PubMed Health⌕ Search

Biomedical subjects

N Dalay

Publications and source records attributed to N Dalay.

At least 19 recordsLinked to original sources
PubMed2006

Microsatellite instability and methylation of the DNA mismatch repair genes in head and neck cancer.

BACKGROUND: Methylation in the promoter region of the DNA mismatch repair genes hMLH1 and hMSH2 and microsatellite instability at three loci were analyzed in the tumor tissue from patients with head and neck cancer. METHODS: Microsatellite instability and promoter methylation were investigated by PCR, denaturing-polyacrylamide gel electrophoresis and digestion with methylation-specific restriction enzymes. RESULTS: Microsatellite instability was observed in 41% of the patients. hMLH1 and hMSH2 genes were methylated in 47% and 30% of the patients, respectively. BAT25 and BAT26 instability were associated with age and histopathology, respectively. Methylation frequency of the hMLH1 gene promoter was significantly higher in patients displaying a high level of microsatellite instability. Instability at the BAT 26 and D2S123 loci were associated with the MSI-high status. CONCLUSIONS: Our results indicate that microsatellite instability and modifications in the hMLH1 and hMSH2 genes are implicated in a significant proportion of the patients with head and neck cancer.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Serum and tissue c-erb B2, bcl-2, and mutant p53 oncoprotein levels in nasopharyngeal cancer.

To date there are no prognostic factors that can account for the biology and disease behavior in nasopharyngeal cancer. Therefore, identification of new factors that can help in predicting the behavior of the disease and characterizing the subgroup with more aggressive tumors more likely to benefitfrom chemotherapy is important. In this study, c-erb B2, bcl-2, and mutant p53 protein levels were investigated in sera and tumor tissue of patients with nasopharyngeal cancer. Serum c-erb B2 levels were significantly higher in the patients than in the healthy subjects. No meaningful difference was observed between the serum and tissue levels of the mutant p53 protein. Tissue bcl-2 concentrations were considerably high. Our results suggest that serum c-erb B2 levels may aid in identifying a subgroup of patients with a poorer response rate to first-line treatment.

Adolescent↗
PubMed2001

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.

Adult↗
PubMed2001

P53 codon 72 genotypes in colon cancer. Association with human papillomavirus infection.

It has been reported that the p53Arg homozygous genotype could be a potential genetic risk factor for cancer. In this study we investigated the proportion of p53 codon 72 genotypes in patients with colon cancer and compared to a control population. A region of the p53 gene containing the polymorphic site was amplified by PCR and the genotypes were determined by restriction enzyme digestion. No significant difference was found between genotype frequencies in the study groups. Infection with human papilloma virus was also investigated in the tumor samples. HPV 18 and HPV 33 infection was observed in a considerable number of the tumor samples. Incidence of HPV infection did not show a correlation with the genotypes. Thus the p53 genotypes do not seem to be associated with risk of colon cancer or HPV infection.

Adult↗
PubMed2000

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.

Adult↗
PubMed2000

BRCA1 and BRCA2 mutations in Turkish breast/ovarian families and young breast cancer patients.

To date, BRCA1 and BRCA2 mutations in breast and/or ovarian patients have not been characterized in the Turkish population. We investigated the presence of BRCA mutations in 53 individuals with a personal and family history of breast and/or ovarian cancer, and 52 individuals with a personal history of breast cancer diagnosed below age 50 without additional family history. We have identified 11 mutations (nine BRCA1 and two BRCA2) using combined techniques involving protein truncation test, direct sequencing and heteroduplex analysis. We found eight out of 53 patients (15.1%) with a family history to carry BRCA gene mutations (seven BRCA1 and one BRCA2). Of these, four were found in 43 families presenting only breast cancer histories, and four were found in families presenting ovarian cancer with or without breast cancer. We also demonstrated two BRCA1 and one BRCA2 mutations in three out of 52 (5.8%) early-onset breast cancer cases without additional family history. Three of nine BRCA1 and both BRCA2 mutations detected in this study were not reported previously. These mutations may be specific to the Turkish population. The BRCA1 5382insC mutation, specific to Ashkenazi and Russian populations, was found twice in our study group, representing a possible founder mutation in the Turkish population.

Adult↗
PubMed2000

c-erbB-2 gene amplification in nasopharyngeal carcinoma.

Amplification of the c-erbB-2 gene has been associated with poor prognosis in different types of cancer. However, there are no data on the c-erbB-2 expression levels in nasopharyngeal cancer. In this study, amplification of the gene has been investigated in the tumor tissue of patients with nasopharyngeal cancer by competitive polymerase chain reaction c-erbB-2 amplification was observed in 43.3% of the patients. The increase in the gene copy number correlated with the T stage. No correlation was found with lymph node involvement, histologic grade, differentiation, presence of metastases, or age and sex. We conclude that c-erbB-2 amplification may contribute to the pathogenesis of nasopharyngeal cancer. Our report is the first study investigating the expression of the c-erbB-2 gene in nasopharyngeal cancer at the DNA level.

Adolescent↗
PubMed2000

Utility of c-erbB-2 expression in tissue and sera of ovarian cancer patients.

In this study, expression of the c-erbB-2 gene in tumors and healthy tissue of patients with ovarian cancer was investigated. Serum c-erbB-2 protein levels were also determined. Elevated serum values were observed in 45% of patients. c-erbB-2 protein levels in the tumors were significantly higher than in healthy tissue. Overexpression of the protein was observed in 60% of patients. However, no association was found between the clinical variables and tumor c-erbB-2 expression. This is the first study in the literature investigating the c-erbB-2 oncoprotein levels in the normal and tumor tissue. We conclude that the role of the c-erbB-2 gene in ovarian cancer warrants further studies.

Adult↗
PubMed2000

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.

Adolescent↗
PubMed1999

Bcl-2 gene rearrangements and apoptosis rates in patients with non-Hodgkin's lymphoma during chemotherapy.

OBJECTIVES: Overexpression of the bcl-2 gene as a result of the t(14,18) translocation leads to neoplastic transformation by suppressing apoptosis. However, apoptotic cell death in response to chemotherapy has not been investigated. This study was planned with the aim to investigate the association between bcl-2 gene rearrangements and apoptotic changes during chemotherapy in patients with non-Hodgkin's lymphoma. DESIGN AND METHODS: Lymphocytes from 33 patients were collected before and during chemotherapy. Bcl-2 gene rearrangements were investigated by PCR. Apoptotic cell death was analyzed by enzyme immunoassay. RESULTS: In 24 cases, mbr gene rearrangements were detected. Apoptosis was successfully induced by chemotherapy in 48% of patients. Two characteristic, clearly distinguishable apoptotic response patterns with transient peaks either following the first or the third course were observed. It was found that apoptosis rates measured after the first course exactly reflect the final response. No correlation was found between bcl-2 gene rearrangements and apoptosis. CONCLUSIONS: Apoptotic cell death rates show transient changes during chemotherapy. Because the midterm response can be misleading, the apoptotic response should be evaluated following the first course of chemotherapy.

Adult↗
PubMed1998

Investigation of the molecular changes during chemotherapy in non-Hodgkin's lymphoma.

In the present study the changes in the detection rate of bcl-2 and IgH gene rearrangements in relation to chemotherapy and therapeutic response in patients with diffuse large B-cell lymphoma have been investigated. Immunoglobulin gene rearrangements were detected in almost all patients during all stages of treatment. Persistence of bcl-2 rearrangements reflected the effect of chemotherapy better. Bcl-2 rearrangements were initially detected in 64% of the patients. Cells bearing the translocation disappeared during therapy in a significant group of cases. In 10 patients bcl-2-rearranged cells were detected for varying periods of time. However, no correlation was found between the molecular persistence or disappearance of cells as detected by PCR and the therapeutic response or recurrence rates.

Adult↗
PubMed1998

A new method for the detection of bcr/abl sequences amplified by polymerase chain reaction (PCR) following bone marrow transplantation.

Disease recurrence is a major problem in patients receiving bone marrow transplantation for chronic myeloid leukemia. Residual malignant cells are the most likely source of recurrence. Detection of minimal residual disease early during therapy may provide an additional prognostic value and help in identifying patients who are at high risk of relapse. PCR followed by hybridization is the most sensitive method to investigate the persistence of leukemic cells. However, more reproducible methods suitable to standardization and quantification are required in clinical practice. In this study, we describe a novel PCR assay combined with immunological and colorimetric detection of the bcr-rearrangement. Residual bcr/abl rearranged cells were observed in 7 patients. Our results show that the assay is equally sensitive as RT-PCR, more versatile in terms of standardization and easily adaptable as a diagnostic test.

Adult↗
PubMed1997

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.

Biomarkers, Tumor↗
PubMed1997

Clinical use of the bcr/abl probe test in the evaluation of chronic myeloid leukemia patients.

CML is characterized by a reciprocal translocation between the abl and bcr genes on chromosomes 9 and 22 and is usually diagnosed by the presence of the Philadelphia (Ph1) chromosome.However, the translocation may also occur without the appearance of the Ph1 chromosome. In this study the diagnostic efficiency of the molecular hybridization assay was investigated in 227 patients using a probe specific for the bcr region of the gene. Gene rearrangements were observed in 96% of Ph1-positive cases and in 92% of the patients in whom no Ph1 chromosome could be detected by karyotype analysis. By using peripheral blood the assay is easy to perform and superior in sensitivity. Thus, it is recommended that this assay should be routinely used as anadjunct to classical cytogenetics.

Blotting, Southern↗
PubMed1997

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.

Adult↗
PubMed1996

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.

Breast Neoplasms↗