Research progress on FASN and MGLL in the regulation of abnormal lipid metabolism and the relationship between tumor invasion and metastasis

Tumorigenesis involves metabolic reprogramming and abnormal lipid metabolism,which is manifested by increased endogenous fat mobilization,hypertriglyceridemia,and increased fatty acid synthesis.Fatty acid synthase(FASN)is a key enzyme for the de novo synthesis of fatty acids,and monoacylglycerol esterase(MGLL)is an important metabolic enzyme that converts triglycerides into free fatty acids.Both enzymes play an important role in lipid metabolism and are associated with tumor-related signaling pathways,the most common of which is the PI3K–AKT signaling pathway.They can also regulate the immune microenvironment,participate in epithelial–mesenchymal transition,and then regulate tumor invasion and metastasis.Current literature have shown that these two genes are abnormally expressed in many types of tumors and are highly correlated with tumor migration and invasion.This article introduces the structures and functions of FASN and MGLL,their relationship with abnormal lipid metabolism,and the mechanism of the regulation of tumor invasion and metastasis and reviews the research progress of the relationship of FASN and MGLL with tumor invasion and metastasis.

BOUNDEDNESS OF A CHEMOTAXIS-CONVECTION MODEL DESCRIBING TUMOR-INDUCED ANGIOGENESIS

This paper is concerned with the parabolic-parabolic-elliptic system■in a bounded domainΩ?Rnwith a smooth boundary,where the parametersχ,ζ1,ζ2are positive constants and m≥1.Based on the coupled energy estimates,the boundedness of the global classical solution is established in any dimensions(n≥1)provided that m>1.

Decreased invasion ability of hypotaurine synthesis deficient glioma cells was partially due to hypomethylation of Wnt5a promoter

Glioma is one of the lethal central nervous system tumors.The infiltrative and invasive growth nature makes it difficult to identify the boundary between glioma and the normal tissues,resulting in inevitable recurrence after surgery operation.Gliomas do not metastasize,so to prevent the residual tumor from proliferating or invading is a key challenge.Previous report indicated that hypotaurine could facilitate glioma invasion and suppress demethylases’activities.Using a hypotaurine synthesis deficient U251 cell line,we proved that the cells invasion ability was impaired.Gene expression profile analysis exhibited that knocking down one of the key enzymes of hypotaurine synthesis,2-aminoethanethiol dioxygenase(ADO),significantly affected the extracellular matrix-receptor process.Of that process,Wnt5a expression was severely upregulated by decreased intracellular ADO expression.Cells cultured at the presence of hypotaurine showed a decrease in intracellular Wnt5a protein and mRNA levels.This phenotype was due to hypermethylation of Wnt5a promoter,which was most likely the result of hypotaurine’s inhibiting demethylases activities.Collectively,this study demonstrated that hypotaurine synthesis deficient U251 cells were prone to epigenetic modification and Wnt5a seemed to be a tumor suppressor under that circumstance.This tumor suppression effect is warranted to be reevaluated in real tumor samples and the relevant evidence might contribute to develop new glioma interference strategies.

Reductive lipid nanoparticles loaded with vinorelbine inhibit chemotherapy-induced invasion of cancer cells by modulating ENPP2

Cancer is a predominant culprit behind worldwide death and accounts for up to 10 million deaths every year.Chemotherapy is the primary therapeutic method employed for cancer in clinical settings and is essential in controlling tumor progression.Despite the advances in this field,tumor invasion and metastasis during treatment remain a significant cause of treatment failure.Nevertheless,the underlying mechanisms involving such a disappointing phenomenon are still not fully elucidated.Vinorelbine(VNB)extends the lifespan of many cancer patients in the clinic as an emerging chemotherapy drug approved by Food and Drug Administration(FDA).However,VNB-induced tumor metastasis is still an intractable problem,which may be closely related to the abnormal oxidative stress generated during VNB-mediated treatment.Hence,the study aims to construct a reductive nanosystem loaded with VNB,called VNB-VNP,to improve cancer cure rates and reduce tumor metastasis.With the reductive component vitamin E,VNB-VNP can effectively reduce oxidative stress and significantly outperform free VNB in preventing tumor progression.The transcriptome analysis shows that VNB-VNP can alleviate the over-expression of ectonucleotide pyrophosphatase/phosphodiesterase 2(ENPP2),which may be the main reason why VNB-VNP can inhibit tumor invasion and metastasis.Overall,the research designs a new platform for VNB treatment,which demonstrates promising efficacy in inhibiting neoplastic progression and identifies a new mechanism associated with VNB-induced tumor metastasis,which may offer several valuable references for enhancing chemotherapy efficacy in clinical anti-tumor therapy.

How useful is rectal endosonography in the staging of rectal cancer?

It is essential in treating rectal cancer to have adequate preoperative imaging,as accurate staging can influence the management strategy,type of resection,and candidacy for neoadjuvant therapy.In the last twenty years,endorectal ultrasound(ERUS) has become the primary method for locoregional staging of rectal cancer.ERUS is the most accurate modality for assessing local depth of invasion of rectal carcinoma into the rectal wall layers(T stage) .Lower accuracy for T2 tumors is commonly reported,which could lead to sonographic overstaging of T3 tumors following preoperative therapy.Unfortunately,ERUS is not as good for predicting nodal metastases as it is for tumor depth,which could be related to the unclear definition of nodal metastases.The use of multiple criteria might improve accuracy.Failure to evaluate nodal status could lead to inadequate surgical resection.ERUS can accurately distinguish early cancers from advanced ones,with a high detection rate of residual carcinoma in the rectal wall.ERUS is also useful for detection of local recurrence at the anastomosis site,which might require fine-needle aspiration of the tissue.Overstaging is more frequent than understaging,mostly due to inflammatory changes.Limitations of ERUS are operator and experiencedependency,limited tolerance of patients,and limited range of depth of the transducer.The ERUS technique requires a learning curve for orientation and identification of images and planes.With sufficient time and effort,quality and accuracy of the ERUS procedure could be improved.

Predictive factors for lymph node metastasis in early gastric cancer

AIM: To analyze the predictive factors for lymph node metastasis (LNM) in early gastric cancer (EGC). METHODS: Data from patients surgically treated for gastric cancers between January 1994 and December 2007 were retrospectively collected. Clinicopathological factors were analyzed to identify predictive factors for LNM. RESULTS: Of the 2936 patients who underwent gas-trectomy and lymph node dissection, 556 were diag-nosed with EGC and included in this study. Among these, 4.1% of patients had mucosal tumors (T1a) with LNM while 24.3% of patients had submucosal tumorswith LNM. Univariate analysis found that female gen-der, tumors ≥ 2 cm, tumor invasion to the submucosa, vascular and lymphatic involvement were significantly associated with a higher rate of LNM. On multivariate analysis, tumor size, lymphatic involvement, and tumor with submucosal invasion were associated with LNM. CONCLUSION: Tumor with submucosal invasion, size ≥ 2 cm, and presence of lymphatic involvement are predictive factors for LNM in EGC.

A nomogram predicting the recurrence of hepatocellular carcinoma in patients after laparoscopic hepatectomy

Background:Patients with hepatocellular carcinoma(HCC)undergoing surgical resection still have a high 5-year recurrence rate(~60%).With the development of laparoscopic hepatectomy(LH),few studies have compared the efficacy between LH and traditional surgical approach on HCC.The objective of this study was to establish a nomo-gram to evaluate the risk of recurrence in HCC patients who underwent LH.Methods:The clinical data of 432 patients,pathologically diagnosed with HCC,underwent LH as initial treatment and had surgical margin>1 cm were collected.The significance of their clinicopathological features to recurrence-free survival(RFS)was assessed,based on which a nomogram was constructed using a training cohort(n=324)and was internally validated using a temporal validation cohort(n=108).Results:Hepatitis B surface antigen(hazard ratio[HR],1.838;P=0.044),tumor number(HR,1.774;P=0.003),tumor thrombus(HR,2.356;P=0.003),cancer cell differentiation(HR,0.745;P=0.080),and microvascular tumor invasion(HR,1.673;P=0.007)were found to be independent risk factors for RFS in the training cohort,and were used for con-structing the nomogram.The C-index for RFS prediction in the training cohort using the nomogram was 0.786,which was higher than that of the 8th edition of the American Joint Committee on Cancer TNM classification(C-index,0.698)and the Barcelona Clinic Liver Cancer staging system(C-index,0.632).A high consistency between the nomogram prediction and actual observation was also demonstrated by a calibration curve.An improved predictive benefit in RFS and higher threshold probability of the nomogram were determined by receiver operating characteristic curve analysis,which was also confirmed in the validation cohort compared to other systems.Conclusions:We constructed and validated a nomogram able to quantify the risk of recurrence after initial LH for HCC patients,which can be clinically implemented in assisting the planification of individual postoperative surveil-lance protocols.