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The convenient cross-coupling of sp2 or sp3 carbons with a specific boron vertex on carborane cage represents significant synthetic values and insurmountable challenges. In this work, we report an Rh-catalyzed reaction between o-carborane and N-acyl-glutarimides to construct various Bcage -C bonds. Under the optimized condition, the removable imine directing group (DG) leads to B(3)- or B(3,6)-C couplings, while the pyridyl DG leads to B(3,5)-Ar coupling. In particular, an unexpected rearrangement of amide reagent is observed in pyridyl directed B(4)-C(sp3 ) formation. This scalable protocol has many advantages, including easy access, the use of cheap and widely available coupling agents, no requirement of an external ligand, base or oxidant, high efficiency, and a broad substrate scope. Leveraging the RhI dimer and twisted amides, this method enables straightforward access to diversely substituted and therapeutically important carborane derivatives at boron site, and provides a highly valuable vista for carborane-based drug screening.

The amplification of oncogenes on extrachromosomal DNA (ecDNA) provides a new mechanism for cancer cells to adapt to the changes in the tumor microenvironment and accelerate tumor evolution. These extrachromosomal elements contain oncogenes, and their chromatin structures are more open than linear chromosomes and therefore have stronger oncogene transcriptional activity. ecDNA always contains enhancer elements, and genes on ecDNA can be reintegrated into the linear genome to regulate the selective expression of genes. ecDNA lacks centromeres, and the inheritance from the parent cell to the daughter cell is uneven. This non-Mendelian genetic mechanism results in the increase of tumor heterogeneity with daughter cells that can gain a competitive advantage through a large number of copies of oncogenes. ecDNA promotes tumor invasiveness and provides a mechanism for drug resistance associated with poorer survival outcomes. Recent studies have demonstrated that the overall proportion of ecDNA in tumors is approximately 40%. In this review, we summarize the current knowledge of ecDNA in the field of tumorigenesis and development.

The tumor microenvironment (TME) is a crucial factor in cancer progression. In breast cancer, cancer-associated fibroblasts (CAFs) and the derived stromal components have been recognized as comprising the majority of the pathological structure of the TME. In this study, we show that metformin (Met), a diabetes drug, transforms CAFs in the TME. Met disrupts tumor-stromal cross talk by preventing breast cancer cell transforming growth factor-β (TGF-β) signaling and the production of stromal-derived factor-1 (SDF-1) and interleukin-8 (IL-8) by CAFs. The suppression of bidirectional signaling between tumor cells and CAFs by Met is attributed to increased phospho-AMP kinase (p-AMPK) levels. By upregulating p-AMPK in CAFs, Met induces prolyl hydroxylases (PHDs), leading to the degradation of hypoxia-inducible factor-1α (HIF-1α) in CAFs. Moreover, interruption of HIF-1α-driven SDF-1 signaling in CAFs by Met leads to decreased breast cancer cell invasion. These findings suggest that Met may be used to target tumor-promoting signaling between CAFs and breast cancer cells in the TME.

Immune checkpoint inhibitors (ICIs) have shown significant efficacy in various solid tumors, but only a small subgroup of patients benefit from them because of immune resistance. Oncorine (formerly H101), a recombinant human adenovirus type 5, has direct anticancer properties and enhances cell‐mediated immune responses. At present, few studies on the role of Oncorine in reversing resistance to ICIs have been reported. Here, we present a case with recurrent non‐small cell lung cancer (NSCLC). The patient developed resistance to nivolumab therapy. After trying immunotherapy plus chemotherapy or antiangiogenesis therapy, the patient only obtained a transient response. The patient then received experimental treatment with Oncorine together with nivolumab and anlotinib. She experienced symptomatic improvement with a performance status score of 1, and achieved stable disease despite partial lung tissue necrosis. This was a successful exploration of oncolytic viruses reversing immune resistance., Our patient with recurrent NSCLC experienced resistance to ICI (nivolumab), and was subsequently treated with nivolumab plus anlotinib with a transient response, followed by the combination of oncolytic virus (Oncorine) at the time of progression with obvious disease control. This was a successful exploration of oncolytic viruses reversing immune resistance.

In this study, a novel type of macromolecular prodrug, N-galactosylated chitosan (GC)−5-fluorouracil acetic acid (FUA) conjugate based nanoparticles, was designed and synthesized as a carrier for hepatocellular carcinoma drug delivery. The GC–FUA nanoparticles were produced by an ionic crosslinking method based on the modified ionic gelation of tripolyphosphate with GC–FUA. The structure of the as-prepared GC–FUA was characterized by Fourier transform infrared and 1H-NMR analyses. The average particle size of the GC–FUA nanoparticles was 160.1 nm, and their drug-loading content was 21.22 ± 2.7% (n = 3). In comparison with that of the freshly prepared nanoparticles, this value became larger after 7 days because of the aggregation of the GC–FUA nanoparticles. An in vitro drug-release study showed that the GC–FUA nanoparticles displayed a sustained-release profile compared to 5-fluorouracil-loaded GC nanoparticles. All of the results suggest that the GC–FUA nanoparticles may have great potential for anti-liver-cancer applications. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42625.