Regular and Maximal Graphs with Prescribed Tripartite Graph as a Star Complement

Let G be a graph of order n andμbe an adjacency eigenvalue of G with multiplicity k≥1.A star complement H forμin G is an induced subgraph of G of order n-k with no eigenvalueμ,and the subset X=V(G-H)is called a star set forμin G.The star complement provides a strong link between graph structure and linear algebra.In this paper,the authors characterize the regular graphs with K2,2,s(s≥2)as a star complement for all possible eigenvalues,the maximal graphs with K2,2,s as a star complement for the eigenvalueμ=1,and propose some questions for further research.

Olmutinib(HM61713) reversed multidrug resistance by inhibiting the activity of ATPbinding cassette subfamily G member 2 in vitro and in vivo

Overexpressing of ATP-binding cassette(ABC) transporters is the essential cause of multidrug resistance(MDR), which is a significant hurdle to the success of chemotherapy in many cancers.Therefore, inhibiting the activity of ABC transporters may be a logical approach to circumvent MDR.Olmutinib is an epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor(TKI), which has been approved in South Korea for advanced EGFR T790 M-positive non-small cell lung cancer(NSCLC). Here,we found that olmutinib significantly increased the sensitivity of chemotherapy drug in ABCG2-overexpressing cells. Furthermore, olmutinib could also increase the retention of doxorubicin(DOX) and rhodamine 123(Rho 123) in ABC transporter subfamily G member 2(ABCG2)-overexpressing cells. In addition, olmutinib was found to stimulate ATPase activity and inhibit photolabeling of ABCG2 with [^(125) I]-iodoarylazidoprazosin(IAAP). However, olmutinib neither altered ABCG2 expression at protein and m RNA levels nor blocked EGFR, Her-2 downstream signaling of AKT and ERK. Importantly,olmutinib enhanced the efficacy of topotecan on the inhibition of S1-MI-80 cell xenograft growth. All the results suggest that olmutinib reverses ABCG2-mediated MDR by binding to ATP bind site of ABCG2 and increasing intracellular chemotherapeutic drug accumulation. Our findings encouraged to further clinical investigation on combination therapy of olmutinib with conventional chemotherapeutic drugs in ABCG2-overexpressing cancer patients.

Cancer cell reprogramming:a promising therapy converting malignancy to benignity

In the past decade, remarkable progress has been made in reprogramming terminally differentiated somatic cells and cancer cells into induced pluripotent cells and cancer cells with benign phenotypes. Recent studies have explored various approaches to induce reprogramming from one cell type to another, including lineage-specific transcription factors-, combinatorial small molecules-, microRNAs- and embryonic microenvironment-derived exosome-mediated reprogramming. These reprogramming approaches have been proven to be technically feasible and versatile to enable re-activation of sequestered epigenetic regions, thus driving fate decisions of differentiated cells. One of the significant utilities of cancer cell reprogramming is the therapeutic potential of retrieving normal cell functions from various malignancies. However, there are several major obstacles to overcome in cancer cell reprogramming before clinical translation, including characterization of reprogramming mechanisms, improvement of reprogramming efficiency and safety, and development of delivery methods. Recently, several insights in reprogramming mecha-nism have been proposed, and determining progress has been achieved to promote reprogramming efficiency and feasibility, allowing it to emerge as a promising therapy against cancer in the near future. This review aims to discuss recent applications in cancer cell reprogramming, with a focus on the clinical significance and limitations of different reprogramming approaches, while summarizing vital roles played by transcription factors, small molecules, microR-NAs and exosomes during the reprogramming process.