Overview of the biochemical and genetic processes in malignant mesothelioma

Abstract

Malignant mesothelioma (MM) is a highly aggressive form of cancer, has a long latency period, and is resistant to chemotherapy. It is extremely fatal, with a mean survival of less than one year. The development of MM is strongly correlated with exposure to asbestos and erionite, as well as to simian virus 40. Although various countries have banned the use of asbestos, MM has proven to be difficult to control and there appears to be a trend toward an increase in its incidence in the years to come. In Brazil, MM has not been widely studied from a genetic or biochemical standpoint. In addition, there have been few epidemiological studies of the disease, and the profile of its incidence has yet to be well established in the Brazilian population. The objective of this study was to review the literature regarding the processes of malignant transformation, as well as the respective mechanisms of tumorigenesis, in MM.

Possible repurposing of pyrvinium pamoate for the treatment of mesothelioma: A pre‐clinical assessment

“…Indeed, at doses of 35 mg/kg, pyrvinium pamoate is safe and without systemic side effects (Smith, Kinkel, Gryczko, & Goulet, ). Considering the previously established inhibitory effect of pyrvinium pamoate on the Wnt/β‐catenin pathway and given the role of this pathway in MM development and resistance to therapies (de Assis & Isoldi, ; Fox et al, ; He et al, ; Perumal et al, ), in this study we explored, for the first time, the effects of pyrvinium pamoate on MM cells. We observed that this compound efficiently inhibited the proliferation of a panel of MM cell lines and reduced MM cell ability both to migrate and to grow as multicellular spheroids under nonadherent conditions.…”

“…The most studied mechanisms of action include the inhibition of the Wnt signaling pathway (Polosukhina et al, ; Wiegering et al, ; Xu et al, ; Zhang, Zhang, Zhang, Wang, & Hu, ), the suppression of mitochondrial respiration (Harada, Ishii, Hatake, & Kasahara, ; Ishii, Harada, & Kasahara, ; Xiang et al, ; Xiao, Zhang, Zhou, Rajoria, & Wang, ), the inhibition of the PI3K/AKT/P70S6K pathway (Carrella et al, ; Venerando, Girardi, Ruzzene, & Pinna, ), the targeting of the androgen receptor (AR)/androgen axis (Jones et al, ; Lim et al, ) and the suppression of tumor‐sphere formation (Xu et al, ). Increasing interest in the role of the Wnt pathway in MM carcinogenesis and resistance to conventional therapies (de Assis & Isoldi, ; Fox et al, ; He et al, ; Perumal, Dharmarajan, & Fox, ) prompted us to investigate the potential anti‐tumor activity of pyrvinium pamoate in MM cell lines. In particular, we analyzed the effects of pyrvinium pamoate on cell proliferation, clonogenic potential, migration, and multicellular tumor spheroid formation.…”

ALK gene expression status in pleural effusion predicts tumor responsiveness to crizotinib in Chinese patients with lung adenocarcinoma

“…Metastatic tumors from lung, breast, gastrointestinal and ovarian cancers, and MPM are the most common tumors of pleural membranes and the major causes of MPE (21,22). The diagnosis of lung adenocarcinoma in MPE has been discussed in the literature (23,24).…”

<b> O adoecimento por mesotelioma na perspectiva do familiar cuidador / The mesothelioma disease in the perspective of the family caregiver

“…Para preservar o anonimato dos participantes foi utilizada a palavra "familiar" seguida de algarismos arábicos crescentes, conforme a inclusão no estudo. Alguns tipos de câncer podem demorar para serem diagnosticados, assim como no caso do mesotelioma, onde os sinais e sintomas iniciais não mostram claramente a gravidade da doença (1) . Tampouco foi possível relacionar com o câncer inicialmente, pois os referidos sintomas podem estar relacionados a uma série de desvios de saúde.…”

“…O mesotelioma é um tipo de câncer que apresenta poucas perspectivas de cura. Ocorre com o comprometimento das células mesoteliais, camada que reveste o pulmão, peritônio, pericárdio e túnica vaginal de testículo (1) . Este câncer tem características peculiares, como dificuldade da obtenção do diagnóstico precoce, agressividade tumoral, manejo terapêutico limitado, baixa sobrevida e qualidade de vida limitante após confirmação do diagnóstico (2) .…”