<i>Mycobacterium chelonae</i> associated with tumor-like skin and oral masses in farmed Russian sturgeons (<i>Acipenser gueldenstaedtii</i>)

Background: Non-tuberculous mycobacteria responsible for piscine mycobacteriosis usually produce visceral granulomas in both freshwater and marine species. In this study, the first occurrence of Mycobacterium chelonae associated with tumor-like lesions in the Russian sturgeon (Acipenser gueldenstaedtii) is reported. Fifteen sturgeons from an Italian fish farm showing skin and oral cauliflower-like masses were investigated by histopathology, bacterial culture and molecular analyses. Results: A total of 20 masses different in size located in the mouth and in pectoral and caudal fins (characterized by abundant calcium deposits and by mild to moderate granulomatous inflammation) were observed with a significant different degree of histological severity. All internal organs of the fish were negative for mycobacteria, Ziehl-Neelsen was positive in only one of the oral masses, whereas bacterial and PCR analyses detected the presence of M. chelonae for almost all the skin and oral masses. Based on these results, a calcinosis of dystrophic origin associated with a chronic granulomatous inflammation was considered as a primary diagnosis consequent to tissue injury in areas susceptible to trauma. Conclusions: We hypothesized that the occurrence of M. chelonae in farmed sturgeons was only a secondary event related to its presence in a stressful rearing environment and subsequent to a dystrophic calcinosis occurred in previously damaged tissues

Mycobacterium chelonae associated with tumor-like skin and oral masses in farmed Russian sturgeons (Acipenser gueldenstaedtii)

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Genetic alterations analysis in prognostic stratified groups identified TP53 and ARID1A as poor clinical performance markers in intrahepatic cholangiocarcinoma

The incidence and mortality rates of intrahepatic cholangiocarcinoma have been rising worldwide. Few patients present an early-stage disease that is amenable to curative surgery and after resection, high recurrence rates persist. To identify new independent marker related to aggressive behaviour, two prognostic groups of patient were selected and divided according to prognostic performance. All patients alive at 36 months were included in good prognostic performers, while all patients died due to disease within 36 months in poor prognostic performers. Using high-coverage target sequencing we analysed principal genetic alterations in two groups and compared results to clinical data. In the 33 cases included in poor prognosis group, TP53 was most mutated gene (p\u2009=\u20090.011) and exclusively present in these cases. Similarly, ARID1A was exclusive of this group (p\u2009=\u20090.024). TP53 and ARID1A are mutually exclusive in this study. Statistical analysis showed mutations in TP53 and ARID1A genes and amplification of MET gene as independent predictors of poor prognosis (TP53, p\u2009=\u20090.0031, ARID1A, p\u2009=\u20090.0007, MET, p\u2009=\u20090.0003 in Cox analysis). LOH in PTEN was also identified as marker of disease recurrence (p\u2009=\u20090.04) in univariate analysis. This work improves our understanding of aggressiveness related to this tumour type and has identified novel prognostic markers of clinical outcome

LC3B and ph-S6K are both expressed in epithelioid and classic renal angiomyolipoma: a rationale tissue-based evidence for combining use of autophagic and mTOR targeted drugs

Background: Targeted drugs to the autophagy processes are emerging in clinical trials. The aim of this work is to assess the magnitude of autophagic expression in renal angiomyolipoma. Methods: Fourteen cases of renal angiomyolipoma were recruited. Anti-LC3B-II and anti-phospho-S6K were detected by Western blot analysis. For immunohistochemical staining, sections were stained with the antibodies LC3B-II and cathepsin-K. LC3B-II was also analyzed by immunofluorescence. We have also carried out electron microscopy analysis on tumor cells. Results: 13 classic and 1 epithelioid renal angiomyolipoma were recruited. The Western-blot LC3B-II analysis shows increasing in protein expression in all cases, however quantitative protein expression ranged from 1 to 15 (mean 5). The autophagosome protein LC3B-I also significantly increased in all tumor extraction. The expression of LC3B-II protein was confirmed in tumoral samples by immunofluorescence. The lysosomal marker cathepsin-K was observed by immunohistochemistry on all tumours. The Western-blot ph-S6K analysis showed significant protein overexpression along all cases after evaluation of the quantitative S6K/Ponceaus ratio. In 6/14 (52%) the expression was high, with a quantitative increase of 653 fold induction in 4 angiomyolipoma compared to normal tissue. At electron microscopy, cancer cells evidenced round or oval electron-dense granules associated with membranes and granules with double membrane. Conclusion: Both autophagic LC3B-II and ph-S6K molecules are over-represented in both epithelioid and classic renal angiomyolipoma and a combined use of inhibitors to the autophagic and mTOR processes may be designed in clinical trials, when enrolling patients affected by tumours in tuberous sclerosis or angiomyolipoma at risk of bledding

A survey of bacterial infections in sturgeon farming in Italy

Sturgeon aquaculture production has increased worldwide, particularly in Italy, yet there is little information about diseases that affect sturgeons. With this study we describe the results of screening for bacterial infections during monitoring campaigns carried out from 2014 to 2017. A total of 402 sturgeons from six sturgeon farms with one or more reared sturgeon species among five species and two hybrids were analysed. Bacteriological exam was positive in 93 individuals (23%) and negative in the remaining 309 (77%). Generally, no external or internal macroscopic lesions were present, though some specimens showed skin lesions, liver anaemia or splenomegaly, which are non\u2010pathognomonic signs of bacterial infection. The majority of the isolated bacteria were opportunistic. This knowledge base is important to help create a bacterial profile of sturgeons reared in Italy

The Old and the New on Viral Diseases in Sturgeon

Although sturgeon production by aquaculture has increased worldwide, a major factor limiting its expansion are infectious diseases, although few data about viral diseases are available however. This review provides a rapid overview of viral agents detected and described to date. Following a general introduction on viral diseases are four sections arranged by virus classification: sturgeon nucleocytoplasmic large DNA viruses, herpesviruses, white sturgeon adenovirus 1, and other viruses. Molecular diagnosis is currently the best tool to detect viral diseases, since cell culture isolation is not yet applicable for the detection of most sturgeon viruses

PRIMO CASO DI IRIDOVIROSI IN STORIONE COBICE (ACIPENSER NACCARII) IN ITALIA: UNA NUOVA PROBLEMATICA PER LA CONSERVAZIONE DI UNA SPECIE MINACCIATA

Adriatic sturgeon (Acipenser naccarii) is an endemic species of the Adriatic basin, evaluated as Critically Endangered (CR) by IUCN and therefore near to extinction. This species has a commercial interest and is threaten by overfishing and habitat destruction. These issues caused a dramatic decline of populations that depend on artificial spawning in farms and fish stocking performed by public administrations. The presence of an intensive breeding for conservation purpose have led to the onset of diseases. Among these, viral diseases represent the major issue. In this respect, from 2016 first and foremost in Europe, and then in Italy has been reported the presence of a new Iridovirus (Acipenser Iridovisrus-European) in different sturgeon\u2019s species. Fish Disease laboratory (IZS PLV) received two plots of five individuals belonged to A. naccarii from sturgeon farm located in North Italy. Clinical signs could be attributed to Iridovirus. Subjects have been tested using molecular protocol proposed by Bigarr\ue8 et al., (2016). All samples were positive for Iridovirus. This case is the first record of Iridovirus in Adriatic sturgeon in Italy. Unfortunately, the lack of epidemiological data requires a health monitoring to implement prevention measures. Particularly, all sturgeons intended for stoking purpose should be tested to avoid the transmission of disease in wild populations

VEGFA amplification/increased gene copy number and VEGFA mRNA expression in renal cell carcinoma with TFEB gene alterations

Amplification of vascular endothelial growth factor A (VEGFA) has been recently reported in TFEB-amplified renal cell carcinomas regardless the level of TFEB amplification. We sought to determine VEGFA amplification by fluorescent in situ hybridization (FISH) and VEGFA mRNA expression by in situ hybridization (RNAscope 2.5) in a series of 10 renal cell carcinomas with TFEB gene alterations, either amplification and/or rearrangement (t(6;11) renal cell carcinoma). TFEB gene rearrangement was demonstrated in eight cases, whereas the remaining two cases showed a high level of TFEB (>\u200910 copies of fluorescent signals) gene amplification without evidence of rearrangement. Among the eight t(6;11) renal cell carcinomas (TFEB-rearranged cases), one case displayed a high level of TFEB gene amplification and two showed increased TFEB gene copy number (3-4 copies of fluorescent signals). Those three cases behaved aggressively. By FISH, VEGFA was amplified in all three cases with TFEB amplification and increased VEGFA gene copy number was observed in the two aggressive cases t(6;11) renal cell carcinomas with an overlapping increased number of TFEB fluorescent signals. Overall, VEGFA mRNA expression was observed in 8 of 10 cases (80%); of these 8 cases, 3 cases showed high-level TFEB amplification, one case showed TFEB rearrangement with increased TFEB gene copy number, whereas four showed TFEB gene rearrangement without increased copy number. In summary, VEGFA amplification/increased gene copy number and VEGFA mRNA expression occur in TFEB-amplified renal cell carcinoma, but also in a subset of t(6;11) renal cell carcinoma demonstrating aggressive behavior, and in unamplified conventional t(6;11) renal cell carcinoma suggesting VEGFA as potential therapeutic target in these neoplasms even in the absence of TFEB amplification. We finally propose that all the renal tumors showing morphological characteristics suggesting t(6;11) renal cell carcinoma and all unclassified renal cell carcinomas, either high grade or low grade, should immunohistochemically be evaluated for cathepsin K and/or Melan-A and if one of them is positive, tested for TFEB gene alteration and VEGFA gene amplification