MMP7 Modulation by Short- and Long-term Radiotherapy in Patients with Rectal Cancer

Stene, Christina; Polistena, Andrea; Gaber, Alexander; Nodin, Björn; Ottochian, Bianca; Adawi, Diya; Avenia, Nicola; Jirström, Karin; Johnson, Louis Banka

doi:10.21873/invivo.11215

Cited by 6 publications

(6 citation statements)

References 37 publications

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“…Clinically, short‐term and long‐term regimes are widely used in the radiotherapy 15 . Taking colorectal cancer as an example, preoperative short‐term irradiation of 5 Gy × 5 for 1 week is applied before surgery to treat resectable rectal cancer, and long‐term irradiation of 1.8 Gy × 28 for 5 weeks is used to downsize locally advanced tumours 16 . As the enhancement of viral infection occurred in a dose‐dependent manner, a long‐term regimen in which cumulative radiation is delivered in lower doses may be more instrumental than short‐term irradiation for avoiding COVID‐19.…”

Section: Resultsmentioning

confidence: 99%

Irradiation accelerates SARS‐CoV‐2 infection by enhancing sphingolipid metabolism

Wei

Jiang

Zhao

et al. 2022

Journal of Medical Virology

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Cancer patients who receive radiotherapy have a high risk of severe acute respiratory syndrome‐coronavirus‐2 (SARS‐CoV‐2) infection, but the concrete reason remains unclear. Herein, we investigated the influence of irradiation on the vulnerability of cancer cells to SARS‐CoV‐2 using S pseudovirions and probed the underlying mechanism via RNA‐seq and other molecular biology techniques. Owing to the enhancement of sphingolipid metabolism, irradiation accelerated pseudovirion infection. Mechanistically, irradiation induced the expression of acid sphingomyelinase (ASM), which catalyses the hydrolysis of sphingomyelin to ceramide, contributing to lipid raft formation and promoting SARS‐CoV‐2 invasion. Inhibition of lipid raft formation with methyl‐β‐cyclodextrin (MβCD) or the tyrosine kinase inhibitor genistein and ASM suppression through small interfering RNA or amitriptyline (AMT) treatment abolished the enhancing effect of irradiation on viral infection. Animal experiments supported the finding that irradiation promoted SARS‐CoV‐2 S pseudovirion infection in A549 cell tumour‐bearing BALB/c nude mice, whereas AMT treatment dramatically decreased viral infection. This study discloses the role of sphingolipid metabolism in irradiation‐induced SARS‐CoV‐2 infection, thus providing a potential target for clinical intervention to protect patients receiving radiotherapy from COVID‐19.

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Section: Resultsmentioning

confidence: 99%

Irradiation accelerates SARS‐CoV‐2 infection by enhancing sphingolipid metabolism

Wei

Jiang

Zhao

et al. 2022

Journal of Medical Virology

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“…MMP-7 or matrilysin is one such MMP that cleaves the macromolecules of ECM such as casein, aggrecan, laminin, gelatins, fibronectin, entactin, elastin, decorin, collagen IV, and tenascin casein [ 39 , 40 ]. Hence, MMP-7 has been found to be highly expressed in gastrointestinal, ovarian, lung, and colorectal cancer cells, and it enhances tumor proliferation and metastasis [ 41 , 42 , 43 ]. Fortunately, cells have endogenous inhibitors for MMPs, called TIMPs that prevent metastasis [ 44 ].…”

Section: Resultsmentioning

confidence: 99%

Andrographolide as a therapeutic agent against breast and ovarian cancers

Beesetti¹,

Mavuluri²,

Subhashini³

et al. 2019

Open Life Sciences

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Andrographolide (ANDR), isolated from Andrographis paniculata, is a medicinal compound effective against infections, inflammatory disorders, and various cancers. In the present study, the effects of ANDR on NFkB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation, caspase-8-mediated apoptosis and pyroptosis, and extra cellular matrix (ECM) degradation were analyzed in A431, MDA-MB231, and SKOV-3 cell lines. Results showed that ANDR inhibited the growth and proliferation of cancer cell lines by inhibiting NFkB signaling. A significant decrease in phospho-p65 level was observed upon increasing ANDR concentration in epidermoid carcinoma and breast cancer cell lines, A431 and MDA-MB231, respectively. Accordingly, upon ANDR treatment, the expression of caspase-8 was increased, whereas no significant induction of caspase-1 expression was observed. Moreover, we observed a significant increase in the expression of tissue inhibitor of metallopeptidase-1 (TIMP1) upon increasing ANDR concentration. Such induction of TIMP1 inhibited the activity of matrix metallopeptidase-7 (MMP-7), thus preventing the degradation of ECM. Therefore, as ANDR shows cytotoxicity towards cancer cells via the NFkB signal transduction pathway without inducing pyroptosis and blocks breast and ovarian cancer invasion by inhibiting MMP-7 expression through TIMP1 up-regulation, it has the potential to be developed as a drug targeting ovarian and breast cancers.

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“…The encoded preproprotein is proteolytically processed to generate the mature protease (34). The gene is highly expressed in digestive, urinary, breast, and lung cancer tissues (35,36).…”

Section: Discussionmentioning

confidence: 99%

Screening and Identification of Key Biomarkers of Gastric Cancer: Three Genes Jointly Predict Gastric Cancer

et al. 2021

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BackgroundGastric cancer (GC) is one of the most common cancers all over the world, causing high mortality. Gastric cancer screening is one of the effective strategies used to reduce mortality. We expect that good biomarkers can be discovered to diagnose and treat gastric cancer as early as possible.MethodsWe download four gene expression profiling datasets of gastric cancer (GSE118916, GSE54129, GSE103236, GSE112369), which were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between gastric cancer and adjacent normal tissues were detected to explore biomarkers that may play an important role in gastric cancer. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of overlap genes were conducted by the Metascape online database; the protein-protein interaction (PPI) network was constructed by the STRING online database, and we screened the hub genes of the PPI network using the Cytoscape software. The survival curve analysis was conducted by km-plotter and the stage plots of hub genes were created by the GEPIA online database. PCR, WB, and immunohistochemistry were used to verify the expression of hub genes. A neural network model was established to quantify the predictors of gastric cancer.ResultsThe relative expression level of cadherin-3 (CDH3), lymphoid enhancer-binding factor 1 (LEF1), and matrix metallopeptidase 7 (MMP7) were significantly higher in gastric samples, compared with the normal groups (p<0.05). Receiver operator characteristic (ROC) curves were constructed to determine the effect of the three genes’ expression on gastric cancer, and the AUC was used to determine the degree of confidence: CDH3 (AUC = 0.800, P<0.05, 95% CI =0.857-0.895), LEF1 (AUC=0.620, P<0.05, 95%CI=0.632-0.714), and MMP7 (AUC=0.914, P<0.05, 95%CI=0.714-0.947). The high-risk warning indicator of gastric cancer contained 8<CDH3<15 and 10<expression of LEF1<16.ConclusionsCDH3, LEF1, and MMP7 can be used as candidate biomarkers to construct a neural network model from hub genes, which may be helpful for the early diagnosis of gastric cancer.

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MMP7 Modulation by Short- and Long-term Radiotherapy in Patients with Rectal Cancer

Abstract: Abstract. Background

Cited by 6 publications

References 37 publications

Irradiation accelerates SARS‐CoV‐2 infection by enhancing sphingolipid metabolism

Irradiation accelerates SARS‐CoV‐2 infection by enhancing sphingolipid metabolism

Andrographolide as a therapeutic agent against breast and ovarian cancers

Screening and Identification of Key Biomarkers of Gastric Cancer: Three Genes Jointly Predict Gastric Cancer

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