Ovarian cancer is the fifth most common malignancy in the world's female population and with the highest lethality index among gynecological tumors. The prognosis of metastatic disease is usually poor, especially in platinum-resistant cases. There are several options for the treatment of metastatic disease resistant to platinum derivates (e.g. paclitaxel, topotecan and pegylated liposomal doxorubicin), all of which are considered equipotent. Pegylated liposomal doxorubicin (PLD) is a liposomal form of the anthracycline antibiotic doxorubicin. It is characterized by more convenient pharmacokinetics and a different toxicity profile. Cardiotoxicity, the major adverse effect of conventional doxorubicin, is reduced in PLD as well as hematotoxicity, alopecia, nausea and vomiting. Skin toxicity and mucositis, however, emerge as serious issues since they represent dose and schedule-limiting toxicities. The pharmacokinetics of PLD (prolonged biological half-life and preferential distribution into tumor tissue) provide new possibilities to address these toxicity issues. The extracorporeal elimination of circulating liposomes after PLD saturation in the tumor tissue represents a novel and potent strategy to diminish drug toxicity. This article intends to review PLD characteristics and the importance of extracorporeal elimination to enhance treatment tolerance and benefits. and O. Kubeček, M. Bláha, D. Diaz-Garcia, S. Filip
Nádorová tkáňová banka obsahující kryokonzerované vzorky nádorových tkání umožňuje rozvoj nových diagnostických postupů založených na metodách molekulárně-biologických a genetických analýz. Naše studie byla zahájena v červnu 2008. Prezentované výsledky představují období pěti let (follow up). Celkový počet nemocných žen s karcinomem prsu, které byly zařazeny do projektu, byl 233 pacientek, průměrný věk 65,2 roku (věkový rozdíl 27–88 let). V naší studii byly odebrány a kryokonzervovány vzorky od 156 nemocných žen. Cílem naší studie je vytvořit program evidence a hodnocení prediktivních a prognostických faktorů analyzovaných novými molekulárně-biologickými a genetickými metodami. Využívání nových technologických postupů v léčbě nádorových onemocnění jako jsou např. biotechnologie a nanotechnologie, vyžadující hledání „nových“ prediktivních a prognostických faktorů, které budou vhodně doplňovat výběr léčby., The Tumor Tissue Bank containing cryopreserved samples unables development of new diagnostic methods based on molecular biologic and genetic analyses. Our study started in June 2008. In our study were taken and samples from 156 female patients. The results reported here represent the 3-year period of follow up. 316 women with breast carcinoma, mean age 65.2 years (age range 27 to 88 years) were admitted to this project. The aim of our study was to design a program of record-keeping and assessment of predictive and prognostic factors obtained with new molecular biologic and genetic methods. Utilization of new technologies in the treatment of cancer such as biotechnology and nanotechnology demand searching of „new“ predictive and prognostic factors that will suitably supplement the choice of therapy., Alžběta Filipová, Zuzana Mačingová, Pavel Jandík, Pavel Měřička, Martina Řezáčová, Stanislav Filip, and Literatura
High grade gliomas are some of the deadliest human tumours. Conventional treatments such as surgery, radiotherapy and chemotherapy have only a limited effect. Nowadays, resection is the common treatment of choice and although new approaches, such as perioperative magnetic resonance imaging or fluorescent microscopy have been developed, the survival rate of diagnosed patients is still very low. The inefficacy of conventional methods has led to the development of new strategies and the significant progress of nanotechnology in recent years. These platforms can be used either as novel imaging tools or to improve anticancer drug delivery into tumours while minimizing its distribution and toxicity in healthy tissues. Amongst the new nanotechnology platforms used for delivery into the brain tissue are: polymeric nanoparticles, liposomes, dendrimers, nanoshells, carbon nanotubes, superparamagnetic nanoparticles and nucleic acid based nanoparticles (DNA, RNA interference [RNAi] and antisense oligonucleotides [ASO]). These nanoparticles have been applied in the delivery of small molecular weight drugs as well as macromolecules - proteins, peptides and genes. The unique properties of these nanoparticles, such as surface charge, particle size, composition and ability to modify their surface with tissue recognition ligands and antibodies, improve their biodistribution and pharmacokinetics. All of the above mentioned characteristics make of nanoplatforms a very suitable tool for its use in targeted, personalized medicine, where they could possibly carry large doses of therapeutic agents specifically into malignant cells while avoiding healthy cells. This review poses new possibilities in the large field of nanotechnology with special interest in the treatment of high grade brain tumours. and P. Krůpa, S. Řehák, D. Diaz-Garcia, S. Filip
The colorectal cancer ranks high among the malignant tumours in incidence and mortality and irinotecan is standardly used in palliative treatment of metastatic disease in every therapeutic line. Unfortunately, the treatment with irinotecan is often associated with severe toxicities, especially neutropenia and diarrhea. The majority of the toxic manifestation is caused by the insufficient deactivation (glucuronidation) of irinotecan active metabolite SN-38 by UGT1A enzyme. The elevated SN-38 plasma concentration is responsible for the hematological and gastrointestinal toxicity that can become life-threatening. The patients carrying the mutation of the gene encoding UGT1A enzyme lack the ability of bilirubin glucuronidation, and suffer from the inherited un-conjugated hyperbilirubinemia (Gilbert syndrome, Crigler-Najjar type 1 and 2 syndrome). The mutations in other enzyme systems also play role in the etiopathogenesis of the irinotecan toxicity: CYP3A (cytochrome P-450), ABC family of transmembrane transporters (adenosine-triphosphate binding cassette). The goal of the contemporary research is to determine the predictive factors that will enable the individual adjustment of the individual drug dosage while minimising the adverse effects and maintaining the treatment benefit. and A. Paulík, J. Grim, S. Filip
INTRODUCTION: Annually more than 27,000 persons die of cancer in the Czech Republic and the overall incidence of malignancies is still increasing. These data shows the need for affordable and good follow-up care especially for patients without any cancer treatment due to irreversible progression of tumor. Currently the outpatient palliative cancer care gets more into the forefront. Prerequisite for a well working outpatient palliative care is cooperation with general practitioners and home health care agencies. The purpose of the so called program of palliative cancer care is to guide a patient in palliative cancer care and to improve the cooperation among health care providers. METHODS: During the period from January 2008 to October 2010 we evaluated in patient without any oncology treatment due to irreversible progression of tumor. RESULTS: In palliative outpatient clinic we treated 446 patients, 119 of them received home care services with average length of 27.8 days. 77 patients died at home, 51 in health facilities and 41 in inpatient hospice care. CONCLUSION: We present pilot study focusing on outpatient palliative cancer care which shows the real benefit from early indication of palliative cancer care. This type of care allows patients to stay as long as possible at home among their close relatives. and I. Slánská, J. Kopecký, S. Filip