DEVELOPMENTAL INSTABILITY IN WILD CHROMOSOMAL HYBRIDS OF THE HOUSE MOUSE

In wild populations of the house mouse from Tunisia, fluctuating asymmetry and character size of tooth traits were compared between chromosomal races (2n = 40, all acrocentric standard karyotype, and 2n = 22, with nine fixed Robertsonian fusions) and their natural hybrids. Developmental stability was impaired in hybrids compared to both parental groups. Because genetic divergence measured by allozyme markers was low, genomic incompatibilities were not expected between the chromosomal races. This suggests that differentiation of gene systems specifically involved in development may have occurred between the chromosomal races. Support for the latter was found in the study of character size which showed that the 2n = 22 mice had smaller teeth than either the hybrid or the standard mice. The study of Tunisian chromosomal races thus shows that chromosomal evolution may lead to important changes in coadapted gene systems without involving extensive genic differentiation.     

Limites de la scintigraphie osseuse dans le suivi des métastases osseuses du carcinome mammaire : étude du centre tunisien

Bone metastases, a relatively frequent complication of breast carcinoma, are more and more associated with better survival. This in part through a specific detection and monitoring. In Sousse (Tunisia), bone scan is the exam most frequently performed for monitoring bone metastases, which is also the only functional exam available until December 2011. We studied the place of bone scan in the monitoring of these bone metastases. We followed 115 patients between 2000 and 2004 with a follow-up of 7 to 11 years. We used Measurable Criteria Disease response of Anderson (MDA) scintigraphic criteria. Complete remission was rare. Partial remission rate decreased gradually over time. Partial remission rate was 22.6% at the first evaluation and became equal to 10% at the fourth assessment. Stability is a false reassuring category since among the 27 cases judged to be stable after the first evaluation, only nine continued to be stable at the fourth evaluation and one at the sixth. In conclusion, bone scan is reliable only in cases of complete or partial remission. For other stages bone scintigraphy had many limitations since this examination informs about the osteoblastic reaction around metastases and not the tumour itself. ¹⁸F-FDG-PET/CT (¹⁸Fluoro-deoxy-glucose) indeed shows the metastasis metabolism itself, so is better positioned to evaluate the therapeutic response.     

Sequential events of apoptosis induced by zearalenone in cultured hepatocarcinoma cells

Zearalenone (ZEA) is a fungal metabolite that can contaminate feed and foodstuffs and can cause serious health problems for animals as well as for humans. The present investigation was conducted to determine the chronological succession of the main events that characterise ZEA-induced toxicity in human hepatocarcinoma cells. To this aim, we have monitored the effects of ZEA on (1) cell viability, (2) heat-shock protein expression, (3) oxidative damage, (4) DNA fragmentation, (5) the cell cycle and (6) the cell-death-signalling pathway. Our results demonstrated that ZEA reduced cell viability in a time- and dose-dependent manner. When we exposed HepG2 cells to 100 μM ZEA (80% of cells are viable) for different treatment times (2, 4, 8, 24, 30, 48 and 60 h), we demonstrated an induction of Hsp70 protein, an increase in reactive oxygen species (ROS) generation, DNA fragmentation and cell-cycle arrest. These events begin after only 2 h of mycotoxin exposure and are earlier than those implicated in the execution of apoptosis. However, significant apoptotic cell death was observed after at least 30 h of ZEA exposure as a consequence of increased Bax expression, decreased Bcl-2 expression and mitochondrial membrane potential (Δψm)-released cytochrome c and activated caspase-3 and caspase-9.     

UV-C pre-adaptation of Salmonella: effect on cell morphology and membrane fatty acids composition

The present study was carried out to evaluate the effects of ultraviolet radiations (UV-C) on the fatty acids composition of three serovars of Salmonella: S. typhimurium, S. hadar and S. zanzibar. Results obtained show that UV-C treatment increases significantly (P ≤ 0.05) the percentage of cyclic fatty acids. The atomic force microscopy was used to study the morphology and cell surface of irradiated strains. Results show that UV-C rays induce morphological changes and alter the bacterial cell surface (presence of grooves and irregularities).     

Cabozantinib-induced edema in zebrafish represents an adverse effect characterized by defects in lymphatic vasculature and renal function

Tyrosine kinase inhibitors (TKIs) are a major class of targeted cancer therapy drugs. Overcoming the limitations of approved TKIs and the development of new TKIs continues to be an important need. The adoption of higher throughput and accessible animal models to evaluate TKI adverse effects will help in this regard. We exposed zebrafish larvae to a set of 22 Food and Drug Administration-approved TKIs and assessed mortality, early developmental abnormalities, and gross morphological abnormalities posthatching. We found edema posthatching as a consistent and prominent consequence of VEGFR inhibitors, and of cabozantinib in particular. The edema occurred at concentrations that did not cause lethality or any other abnormality, and was independent of the developmental stage. Further experiments identified loss of blood and lymphatic vasculature, and suppression of renal function in larvae exposed to 10 µM cabozantinib. Molecular analysis showed downregulation of the vasculature marker genes vegfr, prox1a, sox18, and the renal function markers nephrin and podocin as the potential molecular basis for the above defects, implicating them in the mechanism of cabozantinib-induced edema. Our findings reveal edema as a previously unreported phenotypic effect of cabozantinib and identify the likely mechanistic basis. These findings also highlight the need for studies investigating edema due to vascular and renal dysfunction as a potential clinical adverse effect of cabozantinib, and possibly other VEGFR inhibitors.