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J Zaloudík

Publications and source records attributed to J Zaloudík.

At least 19 recordsLinked to original sources
PubMed2006

Comparative transcriptome maps: a new approach to the diagnosis of colorectal carcinoma patients using cDNA microarrays.

The progression of colorectal cancer involves accumulation of various genetic and epigenetic events that dramatically change gene expression. The aim of this study was to investigate a possible new approach to the diagnosis of colorectal carcinoma patients, based on their gene expression profiles. Human 19K cDNA microarrays were used to analyze the gene expression profiles of 18 colorectal carcinoma patients. Transcriptome maps (TMs) were analyzed to detect chromosomal regions that could serve as potential diagnostic markers for colon cancer. A comparison of TMs showed chromosome regions with conserved changes of gene expression typical of colorectal cancer in general, and also patient-specific variable regions. We identified 195 genes with significantly altered expression in colon cancer. Functional analysis of the regulated genes distinguished three main categories: biological processes, cellular components, and molecular functions. We found that different patients had chromosome regions characterized by very similar changes of gene expression, probably linked to the most fundamental events in carcinogenesis. On the other hand, variable chromosome regions can be patient-specific. The variable regions may provide further information on the individual pathogenesis and prognosis of the patient. Comparison of TMs is proposed as a tool to facilitate diagnosis and treatment planning for individual patients.

Biomarkers, Tumor↗
PubMed2006

[Preoperative radiotherapy in hypoxia in the complex treatment of the rectal carcinoma--complications].

INTRODUCTION: Preoperative radiotherapy is considered to be the standard approach in the treatment of the rectal carcinoma. Acute hypoxia decreases partial pressure of oxygen in healthy tissues immediately, but in the tumor after 30 min of duration. There is a higher radioresistance of healthy tissues in this interval because of lower oxygenation compared with normooxic status and the tumor is still relatively good oxygenated. This fact theoretically enables higher doses of radiotherapy and lower adverse effects. The aim of this study was to evaluate short and long term complications after preoperative radiotherapy of rectal carcinoma in hypoxia. PATIENTS AND METHODS: Between April 1991 and October 2000, 127 patients with the rectal carcinoma were treated preoperatively with locoregional accelerated hypofractionated radiotherapy in hypoxic conditions in Masaryk Memorial Cancer Institute. The dosis was up to 8 x 4 Gy. Acute hypoxia was induced during irradiation by ventilation of a hypoxic gas mixture containing 7.8-8.0% oxygen for totally 7-8 min. Operation was performed till 24 hours. RESULTS: There was no complication concerning with breathing of hypoxic gas mixture. A 30 day postoperative mortality was 0.8%. A 30 day postoperative morbidity was 31.7%. An anastomotic leakage occurred in 6.5%. Chronic gastrointestinal disorders occurred in 16.1% patients. CONCLUSION: Preoperative irradiation in hypoxic conditions is safe and efficient procedure. It permits safe administration of doses higher than those tolerated by normooxic conditions. Type and frequency of complications are comparable with other preoperative regimens.

Adult↗
PubMed2004

Perioperative fractionated high-dose rate brachytherapy in the treatment of soft tissue sarcomas.

The purpose of the study was to investigate the viability of perioperative fractionated high dose rate brachytherapy (HDR BT) for primary and reccurent soft tissue sarcomas (STS). From February 1998 through June 2002, 21 adult patients, 11 females and 10 males with either low grade or high grade soft tissue sarcomas were treated by perioperative HDR BT. Surgical margin was negative in 10 cases, close in 4 and positive in 4 in cases. In 3 cases it was not described. BT was used as a part of primary treatment in 10 cases and for the treatment of reccurent tumor in 11 cases. The localisation of the tumor was the extremity in 16 patients and the trunk in 5 patients. Ten patients were treated with HDR BT alone (total mean dose 40 Gy) and 11 were treated with combination of external beam radiotherapy (EBRT) (40-50 Gy) and brachytherapy (total mean dose 24 Gy). Hyperfractionation 2.4-3 Gy twice daily at 10 mm from the source was used for BT. Follow-up periods were between 7--48 months (median: 20 months). Local control in patients treated pro primary STS was 100%.The pulmonal metastases were a cause of death in one case, one patient was alive with dissemination and one patient was disease free after salvage surgery and chemotherapy for lung metastases. Local control was achieved only in 3 of 11 patients treated for reccurent tumor (27%). Six patients were disease free after salvage surgery, 2 patients died of disease progression, one patient died of toxicity of chemotherapy without evidence of disease and 2 patients are alive with distant metastases. Local control was achieved in 5 of 11 (45%) patients with positive, close or not stated surgical margin and in 5 of 10 (50%) patients with negative margin. Local control was 100% in patients treated by EBRT + BT, but only 20% in patients treated by BT alone. No infection or delayed wound healing has occurred after BT. Soft tissue necrosis was seen in 4 cases, subcutanous fistula in one case and peripheral nerve palsy in one case. Despite small number of patients and short follow up our study suggest that perioperative HDR BT is easy and promissing when used as a part of primary treatment for STS. The treatment results for recurrence are poor and in a lot of cases radical surgical approach should have been considered for the salvage.

Adult↗
PubMed2004

Telomerase as a diagnostic and predictive marker in colorectal carcinoma.

In a search for molecular markers providing both informative diagnostics of malignant disease, and rational stratification of a therapeutic strategy to achieve optimal response in a given patient, we examined the possibility of using telomerase for this purpose in colorectal cancer. Telomerase, a ribonucleoprotein enzyme complex catalysing synthesis of chromosome ends (telomeres), has been known as an almost universal tumor marker but its predictive value has been found in only a limited number of malignant tumor types. Telomerase activity and expression of its catalytic subunit hTERT was determined in 82 surgical specimens from 41 patients (a sample of tumor tissue and of adjacent morphologically normal tissue was obtained from each patient). Telomerase activity was present in tumor samples from 34 (83%) patients, reaching an average value of 47.6 telomerase units (T.U.), while adjacent tissue specimens were either negative (in 25 (61%) patients), or slightly positive (in 16 (39%) patients) showing 1.5 T.U. on average. In tumor samples from patients without lymphatic node metastases (pN0), an average of 37.1 T.U was found. In contrast, in tumor samples from patients with lymphatic node involvement (pN1 or pN2) the average activity was significantly higher (60.2 T.U., p<0.05). In patients with distant metastases a tendency towards higher telomerase activity, although lacking statistical significance, could be observed. Among patients that obtained chemotherapy with 5-fluoruracil, those with low telomerase activity showed a tendency to chemosensitivity. Expression of hTERT was detected not only in samples showing telomerase activity, but also in a considerable portion of telomerase-negative samples either from the tumor or the adjacent normal tissue. We demonstrate that some of these apparent discrepancies may be attributed to differential splicing of hTERT mRNA. We conclude that TRAP assay for telomerase activity is more informative than the common testing for hTERT expression. Telomerase activity is useful both as a diagnostic as well as a predictive factor in colorectal cancer.

Alternative Splicing↗
PubMed2004

Breast cancer and neoadjuvant therapy: any predictive marker?

The majority of patients with breast carcinoma receive chemotherapy as a component of multimodality treatment. Over the past decade, it has become increasingly more common to deliver chemotherapy first, but this has raised new questions within all disciplines of cancer management. However, the effect of cytotoxic treatment cannot be predicted on individually specific basis, then identification of tumor characteristics associated with tumor therapeutic response and outcome is then of great clinical interest. We studied 141 patients at Masaryk Memorial Cancer Institute, who received neoadjuvant chemotherapy and/or chemotherapy + radiotherapy (CHT/CHT+RT) between 1994-2002. Tumor samples were taken prior to and after neoadjuvant therapy. We quantified the response to therapy pathologically and determined histological and molecular tumor characteristics (steroid receptors, CEA, Ca 15-3). In addition to therapeutic response as immediate outcome, event free survival (EFS) was examined as more complex primary end-point of the study. Complete remission (CR) has been achieved in 6.5%, partial remission (PR) in 49.6%, stable disease (SD) in 26.2% and progression disease (PD) in 17.7% patients. Patients were divided into two groups according to the result of neoadjuvant therapy--responders (CR+PR+SD, who successfully underwent surgery), and risk group (patients with SD or PD, who could not undergo surgery). Responders to neoadjuvant CHT/CHT+RT regimens reached statistically significant better EFS than non-responders, low tumor size (T2) and stage (II) categories were confirmed as additional predictive factors not only for EFS but for therapeutic response as well. The study primarily examined predictive power of tumor markers as CEA, Ca 15-3, and steroid receptors (ER/PR) and searched for their role in the prospective evaluation of neoadjuvant therapy. We evaluated these factors as potential predictors of EFS, independent in predictive power on therapeutic response to neoadjuvant therapy. Diagnostically valuable cut off points were proposed in ROC analysis for all these markers. Responders to the neoadjuvant therapy with Ca 15-3 <23.0 kU/l, CEA <5.0 mg/l, estrogen receptors (ER) >5.0 fmol/mg or both estrogen /progesterone receptors (ER/PR) positive had statistically significantly better EFS in comparison to patients with Ca 15-3 >23.0 kU/l, CEA >5.0 mg/l, ER <5.0 fmol/mg, or other cases than patients double positive in ER/PR. Marker Ca 15-3 revealed significant predictive power even within the group of non- responders, these patients with Ca 15-3 <23.0 kU/l had better EFS as compared to patients with Ca 15-3 >23.0 kU/l. Tumor size and low stage proved predictive value for immediate response to neoadjuvant therapy. Risk parameters for neoadjuvant therapy were T4, stage III, namely if RT was necessary. Therapeutic response to neoadjuvant therapy was independent on investigated molecular parameters, but there was strong predictive association of Ca 15-3, CEA and ER/PR receptors with event free survival development. Diagnostically valuable cut-off points were proposed and validated for sensitivity and specificity in ROC analysis.

Adult↗
PubMed2003

[Do we comply with the standard classification of staging in colorectal carcinoma after curative resection?].

BACKGROUND: Lymph node status is the most important prognostic and predictive factor in curatively resected colorectal cancer. According to TNM staging system, a minimum number of 12 regional lymph nodes is to be examined for the correct staging. In addition to the status of lymph nodes other important prognostic factors should be reported by the pathologist. METHODS: A retrospective study was performed to analyze how many of regional lymph nodes were examined in colorectal cancer specimens in two hospitals (Czech Republic) during the last few years. Availability of other prognostic factors important for the management of the disease after surgery was always investigated. RESULTS: In the hospital "A", the examination of lymph nodes were not sufficient in 43.8% of 121 cases analyzed, in the hospital "B", the number of examined lymph nodes was less than a minimum of 12 in all 162 cases. There were often no data available regarding to a histological examination of resection margins, grading and angioinvasion. CONCLUSION: Reporting of the standard and most important prognostic factors in colorectal cancer was not sufficient in two selected hospitals and it may not be much better in others. It might have a deteriorating influence on the outcomes despite of successfully performed primary surgery. Search for the new prognostic and predictive factors, that would help us to stratify the patients for the optimal tailored therapy is surely needed, but the standard staging parameters, as are the lymph node involvement, resection margins, grading and angioinvasion, must not be forgotten as occurred to be in many cases of our study.

Biopsy↗
PubMed2003

[Principles of post-resection brachytherapy of solid tumors using high dose rate (HDR) afterloading].

Postresection interstitial brachytherapy is one of the modern methods of radiotherapy the aim of which is to administer a larger radiation dose without greater irradiation of the surrounding sound tissues. The administration of higher radiation doses leads in some solid tumours to better local control of the disease and makes it thus possible to use the organ and its function after preserving surgical operations. Post-resection interstitial brachytherapy belongs in the wider concept to intraoperative radiotherapy the advantage of which is direct control of the irradiated area during surgery. The method of introduction of the radiation source into the applicators in the tumour during surgery (afterloading technique) makes its possible to start radiotherapy after obtaining the definite histological result. Post-resection brachytherapy reduces markedly the total time of irradiation treatment.

Brachytherapy↗
PubMed2003

[Sentinel node biopsy in colorectal carcinoma--pilot study].

BACKGROUND: Sentinel lymph node biopsy is a widely accepted method for staging melanoma and breast cancer in indicated cases. However, the use of the method in colorectal cancer is under clinical investigation. The aim of the pilot study was to introduce the technique into the surgical practice in colon carcinoma, to determine the feasibility and potential problems and to evaluate the first experience. METHODS: Twenty patients with colon cancer underwent lymphatic mapping and sentinel node biopsy using blue dye, fluorescein or lymphoscintigraphy followed by standard surgical resection. The acquired sentinel nodes were investigated with both standard hematoxylin-eosin staining and immunohistochemical staining for cytokeratin. RESULTS: Lymphatic mapping adequately identified at least one sentinel node (SN) intraoperatively or by a modified ex vivo technique in 20 patients (100%). The average number of SN was 1.5 (range 1-3), non-SN 13.6 (range 1-38) per patient. SN correctly predicted the regional lymphatic basin status in 14 cases (70%). The false negative rate was 40%. No patient has been upstaged on the basis of immunohistochemical staining. CONCLUSIONS: Lymphatic mapping and sentinel node biopsy in colon cancer is feasible and safe method with a high SN identification rate. The role and significance of sentinel node biopsy in colon cancer is not as clear as its role in other tumors and remains controversial. Further large prospective studies with standardized techniques are needed to evaluate the potential benefit of this new method.

Adult↗
PubMed2002

Malignant melanoma associates with Th1/Th2 imbalance that coincides with disease progression and immunotherapy response.

The immunological dysfunction associated with human cancer is well known phenomenon. It comprises number of pathological changes within immune network including imbalance in cytokines of Th1/Th2 origin. The objectives of our study were (i) to evaluate the abnormalities in serum levels of selected cytokines in malignant melanoma patients with regional lymph node metastases as compared to normal values, (ii) to examine the relationship between postoperative cytokine levels and disease progression and (iii) to correlate cytokine profile changes during IFN-alpha therapy with the disease progression and potential therapeutical response. Nine Th1/Th2 related cytokines and sIL-2R were determined in 26 malignant melanoma patients at clinical stage III prior and during adjuvant immunotherapy. Control group consisted of 26 healthy persons. Patients were treated with rIFN-alpha according to EORTC Melanoma group protocol 18952. Cytokines were quantified in patients sera using commercial ELISA kits. Majority of melanoma patients showed significantly lower values of IL-2 and IFN-gamma and pathologically elevated levels of IL-4, IL-6, IL-10 as compared to healthy subjects what indicates disease associated Th1/Th2 imbalance. In addition increased IL-12 and IL-15 values were noted in some patients (54% and 27%, respectively). All patients who manifested early relapse during immunotherapy had significantly lower pretreatment levels of IL-2 and IL-12 than those remaining without progression and probably benefiting from the treatment. Cytokine changes during immunotherapy disclosed that decreases in IL-2 and IL-12 and raises in IL-6 and IL-10 values occurred at least one month prior to relapse. Moreover, the continuous elevation of TNF-alpha and sIL-2R could be observed in patients who remained without progression during 10 months lasting immunotherapy. Our data illustrate that malignant melanoma associates with Th1/Th2 perturbances which are directed towards extended Th2 responses and that measurement of selected cytokines of Th1/Th2 category may be used as an early signal of disease deterioration and for evaluation of immunotherapy response.

Adult↗
PubMed2002

[Tumor biopsy--a trivial matter or a basic procedure?].

The surgeon is frequently faced with the task of bioptic sampling of tissues from patients with tumourous diseases. The importance of such frequently minor procedures is incorrectly underrated. The importance of biopsy is in the foreground in particular at present at a time of individualization of treatment of malignant tumours, based on the development of new diagnostic-therapeutic methods. The bioptic specimen is the fundamental link in the basic decision--benignity or malignity--and also a unique source for assessment of prognostic and predictive factors on the basis of which we select the optimal therapeutic procedure. Contrary to current histopathological examination where the principles of correct collection of tissues specimens are generally known, in recent years the importance of molecular examinations is increasing where the surgeon must respect certain different principles to make the sampling successful. The authors working in a department of surgical oncology along with authors from specialized laboratories formulate rules of correct implementation of biopsies and transport of biological material in conjunction with recent laboratory methods, and based on examples of their own practice, they demonstrate how the initial approach of the surgeon can influence in a decisive way the correct diagnosis and therapeutic procedure in oncological patients.

Biopsy↗
PubMed2001

Seasonal variation in estrogen and progesterone receptor levels in breast cancer--a factor in data interpretation.

It is still widely accepted that evaluation of estrogen and progesterone receptors (ER, PR) in breast cancer tissue is one of the basic predictive indicators of hormonal therapy success. Evaluation of hormonal receptors is usually done once at the time of biopsy or surgery on the breast regardless of the effect of time. In a retrospective evaluation of 1301 medical records of breast cancer patients the authors wanted to identify any time period dependence in quantitative or qualitative hormonal status. Steroid receptors were measured in breast cancer tissues by cytosol-based ligand-binding technique. The results suggest a strong time period dependence in hormonal status. In premenopausal patients simultaneous evaluation of ER/PR revealed an increased frequency of both positive receptors in the autumn months, and a decrease in the spring months. In postmenopausal patients, both positive receptors were found more likely in the summer months and both negative in the late winter months. Our results suggest that one evaluation of hormonal receptor status does not necessarily provide an accurate estimate of the hormonal status in breast cancer patients.

Breast Neoplasms↗
PubMed2001

[In vitro testing for drug resistance and drug sensitivity in clinical oncology].

In vitro methods for testing chemosensitivity and chemoresistance can contribute considerably to more individual chemotherapy of a given patient. Different tests which reflect with a different reliability and specificity the probable ineffectiveness of chemotherapy can be divided into several categories: 1. Indirect tests associated with general biological activity of the tumour. 2. Tests based on the specific relationship to a certain cytostatic. 3. Examination of hormonal receptors. 4. Direct tests based on testing of the sensitivity or resistance of a tumour to different cytostatics in primocultures or stabilized cultures. The submitted review presents information on different methods.

Animals↗
PubMed2001

[Trends in cancer incidence in the Czech Republic].

In general, the cancer incidence becomes stabilized in the Czech Republic during last years. However, the incidence of colorectal and renal cancers remains increasing and dominates also in European comparisons. A program of cancer prevention and early detection needs to be established at least for six so called preventable cancers as breast, lung, colorectal, cervical and prostatic carcinomas and malignant melanoma, which represent together 40 % of all oncological cases. The aim is reduction of cancer mortality as well as improved effectivity of cancer treatment and cost reduction. More efficient utilisation of the National Cancer Registry data for monitoring of the cancer management is suggested with an application of the project SVOD - the software system of visualisation of oncological data.

Czech Republic↗
PubMed2000

Topography of genetic loci in tissue samples: towards new diagnostic tool using interphase FISH and high-resolution image analysis techniques.

Using single and dual colour fluorescence in situ hybridisation (FISH) combined with image analysis techniques the topographic characteristics of genes and centromeres in nuclei of human colon tissue cells were investigated. The distributions of distances from the centre-of-nucleus to genes (centromeres) and from genes to genes (centromeres to centromeres) were studied in normal colon tissue cells found in the neighbourhood of tumour samples, in tumour cell line HT-29 and in promyelocytic HL-60 cell line for comparison. Our results show that the topography of genetic loci determined in 3D-fixed cell tissue corresponds to that obtained for 2D-fixed cells separated from the tissue. The distributions of the centre-of-nucleus to gene (centromere) distances and gene to gene (centromere to centromere) distances and their average values are different for various genetic loci but similar for normal colon tissue cells, HT-29 colon tumour cell line and HL-60 promyelocytic cell line. It suggests that the arrangement of genetic loci in cell nucleus is conserved in different types of human cells. The investigations of trisomic loci in HT-29 cells revealed that the location of the third genetic element is not different from the location of two homologues in diploid cells. We have shown that the topographic parameters used in our experiments for different genetic elements are not tissue or tumour specific. In order to validate high-resolution cytometry for oncology, further investigations should include more precise parameters reflecting the state of chromatin in the neighbourhood of critical oncogenes or tumour suppresser genes.

Cell Nucleus↗