Preclinical studies of the falnidamol as a highly potent and specific active ABCB1 transporter inhibitor.

Background: ABCB1 overexpression is a key factor in causing multidrug resistance (MDR). As a result, it is crucial to discover effective medications against ABCB1 to overcome MDR. Falnidamol, a tyrosine kinase inhibitor (TKI) targeting the epidermal growth factor receptor (EGFR), is currently in phase 1 clinical trials for the treatment of solid tumors.

[Alpha-bisabolol reverses ABCB1-mediated multidrug resistance in tumor and its mechanisms].

Objective To investigate whether alpha-bisabolol can effectively reverse ATP binding cassette subfamily B member 1 (ABCB1)-mediated multidrug resistance (MDR) in tumors and to explore the underlying mechanisms. Methods The network pharmacology was utilized to analyze the active components of Agrimonia Eupatoria, predict target genes, and perform GO and KEGG pathway analysis. Molecular docking and thermal stability assays were conducted to examine the interaction between alpha-bisabolol and ABCB1.

MYC Family Amplification Dictates Sensitivity to BET Bromodomain Protein Inhibitor Mivebresib (ABBV075) in Small-Cell Lung Cancer.

Small-cell lung cancer (SCLC) accounts for nearly 15% of all lung cancers. Although patients respond to first-line therapy readily, rapid relapse is inevitable, with few treatment options in the second-line setting. Here, we describe SCLC cell lines harboring amplification of MYC and MYCN but not MYCL1 or non-amplified MYC cell lines exhibit superior sensitivity to treatment with the pan-BET bromodomain protein inhibitor mivebresib (ABBV075).

Overexpression of ABCB1 confers resistance to FLT3 inhibitor FN-1501 in cancer cells: in vitro and in vivo characterization.

FN-1501 is a potent FLT3 inhibitor with antitumor activity. A phase 1 trial of FN-1501 monotherapy in patients with advanced solid tumors and R/R AML is in progress. Since one of the primary causes of multidrug resistance (MDR) is the overexpression of ATP-binding cassette superfamily B member 1 (ABCB1), the objective of this study was to investigate the potential relationship between FN-1501 and the ABCB1 transporter.

Cell division cycle 42 effector protein 4 inhibits prostate cancer progression by suppressing ERK signaling pathway.

Prostate cancer (PCa) is the most common malignancy among men worldwide. The cell division cycle 42 effector protein 4 (CDC42EP4) functions downstream of CDC42, yet its role and molecular mechanisms in PCa remain unexplored. This study aimed to elucidate the role of CDC42EP4 in the progression of PCa and its underlying mechanisms.

Antimicrobial peptides for combating drug-resistant bacterial infections.

The problem of drug resistance due to long-term use of antibiotics has been a concern for years. As this problem grows worse, infections caused by multiple bacteria are expanding rapidly and are extremely detrimental to human health. Antimicrobial peptides (AMPs) are a good alternative to current antimicrobials with potent antimicrobial activity and unique antimicrobial mechanisms, which have advantages over traditional antibiotics in fighting against drug-resistant bacterial infections.

Ribosomal protein L22-like1 promotes prostate cancer progression by activating PI3K/Akt/mTOR signalling pathway.

Prostate cancer (PCa) is one of the most common malignancies in men. Ribosomal protein L22-like1 (RPL22L1), a component of the ribosomal 60 S subunit, is associated with cancer progression, but the role and potential mechanism of RPL22L1 in PCa remain unclear. The aim of this study was to investigate the role of RPL22L1 in PCa progression and the mechanisms involved.

Microcystin‑leucine arginine promotes colorectal cancer cell proliferation by activating the PI3K/Akt/Wnt/β‑catenin pathway.

Microcystin‑leucine arginine (MC‑LR) is an environmental toxin produced by cyanobacteria and is considered to be a potent carcinogen. However, to the best of our knowledge, the effect of MC‑LR on colorectal cancer (CRC) cell proliferation has never been studied. The aim of the present study was to investigate the effect of MC‑LR on CRC cell proliferation and the underlying mechanisms.

Microcystin-LR induced microfilament rearrangement and cell invasion by activating ERK/VASP/ezrin pathway in DU145 cells.

Microcystin-LR (MC-LR) is an environmental toxin that is synthesized by cyanobacteria and considered a potential human carcinogen. However, the role of MC-LR in prostate cancer progression has not been elucidated. The purpose of this study was to investigate the effect of MC-LR on prostate cancer cell invasion and its underlying mechanisms.

Selective Inhibition of the Second Bromodomain of BET Family Proteins Results in Robust Antitumor Activity in Preclinical Models of Acute Myeloid Leukemia.

Dual bromodomain BET inhibitors that bind with similar affinities to the first and second bromodomains across BRD2, BRD3, BRD4, and BRDT have displayed modest activity as monotherapy in clinical trials. Thrombocytopenia, closely followed by symptoms characteristic of gastrointestinal toxicity, have presented as dose-limiting adverse events that may have prevented escalation to higher dose levels required for more robust efficacy. ABBV-744 is a highly selective inhibitor for the second bromodomain of the four BET family proteins.

Bruton's Tyrosine Kinase (BTK) Inhibitor RN486 Overcomes ABCB1-Mediated Multidrug Resistance in Cancer Cells.

Overexpression of ATP-binding cassette subfamily B member 1 (ABCB1) remains one of the most vital factors leading to multidrug resistance (MDR). It is important to enhance the effect and bioavailability of chemotherapeutic drugs that are substrates of ABCB1 transporter in ABCB1-overexpression cancer cells and reverse ABCB1-mediated MDR. Previous, we uncovered that the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib is a potent reversal agent to overcomes paclitaxel resistance in ABCB1-overexpressing cells and tumors.

Enhanced targeted delivery of adenine to hepatocellular carcinoma using glycyrrhetinic acid-functionalized nanoparticles in vivo and in vitro.

Hepatocellular carcinoma (HCC), a common malignancy in China and globally, is primarily treated through surgical resection and liver transplantation, with chemotherapy as a significant synergistic option. Adenine (Ade), a nucleobase, exhibits antitumor effects by blocking human hepatic carcinoma cells in S phase and inhibiting tumor cell proliferation. However, its use is limited owing to its low solubility, poor targeting ability, and nephrotoxicity.

NVP-CGM097, an HDM2 Inhibitor, Antagonizes ATP-Binding Cassette Subfamily B Member 1-Mediated Drug Resistance.

Multidrug resistance (MDR) is a major challenge in the treatment of tumors. It refers to cancer cells become resistant to not only the therapeutic drug, but also cross-resistant to multiple drugs with distinct structures and mechanisms of action when they are exposed to a drug for a period of time. An essential mechanism of MDR is the aberrant expression and function of ATP-binding cassette (ABC) transporters.

Erdafitinib Antagonizes ABCB1-Mediated Multidrug Resistance in Cancer Cells.

ABCB1 overexpression is known to contribute to multidrug resistance (MDR) in cancers. Therefore, it is critical to find effective drugs to target ABCB1 and overcome MDR. Erdafitinib is a tyrosine kinase inhibitor (TKI) of fibroblast growth factor receptor (FGFR) that is approved by the FDA to treat urothelial carcinoma.

Improved efficacy of doxorubicin delivery by a novel dual-ligand-modified liposome in hepatocellular carcinoma.

Liposomes have been widely used as drug carriers in both biomedical research and for clinical applications, allowing the stabilisation of therapeutic compounds and overcoming obstacles to cellular and tissue uptake. However, liposomes still have low targeting efficiency, resulting in insufficient killing of tumour cells and unnecessary damage to normal cells. In this study, glycyrrhetinic acid (GA) and peanut agglutinin (PNA) were used as ligands to prepare dual-ligand-modified doxorubicin-loaded liposomes (DOX-GA/PNA-Lips) to enhance the targeting accuracy and efficacy of drug delivery against malignant liver cancer.

Elevated microRNA-125b inhibits cytotrophoblast invasion and impairs endothelial cell function in preeclampsia.

Preeclampsia (PE) is a life-threatening disorder of human pregnancy affecting 5-8% of all pregnancies. Currently, PE remains an elusive complicated and heterogenous medical condition with no early marker or symptoms is recognized for this serious pregnancy complications. Here, we profiled the plasma miRNA expression patterns associated with preeclampsia and found 16 miRNAs were deregulated ( < 0.

A human lung tumor microenvironment interactome identifies clinically relevant cell-type cross-talk.

Background: Tumors comprise a complex microenvironment of interacting malignant and stromal cell types. Much of our understanding of the tumor microenvironment comes from in vitro studies isolating the interactions between malignant cells and a single stromal cell type, often along a single pathway.

Result: To develop a deeper understanding of the interactions between cells within human lung tumors, we perform RNA-seq profiling of flow-sorted malignant cells, endothelial cells, immune cells, fibroblasts, and bulk cells from freshly resected human primary non-small-cell lung tumors.

Mechanical Changes and Microfilament Reorganization Involved in Microcystin-LR-Promoted Cell Invasion in DU145 and WPMY Cells.

Microcystin-leucine arginine (MC-LR) is a potent tumor initiator that can induce malignant cell transformation. Cellular mechanical characteristics are pivotal parameters that are closely related to cell invasion. The aim of this study is to determine the effect of MC-LR on mechanical parameters, microfilament, and cell invasion in DU145 and WPMY cells.

Identification of potential diagnostic and prognostic biomarkers for prostate cancer.

Prostate cancer (PCa) is one of the most common malignant tumors worldwide. The aim of the present study was to determine potential diagnostic and prognostic biomarkers for PCa. The GSE103512 dataset was downloaded, and the differentially expressed genes (DEGs) were screened.

RUNX2 contributes to TGF-β1-induced expression of Wdr72 in ameloblasts during enamel mineralization.

The elaborate modulation of the transforming growth factor β (TGF-β) superfamily signaling network plays an essential role in tooth morphogenesis and differentiation. In our previous studies, we have demonstrated that TGF-β1 promotes enamel mineralization and maturation using TGF-β1 gene conditional knockout (TGF-β1-cKO) mice. However, the specific regulatory mechanisms of TGF-β1 during enamel development remain unclear.

TRIM62-mediated restriction of avian leukosis virus subgroup J replication is dependent on the SPRY domain.

Emerging evidence suggests that some members of the tripartite motif (TRIM) family play a crucial role in antiretroviral. However, the chicken TRIM62 antiretroviral activity is unknown. Avian leukosis virus subgroup J (ALV-J) is an avian retrovirus mainly inducing tumor formation and immunosuppression.

Transition from vesicles to nanofibres in the enzymatic self-assemblies of an amphiphilic peptide as an antitumour drug carrier.

Amphiphilic peptides modified by molecular design can self-assemble into specific nanostructures with interesting applications in the fields of biomedicine and biotechnology. Lysyl oxidase (LO) is ubiquitous in human serum. However, enzymatic self-assembly of amphiphilic peptides remains a challenge for lipid-soluble drug delivery under the induction of LO.

Identification of candidate diagnostic and prognostic biomarkers for human prostate cancer: RPL22L1 and RPS21.

Prostate cancer (PCa) is one of the most common malignancies in men worldwide. This study was designed to investigate the potential of Ribosomal Protein L22-like1 (RPL22L1) and Ribosomal Protein S21 (RPS21) as diagnostic and prognostic biomarkers for PCa. First, RPL22L1 and RPS21 were screened as the key molecular of PCa by bioinformatics analysis.

Identification of the key genes and pathways in prostate cancer.

Prostate cancer (PCa) is one of the most common malignancies in men globally. The aim of the present study was to identify the key genes and pathways involved in the occurrence of PCa. Gene expression profile (GSE55945) was downloaded from Gene Expression Omnibus, and the differentially expressed genes (DEGs) were identified.

ZNF185-derived peptide induces fertility suppression in mice.

Zinc finger protein 185 (ZNF185) belongs to the ZNF family and is involved in male reproduction. However, it is unclear whether ZNF185 may be a target candidate for contraceptive vaccines. In this study, antigenic peptides derived from ZNF185 were prepared, and their immune contraceptive effects were investigated using mice.