Recent Patents on Anti-Cancer Drug Discovery - Online First

This study aims to enhance the understanding of underlying mechanisms and potential therapies of the solute carrier organic anion (SLCO) transporter family in internal environment disorder (IED)-induced hepatocellular carcinoma (HCC). This could lead to new therapeutic strategies and offer new directions for the creation of new patents for HCC treatment products.

The orthotopic transplantation (OT), IED and IED-based OT (IED-OT) mouse models were established. Expression patterns of Slco4a1 and Slco1b2 were determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), western blotting (WB) and immunohistochemistry (IHC) in various tissues, including lung, stomach, liver, spleen, kidney, colon, small intestine, HCC tissues and adjacent non-cancerous tissues.

Animals exhibited symptoms, including weight loss, lethargy, chills, dyspnea, altered hair texture, and gastrointestinal disturbances, confirming the successful establishment of the IED model. The analysis demonstrated differential expression and tissue-specific distribution of Slco4a1 and Slco1b2, which are associated with IED-induced changes. These alterations potentially disrupt organ transport functions, thereby promoting the development of HCC. Additionally, they suggest a role in rebalancing the tumor microenvironment and mitigating damage resulting from abnormal substance accumulation.

Changes in SLCO expression and distribution induced by IED may play pivotal roles in the development of HCC. These findings contribute insights that could inform novel therapeutic strategies against HCC.

This study aimed to evaluate IMRT and 3D-CRT in the therapy of brain tumor (BT) in relation to dose-volume histograms (DVHs) parameters, such as Heterogeneity Index (HI), Conformity index (CI), Equivalent Uniform Dose (EUD), and mean dose (Dmean) outcomes, including the program for the tumors of the brain and estimate whether a favored procedure can be found through the features of the pretreatment.

A search of the PubMed, Cochrane Library, and Embase datasets from their beginnings from January 2006 to September 2022 was conducted. The authors separately selected and evaluated studies for qualifying criteria and bias risk.

Seven studies in total were included. Of them, a total of 387 patients were integrated for the Heterogeneity index (HI), Conformity Index (CI), Equivalent Uniform Dose (EUD), and mean dose (Dmean) comparison analysis, which showed 3D-CRT & IMRT with odd ratio (OR) =1.93; 95% confidence interval (95% CI) =1.63, 2.22; and P value=0.00. For brain tumor patients, CI was higher in IMRT than 3D-CRT with OR= 0.72; 95% CI =0.41, 1.03; p value <0.001. EUD was higher in IMRT than 3D-CRT, resulting in an increased overall survival with OR=-0.86; 95% CI =-1.30, 0.42; and p value<0.001. However, no statistically significant variance was perceived in Dmean between 3D-CRT and IMRT.

Our records suggested that IMRT with conventional linacs results in a meaningfully lower regular percentage of brain tumor volumes compared to 3D-CRT. Finally, this meta-analysis indicated that IMRT is better than 3D-CRT and decreases the average percent irradiated amount of the brain.

To investigate the underlying mechanism by which quercetin (Que) regulates macrophage polarization and its subsequent therapeutic effect on liver fibrosis, an important pathological precondition for hepatocellular carcinoma (HCC).

In vitro experiments were performed on the RAW264.7 mouse macrophage line. After the induction of M1-type macrophages with LPS, the effects of Que on cell morphology, M1/M2 surface marker expression, cytokine expression, and JAK2/STAT3 expression were analyzed. In vivo, male SD rats were used as a model of CCL4-induced hepatic fibrosis, and the effects of Que on serum aminotransferase levels, the histopathological structure of liver tissues, and macrophage-associated protein expression in liver tissues were analyzed.

In vitro experiments revealed that Que can suppress the activation of the JAK2/STAT3 signaling pathway, leading to decreases in the expression of M1 macrophage surface markers and cytokines. Additionally, Que was found to increase the expression of M2 macrophage surface markers and cytokines. In vivo, assays demonstrated that Que significantly ameliorated the development of inflammation and fibrosis in a rat liver fibrosis model.

Que can inhibit hepatic fibrosis by promoting M1 to M2 macrophage polarization, which could be associated with its ability to suppress the JAK2/STAT3 signaling pathway in macrophages.