Search

We present the case of a 35-year-old woman who had a high-risk pulmonary embolism (according to ESC risk stratification for pulmonary embolism) after she had undergone a Caesarion section. Postoperatively, she presented with acute left lower limb pain, swelling and erythema. A diagnosis was made of deep vein thrombosis (DVT) of the ilio-femoral and popliteal veins. She was started on anticoagulant therapy, which proved to be inefficient, the patient developing a left calf and thigh oedema and shortness of breath. A CT scan revealed high-risk embolus located in the right atrium and through the tricuspid valve. The decision was made to refer her to a cardiovascular surgeon. During her preoperative evaluation, the patient became hemodynamically unstable and was rushed into the operating room, severely desaturated, bradycardic, without consciousness, with severe hypotension. On the basis of the severe state of the patient and the CT scan findings we performed an emergency pulmonary embolectomy, with the patient on cardio-pulmonary by-pass, without cross-clamping the aorta, using a modified Trendelenburg procedure. This case supports using open pulmonary embolectomy for patients with hemodynamic instability on the basis of clinical diagnosis.

Coronavirus disease 2019 (COVID-19) has rapidly evolved into a worldwide pandemic causing a serious global public health problem. The risk of vertical transmission of SARS-CoV-2 is still debated, and the consequences of this virus on pregnant women and their fetuses remain unknown. We report a case of pregnancy complicated with hydrops fetalis that developed 7 weeks after recovery from a mild SARS-CoV-2 infection, leading to intrauterine death of the foetus. Evidence of SARS-CoV-2 placentitis was demonstrated by the presence of viral particles in the placenta identified by immunohistochemistry. As we excluded all possible etiological factors for non-immunologic hydrops fetalis, we believe that the fetal consequences of our case are related to vertical transmission of SARS-CoV-2 virus. To the best of our knowledge, this is the second reported case in the literature of COVID-19 infection complicated with hydrops fetalis and intrauterine fetal demise.

Tear composition is a source of information on the health state of the eye. Dry eye syndrome represents nowadays a common disorder that can be associated with other eye diseases, in particular keratoconus. As such, we focussed on the correlation of selected protein levels with ophthalmic parameters and, as a novelty, we explored the possible correlation of these data, classically used in examination, with electron paramagnetic resonance (EPR) spectral parameters of spin probes. Three groups of patients with (i) dry eye syndrome, (ii) dry eye syndrome and keratoconus and (iii) healthy eyes were considered. Tears were collected from the subjects to determine the levels of total protein, lactoferrin, lysozyme and human serum albumin, and to record the EPR spectra of spin probes with fatty acid-like structures: 5-doxyl stearic acid (5-DSA) and 4-(N,N′-dimethyl-N-hexadecyl)ammonium-2,2′,6,6′-tetramethylpiperidine-1-oxyl iodide (CAT16). In tear secretion, the EPR spectra of spin probes showed two components, one with slow dynamics and another one revealing a quasi-isotropic, rapid motion. We analysed in depth the changes observed in the EPR spectra of 5-DSA for the reason that the differences in dynamics between the 5-DSA components are more evident. The challenge of this study was to provide an alternative to biochemical analysis in monitoring the evolution of the health state of patients diagnosed with dry eye syndrome or keratoconus using the information provided by EPR spectra of spin probes. The results indicate a decreased contribution of the EPR component with rapid motion following treatment, and a significant correlation with the Schirmer and/or BUT values.

Background and Objectives: Toxoplasma gondii, cytomegalovirus (CMV) and rubella virus, besides other agents, belong to a group named the TORCH complex. Research on the epidemiology of these agents in women is of particular interest, as primary infection during pregnancy could cause severe damage to the fetus. Women who had contracted infection before pregnancy develop IgG antibodies, so the fetus is protected in case of contact with the same agent. Our scope was to identify the childbearing women simultaneously protected or susceptible to a primary infection to two or three agents mentioned above. Materials and Methods: A cross-sectional study was performed on 6961 fertile Caucasian women from Western Romania, to analyze the simultaneous seroprevalence to two or three of the pathogens from the TORCH complex: Toxoplasma gondii, CMV, and rubella virus. Sampling was conducted at two time points: 2008–2010 (group 1, 1461 participants) and 2015–2018 (group 2, 5500 participants). Results: The percentage of women simultaneously seropositive to IgG-anti-Toxoplasma gondii/IgG-anti-CMV, IgG-anti-Toxoplasma gondii/IgG-anti-rubella, IgG-anti-CMV/IgG-anti-rubella or IgG-anti-Toxoplasma gondii and IgG-anti-CMV/IgG-anti-rubella antibodies decreased between the two groups (2008–2010 vs. 2015–2018): 41.4% vs. 36.1%, OR = 0.79, p = 0.0002, 41.8% vs. 35.7%, OR = 0.77, p &lt, 0.0001, 88.9% vs. 83.6%, OR = 0.63, p &lt, 39.6% vs. 33.2%, OR = 0.75, p &lt, 0.0001. When comparing women from urban and rural areas, the simultaneous seroprevalence was higher in rural areas. In women tested 2008–2010 (group 1) the simultaneous seroprevalence (urban vs. rural) was: 38.4% vs. 49.1%, OR = 1.54, p = 0.0002, 38.4% vs. 50.6%, OR = 1.64, p &lt, 88.8% vs. 89.2%, OR = 1.04, NS, 36.4% vs. 47.7%, OR = 1.58, p = 0.0001. A similar trend was found in women tested in group 2. Conclusions: The rate of simultaneous seropositivity to Toxoplasma gondii, CMV and rubella virus among Romanian women of reproductive age decreased significantly between 2008–2010 and 2015–2018 and the susceptibility to infections increased. It is necessary to apply increased prevention measures among susceptible pregnant women.

Background Dapagliflozin is a sodium-glucose cotransporter-2 inhibitor approved for the treatment of type 2 diabetes. We aimed to assess the efficacy and safety of dapagliflozin as an add-on to adjustable insulin in patients with inadequately controlled type 1 diabetes. Methods DEPICT-1 was a double-blind, randomised, parallel-controlled, three-arm, phase 3, multicentre study done at 143 sites in 17 countries. Eligible patients were aged 18–75 years and had inadequately controlled type 1 diabetes (HbA1c between ≥7·7% and ≤11·0% [≥61·0 mmol/mol and ≤97·0 mmol/mol]) and had been prescribed insulin for at least 12 months before enrolment. After an 8 week lead-in period to optimise diabetes management, patients were randomly assigned (1:1:1) using an interactive voice response system to dapagliflozin 5 mg or 10 mg once daily, given orally, or matched placebo. Randomisation was stratified by current use of continuous glucose monitoring, method of insulin administration, and baseline HbA1c. The primary efficacy outcome was the change from baseline in HbA1c after 24 weeks of treatment in the full analysis set, which consisted of all randomly assigned patients who received at least one dose of study drug. An additional 55 patients who were incorrectly and non-randomly allocated to only dapagliflozin treatment groups were included in the safety analysis set. This study was registered with ClinicalTrials.gov, number NCT02268214; data collection for the present analysis was completed on Jan 4, 2017, and a 28 week extension phase is ongoing. Findings Between Nov 11, 2014, and April 16, 2016, 833 patients were assigned to treatment groups and included in safety analyses (dapagliflozin 5 mg [n=277] vs dapagliflozin 10 mg [n=296] vs placebo [n=260]; 778 of these patients were randomly assigned and included in the full analysis set for efficacy analyses (259 vs 259 vs 260; difference due to randomisation error affecting 55 patients). Mean baseline HbA1c was 8·53% (70 mmol/mol; SD 0·67% [7·3 mmol/mol]). At week 24, both doses of dapagliflozin significantly reduced HbA1c compared with placebo (mean difference from baseline to week 24 for dapagliflozin 5 mg vs placebo was −0·42% [95% CI −0·56 to −0·28; p

// Cristiana Pistol Tanase 1,2 , Elena Codrici 1 , Ionela Daniela Popescu 1 , Simona Mihai 1 , Ana-Maria Enciu 1,3 , Laura Georgiana Necula 1,4 , Adrian Preda 5 , Gener Ismail 6,8 and Radu Albulescu 1,7 1 Department of Biochemistry-Proteomics, Victor Babes National Institute of Pathology, Bucharest, Romania 2 Titu Maiorescu University, Faculty of Medicine, Bucharest, Romania 3 Department of Cell Biology and Histology, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania 4 Stefan S Nicolau Institute of Virology, Bucharest, Romania 5 Center for Uronephrology and Renal Transplantation, Fundeni Clinical Institute, Bucharest, Romania 6 Center of Internal Medicine-Nephrology, Fundeni Clinical Institute, Bucharest, Romania 7 National Institute for Chemical Pharmaceutical R&D, Bucharest, Romania 8 Carol Davila University of Medicine and Pharmacy, Faculty of Medicine, Bucharest, Romania Correspondence to: Cristiana Tanase, email: // Keywords : prostate cancer, biomarkers, proteomics, mass spectrometry, prostasomes Received : July 29, 2016 Accepted : December 27, 2016 Published : January 04, 2017 Abstract The clinical and fundamental research in prostate cancer - the most common urological cancer in men - is currently entering the proteomic and genomic era. The focus has switched from one single marker (PSA) to panels of biomarkers (including proteins involved in ribosomal function and heat shock proteins). Novel genetic markers (such as Transmembrane protease serine 2 (TMPRSS2)-ERG fusion gene mRNA) or prostate cancer gene 3 (PCA3) had already entered the clinical practice, raising the question whether subsequent protein changes impact the evolution of the disease and the response to treatment. Proteomic technologies such as MALDI-MS, SELDI-MS, i-TRAQ allow a qualitative/quantitative analysis of the proteome variations, in both serum and tumor tissue. A new trend in prostate cancer research is proteomic analysis of prostasomes (prostate-specific exosomes), for the discovery of new biomarkers. This paper provides an update of novel clinical tests used in research and clinical diagnostic, as well as of potential tissue or fluid biomarkers provided by extensive proteomic research data.

Chronic kidney disease (CKD) is an irreversible loss of kidney function, and it represents a major global public health burden due to both its prevalence and its continuously increasing incidence. Mineral bone disorders (MBDs) constitute a hallmark of CKD, and alongside cardiovascular complications, they underlie a poor prognosis for these patients. Thus, our study focused on novel CKD biomarker patterns and their impact on the clinical staging of the disease. As a first testing approach, the relative expression levels of 105 proteins were assessed by the Proteome Profiler Cytokine Array Kit for pooled CKD stage 2–4 serum samples to establish an overall view regarding the proteins involved in CKD pathogenesis. Among the molecules that displayed significant dysregulation in the CKD stages, we further explored the involvement of Dickkopf-related protein 1 (Dkk-1), a recognised inhibitor of the Wnt signalling pathway, and its crosstalk with 1,25OH2D3 (calcitriol) as new players in renal bone and vascular disease. The serum levels of these two molecules were quantified by an ELISA (76 samples), and the results reveal decreasing circulating levels of Dkk-1 and calcitriol in advanced CKD stages, with their circulating expression showing a downward trend as the CKD develops. In the next step, we analysed the inflammation and MBD biomarkers’ expression in CKD (by xMAP array). Our results show that the molecules involved in orchestrating the inflammatory response, interleukin-6 (IL-6) and tumour necrosis factor alpha (TNFα), as well as the mineral biomarkers osteoprotegerin (OPG), osteocalcin (OC), osteopontin (OPN), and fibroblast growth factor 23 (FGF-23), correlate with Dkk-1 and calcitriol, raising the possibility of them being potential useful CKD biomarkers. These results reveal the impact of different biomarker patterns in CKD staging and severity, thus opening up novel approaches to be explored in CKD clinical management.

The case of a 61-year-old male with a recent total gastrectomy for a hemorrhagic gastric tumor is presented, with the important co-morbidities of type II diabetes mellitus requiring insulin, chronic hepatitis C with liver dysfunction, stage II essential hypertension, chronic stage III renal disease peripheral type II aorto-iliac disease with stage II ischemia of both legs, and chronic anemia. About one month following the gastrectomy, the patient presented with fever and acute inflammatory syndrome. Severe aortic insufficiency, aortic valvular vegetations, and positive blood cultures with Staphylococcus saprophytic were found. The diagnosis of infectious endocarditis on the aortic valve was established (positive blood cultures with echocardiographic features of vegetations, fever), and antibiotic treatment with Levofloxacin and Vancomycin was initiated. The evolution was favorable with the remission of the inflammatory syndrome and quick cessation of fever. However, the hemodynamic aspect showed progressive heart failure with acute pulmonary edema. The transesophageal echocardiographic examination confirmed the existence of severe aortic insufficiency and valvular vegetations with a left ventricular ejection fraction of 38%. The coronary angiography revealed double vessel disease. The calculated Euroscore II was 33.4%. Aortic valve replacement with porcine xenograft and double coronary artery bypass graft surgery was performed. The patient had a favorable postoperative course remaining afebrile and out of heart failure, with the markers of inflammation largely within normal limits. The left ventricular ejection fraction increased to 50%. The successful outcome of this case, represented by a rare association of cancer, endocarditis, and coronary disease, reveals the importance of the multidisciplinary teams involved in this case: gastroenterology, general surgery, cardiology, infectious diseases, cardiac surgery, and intensive care. Therefore, in such cases with high risk, complex patients, a strong collaboration between all specialties is needed to overcome all of the limitations of the patient’s co-morbidities.

Retinopathy of prematurity (ROP) represents a determinate cause of blindness in children that could be avoided. Blindness due to ROP and the stage of it when its being diagnosed is mostly determined by: socioeconomic degree of country development; availability of the screening in neonatal care; gestational age and hospital screenings; treatment programs available at any given time in the country; screening and treatment costs (material and human resources). ROP is the number one cause of blindness in Romania at the time being. Early discovery decreases exponentially the chances of blindness onset. Low birth weight (LBW), fewer than 1,500 g, represents an additional risk factor together with the degree of prematurity. Mandatory screening both during hospitalization as well as in the first 4-6 weeks after birth may avoid a major social problem. It is a simple process – eye exam with fundus examination – and it depends entirely on the availability, consistency and seriouseness of the parents. Thus a major social impact with disastrous consequences could be avoided.

Malignant gliomas are aggressive brain tumors with limited therapeutic options, possibly because of highly tumorigenic subpopulations of glioma stem cells. These cells require specific microenvironments to maintain their “stemness,” described as perivascular and hypoxic niches. Each of those niches induces particular signatures in glioma stem cells (e.g., activation of Notch signaling, secretion of VEGF, bFGF, SDF1 for the vascular niche, activation of HIF2α, and metabolic reprogramming for hypoxic niche). Recently, accumulated knowledge on tumor-associated macrophages, possibly delineating a third niche, has underlined the role of immune cells in glioma progression,viaspecific chemoattractant factors and cytokines, such as macrophage-colony stimulation factor (M-CSF). The local or myeloid origin of this new component of glioma stem cells niche is yet to be determined. Such niches are being increasingly recognized as key regulators involved in multiple stages of disease progression, therapy resistance, immune-escaping, and distant metastasis, thereby substantially impacting the future development of frontline interventions in clinical oncology. This review focuses on the microenvironment impact on the glioma stem cell biology, emphasizing GSCs cross talk with hypoxic, perivascular, and immune niches and their potential use as targeted therapy.

Chronic kidney disease, despite being a “silent epidemic” disease, represents one of the main causes of mortality in general population, along with cardiovascular disease, which is the leading cause of poor prognosis for these patients. The specific objective of our study was to characterize the relationship between the inflammatory status, the bone disorders markers, and kidney failure in chronic kidney disease patient stages 2–4, in order to design a novel biomarker panel that improves early disease diagnosis and therapeutic response, thus being further integrated into clinical applications. A panel of proteomic biomarkers, assessed by xMAP array, which includes mediators of inflammation (IL-6, TNF-α) and mineral and bone disorder biomarkers (OPG, OPN, OCN, FGF-23, and Fetuin-A), was found to be more relevant than a single biomarker to detect early CKD stages. The association between inflammatory cytokines and bone disorders markers, IL-6, TNF-α, OPN, OPG, and FGF-23, reflects the severity of vascular changes in CKD and predicts disease progression. Proteomic xMAP analyses shed light on a new approach to clinical evaluation for CKD staging and prognosis.

Starting from the recent identification of CD36 and CD97 as a novel marker combination of fibroblast quiescence in lung during fibrosis, we aimed to survey the literature in search for facts about the separate (or concomitant) expression of clusters of differentiation CD36 and CD97 in either tumor- or pancreatic-cancer-associated cells. Here, we provide an account of the current knowledge on the diversity of the cellular functions of CD36 and CD97 and explore their potential (common) contributions to key cellular events in oncogenesis or metastasis development. Emphasis is placed on quiescence as an underexplored mechanism and/or potential target in therapy. Furthermore, we discuss intricate signaling mechanisms and networks involving CD36 and CD97 that may regulate different subpopulations of tumor-associated cells, such as cancer-associated fibroblasts, adipocyte-associated fibroblasts, tumor-associated macrophages, or neutrophils, during aggressive pancreatic cancer. The coexistence of quiescence and activated states in cancer-associated cell subtypes during pancreatic cancer should be better documented, in different histological forms. Remodeling of the local microenvironment may also change the balance between growth and dormant state. Taking advantage of the reported data in different other tissue types, we explore the possibility to induce quiescence (similar to that observed in normal cells), as a therapeutic option to delay the currently observed clinical outcome.

Neoangiogenesis plays an important role in cutaneous lymphoma pathogenesis. Cutaneous T-cell lymphoma (CTCL) is characterized by the presence of malignant T-cell clones in the skin. Vascular microenvironment of lymphomas accelerates neoangiogenesis through several factors released by tumoral cells: VEGF family, bFGF and PIGF. Tumor stroma (fibroblasts, inflammatory and immune cells) also plays a crucial role, by providing additional angiogenic factors. The angiogenic process through the VEGF-VEGFR axis can promote survival, proliferation and metastasis via autocrine mechanisms in cutaneous lymphomas. Microvascular density (MVD) measures the neo-vascularization of cutaneous lymphoma, generated by the response of tumor cells, proangiogenic stromal cells, and benign T/B lymphocytes within the tumor inflammatory infiltrate. Pro-angiogenic proteins have been found to indicate the evolution and prognosis in patients with CTCL. In conclusion, anti-angiogenic therapeutic protocols can target tumor vasculature or malignant tumor cells directly or through a large number of combinations with other drugs. The integration of proteomics into clinical practice based on high-throughput technologies leads to the development of personalized medicine, adapting the specific biomarkers to the application of cancer-type specific individual drug targets.

Persistent, low-grade inflammation is now considered a hallmark feature of chronic kidney disease (CKD), being involved in the development of all-cause mortality of these patients. Although substantial improvements have been made in clinical care, CKD remains a major public health burden, affecting 10–15% of the population, and its prevalence is constantly growing. Due to its insidious nature, CKD is rarely diagnosed in early stages, and once developed, its progression is unfortunately irreversible. There are many factors that contribute to the setting of the inflammatory status in CKD, including increased production of proinflammatory cytokines, oxidative stress and acidosis, chronic and recurrent infections, altered metabolism of adipose tissue, and last but not least, gut microbiota dysbiosis, an underestimated source of microinflammation. In this scenario, a huge step forward was made by the increasing progression of omics approaches, specially designed for identification of biomarkers useful for early diagnostic and follow-up. Recent omics advances could provide novel insights in deciphering the disease pathophysiology; thus, identification of circulating biomarker panels using state-of-the-art proteomic technologies could improve CKD early diagnosis, monitoring, and prognostics. This review aims to summarize the recent knowledge regarding the relationship between inflammation and CKD, highlighting the current proteomic approaches, as well as the inflammasomes and gut microbiota dysbiosis involvement in the setting of CKD, culminating with the troubling bidirectional connection between CKD and renal malignancy, raised on the background of an inflammatory condition.

Aim: Pituitary adenomas are typically slow-growing and histologically benign tumors that can occasionally behave in a malignant-like manner, invading adjacent structures or recurring after treatment. Using protein analysis methods and multiplex xMAP assays, we aimed to find out if these particular types of tumors express angiogenic markers VEGF and basic FGF (bFGF), which are associated with tumor growth and invasiveness, and quantify them in order to establish their usefulness as biomarkers. Materials & methods: We have analysed the expression of angiogenic markers VEGF and bFGF in serum and tissue specimens from 66 pituitary adenomas (43 invasive and 23 noninvasive). For serum analysis, we used xMAP and ELISA, and for tissue analysis, we performed histopathology and immunohistochemistry. Results & conclusion: We measured the serum angiogenic factors in pituitary adenomas. The quantification methods revealed significant differences between pituitary adenoma patients and controls, for both VEGF (212.4 vs 112.5 pg/ml in controls) and bFGF (mean value of 12.6 vs 10.8 pg/ml in controls), and also differentiated between invasive and noninvasive adenomas (p < 0.05). The tissue expression of VEGF and bFGF strongly correlated with their serum level increase. Our findings can be further developed into methods for selection of patients suitable for personalized, antiangiogenic therapy.

Keratoconus is a progressive corneal ectasia that may lead to severe visual impairment due to the irregular astigmatism caused by corneal thinning. In addition to its association with atopy, eye rubbing, or genetic component, late reports suggest the involvement of inflammation in the pathogenesis of the disease. Our aim was to determine the concentration of IL-4, IL-6, IL-10, RANTES, IFN gamma, and TNF alpha in the tear film of patients with keratoconus and their first degree family members. We analyzed forty-eight participants in an observational cross-sectional study. The diagnosis of keratoconus had to be confirmed in addition to a minimum of 47 D corneal refractive power by corneal topography readings provided by a Placido-based topography system and analysis of the pattern: irregular astigmatism with an asymmetric “bow-tie.” As for the other groups, the most important diagnosis criteria were a normal topographic pattern with a regular astigmatism. 17 keratoconus patients, 16 relatives, and 15 controls were recruited after clinical assessment as part of the research. The cytokine’s mean values were similar in the keratoconus group and the relatives’ samples but significantly higher compared to the controls. Important differences were found in IL-4 levels between keratoconus patients and relatives and between relatives and controls (mean difference of 302.42, p<0.0016 and 219.16, p<0.033, Tukey’s HSD procedure). In the keratoconus group, using the CORR procedure, we found statistically strong correlations of IL-6 lacrimal concentrations with the disease stage (r=0.56, p<0.01), keratometry (r=0.55, p<0.02), pachymetry (r=−0.64, p<0.048), and corneal hysteresis (r=−0.53, p<0.02). Cytokine overexpression may be relevant for the inflammatory etiology of keratoconus. In conclusion, in the case of some first degree family members, the elevated tear biomarkers may represent a supplementary risk factor.

Metastasis requires cellular changes related to cell-to-cell and cell-to-matrix adhesion, immune surveillance, activation of growth and survival signalling pathways, and epigenetic modifications. In addition to tumour cells, tumour stroma is also modified in relationship to the primary tumour as well as to distant metastatic sites (forming a metastatic niche). A common denominator of most stromal partners in tumour progression is CD36, a scavenger receptor for fatty acid uptake that modulates cell-to-extracellular matrix attachment, stromal cell fate (for adipocytes, endothelial cells), TGFβactivation, and immune signalling. CD36 has been repeatedly proposed as a prognostic marker in various cancers, mostly of epithelial origin (breast, prostate, ovary, and colon) and also for hepatic carcinoma and gliomas. Data gathered in preclinical models of various cancers have shown that blocking CD36 might prove beneficial in stopping metastasis spread. However, targeting the receptor in clinical trials with thrombospondin mimetic peptides has proven ineffective, and monoclonal antibodies are not yet available for patient use. This review presents data to support CD36 as a potential prognostic biomarker in cancer, its current stage towards achievingbona fidebiomarker status, and knowledge gaps that must be filled before further advancement towards clinical practice.

Inflammation represents the immune system response to external or internal aggressors such as injury or infection in certain tissues. The body’s response to cancer has many parallels with inflammation and repair; the inflammatory cells and cytokines present in tumours are more likely to contribute to tumour growth, progression, and immunosuppression, rather than in building an effective antitumour defence. Using new proteomic technology, we have investigated serum profile of pro- (IL-1β, IL-6, IL-8, IL-12, GM-CSF, and TNF-α) and anti-inflammatory cytokines (IL-4, IL-10), along with angiogenic factors (VEGF, bFGF) in order to assess tumoural aggressiveness. Our results indicate significant dysregulation in serum levels of cytokines and angiogenic factors, with over threefold upregulation of IL-6, IL-1β, TNF-α, and IL-10 and up to twofold upregulation of VEGF, FGF-2, IL-8, IL-2, and GM-CSF. These molecules are involved in tumour progression and aggressiveness, and are also involved in a generation of disease associated pain.

Cristiana Tanase,1 Radu Albulescu,1,2 Elena Codrici,1 Bogdan Calenic,1,3 Ionela Daniela Popescu,1 Simona Mihai,1 Laura Necula,1,4 Maria Linda Cruceru,5 Mihail Eugen Hinescu1,5 1“Victor Babes” National Institute of Pathology, Biochemistry-Proteomics Department, 2National Institute for Chemical Pharmaceutical R&D, 3“Carol Davila” University of Medicine and Pharmacy, Department of Biochemistry, 4Stefan S. Nicolau Institute of Virology, Cellular and Molecular Pathology, 5“Carol Davila” University of Medicine and Pharmacy, Cellular and Molecular Medicine Department, Bucharest, Romania Purpose: Apoptotic protease-activating factor-1 (APAF-1) and cathepsin B are important functional proteins in apoptosis; the former is involved in the intrinsic (mitochondrial) pathway, while the latter is associated with both intrinsic and extrinsic pathways. Changes in the expression of apoptosome-related proteins could be useful indicators of tumor development since a priori defects in the mitochondrial pathway might facilitate the inception and progression of human neoplasms. Our aim was to evaluate the profiles of APAF-1 and cathepsin B in relation with other molecules involved in apoptosis/proliferation and to correlate them with the aggressive behavior of invasive pituitary adenomas. Materials and methods: APAF-1 and cathepsin B were assessed in tissue samples from 30patients with pituitary adenomas, of which 16 were functional adenomas and 22 were invasive adenomas. Results: A positive relationship between high proliferation and invasiveness was observed in invasive pituitary adenomas when compared to their noninvasive counterparts (Ki-67 labeling index – 4.72% versus 1.75%). Decreased expression of APAF-1 was recorded in most of the invasive adenomas with a high proliferation index, while the cathepsin B level was elevatedin this group. We have noticed a negative correlation between the low level of APAF-1 and invasiveness (63.63%; P

Objectives: This study was designed to assess the incidence of child emotional and physical abuse, associated risk factors and psychosocial symptoms in a cross-cultural comparison between post-communist bloc countries. Method: One-thousand one-hundred forty-five children ages 10–14 from Latvia (N=297), Lithuania (N=300), Macedonia (N=302), and Moldova (N=246) participated in the study. They completed questionnaires assessing their experience of emotional or physical abuse, and provided information about family risk-factors and psychosocial symptoms, including PTSD-related symptoms. Results: Incidence rates of maltreatment differed by country, as did levels of reported psychosocial symptoms. Incidence of emotional and physical abuse differed by region, with higher levels of abuse reported in the rural regions. In all four countries, a similar association between emotional/physical abuse and psychosocial symptoms was found, with the uniformly largest correlation between emotional abuse and anger. When examining the combined scores of emotional and physcial abuse, even higher correlation’s were found, particularly in relation to anger and depression. In all four countries, parental overuse of alcohol was associated with emotional and/or physical abuse. Conclusions: Findings show differences by country in child-reported levels of emotional and physical abuse, but similar patterns of correlation with psychosocial symptoms and the risk factors of parental alcohol overuse and living in a rural area.

Background: The objective of this study is to assess the outcome of the patients treated for hepatocellular carcinoma (HCC) in a General Surgery and Liver Transplantation Center. Methods: This retrospective study includes 844 patients diagnosed with HCC and surgically treated with curative intent methods. Curative intent treatment is mainly based on surgery, consisting of liver resection (LR), liver transplantation (LT). Tumor ablation could become the choice of treatment in HCC cases not manageable for surgery (LT or LR). 518 patients underwent LR, 162 patients benefited from LT and in 164 patients radiofrequency ablation (RFA) was performed. 615 patients (73%) presented liver cirrhosis. Results: Mordidity rates of patient treated for HCC was 30% and mortality was 4,3% for the entire study population. Five year overall survival rate was 39 % with statistically significant differences between transplanted, resected, or ablated patients (p 0.05) with better results in case of LT followed by LR and RFA. Conclusions: In HCC patients without liver cirrhosis, liver resection is the treatment of choice. For early HCC occurred on cirrhosis, LT offers the best outcome in terms of overall and disease free survival. RFA colud be a curative method for HCC patients not amenable for LT of LR.

Background The rapid progress of proteomics over the past years has allowed the discovery of a large number of potential biomarker candidates to improve early tumor diagnosis and therapeutic response, thus being further integrated into clinical environment. High grade gliomas represent one of the most aggressive and treatment-resistant types of human brain cancer, with approximately 9–12 months median survival rate for patients with grade IV glioma (glioblastoma). Using state-of-the-art proteomics technologies, we have investigated the proteome profile for glioblastoma patients in order to identify a novel protein biomarker panel that could discriminate glioblastoma patients from controls and increase diagnostic accuracy. Results In this study, SELDI-ToF MS technology was used to screen potential protein patterns in glioblastoma patients serum; furthermore, LC-MS/MS technology was applied to identify the candidate biomarkers peaks. Through these proteomic approaches, three proteins S100A8, S100A9 and CXCL4 were selected as putative biomarkers and confirmed by ELISA. Next step was to validate the above mentioned molecules as biomarkers through identification of protein expression by Western blot in tumoral versus peritumoral tissue. Conclusions Proteomic technologies have been used to investigate the protein profile of glioblastoma patients and established several potential diagnostic biomarkers. While it is unlikely for a single biomarker to be highly effective for glioblastoma diagnostic, our data proposed an alternative and efficient approach by using a novel combination of multiple biomarkers.

Aims: Apaf-1 (apoptotic protease-activating factor 1), is commonly known as an indicator of apoptosis regulation. It is the core protein of the apoptosome and its dosage is also critical in various cancer types. The aim of our study was to investigate the expression of Apaf-1 and cathepsin B (as caspase-dependent and non-caspase-dependent) effectors of cell death, in order to correlate them with the invasivity of pituitary adenoma. Design: Immunohistochemical analysis was performed on 30 paraffin-embeded pituitary adenomas: 21 functioning and 9 non-functioning; 22 with local invasiveness, 16 invasive in cavernous sinus; 4 were recidives. The following antibodies were used: Apaf-1– rabbit polyclonal (1:100), cathepsin B – mouse monoclonal NCL-Cath-B (CB131) (1:40), and Ki67– MIB1 (1:50). Apoptosis was measured as apoptotic index by TUNEL method. Results: A positive relation between high proliferation and high apoptotic index in invasive adenomas was revealed. The loss of Apaf-1 expression was observed in most of the invasive adenoma with increased Ki67 proliferative index. In low-grade invasive tumors Apaf-1 was expressed in variable degree with a zonal distribution. Most of the non-invasive adenoma presented positive Apaf-1 reaction, with zonal or diffuse aspect. On the contrary, cathepsin B was commonly expressed with a granular pattern, routinely lying on the plasma membrane, in invasive pituitary tumors. In cells undergoing apoptosis, cathepsin B appeared diffusely re-distributed in the cytosol. A negative correlation between Apaf-1 and invasiveness was noted. On the other hand, a positive correlation between cathepsin-B and invasiveness was recorded. Conclusion: These data demonstrated an inverse correlation between Apaf-1 and cathepsin B expressions. Shifting the balance between cell death mediators might result in changes in tumor behavior.

Aim: To evaluate the metacarpophalangeal (MCP) joints (MCP2 and 5) in healthy subjects by ultrasonography (US) using a high frequency transducer (18 MHz) and to verify the interobserver agreement. Material and methods: We enrolled 50 healthy volunteers (37 women, age between 30-58 years, mean age 41.7 years, divided into 3 groups according to age: 30-39, 40-49, and 50-58 years). The subjects were successively evaluated by 4 rheumatologists: 2 experienced (team A) and 2 beginners (team B) in US. Seven dorsal and palmar longitudinal scanning positions and a supplementary scan for MCP cartilage were performed. The bone surface (erosions, osteophytes), the intra-articular content (synovial thickening and vascularization, 4 grade scale), and the aspect of the metacarpal head cartilage were analyzed. The anterior palmar recess was measured. The time for examination was recorded. Results: Erosions were detected in 7% of joints by team A and 2% by team B (p0.05, kappa value 0.421). No grade 1 synovitis was observed by team A but 4 joints with grade 1 synovitis were identified by team B (p0.05). No statistical significant correlations were obtained between the dimensions of palmar recess and the body mass index or dominant hand (all p>0.05). No pathological findings were found in the examination of the metacarpal head cartilage. Power Doppler investigation found the presence of grade 1 signal in 2.5% joints by team A and 1.5% by team B (p>0.05) only in the dorsal scans. The mean time for examination was 7.8±1.74 min in team A and 13.78±2.96 min in team B (p

Standard cytotoxic chemotherapy is effective for certain type of cancer; however, as far as many other types are concerned, the available treatments only offer a limited survival benefit. Lung cancer represents one of these types of cancer. The development of specific therapies is the greatest promise for the successful treatment of this disease; nevertheless, an oriented approach depends on the understanding of the tumor cells genome. The exon sequencing of a large number of lung cancer samples has provided an initial insight of the somatic mutation profile of these tumors. These studies have confirmed the high frequency of TP53 and KRAS mutations in lung cancer. They have discovered mutational inactivation in some suppressor genes of known tumors that have not been previously associated with lung cancer. In addition, they have identified oncogene mutations of EGFR, which has led to the first targeted therapy in pulmonary adenocarcinoma. There are other oncogene candidates awaiting for functional validation. It is expected for the future sequencing of the entire exome and of the entire genome of lung cancer to reveal a more thorough view of somatic mutations that can be exploited for therapeutical purposes.