Breast Cancer and p16: Role in Proliferation, Malignant Transformation and Progression.

The definition of new molecular biomarkers could provide a more reliable approach in predicting the prognosis of invasive breast cancers (IBC). The aim of this study is to analyze the expression of p16 protein in IBC, as well as its participation in malignant transformation. The study included 147 patients diagnosed with IBC. The presence of non-invasive lesions (NIL) was noted in each IBC and surrounding tissue. p16 expression was determined by reading the percentage of nuclear and/or cytoplasmic expression in epithelial cells of IBC and NIL, but also in stromal fibroblasts. Results showed that expression of p16 increases with the progression of cytological changes in the epithelium; it is significantly higher in IBC compared to NIL (p < 0.0005). Cytoplasmic p16 expression is more prevalent in IBC (76.6%), as opposed to nuclear staining, which is characteristic of most NIL (21.1%). There is a difference in p16 expression between different molecular subtypes of IBC (p = 0.025). In the group of p16 positive tumors, pronounced mononuclear infiltrates (p = 0.047) and increased expression of p16 in stromal fibroblasts (p = 0.044) were noted. In conclusion, p16 protein plays an important role in proliferation, malignant transformation, as well as in progression from NIL to IBC.

Evaluation of Toxic Effects of Novel Platinum (IV) Complexes in Female Rat Liver: Potential Protective Role of Resveratrol.

The use of cisplatin in chemotherapy may provoke a deteriorating impact in many vital organs, suggesting the need for more selective derivatives and effective protective cotreatments. This study assesses the effects of three novel Pt(IV) complexes containing ethyl-, propyl- and butyl-esters of the ethylenediamine-N, N'-di-S, S- (2,2'-dibenzyl) acetic acid on liver injury markers, redox parameters, and cell morphology of female rat liver tissue in comparison to cisplatin. In addition, the study evaluates the possible protective effects of resveratrol as well. The rats were divided into ten groups and were administered intraperitoneally with a single dose of cisplatin (7.5 mg/kg) or Pt(IV) complexes (10 mg/kg) and/or resveratrol (25 mg/kg). All treatments caused changes in body weight, food intake, and liver/bw ratio. Acute treatment with novel complexes decreased the levels of TB and TP while elevated the activity of ALT, AST, GGT, ALP which subsequently indicated on the liver damage. All three complexes significantly reduced the levels of LPO, O2.-, NO2- and activity of CAT, while increasing the activity of SOD, GSH-Px, GR, GST, and level of GSH, implying that these compounds could provoke redox balance disruption in liver cells. Moreover, according to the histopathological observations, the novel Pt(IV) complexes exerted stronger hepatotoxicity than cisplatin. Possible protective effects of resveratrol were not detected and even combined with examined compounds it abolished the activity of the antioxidative system of the liver cells causing more intense toxicity. Further investigation is required to elucidate the effects of Pt-based drugs and resveratrol in the estradiol-rich environment of female rats as well their influence on male rats' tissues.

Correlation of Clinicopathological Characteristics of Breast Carcinoma and Depression.

The prevalence of depression among women with breast cancer (BC) is extremely variable in research studies. The aim of this study was to determine the prevalence of depressive disorder in women suffering from BC as well as to examine its relationship with clinical-pathological and immunophenotypic characteristics of BC. The study included 194 patients with BC who were diagnosed with the disease between 2009 and 2015 in the Clinical Center Kragujevac, Serbia. Pathohistological and immunohistochemical analyses was used on the material obtained after the surgical removal of breast tumors, determining all significant clinical and morphological parameters. The level of depression among the examinees confirmed that the differences in the level of depression between the histological grades were statistically significant. According to the univariate binary logistic regression, the depression of a patient correlates with the category of molecular tumor subtype/Luminal A (p < 0.0005), PR expression (p = 0.050) and lymphatic invasion (p = 0.025). Multivariate binary logistic regression showed that the onset of depression associated with the present molecular subtype of the tumor of a worse prognostic character (p = 0.019). Depression is a common disorder in women with breast cancer. The level of depression is correlates with some of the clinicоmorphological and immunophenotypic characteristics of BC.

Impact of the toxicity of Cylindrospermopsis raciborskii (Woloszynska) Seenayya & Subba Raju on laboratory rats in vivo.

In vivo laboratory studies of toxicity were performed on Wistar rats using a methanol extract produced by the natural population of Cylindrospermopsis raciborskii (abundance of 2.13 × 105 trichomes mL-1) collected at Aleksandrovac Lake (Serbia). HPLC analysis showed that the extract contains 6.65 µg cylindrospermopsin (CYN) mg-1. The rats were killed 24 or 72 h after a single intraperitoneal injection of C. raciborskii extract in concentrations of 1500, 3000, 6000 and 12,000 µg kg-1 body weight (bw) and an equivalent amount of CYN as present in the highest dose of the extract (79.80 µg CYN kg-1 bw). The genotoxic effect on the livers treated with C. raciborskii was evaluated using comet assay and potential induction of oxidative stress as the toxicity mechanism associated with the presence of CYN in extract. The results from the analyses of DNA damage in the comet tail length, tail moment and percentage of DNA in the tail in the liver indicated that administration of extract and CYN present statistically significant difference when compared with the negative control group. Although an increase in the frequency of selected parameters induced by the CYN was observed in the liver, this damage was less than the damage resulting from the administration of the highest dose of extract. The changes in the biochemical parameters of the hepatic damage showed that the application of single doses of the extract and CYN did not cause serious liver damage in rats. The extract and CYN significantly increased oxidative stress in rats' liver after a single exposure.

Expression of vascular endothelial growth factor and microvascular density assessment in different histotypes of basal cell carcinoma.

PURPOSE: In this study, we investigated the expression of vascular endothelial growth factor (VEGF) and tumor microvascular density (MVD) in different histotypes of basal cell skin carcinoma (BCC). METHODS: We used a total 101 histological archival specimens, including superficial, nodular, cystic, keratinocytic, adenoid infiltrative types and cases of metatypical BCC. Routine hematoxylin/eosin (H&E) and immunohistochemical ABC method with NOT AE1/AE3, anti VEGF anti CD34 antibodies were used. VEGF expression in tumor cells was studied in relation to the BCC histotype and demographic characteristics. For statistical analysis ANOVA (F test), Student's t-test, and Karl Pearson coefficient were used. RESULTS: VEGF expression was significantly lower in the superficial histotype compared to all other types of BCC. No significant difference in VEGF expression between infiltrative, metatypical, adenoid and nodular types was found, but the highest expression of VEGF was seen in the infiltrative and metatypical types. Significantly higher MVD was found in infiltrative, adenoid, metatypical and nodular types. CONCLUSION: Our results suggest that the angiogenic potential of BCC correlated with tumor histotype, and histological growth pattern BCC enable distinction of the patients with increased risk of recurrence and / or metastasis.

Subcutaneous fat necrosis in newborns.

Subcutaneous fat necrosis of newborns is a transient, benign process in full- term or postmature neonates. It is associated with perinatal distress. Newborn stress inhibits immature enzyme system, which already has relative inability to desaturate saturated fatty acids. It leads to fat crystillisation and necrosis. Skin biopsy revealed necrotic focus and crystallisation in fat cells. Hypercalcemia may be a potential complication.