bims-mesote 2021-12-05 papers

Issue of 2021–12–05
five papers selected by
Laura Mannarino, Humanitas Research

Bull Cancer. 2021 Nov 27. pii: S0007-4551(21)00437-9. [Epub ahead of print]

[New MAA: First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma].

Keywords: First-line; Immunotherapy; Immunothérapie; Mésothéliome pleural malin; Nivolumab plus ipilimumab; Pleural Mesothelioma; Première ligne

DOI: https://doi.org/10.1016/j.bulcan.2021.09.013

J Nippon Med Sch. 2021 Nov 26.

Cytological assessment of desmoplastic malignant pleural mesothelioma in an autopsy case.

Yoko Kawamoto, Shoko Kure, Hironori Katayama, Kiyoko Kawahara, Kiyoshi Teduka, Shinobu Kunugi, Munehiko Onda, Norio Motoda, Ryuji Ohashi.

INTRODUCTION: Desmoplastic malignant pleural mesothelioma (DMPM) is a sarcoma type mesothelioma, comprising about 5% of malignant pleural mesotheliomas. Although effusion cytology is commonly used as the primary diagnostic approach for mesothelioma, this may not be useful for DMPM due to its desmoplastic nature and bland cellular atypia. We hereby report a case of DMPM diagnosed through autopsy along with its cytological features that have not been described previously.
CASE PRESENTATION: A male in his 60s with a history of occupational asbestos exposure was referred to our hospital with right chest pain. Chest computed tomography scan showed right pleural effusion. Thirteen months later, the patient died of respiratory failure. In autopsy, the scrape-imprint smear and the pleural effusions cytology were performed. The scrape-imprint smear samples exhibited spindle cells with mild nuclear atypia and grooves with fibrous stroma. In the pleural effusion cytology, spindle cells having mild nuclear atypia and grooves with loose epithelial connections were observed. Histological examination of the right pleura showed spindle cells proliferating with dense collagen fibers, as seen in cytological samples, thus rendering the diagnosis of DMPM. Diagnosis was confirmed by fluorescence in situ hybridization.
CONCLUSION: Cytological procedures, such as pleural effusion cytology and scrape-imprinting method, may be useful as an ancillary tool in the diagnosis of rare tumors such as DMPM.

Keywords: Fluorescence in situ hybridization (FISH); autopsy; cytology; desmoplastic malignant pleural mesothelioma (DMPM); immunohistochemistry (IHC)

DOI: https://doi.org/10.1272/jnms.JNMS.2022_89-605

Ann Oncol. 2021 Nov 29. pii: S0923-7534(21)04820-1. [Epub ahead of print]

Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.

ESMO Guidelines Committee

Keywords: clinical practice guideline; diagnosis; follow-up; malignant pleural mesothelioma; treatment

DOI: https://doi.org/10.1016/j.annonc.2021.11.005

Oncol Rep. 2022 Feb;pii: 27. [Epub ahead of print]47(2):

Downregulation of lncRNA PVT1 inhibits proliferation and migration of mesothelioma cells by targeting FOXM1.

Yutaro Fujii, Vishwa Jeet Amatya, Kei Kushitani, Rui Suzuki, Yuichiro Kai, Takahiro Kambara, Yukio Takeshima.

Malignant mesothelioma is a highly aggressive tumor, and an effective strategy for its treatment is not yet available. Long non‑coding RNAs (lncRNAs) have been reported to be associated with various biological processes, including the regulation of gene expression of cancer‑related pathways. Among various lncRNAs, plasmacytoma variant translocation 1 (PVT1) acts as a tumor promoter in several human cancers, but its mechanism of action has not yet been elucidated. Increased PVT1 expression was identified in ACC‑MESO‑1, ACC‑MESO‑4, CRL‑5915, and CRL‑5946 mesothelioma cell lines. PVT1 expression was investigated in mesothelioma cell lines by reverse transcription‑quantitative polymerase chain reaction and its functional analysis by cell proliferation, cell cycle, cell migration, and cell invasion assays, as well as western blot analysis of downstream target genes. Knockdown of PVT1 expression in these cell lines by small interfering RNA transfection resulted in decreased cell proliferation and migration and increased the proportion of cells in the G2/M phase. The results of reverse transcription‑quantitative polymerase chain reaction analysis revealed that PVT1 knockdown in mesothelioma cell lines caused the downregulation of Forkhead box M1 (FOXM1) expression, while the results of western blot analysis revealed that this knockdown reduced FOXM1 expression at the protein level. In addition, combined knockdown of PVT1 and FOXM1 decreased the proliferation of mesothelioma cell lines. In conclusion, PVT1 and FOXM1 were involved in the proliferation of cancer cells. Therefore, PVT1‑FOXM1 pathways may be considered as candidate targets for the treatment of malignant mesothelioma.

Keywords: FOXM1; long non‑coding RNA; malignant mesothelioma; plasmacytoma variant translocation 1; small interfering RNA

DOI: https://doi.org/10.3892/or.2021.8238

Clin Chim Acta. 2021 Nov 26. pii: S0009-8981(21)00414-9. [Epub ahead of print]

Lipid Profiling in Malignant Mesothelioma Reveals Promising Signatures for Diagnosis and Prognosis: A Plasma-Based LC-MS Lipidomics Study.

Zhongjian Chen, Siyu Song, Chenxi Yang, Ziyi Dai, Yun Gao, Na Li, Jing Zhu, Weimin Mao, Junping Liu.

BACKGROUND AND AIM: Malignant mesothelioma (MM), being a rare and aggressive carcinoma, can barely be cured. Incidence of this cancer will keep climbing up in the next few decades since its major carcinogen, asbestos, is still in use in many countries. Unfortunately, prognosis of MM is unsatisfactory principally due to poor early diagnosis as a result of its long latency period and ambiguous symptoms. Lipids are known to contribute to cellular structure, signaling, and energy storage, and are widely reported to be related with tumorigenesis. Therefore, we aim to discover novel lipid biomarkers by plasma-based lipidomics that may improve MM diagnosis.
METHODS: Plasma samples from 25 MM patients and 32 healthy controls (HCs) were collected and analysed using a high-throughput liquid chromatography-mass spectrometry (LC-MS). Univariate and multivariate analyses were subsequently performed to visualize the separation trend between two groups and to screen for differential feature ions. Ions were annotated using LipidSearch 4.2 and their enriched pathways were detected on LIPEA. Receiver operating curves (ROC) were used for analysing each annotated lipid's diagnostic value. Survival analyses were performed to investigate each lipid's prognostic value.
RESULTS: In supervised partial least squares discriminant analysis (PLS-DA), clear separation between MM and HC groups was observed. A total of 34 differential lipids were annotated, among which 5 upregulated and 29 downregulated. Levels of plasma triacylglycerols (TGs) were higher in smoking versus non-smoking patients, and lower in female versus male patients. The top six lipids possessing highest diagnostic value included two phosphatidylethanolamines (PEs), two phosphatidylcholines (PCs) and two ceramides. Moreover, elevated circulating TG levels were associated with poorer survival, whereas increased monohexosylceramide (Hex1Cer) might be beneficial.
CONCLUSIONS: Our study revealed differentially expressed lipid patterns in MM and HC. PC, PE, and ceramides showed outstanding diagnostic performance, while TG and Hex1Cer exhibited significant prognostic values. Nevertheless, more studies should verify these trends as well as further investigating underlying mechanisms.

Keywords: LC-MS; PC; PE; TG; biomarker; ceramide; lipidomics; malignant mesothelioma

DOI: https://doi.org/10.1016/j.cca.2021.11.024