In vitro and in vivo activity of the nuclear factor-kappa B inhibitor sulfasalazine in human glioblastomas.

in Clinical Cancer Research : An Official Journal of the American Association for Cancer Research (2004), 10(16), 5595-603

Glioblastomas, the most common primary brain cancers, respond poorly to current treatment modalities and carry a dismal prognosis. In this study, we demonstrated that the transcription factor nuclear ... [more ▼]

Glioblastomas, the most common primary brain cancers, respond poorly to current treatment modalities and carry a dismal prognosis. In this study, we demonstrated that the transcription factor nuclear factor (NF)-kappaB is constitutively activated in glioblastoma surgical samples, primary cultures, and cell lines and promotes their growth and survival. Sulfasalazine, an anti-inflammatory drug that specifically inhibits the activation of NF-kappaB, blocked the cell cycle and induced apoptosis in several glioblastoma cell lines and primary cultures, as did gene therapy with a vector encoding a super-repressor of NF-kappaB. In vivo, sulfasalazine also significantly inhibited the growth of experimental human glioblastomas in nude mice brains. Given the documented safety of sulfasalazine in humans, these results may lead the way to a new class of glioma treatment. [less ▲]

In vitro and in vivo antimalarial and cytotoxic activity of five plants used in Congolese traditional medicine.

in Journal of Ethnopharmacology (2010), 129

AIM OF THE STUDY: The in vitro antiplasmodial activity and cytotoxicity of methanolic and dichloromethane extracts from five Congolese plants were evaluated. The plants were selected following an ... [more ▼]

AIM OF THE STUDY: The in vitro antiplasmodial activity and cytotoxicity of methanolic and dichloromethane extracts from five Congolese plants were evaluated. The plants were selected following an ethnobotanical survey conducted in D.R. Congo and focusing on plants used traditionally to treat malaria. The in vivo antimalarial activity of aqueous and methanolic extracts active in vitro was also determined in mice infected by Plasmodium berghei berghei. MATERIALS AND METHODS: The growth inhibition of Plasmodium falciparum strains was evaluated using the measurement of lactate dehydrogenase activity. The extracts (aqueous, CH(3)OH, EtOH and CH(2)Cl(2)) were prepared by maceration and tested in vitro against the 3D7 (chloroquine sensitive) and W2 (chloroquine resistant) strains of Plasmodium falciparum and against the human normal fetal lung fibroblasts WI-38 to determine the selectivity index. Some extracts were also used at the dose of 300mg/kg to evaluate their activity in mice infected since 4 days by Plasmodium berghei. RESULTS: Two plants presented a very high activity (IC(50)<3mug/ml). These plants were Strychnos icaja roots bark (MeOH and CH(2)Cl(2)) and Physalis angulata leaves (MeOH and CH(2)Cl(2)). One plant (Anisopappus chinensis whole plant, MeOH and CH(2)Cl(2)) presented a high activity (IC50<15mug/ml). The extracts of Anisopappus chinensis and Physalis angulata showed also a good inhibition of parasitemia in vivo. Flavonoids, phenolic acids and terpenes were identified in these plants by a general phytochemical screening method. CONCLUSION: Three plants showed a very interesting antiplasmodial activity (Anisopappus chinensis, Physalis angulata and Strychnos icaja) and one of them showed a good selectivity index (>10, Anisopappus chinensis). Anisopappus chinensis and Physalis angulata were also active in vivo. [less ▲]

The In Vitro and In Vivo Antitumor Activity of Vitamin C: K3 Combinations Against Prostate Cancer

in Lucas, John N (Ed.) Horizons cancer Res. , Trends in prostate cancer research (2005)

Neoplasms of the urinary tract and male genital tract account for 32% of new cancers in males. Prostatic carcinoma is one of the most prevalent malignant tumors of the male reproductive organs, with an ... [more ▼]

Neoplasms of the urinary tract and male genital tract account for 32% of new cancers in males. Prostatic carcinoma is one of the most prevalent malignant tumors of the male reproductive organs, with an estimated 230,110 new cases and 29,900 deaths during the year 2004 in the United States. Although prostate cancer in its early stages is responsive to the standard treatments, no currently available treatment produces a survival advantage to patients with hormone-refractory prostate cancer. This lack of efficacy for the existing protocols points to the need for the development of effective regimens for treating or preventing these tumors. Vitamin C (VC) and vitamin K3 (VK3) administered to androgen independent prostate cancer cell lines in a VC:VK3 ratio of 100:1 exhibit synergistic antitumor activity and preferentially kill tumor cells by autoschizis, a novel type of cell death characterized by exaggerated membrane damage and progressive loss of organelle-free cytoplasm through a series of self-excisions. During this process, the nucleus becomes smaller; cell size decreases to 1/2 - 1/3 of its original size and most organelles surround an intact nucleus in a narrow rim of cytoplasm. While the mitochondria are condensed, tumor cell death does not result from ATP depletion. However, administration of the vitamin combination does: induce a G1/S and a G2/M block in the cell cycle, diminish DNA synthesis, increase hydrogen peroxide (H2O2) production and decrease cellular thiol levels. These effects can be prevented by the addition of catalase to scavenge the H2O2. There is a concurrent 8- to 10-fold increase in intracellular Ca2+ levels. Electrophoretic analysis of DNA reveals degradation due to the caspase-3 independent reactivation of DNase I by VK3 and DNase II by VC. Redox cycling of the vitamins is believed to increase oxidative stress until it surpasses the reducing ability of cellular thiols and induces Ca2+ release which triggers activation of Ca2+ dependent DNase and leads to degradation of DNA. Recent experiments indicate oral VC :VK3 increases the life span of tumor bearing nude mice and significantly reduces the growth rate of solid tumors without any significant toxicity by reactivating DNase I and II. Experimental animal studies indicate that autoschizis is also evident when the vitamin combination is administered to nude mice with implanted human prostate tumors. In a pilot clinical trial, end-stage prostate cancer patients given oral VC:VK3 are monitored by measuring prostate-specific antigen (PSA, a known serum marker of prostate tumor cells specific activity) and total serum homocysteine (a marker of tumor cell numbers with sensitivity for early detection of tumor cell death). The results show that the vitamin combination induces an immediate drop in tumor cell numbers, while serum PSA levels show an initial rise and a subsequent drop to below pretreatment levels. Taken together these facts suggest that the vitamin combination may offer great potential as a new antitumoral chemotherapy. The following chapter discusses the mechanisms of action employed by these vitamins to induce tumor specific death by autoschizis and examines the potential of the vitamin combination as an antitumor agent, chemosensitizer or a radiosensitizer in the treatment of prostatic neoplasms. [less ▲]

. In vitro and in vivo effect of UV-B radiation on growth of Pichia anomala strain K and Candida oleophila strain O.

Poster (2004)

In vitro and in vivo effects of salbutamol acetonide on cat airways

in Proceedings: Société Belge de Physiologie et de Pharmacologie Fondamentales et Cliniques (2005)

In vitro and in vivo evaluation of [I-123]-VEGF(165) as a potential tumor marker

in Nuclear Medicine & Biology (2005), 32(5), 431-436

One of the research challenges in oncology is to develop new biochemical methods for noninvasive tumor therapy evaluation to determine,whether the chemotherapeutics is effective. Vascular endothelial ... [more ▼]

One of the research challenges in oncology is to develop new biochemical methods for noninvasive tumor therapy evaluation to determine,whether the chemotherapeutics is effective. Vascular endothelial growth factor (VEGF) was labeled with radioiodine and evaluated in vitro as well as in vivo, using A2058, a melanoma cell line overexpressing VEGFR-1 and -2. Saturation binding analysis with [I-125]-VEGF resulted in a K-d of 0.1 nM. Internalization assays indicate the preserved ligand induced internalization and metabolization of the tracer. Biodistribution studies with [I-123]-VEGF in wild type and A2058 tumor-bearing athymic mice showed low background activity and a tumor to reference tissue ratio of maximum 6.12. These results suggest that [I-123]-VEGF is a potentially suitable tracer for tumor therapy evaluation. (c) 2005 Elsevier Inc. All rights reserved. [less ▲]

In vitro and in vivo models of varicella-zoster virus persistence in the nervous system

in Journal of Cellular Biochemistry (1988), 12C

In vitro and in vivo modulation of neurotransmitter phenotype in adult dorsal root ganglion neurons.

Conference (1990, June 16)

In vitro and in vivo modulation of neurotransmitter phenotype in adult rat DRG neurons

in Rapport annuel de la Fondation Médicale Reine Elisabeth (1990)

In Vitro And In Vivo Oncogenic Potential Of Bovine Leukemia Virus G4 Protein

in Journal of Virology (1998), 72(3),