HPMA copolymer platinates as novel antitumour agents: in vitro properties, pharmacokinetics and antitumour activity in vivo

1999 ◽  
Vol 35 (6) ◽  
pp. 994-1002 ◽  
Author(s):  
E Gianasi ◽  
M Wasil ◽  
E.G Evagorou ◽  
A Keddle ◽  
G Wilson ◽  
...  
Keyword(s):  
Antitumour Activity ◽  
Hpma Copolymer ◽  
Antitumour Agents

The In Vitro and In Vivo Antitumour Activities of Nitrosyl Ruthenium Amine Complexes

2012 ◽  
Vol 65 (9) ◽  
pp. 1333 ◽  
Author(s):  
Renata Z. Osti ◽  
Fabiana A. Serrano ◽  
Thaysa Paschoalin ◽  
Mariana H. S. Massaoka ◽  
Luiz R. Travassos ◽  
...  
Keyword(s):  
Antitumour Activity ◽  
Ruthenium Complexes ◽  
Morphological Alterations ◽  
Antitumour Agents ◽  
Murine Melanoma ◽  
Human Tumour Cells ◽  
Ruthenium Compounds ◽  
Ic50 Values

Ruthenium compounds of the type trans-[Ru(NO)(NH3)4(L)]X3, L = N-heterocyclic ligands, P(OEt)3, SO32–, X = BF4– or PF6–, or [Ru(NO)Hedta], were tested for antitumour activity in vitro against murine melanoma and human tumour cells. The ruthenium complexes induced DNA fragmentation and morphological alterations suggestive of necrotic tumour cell death. The calculated IC50 values were lower than 100 μM. Complexes for which L = isn or imN were partially effective in vivo in a syngeneic model of murine melanoma B16F10, increasing animal survival. In addition, the same ruthenium complexes effectively inhibited angiogenesis of HUVEC cells in vitro. The results suggest that these nitrosyl complexes are a promising platform to be explored for the development of novel antitumour agents.

scholarly journals A New Smoothened Antagonist Bearing the Purine Scaffold Shows Antitumour Activity In Vitro and In Vivo

2021 ◽  
Vol 22 (16) ◽  
pp. 8372
Author(s):  
Ana María Zárate ◽  
Christian Espinosa-Bustos ◽  
Simón Guerrero ◽  
Angélica Fierro ◽  
Felipe Oyarzún-Ampuero ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Human Cancer ◽  
Antitumour Activity ◽  
Anticancer Compounds ◽  
Human Cancer Cells ◽  
Cycle Arrest ◽  
Apoptosis Inducer ◽  
Purine Ring

The Smoothened (SMO) receptor is the most druggable target in the Hedgehog (HH) pathway for anticancer compounds. However, SMO antagonists such as vismodegib rapidly develop drug resistance. In this study, new SMO antagonists having the versatile purine ring as a scaffold were designed, synthesised, and biologically tested to provide an insight to their mechanism of action. Compound 4s was the most active and the best inhibitor of cell growth and selectively cytotoxic to cancer cells. 4s induced cell cycle arrest, apoptosis, a reduction in colony formation and downregulation of PTCH and GLI1 expression. BODIPY-cyclopamine displacement assays confirmed 4s is a SMO antagonist. In vivo, 4s strongly inhibited tumour relapse and metastasis of melanoma cells in mice. In vitro, 4s was more efficient than vismodegib to induce apoptosis in human cancer cells and that might be attributed to its dual ability to function as a SMO antagonist and apoptosis inducer.

scholarly journals Overcoming multidrug-resistance in vitro and in vivo using the novel P-glycoprotein inhibitor 1416

2012 ◽  
Vol 32 (6) ◽  
pp. 559-566 ◽  
Author(s):  
Yan Xu ◽  
Feng Zhi ◽  
Guangming Xu ◽  
Xiaolei Tang ◽  
Sheng Lu ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Cancer Chemotherapy ◽  
Antitumour Activity ◽  
Multidrug Resistant ◽  
The Novel ◽  
Mice Model ◽  
P Glycoprotein ◽  
Channel Currents

MDR (multidrug-resistance) represents a major obstacle to successful cancer chemotherapy and is usually accomplished by overexpression of P-gp (P-glycoprotein). Much effort has been devoted to developing P-gp inhibitors to modulate MDR. However, none of the inhibitors on the market have been successful. 1416 [1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenylethylamino)propane hydrochloride (phenoprolamine hydrochloride)] is a new VER (verapamil) analogue with a higher IC50 for blocking calcium channel currents than VER. In the present paper, we examined the inhibition effect of 1416 on P-gp both in vitro and in vivo. 1416 significantly enhanced cytotoxicity of VBL (vinblastine) in P-gp-overexpressed human multidrug-resistant K562/ADM (adriamycin) and KBV cells, but had no such effect on the parent K562 and KB cells. The MDR-modulating function of 1416 was further confirmed by increasing intracellular Rh123 (rhodanmine123) content in MDR cells. Human K562/ADM xenograft-nude mice model verified that 1416 potentiates the antitumour activity of VBL in vivo. RT-PCR (reverse transcriptase-PCR) and FACS analysis demonstrated that the expression of MDR1/P-gp was not affected by 1416 treatment. All these observations suggest that 1416 could be a promising agent for overcoming MDR in cancer chemotherapy.

scholarly journals BET bromodomain inhibitor birabresib in mantle cell lymphoma: in vivo activity and identification of novel combinations to overcome adaptive resistance

ESMO Open ◽  
2018 ◽  
Vol 3 (6) ◽  
pp. e000387 ◽  
Author(s):  
Chiara Tarantelli ◽  
Elena Bernasconi ◽  
Eugenio Gaudio ◽  
Luciano Cascione ◽  
Valentina Restelli ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lines ◽  
Cell Lymphoma ◽  
Antitumour Activity ◽  
Single Agent ◽  
Treatment Strategies ◽  
Bet Inhibitor ◽  
Mantle Cell

BackgroundThe outcome of patients affected by mantle cell lymphoma (MCL) has improved in recent years, but there is still a need for novel treatment strategies for these patients. Human cancers, including MCL, present recurrent alterations in genes that encode transcription machinery proteins and of proteins involved in regulating chromatin structure, providing the rationale to pharmacologically target epigenetic proteins. The Bromodomain and Extra Terminal domain (BET) family proteins act as transcriptional regulators of key signalling pathways including those sustaining cell viability. Birabresib (MK-8628/OTX015) has shown antitumour activity in different preclinical models and has been the first BET inhibitor to successfully undergo early clinical trials.Materials and methodsThe activity of birabresib as a single agent and in combination, as well as its mechanism of action was studied in MCL cell lines.ResultsBirabresib showed in vitro and in vivo activities, which appeared mediated via downregulation of MYC targets, cell cycle and NFKB pathway genes and were independent of direct downregulation of CCND1. Additionally, the combination of birabresib with other targeted agents (especially pomalidomide, or inhibitors of BTK, mTOR and ATR) was beneficial in MCL cell lines.ConclusionOur data provide the rationale to evaluate birabresib in patients affected by MCL.

Mechanism of Action of the Antitumour Effect of K18

1989 ◽  
Vol 17 (2) ◽  
pp. 132-140
Author(s):  
T. Fujii ◽  
K. Niimura ◽  
T. Furusho ◽  
N. Sugita ◽  
M. Oikawa ◽  
...  
Keyword(s):  
Nude Mice ◽  
Immunoglobulin G ◽  
Antitumour Activity ◽  
Inhibitory Effect ◽  
Human Lung Cancer ◽  
Covalently Bonded ◽  
Human Lung Cancer Cells ◽  
Rpmi 8226

K18 is an anticancer drug for oral administration comprising about five molecules of melphalan, an alkylating drug, covalently bonded to human immunoglobulin G. This study measured the in vitro antitumour activity of K18, melphalan and immunoglobulin G on human myeloma cells (RPMI-8226) and the in vivo antitumour effects of K18 and melphalan in BALB/c nude mice bearing human lung cancer cells (LC-10). The relative tumour-inhibitory effect, in vitro, was found to be: immunoglobulin G <K18 <melphalan. This activity of K18 was about half the theoretical value indicating that melphalan molecules are not released easily from the conjugate. K18 showed strong antitumour activity in vivo which continued after stopping administration. On the other hand, the effects of melphalan did not continue after administration was stopped. The distribution of [125I]K18 and [14C]melphalan was examined in BALB/c nude mice 14 days after implantation of LC-10 cells. Radioactivity levels in the major organs showed a transient rapid increase followed by a gradual decline. In tumours, [14C]melphalan levels increased transiently and then decreased, whereas [125I]K18 levels persisted following intravenous administration.

Antitumour activity of S-p-bromobenzylglutathione cyclopentyl diester in vitro and in vivo

1996 ◽  
Vol 51 (10) ◽  
pp. 1365-1372 ◽  
Author(s):  
Paul J. Thornalley ◽  
Linda G. Edwards ◽  
Yubin Kang ◽  
Catherine Wyatt ◽  
Nathan Davies ◽  
...  
Keyword(s):  
Antitumour Activity

Iminoethers as Carrier Ligands: A Novel trans-Platinum Complex Possessing in Vitro and in Vivo Antitumour Activity

1996 ◽  
pp. 27-35 ◽  
Author(s):  
Mauro Coluccia ◽  
Maria A. Mariggiò ◽  
Angela Boccarelli ◽  
Francesco Loseto ◽  
Nicola Cardellicchio ◽  
...  
Keyword(s):  
Antitumour Activity ◽  
Platinum Complex

scholarly journals IgE Antibodies against Cancer: Efficacy and Safety

Antibodies ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 55
Author(s):  
Jitesh Chauhan ◽  
Alex J. McCraw ◽  
Mano Nakamura ◽  
Gabriel Osborn ◽  
Heng Sheng Sow ◽  
...  
Keyword(s):  
Perceived Risk ◽  
Immunoglobulin E ◽  
Ex Vivo ◽  
Risk Mitigation ◽  
Antitumour Activity ◽  
Allergic Diseases ◽  
Type I ◽  
Ige Antibodies

Immunoglobulin E (IgE) antibodies are well known for their role in allergic diseases and for contributions to antiparasitic immune responses. Properties of this antibody class that mediate powerful effector functions may be redirected for the treatment of solid tumours. This has led to the rise of a new class of therapeutic antibodies to complement the armamentarium of approved tumour targeting antibodies, which to date are all IgG class. The perceived risk of type I hypersensitivity reactions following administration of IgE has necessitated particular consideration in the development of these therapeutic agents. Here, we bring together the properties of IgE antibodies pivotal to the hypothesis for superior antitumour activity compared to IgG, observations of in vitro and in vivo efficacy and mechanisms of action, and a focus on the safety considerations for this novel class of therapeutic agent. These include in vitro studies of potential hypersensitivity, selection of and observations from appropriate in vivo animal models and possible implications of the high degree of glycosylation of IgE. We also discuss the use of ex vivo predictive and monitoring clinical tools, as well as the risk mitigation steps employed in, and the preliminary outcomes from, the first-in-human clinical trial of a candidate anticancer IgE therapeutic.

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