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Biomedical subjects

L Petruzelka

Publications and source records attributed to L Petruzelka.

At least 19 recordsLinked to original sources
PubMed2006

Vinorelbine plus trastuzumab combination as first-line therapy for HER 2-positive metastatic breast cancer patients: an international phase II trial.

The aim of this international phase II trial was to determine the efficacy and safety profile of weekly vinorelbine plus trastuzumab as first-line chemotherapy for women with HER 2-overexpressing metastatic breast cancer. Sixty-nine patients with tumours overexpressing HER 2 received vinorelbine: 30 mg m-2 week-1 and trastuzumab: 4 mg kg-1 on day 1 as a loading dose followed by 2 mg kg-1 week-1 starting on day 8. Sixty-two patients were evaluable for response and 69 patients were evaluable for toxicity. The overall response rate was 62.9%. The median time to response was 8.4 weeks, the median duration of response was 17.5 months, the median progression-free survival was 9.9 months (95% CI, 5.6-12.1) and the one-year progression-free survival was 39.1%. The median survival for all patients was 23.7 months (95% CI, 18.4-32.6). This regimen was safe: grade 3-4 neutropenia were observed over 17.7% of courses in 83.8% of patients, with only two episodes of febrile neutropenia (0.1%) in two patients (2.9%). Only one patient discontinued treatment due to grade 3 symptomatic cardiac dysfunction that resolved with therapy. Vinorelbine plus trastuzumab is one of the most active treatment regimens for patients with HER 2-positive metastatic breast cancer and demonstrates a very favourable safety profile allowing prolonged treatment with long-term survival. This study has been presented in part at the following conferences: The San Antonio Breast Cancer Symposium, San Antonio, TX, USA, 2003; The American Society of Clinical Oncology, Orlando, FL, USA, 2005.

Adult↗
PubMed2006

[Guideline for gynecological malignant tumors I. Standard--a complex therapy of ovarian epithelial malignant tumors].

OBJECTIVE: Elaboration of guideline for primary and secondary treatment of ovarian cancer. DESIGN: Review, consensus between proposers and opponents. METHOD: A retrospective review of published data, analysis of Czech statistics and consensus between proposers and opponents. RESULTS: We underline importance of comprehensive approach in therapy of ovarian cancer. We notice importance of expert ultrasound and CA 125 level in diagnostic algorithm. Extension of surgery depends on result of frozen section. All departments which want to perform surgery for ovarian resistance must have possibility to do peroperative histopathology. We can perform conservative fertility sparing surgery in patient with wishing of pregnancy and low stage disease. The effort of maximal debulking with radical surgery including lymphadenectomy is the standard procedure. When we diagnose ovarian cancer during laparoscopy, we have to convert on laparotomy procedure. We define the role of the neoadjuvant chemotherapy followed by surgery after 3-4 cycles of chemotherapy. We define adequate surgery treatment, indication for adjuvant chemotherapy and indication for second line therapy. CONCLUSION: Guideline for the treatment of epithelial ovarian cancer should become directions for clinicians and others, who participate in the process of treatment of the ovarian cancer. The guidelines include all parts of the process from diagnosis, treatment to follow up. All topics of the guidelines arose from a voting of the proposers and opponents.

Carcinoma↗
PubMed2005

Comparative analysis of thymidylate synthase, thymidine phosphorylase and dihydropyrimidine dehydrogenase expression in colorectal cancer and surrounding normal tissue.

Thymidylate synthase [TS], thymidine phosphorylase [TP] and dihydropyrimidine dehydrogenase [DPD] play the essential role in the activation and catabolism of the fluoropyrimidines used in cancer therapy. Its expression may influence the antitumor activity or toxicity of these drugs. We studied the expression levels of selected enzymes in colorectal tumors and adjacent normal mucosa. The analysis of TS, TP and DPD gene expression was performed using quantitative Real time PCR technique (Roche) in 15 (TS), 64 (TP) and 12 (DPD) of 64 colorectal cancer patients. The mean gene expression of TS, TP and DPD was found to be 3.29; 3.79 and 8.24 in tumors and 1.88; 3.80 and 19.69 in normal mucosa. The corresponding median gene expression was 1.87; 2.32 and 4.50 for tumors and 2.14; 2.63 and 11.64 for normal tissue. We did not find any significant differences in TS, TP and DPD gene expression between colorectal tumor and surrounding mucosa.

Colorectal Neoplasms↗
PubMed2005

[Changes in leptin, leptin receptor and fatty acids levels during chemoradiotherapy for oesophageal cancer].

BACKGROUND: Oesophageal cancer patients with substantial weight loss have worse prognosis. Weight loss is often refractory to the nutritional support. Causes of the weight loss are multiple: oesophageal stricture, frequent alcohol abuse, cancer related cachexia. It may be a consequence of metabolic changes mediated by cytokines, hormones and tumour derived products. Leptin, a protein produced by adipocytes, is an important signalling molecule in energy regulation, metabolism of fatty acids and it can also augment tumour growth of various cancer cell lines. Enhanced intake of poly-unsaturated fatty acids may play an important role in the reversal of cancer related weight loss. METHODS AND RESULTS: In this study we examined the nutritional status (pre-treatment weight-loss, actual weight, body mass index), serum levels of leptin, soluble leptin receptor, TNF-alpha, IGF-1 and plasma phosphatidyl-cholin fatty acids before the beginning of treatment, after the onset of treatment and shortly before its completion. In the group of 38 pts (33 men, 5 women), mean age 58 years, statistically significant mean pre-treatment weight-loss 8 kg and significant mean weight loss 2 kg after chemoradiotherapy was observed. Concomitant chemoradiation led to transient elevation of serum leptin level despite the weight loss during chemoradiotherapy. Significant changes in the distribution of fatty acids in plasmatic phosphatidyl-cholin were observed. CONCLUSIONS: Our results show the possibility for direct influence of chemoradiotherapy on body weight regulation in advanced oesophageal cancer patients.

Adult↗
PubMed2004

Dietary habits and lung cancer risk among non-smoking women.

A case-control study was conducted to investigate the relationship between diet and the risk of lung cancer among women non-smokers and to compare with women smokers in the same population. Data collected by personal interviews from 435 microscopically confirmed cases and 1710 controls were analysed using unconditional logistic regression. In addition to results for all study subjects, associations between diet and lung cancer risk were compared between two highly contrasting groups: smokers (odds ratio (OR) 7.03) and non-smokers (OR 1.00). A protective effect of frequent (daily or several times per week) black tea drinking appeared among non-smoking women (OR 0.65, 95% confidence interval (CI) 0.43-0.99). Among smoking women, protective effects were observed for frequent intake of milk/dairy products (OR 0.56, 95% CI 0.32-0.96), coffee (OR 0.47, 95% CI 0.25-0.88), and wine consumption (daily or weekly OR 0.60, 95% CI 0.37-0.98; monthly OR 0.60, 95% CI 0.39-0.94). Inverse associations with the risk appeared for physical exercise for smokers only, and for the body mass index both among non-smoking and smoking women. Some items of diet may contribute to variation in risk among women in the Czech Republic; their importance seems to vary in relation to their status in smoking, the dominant factor in the aetiology of lung cancer.

Adult↗
PubMed2004

[Neutron capture therapy in the treatment of glioblastoma multiforme. Initial experience in the Czech Republic].

BACKGROUND: Glioblastoma multiforme is the most frequent primary brain tumor in adults. Despite advances in surgery, radiotherapy and chemotherapy, its treatment remains unsatisfactory with very limited overall survival. In the year 2001, in cooperation with Department of Neurosurgery, Nemocnice Na Homolce and Nuclear Research Institute in Rez, we have started to treat glioblastoma patients with boron neutron capture therapy (BNCT). METHODS AND RESULTS: Cells of malignant brain tumors, especially that of glioblastomas, are able to accumulate boron compounds. If BNCT should be successful, it is necessary to reach selective accumulation of sufficient amount of 10B in the tumor and low accumulation in the normal brain tissue. After BSH administration, radiation with low energy thermal neutrons is delivered. It results in nuclear capture and fission reactions with subsequent selective damage of tumor cells. At the time of analysis 9 patients have been enrolled. Therapy was completed in 5 patients. Treatment has been very well tolerated. We observed minimal acute toxicity associated with radiation and no laboratory abnormalities after administrations of BSH. Unfortunately treatment results were quite unsatisfactory. The median time to progression and overall survival were shorter then expected with conventional treatment. CONCLUSIONS: BNCT is very well tolerated with only a modest toxicity. In contrast to standard radiation, BNCT patients receive only one dose of radiation. Nevertheless, in this small pilot study first results were inferior when compared either to outcomes of conventional therapy or to results reported from other BNCT groups. It might be explained that lower dose of radiation had been used. Further study will show whether the higher dose radiation can improve treatment results.

Adult↗
PubMed2004

[Prophylactic adnexectomy].

OBJECTIVE: Analysis of the issue of prophylactic bilateral salpingo-oophorectomy (BSO): a) during pelvic surgery for benign diagnosis; b) in women with hereditary risk of ovarian cancer. DESIGN: Review article. SETTING: Department of Obstetric and Gynecology, Charles University. METHODS: Critical review of published data. CONCLUSION: During pelvic surgery for benign diagnosis a prophylactic BSO is indicated of the age over 45, in younger women an individual approach is required, considering many aspects, including history of ovarian and breast cancer. Another indication for BSO is an increased risk of familial ovarian cancer. The surgery significantly diminished the risk of epithelial cancer of ovary, fallopian tube, and simultaneously the risk of breast cancer. There is a continuing increased risk of peritoneal cancer following the surgery. Bilateral oophorectomy together with bilateral salpingectomy is recommended. The age limit for surgery is about 35 years after careful consideration of individual risk, reproductive plans, type of mutation and age at malignant disease manifestation in previous generation. Potential alternative for women who do not accept prophylactic surgery is tubal ligation. Screening of risk group or chemoprevention by oral contraceptives are not equivalent alternatives to prophylactic surgery.

Fallopian Tubes↗
PubMed2004

Lung cancer risk among nonsmoking women in relation to diet and physical activity.

To investigate the relationship between diet, physical activity, and the risk of lung cancer among female nonsmokers, and to compare it with female smokers in the same population, we conducted a case-control study. Data collected by personal interviews from 419 cases and 1593 controls were analyzed using unconditional logistic regression. As expected, among 130 nonsmoking cases, adenocarcinoma was the predominant cell type (49.2%), followed by squamous cell (20.2%) and small cell cancers (10.5%). The corresponding figures for 289 smoking cases were 29.3%, 27.5%, and 28.2%, respectively. Excess lung cancer risk was associated with consumption of red meat among nonsmokers (OR=2.20, 95%CI 1.07--4.51). Protective effects were observed for vegetables (OR=0.61, 95%CI 0.39--0.96), apples (OR=0.67, 95%CI 0.48--0.95), milk/dairy products (OR=0.54, 95%CI 0.32--0.93), coffee (OR=0.56, 95%CI 0.34--0.91), and wine (OR=0.69, 95%CI 0.49--0.98) among smokers only, and for black tea (OR=0.67, 95%CI 0.46--0.99) among nonsmokers only. An inverse association with risk emerged for physical exercise (or sport, walking), among smokers only. Some items of diet and physical activity appear to be important factors contributing to variation in lung cancer risk among women in the Czech Republic, however, their effects in nonsmokers may differ from those in smokers.

Adult↗
PubMed2004

Mammaglobin A, a novel marker of minimal residual disease in early stages breast cancer.

Mammaglobin A, in contrast to other factors, is a breast specific member of uteroglobin gene family. Expression is restricted to normal and neoplastic breast epithelium. A highly homologous mammaglobin B is not specific to breast tissue. In this pilot feasibility study we examined expression of both markers for minimal residual disease in the bone marrow of patients with breast cancer. We obtained bone marrow aspirates of 34 patients with stage I (41%), II (56%) and III (3%) breast cancer who underwent either immediate complete resection of the tumor or neoadjuvant therapy with subsequent curative surgery. mRNA was isolated using QIAamp RNA blood mini kit (Qiagen). Subsequently two-step nested RT-PCR for the expression of mammaglobin A and mammaglobin B was performed. Mammaglobin A was detected in samples from 4 (12%) out of 34 patients. None of the specimens was positive for mammaglobin B. With a median follow-up of 21 month we observed only 2 recurrences, one in patient with mammaglobin A positive bone marrow.RT-PCR assay for mammaglobin A may be a useful tool for detection of occult breast cancer cells in the bone marrow. Clinical and prognostic relevance of minimal residual disease should be further investigated.

Adult↗
PubMed2003

Lessons from the ("Iressa" Expanded Access Programme: gefitinib in special non-small-cell lung cancer patient populations.

Some subgroups of patients with advanced/metastatic non-small-cell lung cancer (NSCLC) are frequently considered ineligible for the aggressive, platinum-based combination chemotherapy that is the recommended treatment. Elderly patients may have a poorer tolerance of chemotherapy due to impaired organ function and frequent comorbidities; patients with poor performance status (PS; > or =2 due to NSCLC and/or coexisting illnesses) are often considered unfit for chemotherapy; other patients may be unable or unwilling to endure the toxicity or inconvenience of chemotherapy. These patient groups may benefit from novel, relatively nontoxic treatment modalities. Gefitinib ("Iressa", ZD1839) 250 mg day(-1) is well tolerated and has proven antitumour and symptom improvement activity in patients with previously treated NSCLC. Phase II trials (IDEAL 1 and 2) of gefitinib in advanced/metastatic NSCLC included 70 out of 425 (16.5%) patients with PS > or =2, and their response rate, clinical benefit rate and rates of adverse events were similar to those of the overall trial population. In addition, many patients with advanced/metastatic NSCLC with poor PS or advanced age have received gefitinib 250 mg day(-1) in an Expanded Access Programme (EAP). Observations from the EAP support those of IDEAL 1 and 2, and indicate that gefitinib 250 mg day(-1) warrants further investigation in these patient groups.

Adult↗
PubMed2003

Randomized, double-blind, multicenter trial comparing two doses of arzoxifene (LY353381) in hormone-sensitive advanced or metastatic breast cancer patients.

BACKGROUND: This randomized, double-blind, phase II study assessed two doses of the selective estrogen receptor modulator arzoxifene in women with advanced breast cancer. The primary end point was to choose the best of two doses of arzoxifene based on the response rate or the clinical benefit rate (CBR). Pharmacokinetics and toxicities were also assessed. PATIENTS AND METHODS: Ninety-two patients with advanced breast cancer received arzoxifene 20 or 50 mg/day. Tumor response was assessed using World Health Organization criteria. Toxicities were graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) system. Pharmacokinetic data were analyzed using the NONMEM software program (GloboMax, Hanover, MD, USA). RESULTS: Response rates in the 20 mg arm were numerically higher than the 50-mg arm according to the investigator (40.5% versus 36.4%) and the independent review panel (42.9% versus 27.3%). CBR was higher in the 20 mg arm according to the investigator (64.3% versus 61.4%) and the independent review panel (59.5% versus 47.7%). Arzoxifene was well tolerated. There were no study drug-related deaths. Mean observed steady-state plasma concentrations of arzoxifene were 3.62 and 7.48 ng/ml for the 20 and 50 mg doses, respectively. CONCLUSIONS: There were no significant differences in efficacy or safety between 20 and 50 mg of arzoxifene. Accordingly, arzoxifene 20 mg/day was selected for further study in patients with breast cancer.

Aged↗
PubMed2002

[Minimal residual disease in breast carcinoma].

The incidence of breast cancer continuously increases in developed countries. The introduction of screening methods such as mammography or ultrasound lead to higher proportion of early diagnosed tumors. However, even in early stage tumors occult neoplastic cells can spread to the organism. Such tumor cells are very likely precursors of distant metastases. Using several monoclonal antibodies against epithelial mucins or cytokeratins on the cell surface could be detected one tumor cell among 10(5) or 10(6) of normal bone marrow cells. These cells are not detectable by routine histopathologic exam. More sensitive but also more costly and technically demanding are PCR assays. The sensitivity might reach almost 1:10(7). Prospective clinical trials using immunocytochemistry have shown that the presence of stained cells in bone marrow is clearly associated with shorter disease free survival and overall survival. In the near future we may use the bone marrow examination for the presence of occult tumor cells in order to improve current staging system or as a surrogate marker in the decision-making in regard to adjuvant systemic therapy or in the assessment of efficacy of adjuvant treatment. The review summarizes contemporary knowledge assembled in preclinical and clinical studies.

Bone Marrow↗
PubMed2002

Large expansion of morphologically heterogeneous mammary epithelial cells, including the luminal phenotype, from human breast tumours.

Regular expansion of heterogeneous populations of epithelial cells, including the luminal phenotype, was achieved from small biopsies of human breast tumours and cutaneous metastases by optimized feeder layer technique based on irradiated NIH 3T3 cells. Forty-one out of 47 primary tumour specimens and all three cutaneous metastases grew successfully for two to 10 passages in vitro. The main phenotypes of cultured cells and their changes in subcultures were characterized using immunocytochemistry and phase contrast microscopy (in few cases also time-lapse recording). In the majority of cultured cell populations a fraction of cells positive for keratin 19 (K19+), typical for the luminal phenotype, was detected. This is the cell type from which breast carcinoma is supposed to arise. While in cultures derived from benign lesions only basic phenotypes of luminal and myoepithelial cells were found, in cultures derived from malignant tumours unusual phenotypes of epithelial cells, in their majority K19+, were detected. The growth properties of cells from six benign and seven malignant samples were analyzed in detail. In the analyzed cell populations the culture lifetime - related to the number of colony-forming cells varied for cells from malignant tumours between 21 and 51 and from benign tumours between 22 and 40 cell generations. The total number of passages achieved was three to seven for malignant or four to nine for benign cultures. In spite of negative results of tumourigenicity testing in immunologically compromised Nu/nu mice the potential to culture apparently neoplastic cells was indicated by positive immunostaining for the p53 oncoprotein (seven of 23 tested malignant cases), the src oncoprotein (five of eight), and overexpression of the c-erbB-2 protein (five of 26). This was further confirmed by successful cultivation of malignant cells from cutaneous metastases. Two of the three metastasis-derived cultures were nearly homogeneously positive for K19 while the third was almost negative. The results proved the optimized feeder layer technique to be useful for regular yielding of large amounts of epithelial cells from small tumour biopsies and for supporting the majority of cell phenotypes present in the original tumour. Therefore, it appeared to be a promising tool for further analysis of interactions between luminal and myoepithelial cells in the development of human breast carcinoma and for the study of individual tumours.

3T3 Cells↗
PubMed2001

[Meningeal carcinomatosis as the first manifestation of gastric adenocarcinoma].

Gastric adenocarcinoma is rarely observed in patients under the age of 40. Meningeal carcinomatosis as a first manifestation of disease is absolutely unique. If meningeal involvement occurs it is usually secondary event in previously diagnosed tumor. The prognosis is very unfavorable associated with short term survival. In the treatment of this disease there night be used either chemotherapy administered via lumbar injection or radiotherapy or combination of both. This case study is one of very few cases reported in literature when meningeal carcinomatosis was a first sign of advanced gastric adenocarcinoma. 39 years old woman was admitted to our hospital with severe headache, diplopia and vomiting. Meningeal carcinomatosis with gastric primary was diagnosed. She was treated with combination of cytosine arabinosid (Cytosar), methotrexate (Methotrexat), hydrocortisone (Hydrocortisone) administered via intrathecal lumbar injection and whole brain radiation. As a main complication she experienced disseminated intravascular coagulopathy. The improvement of patient's condition following the initial treatment had a very limited duration and the patient died of bilateral pneumonia and cerebral edema 44th day after the admission.

Adenocarcinoma↗
PubMed2001

Prognostic significance of c-erbB-2 gene expression in pancreatic cancer patients.

Molecular methods tend to belong to the standard armamentarium of modern pathology. In some instances, these methods are able to identify nosological entities with better accuracy than conventional technique. These methods give useful complementary information to choose appropriate therapeutic strategy. C-erbB-2 overexpression in pancreatic cancer vary widely between 17 to 82%. C-erbB-2 gene is perspective target of anticancer therapies. 57 histologically confirmed tumors (51 pancreatic adenocarcinoma, 5 pancreatic neuroendocrine tumors and 1 carcinoma of Vater's ampullae) were analyzed for the presence of c-erbB-2 expression by immunohistochemistry. Correlation with time from initial symptoms until diagnosis, tumor size and TNM stage at diagnosis, tumor grade, type of operation and overall survival were investigated. C-erbB-2 overexpression was detected in 19.6% samples of pancreatic adenocarcinoma and in one case of Vater's ampullae carcinoma. C-erbB-2 overexpression was found in two of four insulinomas. Univariate statistical correlation stage between c-erbB-2 overexpression and time from initial symptoms until diagnosis, tumor size and TNM at diagnosis, tumor grade, type of operation and overall survival did not reach statistical significans in any parameter studied. C-erbB-2 oncogene was not found to be prognostic factor in pancreatic cancer. Its value to predict therapeutical response remains to be determined in prospective clinical trials.

Adenocarcinoma↗
PubMed2001

Diet and the risk of lung cancer among women. A hospital-based case-control study.

Variation in diet has been suspected to be one of cofactors related to geographic variation in lung cancer risk, namely for women, or other population groups with a low exposure to cigarette smoking. The study has been designed to obtain more insight into possible associations between diet and lung cancer risk among women in a country with a Central European socioeconomic background. In a hospital-based case-control study personal interviews of 282 female lung cancer cases and 1120 female controls were done using a structured standard questionnaire. Cigarette smoking was the most important factor associated with excess risk for lung cancer among women. Significantly increased risk was found both among current smokers (OR = 9.22), and ex-smokers (OR = 7.11). Positive dose-response gradients (p < 0.001) were observed between lung cancer risk and the daily number of cigarettes, duration of smoking, and number of pack-years. For squamous-, small- and large-cell cancers combined, significant associations of lung cancer risk with the consumption of red meat and poultry (OR = 2.33, and OR = 8.67, respectively), and an inverse association with the consumption of vegetables (OR = 0.55) were found. No such variations in risk were observed for adenocarcinoma, including the bronchioalveolar cancer type. For all lung cancer types combined, coffee drinking showed a significant inverse association with lung cancer risk risk (OR = 0.66). While smoking is the major risk for lung cancer, diet may have a contributory role. Variations in the intake of some components of diet, namely red meat, poultry, vegetables, and coffee may contribute to understanding variations in the risk of lung cancer among Czech women.

Adenocarcinoma↗