The Expression of Tumor-Associated Macrophages and Multinucleated Giant Cells in Papillary Thyroid Carcinoma

BACKGROUND: Inflammation that occurred in the tumor microenvironment was characterized by abundant macrophage infiltration, playing role in innate immunity. Multinucleate giant cells (MGCs) occur in a variety of inflammatory, hyperplastic, and neoplastic thyroid disorders. They also have been recognized as a feature of papillary thyroid carcinoma (PTC). AIM: The aim of this study was to evaluate cases of PTC for the presence of macrophages, and estimate CD68+ TAMs density in tumor stroma, margin and the surrounding tissue. We assessed also MGCs. METHODS: Macrophages and MGCs densities were correlated with clinicopathologic parameters to assess the possible prognostic significance. We investigated 56 patients immunohistochemically and immunofluorescence with antibodies against CD68 and IL-17. RESULTS: A statistically significant correlation was established between PTC patients in III stage, containing many MGCs, and PTC in I and II stage, with many MGCs. Eighty Percent of patients in III stage showed many MGCs in comparison with patients in I and II stage, where many MGCs were found only in 21,1% (χ2 = 6.189, p = 0.013). CONCLUSION: Our study demonstrates that the increased density of MGCs is associated with advanced stage of PTC, and therefore with tumor progression and that cases of PTC should be carefully screened for their presence

Cerebral Aspergilloma in Patient with Diabetes – A Case Report with Short Literature Review

BACKGROUND: In the recent years, the incidence of fungal brain abscess has been rising as a result of the increased use of corticosteroid therapy, broad-spectrum antimicrobial therapy, and immunosuppressive agents. Aspergillosis of the central nervous system (CNS) is reported in 10%–20% of the patients having invasive fungal disease. Commonly, the disease is observed in immunocompromised or immunosuppressed patients; also, patients who suffered traumatic head injury are reported as well to develop the infection due to due cranial defect accompanied by dural tearing. Symptoms are non-specific neurologic manifestations. CASE PRESENTATION: We presented a case of a 68-year-old man who had diabetes mellitus type II. He was admitted to in neurosurgery clinic due reported head trauma. Initially, he complained of a headache, dizziness, slurred speech, nausea, and pain in the right ear with tinnitus and pain in his right upper teeth – continuous for a month. The patient was conscious, adequate, Glasgow Coma Scale – 15 points, with left-sided hemiparesis, general symptomatic syndrome. An emergent computed tomography scan was performed, which showed tumorous formation in patient’s right temporal lobe that had mass effect and compression of the right lateral ventricle. The patient was discussed on a emergent clinical counsel and it was decided that he was shown for surgical treatment. An informed consent was signed by the patient and his relatives. After the surgery intervention – the histological result of the biopsy was aspergilloma of the brain and the microbiological result was Aspergillus fumigatus. CONCLUSION: The prognosis for CNS aspergillosis is poor, but the early diagnosis and effective medical and surgical treatments may reduce morbidity and mortality. &nbsp

The Position of Neutrophils-To-Lymphocytes and Lymphocytes-To-Platelets Ratio as Predictive Markers of Progression and Prognosis in Patients with Non-Small Cell Lung Cancer

BACKGROUND: Non-small cell lung cancer (NSCLC) is an insidious metastasis condition of the lungs often presenting no symptoms at the onset. Defining markers for quick determination of prognosis is essential for building up a treatment strategy.AIM: The aim of this study is to define the role of the Neutrophils-to-Lymphocytes ratio (NLR) and Platelets-to- Lymphocytes ratio (PLR) as biomarkers in patients with NSCLC, according to the stage and prognosis of the disease.METHODS: We investigated 20 patients with NSCLC. NLR and PLR are calculated and are evaluated according to the presence or absence of metastasis, stage of the disease, histological type and survival rate.RESULTS: We found that thirteen of the patients had low NLR, while the rest 7 had high NLR (mean 3.15). By analysing PLR we found that 11 patients have low and 9 have high level of PLR (mean 1.42). After the correlations have been made we discovered that in 90.1% of the patients with low PLR no lymph metastasises were detected, while in 50% of the patients with high PLR lymph metastasises were observed (c2 = 3.99; P = 0.046). We also discovered that in 84.6% of the patients with low NLR lymph metastases were absent, while in 42.9% with high NLR lymph metastasises were present (c 2 = 1.83; P = 0.176).CONCLUSION: In conclusion, NLR and PLR were discovered as prominent biomarkers which provide relatively fast determination for prognosis in patients with NSCLC

Immunohistochemical Expression of TGF-Β1, SMAD4, SMAD7, TGFβRII and CD68-Positive TAM Densities in Papillary Thyroid Cancer

BACKGROUND: Papillary thyroid carcinoma (PTC) accounts for 80% of the thyroid malignancies that are characterised by slow growth and an excellent prognosis. Over-expression of SMAD4 protein restores TGF-β signalling, determines a strong increase in anti-proliferative effect and reduces invasive potential of tumour cells expressing it.AIM: The study aimed to analyse the immunohistochemical expression of TGF-β1 and its downstream phosphorylated SMAD4, element and of the inhibitory SMAD7 PTC variants and their association with the localisation of TAMs within the tumour microenvironment.METHODS: For this retrospective study we investigated 69 patients immunohistochemistry with antibodies against TGF-β, TGF – β-RII, SMAD4, SMAD7, CD68+ macrophages.RESULTS: Patients with low infiltration with CD68+ cells in tumour stroma has significantly shorter survival (median of 129.267 months) compared to those with high CD68+ cells infiltration (p = 0.034). From the analysis of CD68+ cells in tumour border and tumour stroma correlated with expression of TGF-β1 / SMAD proteins, we observed that the positive expression of TGF-β1 in tumour cytoplasm, significantly correlated with increased number of CD68+ cells in tumour border (X2 = 5,945; р = 0.015).CONCLUSION: TGF-β enhances motility and stimulates recruitment of monocytes, macrophages and other immune cells while directly inhibiting their anti-tumour effector functions

The Role of the Molecular Subtypes in the Prognosis of Breast Cancer Patients

BACKGROUND: Understanding the biology of the tumor, by dividing it into molecular subtypes, has made it possible to individualize the therapeutic approach in high-risk patients. AIM: We aimed to determine the importance of established molecular subtypes in the prognosis and the importance of disease-free and overall survival (OS) in patients with non-metastatic breast cancer. MATERIALS AND METHODS: We analyzed 94 patients with non-metastatic breast cancer for the period 2010–2018. The median follow-up time was 60 months. The mean age in the study group was 60.03 years (SD ± 10.52). According to the characteristics of the studied indicators, we divided the group into Luminal A (n-59 [62.7%]), Luminal B/HER2 (−) (n-2 [2.1%]), Luminal B/HER2 (+) (n-8 [8.5%]), HER2 overexpressing (n-3 [3.2%]), and triple-negative subtype (n-22 [23.5%]). In all patients in the study group, we analyzed the 5-year overall survival (OS) and disease-free survival (DFS) and referred it to molecular subtypes, lymphatic status, HER-2 status, the presence or absence of endocrine therapy for the follow-up period, tumor differentiation, and type of surgery. RESULTS: We observed the 5-year OS in 92% of patients identified as Luminal A; at 50% of Luminal B/HER2 (−) neg.; in 62.5% with Luminal B/HER2 (+), in 67% with HER2-overexpressing carcinoma; and in 66.7% of patients with triple-negative subtype. The total cancer-associated mortality rate in the analyzed period reached 15.9% (n = 15). Patients with mastectomy (p = 0.019, p = 0.027), positive axilla with more than 4 lymph node (LN) (p = 0.000; p = 0.000), and Luminal B/HER-2 (+) tumors (p = 0.004; p = 0.003) were the independent prognostic factors for worse DFS and OS in our study group. Histological differentiation and HER-2 expression were in unsatisfactory correlation (p = 0.077; p = 0.044 and p = 0.081; p = 0.055, respectively). CONCLUSION: Molecular subtypes are essential in the prognosis of breast cancer and maybe a criterion for an individualized therapeutic approach

NAFLD IN WISTAR RATS AFTER FRUCTOSE CONSUMPTION - ULTRASOUND, BIOCHEMICAL AND HISTOLOGICAL CHANGES

The aim of the study was to model hepatic steatosis as a manifestation of metabolic syndrome in male Wistar rats after an 8-week administration of 15% fructose. Ultrasonographic evaluation of the experimental group showed evidence of non-alcoholic fatty liver disease (NAFLD). Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and uric acid were significantly elevated in sera from the treated rats. Histological examination found development of hepatic steatosis in rats of the fructose group compared with controls. The current study showed the risk associated with fructose overconsumption in food and beverages for the development of metabolic syndrome and related fatty liver disease, gout, type 2 diabetes, arterial hypertension and other disorders

Expression of E-Cadherin/Beta-Catenin in Epithelial Carcinomas of the Thyroid Gland

BACKGROUND: The aberrant activation of Wnt signalling pathway may be a common denominator for the development of thyroid tumorigenesis. It was announced that the loss of E-cadherin rather than β-catenin mutation represents a crucial event in determining the degree of differentiation of thyroid carcinomas.AIM: The aim of the study was to evaluate the expression of E-cadherin and β-catenin in the thyroid cancer tissue and to correlate these data with some histological and clinical parameters of the tumours.MATERIAL AND METHODS: We investigated 112 patients, having thyroid tumours – papillary, follicular, anaplastic and oncocytic carcinomas immunohistochemically with antibodies against E-cadherin and β-catenin. Survival analyses were done.RESULTS: E-cadherin expression was focally retained in the tumour cell membranes and the tumour cell cytoplasm of the papillary, follicular and oncocytic thyroid cancers, weather in anaplastic cancers it was almost lost (p = 0.0042, and р = 0.019, respectively, Fisher's Exact Test). The expression of β-catenin in tumour cytoplasm and membrane in papillary cancers was higher as compared to that in the other tumours (p = 0.111, and р = 0.0104, respectively).CONCLUSION: Not surprisingly, the presence of aberrant expression of E-cadherin and β-catenin in thyroid cancer has been associated with better patients' prognosis and better differentiated tumour histology

IL-6 Activities in the Tumour Microenvironment. Part 1

The predominant role of IL-6 in cancer is its key promotion of tumour growth. IL-6 binds IL-6 receptor (IL-6R) and the membrane-bound glycoprotein gp130. The complex I-6/IL-6R/gp130 starts the Janus kinases (JAKs) and signal transducer and activator of transcription 3 (STAT3) or JAK/STAT3 pathway. IL-6R exits in two forms: a membrane-bound IL-6Rα subunit (mIL-6R) that participates in classic signalling pathway and soluble IL-6R subunit (sIL-6R) engaged in trans-signalling. The pro-tumour functions of IL-6 are associated with STAT3, a major oncogenic transcription factor that triggers up-regulation of target genes responsible for tumour cell survival. IL-6 combined with TGF-β induces proliferation of pathogenic Th17 cells. The anti-tumour function of IL-6 is the promotion of anti-tumour immunity. IL-6 trans-signaling contributed to transmigration of lymphocytes in high endothelial venules (HEV). Dendritic cell (DC) secreted IL-6 in the lymph node influences the activation, distribution and polarisation of the immune response. Elevated serum levels of IL-6 and increased expression of IL-6 in tumour tissue are negative prognostic marker for patients’ survival