Circulating osteocyte-related biomarkers (vitamin D, sclerostin, dickkopf-1), hepcidin, and oxidative stress markers in early breast cancer: Their impact in disease progression and outcome.

Breast cancer (BC) is a major concern to female health worldwide. We assessed the circulating osteocyte-related biomarkers, hepcidin, and oxidative stress status among early-stage BC patients in aspects of clinical severity and impact on the outcome. The study incorporated 73 patients categorized into 57 early-stage BC and 16 benign breast diseases and 30 healthy controls. Serum 25-hydroxyvitamin D [25(OH)D], sclerostin (SOST), dickkopf-1(DKK1), and hepcidin were measured using ELISA, while, serum oxidative stress markers were assessed by spectrophotometry. Our results show that patients with BC showed significant increase in the mean levels of DKK1, SOST, hepcidin, and LPER and significant decrease in the mean levels of 25(OH)D, SOD, GPx, and Hb when compared with controls and benign breast diseases. Significantly higher DKK1, hepcidin, and SOD levels among benign breast diseases were found in comparison to control group. There were significantly lower levels of 25(OH)D, SOD, and Hb and significantly higher levels of SOST, DKK1, hepcidin, No, and LPER with advanced grade. Lower levels of 25(OH)D, SOD and higher levels of SOST, hepcidin were observed with increasing the malignant stage. Reduced levels of 25(OH)D, and SOD were significantly associated with poor prognosis and were strong predictors among BC. There were significant negative correlations between 25(OH)D with LPER, SOST, and hepicidin. We conclude that low 25(OH)D, high SOST, DKK1, and hepcidin, and dysregulated oxidative stress could be helpful in early detection and assessment of BC. 25(OH)D, and SOD were the most relevant to tumor progression and prognosis which indicate a significant role in the BC pathogenesis and could be promising targets in management. Our research paves the way to disrupt vicious circle between these biomarkers to obtain the best care of BC.

The adipokine Chemerin and Fetuin-A Serum Levels in Type 2 Diabetes Mellitus: Relation to Obesity and Inflammatory Markers.

Chemerin and fetuin-A are recently discovered as metabolic regulator hormone in obesity and type 2 diabetes mellitus. However, elevated levels of chemerin and fetuin-A have been associated with insulin resistance and systemic inflammation. The present study aimed to investigate the significance of serum chemerin and fetuin-A levels in obese diabetic patients. Also, to determine whether, chemerin and fetuin-A along with markers of inflammation (IL6 and CRP) and obesity-related parameters in T2DM patients. Serum levels of chemerin and fetuin-A were evaluated using ELISA in 71 T2DM patients and 14 apparently healthy controls. Both groups were subdivided into obese and lean. Serum chemerin and fetuin-A levels were significantly higher in T2DM patients compared to controls (P < 0.001, for both) and significantly higher in obese T2DM in comparison to obese control group (P < 0.01 & P < 0.05, respectively). Serum chemerin and fetuin-A levels correlated positively with HbA1c, HOMA-IR, FBG, IL6 and CRP. In obese patients, serum chemerin and fetuin-A levels correlated positively with BMI and waist circumference. In conclusion, the strong association of chemerin and fetuin-A with insulin resistance and some inflammatory markers may provide an interesting link between obesity, inflammation and diabetes mellitus in human.

Tissue Indices of Telomere Length and p53 in Patients with Different Gastrointestinal Tumors: Correlation with Clinicopathological Status.

Telomere length dysfunction is involved in the generation of genomic rearrangements that drive progression to malignancy. A set of serological markers for telomere dysfunction, namely chitinase and N-acetylglucosaminidase (NAG), DNA damage, and tissue alteration of p53 have been identified. The probability that genomic damage, accumulation of reactive oxygen species, and shorter telomeres may be related to the onset and advancement of gastrointestinal (GI) tumors. A total of 40 patients with GI tumors and 20 healthy controls with matched age and sex were included. Estimation of serum chitinase, NAG, lipid peroxide (LPER), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase by colorimetric methods, and p53 by ELISA were assessed. Related clinicopathological features were determined. Serological chitinase, NO, LPER, and p53 were significantly increased, SOD was significantly decreased (p Ë‚ 0.001 for each) in GI tumor patients compared with controls and correlated significantly with age. There was a significant correlation between telomere dysfunction indices, p53, oxidative stress indices, and malignant stages of GI cancer patients. Moreover, a significant difference in the mean serum levels of indices between control, malignant, and benign subjects was found. Accordingly, these biomarkers play an important role in the pathogenesis of GI cancer and their estimation may predict the GI tumor behavior.

Apoptosis, angiogenesis, inflammation, and oxidative stress: basic interactions in patients with early and metastatic breast cancer.

PURPOSE: Breast cancer (BC) is a complex, multi-stage disease involving deregulation of different signaling cascades. The present study was conducted to determine the extent of apoptosis, angiogenesis, inflammation, and oxidative stress in patients with different stages of BC as an approach to disease biological behavior. Therefore, plasma levels of soluble (s) Fas, bcl-2 as antiapoptotic indices; interleukin (IL)-8, tumor necrosis factor (TNF)-α as apoptotic, inflammatory, angiogenic indices; lipid peroxides (LPO), nitric oxide (NO) as oxidative stress and angiogenic indices were measured in patients with BC. METHODS: Thirty-seven newly diagnosed patients with BC, 30 patients with benign breast masses, and 30 healthy controls were recruited. Plasma levels of sFas, bcl-2, IL-8, and TNF-α were measured by immunosorbent assay kits and LPO and NO by chemical methods. RESULTS: Plasma sFas and LPO were significantly higher in BC patients versus benign breast masses and healthy controls (P < 0.0001). Bcl-2, IL-8, TNF-α, and NO were significantly higher in benign breast masses (P < 0.0001, P < 0.037, P < 0.0001, P < 0.001) and BC (P < 0.0001) versus controls and in BC versus benign breast masses (P < 0.0001). sFas, bcl-2, IL-8, TNF-α, LPO, and NO were increased with advanced tumor stages. There were positive correlations between sFas, bcl-2, IL-8 TNF-α, LPO, and NO. CONCLUSIONS: BC tumor cells overexpress bcl-2 and sFas to secure their outgrowth and survival. However, this coincides with activation of physiologic regulatory mechanisms, as increased IL-8, TNF-α, LPO, and NO, which try to stop tumor cells by inducing apoptosis. Outcompeting of these mechanisms result in tumor progression as IL-8, TNF-α, and NO are also angiogenic stimulators.

Biological markers and response to neoadjuvant taxane-based chemotherapy in patients with locally advanced breast cancer.

Introduction. Biological markers as Her2/neu, p53, and hormonal receptors (HmRs) may be reliable parameters for prognostic assessment of patients of locally advanced breast cancer (LABC). This work aims at assessing the potential value of these biological markers for the prediction of disease outcome after neoadjuvant taxane-based chemotherapy and its implication on the surgical role. Patients and Methods. From March 2006 to September 2011, 95 patients with LABC were treated by neoadjuvant taxane-based chemotherapy given at intervals of 3 weeks. Expression of Her2/neu and p53 was examined in the initial tissue biopsy by using ELISA technique. Status of HmRs was determined using a commercial enzyme immunoassay. Three weeks after the third cycle, patients underwent surgical resection followed by 3 more cycles of taxane-based chemotherapy and radiotherapy as an adjuvant therapy. Relations of Her2/neu overexpression to p53, HmRs, and conventional prognostic factors were analyzed. Results. Median followup was 61 months. The 5-year DFS and OAS rates were significantly higher in patients with positive HmRs than in those with negative HmRs, patients with Her2- than those with Her2+ breast cancer, and patients with intact p53 breast cancer than those with inactive p53. HER-2 overexpression was statistically significant associated with loss of HmR positive immunostaining (P < 0.0001), grade III breast cancer (P < 0.0001), advanced nodal status (P = 0.0039), and younger (<50 years) age (P = 0.0108). Conclusion. Her2/neu overexpression was associated with poor DFS and OAS rates, as it was significantly associated with negative HmR and high grade.