MRI u ginekološkoj onkologiji

The use of magnetic resonance imaging ( MRI) in gynecological oncology is rapidly expanding. Pelvic MRI has excellent soft tissue contrast and multiplanar imaging ability to demonstrate either normal or pathological processes. In gynecological oncology the rapidly evolving role of MRI includes not only diagnosis but also disease staging, planning of therapy and monitoring response to treatment. We perform around 350 preoperative gynecology MRI annually, mostly in patients with suspected malignancy. In this paper we review the role of MRI in endometrial, cervical and ovarian cancerSvakodnevno raste uporaba magnetske rezonancije (MR) u ginekološkoj onkologiji. MR zdjelice ima odličnu prostornu i kontrastnu rezoluciju za prikaz kako fi zioloških tako i patoloških procesa. Sve je veća uključenost MR pregleda ne samo u dijagnostici već i u određivanju stadija bolest i praćenju terapije. U našem radiološkom odjelu obavi se oko 350 preoperativnih ginekoloških MR pregleda godišnje, najčešće kod pacijenata sa sumnjom na malignu bolest. U ovom radu osvrnuti ćemo se na ulogu MR u karcinomima endometrija, grlića maternice i jajnika

Cathepsin B-Cleavable Cyclopeptidic Chemotherapeutic Prodrugs

Cyclopeptidic chemotherapeutic prodrugs (cPCPs) are macromolecular protease-sensitive doxorubicin (DOX) prodrugs synthesized from a cyclodecapeptidic scaffold, termed Regioselectively Addressable Functionalized Template (RAFT). In order to increase the chemotherapeutic potential of DOX and limit its toxicity, we used a Cathepsin B (Cat B)-sensitive prodrug concept for its targeted release since this enzyme is frequently overexpressed in cancer cells. Copper-free “click” chemistry was used to synthesize cPCPs containing up to four DOX moieties tethered to the upper face of the scaffold through a Cat B-cleavable peptidic linker (GAGRRAAG). On the lower part, PEG 5, 10 and 20 kDa and a fifth peptidyl DOX moiety were grafted in order to improve the solubility, bioavailability and pharmacokinetic profiles of the compound. In vitro results on HT1080 human fibrosarcoma cells showed that cPCPs display a delayed action that consists of a cell cycle arrest in the G2 phase comparable to DOX alone, and increased cell membrane permeability

Design, synthesis and in vitro evaluation of β-glucuronidase-sensitive prodrug of 5-aminolevulinic acid for photodiagnosis of breast cancer cells

Treatment of cancer cells by clinically approved hexyl ester of 5-aminolevulinic acid (ALA-Hex) induces accumulation of fluorescent porphyrins in tumors. This allows fluorescence photodiagnosis (PD) of bladder cancer by blue light illumination. However, PD of other cancers is hampered by acute toxicity of the compound limiting its use to local applications. We have designed and synthesized a new prodrug of ALA-Hex that tackles the stability-activity paradox of amino-modified 5-ALA prodrugs. The glucuronide prodrug Glu-ALA-Hex demonstrates excellent stability under physiological conditions and activation in the presence of the target enzyme. β-glucuronidase-triggered release of 5-ALA is programmed to yield fluorescence in tumor environment with elevated β-glucuronidase activity, a characteristic of many solid tumors. Glu-ALA-Hex produces similar levels of fluorescence as ALA-Hex in breast cancer MCF7 cells in vitro but with much lower non-specific cell toxicity