The aim of the present study was to evaluate genome damage induced in peripheral blood lymphocytes of Croatian health care workers occupationally exposed to cytotoxic drugs. A comprehensive ...multi-biomarker approach using the alkaline comet assay and cytogenetic endpoints (analysis of structural chromosome aberrations, SCE assay, lymphocyte proliferation kinetics and cytokinesis-block micronucleus assay) was employed. The study included two populations of subjects: 50 health care workers occupationally exposed to cytotoxic drugs and 50 control subjects matched in age, gender and smoking habit. An investigation regarding the handling practice with cytotoxic drugs was conducted in parallel. Results obtained indicate high exposure levels at workplace that should be reduced. The values recorded among the occupationally exposed subjects were as follows: mean comet tail length: 17.46±0.08
μm; the incidence of long-tailed nuclei: 54.68±3.93%; 4.48±0.33 structural chromosome aberrations per 200 cells; 5.81±0.04 SCE per 50 cells; 29.28±2.21% of high-frequency cells; proliferation rate index: 1.97±0.12; and 16.32±0.85 micronuclei per 1000 binuclear cells. All these values indicated higher levels of DNA and cytogenetic damage compared to the general population. Obtained results also confirmed that the frequency of long-tailed nuclei in the alkaline comet assay represents a helpful complement to other well-established comet parameters. The age of subjects and smoking habit significantly influenced the values of both comet and cytogenetic endpoints. Overall results of this study confirmed that handling cytotoxic drugs without appropriate safety precautions involves a potential genotoxic risk for exposed subjects. Before a strict monitoring of exposure levels on each workplace becomes a standard practice in Croatian hospitals, cytogenetic surveillance of exposed workers is also recommended, at least in cases of accidental exposure.
The key organic constituents of marine macroaggregates (macrogels) of prevalently phytoplankton origin, periodically occurring in the northern Adriatic Sea, are proteins, lipids and especially ...polysaccharides. In this article, the reactivity of various macroaggregate fractions in relation to their composition in order to decode the potentially »bioavailable« fractions is summarized and discussed. The enzymatic hydrolysis of the macroaggregate matrix, using α-amylase, β-glucosidase, protease, proteinase and lipase, revealed the simultaneous degradation of polysaccharides and proteins, while lipids seem largely preserved. In the fresh surface macroaggregate samples, a pronounced degradation of the α-glycosidic bond compared to β-linkages. Degradation of the colloidal fraction proceeded faster in the higher molecular weight (MW) fractions. N-containing polysaccharides can be important constituents of the higher MW fraction while the lower MW constituents can mostly be composed of poly- and oligosaccharides. Since the polysaccharide component in the higher MW fraction is more degradable compared to N-containing polysaccharides, the higher MW fraction represents a possible path of organic nitrogen preservation. Enzymatic hydrolysis, using α-amylase and β-glucosidase, revealed the presence of α- and β-glycosidic linkages in all fractions with similar decomposition kinetics. Our results indicate that different fractions of macroaggregates are subjected to compositional selective reactivity with important implications for macroaggregate persistence in the seawater column and deposition.
Present study aimed at an integral assessment of sister chromatid exchange (SCE) frequencies in the health care workers occupationally exposed to cytostatics. The results of 500 individual analyses ...were evaluated. Drug handling practice was investigated in parallel and the results showed that cytostatics are mostly prepared outside hospital pharmacy (98%) and mainly handled by nurses (96%). Mean frequency of SCE was 5.63 ± 2.28, while HFC represented 9.65% of the cells analysed. Both values were higher compared to previously established control values for Croatian population. The duration of exposure, profession, age, gender, smoking habit, medical exposures, and simultaneous exposure to other occupational mutagens significantly contributed to SCE and HFC values. The usefulness both biomarkers in the assessment of cytogenetic damage is confirmed. Since current practice in Croatian hospitals does not include regular monitoring of workplaces, to ensure maximal occupational safety, a surveillance on exposed health care workers, including periodic biomonitoring, is recommended.
Rak debelog crijeva najčešći je zloćudni tumor probavnog sustava. U ovom se radu raspravlja o protokolima koji se primjenjuju u liječenju raka debelog crijeva, uključujući adjuvantnu i neoadjuvantnu ...terapiju resektabilne bolesti te kemoterapiju uznapredovalog i metastatskog raka debelog crijeva. Kirurgija je jedini kurativni modalitet liječenja lokaliziranog raka debelog crijeva (stadij bolesti I-III). Adjuvantna kemoterapija predstavlja standard u liječenju bolesnika sa stadij bolesti III . Međutim, njezina uloga kod stadija bolesti II je kontroverzna te se trenutno provode studije koje traže biljege pomoću kojih bi se mogli prepoznati bolesnici koji bi mogli imati koristi od primjene adjuvantne kemoterapije. Kirurška resekcija potencijalno predstavlja jedinu kurativnu mogućnost za bolesnike s bolešću ograničenom na jetru i/ili pluća (stadij IV). U liječenju metastatske bolesti standard predstavlja kemoterapija, prije nego kirurgija. Biološki lijekovi imaju ulogu u liječenju metastatske bolesti, s tim da se njihov izbor sve više temelji na genetskoj analizi tumora.
: Toxic effects of the antineoplastic drug irinotecan on human blood cells at concentrations of 9.0 µg/ml and 4.6 µg/ml were evaluated in vitro. Using the alkaline and neutral comet assay ...significantly increased levels of primary DNA damage in lymphocytes were detected. The induction of apoptosis/necrosis, as determined by a fluorescent assay, was also notably increased. Cytogenetic outcomes of the treatment were assessed by the analysis of structural chromosome aberrations and fluorescence in situ hybridization. A significantly higher incidence of chromatid breaks and complex quadriradials was observed. Painted chromosomes 1, 2 and 4 were equally involved in translocations, but only the chromosome 1 was involved in the formation of quadriradials. Sister chromatid exchange analysis was performed in parallel with the analysis of lymphocyte proliferation kinetics. The higher concentration of irinotecan caused almost seven‐time increase, while the lower one caused a five‐time increase of the basal sister chromatid exchange frequency, accompanied with significant lowering of the lymphocyte proliferation index. Using the cytokinesis‐block micronucleus assay, a dose‐dependent increase in micronucleus frequency along with the formation of nuclear buds and nucleoplasmic bridges was noticed. Inhibitory effects of irinotecan on enzyme acetylcholinesterase (AChE) were studied in erythrocytes. An IC50 value of 5.0 × 10−7 was established. Irinotecan was found to be strong inhibitor of the acetylcholine hydrolysis and to cause a continuous decrease of catalytic activity of AChE. The results obtained on a single donor may contribute to the understanding of irinotecan toxicity, but further in vitro and in vivo studies are essential in order to clarify remaining issues, especially on possible inter‐individual variability in genotoxic responses to the drug.
Taksani u liječenju ranog raka dojke Tečić Vuger, Ana; Pavlović, Mirjana; Lonjak, Nikolina ...
Libri Oncologici,
07/2018, Letnik:
46, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Taksani su nezamjenjivi lijekovi u liječenju mnogih solidnih tumora. U karcinomu dojke predstavljaju okosnicu adjuvantne terapije i važna su opcija u liječenju uznapredovale i metastatske bolesti. Od ...njihovog otkrića 1960-ih prošli su dugi put kliničkog razvoja i pozicioniranja u kliničkoj praksi liječenja ranog raka dojke. Taksani pripadaju četvrtoj skupini citotoksičnih lijekova koji djeluju kao inhibitori mitoze, koji uzrokuju smrt stanice u metafazi. Klinička istraživanja provedena
na bolesnicama s karcinomom dojke procjenjivala su različite kombinacije drugih kemoterapeutika s taksanima, različite načine primjene, djelotvornost različitih kemoterapijskih protokola koji uključuju taksane u različitim podtipovima i stadijima bolesti te učinkovitosti pojedinih taksana u usporedbi s drugim. Na temelju rezultata tih pokusa, danas relevantne globalne onkološke udruge preporučuju uporabu taksana u liječenju ranog raka dojke, pokazujući njihovu značajnu korist u ukupnom smanjenju rizika od smrti i povrata bolesti za 20-30% u odnosu na protokole bazirane samo na antraciklinu. Svrha ovog pregleda literature je pružanje sveobuhvatne informacije o razvoju taksana i njihove pozicije u rutinskoj svakodnevnoj kliničkoj praksi.
To identify malnourishment of surgical and oncologic patients or those at risk of becoming malnourished at four hospital centers in Croatia by use of nutritional screening questionnaire developed ...specifically for the purpose of this study.
The study included 1639 adult patients: 1475 scheduled for various surgical treatments and 164 oncologic patients receiving primary or adjuvant radio- and/or chemotherapy. The nutritional screening questionnaire consisted of data on recently reduced food intake and weight loss, body mass index (BMI), estimated period of perioperative fasting or oncologic disease status, categorization of surgical procedure, and additional stress expected. Each component was rated on a 0-2 or 0-3 scale. A score of seven points was chosen as the borderline between patients at risk of malnutrition (score <or=7) and those at no such risk (score 8-11). The questionnaire also included data on blood albumin, blood urea, blood lymphocyte count, blood creatinine, and overall patient evaluation by the physician.
Reduced food intake and weight loss were reported by 20% and 33% of the patients, respectively. Median BMI was 26 (range, 23.2-28.9) and underweight BMI values (<20) were found in 7% of the patients. Screening questionnaire score of <or=7, indicating the risk of malnutrition, was obtained in 23% of 1639 patients. Decreased albumin and lymphocytes were found in 10% and 17% of the patients, respectively. Increased urea and creatinine were found in 13% and 7% of the patients, respectively. Of the 288 patients examined by the physician, 41% were assessed as at risk of malnutrition and 9% as malnourished.
Nutritional screening questionnaire could be used for the identification of patients being at risk of malnutrition. An adequate prospective study is required for its final validation.
Iako je danas među onkološkim bolesnicima sve učestalija uporaba različitih pripravaka komplementarne i alternativne medicine, za njihovu uporabu nema nedvojbene znanstvene potvrde. Među češće ...primjenjivanim pripravcima, osobito u liječenju karcinomske boli, je i kanabis i njegovi derivati. Kanabinoidi djeluju u organizmu preko endokanabinoidnog sustava, s rasprostranjenim receptorima u središnjem živčanom sustavu i perifernim tkivima. Iako je farmakologija kanabinoida još uvijek uglavnom nepoznata, do sada su istraživani njihovi brojni učinci. U onkologiji su provedena istraživanja utjecaja na mučninu i povraćanje prilikom onkološkog liječenja, na karcinomsku bol te neuropatiju, na apetit i gubitak tjelesne mase te utjecaj na raspoloženje, depresiju i tjeskobu. Također je opažen antitumorski, ali i protumorski učinak nekih kanabinoida. Zabilježeni su brojni različiti neželjeni učinci kanabinoida, a u manjem postotku i razvoj ovisnosti. Najpoznatiji pripravci danas jesu dronabinol, nabilon i nabiksimol. Sveukupno, za sada nisu osigurani dovoljno snažni i nedvojbeni dokazi i potrebne su velike randomizirane kliničke studije, koje bi potvrdile do sada opažene pozitivne rezultate istraživanja.
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