245 research outputs found

    Cell wall composition and biofilm formation of azoles-susceptible and -resistant Candida glabrata strains

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    In the present study, three strains of Candida glabrata have been investigated to shed light on the mechanisms involved in azole resistance during adherence and biofilm formation. In particular, a clinical isolate, susceptible to azole-based drugs, DSY562 and two different resistant mutagenic strains deriving from DSY562, SFY114 and SFY115, have been analysed with different approaches for their cell wall composition and properties. A proteomic analysis revealed that the expression of six cell wall-related proteins and biofilm formation varied between the strains. The SFY114 and SFY115 strains resulted to be less hydrophobic than the susceptible parental counterpart DSY562, on the other hand they showed a higher amount in total cell wall polysaccharides fraction in the total cell wall. Accordingly to the results obtained from the hydrophobicity and adherence assays, in the resistant strain SFY115 the biofilm formation decreased compared to the parental strain DSY562. Finally, the total glucose amount in resistant SFY115 was about halved in comparison to other strains. Taken together all these data suggest that azole drugs may affect the cell wall composition of C. glabrata, in relation to the different pathogenic behaviours

    Cell wall composition and biofilm formation of azoles-susceptible and -resistant Candida glabrata strains

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    In the present study, three strains of Candida glabrata have been investigated to shed light on the mechanisms involved in azole resistance during adherence and biofilm formation. In particular, a clinical isolate, susceptible to azole-based drugs, DSY562 and two different resistant mutagenic strains deriving from DSY562, SFY114 and SFY115, have been analysed with different approaches for their cell wall composition and properties. A proteomic analysis revealed that the expression of six cell wall-related proteins and biofilm formation varied between the strains. The SFY114 and SFY115 strains resulted to be less hydrophobic than the susceptible parental counterpart DSY562, on the other hand they showed a higher amount in total cell wall polysaccharides fraction in the total cell wall. Accordingly to the results obtained from the hydrophobicity and adherence assays, in the resistant strain SFY115 the biofilm formation decreased compared to the parental strain DSY562. Finally, the total glucose amount in resistant SFY115 was about halved in comparison to other strains. Taken together all these data suggest that azole drugs may affect the cell wall composition of C. glabrata, in relation to the different pathogenic behaviours

    Early diagnosis of liver cancer: an appraisal of international recommendations and future perspectives

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    AbstractAll Societies, AASLD, EASL, APASL and JSH, identify patients with cirrhosis as a target population for surveillance, with minor differences for additional categories of patients, such as chronic hepatitis B and hepatitis C patients with advanced fibrosis. According to AASLD, liver disease related to metabolic diseases including diabetes and obesity is a recognized target of screening, since those conditions have been causally related to HCC. All societies endorse radiological non‐invasive techniques as the mainstay for early diagnosis of HCC, but discrepancies exist between Societies on the utilization of contrast‐enhanced ultrasound and utilization of serum markers for surveillance and diagnosis of HCC. The diagnostic algorithm of the international societies differ substantially in the anatomic paradigm of EASL and APASL which identify 1 cm size as the starting point for radiological diagnosis of HCC compared to APASL algorithm based on the dynamic pattern of contrast imaging, independently on tumour size. While strengthening prediction in individual patients is expected to improve cost‐effectiveness ratios of screening, the benefits of pre‐treatment patient stratification by clinical, histological and genetic scores remain uncertain and exclusion of patients with severe co‐morbidities and advanced age is still debated

    Eosinophilic cystitis associated with urethral stricture disease from pelvic trauma. Case report and literature review

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    We report a case of eosinophilic cystitis (EC) in a 65-year-old man with urethral stricture disease from blunt pelvic traumatic event. EC is a rare condition characterized by eosinophilic infiltration of the bladder wall, that usually presents with irritative voiding symptoms, suprapubic pain and hematuria. Etiology is still not clear although a review of the literature suggests that pathogenetic mechanisms probably engage an altered immune response in the bladder, with the inflammatory reaction caused by factors such as exogenous allergens and previous bladder injury or surgery to the bladder or the prostate. The diagnosis of EC has to be confirmed by biopsy, since in some cases it may manifest as other inflammatory and malignant bladder disorders. A conservative medical management is indicated initially, since this disease may be self-limited, with a benign course especially in children and young patients. In adults EC is more often a chronic recurrent condition that requires close follow-up since it may lead to serious progressive bladder and/or upper urinary tract disease. More invasive therapies (including transurethral resection, partial or total cystectomy) may also be required when conservative therapy fails

    Indolent cancer and pattern of progression: Two missing parameters in trial design for hepatology

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    The indolent and aggressive behaviors of HCC might have a role in clinical trial (CT) results; however, the indolent HCC is less analyzed compared to others cancer. Indolent profile could be characterized as follows: (1) patients with low risk of progression itself due to the HCC molecular profile and/or due to the interaction between cancer cell their microenvironment; (2) patients who achieve objective response or present spontaneous regression; and (3) patients who develop radiological progression with no consequence on either the liver function or general status, and without trigger a change in the tumor stage. Patients with "indolent HCC" generally never develop cancer-related symptoms neither die for HCC-related causes. Thus, we hypothesize that the imbalance in the proportion of "indolent" versus "aggressive HCC" between arms or the underestimation/overestimation of HCC behavior at baseline in single-arm CT could be associated with CT failure or under-overestimation of trial results. The "indolent progression" may also explain the discrepancy between radiological progression-based end points and survival. Moreover, we discuss the related causes that explain the indolent profile of HCC and propose (1) refining the progression-related end point by the pattern of progression to minimize the limitations of the current end points; (2) considering alternative statistical tools for survival analysis such as milestone survival, or restricted mean survival time to capture the value of indolent HCC. According to these considerations, we propose incorporating novel end points into the single arm of phase I/II CT as exploratory analysis or as a secondary end point in phase III CT

    Eosinophilic cystis associated with urethral stricture disease from pelvic trauma. Case report and literature review

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    We report a case of eosinophilic cystitis (EC) in a 65-year-old man with urethral stricture disease from blunt pelvic traumatic event. EC is a rare condition characterized by eosinophilic infiltration of the bladder wall, that usually presents with irritative voiding symptoms, suprapubic pain and hematuria. Etiology is still not clear although a review of the literature suggests that pathogenetic mechanisms probably engage an altered immune response in the bladder, with the inflammatory reaction caused by factors such as exogenous allergens and previous bladder injury or surgery to the bladder or the prostate. The diagnosis of EC has to be confirmed by biopsy, since in some cases it may manifest as other inflammatory and malignant bladder disorders. A conservative medical management is indicated initially, since this disease may be self-limited, with a benign course especially in children and young patients. In adults EC is more often a chronic recurrent condition that requires close follow-up since it may lead to serious progressive bladder and/or upper urinary tract disease. More invasive therapies (including transurethral resection, partial or total cystectomy) may also be required when conservative therapy fails

    Activation of the Erk8 Mitogen-activated Protein (MAP) Kinase by RET/PTC3, a Constitutively Active Form of the RET Proto-oncogene

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    Mitogen-activated protein (MAP) kinases have a central role in several biological functions, including cell adhesion and spreading, chemotaxis, cell cycle progression, differentiation, and apoptosis. Extracellular signal-regulated kinase 8 (Erk8) is a large MAP kinase whose activity is controlled by serum and the c-Src non-receptor tyrosine kinase. Here, we show that RET/PTC3, an activated form of the RET proto-oncogene, was able to activate Erk8, and we demon- strate that such MAP kinase participated in RET/PTC3-dependent stimulation of the c-jun promoter. By using RET/PTC3 molecules mutated in specific tyrosine autophosphorylation sites, we charac- terized Tyr981, a known binding site for c-Src, as a major determi- nant of RET/PTC3-induced Erk8 activation, although, surprisingly, the underlying mechanism did not strictly depend on the activity of Src. In contrast, we present evidence that RET/PTC3 acts on Erk8 through Tyr981-mediated activation of c-Abl. Furthermore, we localized the region responsible for the modulation of Erk8 activity by the RET/PTC3 and Abl oncogenes in the Erk8 C-terminal domain. Altogether, these results support a role for Erk8 as a novel effector of RET/PTC3 and, therefore, RET biological functions

    Salivary Proteomic Analysis and Acute Graft-versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation

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    Abstract Graft-versus-host disease (GVHD) is the major life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), developing in 35%-70% of all allo-HSCT recipients despite immunosuppressive prophylaxis. The recent application of proteomic tools that allow screening for differentially expressed or excreted proteins in body fluids could possibly identify specific biomarkers for GVHD. Whole saliva is highly attractive for noninvasive specimen collection. In the present study, we collected saliva specimens from 40 consecutives patients who underwent allo-HSCT between December 2008 and March 2011 at our institution. The specimens were analyzed by HPLC coupled to electrospray-ionization mass spectrometry. Variable expression of S100 protein family members (S100A8, S100A9, and S100A7) was detected. Fourteen of 23 patients with GVHD demonstrated the presence of S100A8, compared with only 2 patients without GVHD and 0 patients in the control group ( P = .001). S100A7 was detectable in 11 of the 23 patients with GVHD but was absent in the other 2 groups ( P = .0001). S100A9-short was detected in 20 patients with GVHD, in 9 patients without GVHD, and in 8 healthy volunteers ( P = .01) Further studies are needed to clarify the role of these proteins as a marker of GVHD or as an index of mucosal inflammation
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