Camrelizumab and apatinib plus induction chemotherapy and concurrent chemoradiotherapy in stage N3 nasopharyngeal carcinoma: a phase 2 clinical trial.

The antiangiogenic agent apatinib has been shown to clinically improve responses to immune checkpoint inhibitors in several cancer types. Patients with N3 nasopharyngeal carcinoma have a high risk of distant metastasis, however, if the addition of immunotherapy to standard treatment could improve efficacy is unclear. In this phase II clinical trial (ChiCTR2000032317), 49 patients with stage TanyN3M0 nasopharyngeal carcinoma were enrolled and received the combination of three cycles of induction chemotherapy, camrelizumab and apatinib followed by chemoradiotherapy. Here we report on the primary outcome of distant metastasis-free survival and secondary end points of objective response rate, failure-free survival, locoregional recurrence-free survival, overall survival and toxicity profile. After induction therapy, all patients had objective response, including 13 patients (26.5%) with complete response. After a median follow-up of 28.7 months, the primary endpoint of 1-year distant metastasis-free survival was met for the cohort (1-year DMFS rate: 98%). Grade≥3 toxicity appeared in 32 (65.3%) patients, with the most common being mucositis (14[28.6%]) and nausea/vomiting (9[18.4%]). In this work, camrelizumab and apatinib in combination with induction chemotherapy show promising distant metastasis control with acceptable safety profile in patients with stage TanyN3M0 nasopharyngeal carcinoma.

Guided isolation of secondary metabolites from Nectria sp. MHHJ-3 by molecular network strategy.

The fungus Nectria sp. MHHJ-3 was isolated from Illigera rhodantha. A molecular networking-guided the secondary metabolites investigation of Nectria sp. MHHJ-3 led to the isolation of ten metabolites (1-10), including two new naphthalenone derivatives, nectrianaphthalenones A (1) and B (2), and two new steroids, nectriasteroids A (3) and B (4). Their structures were elucidated by extensive spectroscopic analysis including the HRESIMS, 1D/2D NMR and electronic circular dichroism (ECD) spectra. A plausible biosynthetic pathway for 1-2 was proposed. Compounds 1 and 2 exhibited moderate acetylcholinesterase (AChE) inhibitory activities. Compounds 3 and 4 showed significant cytotoxic activity against selected tumor cells. Particularly, compound 3 exhibited the strongest activity against A549 cells with an IC50 value of 13.73 ± 0.03 µM, which was at the same grade with that of positive control cisplatin.

Quassinoids: Phytochemistry and antitumor prospect.

Quassinoids, originating from the oxidative degradation of tetracyclic tirucallane triterpene, are a diverse class of secondary metabolites identifying from nature mostly in Simaroubaceae family. The crucial pharmacological activities and structural complexity of quassinoids have long fascinated scientists due to their medicinal uses, infamous toxicity, and unique biosynthesis. In the past few decades, 482 quassinoids, assigned to 6 skeletons, have been isolated and identified from plants. The names, classes, molecular formula, and plant sources of these secondary metabolites are collated here. This review will be a detailed update of the naturally occurring quassinoids reported from the plant kingdom, providing an in-depth discussion of their diversity, antitumor activities, structure-activity relationship.

Modified lanostane-type triterpenoids with neuroprotective effects from the fungus Inonotus obliquus.

Six undescribed lanostane triterpenoids (1-6), together with three known compounds (7-9) were isolated from Inonotus obliquus. Compounds 3-5 are the rare natural compounds featuring a 4,5-seco-lanostane core with a 5,7,9-trien-21,24-cyclopentane moiety. The structure elucidation of the compounds was conducted by spectroscopic techniques and the ECD method. The absolute configuration of compound 1 was confirmed by single-crystal X-ray diffraction analysis. All isolated compounds were assayed for their neuroprotective activity against H2O2-induced cell injury using human neuroblastoma SH-SY5Y cells. Compound 9 exhibited the most potent neuroprotective activity and the flow cytometry analysis indicated that 9 could protect SH-SY5Y cells from oxidative damage by inhibiting cell apoptosis.

Targeted isolation of cytotoxic germacranolide sesquiterpenes from Elephantopus scaber L. using small molecule accurate recognition technology.

Small molecule accurate recognition technology (SMART) is an emerging method for the rapid structural prediction of major constituents from crude extracts and fractions. In the present study, a targeted isolation of an Elephantopus scaber extract by SMART resulted in the obtention of 15 new (1-15) and five known germacranolide sesquiterpenes (16-20). Their structures were assigned by extensively analyzing HRESIMS, NMR, X-ray crystallographic analyses, modified Mosher's method results, and quantum chemical calculate electronic circular dichroism (ECD) spectra. All germacranolide sesquiterpenes were screened to determine their inhibitory effects with two hepatoma cell lines (HepG2 and Hep3B), and compounds 14, 16, 18, 19 and 20 showed significant cytotoxic activities against the HepG2 (IC50, 3.3-9.9 µM) and Hep3B (IC50, 4.5-8.6 µM) cell lines. Further study suggested that 18 can induce the apoptosis of hepatoma cells via mitochondrial dysfunction.

Germacranolides from Elephantopus scaber L. and their cytotoxic activities.

Seven undescribed germacranolides, named as scabertopinolide A-G were obtained from whole herbs of Elephantopus scaber L. The determination of their structures was conducted via comprehensive spectroscopic analyses combined with experimental electronic circular dichroism (ECD) spectroscopic data and quantum mechanical ECD calculations. The absolute configuration of scabertopinolide A was determined by X-ray crystallography data analysis. The cytotoxicity of all compounds was evaluated against three human cancer cell lines HepG2, Hep3B (human hepatocellular carcinoma cell lines), and MCF-7 (human breast adenocarcinoma cell line). Scabertopinolide G exhibited the most significant cytotoxic activities against the three cancer cell lines with IC50 values between 7.0 and 10.3 µM. Furthermore, flow cytometry analysis has suggested that scabertopinolide G may cause death of cancer cells through apoptosis induction.

Elephantopinolide A-P, germacrane-type sesquiterpene lactones from Elephantopus scaber induce apoptosis, autophagy and G2/M phase arrest in hepatocellular carcinoma cells.

Chromatographic purification of Elephantopus scaber led to 16 new germacrane-type sesquiterpene lactones (1-16), named elephantopinolide A-P, along with a known analogue (17). Their structures were confirmed by comprehensive spectroscopic analyses, single-crystal X-ray diffraction, and comparison between the experimental and calculated ECD spectra. Their hepatocellular inhibition activities against Hep3B and HepG2 cells were screened by MTT assay, and the structure-activity relationships were examined. The results revealed that 10 (IC50 value of 2.83 µM and 1.98 µM) is more potent than sorafenib. The underlying mechanism study demonstrated that 10 could markedly induce apoptosis accompanied by increased ROS production and decreased mitochondrial membrane potential, resulting in the autophagy and G2/M phase cell arrest in Hep3B and HepG2 cells. Furthermore, signal pathways including MAPKs and AKT may play important roles in 10-induced hepatocellular carcinoma cells death.