Induction of apoptosis in Jurkat cells by photoexcited psoralen derivatives: Implications of mitochondrial dysfunctions and caspases activation.

The prevailing form of cell death in lymphocytes exposed to psoralen plus UVA light (PUVA), was investigated. We studied the well known drug 8-methoxypsoralen (8-MOP) and an angular derivatives: angelicin (ANG). We evaluated the induction of apoptosis in a human tumor T-cell line (Jurkat). Both compounds provoke a significant induction of apoptosis at 24h from irradiation as demonstrated by a remarkable percentage of cells Annexin-V positive. We investigated the effects of the psoralen derivatives upon UVA irradiation on the cell cycle. The flow cytometric analysis of propidium labeled cells indicates that treatment induces, in a dose dependent manner, a massive accumulation of cells, for both compounds, in G2-S phase after 24h from the irradiation. We have focused our attention on the mitochondrial functionality after irradiation in the presence of psoralen derivatives. We evaluated, by flow cytometry, (i) the mitochondrial potential (Deltapsi(mt)), (ii) the production of reactive oxygen species (ROS) and (iii) the oxidation of cardiolipin, a phospholipid restricted to the inner mitochondrial membrane. Furthermore the activation of caspases -3, -8 and -9 was also investigated. The obtained data indicated that, upon UVA irradiation, the two compounds induce a strong decrease in mitochondrial functions and activate caspase-3, -8 and -9

Simulation of electromagnetic field (EM) focusing capability on biological tissue through the application of C-type excitation coil screen

In Magnetic Induction Tomography (MIT) or Electromagnetic Therapy system, excitation coil is applied with AC source in generating the electromagnetic (EM) field which then propagate and penetrate the object located in the region of interest (ROI). However, instead to the target object, the fields also propagate around the coil and create interference to the nearby circuit which contributes noise to the system while at the same time wasting the energy. This paper is focusing on the use of C-type excitation coil screen in focusing the EM field to the ROI and measure the penetration depth when different frequency is applied to the generation system

Synthesis, cytotoxicity and apoptosis induction in human tumor cells by geiparvarin analogues

A series of geiparvarin analogues modified on the unsaturated alkenyloxy bridge, where a H-atom replaced the 3'-Me group, were synthesized and evaluated against a panel of human tumor cell lines in vitro. These compounds demonstrated a stronger increase in growth inhibitory activity when compared to the parent compound geiparvarin (8). In particular, the activity increased even further in the series of demethylated compounds when a Me substituent in the coumarin moiety is introduced. On the contrary, the same modifications exerted on the parent compound led to an activity reduction. Interestingly, the new derivatives proved to be fully inhibitory to drug-resistant cell lines, thus suggesting that they are not subject to the pump-mediating efflux of antitumor drugs. On the basis of their cytotoxic profiles, the most-active compounds were selected for further biological evaluation. The extracellular acidification rate by the new geiparvarin analogues was measured with the Cytosensor microphysiometer. The new derivatives significantly increased the acidification rate during the 24-48 h of incubation in a concentration-dependent manner. Cell-cycle analysis, evaluated by flow cytometry, revealed a strong apoptotic induction by these compounds confirmed by DNA laddering and observation by electron microscopy. Interestingly, the apoptotic pathway did not appear to be mediated by the activation of caspase-3

Lo studio della malattia residua minima mediante RT-PCR nel sangue periferico pu\uf2 rappresentare uno strumento valido e non invasivo per la valutazione della risposta alla terapia: un caso clinico

Case report sull'uso della malattia residua minima per la valutazione della risposta alla terapi

Two consecutive immunophenotypic switches in a child with MLL-rearranged acute lymphoblastic leucemia.

An 18-month-old girl was diagnosed with pre-pre-B ALL/t(4;11) leukemia, which during the treatment and after matched bone marrow transplantation (BMT), underwent two consecutive switches from lymphoid to myeloid lineage and vice versa. The high expression of HOXA9 and FLT3 genes remaining genotypically stable in a leukemia throughout phenotypic switches, suggests that this leukemia may have originated as a common B/myeloid progenitor