Hilal Oguz Soydinc

Serum IL-8 and IL-12 levels in breast cancer

Interleukins (ILs) are known to play a fundamental role in cancer. We investigated the serum levels of IL-8 and IL-12, in breast cancer patients, and their relationship with the prognostic parameters and therapy. Fortyeight patients with pathologically verified breast carcinoma and 21 healthy controls were enrolled into the study. Serum samples were obtained at baseline and after two cycles of chemotherapy. Serum IL-8 and IL-12 levels were determined using enzyme-linked immunosorbent assay (ELISA). There was no significant difference in the baseline serum IL-8 and IL-12 levels between breast cancer patients and healthy controls (p = 0.365 andp = 0.871, respectively), no significant correlation between the prognostic parameters and the serum IL-8, IL-12 levels. However, in the subgroup consisting of metastatic breast cancer patients, baseline serum IL-8 levels were significantly higher compared with non-metastatic disease (p = 0.047). Anthracycline-based chemotherapy and the addition of taxane did not change the levels of both serum IL-8 and IL-12. Serum IL-8 level may be useful in determining metastatic breast cancer. Larger studies are needed to confirm this finding.

Variations in systemic biomarkers of oxidative/nitrosative stress and DNA damage before and during the consequent two cycles of chemotherapy in breast cancer patients.

Abstract Background: Previous studies have suggested the importance of redox regulation in carcinogenesis. The aim of this study was to evaluate the prognostic role of altered redox homeostasis and oxidative DNA damage in patients with breast carcinoma before and during two cycles of chemotherapy. Methods: This study included 30 patients whose serum samples were obtained on admission before treatment, and after the first and second cycles of chemotherapy, and 20 controls. We investigated serum total antioxidant status (TAS), thiobarbituric acid reacting substances (TBARS), total nitrite/nitrate (NOx), nitrotyrosine (NT), and 8-hydroxydeoxy-guanosine (8-OHdG), as well as antioxidant enzyme activities, such as glutathione peroxidase (GPx), glutathione reductase (GRx). Results: TBARS, NOx, NT and 8-OHdG concentrations were significantly increased, while antioxidant enzyme activities and TAS were significantly decreased in patients when compared to controls. A concurrent increase in TBARS, NOx, NT, and 8-OHdG and a decrease in antioxidant enzyme activities and TAS were also seen after chemotherapy. No difference was observed in the second cycle of chemotherapy when compared with the first course. Conclusions: In conclusion, decreased activities of these antioxidant enzymes and low TAS concentrations observed in our study might be due to the depletion of the antioxidant defense system to combat the free radical storm produced by chemotherapy. We suggest that the increased 8-OHdG and other oxidative/nitrosative stress products that we have measured in breast cancer patients may be prognostic risk factors for the magnitude of oxidation in serum. Clin Chem Lab Med 2010;48:1487–95.

Matrix metalloproteinase-9 decreased after chemotherapy in patients with non-small cell lung cancer

AIMS AND BACKGROUND The aim of the study was to investigate the alteration in serum matrix metalloproteinase-9 (MMP-9) levels after chemotherapy and the association between the changes in serum levels of MMP-9 and response to chemotherapy in patients with advanced stage non-small cell lung cancer. METHODS AND STUDY DESIGN Twenty-eight consecutive patients with advanced non-small cell lung cancer and 24 healthy controls were enrolled in the study. The patients were treated with cisplatin-based combination chemotherapy. After two cycles, the response was evaluated. Before and after two cycles of chemotherapy, serum samples were collected from the patients. RESULTS Prechemotherapy MMP-9 (ng/ml) levels were significantly higher in patients with advanced stage non-small cell lung cancer than in controls (7.2 ± 2.8 vs 4.5 ± 2.1, P <0.001). Prechemotherapy MMP-9 levels were elevated compared to postchemotherapy levels as well (7.2 ± 2.8 vs 5.2 ± 3.3, P = 0.005). Prechemotherapy MMP-9 levels were significantly higher than postchemotherapy MMP-9 levels in patients with partial response (7 patients) (8.2 ± 1.8 and 3.2 ± 2.3, respectively; P = 0.018), but the pre- and postchemotherapy MMP-9 levels were no different in patients with stable disease or progressive disease (21 patients) (7 ± 3.1 and 5.9 ± 3.3, respectively; P = 0.08). CONCLUSIONS The difference between pre- and postchemotherapy MMP-9 levels in responders was more prominent than that in nonresponders. Whether the decline in serum MMP-9 levels might be used as a marker of response to chemotherapy should be investigated in larger studies.

Effects of intraperitoneal bevacizumab administration on colonic anastomosis and early postoperative adhesion formation.

Aim. The purpose of this study is to investigate the effect of intraperitoneal (IP) bevacizumab on colonic anastomosis and evaluate the effects on early postoperative adhesion formation. Materials and Methods. A total of 24 mature female Sprague-Dawley rats were used for this study. Rats were randomly assigned to a control group that received saline (n = 8) or to experimental groups (n = 8 each) that received bevacizumab at a dose of 2.5 mg/kg (group 1) or 5 mg/kg (group 2). Animals were killed humanely on the seventh day after operation, and measurements of anastomotic strength and biochemical variables were performed. Results. The mean adhesion grade was 2.63 ± 0.92, and 1 ± 0.93 and 0.75 ± 0.71 for the control and test groups, respectively. Bevacizumab significantly reduced adhesion formation in both low-dose and high-dose IP applications (P < .05). When all groups were compared, it was found that VEGF levels decreased significantly only in the tissue (P = .001), whereas there was no significant difference in the blood and the IP fluid (P = .73 and .08, respectively). We evaluated hydroxyproline levels, anastomosis bursting pressure, and histopathological healing scores. When each of these parameters were examined, there was statistical difference between groups (P = .01, .004, and .01, respectively). It was found that these parameters significantly decreased depending on increasing drug dose. Conclusion. IP administration of bevacizumab effectively reduced the formation of adhesions and caused significant impairment of anastomotic wound healing when standard doses were administered (5 mg/kg), but the 2.5-mg/kg dosage did not affect the anastomotic wound healing and also effectively reduced the formation of adhesions.

Utility of Serum and Urine uPAR Levels for Diagnosis of Breast Cancer

Malignant tumors have a capacity to degrade the extracellular matrix by controlled proteolysis. One system involved in these processes is the urokinase-type plasminogen activator (uPA) system. uPAR levels are elevated in tumors from several types of cancer. Our study was planned to investigate serum and urine levels of uPAR in breast cancer patients (n=180) and healthy controls (n=60) by ELISA. Serum (p<0.001) and urine (p<0.001) uPAR values in the patients were both significantly elevated. High serum and urine levels of uPAR can be used as diagnostic tools in lymph node positive patients.

For Which Cancer Types can Neuron-Specific Enolase be Clinically Helpful in Turkish Patients?

BACKGROUND The aim of the present study was to evaluate the serum neuron-specific enolase (NSE) levels in patients with prostate cancer, Hodgkin lymphoma, lung cancer and peripheral nerve tumors. MATERIALS AND METHODS NSE levels were determined by ELISA in the sera of 100 prostate cancer, 47 Hodgkin lymphoma, 35 lung cancer and 35 peripheral nerve tumor patients and also in 132 healthy controls. RESULTS The median levels of serum NSE were elevated in patients with lung cancer (p=0.018) and peripheral nerve tumors (p=0.008). NSE levels in prostate cancer and Hodgkin lymphoma patients were higher than the controls but there was no statistically significant difference (p>0.05). CONCLUSIONS We conclude that NSE may be applied in routine to gain insight about the clinical statuses of various cancer patients, but more studies are needed to determine the organ specificity.

Markers of Bone Metastases in Breast and Lung Cancers

AIM AND BACKGROUND The aim of the present study was to evaluate correlations between serum osteocalcin, osteoprotegerin and NTX (Cross-linked N-telopeptides of Type I Collagen) and urinary NTX in breast and lung cancer patients with bone metastases. These four markers are considered to have important roles in bone formation, resorption and metastases. METHODS Four markers were determined in the sera of 60 breast cancer and 21 lung cancer patients and healthy controls (n=30). Serum levels were studied using ELISA and EIA. RESULTS The median levels of serum osteoprotegerin (p<0.001) and osteocalcin (p=0.003) were higher in patients. Significant correlations were observed between the serum NTX-osteocalcin (r=0.431; p<0.001), serum NTX- osteoprotegerin (r=0.42; p=0.003) and serum NTX - urine NTX (r=0.255; p=0.022). CONCLUSION We conclude that osteocalcin, osteoprotegerin and NTX are independent diagnostic tools. Due to the ease of urine collection, urine NTX may be applied routinely to allow early detection of bone metastases and indicate progression of the disease.

Effect of intraperitoneal cetuximab administration on colonic anastomosis and early postoperative adhesion formation in a rat model

OBJECTIVE We aimed to evaluate the effect of intraperitoneal cetuximab administration on the healing of anastomosis and development of early adhesion formation in a rat model. MATERIALS AND METHODS Twenty-four female rats were used. A colon segment was resected and end-to-end anastomosis was performed. The rats were randomized into three groups after the performance of colonic anastomosis and received 10 mL of intraperitoneal solution including study drugs after closure of abdominal cavity: normal saline was administered to the normal saline group (n=8), cetuximab (400 mg/m(2)) was administered to the postoperative 1 group (n=8) 1 day after surgery, and cetuximab (400 mg/m(2)) was administered to the peroperative group (n=8) during surgery. RESULTS The mean adhesion grade was 2.63±0.92, and 0.50±0.76 and 0.63±0.74 for control and test groups, respectively. Cetuximab reduced adhesion formation in test groups (p<0.05). When all groups were compared, it was found that vascular endothelial growth factor levels decreased significantly only in the abdomen (p<0.05). Hydroxyproline levels and anastomosis bursting pressure were examined, and a statistical difference was found between groups (hydroxyproline p<0.05, bursting pressure p<0.05). However, when postoperative 1 day group was compared with the control group, it was found that there was no difference between groups according to these parameters (p>0.05), but when peroperative group was compared with the control group a significant decrease was observed in both parameters. Histopathological healing score was also evaluated. No statistical difference between groups was found. CONCLUSION Twenty-four hours later from the operation, intraperitoneal cetuximab therapy may be a safe and feasible treatment for metastatic colorectal patients.

Circulating serum levels of angiopoietin-1 and angiopoietin-2 in nasopharynx and larynx carcinoma patients.

We aimed to determine the serum levels of angiogenic factors, namely angiopoietins, in nasopharyngeal and laryngeal carcinoma patients. We also aimed to seek the relation of these molecules with tumor grade and their utility as diagnostic biomarkers. We evaluated angiopoietin 1 and 2 levels innasopharynx and larynx cancer patients before treatment. Angiopoietin 2 levels were significantly elevated in larynx carcinoma patients and tended to be elevated in nasopharynx cancer patients compared with healthy controls. However, angiopoietin 1 levels were similar in cancer patients and controls. Angiopoietin 1 levels were significantly higher in nasopharyngeal cancer patients with advanced stages compared to earlier stages. On the other hand, angiopoietin 2 levels were similar in advanced and earlier stage cancer patients.

Role of several cytokines and adhesion molecules in the diagnosis and prediction of survival of hepatocellular carcinoma

BACKGROUND AND STUDY AIMS There is still need for accurate markers for early diagnosis of hepatocellular carcinoma (HCC) and assessment of prognosis. The aim of this study is to investigate interleukin (IL)-32, IL-1 beta, IL-18, vascular cell adhesion molecule (VCAM)-1, and epithelial cell adhesion molecule (EpCAM) in the diagnosis and assessment of prognosis of HCC. PATIENTS AND METHODS Fifty patients with HCC and 15 healthy volunteers were enroled into this prospective study. Serum samples were obtained at the first admission before any treatment was given. Serum IL-32, IL-1 beta, IL-18, VCAM-1, and EpCAM levels were determined using ELISA kits. RESULTS The mean age of the patient group and controls was 60±9years and 56±8years, respectively. The mean serum level of IL-32 was higher in patients with HCC than in the control subjects (65.1 vs. 14.1pg/mL; p<0.001). IL-18 levels were significantly higher in the HCC group (546.5 vs. 157.8pg/mL; p<0.001). EpCAM (20.3 vs. 1.5pg/mL; p<0.001) and VCAM (6.5 vs. 1.8μg/mL; p<0.001) levels were also higher in patients with HCC. The mean level of IL-1 beta in the HCC group was similar to that in the control subjects (1.9 vs. 1.9pg/mL; p=0.97). Fifty-eight per cent of the patients with HCC died at 7.3months (median). Cytokine levels except EpCAM did not correlate with survival (p>0.05). Alpha-foetoprotein, IL-32, IL-18, EpCAM, and VCAM had valuable cutoff levels to differentiate between patients with HCC and control group (p<0.001). CONCLUSIONS Although cytokines can be a diagnostic marker for HCC, they did not have any significant prognostic value in patients with HCC. Only EpCAM may be used to determine the prognosis of HCC, thereby assisting with treatment management.