Assessing hexavalent chromium tissue-specific accumulation patterns and induced physiological responses to probe chromium toxicity in Coturnix japonica quail.

Hexavalent chromium (Cr(VI)) is an environmental pollutant with vast mutagenic and carcinogenic potential. Various past and recent studies confirm the deleterious effects of Cr(VI) in different models, from invertebrates to mammalians. However, there is a lack of studies that comprehensively assess and correlate Cr(VI) accumulation patterns and the resulting physiological responses. Here we used an attractive toxicological model, male Japanese quail (Coturnix japonica), as an alternative probing system to evaluate Cr(VI) accumulation in the vital organs, including the brain, heart, kidneys, liver, and testes after 20 days of exposure to 1.2 µg/mL and 2.4 µg/mL potassium dichromate-K2Cr2O7 ingested in the form of drinking water. The observed effects were correlated with the shift in immune system readiness, hematological indices, serum biochemistry and enzyme activity. Regardless of the exposure dose, the Cr(VI) distribution and accumulation pattern in terms of relative Cr(VI) concentration in tissues was: testes > kidneys > liver > heart > brain. Moreover, Cr(VI) triggered the development of microcytic and hypochromic anemia and reduced the immune system's readiness to cope with challenges. Besides, serum biochemistry presented significant shifts, including reduction of serum electrolytes and proteins and an increase in creatine kinase (CK) and lactate dehydrogenase (LDH) activity. Our study provides novel toxicological data that can be translated to higher animal models to help in the extrapolation of Cr(VI) toxicity in humans.

Chemical toxicity and radioactivity of depleted uranium: The evidence from in vivo and in vitro studies.

The main aim of this review is to summarize and discuss the current state of knowledge on chemical toxicity and radioactivity of depleted uranium (DU) and their effect on living systems and cell lines. This was done by presenting a summary of previous investigations conducted on different mammalian body systems and cell cultures in terms of potential changes caused by either chemical toxicity or radioactivity of DU. In addition, the authors aimed to point out the limitations of those studies and possible future directions. The majority of both in vitro and in vivo studies performed using animal models regarding possible effects caused by acute or chronic DU exposure has been reviewed. Furthermore, exposure time and dose, DU particle solubility, and uranium isotopes as factors affecting the extent of DU effects have been discussed. Special attention has been dedicated to chromosomal aberrations, DNA damage and DNA breaks, as well as micronuclei formation and epigenetic changes, as DU has recently been considered a possible causative factor of all these processes. Therefore, this approach might represent a novel area of study of DU-related irradiation effects on health. Since different studies offer contradictory results, the main aim of this review is to summarize and briefly discuss previously obtained results in order to identify the current opinion on DU toxicity and radioactivity effects in relation to exposure type and duration, as well as DU properties.

The Efficacy of Generic Imatinib as First- and Second-line Therapy: 3-Year Follow-up of Patients With Chronic Myeloid Leukemia.

INTRODUCTION: Generics of imatinib mesylate, the first tyrosine kinase inhibitor targeting the BCR-ABL1 fusion protein, have recently been approved in many countries as the alternative, low-cost forms for the treatment of patients with chronic myeloid leukemia (CML). The aim of this study was to evaluate the long-term clinical outcomes of patients with CML receiving first-line and second-line generic imatinib in Bosnia and Herzegovina. PATIENTS AND METHODS: This was a multicenter retrospective cohort study of patients (n = 41) treated with generic imatinib in Bosnia between September 1, 2013 and August 5, 2016. Patients were categorized into 2 study groups: Group 1 (n = 27) included newly diagnosed patients with CML receiving front-line generic imatinib, and Group 2 (n = 14) consisted of patients who started with front-line Glivec and were mandated to switch to the second-line generic imatinib. RESULTS: The median follow-up for Group 1 (first-line generic imatinib) and Group 2 (second-line generic imatinib) was 16 and 36 months, respectively. At 36 months, the overall survival for patients in Group 1 was 85%, and the achievement of complete cytogenetic response was 81%. At 24 months, the major molecular response rate was 48%. Overall, 52% of patients switched from first-line generic imatinib to nilotinib owing to treatment failure and side-effects. In Group 2, 93% of patients sustained cytogenetic and molecular response at 3 years after the switch from branded to generic imatinib. CONCLUSION: Our results lead us to conclude that generic imatinib as second-line therapy does not have deleterious effects on patient outcomes. However, first-line generic imatinib showed suboptimal efficacy compared with branded imatinib.

The reality of cancer treatment in a developing country: the effects of delayed TKI treatment on survival, cytogenetic and molecular responses in chronic myeloid leukaemia patients.

Cancer patients in developing and low-income countries have limited access to target therapies. For example, tyrosine kinase inhibitor (TKI) therapy for chronic myeloid leukaemia patients (CML) is often delayed. In Bosnia, 16% of patients received immediate TKI treatment (<3 months of diagnosis), while 66% of patients received therapy after a median 14-month wait period. To assess the effect of delayed treatment on outcome, three patient groups were studied according to the time they received TKI treatment (0-5 months, 6-12 months and >13 months delay). The primary endpoints were complete cytogenetic (CCyR) and major molecular response (MMR) at 12 months. At 12 months of therapy, CCyR and MMR rates on imatinib decreased significantly: CCyR was achieved in 67% of patients in the immediate imatinib treatment group, 18% of patients in 6-12 months group and 15% of patients in >13 months wait group. MMR rates at 12 months occurred in 10% of patients with immediate treatment, 6% of those in 6-12 months group and 0% of patients in >13 months wait group. However, CCyR and MMR rates in patients on nilotinib were not associated with duration of treatment delay. Our data suggests that the deleterious effect of a prolonged TKI therapy delay may be ameliorated by the more active TKI nilotinib.