A readily interpretable rule involving multiple forms of pairwise molecule comparisons with applications for clinical make-decision of breast cancer management.

Norepinephrine promotes colorectal cancer liver metastasis via mechanisms dependent on Kupffer cells.

The ZNF737-CXCL10 axis drives immune exclusion and resistance to anti-PD-1 therapy in bladder cancer.

NIR-II conjugated polymer/emodin nanoplatform for mild photothermal therapy/pyroptosis of head and neck squamous cell carcinoma.

Sishen Wan suppresses colon cancer through dual inhibition of PI3K/AKT/mTOR and STAT3-mitophagy pathways: Network pharmacology and experimental validation.

An ultralow-concentration, red-emissive dual-responsive fluorescent probe for real-time mitochondrial viscosity/polarity imaging.

A protein called cytolysin A or ClyA, encoded by certain bacteria species, can cause cytotoxicity. Although the ClyA protein is not typically expressed at detectable levels in most E. coli strains, here it was successfully overproduced and purified by cloning the structural gene into an hns mutant strain. The cytotoxicity of the purified cytolysin was assessed on two MCF-7 cancer cell lines and HDF normal cell line using the MTT assay. Flow cytometry was employed to examine the cytolysin's ability to induce apoptosis in cancer cells. In addition, a Western blot analysis was carried out to evaluate the expression levels of P53, Bcl2, and Bax proteins. The results revealed that cytolysin exhibited dose-dependent and time-dependent toxicity towards cancer cells, while showing minimal toxicity against normal cells, indicating its selective action against cancer cells. Cytolysin had an IC50 value of 3.29µg/ml against MCF-7 cancer cells and 12.6µg/ml against HDF normal cells. Flow cytometry results further demonstrated that cytolysin induced apoptosis in cancer cells, evidenced by increased expression of p53 and BCL2, as well as decreased in Bax, in gene and protein levels. These findings underscore the potential of cytolysin as a targeted therapy for cancer, highlighting its selective cytotoxic effect on cancer cells.

Impact of mechanical property alterations on cancer cell motility and metastasis.

Breast cancer progression involves extensive remodeling of the extracellular matrix (ECM), including increased stiffness, altered viscoelasticity (stress relaxation), and elevated collagen levels. While in vitro experiments have revealed a role for each of these factors in individually promoting malignant behavior, their combined effects remain unclear. Here, we engineered alginate-collagen hydrogels with independently tunable stiffness, stress relaxation, and collagen density to dissect how the complex ECM environment regulates cancer cell phenotype. We show that high stiffness, fast stress relaxation, and high collagen density led to changes in cell morphology, marked by decreased roundness, and promoted spheroid invasion in both breast cancer and non-transformed mammary epithelial cells. Single cell migration speed and displacement were greatest in matrices of high stiffness, low collagen density, and slow stress relaxation. RNA-seq and Cleavage Under Targets and Tagmentation (CUT&Tag)-seq revealed that high stiffness and fast stress relaxing groups were enriched for Sp1 target gene expression as well as increased Sp1 binding at genomic loci. Notably, analysis of publicly available claudin-low breast cancer data showed that high expression of the Sp1-regulated genes in fast stress relaxing groups was correlated with significantly reduced patient survival. Mechanistically, we found that phosphorylated Sp1 (T453) exhibited increased nuclear localization in matrices with high stiffness and fast stress relaxation. Furthermore, Sp1 phosphorylation was regulated by PI3K and ERK1/2 activity, as well as actomyosin contractility. Our tunable hydrogel platform reveals that multiple tumor-mimicking cues within complex viscoelastic microenvironments reinforce malignant traits, with Sp1 acting as a mechanoresponsive transcription factor that transduces these signals.

Targeting Warburg effect: involvement of lactate transporter MCT1 and its chaperone in cancer cell killing by 18β-glycyrrhetinic acid.

Mineralized bone matrix attenuates breast cancer cell malignancy by altering MSC mechanoregulation.

Identification of glycosylation-related changes in migratory and mechanical properties of bladder cancer cells.

Effect of proton therapy and chemoradiotherapy on biochemistry of radioresistant prostate cancer cells studied by Raman microspectroscopy.

Programmed Cell Death Protein-1 (PD-1)/Programmed Cell Death-Ligand 1 (PD-L1) interaction has a crucial role in maintaining the immune system's self-tolerance by downregulating T cell activation. This mechanism is also used by several types of cancers. By overexpressing the PD-L1 protein, cancer cells can evade the immune response and, therefore, become invisible to the immune system. Herein, we present a detailed characterization of the activity of improved N-terphenylpicolinamides, a class of small molecular blockers targeting the PD-L1 protein disclosed in our recent patent and following patent applications. In our studies, we utilized a cell-based structure-activity relationship (SAR) analysis, which allowed us to discriminate the bioactivity of molecules beyond the detection limits of the protein-based HTRF assay. Our final molecules display high affinity to the molecular target and in vitro bioactivity approaching the activity of a positive control ARB-272572 molecule. An optimized molecule activates primary immune cells, leading to enhanced elimination of cancer cells, as we show in a newly developed co-culture setup. In addition, a co-crystal structure described here confirms the intended mode of binding of the small molecule to PD-L1. Our pharmacokinetics (PK) results rationalize the choice of a representative molecule for further in vivo testing.

Oridonin downregulates PD-L1 expression and promotes anti-tumor immunity via inhibiting NLRP3 and STAT3.

Targeting epithelial-mesenchymal transition and apoptosis: novel histone methyltransferase inhibitors for colon cancer suppression.

Colloid-patterned surfaces distinguish malignant mechanophenotypes.

Experimental adaptation of pigeon rotavirus A (pRVA) in human colorectal cancer cells reveals interferon-driven host responses and immune checkpoint modulation.

Assessment of survival and clinicopathologic characteristics associated with lymph node isolated tumor cells in epithelial ovarian cancer.

Heterogeneous expression of the laminin-binding O-mannosyl glycan on α-dystroglycan in pancreatic cancer cell line MIA PaCa-2 and the correlation with cell properties.