Novel insights into mesothelioma biology and implications for therapy

Yap, Timothy A.; Aerts, Joachim G.J.V.; Popat, Sanjay; Fennell, Dean A.

doi:10.1038/nrc.2017.42

Nat Rev Cancer

2017

DOI: 10.1038/nrc.2017.42

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Novel insights into mesothelioma biology and implications for therapy

Timothy A. Yap

¹

,

Joachim G.J.V. Aerts

²

,

Sanjay Popat

³

et al.

Abstract: Malignant mesothelioma is a universally lethal cancer that is increasing in incidence worldwide. There is a dearth of effective therapies, with only one treatment (pemetrexed and cisplatin combination chemotherapy) approved in the past 13 years. However, the past 5 years have witnessed an exponential growth in our understanding of mesothelioma pathobiology, which is set to revolutionize therapeutic strategies. From a genomic standpoint, mesothelioma is characterized by a preponderance of tumour suppressor alte… Show more

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Cited by 334 publications

(342 citation statements)

References 158 publications

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“…Again, Trp53 loss was not causative, but likely potentiated the effusion‐promoting effects of KRAS , which we recently identified in metastatic effusions (Agalioti et al , 2017). Taken together with published work, our findings functionally validate the role of TP53 mutations in human MPM in driving biphasic histology, tumor progression and metastasis, and poor survival (Bueno et al , 2016; Yap et al , 2017). Hence, TP53‐targeted therapies may be prioritized for biphasic MPM when available (Brown et al , 2009).…”

Section: Discussionsupporting

confidence: 86%

KRAS signaling in malignant pleural mesothelioma

Marazioti

¹

,

Krontira

²

,

Behrend

³

et al. 2021

Get access via publisher Add to collection Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

“…Again, Trp53 loss was not causative, but likely potentiated the effusion‐promoting effects of KRAS , which we recently identified in metastatic effusions (Agalioti et al , 2017). Taken together with published work, our findings functionally validate the role of TP53 mutations in human MPM in driving biphasic histology, tumor progression and metastasis, and poor survival (Bueno et al , 2016; Yap et al , 2017). Hence, TP53‐targeted therapies may be prioritized for biphasic MPM when available (Brown et al , 2009).…”

Section: Discussionsupporting

confidence: 86%

KRAS signaling in malignant pleural mesothelioma

Marazioti

¹

,

Krontira

²

,

Behrend

³

et al. 2021

Get access via publisher Add to collection Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

“…This is in agreement with reduced VEGF levels in myeloma tumors treated with the heparanase inhibitor Roneparstat (SST0001) (14) and the involvement of heparanase in VEGF gene regulation (36). These results are important because they echo recent data showing that the addition of anti-VEGF monoclonal antibody (bevacizumab; Avastin) to pemetrexed and cisplatin chemotherapy improved survival, probably by targeting the tumor vasculature (24,37), which plays an important role in the progression of mesothelioma (38). Moreover, tumor cells were often detected in blood vessels of control mice but not in PG545treated tumor vessels or tumors developed in heparanase-KO mice.…”

Section: Discussionsupporting

confidence: 77%

Involvement of Heparanase in the Pathogenesis of Mesothelioma: Basic Aspects and Clinical Applications

Barash¹,

Lapidot

²

,

Zohar

³

et al. 2018

Jnci Journal of the National Cancer Institute

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Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

“…In the latter, BAP1 inactivation occurs in ~60-80% and 70-85% of pleural and peritoneal MM, respectively, 27,28 while CDKN2A alterations are present in 50-100% of cases. 1 We corroborated the molecular differences in testicular cases with MTAP and BAP1 IHC, which, unlike pleural and peritoneal MM, showed infrequent loss of expression (17 and 22%, respectively). Overall, loss of MTAP or BAP1 expression occurred in non-overlapping tumours (i.e.…”

Section: Discussionsupporting

confidence: 73%

“…However, we found the frequency of alterations in CDKN2A (44%) and BAP1 (29%) to be lower in the testis than in mesotheliomas at other sites. In the latter, BAP1 inactivation occurs in ~60–80% and 70–85% of pleural and peritoneal MM, respectively, 27,28 while CDKN2A alterations are present in 50–100% of cases 1 . We corroborated the molecular differences in testicular cases with MTAP and BAP1 IHC, which, unlike pleural and peritoneal MM, showed infrequent loss of expression (17 and 22%, respectively).…”

Section: Discussionsupporting

confidence: 70%

Molecular and immunohistochemical characterisation of mesothelioma of the tunica vaginalis^*

Anderson

¹

,

Sholl

²

,

Fletcher

³

et al. 2022

Get access via publisher Add to collection Cite

Exaggerated anticipatory anxiety is common in social anxiety disorder (SAD). Neuroimaging studies have revealed altered neural activity in response to social stimuli in SAD, but fewer studies have examined neural activity during anticipation of feared social stimuli in SAD. The current study examined the time course and magnitude of activity in threat processing brain regions during speech anticipation in socially anxious individuals and healthy controls (HC). Method Participants (SAD n = 58; HC n = 16) underwent functional magnetic resonance imaging (fMRI) during which they completed a 90s control anticipation task and 90s speech anticipation task.

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