Biomedical subjects

E Chyczewska

Publications and source records attributed to E Chyczewska.

At least 19 recordsLinked to original sources

PubMed2005

Serum endostatin levels in patients with lung carcinoma.

UNLABELLED: The purpose of our study was to evaluate the clinical usefulness of serum endostatin levels during chemotherapy of lung cancer in relation to the histopathological type of the tumor, clinical stage and response to therapy. MATERIALS AND METHODS: Serum concentrations of endostatin were determined in 37 patients (24 with non-small cell lung cancer and 13 with small cell lung cancer), 10 healthy subjects constituted controls. To determine endostatin levels (ELISA), venous blood samples were collected from each patient before treatment and after 4-6 courses of chemotherapy. RESULTS: The serum concentrations of endostatin were found significantly higher in patients in comparison with controls (p=0.003). No statistically significant differences were established between the concentrations of endostatin with regard to such clinical features, as: performance status, clinical stage (III and IV) and histopathological type (non-small cell lung cancer and small cell lung cancer). The concentrations of endostatin did not change after chemotherapy. There was no change of endostatin concentration caused by the response to treatment. CONCLUSIONS: The serum endostatin concentrations were elevated in lung cancer patients.

Aged↗

PubMed2004

Serum levels of IGF-I and IGF-II in patients with lung cancer during chemotherapy.

UNLABELLED: The AIM of this study was to assess the influence of chemotherapy on the serum levels of IGF-I and IGF-II in patients with lung cancer. METHODS: The study included 38 patients (33 males and 5 females) at mean age of 59.8, diagnosed histologically with lung cancer. Twenty five patients had non-small cell lung cancer (NSCLC) including 11 patients with squamous cell carcinoma (SCC), 5 patients with adenocarcinoma and 9 patients without an essential histological type of NSCLC. A total of 13 patients had small cell lung cancer (SCLC). The control group consisted of 10 healthy volunteers. The peripheral blood samples were taken before and after 4 cycles of chemotherapy. IGF-I and IGF-II levels were assessed by ELISA method. RESULTS: Serum levels of IGF-I and IGF-II measured before chemotherapy were significantly higher in both NSCLC and SCLC groups in comparison with controls. There were no significant differences of serum levels of both growth factors before and after 4 cycles of chemotherapy. Serum levels of IGF-I and IGF-II were still high after chemotherapy in patients with NSCLC and SCLC. Patients with SCC and adenocarcinoma had similar serum levels of IGF-I and IGF-II without statistical differences. CONCLUSION: Serum levels of IGF-I and IGF-II were significantly higher in patients with NSCLC and SCLC before chemotherapy than in controls. Chemotherapy had no influence on the serum levels of insulin-like growth factors (IGFs). Serum levels of IGF-I and IGF-II did not depend on a histological type of NSCLC either.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2004

Serum levels of interleukin-18 (IL-18) and soluble interleukin-2 receptor (sIL-2R) in lung cancer.

PURPOSE: We evaluated the clinical usefulness of interleukin-18 (IL-18) and soluble interleukin-2 receptor (sIL-2R) during chemotherapy of lung cancer in relation to the histological type of the tumor, clinical stage, response to therapy and time survival. MATERIAL AND METHODS: Serum levels of IL-18 and sIL-2R were determined in 73 patients (62 males; mean age 64 years; 41 with non-small cell lung cancer-NSCLC, 32 with small cell lung cancer-SCLC); 12 healthy subjects served as controls. To determine IL-18 serum concentrations (Elisa), venous blood samples were collected from each patient before and after chemotherapy. RESULTS: The mean serum IL-18 level in all patients with lung cancer was significantly higher compared with healthy volunteers (p = 0.0001; NSCLC vs control p = 0.0001; SCLC vs control p = 0.004). In NSCLC group with stage IV the mean IL-18 level was significantly higher than those with stage IIIB (p = 0.04). Regarding tumor stage and response to therapy, no significant differences in IL-18 were observed. Using cut-off serum IL-18 concentration of 319.6 pg/ml, the prognoses of the two groups were different, but it was not statistically significant. The serum levels of sIL-2R in NSCLC patients were significantly higher than in controls (p = 0.018). There were no significant differences in serum sIL-2R levels in relation to clinical stage of lung cancer and response to therapy. The cut-off value between high and low serum sIL-2R concentration was defined as 582.27 U/ml. The difference in survival rate between the high and low sIL-2R groups was not significant. CONCLUSIONS: Serum IL-18 and sIL-2R levels can be useful in clinical practice, but their practical significance needs further studies.

Antineoplastic Agents↗

PubMed2004

Serum levels of osteoprotegerin (OPG) and pro gastrin releasing peptide (ProGRP) during chemotherapy of lung cancer.

The aim of our study was to evaluate the usefulness of serum OPG and ProGRP during chemotherapy of lung cancer in relation to the histological type of the tumour, its clinical stage and the response to therapy. The levels of OPG and ProGRP were determined in 39 patients (20 NSCLC, 19 SCLC) and 10 healthy subjects. Blood samples were collected from each patient before and after chemotherapy. OPG and ProGRP levels in all the patients with lung cancer were higher than those in the controls. ProGRP were higher in SCLC group than in those NSCLC. In NSCLC group (after chemotherapy), OPG level in patients with Stage IV tumour was higher than in those with Stage IIIB (p=0.03). OPG in ED SCLC were higher than those in LD SCLC (p=0.04). In SCLC group, ProGRP were higher in LD patients than those with ED (p=0.04). Concluding, the measuring of OPG and ProGRP in lung cancer patients may be useful in clinical practice.

Biomarkers, Tumor↗

PubMed2003

Therapy increases poly-ADP-ribose and p53-Ser392-P levels in recurrent squamous cell lung cancer.

p53 protein is a critical regulator of the cell cycle and apoptosis and its levels and functions change in response to many stimuli. To assess whether the cytotoxic drugs induce DNA changes, affect phosphorylation and stability of p53 protein, we determined poly-ADP-ribose levels, the expression of p53 protein and its carboxyl-terminal Ser-392 phosphate levels in fiberoptic bronchoscopy biopsy samples taken from patients suffering from recurrent squamous cell lung cancer before and after radiotherapy and chemotherapy. All 14 patients included in this study were in IA-IIIA clinical stage prior to surgery. Radiation/chemotherapy decreased G2/M cell numbers but increased S-phase cells by almost 50% compared to ploidy status before therapy, while median p53 expression was doubled (109% increase). p53 phosphorylated on Ser-392 was also increased by approximately 70% in patients treated with radiotherapy and with chemotherapy and correlated with elevated poly-ADP-ribose levels. Our data suggest that apart from changes in p53 quantity, posttranslational phosphorylation/dephosphorylation-mediated alterations may play an important role in neoplastic cell proliferation as well as in antiproliferative activity of drugs inducing DNA damage and apoptosis.

Aged↗

PubMed2001

Morphological aspects of carcinogenesis in the lung.

The origins of the various histological types of primary lung cancer are not well understood. Numerous recent studies have indicated that lung cancer is not a result of a sudden transforming event in the bronchial and alveolar epithelium and in the neuroendocrine cells, but a multistep process in which a sequence of morphological and genetic changes is occurring. New modern technical approaches like fluorescence bronchoscopy techniques and microdissection, provide facilities to obtain valuable specimens for morphological and genetic verification of the sequentional changes in lung cancerogenesis. With their help, cells with morphologically recognized changes thought to be preneoplastic, may be removed and prepared for molecular and genetic studies. Therefore, the knowledge of the morphological aspects of lung preneoplastic lesions is crucial to make progress in molecular studies of lung carcinogenesis. Presently the knowledge about the sequence of molecular events in the lung carcinogenesis and their relationship to morphology is not perfect. In this review we will describe morphological aspects of various preneoplastic lesions occurring in the bronchial and bronchiolo-alveolar compartments including neuroendocrine cells.

Cell Differentiation↗

PubMed2001

Prognostic molecular markers in non-small cell lung cancer.

Although TNM stage is the most significant prognostic parameter in lung cancer, additional parameters are required for explaining variability of survival. Hence molecular alterations in lung cancer have been extensively studied. Most prominent among them are alterations in the p53-p21 pathway, controlling the G1/S transition. They are the most commonly observed aberrations in non-small cell lung cancer (NSCLC). The results of p53 mutations on an individual patient's changes for survival are rather controversial. In a recent study however, after analyzing p53 abnormalities both by direct sequencing and immunohistochemistry together with evaluation of bcl-2 protein expression, we have found that p53 alterations were significantly associated with poor overall survival. Recently, a more sensitive yeast functional assay for altered p53 protein has been developed, with about 70% positivity in NSCLC patients and a correlation with shortened survival. The clinical significance of p21WAF1, the protein encoded by the target gene of p53 transcription, is still controversial; however expression has been associated with favorable prognosis in squamous cell carcinoma type. The 'Rb pathway' involving two oncogenes (cyclins D and E) and two tumor suppressor genes (Rb and p16) represents another major source of molecular alterations in lung cancer. Loss of Rb does not seem to significantly influence prognosis, white loss of p16 has been show repeatedly to be a factor for poor survival. Hypermethylation of the promoter region has been proposed as an alternative mechanism for inactivation of the p16 gene. The relation between cyclin D and E expression and prognosis, still is matter of controversy. Ras mutations are reported especially in adenocarcinoma; considered alone they bear no clear relation with prognosis, in opposition when considering them together with other molecular alterations. As a conclusion, a variety of molecular markers have been implicated in the prognosis of NSCLC. However, conflicting results were reported in the literature. Thus further investigations will be required, especially the use of newer molecular assays and the development of appropriate markers or panels of molecular markers.

Biomarkers, Tumor↗

PubMed2001

The impact of immune responses on lung cancer and the development of new treatment modalities.

OBJECTIVE: This presentation covers predominantly review data in relation with immune responses initiating and accompanying lung carcinogenesis or- on the contrary-contributing to novel therapeutic developments. Occasionally, personal findings will be considered. RESULTS 1 OF IMMUNE DEFICIENCY: It is known for several decades that cancer incidence (several sites) is increased in subjects receiving immunosuppressive therapy, e.g. to avoid transplant rejection, or suffering from AIDS. We have observed that in areas heavily polluted by industrial activities, resulting in immune deficiency, cancer incidence is increased, notably for lung cancer. On the other hand, neoplastic cells are able to escape the host's immune responses by inducing apoptosis of the effector T lymphocytes. Apoptosis in T-cells is triggered by the interaction of the membrane receptor Fas with its normal ligand Fas L, or an activating antibody. Now lung carcinoma cells have been shown to express Fas L, enabling them to destroy cytolytic T cells. RESULTS 2 OF IMMUNE TREATMENT: It is well over a century ago that interest in the immunotherapy of cancer was aroused by the observation of tumour regressions concomitant with bacterial infection, an observation leading to the development of 'Coley's toxin', a mixture of killed bacteria (presently known to act through the presence of TNF-alpha). Since these long-standing empirical attempts, a lasting search for immune control of cancer has been initiated, comprising such different approaches as active non-specific immunotherapy, active specific immunotherapy, approaches based on the use of monoclonal antibodies, as well as those depending on cellular immunity and the development of adoptive immunotherapy, and the use of peptide vaccines. These different approaches will be described and their results presented. CONCLUSION: Present state-of-the-art will be discussed and new pathways for development evoked; better understanding of immune mechanisms is opening new avenues for improved treatment efficacy.

Antibodies, Monoclonal↗

PubMed2001

Detection of human papillomavirus in non-small cell lung carcinoma by polymerase chain reaction.

Human papillomavirus (HPV) infection is one of the risk factors contributing to the pathogenesis of lung cancer. The aim of the study was to determine the presence of HPV in non-small cell carcinomas of the lung. The study included 40 tumors: 22 squamous cell carcinomas, 13 adenocarcinomas and 5 large cell carcinomas. HPV was found in 4 cases (10%). High risk HPV was present in 3 tumors: in one squamous cell carcinoma, one large cell carcinoma and one adenocarcinoma, while low risk HPV was detected in one adenocarcinoma.

Carcinoma, Non-Small-Cell Lung↗

PubMed2001

Morphological and molecular aspects of cancerogenesis in the lung.

Morphology and some molecular aspects of hyperplastic (bronchial basal cell hyperplasia and alveolar cell hyperplasia), metaplastic (squamous metaplasia), preneoplastic and early neoplastic (dysplasia in squamous metaplasia, cancer in situ and atypical alveolar cell hyperplasia) changes were studied in 180 lungs resected due to non-small cell lung cancer: 106 cases (58.9%) of squamous cell carcinoma, 42 (23.3%) of adenocarcinoma and 32 (17.8%) of large cell carcinoma. P53 protein and PCNA expressions were detected immunohistochemically (using formalin-fixed, paraffin-embedded sections). DNA extracted from the microdissected P53-positive cells was analysed for point mutations in the P53 gene. No P53 immunostaining was observed in normal mucosa, hyperplasia of basal cells, squamous metaplasia without and with minor and moderate dysplasia of bronchial mucosa as well as alveolar cell hyperplasia. Overexpression of P53 protein occurred in 3 out of 12 (25%) cases of severe bronchial dysplasia, 5 out of 11 (45.5%) cases of intraepithelial carcinoma and 6 out of 45 (13.3%) cases of alveolar cell hyperplasia. Using direct sequencing, mutations in the P53 gene were detected in 11 out of 14 (87%) P53-immunopositive samples, including all severe dysplasias, all carcinomas in situ and 3 of 6 alveolar cell hyperplasias. A significant association was observed between PCNA expression and preinvasive as well as invasive lesions. The data clearly show that lung resected due to primary cancer ought to be treated as "field cancerization" in which one can find early morphologic events of multi-step cancerogenesis. P53 protein alterations and P53 gene mutations can occur before invasion and its frequency depends on the degree of dysplasia.

Carcinoma, Non-Small-Cell Lung↗

PubMed2001

Strong association between P53 protein accumulation, serum antibodies and gene mutation in non-small cell lung cancer.

DNA sequencing is the gold-standard method, but it is not feasible on a routine clinical basis. Immunohistochemistry is the most widely used method for assessing P53 alterations in human cancers. It can be performed during routine analysis, but some mutations may not lead to P53 protein accumulation, or P53 overexpression may be detected in the absence of mutations of the P53 gene. Recent studies have demonstrated the appearance of P53 antibodies in the serum of patients with lung cancer, probably due to the accumulation of mutant P53 protein in tumor cells. Using a logistic regression model applied to data for 102 non-small cell lung cancer (NSCLC) patients, we show a strong association between results of P53 mutation (P53-M) test, TNM stage and results of anti-P53 antibody in serum (P53-Abs) and P53 protein expression (P53-PE) tests. According to that model, we propose a procedure allowing for prediction of result of P53-M test. The percentage of correct predictions for independent data of 15 NSCLC patients was 80%. We conclude that in the absence of P53-M test result, a reasonably precise prediction of the test can be obtained using TNM stage and results of P53-Abs and P53-PE tests. The prediction can in turn be used to evaluate prognosis of NSCLC patients.

Antibodies, Neoplasm↗

PubMed2001

Endothelial cells and angiogenesis intensity in lung cancer.

We focused our studies on single endothelial cells (ECs) scattered in extracellular matrix in lung cancer tumors. Neovascularization was evaluated in 100 tumors obtained from patients operated for lung cancer, in relation to histological type, tumor differentiation and clinical stage of the disease. Angiogenic objects (single endothelial cells and microvessels) were identified by immunohistochemistry using monoclonal antibodies against von Willebrand factor. The count of angiogenic objects per 1 mm2 in each section was determined in a "hot spot" located at the margin of the tumor. We used an arbitrary scale of angiogenesis intensity: 1 - 0-200, 2 - 201-400, 3 - >400 angiogenic objects/mm2. A majority (57%) of the examined cases belonged to the group 2. The angiogenesis intensity measured by the single EC numbers/mm2 correlates with the histological type and the differentiation of the tumors. There was no such a correlation when the angiogenesis intensity was measured by counting total angiogenic objects (microvessels + EC) number/mm2. Single EC number/mm2 in different histological types of cancer were as follows: 162+/-121 in squamous cell (SqCC), 194+/-71 in adenocarcinoma (AdC), 225+/-145 in large cell (LCC), 264+/-52 in small cell (SCC), 279+/-173 in combined cancer. The differences between the EC counts in the different histological types of lung cancers were statistically significant in the following pairs: SqCC vs SCC (p=0.0233) and AdC vs SCC (p=0.0409). The correlation between EC count in the "hot spot" and the grade of tumor differentiation was statistically significant for G1 vs G4 (p=0.0007) and G1 vs G2 (p=0.0411). Our results suggest that higher numbers of EC/mm2 may confirm rapid development of angioneogenesis. These relations should be examined in larger series of cases.

Adenocarcinoma↗

PubMed2001

[Allergic broncho-pulmonary tuberculosis--a case without bronchial asthma].

Aspergillus fumigatus can cause a number of lung diseases. One of them is allergic bronchopulmonary aspergillosis (ABPA) characterized by pulmonary eozynophilia, asthma, an allergic type of immune response in the bronchi and proximal bronchiectases. ABPA was recognised in 28-years old man (round shadows in the lung, obturated bronchus with mucoid impaction, positive skin tests with aspergillin and presence of precipitins to Aspergillus fumigatus, elevated serum IgE level). Patient was treated for 6 months with corticosteroids. After 2 years of regression there was an exacerbation of ABPA was recognised. The steroid therapy was repeated.

Adult↗

PubMed2001

Proliferating activity, DNA ploidy changes of lung cancer cells before and after chemotherapy.

To assess proliferating activity, DNA ploidy changes of lung cancer cells before and after chemotherapy, we performed a flow cytometry analysis (FC) using fresh bronchoscopy specimens from 38 patients with lung cancer. Among 33 males and 5 females, squamous cell carcinoma (NSLC) was recognized in 12 males, 15 males had small cell lung cancer (SCLC) and 6 males had lung cancer with no histological type (LC) defined. Three women had SCLC, 1 had NSCLC and one had LC. Control consisted of 11 COPD patients. The percentage of diploid cells was significantly lower and cells with hypoploid cells were significantly higher in study group before treatment. High percentage of G2M cells characterised NSCLC and LC groups, whether high number of S phase cells characterised NSCLC and SCLC group before treatment. The treatment lowered percentage of G2M cells in NSCLC and CA group, whether diploid, hypoploid and S phase cells did not differ than those from before treatment.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2001

The clinical significance of serum soluble interleukin 2 receptor (sIL-2R) concentration in lung cancer.

The activated mononuclear cells can release a soluble form of interleukin 2 receptor (sIL-2R) in the blood. Serum sIL-2R level is a sensitive and quantitative marker of circulating peripheral blood mononuclear cell activation. This molecule acts as an antagonist of IL-2-mediated responses. The present study was carried out to analyze the circulating levels of sIL-2R in lung cancer in relation to the histological type of the tumour, clinical stage, response to therapy, time survival for patients. The study included 62 patients (30 SCLC, 32 NSCLC) and 10 healthy subjects as controls. SIL-2R serum levels were measured with a sandwich enzyme immunoassay using commercial kits (ENDOGEN). The mean serum values of sIL-2R were significantly higher in cancer patients than in controls (p=0.01). There was no significant difference in relation to tumour histological type. Within the NSCLC chemotherapy group, sIL-2R mean levels observed at the end of chemotherapy were higher in the progressing patients than in the responding patients. The metastatic patients had higher levels of sIL-2R than those with locally limited disease. In the case of SCLC classified to extensive disease mean levels of sIL-2R were higher than SCLC classified to limited disease. The mean serum values of sIL-2R were significantly higher in weight loss patients than no weight ones (p=0.03). Within NSCLC group there was a correlation between sIL-2R mean levels and the age of patients (p=0.04). In SCLC group there was a correlation between levels of sIL-2R and time survival for patients (p=0.009).

Aged↗

PubMed2001

Detection of p16 abnormalities in early-stage non-small cell lung cancer.

We investigated the clinical significance of p16 abnormalities (mutations by sequencing and hypermethylation by methylation-specific PCR) in 52 radically resected stage I-II non-small cell lung cancers (NSCLCs). P16 abnormalities were detected in 20 (38%) patents (point mutations in 4 (8%) and promoter hypermethylation in 16 (31%) cases. No correlation was found between p16 abnormalities and various clinicopathologic factors, including sex, histological type of tumor and TNM (I vs. II) stage. The multivariate analysis of survival was performed using the Cox proportional hazard model. When the types of 16 inactivation were analyzed, p16 hypermethylation rather than point mutation was associated with poor Prognosis. The presented results prompt the conclusion that hypermethylation of p16 is the major mechanism for p16 gene inactivation in early stage NSCLC and could be a useful molecular marker for the prognosis.

Carcinoma, Non-Small-Cell Lung↗

PubMed2001

P16INK4a point mutations and promoter hypermetylation in bronchial preneoplastic lesions.

The aim of this study was to determine p16INK4a point mutations and promoter hypermethylation in tumour cells and bronchial preneoplastic lesions in 32 surgically resected lungs due to primary squamous cell carcinoma. P16 point mutations were detected in 1 (3%) and promoter hypermethylation in 12 (31%) of 32 squamous cell carcinomas. The status of p16 was further characterized in 38 premalignant lesions including squamous metaplasias without dysplasia, squamous metaplasias with mild, moderate and severe dysplasias and 4 carcinomas in situ. No p16 point mutations have been found in premalignant or CIS lesions. Methylation of p16 was detected in 1 of 8 (12.5%) cases of squamous metaplasias without dysplasia, in 1 of 10 (10%) cases of squamous metaplasias with mild dysplasia, in 1 of 9 (11%) cases of squamous metaplasia with moderate dysplasia and in 2 of 7 (28.5%) cases of severe dysplasias, as well as in 1 of 4 (25%) carcinomas in situ. This investigation indicates that P16INK4a supressor gene point mutations are rather late event and inactivation of this gene by promoter hypermethylation is early and likely critical in bronchial cancerogenesis.

Bronchial Neoplasms↗

PubMed2001

K-ras codon 12 mutations detected with enriched PCR method in operable non-small cell lung cancer.

Activated point mutations of the K-ras gene are one of the most common genetic alterations found in human malignancies, including lung cancer, and are largely limited to adenocarcinomas. Using a highly sensitive assay for codon 12 K-ras mutation detection, called enriched PCR, we investigated 130 radically resected stage I-IIIa non-small cell lung cancer (NSCLC). There were statistically less positive results for squamous cell carcinoma (1.3%) than for adenocarcinoma (42.4%) and large cell carcinoma (27.8%). No statistically significant association between results of K-ras mutations and TNM stage of disease was found. In stage I of adenocarcinoma patients the incidence of K-ras mutations was similar to that in stage II or IIIa (40%, 42.9% and 42.9%, respectively). The results of our study showed that K-ras mutations might play an important role in pathogenesis of pulmonary adenocarcinoma due to its high prevalence in the operable tumours.

Adult↗