Hilal Oguz

Serum levels of leptin and proinflammatory cytokines in advanced-stage non-small cell lung cancer

In this study, we aimed to investigate the diagnostic and prognostic roles and the effects of chemotherapy of serum proinflammatory cytokines consisting of IL-6, TNF-α, CRP, and leptin levels in patients with advanced-stage non-small cell lung cancer. Twenty-eight patients newly diagnosed of non-surgical advanced non-small cell lung cancer and 15 healthy controls were included. All patients with good performance status were treated with combination therapy consisting of cisplatin plus vinorelbine chemotherapy. Blood samples were obtained in fasting conditions before chemotherapy first and after two cycles of chemotherapy. IL-6 and TNF-α immunoassays employ the quantitative sandwich enzyme immunoassay technique. Leptin (Sandwich) ELISA is a solid-phase enzyme-linked immunosorbent assay based on the sandwich principle. CRP is a photometric immunoturbidimetric test. Most of the patients were elderly, male predominance, good performance status, and no or less than 10% weight loss. Higher serum TNF-α (p<0.001) and CRP (p<0.001), and lower leptin (p=0.021) levels in patients than in controls. Serum IL-6 cytokine (p=0.693) levels were not significantly different. No statistically significant relationships between investigated serum parameters and various characteristics of patient and disease. Likewise, serum levels of leptin, IL-6, TNF-α, and CRP were all similar in lung cancer patients independently from severity of weight loss (p>0.05). A direct relationship was found between serum IL-6 and TNF-α levels (r=0.530, p=0.004). We found that both serum leptin (p=0.046) and IL-6 (p=0.002) levels were decreased owing to the chemotherapy effect independently from chemotherapy response. However, serum TNF-α and CRP levels were not changed by the chemotherapy effect. The stage of the disease, serum LDH levels, performance status, and responsiveness to chemotherapy yielded prognostic value. Only serum IL-6 levels out of the parameters showed a trend (p=0.06) related to a worse prognosis.

Serum Vascular Endothelial Growth Factor (VEGF) and Interleukin-8 (IL-8) Levels in Small Cell Lung Cancer

This study was conducted to determine the value of the angiogenic serum factors, vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8), in patients with small cell lung cancer (SCLC). These serum angiogenic factors were measured of 34 SCLC patients on the before and after chemotherapy in comparison with 20 healthy controls using ELISA method. Serum levels of VEGF and IL-8 were significantly increased in SCLC patients compared with healthy controls (p < 0.001). No statistically significant relationships was found between investigated elevated serum angiogenic parameters and various characteristics of patients and disease such as disease stage and tumor burden. Likewise, we also found no correlation between serum angiogenic factors. Cytotoxic therapy of patients was accompanied by unchanged serum levels of angiogenic factors. Contrary to serum IL-8, elevated serum levels of VEGF was determined as a prognostic factor for survival by univariate analysis (p = 0.05). Multivariate analysis revealed that independent prognostic factors of overall survival included only response to chemotherapy and weight loss (p < 0.001 for both). In conclusion, our data suggest that the angiogenic serum factors, VEGF and IL-8, are useful diagnostic factors, but not predictive and prognostic markers for overall survival in SCLC patients.

The value of serum levels of IL-6, TNF-alpha, and erythropoietin in metastatic malignant melanoma: serum IL-6 level is a valuable prognostic factor at least as serum LDH in advanced melanoma.

In order to study the relation to the metastatic profile and survival, we evaluated the association between pretreatment serum levels of IL-6, TNF-alpha, and erythropoietin (EPO) and metastatic distribution and survival in 16 patients with metastatic malignant melanoma. IL-6 and TNF-alpha immunoassay (R&D Systems, Inc. Minneapolis, USA) employs the quantitative sandwich enzyme immunoassay technique. The Quantikine IVD EPO ELISA (R&D Systems, Inc.) is based on the double-antibody sandwich method. The baseline serum IL-6 and EPO levels were significantly higher in patients with metastatic malignant melanoma than in the control group (p=0.009 and p=0.033, respectively). Serum IL-6 levels were higher in patients with weight loss (p=0.02), who were anemic (p=0.026), with elevated serum LDH levels (p=0.028), and who were chemotherapy nonresponding (p=0.016). The relationship of serum IL-6 concentration to the tumor burden was not determined. Only serum EPO level was influenced by hemoglobin status (p=0.001). No difference was shown among these three parameters. Elevated serum IL-6 concentration (p=0.002) was found to be an adverse prognostic factor in patients with poor performance status, weight loss, low serum hemoglobin, elevated serum LDH, and unresponsive to chemotherapy. On the other hand, both serum TNF-alpha and EPO levels were of no prognostic value. Serum levels of IL-6 were found to be prognostic factors as valuable as serum LDH levels in patients with metastatic malignant melanoma. Their prognostic value should be further evaluated in a larger patient population.

Macrophage Migration Inhibitory Factor in Cancer

The objective of this study was to investigate the expression of macrophage migration inhibitory factor (MIF) in patients with colorectal cancer (GIS) and malignant melanoma (MM). The study group consists of pathologically verified colorectal cancer (n = 63) and malignant melanoma (n = 65) pateints and healthy controls (n = 25). Serum MIF concentrations were determined by enyzme-linked immunosorbent assay. Serum values of the patients were significantly higher than the controls (p < 0.001 for GIS, p = 0.032 for MM). Diagnostic sensitivity and specificity were calculated for MIF for colorectal and malignant melanoma. The results demonstrate that colorectal cancer express and secrete large amounts of MIF.

The Diagnostic Value of Macrophage Migration Inhibitory Factor (MIF) in Gastric Cancer

The present study was conducted to investigate the sensitivity, specificity, predictive values and accuracy of serum MIF, CEA, CA 19-9 levels and their various combinations in patients with gastric cancer. Study group consists of pathologically verified, gastric cancer (n = 63) and apparently healthy controls (n = 50). Serum MIF concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Serum values of patients were significantly higher than the controls (p = 0.011). Diagnostic sensitivity and specificity, predictive values and accuracies were calculated for each marker and their various combinations. The best results were achieved with the marker combination of MIF–CEA–CA 19-9 and MIF–CEA combination. In our opinion, the combination of the markers MIF–CEA is a valuable diagnostic tool for gastric cancer.

Serum matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 in patients with malignant melanoma.

Degradation of basement membranes and extracellular matrix is an essential step in cancer invasion and metastasis. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play key roles in this step. The present study was conducted to investigate the levels of MMP-3 and TIMP-1 in serum of patients with malignant melanoma and the relationship to tumor progression and known prognostic parameters. Seventy patients with cutaneous malignant melanoma were investigated. Serum samples were obtained on first admission before any adjuvant and metastatic treatment was given or follow-up of patients. Serum TIMP-1 and MMP-3 levels were determined by the solid-phase sandwich ELISA (Oncogene Science Inc.) method. The elevation of serum MMP-3 and TIMP-1 levels between the patients with malignant melanoma and healthy controls were not significantly different (p>0.05). The serum levels of MMP-3 were significantly different in males and females (p=0.001) and serum TIMP levels were influenced by age (p=0.047). Except for the ulceration status of the tumor, serum levels of MMP-3 and TIMP-1 were not related to the known prognostic factors such as tumor histology, localization, stage of the disease, Breslow thickness, Clark invasion, mitosis, TIL, and regression of tumor (p>0.05). In patients with ulceration positive, the serum levels of MMP-3 were higher (p=0.04) and TIMP-1 were lower (p=0.008) than those in patients without ulceration. No significant relationship was found between serum levels of MMP-3 and TIMP-1. In conclusion, these results suggest that neither of the serum levels of MMP-3 and TIMP-1 could be a good indicator of invasion and metastasis nor can be recommended as a tumor marker in the management of melanoma patients owing to lack of sensitivity and specificity. However, much research still continues in this field and exciting new knowledge will ultimately emerge.

The value of serum bcl-2 levels in advanced epithelial ovarian cancer.

The present study was conducted to investigate the value of serum bcl-2 levels in advanced epithelial ovarian cancer patients. Twenty-two patients with advanced ovarian carcinoma pathologically verified were investigated. Serum samples were obtained on the first admission before the chemotherapeutic treatment were given. Serum bcl-2 protein was determined by using ELISA. The baseline serum bcl-2 levels were significantly higher in patients with ovarian cancer than in the control group (p<0.001). The sensitivity and specificity of serum bcl-2 were determined as 100% and 78%, respectively. None of the prognostic parameters analyzed such as age of patient, stage of disease, serum CA-125, albumin, hemoglobin, LDH, and response to chemotherapy was significantly correlated with bcl-2 serum concentrations. No prognostic value of serum bcl-2 was determined. In conclusion, the results of the present study suggest that decreased apoptosis occurred due to the effect of serum bcl-2 elevation in advanced ovarian cancer patients. Also, serum bcl-2 level was a diagnostic but not a prognostic value in ovarian cancer. However, much researchs still continues in this field, and exciting new knowledge will ultimately emerge.

The value of serum Bcl-2 levels in advanced lung cancer patients

Overexpression of the Bcl-2 protein was associated with a favorable prognostic factor for survival in lung cancer patients, especially nonsmall cell lung carcinoma. The present study was conducted to investigate the value of serum Bcl-2 levels in advanced lung cancer patients. Fifty patients with advanced lung carcinoma pathologically verified and 18 healthy controls were investigated. Serum samples were obtained on the first admission before the chemotherapeutic treatment were given. Serum Bcl-2 levels were determined by using anti-Bcl-2 monoclonal coating antibody. The baseline serum Bcl-2 levels were significantly higher in patients with lung cancer than in the control group (p<0.001). Serum Bcl-2 levels were elevated in 48 (96%) advanced lung cancer patients. None of the prognostic parameters analyzed, such as age of patient, gender, histology, stage of disease, erythrocyte sedimentation rate, serum albumin, hemoglobin, CEA, NSE, LDH, performance of patient, weight loss, and response to chemotherapy, was significantly correlated with Bcl-2 serum concentrations. The serum Bcl-2 concentrations were not changed with cisplatin-based cytotoxic chemotherapy regardless of response (p=0.76). No prognostic value of serum Bcl-2 was determined. In conclusion, the results of the present study, which is the first study to determine serum Bcl-2 levels in lung cancer, suggest that decreased apoptosis occurred due to the effect of serum Bcl-2 elevation in lung cancer patients. Serum Bcl-2 level was of diagnostic but not prognostic value in lung cancer patients. However, more studies are needed to define the role of Bcl-2 in the diagnosis and prognosis of lung cancer.

Clinical significance of serum claudin-1 and claudin-7 levels in patients with colorectal cancer.

The present study aimed to investigate the serum levels and clinical relevance of claudin (CLDN) 1 and CLDN7 in patients with colorectal cancer (CRC). A total of 140 patients with a pathologically confirmed diagnosis of CRC were enrolled in this study. The serum levels of CLDN1 and CLDN7 were determined using the solid-phase sandwich ELISA method. A total of 40 healthy age- and gender-matched controls were included in the analysis. The median age of the patients was 60 years (range, 24–84 years). The localization of the tumor in the majority of the patients was the colon (n=81, 58%). Of the 55 metastatic patients who received palliative chemotheraphy, 31% were chemotherapy-responsive. The baseline median serum CLDN1 and CLDN7 levels were significantly lower in non-metastatic and metastatic patients compared with those in healthy controls (CLND1, P=0.008 and 0.002; and CLND7, P=0.002 and 0.002, respectively). Moreover, known clinical variables, including poor performance status and high carcinoembryonic antigen (CEA) levels were found to be associated with lower serum CLDN1 concentrations for all patients (P=0.03 and P=0.03, respectively). High T stage and high CEA levels were found to be correlated with lower serum CLDN7 concentrations for all patients (P=0.04 and 0.03, respectively). A correlation was identified between CLDN1 and CLDN7 levels in non-metastatic and metastatic CRC patients (both P-values <0.001). Our study results did not reveal any statistical significance for serum CLDN1 or CLND7 concentrations regarding progression-free and overall survival rate. Therefore, reduced serum levels of CLDN1 and CLND7 may be useful markers in the differential diagnosis of CRC.

Apoptosis of lymphocytes in peripheral blood of patients with melanoma.

In cancer, spontaneous apoptosis of circulating peripheral blood lymphocytes (PBLs) is a general phenomenon. In this study we aimed to determine whether spontaneous apoptosis of circulating PBLs of patients with malignant melanoma occurs. Pathologically proven 45 patients with malignant melanoma and 19 healthy controls were included in this study. Samples were obtained both on first admission before treatment, either adjuvant or metastatic, and follow-up period of patients. Human active caspase-3 immunoassay (R&D Systems, Inc. MN, USA) employs the quantitative sandwich enzyme immunoassay technique. A monoclonal specific for caspase-3 has been used. The spontaneously apoptotic PBLs in melanoma patients were not significantly different from those obtained for normal controls (p=0.25). None of the clinical characteristics were significantly correlated with spontaneous apoptosis (p>0.05). Likewise, we found that apoptosis in PBLs was not a prognostic factor in melanoma patients (p=0.79). In conclusion, we did not observe accelerated apoptosis of PBLs in patients with melanoma. Further studies are necessary to determine the potential prognostic importance of this observation.