Search results for " Antitumor"
showing 10 items of 416 documents
HSPH1 inhibition downregulates Bcl-6 and c-Myc and hampers the growth of human aggressive B-cell non-Hodgkin lymphoma
2015
We have shown that human B-cell non-Hodgkin lymphomas (B-NHLs) express heat shock protein (HSP)H1/105 in function of their aggressiveness. Here, we now clarify its role as a functional B-NHL target by testing the hypothesis that it promotes the stabilization of key lymphoma oncoproteins. HSPH1 silencing in 4 models of aggressive B-NHLs was paralleled by Bcl-6 and c-Myc downregulation. In vitro and in vivo analysis of HSPH1-silenced Namalwa cells showed that this effect was associated with a significant growth delay and the loss of tumorigenicity when 10(4) cells were injected into mice. Interestingly, we found that HSPH1 physically interacts with c-Myc and Bcl-6 in both Namalwa cells and pr…
An update on the xenograft and mouse models suitable for investigating new therapeutic compounds for the treatment of B-cell malignancies
2008
B-cell malignancies account for over the 90% of all lymphoid neoplasms. The clonal proliferations of B-cells show a high degree of variation in terms of clinical and presenting features, histopathology, immuophenotype, and genetics. Primary tumor samples are useful for examining the characteristics of a patients own tumor, although both primary leukemic cells and cell lines provide an initial step for screening novel compounds for their activity in some hematological malignancies, they should be followed by models in intact animals. In this review, we try to summarize the animal models generated to study B-cell malignancies, in particular, B-cell lymphoma, B-cell CLL and MM that represent t…
Evaluation and clinical analyses of downstream targets of the Akt inhibitor GDC-0068.
2013
Abstract Purpose: The oncogenic PI3K/Akt/mTOR pathway is an attractive therapeutic target in cancer. However, it is unknown whether the pathway blockade required for tumor growth inhibition is clinically achievable. Therefore, we conducted pharmacodynamic studies with GDC-0068, an ATP competitive, selective Akt1/2/3 inhibitor, in preclinical models and in patients treated with this compound. Experimental Design: We used a reverse phase protein array (RPPA) platform to identify a biomarker set indicative of Akt inhibition in cell lines and human-tumor xenografts, and correlated the degree of pathway inhibition with antitumor activity. Akt pathway activity was measured using this biomarker se…
Emerging Raf inhibitors
2009
The Raf/MAPK kinase/extracellular-signal-regulated kinase pathway is often activated by genetic alterations in upstream signaling molecules. An integral component of this pathway, BRAF, is also activated by mutation, especially in melanoma and thyroid cancers. The Raf/MAPK kinase/extracellular-signal-regulated kinase pathway has profound effects on proliferative, apoptotic and differentiation pathways as well as the sensitivity and resistance to chemotherapeutic drugs.This review discusses targeting of Raf which could control abnormal proliferation in cancer and other proliferative diseases. The important roles that genetics plays in the response of patients to Raf inhibitors is also evalua…
Sodium butyrate with UCN-01 has marked antitumour activity against cervical cancer cells.
2010
The effect of combining sodium butyrate (NaB), a histone deacetylase inhibitor, and 7-hydroxy-staurosporine (UCN-01) on cytotoxicity in human cervical carcinoma cells was evaluated.HeLa and CaSki cells were treated using NaB alone or in combination with staurosporine (STS) or its analog UCN-01. Cytotoxicity was determined by flow cytometry and morphological assays. Apoptotic pathways were characterized by Western blotting and immunostaining. CaSki cells were also xenografted into nude mice to assess the in vivo effects of NaB/UCN-01 combination.Treatment with NaB and STS or UCN-01 resulted in enhanced apoptosis of cancer cells. Apoptosis involved mitochondrial pathways and overexpression of…
Use of CDC2 from etoposide-treated cells as substrate to assay CDC25 phosphatase activity
1999
International audience; Cyclin-dependent kinases (CDKs) regulate the key transition of the cell cycle in all organisms. In response to Etoposide (VP-16) induced DNA damage, cells undergo a G2-phase arrest resulting in the accumulation of inactive CDK1 (CDC2) kinase complexes. Here we report that upon Etoposide treatment CDC2 is phosphorylated on tyrosine 15 and is dephosphorylated and activated in vitro by recombinant CDC25 phosphatase. We also show that inactive CDC2 kinase from Etoposide-treated cells can be used as a substrate in a sensitive two-step assay of CDC25 phosphatase. This assay, which is very simple to set-up, is based on the monitoring of CDC2 kinase activity after CDC25-depe…
The cytotoxic properties of Natural Coumarins Isolated from roots of Ferulago campestris (Apiaceae) and of synthetic ester derivatives aegelinol
2010
Grandivittin (1), agasyllin (2), aegelinol benzoate (3) and felamidin (20), four natural coumarins isolated from Ferulago campestris, and several synthetic ester derivatives of aegelinol (4) were tested against four tumor cell lines. Some of them were shown to be marginally cytotoxic against the A549 lung cancer cell line.
Acid rearrangment of epoxy-germacranolides and absolute configuration of 1beta, 10alpha-epoxy-salonitenolide
2010
The acid-catalyzed cyclization of mono epoxides of cnicin acetonide (3) was investigated. Several 6,12-eudesmanolides were obtained, and their stereochemistry established by extensive spectroscopic analyses. Chemical correlations also led to the assignment of the absolute configuration of 1beta,10alpha-epoxy-salonitenolide (13), a previously isolated natural product. The cytotoxic activities of some compounds were determined against A549 and MCF-7 tumor cell lines. The esterified germacranolides 2-6 were selectively cytotoxic against the MCF-7 breast cancer cell line.
Synthesis and Anti-Tumor Activity of Novel Aminomethylated Derivatives of Isoliquiritigenin
2014
A series of new aminomethylated derivatives of isoliquiritigenin was synthesized. The structures of the compounds were confirmed by IR, MS, NMR, 13C-NMR and elemental analyses. Cytotoxic activities of these derivatives towards the human prostatic cell line PC-3, human mammary cancer cell line MCF-7 and human oophoroma cell line HO-8910 in vitro were tested. The IC50 values showed cytotoxic activities of some of these new derivatives were relatively strong. Furthermore, tumor growth inhibition in vivo of aminomethylated derivatives of isoliquiritigenin 15 was superior to that of isoliquritigenin and reached inhibition rates of 71.68%. The detailed synthesis, spectroscopic data, biological an…
A New Cacospongionolide Inhibitor of Human Secretory Phospholipase A2 from the Tyrrhenian Sponge Fasciospongia cavernosa and Absolute Configuration o…
1998
A new inhibitor of human secretory phospholipase A2 (PLA2), cacospongionolide E (4a), has been isolated from the Tyrrhenian sponge Fasciospongia cavernosa. The structure was proposed on the basis of spectroscopic data and by chemical transformations. The absolute configuration of cacospongionolides 2a-4a was established using the modified Mosher's method. Cacospongionolide E was the most potent inhibitor toward human synovial PLA2, showing higher potency than the reference compound manoalide and exerting no signs of toxicity on human neutrophils. It showed high activity in the Artemia salina bioassay and moderate toxicity in the fish (Gambusia affinis) lethality assay.