Vildan Yasasever

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.

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.

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.

Serum and urine survivin levels in breast cancer.

This study was conducted to investigate the serum and urine levels of survivin in patients with breast cancer and the relationships with known prognostic parameters and therapy. Forty-three patients with breast cancer and 21 healthy control subjects were investigated. Serum samples were obtained on the first admission before adjuvant and metastatic treatment were given and after two cycles of chemotherapy. Serum and urine survivin levels were determined using enzyme immunometric assay (EIA) and enzyme-linked immunosorbent assay (ELISA), respectively. There was no significant difference in the baseline serum and urine levels between patients with breast carcinoma and healthy controls (p=0.19 and p=0.84, respectively). None of the prognostic parameters analyzed were significantly correlated with the urine survivin concentrations. This was also true for serum survivin values, except for nodal involvement. Serum survivin levels were significantly higher in the patients with nodal involvement compared with node negatives (p=0.043). However, serum survivin levels were not influenced by the number of involved nodes (p=0.77). No significant correlation was found between the serum and urine levels of survivin (r=0.15, p=0.27). Serum and urine levels did not change significantly after chemotherapy (p=0.59 and p=0.50, respectively). In conclusion, the result of this study suggested that serum survivin level could be a sensitive marker for detecting metastases in lymph nodes from breast cancer patients. However, much research continues in this field, and exciting new knowledge will ultimately emerge.

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.

Prognostic significance of marker half-life during chemotherapy in non-seminomatous germ cell testicular tumors.

Decrease in serum alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) levels is considered as a response during chemotherapy of non-seminomatous germ cell testicular tumors, but data on the prognostic significance of marker half-life remains inconclusive. Serum marker half-life was evaluated in 34 patients with elevated markers, receiving chemotherapy (CT). Marker half-life was calculated from the natural logarithm of the sequential AFP or HCG concentrations. The correlation between event-free (EFS) and overall survival (OS) with unfavorable half-lives of AFP and HCG was evaluated. Median actual half-life (AHL) AFP was 3.9 days (range, 1.4-21.5) and median AHL HCG was 4.4 days (range, 1.4-21.0); 82% of the patients had a satisfactory initial decline in AFP, and 71% had a satisfactory initial decline in HCG. There was a significant difference in EFS and OS between the two groups of patients with an AFP half-life < 7 days and > 7 days. HCG half-life did not adversely affect EFS and OS. The correlation of better EFS and OS with appropriate AFP marker half-life during chemotherapy could provide a dynamic method, which could complement the standard baseline prognostic factors, for the prediction of prognosis.

Serum levels of the soluble adhesion molecules in patients with malignant melanoma.

The incidence of malignant melanoma has been steadily increasing over the past decades. CD 44 is a transmembrane glycoprotein which is implicated in a number of adhesive and migratory events. Downregulation of CD 44 is implicated in the metastatic process. P-Selectin is a member of the selectin family of cell surface molecules. The levels of P-Selectin in biological fluids may be elevated in subjects with a variety of pathological conditions. In malignant melanoma, elevation of the plasma level of soluble intercellular adhesion molecule-1 (sICAM-1) has been associated with a reduction in disease-free survival. This study was performed to investigate the differences in the serum concentrations of the adhesion molecules in patients with malignant melanoma.The study group consisted of 52 patients with malignant melanoma and 20 healthy subjects. No meaningful difference was observed for P-selectin and sICAM 1 levels. A statistically significant decrease was observed in the cancer patients for serum CD 44 levels.

SERUM TUMOR MARKERS FOR DETECTION OF BONE METASTASIS IN BREAST CANCER PATIENTS

For the diagnosis of bone metastasis in breast cancer patients during systemic treatment serum tumor markers, including carbohydrate antigens 15-3 (CA 15-3) and 19-9 (CA 19-9), cancer antigen 125 (CA 125), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), beta-2 microglobulin (BMG), ferritin, and tissue polypeptide antigen (determined by the M3 monoclonal antibody, TPS) were measured in 22 patients with known bone metastases and in 30 patients without documented metastases. The most useful single marker was CA 15-3. By stepwise discriminant analysis, it was found that 90% of the patients could be diagnosed truly by using the markers CA 15-3, BMG and ferritin. It is concluded that monitoring with combinations of tumor markers at regular intervals increases the diagnostic efficiency.