Search

Recent single-arm studies involving neoadjuvant camrelizumab, a PD-1 inhibitor, plus chemotherapy for resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC) have shown promising results. This multicenter, randomized, open-label phase 3 trial aimed to further assess the efficacy and safety of neoadjuvant camrelizumab plus chemotherapy followed by adjuvant camrelizumab, compared to neoadjuvant chemotherapy alone. A total of 391 patients with resectable thoracic LA-ESCC (T1b-3N1-3M0 or T3N0M0) were stratified by clinical stage (I/II, III or IVA) and randomized in a 1:1:1 ratio to undergo two cycles of neoadjuvant therapy. Treatments included camrelizumab, albumin-bound paclitaxel and cisplatin (Cam+nab-TP group; n= 132); camrelizumab, paclitaxel and cisplatin (Cam+TP group; n= 130); and paclitaxel with cisplatin (TP group; n= 129), followed by surgical resection. Both the Cam+nab-TP and Cam+TP groups also received adjuvant camrelizumab. The dual primary endpoints were the rate of pathological complete response (pCR), as evaluated by a blind independent review committee, and event-free survival (EFS), as assessed by investigators. This study reports the final analysis of pCR rates. In the intention-to-treat population, the Cam+nab-TP and Cam+TP groups exhibited significantly higher pCR rates of 28.0% and 15.4%, respectively, compared to 4.7% in the TP group (Cam+nab-TP versus TP: difference 23.5%, 95% confidence interval (CI) 15.1–32.0, P< 0.0001; Cam+TP versus TP: difference 10.9%, 95% CI 3.7–18.1, P= 0.0034). The study met its primary endpoint of pCR; however, EFS is not yet mature. The incidence of grade ≥3 treatment-related adverse events during neoadjuvant treatment was 34.1% for the Cam+nab-TP group, 29.2% for the Cam+TP group and 28.8% for the TP group; the postoperative complication rates were 34.2%, 38.8% and 32.0%, respectively. Neoadjuvant camrelizumab plus chemotherapy demonstrated superior pCR rates compared to chemotherapy alone for LA-ESCC, with a tolerable safety profile. Chinese Clinical Trial Registry identifier: ChiCTR2000040034.

ABSTRACTLung cancer (LC) is a malignant tumor with the highest incidence in the world, and its specific pathogenesis is still unclear. Circular RNAs (circRNAs) are a group of non-coding RNAs that play a key role in the development and progression of various cancers. The expression pattern and function of circRNAs in LC are still not completely distinct. In this study, it was aimed to study the expression and potential mechanism of circ-UBR1 in LC cells. Then it was found that circ-UBR1 was up-regulated in LC cells, and had microRNA (miR)-545-5p binding sites. Meanwhile, it was confirmed by dual-luciferase reporter assay that circ-UBR1 directly bound to miR-545-5p and then repressed its expression. MiR-545-5p was down-regulated in LC cells and refrained its expression by binding to the downstream target gene SSFA2. Knockdown circ-UBR1 or enhancive miR-545-5p repressed A549 cell proliferation, migration, and invasion, but accelerated apoptosis. After transfection with circ-UBR1 low expression vector, upregulation of SSFA2 apparently reversed the depression of reduced circ-UBR1 on cell proliferation, migration, and invasion, and the promotion of cell apoptosis. Further tumor xenograft experiments in nude mice also confirmed that knockdown of circ-UBR1 could increase the expression of miR-545-5p, but decrease the expression of SSFA2, thus alleviating the progression of LC in vivo. Therefore, these results fully indicate that circ-UBR1 promotes LC cell proliferation, migration, and invasion, but represses apoptosis via the circ-UBR1 axis, which may be a closely related marker and therapeutic target of LC.

ABSTRACTIt is necessary to explore new molecules for the improvement of precise diagnosis and antitumor therapies in lung cancer. LncRNAs (long non-coding RNAs) play an important role in the regulation of cancer cell malignant behavior and tumor development. In this work, we found that a newly discovered lncRNA, lncRNA PGM5P4-AS1, was lower expressed in lung cancer tissues than adjacent tissues. Then, the lncRNA PGM5P4-AS1 was overexpressed or knocked-down in different lung cancer cells, and its effects on the malignant phenotypes were measured by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, cell cycle assay, wound healing assay, and transwell assay. The results showed that the overexpression of PGM5P4-AS1 inhibited lung cancer cell proliferation, migration, and invasion activities, while these abilities were prominently promoted by the interference of PGM5P4-AS1. Further, the growth of lung cancer tumors in nude mice was also inhibited by PGM5P4-AS1 overexpression. In mechanism, PGM5P4-AS1 has the binding site of miR-1275 and could positively regulate the expression of LZTS3 via sponging miR-1275. In conclusion, PGM5P4-AS1 could be a potential precise diagnosis and therapeutic target biomarker of lung cancer.

The Hefei Basin of eastern China developed in response to uplift of the Dabie Orogen, and zircon dating can be used to assess the exhumation history of the orogen. Zircons were collected from samples of the Lower Jurassic Fanghushan Formation and Middle Jurassic Sanjianpu Formation in the southern Hefei Basin, and mica-quartz schist and biotite granite gneiss from the Susong Complex of the Dabie Orogen. The zircon U-Pb dating was undertaken using laser ablation-inductively coupled plasma-mass spectrometry. The detrital zircons from conglomerates of the Fanghushan Formation and from clasts within the conglomerates have age-frequency distributions with the main clusters between 2.0 and 1.8 Ga, similar to age data of the Susong Complex. On the other hand, the zircons of the Fanghushan Formation do not show the age cluster at 1000-900 Ma that characterizes zircons in the underlying metasediments of the lower Paleozoic Foziling Group. A cluster of Triassic zircon ages also appears in the arkosic sandstones of the Fanghushan Formation. These data indicate that the provenance of the Fanghushan Formation was a mixture of high-pressure (HP) and ultrahigh-pressure (UHP) Triassic metamorphic rocks, Paleozoic magmatic rocks, and the Susong Complex, but not the lower Paleozoic Foziling Group even though it directly underlies the sediments of the Hefei Basin. Two samples from the Sanjianpu Formation show zircon age clusters at 797 and 791 Ma (middle Neoproterozoic) and 226 Ma (Triassic), and again, these are markedly different from the age clusters that characterize the Foziling Group. It seems, therefore, that despite the Foziling Group being at the surface in the underwater depositional area of the Hefei Basin, it was not exposed in the source area of the Hefei basinal sediments during the Jurassic, and there are two possible reasons for this. First, the exhumation of the Dabie Orogen was directed partly towards the north, in the process of which some of the Foziling Group was covered. Second, the Susong Complex rocks became involved in the development of an accretionary wedge, thus covering some of the Foziling Group during the process of subduction.