Thalidomide in Multiple Myeloma

Michel, Thomas; Hillengaß, Jens; Glasmacher, Axel; Goldschmidt, Hartmut

doi:10.2174/138920106779116919

Cited by 15 publications

(3 citation statements)

References 69 publications

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“…Accordingly, we did not observe effects of thalidomide on apoptosis or induction of cell death by thalidomide even at higher concentrations. Since being withdrawn from the market in the 1960s thalidomide has been reintroduced in 1998 and is expanding its therapeutic value in treating various diseases 50 …”

Section: Discussionmentioning

confidence: 99%

Inhibition of human prostate stromal cell growth and smooth muscle contraction by thalidomide: A novel remedy in LUTS?

et al. 2021

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Background Medical treatment in benign prostatic hyperplasia targets prostate size to prevent disease progression, complications, and surgery, and prostate smooth muscle tone for rapid relief of lower urinary tract symptoms. Combination therapies are still required to target both at once. However, current medications are insufficient, due to an unfavorable balance between side effects and efficacy. The limited efficacy of α1‐blockers may be due to nonadrenergic mediators like endothelin‐1 and thromboxane A2 (TXA2), which keep up prostate smooth muscle contraction even in the presence of α1‐blockers. Consequently, future options with higher efficacy need to target α1‐adrenergic and nonadrenergic contractions as well as stromal cell growth at once. Thalidomide has been approved as an oral medication for various diseases, including the treatment of prostate cancer. Therefore, we investigated the effect of thalidomide on cellular functions of prostate stromal cells and human prostate smooth muscle contraction. Methods Cytoskeletal organization was visualized by phalloidin staining, cell growth was assessed by 5‐ethynyl‐2ʹ‐deoxyuridine assay, cell viability by cell counting kit‐8, and apoptosis and cell death by flow cytometry in cultured prostate stromal cells (WPMY‐1). Contractions of human prostate tissues from radical prostatectomy were studied in an organ bath, where they were induced by the α1‐adrenoceptor agonists methoxamine, noradrenaline, phenylephrine, and the nonadrenergic agonists endothelin‐1, TXA2 analog U46619, or electric field stimulation (EFS). Results Thalidomide significantly reduced the proliferation of WPMY‐1 cells, which was time‐ and concentration‐dependent (10–300 µM). In parallel, organization of actin filaments collapsed after treatment with thalidomide. Thalidomide (30–100 µM) inhibited noradrenaline‐, phenylephrine‐, and methoxamine‐induced contractions, as well as nonadrenergic contractions induced by endothelin‐1 and U46619, and neurogenic contractions induced by EFS. No reduction in viability and no increases in apoptosis or in cell death were observed in WPMY‐1 cells. Conclusions Thalidomide impairs the growth of human prostate stromal cells, without showing a decrease in cell viability. In parallel, thalidomide inhibits adrenergic, neurogenic, and nonadrenergic contractions. This may be explained by a breakdown of the actin cytoskeleton. In vivo, urodynamic effects of thalidomide appear possible and may even exceed those of α1‐blockers or combination therapies.

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Section: Discussionmentioning

confidence: 99%

Inhibition of human prostate stromal cell growth and smooth muscle contraction by thalidomide: A novel remedy in LUTS?

et al. 2021

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“…Distal loss of all sensory modalities is the predominant feature, although motor involvement is usually mild. There are increasing reports of more severe neuropathy as the drug is more widely used for the treatment for myeloma [51,52].…”

Section: Other Chemotherapeutic Agentsmentioning

confidence: 99%

Chemotherapy-induced peripheral neuropathy: clinical features, diagnosis, prevention and treatment strategies

et al. 2010

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Chemotherapy-induced peripheral neuropathy (CIN) is a common toxicity of anticancer treatment and its incidence is growing. It significantly affects quality of life and is a dose-limiting factor that interferes with treatment. Its diagnosis can be established in clinical terms but some complementary tests can help when the diagnosis is difficult. There is still no proven method to prevent it that has become a standard of care in spite of the huge amount of investigation carried out in recent years. There are promising strategies that could help reduce the burden of this complication. This review will suggest an approach to the diagnosis of these disorders and provide an update on new therapies.

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“…94 Although its mechanism of action is unclear, it is an effective agent in the treatment of multiple myeloma, acute myeloid leukemia, and Kaposi's sarcoma. 95 Thalidomide has been implicated in causing bradycardia in around 50% of patients. 96 This seems to be dose-dependent and frequently occurs at the start of treatment.…”

Section: Commonly Implicated Agentsmentioning

confidence: 99%

Chemotherapy-Induced Arrhythmias

Essa

Dobson

Lip

2022

Journal of Cardiovascular Pharmacology

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:Cardio-oncology is a subspeciality within cardiology that has developed primarily as a consequence of the cardiovascular implications of cancer and its therapeutics. Arrhythmias are increasingly recognized as an adverse feature of many chemotherapeutic agents. This relationship is poorly defined and studied in the literature compared with other side effects of chemotherapy. In this review, we appraise the published literature on arrhythmogenic consequences of chemotherapeutic agents and summarize the available evidence. Atrial fibrillation (AF) and other supraventricular tachycardias are frequently observed in patients receiving chemotherapy. High rates of AF are seen with certain agents such as tyrosine kinase inhibitors eg, ibrutinib and the mechanism for this is poorly defined but likely related to off-target effects. The management of AF in cardio-oncology is similar to that of the noncancer patient with certain nuances. Mainly that bleeding and stroke risk stratification tools are not validated in the cancer population. In this patient cohort, treatment decisions are usually led by anecdotal evidence rather than an evidence base. This leads to treatment heterogeneity between clinicians. Furthermore, various drug interactions can limit the choice of therapy, particularly with respect to anticoagulant drugs. Many chemotherapeutic agents have been implicated in QT interval (A Measurement calculated from the start of the Q wave to the end of the T wave on the electrocardiogram approximating the time taken for ventricular relaxation.) of these, arsenic trioxide and several tyrosine kinase inhibitors are classic culprits. In patients receiving these agents, it is advisable to perform a baseline electrocardiogram and monitor the QT interval. If the (QT interval corrected for heart rate) increases by 60 milliseconds from baseline or is greater than 500 milliseconds, it is advisable to suspend treatment temporarily. Moving forward, further trials are required in the field of cardio-oncology to better understand the relationship between chemotherapeutic agents and arrhythmia.

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Thalidomide in Multiple Myeloma

Cited by 15 publications

References 69 publications

Inhibition of human prostate stromal cell growth and smooth muscle contraction by thalidomide: A novel remedy in LUTS?

Inhibition of human prostate stromal cell growth and smooth muscle contraction by thalidomide: A novel remedy in LUTS?

Chemotherapy-induced peripheral neuropathy: clinical features, diagnosis, prevention and treatment strategies

Chemotherapy-Induced Arrhythmias

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