Serum N-terminal brain natriuretic peptide indicates exercise induced augmentation of pulmonary artery pressure in patients with mitral stenosis.

INTRODUCTION: To determine whether elevated N-terminal pro-BNP (NT pro-BNP) predicts pulmonary artery systolic pressure increase on exercise stress echocardiography in asymptomatic or mildly symptomatic patients with moderate to severe mitral stenosis. METHODS AND RESULTS: Forty-one asymptomatic or mildly symptomatic patients with moderate to severe mitral stenosis and 21 age- and sex-matched healthy subjects. Transthoracic echocardiography was performed in all patients to assess the severity of the valve disease and to measure pulmonary artery pressure before and immediately after treadmill exercise. Blood samples for NT pro-BNP were also collected before and immediately after treadmill exercise at the time of echocardiographic examination. The plasma concentrations of NT pro-BNP levels were significantly higher in patients with mitral stenosis than in control subjects before and after exercise (P < 0.001). Patients with atrial fibrillation had significantly higher NT pro-BNP levels compared to those with sinus rhythm (P < 0.001). Pre- and postexercise NT pro-BNP levels correlated statistically significantly with the left atrial (LA) dimension, right ventricle enddiastolic diameter, exercise duration, heart rate, rest, and exercise pulmonary artery systolic pressure, after exercise mitral valve mean gradient. Area under the receiver-operating characteristic curve for NT pro-BNP as an exercise induced augmentation of pulmonary artery pressure was 0.78. Using an optimized cutoff value of 251 pg/mL for NT pro-BNP, sensitivity was 89.47%. The independent determinants of higher pulmonary artery pressure were LA diameter and pretest NT pro-BNP levels in multivariante analysis. CONCLUSION: NT pro-BNP levels correlate with functional class and echocardiographic findings in patients with mitral stenosis and indicate exercise induced augmentation of peak PAP > 60 mmHg. (Echocardiography 2011;28:8-14).

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

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.

Polymorphisms in the microsomal epoxide hydrolase gene: role in lung cancer susceptibility and prognosis.

AIMS AND BACKGROUND: The aim of this study was to investigate the relationship between EPHXI exon 3 Tyr113His and exon 4 His139Arg polymorphisms, predicted microsomal epoxide hydrolase (mEH) activity, and lung cancer development. mEH is a protective enzyme involved in oxidative defences against a number of environmental chemicals and pollutants, but it is also responsible for the xenobiotic activation of carcinogens. METHODS: We investigated the two polymorphisms of the mEH gene (EPHX1) in 58 lung cancer patients and 41 controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The exon 3 Tyr113His polymorphism was associated with lung cancer (P < 0.001). The frequency of the His113His homozygote genotype in exon 3 was significantly increased in patients compared with controls (P < 0.001). In contrast, there was no significant difference in exon 4 polymorphisms between patients and controls. When the exon 3 and 4 polymorphisms were considered together, the combined EPHX1 His113His113/His139His139 genotype (very low predicted enzyme activity) was found to be associated with an increased risk of lung cancer (P = 0.044, OR = 3.063, CI = 0.932-10.069). We observed that patients with T3 + T4 tumors had an approximately 3-fold higher risk of the Tyr113/His113 genotype than patients with T1 + T2 tumors. Lung cancer patients carrying a heterozygote Tyr113/His 113 genotype had a 2-fold increased risk of lymph node metastases (P = 0.051). CONCLUSION: These findings suggest that the exon 3 Tyr113His and exon 4 His139Arg polymorphisms of EPHXI may be associated with a increased risk of lung cancer and a worse prognosis.

The effect of glyceryl trinitrate ointment on posthemorrhoidectomy pain and wound healing: results of a randomized, double-blind, placebo-controlled study.

PURPOSE: Spasm of the internal sphincter may be a source of anal pain and delayed healing after hemorrhoidectomy. This study assessed whether glyceryl trinitrate (GTN) ointment reduces pain and promotes wound healing after hemorrhoidectomy. METHODS: A prospective, randomized, double-blind, placebo-controlled trial was conducted comparing effects of an ointment containing GTN (0.2 percent) vs. a placebo ointment. The study preparations were self-applied by the patient to the surgical site twice per day for two weeks after the hemorrhoidectomy. Pain was assessed with a visual analog scale, and 24-hour analgesic use was recorded on postoperative days 1, 3, and 7. Complete healing was defined as complete epithelialization and evaluated at the end of the third postoperative week. RESULTS: Sixty-nine patients were randomly assigned to receive topical 0.2 percent GTN group or placebo. Data from 30 patients in each group were available for analyses. Patients in the GTN group experienced significantly less postoperative pain than those with placebo on days 1, 3, and 7 (P < 0.05). Use of prescribed analgesics (metamizole and acetaminophen) was significantly greater for the placebo group on days 1 and 3. Wound healing at the end of the third postoperative week was significantly greater with GTN compared with placebo (76.7 percent vs. 46.7 percent, P = 0.02). CONCLUSIONS: Compared with placebo, perianal application of 0.2 percent GTN ointment significantly decreases postoperative pain after hemorrhoidectomy and reduces analgesic requirements in the immediate postoperative period. GTN ointment also achieves more rapid healing of wounds.

Serum levels of apoptosis biomarkers, survivin and TNF-alpha in nonsmall cell lung cancer.

CONTEXT: This study was conducted to investigate the prognostic role and the effects of chemotherapy on serum apoptosis biomarkers consisting of survivin and tumor necrosis factor alpha (TNF-alpha) in patients with advanced stage nonsmall cell lung cancer (NSCLC). MATERIALS AND METHODS: Fifty-seven patients with newly diagnosed NSCLC were enrolled into study. Performance status was 0 or 1 in 47 patients and 2 in 10 patients. Thirty-two of them were no or less than 10% weight loss. Patients were treated with platinum-based chemotherapy. Serum levels of TNF-alpha and survivin were determined by enzyme-linked immunosorbent assay (ELISA) technique. RESULTS: While serum survivin levels in patients were not significantly different from controls (p=0.321), serum TNF-alpha levels in patients were found significantly higher than in controls (p=0.029). We found that serum TNF-alpha levels were increased (p<0.001), whereas serum levels of survivin (p=0.025) were decreased by the chemotherapy effects. The changes of the TNF-alpha and survivin serum levels due to chemotherapy effect showed a significant negative correlation (r=-0.36 p=0.007). The increase of serum TNF-alpha levels was independent from chemotherapy response; however, the reduction of serum survivin levels was found only significant in the chemoresponsive group (p=0.039). While older age, weight loss and performance status yielded prognostic value, neither TNF-alpha nor survivin levels proved to be significant for survival. CONCLUSION: Our findings suggest that the reduction in the serum survivin levels of advanced NSCLC patients after chemotherapy can be used as a predictor of response to the chemotherapy but not that of survival.

Temozolomide in combination with fotemustine in patients with metastatic melanoma.

PURPOSE: Temozolomide and fotemustine are both active drugs for treating metastatic melanoma. The present study was designed to assess the efficacy and safety of combination therapy with temozolomide + fotemustine in patients with metastatic melanoma. METHODS: Forty patients (median age 50.5 and 22 males) with pathologically confirmed, unresectable, AJCO stage IV melanoma were enrolled into the study. The primary endpoints were tumor response and safety. Patients received oral temozolomide 125 mg/m(2) on days 1-7 and intravenous fotemustine 80 mg/m(2) on day 3 every 3 weeks. RESULTS: Fourteen (35%) patients achieved an objective response, including 3 (7.5%) complete and 11 (27.5%) partial responses. Median overall survival time was 6.7 months and 6-month survival rate was 57.4%. Myelosupression, particularly thrombocytopenia, was the primary toxicity. CONCLUSION: The regimen, temozolomide combined with fotemustine, is an active and moderately safe first-line chemotherapy regimen with acceptable and easily manageable toxicities in patients with metastatic melanoma.

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.

Effect of zoledronic acid on serum angiogenic factors in patients with bone metastases.

In this study we have investigated changes in circulating angiogenic factors after a single zoledronic acid intravenous infusion. Thirty consecutive patients who had histologically confirmed breast (n=20) and lung cancer (n=10) associated with confirmation of bone metastases were included in the study. Serum was also available from 10 healthy volunteers. Four mg of Zoledronic acid (Zometa, Novartis) was administered as a 15-min infusion in 100-ml normal saline on an outpatient basis. Venous blood for assessment of serum parameters was drawn just before the beginning of drug infusion and again at 7 and 28 days after the zoledronic acid infusion. Serum levels of VEGF and bFGF were assayed with ELISA kits. Serum VEGF and bFGF levels were not significantly different from healthy control groups (P>0.05). However, we found that serum VEGF levels in lung cancer patients were significantly higher than in patients with breast cancer and controls (P=0.009, and P=0.022, respectively). We found no significant correlation between serum VEGF and bFGF levels. No statistically significant changes were seen following infusion of zoledronic acid in patients with bone metastases for both serum VEGF and bFGF levels (P>0.05). Unlike previous studies, zoledronic acid did not appear to exert an angiogenic activity as there was no reduction of VEGF and bFGF circulating levels after zoledronic acid infusion.

Circulating levels of vascular endothelial growth factor (VEGF), matrix metalloproteinase-3 (MMP-3), and BCL-2 in malignant melanoma.

Vascular endothelial growth factor (VEGF) is a critical regulator of angiogenesis that stimulates proliferation, migration, and metastasis of melanoma. In literature, all studies concerning influences of matrix metalloproteinases (MMPs) and antiapoptotic proteins on VEGF-induced angiogenesis in melanoma patients have been performed in tissue scale in melanoma. The objective of this study was to determine the value of circulating serum VEGF and its possible mechanisms of angiogenesis by circulating VEGF, MMP-3, and Bcl-2 in patients with melanoma. Fifty-one patients with cutaneous melanoma pathologically verified at different stages, and eighteen healthy controls were investigated. Serum VEGF, MMP-3, and Bcl-2 levels were quantitatively analyzed by ELISA. The serum VEGF (P = 0.034) and Bcl-2 (P = 0.005) levels were significantly higher in patients with melanoma than in the control group. However, there was no significant difference in the serum MMP-3 level between melanoma patients and controls (P = 0.51). The serum levels of VEGF were significantly influenced only by Breslow thickness (P = 0.045) and mitosis (0.039) and were not positively correlated with the stage of the disease. Among serum parameters, a significant relationship was found only between serum levels of VEGF and MMP-3 (r = 0.32, P = 0.023). In conclusion, our study demonstrates increased concentrations of VEGF and Bcl-2, but not MMP-3, in serum of melanoma patients regardless of the stage of the disease. VEGF may be a potential endothelial cell growth and survival factor. The mechanism of VEGF regulation of angiogenesis may be in part due to enhanced proliferation and survival of endothelial cells by differential expression of antiapoptotic genes and in part by activation of MMPs.

Serum levels of intercellular adhesion molecule ICAM-1 and E-selectin in advanced stage non-small cell lung cancer.

Cell adhesion is a basic count in inter- and intra-cellular communication and plays an important role in tumor progression. This study was conducted to investigate the serum levels of intercellular adhesion molecule (ICAM-1) and E-selectin in patients with advanced stage non-small cell lung cancer (NSCLC) and the relationships with known prognostic parameters and therapy. These serum factors were measured of 57 NSCLC patients pathologically verified before and after chemotherapy in comparison with 24 healthy controls by using ELISA method. Serum levels of ICAM-1 were increased significantly in NSCLC patients compared with the healthy controls (P = 0.006). However, serum E-selectin levels were not significantly different from healthy control groups (0.643). No statistically significant relationships were found between investigated all serum parameters and various characteristics of patients, and the diseases such as stage and tumor burden. Likewise, we also found no correlation between serum ICAM-1 and E-selectin (P = 0.78). We found that serum ICAM-1 levels were decreased owing to the chemotherapy effect, independently from chemotherapy response. However, serum E-selectin levels were not changed by the chemotherapy effect. The median survival of all patients was 11.9 months and 1-year survival rate was 47.6%. We found that patients performance status (P = 0.013), age (P = 0.015), and weight loss (P = 0.007) were prognostic factors for survival. Serum E-selectin levels showed a trend (P = 0.08) related to worse prognosis, however serum ICAM-1 levels were determined as ineffective on survival (P = 0.11). Multivariate analysis revealed that only weight loss (P = 0.005) and E-selectin levels (P = 0.002) remained as an independent prognostic factor for survival in patients with advanced NSCLC. In conclusion, our data suggest that higher serum ICAM-1 can be useful for diagnosis while E-selectin levels have prognostic significance and could be a potential prognostic factor in NSCLC patients.

Addition of topotecan to standard cisplatin/etoposide combination in patients with extended stage small cell lung carcinoma.

BACKGROUND: Topotecan is an active agent for the management of untreated and recurrent extensive-disease small cell lung cancer (ED-SCLC). This study was designed to evaluate the efficacy and safety of a triplet combination with topotecan added to the standard PE regimen in previously untreated patients with ED-SCLC. MATERIALS AND METHODS: Twenty-one patients (median age 55 years, and 18 male) with chemotherapy-naive ED-SCLC were enrolled into the study. PET treatment consisted of etoposide 80mg/m(2), cisplatin 20mg/m(2) and topotecan 0.75mg/m(2) and all were given intravenously on days 1 to 3 for every 3 weeks. RESULTS: Leucopoenia and/or neutropenia and to a lesser extent thrombocytopenia were the main dose-limiting toxicities. Severe leucopenia/neutropenia were observed in 14 (67%)/12 (57%) patients, and only two (10%) developed febrile neutropenia. Severe thrombocytopenia was observed in 6 (29%) patients and one patient died due to orbital and cerebral haemorrhage. Dose reductions were required in 13 (62%) patients, delays in 8 (38%) patients and early treatment discontinuation in 3 (14%) patients. The overall response rate was 52.6% (95% CI: 28, 9-75.6) with 2 (10.5%) complete and 8 (42.1%) partial responses. The overall median survival time was 6.6 months (range 0.5-16.5 months) and the 6-month overall survival was 65.3%+/-11.7. The overall median survival time of responders was 9.7 months compared to 5.7 months in non-responders (p=0.026). CONCLUSION: Topotecan combined with PE regimen with this schedule and dosage does not seem to provide any benefit in terms of response and survival in ED-SCLC patients and does not deserve further studies.

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) patients and healthy controls (n = 25). Serum MIF concentrations were determined by enzyme-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.

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. Forty eight 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 and p = 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.

Circulating serum levels of angiogenic factors and vascular endothelial growth factor receptors 1 and 2 in melanoma patients.

Angiogenesis is essential for tumor progression and metastasis; however, the angiogenesis regulators that are biologically relevant for melanoma are still unknown. In this study, we analyzed the circulating serum levels of potent angiogenic factors, including vascular endothelial growth factor (VEGF), angiogenin, transforming growth factor-beta1 and VEGF receptors, VEGFR1 and VEGFR2, in human melanoma patients. One hundred and fourteen patients with histopathologically verified cutaneous melanoma at different stages and 30 healthy controls were investigated. Serum levels of angiogenic factors and VEGF receptors were quantitatively analyzed by solid-phase enzyme-linked immunosorbent assay. The age of the patients (61 men and 53 women) ranged from 18 to 80 years; median age was 51 years. Serum transforming growth factor-beta1 (P < 0.001), VEGF (P = 0.006) and VEGFR1 (P = 0.007) levels were significantly higher in patients with melanoma than in the control group. No significant differences, however, exist in the serum angiogenin and VEGFR2 levels between melanoma patients and the controls. The positive correlations of elevated serum levels of transforming growth factor-beta1, VEGF and VEGFR1 with advanced stages of disease were found. Significant relationship was found only between serum levels of VEGF and VEGFR2. Elevated serum transforming growth factor-beta1 (P < 0.001) and VEGF levels (P = 0.0012) were found to be poor prognostic factors. Serum level of angiogenin and VEGF receptors, however, had no effect on survival. Our data suggest that the angiogenic serum factors, including VEGF, transforming growth factor-beta1 and VEGFR1, but not angiogenin and VEGFR2 were increased in melanoma patients, especially associated with advanced disease stages. The mechanism of VEGF regulation of angiogenesis may in part be due to enhanced proliferation of VEGFRs, especially VEGFR1.

Intermediate dose interferon alpha in adjuvant treatment for high-risk melanoma: a single institution's experience.

Interferon is widely used as the most effective agent in the adjuvant therapy of patients with melanoma. However, little is known about the effect of intermediate dose interferon (IDI) in adjuvant therapy. We conducted this study to determine whether intermediate doses of interferon-alpha 2 could be beneficial for these patients. A series of 84 melanoma patients with high-risk relapse potential (stage II-III) after excisional biopsy were enrolled for adjuvant therapy with IDIs, either IFN-alpha 2a, 9 MU or IFN alpha 2b, 10 MU per day, subcutaneously, for 1 yr consisted of an induction period (5 d/wk for 4 wk) followed by 48 wk of same dose administered three times per week. The median follow-up was 25.9 mo with range 4-90.4 mo. Thirty-three (39%) patients had progressed; 18 (55%) of them while on treatment. The median (range) time of the failure occurrence was 9.1 mo (1.7-47.3 mo). Distribution of failure site was identical and the majority of the recurrences were found as single metastasis. For distant metastasis-free interval, mean (+/- SE) value was 28.8+/-3.6 mo; 1- and 2-yr survival rates were 87.8+/-5.7% and 61.6+/-9.3%, respectively. Twenty-two deaths were observed. Five-year survival rates of progression-free survival and overall survival were 50% and 60%, respectively. Generally, the treatment was found well-tolerated; drug-induced dose reduction or treatment discontinuation due to toxicity was minimal. Severe toxicity was rare. In conclusion, the small number of patients and the short follow-up does not permit any conclusion. However, the preliminary data seem to show that treatment with IDI was usually well tolerated with low toxicity of the patients during the adjuvant therapy.

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 researches still continues in this field, and exciting new knowledge will ultimately emerge.

Temozolomide in combination with cisplatin in patients with metastatic melanoma: a phase II trial.

The present study was designed to assess the efficacy and safety of combination therapy with temozolomide plus cisplatin in patients with metastatic melanoma. Thirty patients with metastatic melanoma were enrolled. Treatment consisted of intravenous cisplatin (75 mg/m) on day 1 and oral temozolomide (200 mg/m) on days 1 to 5, every 4 weeks. Nine patients (30.0%) achieved an objective response, including two complete (6.7%) and seven partial (23.3%) responses. The median response duration was 161 days. The median progression-free and overall survival times were 72 and 120 days, respectively. Myelosuppression and emesis were the primary toxicities. In conclusion, temozolomide combined with cisplatin is an active and safe first-line chemotherapy regimen with acceptable and easily manageable toxicities in patients with metastatic melanoma.

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-alpha, 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-alpha 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-alpha (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-alpha, 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-alpha 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-alpha 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.

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.

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.