their disease. To date, there is no consensus on biological markers that add value to usual parameters (which comprise the International Prognostic Score) used at diagnosis to predict outcome. We evaluated 59 patients (18 with primary refractory or early relapse disease and 41 responders) for bcl2, Ki67, CD20, TiA1 and c-kit expression by semi-quantitative immunohistochemical study and correlated the results with the response to treatment

Novel in-situ observations on the diel surface activity of the Romanian hamster, Mesocricetus newtoni (Rodentia, Cricetidae), during pup rearing

The Romanian hamster Mesocricetus newtoni is a threatened and cryptic species, with a distribution limited to North-eastern Bulgaria and South-eastern Romania (Dobruja region). Current literature does not provide sufficient data regarding diel activities and behavior of this species, especially under field conditions. In this context, one female M. newtoni, during the rearing period of her four pups, was monitored for ten days using camera traps. For each documented activity, the date, time, age of the individual, type of activity, and duration were recorded. In total, from the 26140 media files, 72968 seconds were recorded as active behaviors. Data analysis revealed that diurnal activity was predominant and documented for all monitored days; however, the animals spent more time per each activity during the night. The nocturnal activity was present but erratic, without significant patterns. No significant differences were observed in the median duration of activities of the adult compared to the immature individuals. Both the adult female and pups spent time exploring the burrow entrance, especially during the day, but immatures were more reserved to leave the burrow than the female. The female used four burrows for rearing the pups. During this time, food storage behaviors and transferring of immatures between burrows, as well as the weaning of the pups were documented. This study demonstrates that M. newtoni exhibits significant diurnal activity, at least in certain ecological and physiological conditions

Preliminary observations on the food availability and diet composition of the Romanian hamster Mesocricetus newtoni (Rodentia, Cricetidae)

The Romanian hamster Mesocricetus newtoni is endemic to South-Eastern Romania (Dobruja region) and North-Eastern Bulgaria, and prefers steppic, arid, uncultivated habitats, but is also found in alfalfa fields, less often in corn cultures and field-protecting vegetation belts. Previous studies provide only limited data regarding the diet of this cryptic species. The diet of one family group (one female and four pups) was monitored for 10 days, during the vernal season. The data was collected using camera traps and direct observations, supplemented by photos. Plants were identified at the species level. A vegetation survey was performed in a radius of 25 m2 around the burrows using the pratological method, estimating a percentage of each plant species present in the habitat. A number of 16 plants were identified as part of the diet of the Romanian hamster, mostly herbaceous species within the Brassicaceae family. According to the observations, Erodium cicutarium (Geraniaceae) and Papaver rhoeas (Papaveraceae) were consumed most frequently, followed by Descurainia sophia (Brassicaceae), Sisymbrium orientale (Brassicaceae), Medicago minima (Fabaceae) and Buglossoides arvense (Boraginaceae). In the studied area, 38 plant taxa were determined and characterized as ruderal and segetal (weeds of arable land) plants, mostly native to Eurasia. The purpose of this study is to provide novel data on the diet composition of the Romanian hamster in accordance with plant taxa availability and to emphasize the importance of conservation measures of its preferred habitats, which are crucial to the survival of the species

Germline hepatocyte nuclear factor 1 alpha and 1 beta mutations in renal cell carcinomas

Mutations in one copy of the hepatocyte nuclear factors (HNF) 1alpha and 1beta homeodomain containing transcription factors predispose the carrier to maturity-onset diabetes of the young (MODY) types 3 and 5, respectively. Moreover, previous identification of biallelic inactivation of HNF1alpha in hepatocellular adenoma identified its tumor suppressor function in hepatocarcinogenesis. The seminal observation of an ovarian carcinoma in a MODY5 patient who subsequently developed a chromophobe renal cell carcinoma, prompted us to screen for HNF1beta and HNF1alpha inactivation in a series of 20 ovarian and 35 renal neoplasms. Biallelic HNF1beta inactivation was found in two of 12 chromophobe renal carcinomas by association of a germline mutation and a somatic gene deletion. In these cases, the expression of PKHD1 (polycystic kidney and hepatic disease 1) and UMOD (Uromodulin), two genes regulated by HNF1beta, was turned off. Interestingly, in two of 13 clear cell renal carcinomas, we found a monoallelic germline mutation of HNF1alpha with no associated suppression of target mRNA expression. In normal and tumor renal tissues, we showed the existence of a network of transcription factors differentially regulated in tumor subtypes. We identified two related clusters of co-regulated genes associating HNF1beta, PKHD1 and UMOD in the first group and HNF1alpha, HNF4alpha, FABP1 and UGT2B7 in the second group. Finally, these results suggest that germline mutations of HNF1beta and HNF1alpha may predispose to renal tumors. Furthermore, we suggest that HNF1beta functions as a tumor suppressor gene in chromophobe renal cell carcinogenesis through a PKHD1 expression control

Environmental quality assessment of reservoirs impacted by Hg from chlor-alkali technologies: case study of a recovery

Mercury (Hg) pollution legacy of chlor-alkali plants will be an important issue in the next decades with the planned phase out of Hg-based electrodes by 2025 within the Minamata convention. In such a context, the present study aimed to examine the extent of Hg contamination in the reservoirs surrounding the Oltchim plant and to evaluate the possible improvement of the environmental quality since the closure of its chlor-alkali unit. This plant is the largest chlor-alkali plant in Romania, which partly switched to Hg-free technolo- gy in 1999 and definitely stopped the use of Hg electrolysis in May 2012. Total Hg (THg) and methylmercury (CH3Hg) concentrations were found to decrease in the surface waters and sediments of the reservoirs receiving the effluents of the chlor-alkali platform since the closure of Hg units. Hence, calculated risk quotients (RQ) indicated no adverse effect of Hg for aquatic organisms from the ambient water exposure. RQ of Hg in sediments were mostly all higher than 1, showing important risks for benthic organisms. However, ecotoxicity testing of water and sediments suggest possible impact of other contaminants and their mixtures. Hg hotspots were found in soils around the platform with RQ values much higher than 1. Finally, THg and CH3Hg concentrations in fish were below the food safety limit set by the WHO, which contrasts with previous measurements made in 2007 revealing that 92 % of the studied fish were of high risk of consumption. Discontinuing the use of Hg electrodes greatly improved the surrounding environment of chlor-alkali plants within the following years and led to the decrease environmental exposure to Hg through fish consumption. However, sediment and soil still remained highly contaminated and problematic for the river reservoir management. The results of this ecological risk assessment study have important implications for the evaluation of the benefits as well as limits of the Minamata Convention implementation

Birt-Hogg-Dubé renal tumors are genetically distinct from other renal neoplasias and are associated with up-regulation of mitochondrial gene expression.

International audienceBACKGROUND: Germline mutations in the folliculin (FLCN) gene are associated with the development of Birt-Hogg-Dubé syndrome (BHDS), a disease characterized by papular skin lesions, a high occurrence of spontaneous pneumothorax, and the development of renal neoplasias. The majority of renal tumors that arise in BHDS-affected individuals are histologically similar to sporadic chromophobe renal cell carcinoma (RCC) and sporadic renal oncocytoma. However, most sporadic tumors lack FLCN mutations and the extent to which the BHDS-derived renal tumors share genetic defects associated with the sporadic tumors has not been well studied. METHODS: BHDS individuals were identified symptomatically and FLCN mutations were confirmed by DNA sequencing. Comparative gene expression profiling analyses were carried out on renal tumors isolated from individuals afflicted with BHDS and a panel of sporadic renal tumors of different subtypes using discriminate and clustering approaches. qRT-PCR was used to confirm selected results of the gene expression analyses. We further analyzed differentially expressed genes using gene set enrichment analysis and pathway analysis approaches. Pathway analysis results were confirmed by generation of independent pathway signatures and application to additional datasets. RESULTS: Renal tumors isolated from individuals with BHDS showed distinct gene expression and cytogenetic characteristics from sporadic renal oncocytoma and chromophobe RCC. The most prominent molecular feature of BHDS-derived kidney tumors was high expression of mitochondria-and oxidative phosphorylation (OXPHOS)-associated genes. This mitochondria expression phenotype was associated with deregulation of the PGC-1α-TFAM signaling axis. Loss of FLCN expression across various tumor types is also associated with increased nuclear mitochondrial gene expression. CONCLUSIONS: Our results support a genetic distinction between BHDS-associated tumors and other renal neoplasias. In addition, deregulation of the PGC-1α-TFAM signaling axis is most pronounced in renal tumors that harbor FLCN mutations and in tumors from other organs that have relatively low expression of FLCN. These results are consistent with the recently discovered interaction between FLCN and AMPK and support a model in which FLCN is a regulator of mitochondrial function

Characteristics of patients & IHC markers (univariate analysis).

<p><b>Legends</b>: pts = patients sbtype = subtype L = lymphocytes MC = mast cells nber = number IHC:immunohistochemical CV: continuous variable HRS: Hodgkin and Reed Sternberg cells.</p

Figure 1

<p><b>A & B</b>: Rare or no (arrows) H/RS cells stained with CD20 in refractory cHL (<b>A</b>) compared to the overexpression of CD20 on H/RS cells in a responder cHL (arrows) (<b>B</b>) (original magnification ×400). <b>C & D</b>: Numerous H/RS cells stained with bcl2 in a refractory cHL (arrows)(<b>C</b>) comparing to rare cells in a responder case (arrow)(<b>D</b>) (original magnification ×400). <b>E & F</b>: TiA1 expressed on numerous small lymphocytes in a refractory cHL (arrows) (<b>E</b>) and less frequent cells stained with this antibody in a responder cHL (arrows) (<b>F</b>) (original magnification ×400). <b>G & H</b>: c-kit stained frequent mast cells in a refractory cHL (arrows) (<b>G</b>) compared to rare mast cells expressing c-kit in a responder cHL (arrows) (<b>H</b>) (original magnification ×400).</p