Cytotoxic activity of Androctonus australis hector venom and its toxic fractions on human lung cancer cell line

Several studies have showed that animal venoms are a source of bioactive compounds that may inhibit the growth of cancer cells, which makes them useful agents for therapeutic applications. Recently, it was established that venom toxins from scorpions induced cytotoxic, antiproliferative and apoptogenic effects on cancer cells. Therefore, the present study aims to investigate the cytotoxic activity of Androctonus australis hector (Aah) scorpion venom and its toxic fractions (FtoxG-50 and F3) on NCI-H358 human lung cancer cells. Methods: The cytotoxic and antiproliferative activities were estimated using MTT assay, lactate dehydrogenase release and clonogenic assays. Apoptosis was evaluated by Hoechst 33258 staining, DNA fragmentation assay and caspase-3 activity. Oxidative stress was analyzed by reactive oxygen species, nitric oxide, malondialdehyde and protein carbonyl levels along with assessment of antioxidant status. In addition, alteration of mitochondrial membrane potential was analyzed by JC1 fluorescent dye. Results: The present findings showed that F3 fraction was more cytotoxic towards NCI-H358 lung cancer cells with an IC50 of 27.05 ± 0.70 g/mL than venom alone (396.60 ± 1.33 g/mL) and its toxic fraction FtoxG-50 (45.86 ± 0.91 g/mL). Nevertheless, F3 fraction was not cytotoxic at these concentrations on normal human lung fibroblast MRC-5 cells. Inhibition of NCI-H358 cell proliferation after F3 fraction exposure occurred mainly by apoptosis as evidenced by damaged nuclei, significant DNA fragmentation level and caspase-3 activation in a dose dependent manner. Moreover, F3 fraction enhanced oxidative and nitrosative stress biomarkers and dissipated mitochondrial membrane potential in lung cancer cells along with significant depletion in cellular enzymatic and non-enzymatic antioxidants. Further, the apoptosis induced by F3 fraction was markedly prevented by the antioxidant N-acetylcysteine (NAC) suggesting the potential mechanism of oxidative stress. Conclusion: These findings suggest that F3 fraction could induce apoptosis in lung cancer cells through involvement of oxidative stress and mitochondrial dysfunction. Hence, these properties make F3 fraction a promising candidate for development of new anticancer agents.

Tumor neuroendocrino metastásico: de células grandes KI-67 negativo / Neuroendocrines metastatic tumor: of big cells negative ki-67

Los tumores neuroendocrinos se consideran neoplasias poco frecuentes de las células de los sistemas neuroendocrinos diseminados o localizados. Poseen presentaciones clínicas y comportamientos biológicos muy heterogéneos. Baja tasa de proliferación celular y capacidad de liberar mediadores biológicos responsables de síndromes clínicos específicos. Tal heterogeneidad no permite un tratamiento estándar, siendo la terapia biológica y la quimioterapia efectiva en el control de enfermedad avanzada. Se presenta el caso de un paciente masculino de 60 años de edad, con enfermedad caracterizada por edema en región cervical izquierda, dura, fija y no dolorosa. Se le programaron 3 ciclos con protocolo 5-Fu, dacarbazina y epirrubicina obteniendo respuesta clínica del 60 por ciento. La heterogeneidad de estas entidades limita el consenso de su tratamiento.

Neuroendocrines tumors are considered neoplasm lees frequent of the cells of neuroendocrines systems disseminated or localized. They have clinical presentation and biologically conduct very heterogeneous: Low tease cellular proliferation and capacity of liberty biologically products responsibility of specifically clinically syndrome. These kind of heterogeneity don’t permit the application of standard treatment, the biologically therapy and chemotherapy are effective in the control of advance disease. We present a clinical case of a 60 years old male patient, with a disease characterized foe edema in left cervical region, hard, fix and no painful. We program 3 cycles with protocol 5-FU, dacarbazine, epirrubicine and obtain a clinical response of 60 %. The heterogeneous of this entity limit the consensus of treatment.

Differential expression of autophagy in Hodgkin lymphoma cells treated with various anti-cancer drugs.

AIM: autophagy is a pivotal physiological process for survival during starvation, differentiation and normal growth control. It is defined as the process of sequestrating cytoplasmic proteins or even entire organelles into the lytic compartment (lysosome/vacuole). This study investigates the expression of autophagy in Hodgkin lymphoma cells treated with various anti-cancer drugs. METHODS: Hodgkin's lymphoma cells (HD-My-Z cells) were cultured with various anti-cancer drugs, such as bleomycin, adriamycin, gemcitabine and paclitaxel. Autophagy was detected by fluorescent pattern of light chain 3(LC3) proteins and the apoptotic cell death was determined by annexin V binding. RESULTS: autophagy was detected in HD-My-Z cells treated with gemcitabine, but not with bleomycin, adriamycin and paclitaxel. Adriamycin exhibited the strongest cytotoxic action, and the cytotoxic action of bleomycin and gemcitabine was less marked compared with adriamycin. Paclitaxel did not cause significant cell death in the cells. CONCLUSION: autophagy was differentially expressed in Hodgkin lymphoma cells treated with anti-cancer drugs and the expression did not correspond to the apoptotic cell death.

Idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is being more frequently diagnosed in India, due to its increased awareness, better availability of computed tomography (CT) and fiberoptic bronchoscopy. IPF has the histological appearance of usual interstitial pneumonia (UIP) on surgical lung biopsy. Recent research has given a new insight into the etiology of the disease. Clinical criteria have been specified for presumptive diagnosis of IPF and distinguishing IPF from other conditions. The conventional therapy has been steroids and immunosuppressive agents. But only a minority of patients respond to such a therapy. Immunomodulators (interferon Y1b), antioxidants (Acetyl cysteine) and antifibrotic agents (like pirfenidone) are being studied as novel therapies in this, otherwise, fatal condition. Lung transplantation is the only hope for those patients who show progressive deterioration on medical treatment. Living-donor lobar lung transplantation has been developed as a procedure for patients considered too ill to await cadaveric lung transplantation.

Role of chelates in treatment of cancer.

Chelates are used in cancer as cytotoxic agent, as radioactive agent in imaging studies and in radioimmunotherapy. Various chelates based on ruthenium, copper, zinc organocobalt, gold, platinum, palladium, cobalt, nickel and iron are reported as cytotoxic agent. Monoclonal antibodies labeled with radioactive metals such as yttrium-90, indium-111 and iodine-131 are used in radioimmunotherapy. This review is an attempt to compile the use of chelates as cytotoxic drugs and in radioimmunotherapy.

Poliarteritis nodosa sistémica en niños / Systemic poliarteritis nodosa in children

Se presenta una experiencia con diez niños afectados por poliarteritis nodosa sistémica (PAN). Lo más sobresaliente en todos fue la presentación polimórfica clínicamente, por laboratorio y en estudios de gabinete. Los datos más útiles fueron los de los sistemas renal, cardiovascular y aparato digestivo. Todos fueron tratados con esteroides y nueve con inmunodepresores combinados. Un paciente falleció por complicación infecciosa propiciada por inmunodepresores y factores predisponentes para infección. Uno más falleció por ruptura de aneurisma renal y otro más por insuficiencia renal y otro más por insuficiencia renal crónica. Siete pacientes aún viven. La sobrevida es de más de diez años.