Volume 34, Issue 1

Considerable development in the application of injectable drug delivery systems for cancer therapy has occurred in the last few decades. These improvements include liposomes, lipid nanoparticles (LNPs), and other nanoparticles with or without macromolecular conjugates. For example, liposomal doxorubicin modified by poly(ethylene glycol) (Doxil) was the first liposome with anti-cancer effects which was approved by the US Food and Drug Administration, whereas Abraxane (modified albumin nanoparticles loaded by paclitaxel) was recently confirmed for the treatment of breast cancer. Recently, drug delivery systems by LNPs are an emerging technology with numerous advantages over conventional liposomes and chemotherapy using free drug treatment of cancer. These properties are biocompatibility, controlled and sustained release of anti-tumor drugs, and lower toxicity. Valuable experiments on these drug delivery systems offer better treatment of multidrug-resistant cancers and lower cardiotoxicity. LNPs have been presented with high functionality in chemotherapeutic targeting of breast and prostate cancer. The basis for this targeting behavior has been shown to be both passive and active targeting. The main objective of this review was an overview of the current position of the liposome-based drug delivery systems in targeted anticancer chemotherapy.

Background The thiopurine S-methyltransferase (TPMT)/azathioprine (AZA) gene-drug pair is one of the most well-known pharmacogenetic markers. Despite this, few studies investigated the implementation of TPMT testing and the combined evaluation of genotype and phenotype in multidisciplinary clinical settings where patients are undergoing chronic therapy with AZA. Methods A total of 356 AZA-treated patients for chronic autoimmune diseases were enrolled. DNA was isolated from whole blood and the samples were analyzed for the c.460G>A and c.719A>G variants by the restriction fragment length polymorphism (RFLP) technique and sequenced for the c.238G>C variant. The TPMT enzyme activity was determined in erythrocytes by a high-performance liquid chromatography (HPLC) assay. Results All the patients enrolled were genotyped while the TPMT enzyme activity was assessed in 41 patients. Clinical information was available on 181 patients. We found no significant difference in the odds of having adverse drug reactions (ADRs) in wild-type patients and variant allele carriers, but the latter had an extra risk of experiencing hematologically adverse events. The enzyme activity was significantly associated to genotype. Conclusions TPMT variant allele carriers have an extra risk of experiencing hematologically adverse events compared to wild-type patients. Interestingly, only two out of 30 (6.6%) patients had discordant results between genotype, phenotype and onset of ADRs.

Background The present study was conducted with the aim of investigating the prevalence of potentially beneficial and harmful drug-drug interactions (DDIs) in intensive care units (ICUs). Methods The present cross-sectional prospective study was conducted in two ICUs in Shahr-e Kord city, Iran. The study sample was consisted of 300 patients. The Drug Interaction Facts reference text book [Tatro DS. Drug interaction facts. St Louis, MO: Walters Kluwer Health, 2010.] was used to determine the type and the frequency of the DDIs. Results The participants consisted of 189 patients men and 111 women. The mean age of patients was 44.2 ± 24.6 years. Totally, 60.5% of patients had at least one drug-drug interaction in their profile. The total number of DDIs found was 663 (the mean of the total number of drug-drug interactions was 2.4 interactions per patient). Of all the 663 interactions, 574 were harmful and others were beneficial. In terms of starting time, 98 of the potential interactions were rapid and 565 of them were delayed. In terms of severity, 511 of the potential interactions were moderate. Some of the drugs in the patients’ medical records including phenytoin, dopamine, ranitidine, corticosteroid, dopamine, heparin, midazolam, aspirin, magnesium, calcium gluconate, and antibiotics, the type of ventilation, the type of nutrition and the duration of hospital stay were among the factors that were associated with high risk of potential DDIs (p < 0.05). Conclusions The prevalence of potentially beneficial and harmful DDIs, especially harmful drug-drug interactions, is high in ICUs and it is necessary to reduce these interactions by implementing appropriate programs and interventions.

Background Previous studies reported conflicting results regarding association of insulin receptor substrate 1 ( IRS1 ) gene variation with type 2 diabetes (T2D) and insulin resistance (IR) in different ethnic groups. We examined the association of rs7578326, rs2943641, and rs4675095 in the IRS1 gene with T2D and related traits in a population from Bosnia and Herzegovina, which is one of the European countries with the highest T2D prevalence of 12.5%. Methods Our study included 390 T2D patients and 252 control subjects. Biochemical parameters, including fasting glucose (FG), fasting insulin (FI), homeostasis model assessment insulin resistance index (HOMA-IR), and HbA 1c were measured in all participants. Genotyping analysis was performed by Mass Array Sequenom iPlex platform. Results Our results demonstrated that rs7578326 and rs4675095 variants were associated with increased FG levels. The rs7578326 was also associated with higher FI, HOMA-IR (B = 0.08, 95% CI [0.01, 0.15], p add = 0.025; B = 0.079, 95% CI [0.006, 0.150], p add = 0.033, respectively) in T2D, and with HbA 1c (B = 0.034, 95% CI [0.003, 0.065], p dom = 0.035) in non-drug-treated T2D. In contrast, rs2943641 C allele was associated with lower FG levels in control subjects (B = −0.17, 95% CI [−0.03, −0.002], p add = 0.030) and HbA 1c (B = 0.03, 95% CI [0.002, 0.06], p dom = 0.040) in non-drug-treated T2D. Conclusions We report the association between common variants in IRS1 gene with insulin resistance, glucose, and HbA 1c levels in Bosnia and Herzegovina’s population.

Background Menthol is widely used as a constituent of functional foods and chemical drugs. In the present study, we investigated changes in the expression of cytochrome P450 isoform CYP3A4 mRNA after treating human hepatocellular carcinoma HepG2 cells with menthol. We also examined the effects of pretreatment with menthol on the cytotoxic activity of paclitaxel (PAC) and vincristine (VIN), which are substrates of CYP3A4, in the cells. Methods HepG2 cells were maintained in Dulbecco’s Modified Eagle’s Medium. Expression of CYP3A4 was examined by the real-time polymerase chain reaction. Survival rate of HepG2 cells was evaluated by the MTT assay. Results The gene expression level of CYP3A4 in HepG2 cells was significantly reduced by treatment with menthol for 1 day. The viability of HepG2 cells was not affected by treatment with menthol alone once a day for two consecutive days. The degree of reduction in cell viability by PAC or VIN in HepG2 cells was significantly increased by menthol treatment for 24 h prior to exposure to these anti-cancer drugs. Conclusions These results demonstrate that menthol enhanced the anti-tumor effects of PAC and VIN through the downregulation of CYP3A4 in HepG2 cells without exerting cytotoxic activity.

Background Cystathionine γ-lyase enzyme, which is encoded by the CTH gene, is responsible for hydrogen sulfide (H 2 S) production in the endothelium. The CTH 1364 G>T polymorphism may alter the CTH expression and H 2 S bioavailability, thus leading to atherosclerosis and coronary artery disease (CAD). We examined the potential association of the CTH 1364 G>T polymorphism with CAD. Methods The CTH 1364 G>T polymorphism was determined in 178 coronary artery bypass grafting (CABG) patients and 156 non-atherosclerotic controls of Greek Caucasian origin using the PCR–RFLP method. Results No significant difference in the frequency of the CTH 1364 G>T genotypes (p = 0.281) and alleles (p = 0.265) was found between the CABG patients and controls. After conducting stratification according to sex, analysis showed a numerical difference in the CTH 1364 TT genotype frequency in female participants that did not reach statistical significance (16.3% and 8.5% in the CABG and controls, respectively, p = 0.26). The frequency of the CTH 1364 TT genotype between the male CABG patients and controls did not differ (p = 0.507). Conclusions The CTH 1364 G>T polymorphism was not associated with CAD in the studied population. However, interestingly, a higher – if not significantly so – CTH 1364 TT genotype frequency was present in female CABG patients compared with female controls. Larger studies are necessary to conclude on the potential overall or gender-driven association between CTH 1364 G>T gene polymorphism and CAD.