Breast cancer is one of the leading causes of cancer-related mortality in women. During tumor growth, periods of hypoxia are followed by reoxygenation due to neovascularisation leading to disturbed ...redox homeostasis. ROS (Reactive Oxygen Species) produced under hypoxia activate HIF1α. ROS can also activate the major antioxidant transcription factor NRF2, but also cause damage to biomolecules. Lipids are susceptible to peroxidation, as evidenced by the formation of reactive aldehydes, among which, HNE (4-hydroxynonenal) is the most studied one. Knowing that HIF1α (Hypoxia Inducing Factor 1α) is associated with breast cancer malignancy, we aimed to investigate its correlation with HNE and NRF2 (Nuclear factor erythroid 2-related factor 2). Our results show that HIF1α is activated in breast cancer, indicating an increase in ROS but not followed by HNE production. On the other hand, NRF2 was increased in all types of breast cancer suggesting that oxidative stress is present in these pathologies, but also supporting HIF1α. Interestingly, NRF2 was activated in HER2 positive and TNBC, indicating the role of stromal NRF2 in breast cancer malignancy.
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•NRF2 is present and activate in all types of breast cancer.•HNE is present in very low levels in breast cancer.•HNE is absent in HER2 + and TNBC stroma.•NRF2 is present and activated in stroma of HER2 + tumora and TNBC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ
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•200 equally matched case and control volunteers were recruited for this study.•Oxidative status of patients with thyroid diseases was worse compared to controls.•Patients had higher ...baseline genome damage compared to controls.•High prevalence of aberrantly expressed B-Raf and Ret in thyroid was detected.•Cytogenetic biomonitoring might be useful tool in human risk assessment.
Since the incidence of cancer has increased over the years, adequate prevention programmes are needed. Thyroid cancer is one of the fastest growing cancer types in the world. In this study we performed a case-control study of 100 untreated patients with thyroid diseases (papillary thyroid cancer, follicular thyroid adenoma, and other thyroid diseases) and 100 control volunteers. Oxidative status differed among the two investigated groups. The patients’ group had 1.60-fold higher concentrations of malondialdehyde and 1.26-fold higher concentrations of protein carbonyls. At the same time, the concentrations of glutathione and catalase activity were by 32% and 35% lower, respectively. A similar effect was observed for the cytogenetic status where higher comet assay tail intensity (1.84-fold) and the total numbers of chromosome aberrations (1.47-fold), micronuclei (2.32-fold), nucleoplasmic bridges (3.98-fold), and nuclear buds (2.34-fold) were detected. As for protein expression in thyroid tissue, 97.89% were positive for either B-Raf or Ret. Interestingly, the papillary thyroid cancer patients more frequently expressed B-Raf proteins compared to the follicular thyroid adenoma patients and patients with other thyroid diseases. Human biomonitoring studies enable a risk assessment of general population, such data could be used to identify risk subgroups.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The most common nonmelanoma skin cancers (NMSC) are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The incidence of NMSC is 18-20 times higher than the incidence of melanoma. The ...Cyclooxygenase-2 (COX-2) and Matrix Metalloproteinase-1 (MMP-1) enzymes have both been linked to the development of these diseases but their exact significance is unknown. We conducted a retrospective analysis on 148 adult patients with cutaneous BCC and SCC. Cases were divided according to the sub-types of BCC and the degree of SCC differentiation. Immunohistochemical staining for COX-2 and MMP-1 was performed and analyzed to determine if the expression of these biomarkers were associated with BCC subtypes and the degree of SCC. differentiation. We did not find a significant association of the level of differentiation of SCC with the immunohistochemical expression for MMP-1 or COX-2. There was a significant association between BCC subtypes and immunohistochemical expression for MMP-1; positive expression of this enzyme reduces the odds for the infiltrative subtypes by 90%. A marginally significant association between BCC subtypes and immunohistochemical expression for COX-2 was also found. This enzyme was highly expressed in non-infiltrative basal cell carcinoma types (94%) compared with infiltrative types (71%). In conclusion, we did not find a significant predictor for SCC expression levels for either of two biomarkers, while the expression of MMP-1 in BCC was significantly inversely associated with the infiltrative type (moderate sensitivity and high specificity). Further research with larger sample sizes is needed to precisely determine the role these enzymes have in these diseases.
•Genome integrity of 23 untreated papillary thyroid cancer patients was assessed.•Control group was matched in age, gender, and smoking status.•Untreated patients had elevated micronucleus and comet ...assay parameters.•All tissue samples from patients were positive for either Raf-B of Ret protein.•Cytogenetic biomonitoring might be used for better cancer prevention.
Thyroid cancer is one of the fastest growing cancer types worldwide. Using the cytokinesis-block micronucleus (CBMN) and comet assays, we performed a case-control study of 23 untreated papillary thyroid cancer (PTC) patients and 23 healthy volunteers. PTC patients showed higher basal DNA damage in peripheral blood lymphocytes. The CBMN assay indicated that the numbers of micronuclei, nuclear buds, and nucleoplasmic bridges among the cases were 2.67-, 2.79-, and 7.72-fold higher, respectively, than among the controls (p<0.05). Comet assay tail lengths and tail intensities were 1.20- and 1.94-fold higher, respectively (p<0.05). In additional, 14 thyroid tissues from PTC patients were probed for Raf-B and Ret expression; all samples were positive for at least one of these proteins.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The aim was to determine immunohistochemical expression of NEDD9 protein in head and neck squamous cell carcinoma (HNSCC) and the possible relation of its expression with primary tumor size (T), ...regional lymph node status (N), stage of disease (TNM) and survival period. A total of 131 patients with primary tumor localization in the area of oropharynx, hypopharynx and larynx, monitored for at least 5 years after initial surgical treatment were analyzed. The study included 128 male and three female patients, median age 62.0 (range 53.0-68.0) years. Of these, 105 (95%) patients showed positive NEDD9 expressed by dyed cytoplasm. There were no significant differences in NEDD9 expression according to TNM tumor status. Patients with positive NEDD9 expression had a significantly higher median (IQR) survival time 51.0 (15.0-60.0) months as compared to 22.5 (9.0-55.0) months in patients with negative NEDD9 expression (p=0.048). NEDD9 negative expression, controlled for the influence of other variables included in the Cox’s proportional hazards model, had a significant hazard ratio (HR) of 2.10 (95% CI: 1.23-3.58; p=0.006). The results of our study showed that NEDD9 expression might be an independent prognostic marker in patients with HNSCC regarding data on overall survival and mortality.
Androgen receptors (AR) are ligand-dependent nuclear transcription factors. These are steroid receptors, similar to estrogen receptors (ER). They are expressed in numerous cells in the body, with ...different constructive roles. AR signalling can be involved in the development of a variety of human malignant tumors, such as prostate cancer, bladder, liver, salivary glands, kidney, lung, melanoma, sarcoma, breast cancer, and many others. The role of AR is most clear and today best explained in prostate cancer. The mechanism of AR signalling in other human epithelial tumors is still quite unclear and the effects are different to entirely opposite in different tumors. In breast cancer, AR are the most commonly expressed receptors, but still with an incompletely clear role, prognostic and predictive significance. The expression of AR in triple-negative breast cancer (TNBC) is highly variable. Despite the marked differences in the results of the various analyzes, they appear to have a beneficial effect on the prognosis and are potentially the target of antihormone therapy for treatment of TNBC in the future.
Dijagnostika i liječenje karcinoma dojke je posljednjih 20 godina vrlo brzo napredovalo. U prvo vrijeme dijagnoza se postavljala na temelju kliničkih nalaza što se promijenilo uvođenjem mamografije. ...Razvoj radioloških metoda doveo je do otkrivanja malih i nepalpabilnih lezija te su kirurzi počeli primjenjivati poštedne kirurške zahvate nakon kojih slijedi adjuvantno liječenje. Zbog toga je danas vrlo važan multidisciplinarni tim u liječenju bolesnica s karcinomom dojke. Patolog je ključni član multidisciplinarnog tima jer mora odrediti brojne prognostičke i prediktivne čimbenike za bolesnice s karcinomom dojke što sve zahtjeva odgovarajuće standardizirane protokole i postupke za uzorke tkiva.
Recent interest of many investigators is focused on epidermal growth factor receptor (EGFR) family, because of their potential role in the pathogenesis and progression of breast cancer. Paraffin ...tumor sections were collected retrospectively from 181 breast cancer patients diagnosed between 2002 and 2003. Immunohistochemical staining with ErbB-1, ErbB-2, ErbB-3, and ErbB-4 monoclonal antibodies was performed. The ErbB expression was correlated with the other clinicopathological variables. Overexpression of ErbB-1, ErbB-2, ErbB-3, and ErbB-4 was observed in 20.6, 18.2, 14.3, and 5.7% cases, respectively. Overexpression of ErbB-1 and ErbB-2 was associated with poor prognostic features and decreased 5-year disease-free survival. The patients with co-overexpression of ErbB-1 and ErbB-2 had a shorter DFS, although this difference was not statistically significant. ErbB-1 overexpression may indicate a subset of patients with a poor disease prognosis. Assays for ErbB-1 and ErbB-2 may be more useful than a single assay in predicting prognosis of a breast cancer patient.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Thyroid cancer represents 2.1% of new cancer cases, yet it is the most common endocrine cancer and one of the fastest growing cancer types in the world. The incidence of thyroid cancer is the highest ...in elderly population (60-69 years), but novel data suggest decline in age when this cancer is frequently diagnosed to 50-59 years. Thyroid cancer is 2-4-fold more common in female population what is usually associated with female hormones and the differences in oxidative stress levels. Since the WHO suggest that roughly 30% of cancer can be prevented, the aim of this study was to evaluate the role of micronucleus test and comet assay as cancer predictive biomarkers.
In this study, 36 patients with papillary thyroid cancer (PTC) were recruited in accordance with all ethical standards. The average age of the group was 52±14 years, 28:8 female:male ratio, and 33% of active smokers. Control group was matched for age, gender, and smoking habits (52±14 years, 28:8 female:male ratio, and 33% of active smokers).
The number of micronucleated (MNed) cells in human peripheral blood lymphocytes was significantly higher (p<0.05) in PTC group (12.94±5.81) compared to control group (4.36±2.58). Additionally, the comet assay tail moment (TM) was also significantly (p<0.05) higher in the PTC group compared to control group (0.39±0.71 vs 0.14±0.05). These results indicate that people with PTC had more genome damage compared to healthy controls. The immunohistochemical analysis of thyroid revealed 97.2% BRAF positive and 20.6% RET/PTC positive samples.
Taken together, the PTC group had more DNA damage what is associated with high prevalence of BRAF mutations and RET/PTC translocations as a consequence of disrupted genome integrity. The results imply that cytogenetic tools might be used in human biomonitoring for identification of high-risk groups but further research is needed to assess normal and cut-off values.
Multielemental analysis of whole blood can provide significant information for the evaluation of nutritional status and diagnosis of certain diseases as well as for the assessment of exposure to ...potentially toxic metals. However, the quantification of multiple elements in whole blood is not easy partly because of the wide variation in element concentrations (from ng L
−1
to g L
−1
) and the complex matrix. The aim of this work was to develop a fast, sustainable, and reliable analytical method, in combination with low-power TXRF, for multielemental analysis of blood samples. Firstly, a set of experiments were carried out to select the best diluent type and dilution factor using the control material SeronormTM Trace Elements Whole Blood L-1. A critical evaluation of the parameters affecting the sample deposition on the reflector was also carried out including a study of the shape and element distribution of the deposited residue on the reflector by micro X-ray fluorescence spectrometry. Using the best analytical conditions, limits of detection estimated were in the low milligrams per kilogram range and similar to those obtained using more complex sample treatments such as digestion. Accuracy and precision of the results were in most cases acceptable (recoveries 89–102%, RSD 6–8%,
n
= 5). Only underestimated values were obtained for light elements such as potassium. To prove the applicability of the method, several blood samples from control and thyroid disease patients were analyzed. Despite the fact that more samples need to be analyzed, it seems that Zn and Br contents in some of the patients are significantly higher compared to control samples.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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