New drugs in cancer chemotherapy

Tumorske stanice su osjetljivije od normalnih stanica na kemoterapijske lijekove. Cilj lijekova koji se koriste u kemoterapiji tumora je izazivanje apoptoze tumorskih stanica. U ovom radu izložen je pregled antitumorskih lijekova. Postoje dvije vrste antitumorskih lijekova: pametni lijekovi i genski lijekovi. Pametni lijekovi usmjereni su na specifične signalne puteve odgovorne za rast tumora te djeluju na specifične antigene, faktore rasta, receptore i ostale molekule u signalnim putevima od interesa. S druge strane, genski lijekovi su usmjereni na ciljanje molekule DNA.Cancer cells are more vulnerable than normal cells to the effect of chemotherapy agents. Agents in cancer therapies are aimed at inducing apoptosis. In this work, a short review of the most important anticancer drugs, has been presented. There are two types of anticancer drugs: smart drugs and gene drugs. So-called “smart drugs” are directed towards specific signalling pathways responsible for tumor growth and target specific antigen, growth factor, receptor or other molecule in the signalling pathway of interest. On the other hand, so-called ‘‘gene drugs’’ are directed towards targeting the DNA molecule

New drugs in cancer chemotherapy

Tumorske stanice su osjetljivije od normalnih stanica na kemoterapijske lijekove. Cilj lijekova koji se koriste u kemoterapiji tumora je izazivanje apoptoze tumorskih stanica. U ovom radu izložen je pregled antitumorskih lijekova. Postoje dvije vrste antitumorskih lijekova: pametni lijekovi i genski lijekovi. Pametni lijekovi usmjereni su na specifične signalne puteve odgovorne za rast tumora te djeluju na specifične antigene, faktore rasta, receptore i ostale molekule u signalnim putevima od interesa. S druge strane, genski lijekovi su usmjereni na ciljanje molekule DNA.Cancer cells are more vulnerable than normal cells to the effect of chemotherapy agents. Agents in cancer therapies are aimed at inducing apoptosis. In this work, a short review of the most important anticancer drugs, has been presented. There are two types of anticancer drugs: smart drugs and gene drugs. So-called “smart drugs” are directed towards specific signalling pathways responsible for tumor growth and target specific antigen, growth factor, receptor or other molecule in the signalling pathway of interest. On the other hand, so-called ‘‘gene drugs’’ are directed towards targeting the DNA molecule

New drugs in cancer chemotherapy

Tumorske stanice su osjetljivije od normalnih stanica na kemoterapijske lijekove. Cilj lijekova koji se koriste u kemoterapiji tumora je izazivanje apoptoze tumorskih stanica. U ovom radu izložen je pregled antitumorskih lijekova. Postoje dvije vrste antitumorskih lijekova: pametni lijekovi i genski lijekovi. Pametni lijekovi usmjereni su na specifične signalne puteve odgovorne za rast tumora te djeluju na specifične antigene, faktore rasta, receptore i ostale molekule u signalnim putevima od interesa. S druge strane, genski lijekovi su usmjereni na ciljanje molekule DNA.Cancer cells are more vulnerable than normal cells to the effect of chemotherapy agents. Agents in cancer therapies are aimed at inducing apoptosis. In this work, a short review of the most important anticancer drugs, has been presented. There are two types of anticancer drugs: smart drugs and gene drugs. So-called “smart drugs” are directed towards specific signalling pathways responsible for tumor growth and target specific antigen, growth factor, receptor or other molecule in the signalling pathway of interest. On the other hand, so-called ‘‘gene drugs’’ are directed towards targeting the DNA molecule

Neurotoxic Effect of Ethanolic Extract of Propolis in the Presence of Copper Ions is Mediated through Enhanced Production of ROS and Stimulation of Caspase-3/7 Activity

Elevated amounts of copper are considered to be contributing factor in the progression of neurodegenerative diseases as they promote oxidative stress conditions. The aim of our study was to examine the effects of ethanolic extract of propolis (EEP) against copper-induced neuronal damage. In cultured P19 neuronal cells, EEP exacerbated copper-provoked neuronal cell death by increasing the generation of reactive oxygen species (ROS) and through the activation of caspase-3/7 activity. EEP augmented copper-induced up-regulation of p53 and Bax mRNA expressions. Neurotoxic effects of EEP were accompanied by a strong induction of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) expression and decrease in the expression of c-fos mRNA. SB203580, an inhibitor of p38 mitogen-activated protein kinase (MAPK) prevented detrimental effects of EEP, whereas SP600125, an inhibitor of c-Jun N-terminal kinase (JNK), exacerbated EEP-induced neuronal cell death. Quercetin, a polyphenolic nutraceutical, which is usually present in propolis, was also able to exacerbate copper-induced neuronal death. Our data indicates a pro-oxidative and apoptotic mode of EEP action in the presence of excess copper, wherein ROS/p53/p38 interactions play an important role in death cascades. Our study also pointed out that detailed pharmacological and toxicological studies must be carried out for propolis and other dietary supplements in order to fully recognize the potential adverse effects in specific conditions

Altered Expression of Shorter p53 Family Isoforms Can Impact Melanoma Aggressiveness

Cutaneous melanoma is the most aggressive form of skin cancer. Despite the significant advances in the management of melanoma in recent decades, it still represents a challenge for clinicians. The TP53 gene, the guardian of the genome, which is altered in more than 50% of human cancers, is rarely mutated in melanoma. More recently, researchers started to appreciate the importance of shorter p53 isoforms as potential modifiers of the p53-dependent responses. We analyzed the expression of p53 and p73 isoforms both at the RNA and protein level in a panel of melanoma-derived cell lines with different TP53 and BRAF status, in normal conditions or upon treatment with common anti-cancer DNA damaging agents or targeted therapy. Using lentiviral vectors, we also generated stable clones of H1299 p53 null cells over-expressing the less characterized isoforms Δ160p53α, Δ160p53β, and Δ160p53γ. Further, we obtained two melanoma-derived cell lines resistant to BRAF inhibitor vemurafenib. We observed that melanoma cell lines expressed a wide array of p53 and p73 isoforms, with Δ160p53α as the most variable one. We demonstrated for the first time that Δ160p53α, and to a lesser extent Δ160p53β, can be recruited on chromatin, and that Δ160p53γ can localize in perinuclear foci ; moreover, all Δ160p53 isoforms can stimulate proliferation and in vitro migration. Lastly, vemurafenib-resistant melanoma cells showed an altered expression of p53 and p73 isoforms, namely an increased expression of potentially pro-oncogenic Δ40p53β and a decrease in tumor-suppressive TAp73β. We therefore propose that p53 family isoforms can play a role in melanoma cells’ aggressiveness

Synthesis and application of gold nanoparticiples to MDA-MB-231 breast cancer cells

Cilj ovog diplomskog rada bio je utvrditi radiosensitizacijski efekt nano čestica zlata (NZ) na stanicama raka dojke MDA-MB-231. Sintetizirane su tri vrste NZ obavijene citratima, glutationom i amino-dekstranom. Njihova veličina određena je skenirajućim elektronskim mikroskopom i UV-Vis-spektrofotometrom i iznosila je oko 15 nm. NZ su bile aplicirane na MDA-MB-231 stanice i pratilo se kvalitativno i kvantitativno nakupljanje NZ u stanicama. Transmisijski elektronski mikroskop je pokazao nakupljanje NZ u vezikulama, a kvantitativnom analizom je utvrđena točna koncentracija NZ u stanicama. Najveća koncentracija NZ u stanicama je postignuta s NZ obavijenim amino-dekstranom. Stanice tretirane NZ bile su izložene γ-zračenju, te se proučavao radiosensitizacijski efekt NZ na MDA-MB-231 stanice. MTT-testom utvrđeno je smanjenje vijabilnosti stanica uslijed aplikacije NZ i γ-zračenja. Klonogenski test pokazao se kao jako osjetljivi test za utvrđivanje utjecaja γ-zračenja + NZ na citotoksičnost stanica. Međutim, zbog velike citotoksičnosti samog γ-zračenja radiosensitizacijski efekt nije mogao biti utvrđen.The aim of this work was to study the radiosensitization effect of three types of gold nanoparticles (GNPs) on MDA-MB-231 cancer cells in vitro. GNPs were synthesized in order to be coated with citrate, glutathione and amino-dextrane. Their size was determined using electron microscopy and UV-VIS spectrophotometer and was around 15 nm. GNPs were applied to a MDA-MB-231 cancer cell line and their accumulation in cells was investigated. Transmission electron microscopy demonstrated accumulation of GNPs in cytoplasmic vesicles, while the Mass Spectroscopy was used to demonstrate the highest uptake of amino- dextrane coated GNPs. Cells treated with GNPs were γ-irradiated and their radiosensitization effect was studied. Short-term MTT viability assay showed no cells sensitivity to the effect of ionizing radiation, whereas the long-term clonogenic assay showed high sensitivity to the cytotoxic effect of γ-irradiation. However, the high cytotoxicity of γ-irradiation alone to cancer cells did not allow the determination of the radiosensitization effect of synthesized GNPs