Chromosome instability functions as a potential therapeutic reference by enhancing chemosensitivity to BCL-XL inhibitors in colorectal carcinoma.

Chromosome instability (CIN) and subsequent aneuploidy are prevalent in various human malignancies, influencing tumor progression such as metastases and relapses. Extensive studies demonstrate the development of chemoresistance in high-CIN tumors, which poses significant therapeutic challenges. Given the association of CIN with poorer prognosis and suppressed immune microenvironment observed in colorectal carcinoma (CRC), here we aimed to discover chemotherapeutic drugs exhibiting increased inhibition against high-CIN CRC cells. By using machine learning methods, we screened out two BCL-XL inhibitors Navitoclax and WEHI-539 as CIN-sensitive reagents in CRC. Subsequent analyses using a CIN-aneuploidy cell model confirmed the vulnerability of high-CIN CRC cells to these drugs. We further revealed the critical role of BCL-XL in the viability of high-CIN CRC cells. In addition, to ease the evaluation of CIN levels in clinic, we developed a three-gene signature as a CIN surrogate to predict prognosis, chemotherapeutic and immune responses in CRC samples. Our results demonstrate the potential value of CIN as a therapeutic target in CRC treatment and the importance of BCL-XL in regulating survival of high-CIN CRC cells, therefore representing a valuable attempt to translate a common trait of heterogeneous tumor cells into an effective therapeutic target.

Bacillamide F, Extracted from Marine Bacillus atrophaeus C89, Preliminary Effects on Leukemia Cell Lines.

Developing new treatments for leukemia is essential since current therapies often suffer from drug resistance and toxicity. Bacillamides are very promising, naturally occurring compounds with various bioactivities. In the present study, we investigated the use of bacillamide analogues, a new thiazole alkaloid bacillamide F that was isolated from marine Bacillus atrophaeus C89 associated with sponge Dysidea avara. The structure of the new compound bacillamide F with indolyl−thiazolyl−pyrrolidine ring was determined by high resolution mass spectrometry, secondary mass spectrometry, and nuclear magnetic resonance analyses. Intriguingly, bacillamide F is able to inhibit the proliferation of an acute myeloid leukemia cell line HL60 (IC50 (24 h) 21.82 µM), and an acute T-cell leukemia Jurkat (IC50 (24 h) 46.90 µM), rather than inhibit the proliferation of the acute histiocytic lymphoma U-937 cell line, human fetal lung fibroblast MRC-5 cell line, and some solid tumor cell lines (IC50 (24 h) > 100 µM). The study provides a new indication of the pharmacological activity of natural product bacillamides.

Prognostic SLC family genes promote cell proliferation, migration, and invasion in hepatocellular carcinoma.

The solute carrier (SLC) superfamily genes encode more than 300 members that are responsible for the transmembrane transportation of many essential endogenous and exogenous compounds ranging from nutrients to drugs. SLCs are highly expressed in metabolic organs such as the liver, regulating the homeostasis of metabolites and the disposition of drugs. In contrast to their well-studied roles in physiological and pharmacological processes, little is known about the relationship between SLCs and cancer progression. Here, we aimed to explore the potential role of SLCs in progression and prognosis of hepatocellular carcinoma (HCC), one of the most commonly diagnosed cancers and leading causes of death worldwide. By performing bioinformatics analyses of HCC dataset from The Cancer Genome Atlas database, we identified three novel signature SLCs (SLC51B, SLC22A15, and SLC2A1) that are indicative of poor prognosis. Further functional analyses suggested the potential regulation of the three prognostic SLCs on cell proliferation and metastasis. Subsequent knockdown experiments performed in HCC cell lines showed that all three prognostic SLCs positively regulated the proliferation of HCC cells, among which SLC22A15 and SLC2A1 were required for migration and invasion of the cells, demonstrating remarkable consistency with the roles identified by bioinformatics methods in HCC. Therefore, our study provides a novel prognostic biomarker for HCC and reveals the significant roles of SLCs in HCC progression, which might have been undervalued in the past.

The Levels and Potential Carcinogenic Risks of PAHs in Liaohe Estuarine Reed Wetland Soils.

Sixteen polycyclic aromatic hydrocarbons (PAHs) were quantified by GC/MS in 30 soil samples of Liaohe estuarine reed wetland. The total concentrations of 16 PAHs ranged from 235 to 374 ng g-1, and seven carcinogenic PAHs concentrations were in the range of 83-109 ng g-1. A probabilistic carcinogenic potential for three age groups (including children, teenagers, and adults) exposed to soil PAHs via three pathways was quantitatively calculated based on Monte Carlo simulations. The 95th percentiles carcinogenic risks of PAHs for children, teenagers, and adults were 7.80 × 10-8, 4.03 × 10-8, and 1.14 × 10-7, respectively. The carcinogenic risk levels were all below 10-6, indicating no potential for cancer development. Dermal contact and accident ingestion of soil were the dominant exposure pathways to soil PAHs. BaP and DBahA were the major contributors to carcinogenic risk in this study. Sensitivity analysis demonstrated that exposure duration and PAH concentrations in soil were the key exposure parameters in calculating carcinogenic risk. Results from this study will provide valuable information for potential scientific evaluation and prevention for carcinogenic risk exposed to soil PAHs.