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In the KEYNOTE-040 study,[1] published in The Lancet, Ezra Cohen and colleagues reported that pembrolizumab provides a survival benefit compared with standard-of-care treatment (methotrexate, docetaxel, or cetuximab) in patients with recurrent or metastatic head-and-neck squamous cell carcinoma. Human papillomavirus (HPV)-positive metastatic head-and-neck squamous cell carcinomas have stronger T-cell infiltration and increased concentrations of immunoregulatory proteins, including programmed cell death 1 and cytotoxic T lymphocyte-associated protein 4, compared with HPV-negative metastatic head-and-neck squamous cell carcinomas,[3] suggesting that patients with HPV-positive disease could be good candidates for immunotherapy. This suggestion was confirmed by KEYNOTE-012,[4] in which pembrolizumab-treated patients with HPV-positive disease tended to have longer overall survival than that of patients with HPV-negative disease. [Extracted from the article]

Garlic organosulfur components exhibit antitumor activity, but the molecular mechanisms underlying these effects have not been well characterized. We showed that Z-ajoene, a sulfur-rich compound purified from garlic, induced time- and dose-dependent apoptosis in HL-60 cells. This process implied the activation of caspase-3 and the cleavage of the antiapoptotic protein Bcl-2. The caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp-[OMe]-fluoromethylketone inhibited Bcl-2 cleavage and apoptosis induced by Z-ajoene. This effect was partially prevented by treatment of HL-60 cells with the antioxidant N-acetylcysteine. Hence, the transmission of apoptotic signal induced by Z-ajoene involved a reactive oxygen species-dependent pathway leading to caspase-dependent Bcl-2 cleavage. [ABSTRACT FROM AUTHOR]

A novel 3D Co(II) coordination polymer (CP) {Co3(IBT)2(H2O)2}n (1) has been synthesized through the reaction of 4,5-Bis(tetrazol-5-yl)imidazole (H3IBT) with Co(NO3)2 in a mixed solvent of N,N-dimethylformamide (DMF) and water. The structural determination results show that complex 1 is a 3D framework with a (3,4)-connected net. Furthermore, its inhibitory activity on endometrial cancer cells was evaluated and the related mechanism was also discussed in the research. The relative expression of the miRNA29 in endometrial cancer cells was measured with real-time PT-PCR. In addition to this, the western blot was performed to detect the endometrial cancer cell apoptosis after compound treatment for the mechanism exploration. The hypothesis that arises from the experimental observation has been further investigated by using molecular docking simulation, where the possible binding interactions between the ligand and Bcl2 protein are studied explicitly. [ABSTRACT FROM AUTHOR]

Ixeris sonchifolia alias Kudiezi, it was named Ixeris sonchifolia (Bunge) Hance , a synonym for Crepidiastrum sonchifolium (Bunge) Pak & Kawano in the https://www.iplant.cn/. And it was first published in J. Linn. Soc., Bot. 13: 108 (1873), which was named Ixeris sonchifolia (Maxim.) Hance in the MPNS (http://mpns.kew.org). As a widely distributed medicinal and edible wild plant, it possesses unique bitter-cold characteristics and constituents with various pharmacological activities. Its main antitumor substances, same as artemisinin and paclitaxel, are classified as terpenoids and have become research foci in recent years. However, its specific biological activity and role in antitumor treatment remain largely unclear. This study aimed to elucidate the molecular targets and potential mechanisms of hepatocellular carcinoma apoptosis induced by Ixeris sonchifolia. We used network pharmacology methods to analyze and screen the active ingredients and possible underlying mechanisms of Ixeris sonchifolia in treating liver cancer and employed integrative time- and dose-dependent toxicity, transcriptomics, and molecular biology approaches to comprehensively verify the function of Ixeris sonchifolia extract (IsE) in human hepatoblastoma cell (HepG2) apoptosis and its potential mechanism. A total of 169 common targets were screened by network pharmacology, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that IsE inhibited HepG2 cell activity in a time- and dose-dependent manner. Western blot analysis confirmed that IsE promoted HepG2 cell apoptosis by inhibiting the PI3K/AKT signaling pathway and that the PI3K/AKT inhibitor LY294002 also substantially enhanced IsE-induced apoptosis. The PI3K/AKT signaling pathway exhibited significant differences compared to that in the control group. Combining network pharmacology with experimental verification, IsE inhibited mitochondrial function and the PI3K/AKT pathway while inducing hepatoma cell apoptosis. IsE may have promising potential for liver cancer treatment and chemoprevention. [Display omitted] • Ixeris sonchifolia , Its main antitumor substances, same as artemisinin and paclitaxel, are classified as terpenoids. • The antitumor activity of terpenoids has become a research hotspot in recent years. • We predicted the anti-liver cancer components of Ixeris sonchifolia and their possible mechanisms, and verified them. • Ixeris sonchifolia inhibited mitochondrial function and the PI3K/AKT pathway while inducing hepatoma cell apoptosis. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the molecular mechanisms underlying the roles of metformin (MET) and Sorafenib (SOR) in the treatment of endometrial hyperplasia (EH) in polycystic ovary syndrome (PCOS). Effects of MET and SOR on the area of endometrium and myometrium were detected. Western blot analysis and immunohistochemistry assays were carried out to detect the levels of mammalian target of rapamycin complex 1 (mTORC1), mTORC2, LC3‐II, P62, and Caspase‐3 in rats and cultured cells. Furthermore, cell counting kit‐8 assay and flow cytometry analysis was carried out to determine the apoptotic profiles of treated cells. MET and SOR could apparently decrease the areas of endometrium and myometrium in PCOS. MET notably enhanced the expression of LC3‐II and Caspase‐3 in PCOS while substantially reducing the level of mTORC1 and P62. Similarly, SOR also enhanced the expression of LC3‐II and Caspase‐3 in PCOS while substantially reducing the level of mTORC2 and P62. Treatment with MET and SOR significantly inhibited the proliferation of HCC‐94 and HEC‐1‐A cells while promoting their apoptosis by upregulating the expression of Caspase‐3. In cells treated with MET, the expression of mTORC1 and LC3‐II was upregulated while the expression of P62 was downregulated. Similarly, in cells treated with SOR, the expression of mTORC2 and LC3‐II was also upregulated while the expression of P62 was also downregulated. Furthermore, MET showed no effect on mTORC2 expression, while SOR showed no effect on mTORC1 expression. In this study, we suggested that MET and SOR alleviated the risk of EH in PCOS via the mTORC1/autophagy/apoptosis axis and mTORC2/autophagy/apoptosis axis, respectively. [ABSTRACT FROM AUTHOR]

Abstract: In the present study, the effect of a novel derivative of riccardin D (RD-N) against cancer cell lines was investigated in vitro and in vivo. We found that RD-N accumulated in the lysosomes associated with lysosomal swelling. As a result, the destabilized lysosomes induced cathepsins to release from the lysosomes into the cytosol and induced cell death which displayed features characteristic to both apoptosis and necrosis. In vivo tumor xenograft model indicated treatment of RD-N significantly reduced size and weight of the tumor compared with vehicles. These findings suggest RD-N could be a promising candidate for treatment of cancer. [Copyright &y& Elsevier]

Background: Unprecedented durable responses are identified in clinical studies to target the signaling of programmed cell death protein-1 (PD-1) as well as its ligand (PD-L1) in patients with squamous-cell non-small cell lung cancer (NSCLC). However, factors predicting the patient subtypes that are responsive to PD-1/PD-L1inhibitors have not been fully understood yet. Biomarkers, like PD-L1 expression, tumor mutational burden(TMB), DNA mismatch repair deficiency (dMMR), and tumor-infiltrating lymphocytes (TILs), have been utilized to select patients responsive to PD-1/PD-L1inhibitors in the clinic, but each of them has limited use. Lung adenocarcinoma patients with a mutation of TP53 or KRAS, particularly those with co-mutations of TP53 and KRAS, can benefit from anti–PD-1 treatment. Case presentation: In this study, the co-mutations of TP53 and KRAS in a 64-year-old non-smoking man with squamous-cell NSCLC patient was described using the next-generation sequencing (NGS) technology. The patient was treated with the pembrolizumab combined with gemcitabine as the salvage therapy, and a marked partial response could be attained, which had persisted for over 7 months. Conclusion: In addition to testing common driving genes, like EGFR, ALK, ROS1 and BRAF, both TP53, and KRAS should also be considered in advanced or metastatic squamous-cell NSCLC.TP53 and KRAS co-mutations in squamous-cell NSCLC can be a potential factor to assess possible response to PD-1 blockade immunotherapy, but further studies with more cases are needed to confirm the prediction power. [ABSTRACT FROM AUTHOR]