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Out of all benign tumors of the ceruminous glands, syringocystadenoma papilliferum is the rarest and represents only 2% of cases. It is an extremely rare benign tumor that originates from modified apocrine sweat glands. The aim of this paper was to present, according to our findings, the 18th case of syringocystadenoma papilliferum in the external auditory canal, with a detailed review of its clinical, radiological and histomorphological characteristics. A 59-year-old man reported to our clinic due to a 5×5 mm papillomatous growth at the entrance to the right external auditory canal. Histopathology indicated, after an excisional biopsy, that it was a syringocystadenoma papilliferum. The resection lines were free of tumor tissue, and the patient has no signs of tumor recurrence. Although rare, it should be considered as a differential diagnosis of lesions in this region. Complete excision is mandatory in order to avoid recurrence and potential malignant alteration.

Introduction. Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer in Caucasians and one of the most frequent malignancies in general, especially in older adults. Squamous cell carcinoma is the most frequent tumor developing on chronic leg ulceration, while BCC rarely occurs and is often misdiagnosed. In addition, since older adults commonly have coexisting chronic vein insufficiency, the ulcerated BCC is frequently mistaken as being of venous origin. Outlines of cases. We present five cases of BCC presenting as chronic venous ulcers. Conclusion. Long-lasting ulcers with no healing tendency must be considered malignant until proven otherwise. Knowing the characteristics of malignant ulceration may help in early detection and treatment.

Although profoundly studied, etiology of pancreatic cancer (PC) is still rather scarce. Some of established risk factors of PC are connected to an increased cadmium (Cd) body burden. Hence, the aim of this study was to investigate the role of this environmental pollutant in PC development by conducting human observational, experimental and in vitro studies.The case-control study included 31 patients with a histologically based diagnosis of exocrine PC subjected to radical surgical intervention as cases and 29 accidental fatalities or subjects who died of a nonmalignant illness as controls. Animal study included two treated groups of Wistar rats (15 and 30 mg Cd/kg b.w) and untreated control group, sacrificed 24 h after single oral exposure. In in vitro study pancreas hTERT-HPNE and AsPC-1 cells were exposed to different Cd concentrations corresponding to levels measured in human cancerous pancreatic tissue.Cd content in cancer tissue significantly differed from the content in healthy controls. Odds ratio levels for PC development were 2.79 (95% CI 0.91–8.50) and 3.44 (95% CI 1.19–9.95) in the third and fourth quartiles of Cd distribution, respectively. Animal study confirmed Cd deposition in pancreatic tissue. In vitro studies revealed that Cd produces disturbances in intrinsic pathway of apoptotic activity and the elevation in oxidative stress in pancreatic cells.This study presents three different lines of evidence pointing towards Cd as an agent responsible for the development of PC. Keywords: Pancreatic cancer, Cadmium, Carcinogenesis, Risk factors

The aim of this study was to evaluate longitudinal changes in drained dialysate cancer antigen 125 (dCA-125) levels and to assess relationships between dCA-125 and dialysis quality, peritoneal membrane transport rates, dialysate glucose load, peritonitis and use of erythropoiesis stimulating agents (ESA), angiotensin-converting-enzyme inhibitors (ACEi) and statins in patients with end-stage renal failure during the first 6 months of peritoneal dialysis (PD) treatment. This prospective study included 20 patients (11 males and 9 females; mean age 62.90±12.69 years) who were followed-up during the first 6 months of PD using conventional low pH glucose-based dialysis fluids. The concentration of dCA-125 was measured in all patients, and the peritoneal equilibration test (PET), peritoneal dialysis treatment adequacy (Kt/V), normalized protein catabolic rate (nPCR), and total, peritoneal and residual clearances of urea and creatinine were calculated. Information on peritonitis occurrence, the use of ESA, ACEi and statins were collected. Data were analyzed by the Mann-Whitney test, Wilcoxon matched pairs test and Spearman’s rank correlation. The concentration of dCA-125 significantly decreased during the follow-up (p=0.016). After 6 months of PD treatment, the concentration of dCA-125 decreased significantly (p=0.016) in all patients. The decrease was present in all patients, but was statistically significant in patients on ACEi therapy (p=0.006) and in patients not using statins (p=0.005) or ESA (p=0.012). No correlation was found between dCA-125 and glucose load, but a statistically significant negative correlation between dCA-125 and the PET for creatinine was observed (p=0.013). These findings challenge the role of dCA-125 in predicting mesothelial cell integrity in PD patients. https://doi.org/10.2298/ABS170324021J Received: March 24, 2017; Revised: May 7, 2017; Accepted: May 9, 2017; Published onlione: June 12, 2017 How to cite this article: Jovanovic NŽ, Trbojevic-Stankovic JB, Nesic DM, Obrenovic RŽ, Boricic NI, Stojimirovic BB. Cancer antigen 125 concentrations in patients on chronic peritoneal dialysis: Relationship with dialysis quality and membrane transport properties. Arch Biol Sci. 2018;70(1):13-20.

Background: Cadmium and lead are widespread and non-biodegradable pollutants of great concern to human health. In real life scenarios, we are exposed to mixtures of chemicals rather than single chemicals, and it is therefore of paramount importance to assess their toxicity. In this study, we investigated the toxicity of Cd and Pb alone and as a mixture in an animal model of acute exposure. Methods: Experimental groups received a single treatment of aqueous solution of Cd-chloride (15 and 30 mg/kg body weight (b.w.) and Pb-acetate (150 mg/kg b.w.), while the mixture group received 15 mg Cd/kg b.w. and 150 mg Pb/kg b.w. Toxic effects of individual metals and their mixture were investigated on hematological and biochemical parameters, and the redox status in the plasma, liver, and kidneys of treated Wistar rats. Results: Tissue-specific changes were recorded in various parameters of oxidative damage, while the accumulation of metals in tissues accompanied the disturbances of both hematological and biochemical parameters. It was observed that the level of toxic metals in tissues had a different distribution pattern after mixture and single exposure. Conclusions: Comprehensive observations suggest that exposure to Cd and Pb mixtures produces more pronounced effects compared to the response observed after exposure to single metal solutions. However, further research is needed to confirm toxicokinetic or toxicodynamic interactions between these two toxic metals in the organisms.

The possible cardioprotective effects of translocator protein (TSPO) modulation with its ligand 4′-Chlorodiazepam (4′-ClDzp) in isoprenaline (ISO)-induced rat myocardial infarction (MI) were evaluated, alone or in the presence of L-NAME. Wistar albino male rats (b.w. 200–250 g, age 6–8 weeks) were divided into 4 groups (10 per group, total number N = 40), and certain substances were applied: 1. ISO 85 mg/kg b.w. (twice), 2. ISO 85 mg/kg b.w. (twice) + L-NAME 50 mg/kg b.w., 3. ISO 85 mg/kg b.w. (twice) + 4′-ClDzp 0.5 mg/kg b.w., 4. ISO 85 mg/kg b.w. (twice) + 4′-ClDzp 0.5 mg/kg b.w. + L-NAME 50 mg/kg b.w. Blood and cardiac tissue were sampled for myocardial injury and other biochemical markers, cardiac oxidative stress, and for histopathological evaluation. The reduction of serum levels of high-sensitive cardiac troponin T hs cTnT and tumor necrosis factor alpha (TNF-α), then significantly decreased levels of serum homocysteine Hcy, urea, and creatinine, and decreased levels of myocardial injury enzymes activities superoxide dismutase (SOD) and glutathione peroxidase (GPx) as well as lower grades of cardiac ischemic changes were demonstrated in ISO-induced MI treated with 4′-ClDzp. It has been detected that co-treatment with 4′-ClDzp + L-NAME changed the number of registered parameters in comparison to 4′-ClDzp group, indicating that NO (nitric oxide) should be important in the effects of 4′-ClDzp.

Prognostic significance of immune microenvironment has been emphasized using the most advanced analysis, with consecutive attempts to reveal prognostic impact of this findings. The aim of this study was to compare and define prognostic significance of clinical parameters, microvessel density (MVD) in tumour tissue and expression of CD44s as adhesive molecule on tumour cells in diffuse large B cell lymphoma-DLBCL, primary central nervous system DLBCL-CNS DLBCL and follicular lymphoma-FL. A total of 202 histopathological samples (115 DLBCL/65 FL/22 CNS DLBCL) were evaluated. Overall response (complete/partial remission) was achieved in 81.3 % DLBCL patients, 81.8 % primary CNS DLBCL and 92.3 % FL. Absolute lymphocyte count-ALC/Absolute monocyte count-AMC2.6 in DLBCL and ALC/AMC ≥ 4.7 in FL were associated with better event-free survival (EFS) and overall survival (OS) (p 0.05). In DLBCL, MVD 42 blood vessels/0.36 mm(2) correlated with primary resistant disease (p 0.0001), poorer EFS and OS (p = 0.014). High CD44s expression in FL correlated with inferior EFS and OS (p 0.01). In DLBCL, multivariate Cox regression analysis showed that ALC/AMC was independent parameter that affected OS (HR 3.27, 95 % CI 1.51-7.09, p = 0.003) along with the NCCN-IPI (HR 1.39, 95 % CI 1.08-1.79, p = 0.01). Furthermore, in FL, ALC/AMC mostly influenced OS (HR 5.21, 95 % CI 1.17-23.21, p = 0.03), followed with the FLIPI (HR 3.98, 95 % CI 1.06-14.95, p = 0.041). In DLBCL and FL, ALC/AMC is simple and robust tool that is, with current prognostic scores, able to define long-term survival and identify patients with inferior outcome. The introduction of immunochemotherapy might altered the prognostic significance of microenvionmental biomarkers (MVD and CD44s).

Oncogene-induced senescence (OIS) serves as an initial barrier to cancer development, being proposed as a possible explanation for the usually benign behavior of the pituitary adenomas. We aimed to explore the immunohistochemical expression of the OIS markers, senescence-associated lysosomal β-galactosidase (SA-β-GAL), p16, and p21 in different types of 345 pituitary adenomas and compared it with the expression in the normal pituitary and in the specimens from the repeated surgeries. SA-β-GAL was overexpressed in the pituitary adenomas, compared to the normal pituitaries. Growth hormone (GH) producing adenomas showed the strongest SA-β-GAL, with densely granulated (DG)-GH adenomas more reactive than the sparsely granulated (SG). Nuclear p21 was decreased in the adenomas, except for the SG-GH adenomas that had higher p21 than the normal pituitaries and the other adenomas. p16 was significantly lower in the adenomas, without type-related differences. SA-β-GAL was slightly lower and p16 slightly higher in the recurrences. Our findings indicate alterations of the senescence program in the different types of pituitary adenomas. Activation of senescence in the pituitary adenomas presents one possible explanation for their usually benign behavior, at least in the GH adenomas that show a synchronous increase of two OIS markers. However, subdivision into GH adenoma subtypes reveals differences that reflect complex regulatory mechanisms influenced by the interplay between the granularity pattern and the hormonal factors, with possible impact on the different clinical behavior of the SG- and DG-GH adenoma subtypes. p16 seems to have a more prominent role in the pituitary tumorigenesis than in the senescence. Recurrent growth in a subset of the pituitary adenomas is not associated with consistent changes in the senescence pattern.

Adenoid cystic carcinoma (ACC) is one of the most common malignant salivary gland tumors. It is characterized by a high rate of recurrence, perineural invasion and development of distant metastases many years after removal of the primary tumor. Disorders of the induction of apoptosis and its cascade reactions where caspases are involved may be significant in the pathogenesis of this tumor.The immunohistochemical expression of caspase 9 and caspase 3 was analyzed by tissue microarray (TMA) in 50 cases of ACC in relation with different clinicopathological parameters (gender, age, localization, histological type and overall survival).Caspase 9 was expressed in the cytoplasm and nuclei of ACC tumor cells with varying degrees of staining intensity (1+, 6%; 2+, 54%, 3+, 40%). Comparison of caspase 9 expression in tumor cells with clinicopathological parameters (gender, age, localization, histological type and overall survival) showed no statistically significant difference except that the expression was more pronounced in females. Caspase 3 was expressed in the cytoplasm of tumor cells with varying degrees of staining intensity (1+, 22%; 2+, 36%; 3+, 42%). No correlation between the expression of caspase 3 and clinicopathological parameters was noticed.The expression of caspases 9 and 3 in ACC of the salivary glands can contribute in the better characterization of molecules involved in apoptosis of tumor cells.

s of the 52nd Congress of the European Societies of Toxicology (EUROTOX) Fibes Congress Center Seville, Spain, 04th-07th September 2016

Despite major advances in the treatment of diffuse large B cell lymphoma (DLBCL), approximately one third of the patients progress or die, suggesting the existence of additional oncogenic events. The purpose of this study was to evaluate the prognostic value of the "Hans classifier", and BCL2 and MYC protein expression and gene alterations in DLBCL patients treated with CHOP or R-CHOP chemotherapy over a 5-year period. Furthermore, we tried to correlate these parameters with the International Prognostic Index (IPI).The immunohistochemical (IHC) expression of CD10, BCL6, MUM1 and BCL2 on paraffin-embedded formalin-fixed tumor samples from 103 centroblastic DLBCLs was analyzed. IHC expression of MYC and fluorescence in situ hybridization (FISH) for MYC and BCL2 gene alterations was performed on 67 samples using the tissue microarray (TMA) method.The Hans algorithm was not predictive of survival in both therapy groups. No significant difference in BCL2 and MYC alterations or MYC protein expression in relation to complete response (CR), event-free survival (EFS) and overall survival (OS) was observed in our study. High IPI correlated significantly with poor outcome and it was identified as independent prognostic factor for OS and EFS (both p=0.000). The 5-year OS was 61% in the R-CHOP compared to 38% in the CHOP group (p=0.007). Rituximab significantly improved the OS in the BCL2 positive (60 vs 29%, p=0.008), and the BCL6 negative (73 vs 25%, p=0.001) cases.IPI is an independent prognosticator for DL-BCL patients and the addition of rituximab significantly improved survival. Furthermore, patients with BCL2+ and BCL6-DLBCL benefited from R-CHOP.

Normal pituitary tissue is frequently used for comparison with protein expression in tumor tissue, being obtained either at surgery or at autopsy. p16 and p21 proteins are cyclin-dependent kinase inhibitors, belonging to INK4 and Cip/Kip family, respectively. Their expression is increased in response to DNA damage or other cellular stressors, resulting in the activation of cell cycle checkpoints. They also play important roles in cellular senescence. The purpose of this study was to investigate differences in p16 and p21 immunohistochemical expression in normal pituitary tissue adjacent to pituitary adenoma obtained during neurosurgical procedure with pituitary tissue obtained at autopsy, from patients who died from non-endocrinological diseases. Our results show significant difference in p16 nuclear and p21 cytoplasmic immunohistochemical expression between two types of normal pituitary tissues. One of the reasons for this difference could be the age of subjects because those who underwent autopsy for a non-endocrinological disease were significantly older than subjects who underwent neurosurgery for a pituitary adenoma. Our finding that differences are probably not influenced by postmortem changes is supported by no significant correlation between postmortem interval and immunohistochemical p16 and p21 expression. The influence of the presence of a pituitary adenoma could not be evaluated in these specimens.