Effect of thalidomide on bone marrow angiogenesis in multiple myeloma patients

Cury, Priscilla; Higashi, Fabiana; Zacchi, Flávia Fernandes Silva; Palhares, Renata Bacic; Quero, Adriana Alvares; Dias, Ana Luiza Miranda Silva; Crusoé, Edvan; Hungria, Vânia

doi:10.1016/j.htct.2019.04.006

Cited by 6 publications

(6 citation statements)

References 16 publications

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“…The microvessel density (MVD) proliferation was evaluated by measuring the average number of CD31 positive-stained endothelial cells. Paraffin sections with 4 µm thickness from the tongue of mice at the muscular phase (Groups B1–B10) were mounted on electrically positive charged glass slides for the further immune staining procedure according to Cury et al ( 2020 ) and Rayia et al ( 2022 ) using CD31 monoclonal antibody (Cell Marque, Rocklin, CA, USA; clone JC70, mouse monoclonal) at 1:100 dilutions. Standard negative and positive control sections were used.…”

Section: Methodsmentioning

confidence: 99%

Impact of atorvastatin and mesenchymal stem cells combined with ivermectin on murine trichinellosis

Hassan,

El-Sayed,

Zekry

et al. 2023

Parasitol Res

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Trichinellosis is one of the global food-borne parasitic diseases that can cause severe tissue damage. The traditionally used drugs for the treatment of trichinellosis have limited efficacy against the encysted larvae in the muscular phase of the disease. Therefore, this study aimed to evaluate the role of atorvastatin and mesenchymal stem cells combined with ivermectin against different phases of Trichinella in experimentally infected mice. A total of 120 male Swiss albino mice were divided into two major groups (n = 60 of each), intestinal and muscular phases. Then, each group was subdivided into 10 subgroups (n = 6); non-infected control, infected non-treated control, infected ivermectin treated, infected atorvastatin treated, infected mesenchymal stem cells treated, infected combined ivermectin and atorvastatin treated, infected combined mesenchymal stem cells and ivermectin treated, infected combined mesenchymal stem cells and atorvastatin treated, infected combined mesenchymal stem cells and a full dose of (ivermectin and atorvastatin) treated, and infected combined mesenchymal stem cells and half dose of (ivermectin and atorvastatin) treated. Mice were sacrificed at days 5 and 35 post-infection for the intestinal and muscular phases, respectively. The assessment was performed through many parameters, including counting the adult intestinal worms and muscular encysted larvae, besides histopathological examination of the underlying tissues. Moreover, a biochemical assay for the inflammatory and oxidative stress marker levels was conducted. In addition, levels of immunohistochemical CD31 and VEGF gene expression as markers of angiogenesis during the muscular phase were investigated. The combined mesenchymal stem cells and atorvastatin added to ivermectin showed the highest significant reduction in adult worms and encysted larvae counts, the most noticeable improvement of the histopathological changes, the most potent anti-inflammatory (lowest level of IL-17) and anti-angiogenic (lowest expression of CD31 and VEGF) activities, and also revealed the highly effective one to relieve the oxidative stress (lowest level of SOD, GSH, and lipid peroxidase enzymes). These observed outcomes indicate that adding mesenchymal stem cells and atorvastatin to ivermectin synergistically potentiates its therapeutic efficacy and provides a promising candidate against trichinellosis.

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Section: Methodsmentioning

confidence: 99%

Impact of atorvastatin and mesenchymal stem cells combined with ivermectin on murine trichinellosis

Hassan,

El-Sayed,

Zekry

et al. 2023

Parasitol Res

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“…Some authors showed that BM MVD is significantly reduced in responder patients treated with thalidomide alone or in combination with dexamethasone [ 83 , 84 ], without affecting serum levels of angiogenic cytokines [ 84 ]. By contrast, Cury and collaborators [ 85 ] did not find any decrease in BM angiogenesis in patients treated with thalidomide [ 85 ]. Similarly, immunohistochemistry analysis of patients’ BM biopsies after treatment with different anti-MM drugs including thalidomide and lenalidomide did not display any significant difference in MVD between responders and non-responders [ 86 ].…”

Section: Anti-angiogenic Drugs In MMmentioning

confidence: 99%

Anti-Angiogenic Activity of Drugs in Multiple Myeloma

Saltarella

Altamura

Campanale

et al. 2023

Cancers

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Angiogenesis represents a pivotal hallmark of multiple myeloma (MM) that correlates to patients’ prognosis, overall survival, and drug resistance. Hence, several anti-angiogenic drugs that directly target angiogenic cytokines (i.e., monoclonal antibodies, recombinant molecules) or their cognate receptors (i.e., tyrosine kinase inhibitors) have been developed. Additionally, many standard antimyeloma drugs currently used in clinical practice (i.e., immunomodulatory drugs, bisphosphonates, proteasome inhibitors, alkylating agents, glucocorticoids) show anti-angiogenic effects further supporting the importance of inhibiting angiogenesis from potentiating the antimyeloma activity. Here, we review the most important anti-angiogenic therapies used for the management of MM patients with a particular focus on their pharmacological profile and on their anti-angiogenic effect in vitro and in vivo. Despite the promising perspective, the direct targeting of angiogenic cytokines/receptors did not show a great efficacy in MM patients, suggesting the need to a deeper knowledge of the BM angiogenic niche for the design of novel multi-targeting anti-angiogenic therapies.

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“…[ 16 ] In addition, it had a promising activity in patients with multiple myeloma. [ 17 ] It has also been shown to have strong anti‐inflammatory and immunomodulatory properties. [ 18 ]…”

Section: Introductionmentioning

confidence: 99%

“…[16] In addition, it had a promising activity in patients with multiple myeloma. [17] It has also been shown to have strong anti-inflammatory and immunomodulatory properties. [18] Since then, a lot of research has been done to better understand how thalidomide works in the treatment of cancer, lupus, and multiple myeloma.…”

mentioning

confidence: 99%

Novel promising benzoxazole/benzothiazole‐derived immunomodulatory agents: Design, synthesis, anticancer evaluation, and in silico ADMET analysis

Elkady

El‐Adl

Sakr

et al. 2023

Archiv der Pharmazie

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Eleven novel benzoxazole/benzothiazole‐based thalidomide analogs were designed and synthesized to obtain new effective antitumor immunomodulatory agents. The synthesized compounds were evaluated for their cytotoxic activities against HepG‐2, HCT‐116, PC3, and MCF‐7 cells. Generally, the open analogs with semicarbazide and thiosemicarbazide moieties (10, 13a–c, 14, and 17a,b) exhibited higher cytotoxic activities than derivatives with closed glutarimide moiety (8a–d). In particular, compound 13a (IC50 = 6.14, 5.79, 10.26, and 4.71 µM against HepG‐2, HCT‐116, PC3, and MCF‐7, respectively) and 14 (IC50 = 7.93, 8.23, 12.37, and 5.43 µM, respectively) exhibited the highest anticancer activities against the four tested cell lines. The most active compounds 13a and 14 were further evaluated for their in vitro immunomodulatory activities on tumor necrosis factor‐alpha (TNF‐α), caspase‐8 (CASP8), vascular endothelial growth factor (VEGF), and nuclear factor kappa‐B p65 (NF‐κB p65) in HCT‐116 cells. Compounds 13a and 14 showed a remarkable and significant reduction in TNF‐α. Furthermore, they showed significant elevation in CASP8 levels. Also, they significantly inhibited VEGF. In addition, compound 13a showed significant decreases in the level of NF‐κB p65 while compound 14 demonstrated an insignificant decrease with respect to thalidomide. Moreover, our derivatives exhibited good in silico absorption, distribution, metabolism, elimination, toxicity (ADMET) profiles.

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Effect of thalidomide on bone marrow angiogenesis in multiple myeloma patients

Cited by 6 publications

References 16 publications

Impact of atorvastatin and mesenchymal stem cells combined with ivermectin on murine trichinellosis

Impact of atorvastatin and mesenchymal stem cells combined with ivermectin on murine trichinellosis

Anti-Angiogenic Activity of Drugs in Multiple Myeloma

Novel promising benzoxazole/benzothiazole‐derived immunomodulatory agents: Design, synthesis, anticancer evaluation, and in silico ADMET analysis

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