Corrigendum: Rational design of a Gd(III)-Cu(II) nanobooster for chemodynamic therapy against cancer cells.

[This corrects the article DOI: 10.3389/fchem.2022.856495.].

Efficacy and safety of apatinib as second or later-line therapy in extensive-stage small cell lung cancer: a prospective, exploratory, single-arm, multi-center clinical trial.

Background: A paucity of strategies exist for extensive-stage small cell lung cancer (ES-SCLC) patients who fail the first-line chemotherapy. Apatinib is a tyrosine kinase inhibitor (TKI) that selectively inhibits vascular endothelial growth factor receptor-2 (VEGFR-2), which has been demonstrated to have active anti-tumor activity in ES-SCLC when used only or combined with PD-1 inhibitors or chemotherapy with good tolerance. However, the efficacy and safety of apatinib monotherapy is unclear in second-line or beyond treatment of ES-SCLC. Methods: In this prospective, exploratory, single-arm, multi-center study, eligible patients were aged 18 years or older with histologically confirmed ES-SCLC, and had progressed on, or were intolerant to previous systemic treatment. Patients received apatinib 500 mg (orally qd, every 4 weeks a cycle). The efficacy was assessed after 1 cycle and then every 2 cycles based on computed tomography imaging per the Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). The primary endpoint was progression-free survival (PFS). The adverse events (AEs) were assessed per the National Cancer Institute Common Terminology Criteria for Adverse Events 4.0 (NCI-CTCAE 4.0). This study is registered in the Chinese Clinical Trial Registry, number ChiCTR-OPC-17013964. Results: From 28 July 2017 to 21 June 2019, 62 patients were screened for eligibility, among whom 57 patients were available for efficacy and safety analysis. The objective response rate (ORR) was 14.3% and disease control rate (DCR) was 79.6%. The median PFS was 5.6 months [95% confidence interval (CI): 3.3-8.0 months] and the median overall survival (OS) was 11.2 months (95% CI: 7.5-24.0 months). Among the participants who received apatinib as second-line treatment, the median PFS and OS were 6.1 months (95% CI: 2.6-7.6 months) and 12.0 months (95% CI: 7.9 months to not reached), respectively. The most common AEs of all grades were anemia (36.8%), hypertension (33.3%), fatigue (31.6%), blood bilirubin increased (22.8%), elevated transaminase (19.3%), and hand-foot syndrome (17.54%). Grade 3 AEs included 2 (3.5%) cases of hypertension and 1 (1.8%) case of fatigue. No grade 4/5 AEs were observed. Conclusions: Apatinib showed encouraging anti-tumor activity in pretreated ES-SCLC patients with tolerable toxicities. Further larger scale studies are warranted to demonstrate the efficacy of apatinib.

Rational Design of a Gd(III)-Cu(II) Nanobooster for Chemodynamic Therapy Against Cancer Cells.

Copper (II) containing coordination complexes have attracted much attention for chemodynamic therapy (CDT) against cancer cells. In this study, the bimetallic nanobooster [Gd2Cu(L)2(H2O)10]·6H2O was prepared by a solvothermal method based on tetrazole carboxylic acid ligand H4L [H4L = 3,3-di (1H-tetrazol-5-yl) pentanedioic acid]. It showed considerable cytotoxicity toward three kinds of human cancer cells (HeLa, HepG2, and HT29). The MTT assay showed that the IC50 (half-maximal inhibitory concentration) of the complex NPs on HeLa cells (4.9 µg/ml) is superior to that of HepG2 (11.1 µg/ml) and HT29 (5.5 µg/ml). This result showed that [Gd2Cu(L)2(H2O)10]·6H2O NPs can inhibit cell proliferation in vitro and may be potential candidates for chemodynamic therapy. In addition, the cytotoxicity was also confirmed by the trypan blue staining experiment. The results promise the great potential of Gd(III)-Cu(II) for CDT against cancer cells.

Detection of cytokeratin 19, human mammaglobin, and carcinoembryonic antigen-positive circulating tumor cells by three-marker reverse transcription-PCR assay and its relation to clinical outcome in early breast cancer.

AIMS: To investigate the diagnostic, predictive, and prognostic value of the detection of circulating tumor cells (CTCs) using a three-marker (CK19, hMAM and CEA) RT-PCR assay in patients with early breast cancer. PATIENTS AND METHODS: Peripheral blood was obtained from 50 patients with early-stage breast cancer before any systemic adjuvant therapy and analyzed for the presence of CK-19, hMAM and CEA mRNA-positive CTCs using an RT-PCR assay. The specificity of the primers used was evaluated in 20 healthy individuals, 24 patients with benign breast disease, and 30 patients with metastatic breast cancer. The detection of CTCs was correlated with clinical outcome. RESULTS: The detection rate of three-marker-positive CTCs in the blood of patients with early breast cancer was 54.0%, significantly higher than in patients with benign breast disease and healthy blood donors (p=0.002 and p=0.000, respectively). The three-marker RT-PCR assay had 58.8% sensitivity in the parallel test and 100% specificity for CTC detection in the serial test, which was higher than the sensitivity and specificity of single-marker assays. For early breast cancer, correlation analysis between detection of three-marker-positive CTCs and clinicopathological characteristics indicated that detection of threemarker-positive CTCs was significantly correlated with elevated serum CEA levels (p=0.001). After three years of follow-up, 13 of the 27 patients with three-marker-positive CTCs in their blood had relapsed and detection of three-marker-positive CTCs was significantly associated with locoregional recurrence and/or distant metastasis (p=0.002). Detection of three-marker-positive CTCs in peripheral blood was an independent risk factor for reduced median relapse-free interval (p=0.000). CONCLUSION: The three-marker RT-PCR assay can enhance the sensitivity and specificity of CTC detection compared to singlemarker assay. Detection of three-marker-positive CTCs was associated with relapse and might have important predictive and prognostic implications in early breast cancer.

Orally administered DNA vaccine delivery by attenuated Salmonella typhimurium targeting fetal liver kinase 1 inhibits murine Lewis lung carcinoma growth and metastasis.

The vascular endothelial growth factor (VEGF) receptor 2 (VEGFR-2), also called fetal liver kinase 1 (FLK1) in mice and kinase insert domain receptor (KDR) in humans, is an endothelial cell specific receptor tyrosine kinase that mediates lung cancer angiogenesis. We hypothesized that an active immunotherapy approach targeting FLK1 may inhibit lung cancer growth and metastasis. To test this hypothesis, we evaluated whether immune responses to FLK1 could be elicited in mice by immunization with an orally administered DNA vaccine encoding the extracellular domain (ECD) of FLK1 (pcDNA3.1-FLK1(ECD)) carried by attenuated Salmonella typhimurium. We found that the vaccine was effective at protective antitumor immunity in Lewis lung carcinoma models in mice by breaking immune tolerance to FLK1 self-antigen. Both FLK1-specific humoral and cellular immune responses against endothelial cells can be induced in mice by immunization with pcDNA3.1-FLK1(ECD). Immunization with pcDNA3.1-FLK1(ECD) resulted in tumor suppression and prolonged survival in mice challenged with Lewis lung carcinomas cells. Experimental pulmonary metastases were strongly inhibited in pcDNA3.1-FLK1(ECD) immunized mice challenged with Lewis lung carcinoma cells. Thus, we conclude that the plasmid DNA vaccine encoding the extracellular domain of FLK1 could be an important component of FLK1 DNA vaccine to prevent lung carcinoma recurrence and metastasis after surgery.