Role of NuMA1 in breast cancer stem cells with implications for combination therapy of PIM1 and autophagy inhibition in triple negative breast cancer.

Background: Nuclear mitotic apparatus protein 1 (NuMA1) is a cell cycle protein and upregulated in breast cancer. However, the role of NuMA1 in TNBC and its regulation in heterogenous populations remains elusive.

Methods: We performed CRISPR mediated deletion of NuMA1 in mouse TNBC cells, BF3M.

In vivo CRISPR knockout screen identifies p47 as a suppressor of HER2+ breast cancer metastasis by regulating NEMO trafficking and autophagy flux.

Autophagy is a conserved cellular process, and its dysfunction is implicated in cancer and other diseases. Here, we employ an in vivo CRISPR screen targeting genes implicated in the regulation of autophagy to identify the Nsfl1c gene encoding p47 as a suppressor of human epidermal growth factor receptor 2 (HER2)+ breast cancer metastasis. p47 ablation specifically increases metastasis without promoting primary mammary tumor growth.

AZI2 mediates TBK1 activation at unresolved selective autophagy cargo receptor complexes with implications for CD8 T-cell infiltration in breast cancer.

Most breast cancers do not respond to immune checkpoint inhibitors and there is an urgent need to identify novel sensitization strategies. Herein, we uncovered that activation of the TBK-IFN pathway that is mediated by the TBK1 adapter protein AZI2 is a potent strategy for this purpose. Our initial observations showed that RB1CC1 depletion leads to accumulation of AZI2, in puncta along with selective macroautophagy/autophagy cargo receptors, which are both required for TBK1 activation.

Biglycan Promotes Cancer Stem Cell Properties, NFκB Signaling and Metastatic Potential in Breast Cancer Cells.

It is a major challenge to treat metastasis due to the presence of heterogenous BCSCs. Therefore, it is important to identify new molecular targets and their underlying molecular mechanisms in various BCSCs to improve treatment of breast cancer metastasis. Here, we performed RNA sequencing on two distinct co-existing BCSC populations, ALDH and CD29 CD61 from PyMT mammary tumor cells and detected upregulation of biglycan (BGN) in these BCSCs.

Inhibition of autophagy mitigates cell migration and invasion in thyroid cancer.

Background: Autophagy is a highly conserved process for maintaining cellular homeostasis. Upregulation of autophagy promotes metastasis by promoting the cancer stem cell state while also stimulating tumor cell migration and invasion. We hypothesized that autophagy upregulation would be critical for cancer stem cell maintenance as well as cellular migration and invasion in thyroid cancer.

Activation of CD44-Lipoprotein lipase axis in breast cancer stem cells promotes tumorigenesis.

Breast cancer stem cells (CSCs) are distinct CD44-subpopulations that are involved in metastasis and chemoresistance. However, the underlying molecular mechanism of CD44 in breast CSCs-mediated tumorigenesis remains elusive. We observed high CD44 expression in advanced-stage clinical breast tumor samples.

Concise Synthesis of 1,1-Diarylvinyl Sulfones and Investigations on their Antiproliferative Activity Tubulin Inhibition.

Background: Discovery of small molecules that inhibit tubulin polymerization is an attractive strategy for the development of new and improved anti-proliferative agents.

Objective: A series of novel 2-sulfonyl-1,1-diarylethenes were designed towards this end keeping in view the favorable chemical and pharmacological virtues of unsaturated sulfones.

Methods: Rapid, convenient and efficient two-step assembly of the designed molecules was achieved by the vicinal iodo-sulfonylation-Suzuki coupling sequence.

In silico design, synthesis and activity of potential drug-like chrysin scaffold-derived selective EGFR inhibitors as anticancer agents.

Background & Objective: Epidermal growth factor receptor (EGFR) signaling pathway is one of the promising and well-established targets for anticancer therapy. The objective of the present study was to identify new EGFR inhibitors using ligand and structure-based drug designing methods, followed by a synthesis of selected inhibitors and evaluation of their activity.

Methods: A series of C-7-hydroxyproton substituted chrysin derivatives were virtually drawn to generate a small compound library that was screened using 3D QSAR model created from forty-two known EGFR tyrosine kinase inhibitors.

Glutathione S-transferase omega 1 inhibition activates JNK-mediated apoptotic response in breast cancer stem cells.

Glutathione S-transferase omega 1 (GSTO1) contributes to the inactivation of a wide range of drug compounds via conjugation to glutathione during phase reactions. Chemotherapy-induced GSTO1 expression in breast cancer cells leads to chemoresistance and promotes metastasis. In search of novel GSTO1 inhibitors, we identified S2E, a thia-Michael adduct of sulfonamide chalcone with low LC (3.

Total Synthesis of Desmethyl Jahanyne and Its Lipo-Tetrapeptide Conjugates Derived from Parent Skeleton as BCL-2-Mediated Apoptosis-Inducing Agents.

The total synthesis of highly potent and scarcely available marine natural product (-)-jahanyne was attempted resulting in a solution-phase synthesis of pruned versions with comparable activity. A simple and facile synthetic route was employed for the preparation of pruned congeners and would be scalable. The lipophilic tail of the natural product was synthesized from -(+)-citronellol, utilizing easily available chemicals.

Cellular crosstalk mediated by platelet-derived growth factor BB and transforming growth factor β during hepatic injury activates hepatic stellate cells.

Apoptotic hepatocytes release factors that activate hepatic stellate cells (HSCs), thereby inducing hepatic fibrosis. In the present study, in vivo and in vitro injury models were established using acetaminophen, ethanol, carbon tetrachloride, or thioacetamide. Histology of hepatotoxicant-induced diseased hepatic tissue correlated with differential expression of fibrosis-related genes.

Inhibiting epidermal growth factor receptor signalling potentiates mesenchymal-epithelial transition of breast cancer stem cells and their responsiveness to anticancer drugs.

The recurrence of breast cancer in patients is a persistent challenge to the medical fraternity. Breast tumor contains a small population of cells with high tumor initiating and metastatic potential, known as cancer stem cells (CSCs), which are resistant to existing chemotherapeutics. CSCs contribute to the aggressiveness of triple negative breast cancers (TNBCs), thereby necessitating the identification of molecular targets on breast CSCs.

Novel nanocomposites with selective antibacterial action and low cytotoxic effect on eukaryotic cells.

In the present study we synthesized lignin-tetra ethoxysilane (TEOS) nanocomposite and characterized it using UV-spectroscopy, Fourier Transform Infra-red spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), Field Emission-Scanning Electron Microscopy (FE-SEM) and Scanning Electron Microscopy (SEM). XRD spectra and SEM micrographs confirmed a relatively high degree of crystallinity (peaks located at lower angle, 2θ=12° and 2θ=22.0°) and porous nature of nanocomposite.