Biomedical subjects

Rafał Dziadziuszko

Publications and source records attributed to Rafał Dziadziuszko.

9 recordsLinked to original sources

PubMed2006

Increased risk of non-small cell lung cancer and frequency of somatic TP53 gene mutations in Pro72 carriers of TP53 Arg72Pro polymorphism.

The aim of this study was to assess whether the TP53 Arg72Pro polymorphism is associated with an increased risk of non-small cell lung cancer (NSCLC). Additionally, in NSCLC patients, we investigated a potential association between this polymorphism and somatic TP53 gene mutations in tumour cells. The study group included 240 NSCLC patients who underwent curative pulmonary resection. The control group (576 healthy subjects) was matched for sex and cigarette smoking. TP53 Arg72Pro polymorphism was determined by denaturing high-performance liquid chromatography. Tumours from 157 NSCLC patients were analysed for mutation in TP53 exons 5-8 by single strand conformation polymorphism, followed by sequencing of samples with different band pattern. Tumours from the remaining 83 patients were subjected to a direct sequencing of TP53 exons 5-8. The proportion of Pro homo/heterozygotes versus Arg homozygotes was significantly higher in NSCLC patients (54%) than in controls (46%, p = 0.034). The crude odds ratio for NSCLC development in Pro72 allele carriers was 1.39 (95% CI: 1.03-1.88). When adjusted for sex, age and smoking status in the multivariate logistic regression model, odds ratio for NSCLC development was 1.28 (95% CI: 0.91-1.80). Somatic TP53 mutations were found in 62 out of 240 NSCLC patients (26%), more frequently in Pro carriers (31%) than in Arg homozygotes (20%, p = 0.06). These results indicate that the TP53 codon 72 Pro allele may increase the risk of NSCLC. Additionally, the correlation between Pro72 and somatic TP53 mutations suggests that Pro72 allele carriers may be predisposed to tumour development along a p53 associated form of NSCLC, a finding that warrants further investigations.

Adenocarcinoma↗

PubMed2005

[Analysis of prognostic value of TP53 gene mutations in non-small cell lung cancer].

The aim of this study was to assess the frequency and prognostic value of TP53 gene somatic mutations in non-small cell lung cancer. The study group included 240 NSCLC patients who underwent pulmonary resection at the Department of Thoracic Surgery, Medical University of Gdańsk. Tumour samples were evaluated for the presence of TP53 gene mutations in exons 5-8. In 157 cases SSCP method was used as a screening followed by sequencing of positive samples. In the remaining 83 patients mutations were analysed by direct sequencing. A total of 76 mutations (32%) were found, of those a missense type was dominant (67%), followed by silent and null type mutations (14% and 10%, respectively). There was no correlation between mutations and clinical characteristics, including age, sex, histological subtype, differentiation, tumour size, lymph node metastases, pTNM stage and smoking status. A multivariate Cox analysis demonstrated that tumour differentiation and pTNM stage were independent prognostic factors, whereas TP53 gene mutations were not. The results of this study indicate that TP53 gene mutations in NSCLC patients are not correlated with clinical characteristics and have no impact on survival.

Adult↗

PubMed2004

P53 and K-ras mutations are frequent events in microscopically negative surgical margins from patients with nonsmall cell lung carcinoma.

BACKGROUND: The objective of the current study was to determine whether tumor cells harboring P53 and K-ras mutations could be detected in histopathologically tumor-free surgical margins in patients with nonsmall cell lung carcinoma who underwent complete pulmonary resection. METHODS: In 118 consecutive patients, DNA obtained from primary tumors and from surgical margins was extracted for molecular analysis. A fragment of P53 gene encompassing exons 5-8 and codon 12 of the K-ras gene were amplified with the polymerase chain reaction technique and were assayed for the presence of mutations. RESULTS: P53 and K-ras mutations were found in 30% and 39% of primary tumors, respectively, and in 11 (9%) and 22 (18%) apparently tumor-free surgical margins, respectively. At least 1 of those mutations was found in surgical margins in 29 patients (25%), and both mutations were found in 2 patients (1.7%). P53 mutations in surgical margins accompanied mutations in primary tumors in 9 of 35 patients (26%), and K-ras mutations accompanied mutations in primary tumors in 20 of 46 patients (44%). Among patients with either mutation in primary tumors, the incidence of at least 1 mutation in surgical margins was 43% (28 of 65 patients). In four patients, mutations (two K-ras mutations and two P53 mutations) were found in surgical margins despite the absence of the corresponding mutations in primary tumors. The presence of mutations in primary tumors and in surgical margins was not related significantly to clinical characteristics or to patient outcomes. CONCLUSIONS: P53 and K-ras mutations are frequent events in surgical margins determined to be tumor free on light microscopy. The clinical relevance of these findings remains to be established.

Adult↗

PubMed2004

MDM2 gene amplification: a new independent factor of adverse prognosis in non-small cell lung cancer (NSCLC).

The prognostic impact of MDM2 amplification in non-small cell lung cancer (NSCLC) remains unknown. In this study, we investigated the occurrence of MDM2 amplification in surgically treated NSCLC patients. Molecular data were correlated with clinicopathological factors and evaluated for their prognostic value. The study group included 116 NSCLC patients who underwent pulmonary resection between 1996 and 1999. MDM2 amplification was assessed by real-time PCR using hybridization probe format on a LightCycler (Roche). The calculated ratio was a MDM2 value normalized to the amplification of the housekeeping gene phenylalaninhydroxylase (PAH). Survival curves were drawn according to the Kaplan-Meier method and compared with the use of the log-rank test. Multivariate analysis was based on Cox regression analysis. MDM2 amplification was found in 24 patients (21%). There was no relationship between MDM2 amplification and clinicopathological factors, such as sex, age and stage of disease, pT, pN, histology and tumor differentiation. Median disease-free survival (DFS) in patients with and without MDM2 amplification was 3 and 31 months, and 5-year DFS 24 and 33%, respectively (log-rank, P = 0.02). Likewise, median overall survival (OS) in patients with and without MDM2 amplification was 9 and 33 months, respectively, and 5-year OS 24 and 39%, respectively (log-rank, P = 0.01). The strong prognostic relevance of MDM2 amplification for both DFS and OS was confirmed in multivariate analysis (P < 0.01 for both comparisons). Our results suggest that MDM2 gene amplification analysis provides additional prognostic information in surgically treated NSCLC patients.

Adenocarcinoma↗

PubMed2003

[Results of treatment for chronic pleural empyema].

UNLABELLED: The aim of the study was to assess the results of the treatment in 97 patients with chronic pleural empyema treated in the department of thoracic surgery between 1988 and 1997. The majority of patients were between 30 and 50 years old. Most of the group were men and more than a half had a concomitant disease, which may predispose to empyema development. Nevertheless all the empyemas were in the chronic phase 1/3 of patients were successfully treated only with closed chest tube drainage and the remaining group with lung decortication. The Gram-negative bacterial flora dominated in the culture from empyema sac. Spirometric values and blood gas analysis showed significant reduction of lung function before the treatment. We found the relation between an early institution of closed tube drainage and the shorter stay at the hospital. Moreover in a significant proportion of patients pleural drainage was a sufficient way of treatment. CONCLUSIONS: Drainage of the empyema should be performed at early phase of the disease. It should be recommended that pleural drainage precede the surgical management of empyema. Delate of surgical intervention is the main cause of the high mortality rate in empyema following esophageal perforation.

Adolescent↗

PubMed2002

Decortication in chronic pleural empyema - effect on lung function.

OBJECTIVE: The aim of the present study is to evaluate the lung function before and after the lung decortication in patients with chronic pleural empyema (CPE). METHODS: Twenty-six patients with diagnosis of CPE were evaluated in a prospective manner by lung perfusion scintigraphy, blood gas analysis and spirometry before and 35 weeks (+/-17) after the lung decortication. RESULTS: Preoperative scintigraphy showed reduction of lung perfusion on the affected side to 24.5% (+/-12.6%) in 11 right side empyemas (predicted value 55%) and to 18% (+/-8%) in 15 left side empyemas (predicted value 45%). The postoperative measurements showed improvement in perfusion to 45.2% (+/-7.7%) in patients with right side empyema and 34.1% (+/-8.5%) with the left side affection. The preoperative vital capacity (VC) was reduced to 62.3% (+/-13.8%) of the predicted value and forced expiratory volume in 1s (FEV1) to 50% (+/-15.5%) of the predicted value. Postoperatively, slight improvement was achieved to 79.8 % (+/-12.9%) for VC and 69.2% (+/-12.7%) for FEV1. Blood gas analysis showed decreased values in majority of the patients before operation and significant improvement in postoperative evaluation. CONCLUSIONS: Perfusion and spirometry improves significantly in patients with CPE after the lung decortication but function of the affected lung remains impaired. There was no influence of the age, gender, side of the disease, bacteriology or duration of the empyema before operation on lung function.

Adult↗

PubMed2002

[The prevalence of serum IgG antibodies against HTLV viruses type I and II in sarcoidosis patients].

UNLABELLED: The pathogenesis of sarcoidosis remains still unknown. Among numerous factors viruses are considered as potential causes. The aim of the study was investigation of human T-cell lymphotopic virus type I (HTLV-I) in sarcoidosis patients. Studied group (I) consisted of 52 patients: 29 women and 23 men aged from 24 to 62 years; mean age 40 years. The diagnosis of sarcoidosis was confirmed by histologic examination in 46 patients and on the base of clinical, HRCT--chest scan and BAL findings in 6 patients. Control group (II) consisted of 92 various pulmonary disorders patients and healthy subjects in the aged from 20 to 83 years; mean age 54 years. In both groups the ELISA test detecting antibodies against HTLV-I/II was performed with the use the diagnostic kit produced by Organon Teknika, Belgium. Results were interpreted by measuring the optical density (OD). The cut-off point 0.386 was established according to the rule defined by kit's producent. The values of OD ranged in group I from 0.061 to 0.384 and in group II from 0.047 to 0.213; thus, no positive results of the test were observed. The values of OD did not differ significantly in both groups (p = 0.59). CONCLUSION: In our region the participation of HTLV-I in the pathogenesis of sarcoidosis is doubtful.

Adult↗

PubMed2002

[P53 and P16 gene mutations in non-small cell lung cancer].

The aim of this study was to assess prospectively the occurrence of p53 and p16 mutations (considered separately and together) in NSCLC in terms of their clinical and prognostic relevance. Study group included 87 patients who underwent pulmonary resection for cure. p53 and p16 mutations were found in 22 (25%) and 14 (16%) cases, respectively. In eight patients (9%) both mutations were present, and the tendency for their common occurrence was significant (p = 0.02). There was no relation between mutation and clinical characteristics. Median survival in the entire group was 17 months and the 3-year survival probability--41%. There was no correlation between the occurrence of any mutation (considered separately or together) and survival. These results indicate that p53 and p16 gene mutations tend to occur together in NSCLC, however these alterations seem not to have noteworthy clinical and prognostic significance.

Adult↗

PubMed2002

[Serum anti-P53 antibodies (AB-anti-P53) in patients with advanced non-small cell lung cancer (NSCLC)].

The aim of the study was to assess the frequency of serum Ab-anti-p53 in 39 patients with advanced NSCLC and to evaluate the predictive value of the test. Antibodies were present in 10 (25.6%) of patients. There was no correlation between Ab-anti-p53 and clinical characteristics including age, gender, and histological type of tumor. In 17 patients response to chemotherapy (CT) was obtained (in one patient--complete, and in 16--partial response). The percentage of patients responding to CT in group with and without serum antibodies did not differ significantly (33% and 48%, respectively; p = 0.48). The results of the study indicate that serum Ab-anti-p53 are relatively often present in advanced NSCLC patients, however the clinical value of this test needs further evaluation.

Adult↗