Clinical significance of interleukin-4 and interleukin-18 levels in aggressive non-Hodgkin's lymphoma patients.

Strong evidence indicates that tumor growth can be actively controlled by the immune system, and interleukins (ILs) are known to play an influential role in immune response regulation. Moreover, inflammatory cytokines are significantly involved in lymphoma pathogenesis. We aimed to investigate serum levels of IL-4 and IL-18 in aggressive non-Hodgkin's lymphoma (A-NHL) patients and their relationship with prognostic parameters and therapy outcome. These serum factors were measured by enzyme-linked immunosorbent assay in 46 patients with pathologically verified A-NHL before and after chemotherapy, and in 20 healthy controls. No significant difference in serum IL-4 (P = 0.11) and IL-18 (P = 0.261) levels was observed between the A-NHL and controls groups. None of the prognostic parameters analyzed significantly correlated with serum IL-4 concentration, while only lactate dehydrogenase (LDH) measurements were associated with IL-18 values. Serum IL-18 was elevated in the patients with high LDH levels compared to those exhibiting normal values (P = 0.045). In addition, no correlation was found between the concentrations of serum IL-4 and IL-18 in A-NHL patients (r = 0.188, P = 0.187). While IL-18 values did not change, serum IL-4 levels decreased following chemotherapy, independently from treatment response (P = 0.002). Our study is the first to report the response of serum IL-4 levels to chemotherapy. In conclusion, although IL-4 serum concentration has no diagnostic role, it is sensitivite to standard chemotherapy in A-NHL. However, serum IL-18 measurements have no diagnostic or prognostic role in this disease.

Clinical significance of serum hepatocyte growth factor (HGF) levels in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the commonest primary malignant cancer of the liver in the world. This study was conducted to investigate the serum levels of hepatocyte growth factor (HGF)in HCC patients and the relationship with tumor progression and known prognostic parameters. Fifty-four patients with HCC were investigated. Pretreatment HGF levels were employed the quantitative sandwich enzyme immunoassay technique (ELISA). Age and sex matched 20 healthy controls were included in the analysis. The median age of the patients was 60 years (range 36-77 years); where males consistituted of majority of the group (88.8%). All of patients had cirrhotic history. Fourty-six percent (n = 25) of patients had Child-Pugh Score A, 30% (n = 16) had Score B or C. All of the patients were treated with local therapies but none of them received sorafenib. The baseline serum HGF levels were significantly higher in patients with HCC than in the control group (p < 0.001). Male patients had higher serum HGF levels compared with female patients (p = 0.01). Serum HGF levels were significantly higher in the patients with elevated serum ALT levels than others with normal serum ALT levels (p = 0.05). Poor performance status (p < 0.001), viral etiology of cirrhosis (p = 0.03), larger tumor size (p = 0.01), lower serum hemogloblin levels (p = 0.03), and not be treated for HCC (p = 0.001) related to worse survival. However, serum HGF did not have significantly adverse effect on survival (p = 0.58). Despite serum HGF levels were found diagnostic value, serum HGF levels had no prognostic value in patients with HCC.

Prognostic significance of melanoma inhibiting activity levels in malignant melanoma.

This analytic (phase II) study aimed to investigate the hypothesis that the decline in serum melanoma-inhibiting activity (MIA) levels following initiation of treatment might have prognostic value. The mean serum lactate dehydrogenase (LDH), MIA and S100 levels in patients with malignant melanoma before treatment were higher than in the control group. Patients with visceral dissemination had much higher mean serum MIA levels than patients with nodal spread only. A regression model was constructed to analyse the prognostic factors in patients with advanced stage malignant melanoma. Therapy included surgical excision or lymph node dissection, hypofractionated radiotherapy, and immunotherapy or chemotherapy. Blood samples were collected within 24 h before the initiation of systemic treatment and two or three times more at 20-28 day intervals. Overall survival was investigated by univariate analysis, and correlation with clinical factors was compared using the log-rank test. Gender, primary tumour site, surgery, radiation therapy, serum S100 levels before systemic treatment and choice of chemotherapy were not correlated with the outcome. In addition to the stage of disease, low serum LDH levels before systemic treatment and a decline in serum MIA levels following initiation of systemic treatment predicted a favourable outcome. Metastasis to visceral organs was associated with higher serum MIA levels. Persistence of high serum MIA levels despite systemic treatment predicts an unfavourable prognosis.

Measurement of serum CA 19-9 may be more valuable than CEA in prediction of recurrence in patients with gastric cancer.

In 35 patients with recurrent gastric cancer who had undergone curative gastrectomy, serum carcinoembryonic antigen (CEA) and CA 19-9 (carbohydrate antigen) tumor marker levels were investigated. At least one tumor marker was elevated in 24 (68.6%) patients. The levels of serum CA 19-9 and CEA markers were increased in 20 (57.1%) and 12 (34.3%) patients, respectively. This difference was not statistically significant. However, it may be important in terms of clinical practice.

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.

Telomerase activity in patients with chronic myeloid leukemia and lymphoma.

Telomeres are repeated DNA sequences, positioned at the ends of chromosomes and are essential for the stable maintenance of chromosomes. The telomere length serves as a mitotic clock determining the remaining replicative capacity of the cell. Telomeric sequences are lost during each cell division, leading to a process thought to contribute to senescence and cell death. The enzyme telomerase adds 5'-TTAGGG-3' repeats to the mammalian telomeres and maintains the telomere length. Telomerase is normally inactive in most somatic cells but telomerase activity is observed in malignancies. In this study telomerase activity was analyzed in patients with chronic myeloid leukemia (CML) and lymphoma by PCR and ELISA. This approach combines highly specific amplification of the telomerase-mediated elongation products with nonradioactive detection in a highly sensitive photometric ELISA. The PCR products were also analyzed by Southern blotting. The telomerase-specific PCR products were seperated by electrophoresis and transferred to a nylon membrane with subsequent detection of the biotinylated amplificates. High activity levels were detected in 17 CML ( 34%) patients. On the other hand, no activity was observed in lymphoma patients. An increase in the shorter telomeric bands was observed in CML patients who displayed a high level of telomerase activity. In contrast to the low enzyme activity, evidence of telomeric repeats were also found in some lymphoma patients by Southern blotting. This may indicate that lymphoma cells may make use of different pathways for maintaining the length of their telomeres.

Utility of the serum tumor markers: CYFRA 21.1, carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCC) in squamous cell lung cancer.

The aim of this study is to assess the clinical usefulness of serum assays of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and CYFRA 21.1 in the diagnosis of squamous cell lung cancer. Sixty patients with squamous cell, and twenty-four patients with nonsquamous cell histology of nonsmall cell lung cancer were enrolled in this study. Serum CEA, SCC, and CYFRA 21.1 levels were obtained by commercially available kits. Upper cutoff levels were 10 ng/ml, 3.5 ng/ml, and 3.5 ng/ml, respectively. In squamous cell lung cancer, percentages and 95% confidence interval (CI) of the patients with elevated levels were as follows: for CEA 23.3% (13-36), for SCC 20.0% (10-32), and for CYFRA 21.1 85.0% (73-93). The positivity rate of CYFRA 21.1 was more significant than CEA and SCC in both squamous and nonsquamous cell lung cancer. None of the markers were significant in differentiating squamous/nonsquamous histology. Only tumor marker CEA was significantly elevated in metastatic squamous cell lung cancer (p=0.004). A novel tumor marker CYFRA 21.1 can be used as a reliable tumor marker in diagnosing squamous cell lung cancer. In addition, CEA has an important role in determining metastatic disease.

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.

Utility of CA 15-3 and CEA in monitoring breast cancer patients with bone metastases: special emphasis on "spiking" phenomena.

OBJECTIVES: CA 15-3 and CEA are considered useful tumor markers in monitoring breast cancer patients. This study was undertaken to specifically evaluate the transient elevations in these markers that are observed during systemic treatment for metastatic disease. This phenomenon has been termed "spiking." DESIGN AND MATERIALS: Serum tumor marker levels were investigated by enzyme immunoassay in 20 breast cancer patients without metastases and in 20 patients with bone metastases receiving systemic treatment. RESULTS: Both CEA and CA 15-3 levels were significantly elevated in the patients with bone metastases. Serum CEA and CA 15-3 levels in patients with metastases displayed a transient, but significant, elevation days 15 and 30, respectively, after commencing systemic treatment, which returned to pretreatment levels on the 60th day. CONCLUSIONS: The spiking effect observed in the tumor marker levels should be carefully evaluated, and not be misdiagnosed as disease progression.

Evaluation of phosphohexose isomerase as a metastasis marker in breast cancer patients.

In this study the value of PHI serum measurements in breast cancer as an index of metastases was investigated. Serum CA 15-3 and CEA tumor marker and gamma-glutamyltranspeptidase (gamma-GT) levels were also determined in groups of patients with established distant metastases or in patients on follow-up with no evidence of disease. Fifty-one female breast cancer patients were included in the study. The mean values for each parameter were higher when metastases were present. However, the difference was mostly not meaningful. The only significant difference was observed for CA 15-3. Our data do not support the usefulness of the PHI assay for early detection of the metastases in breast cancer.

Amplification in tumors and benign tissue of breast cancer patients.

Inappropriate expression of the c-erb B2 gene has been associated with aggressive tumor behavior in breast cancer. In this study the c-erb B2 amplification was investigated both in the tumors and benign breast tissue of the patients by competitive PCR. The technique combines the sensitivity and speed of PCR with coamplification of a single copy reference gene to achieve quantitative results. Gene copy numbers in excess of 3 copies were observed in tumors of 7 patients but not in the normal tissue samples. We conclude that the increase in the gene copy numbers is a result of the tumorigenic changes occurring in the cancer cell.

The value of TPS in breast cancer.

The serum concentration of the cell proliferation marker TPS (Tissue Polypeptide-Specific Antigen) was compared with 7 different common tumor markers (CEA, CA 12-5, CA 19-9, CA 15-3, ferritin, AFP and beta 2-Microglobulin) in order to assess its practical value in the management of breast cancer. The new monoclonal TPS assay utilizing the specific epitope M3 is used to monitor cell multiplication in cancer patients. The values are not related to tumor burden but rather reflect the tumor proliferation rate. In our study no association was found between the TPS values and the age of the patients and histologic tumor types. Significant correlation was observed between the TPS values and the menopausal status of the patient. The regression analyses between TPS and the other markers did not reveal a correlation. Association between the TPS values and the CA 15-3 was not found. However, strong correlation between CA 15-3 and four other markers was observed. Therefore, it was concluded that TPS can provide additional information when used in combination with CA 15-3.

Diagnostic value of the tumor markers in breast cancer.

The use of the most common tumor markers in breast cancer was reassessed in terms of cost effectiveness and the validity of their predictive information during the evaluation of the patients. Sera from 159 patients were studied. Acceptable diagnostic specificity was found only for CA 15-3. In predicting the presence of metastases the combination of CA 15-3 and CEA was observed to correlate with lymph node metastases. Introduction of MCA did not result in diagnostic improvement. Our results suggest that in practice a diagnostic panel for breast cancer can be confined to CA 15-3 and CEA.

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.

Serum values of CA72.4 in patients with gastrointestinal system tumors comparison with CEA and CA 19.9.

Serum CA 72.4 levels of patients with malignant gastrointestinal disorders (n = 77) were determined in parallel with the CEA and CA 19.9 levels. The values related to healthy individuals were 1.7 U/ml, with a median of 1.7 U/ml, whereas an average of 12.1 U/l (median 2 U/ml) was measured in malignancy. Among all three markers CEA showed the highest positive rate while the values for CA 19.9 and CA 72.4 were lower. Although positive rates among the healthy group were observed with CEA and CA 19.9, no false positives were found with CA 72.4. Elevated CA 72.4 levels were found in 17.6% of patients with gastric carcinoma and 56.3% with colorectal carcinoma. All markers showed significant sensitivity for the malignant state when used alone. However, the regression analysis revealed that only the combination of CA 72.4 and CEA may contribute significantly to the diagnostic potential. Our results indicate that complementation of CEA with CA 72.4 can significantly increase the sensitivity in the serodiagnosis of gastrointestinal system cancers. Combination of positive information from these two sources is likely to lead to a more accurate diagnosis and may therefore improve the efficiency of the follow-up and therapeutic response.

Osteocalcin: a valuable bone metastasis marker.

Osteocalcin (BCG) in an osteoblast product which reflects the bone formation rate. It could be a valuable bone metastasis marker. To investigate this, we measured serum osteocalcin levels by using radioimmunoassay method in 11 healthy subjects and in 79 cancer patients. The cancer patients consisted of 36 non-metastatic, 29 with only bone metastasis and 14 with extraosseous metastases. Significance was found only between bone metastatic patients and non-metastatic patients in both sexes (p. 0.05). There was no significance between non-metastatic patients and patients with other than bone metastases. This study shows that osteocalcin measurements reflect bone formation rates in bone metastasis and could be used as a bone metastasis marker in suspicious cases.

Menstrual cycle values of tumor marker in healthy women and in patients with non-gynecological tumors.

The aim of the present study is to investigate whether the values of CA 12-5 which is considered a specific ovarian tumor marker can be used in patients with non-gynecological tumors whose values in menstrual cycle phases were not previously investigated. In order to determine whether a particular phase or a combination of phase are important, CA 12-5 values were determined by radioimmunoassay technique in a limited number of patients belonging to three different age groups. CA 12-5 were found to be unrelated to age. No statistically significant difference in CA 12-5 values was noted between samples obtained from patients with tumor and healthy women on the first and second days of menstruation. In both cases the normal value exceeded 35 U/ml. The mean values was 42 U/ml in healthy women and 49 U/ml in tumor patients. Mean CA 12-5 values determined between the 12th and 14th days on which estrogen hormone is at its highest level, were found to be 23 U/ml in healthy women and 40 U/ml in patients with tumors. These values are statistically significant, while CA 12-5 values determined in samples obtained on the 20th-25th days are within the normal range. Values of the CA 12-5 tumor marker during the estrogenic phase are important in the diagnosis, management and follow-up of cancer. Determination of estrogen hormone levels as an additional parameter may provide a significant correlation.