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Purpose: The use of volumetric modulated arc therapy (VMAT), simultaneous integrated boost (SIB), and hypofractionated regimen requires adequate patient setup accuracy to achieve an optimal outcome. The purpose of this study was to assess the setup accuracy of patients receiving left‐sided breast cancer radiotherapy using deep inspiration breath‐hold technique (DIBH) and surface guided radiotherapy (SGRT) and to calculate the corresponding setup margins. Methods: The patient setup accuracy between and within radiotherapy fractions was measured by comparing the 6DOF shifts made by the SGRT system AlignRT with the shifts made by kV‐CBCT. Three hundred and three radiotherapy fractions of 23 left‐sided breast cancer patients using DIBH and SGRT were used for the analysis. All patients received pre‐treatment DIBH training and visual feedback during DIBH. An analysis of variance (ANOVA) was used to test patient setup differences for statistical significance. The corresponding setup margins were calculated using the van Herk's formula. Results: The intrafractional patient setup accuracy was significantly better than the interfractional setup accuracy (p < 0.001). The setup margin for the combined inter‐ and intrafractional setup error was 4, 6, and 4 mm in the lateral, longitudinal, and vertical directions if based on SGRT alone. The intrafractional error contributed ≤1 mm to the calculated setup margins. Conclusion: With SGRT, excellent intrafractional and acceptable interfractional patient setup accuracy can be achieved for the radiotherapy of left‐sided breast cancer using DIBH and modern radiation techniques. This allows for reducing the frequency of kV‐CBCTs, thereby saving treatment time and radiation exposure. [ABSTRACT FROM AUTHOR]

The application of wounding stress can induce the accumulation of phenolic antioxidants in carrots. This study aimed to investigate the possible regulation role of invertase (INV) on the biosynthesis of phenolics in wounded carrots. In this study, carrots were cut into two different wounding intensities of slices and cubes, then stored at 20 °C for 2 days. The results showed that wounding stress caused an obvious increase in phenolic content and antioxidant capacity in carrot tissues, and a positive correlation was observed between the biosynthesis of phenolic compounds and the degradation of sucrose. Simultaneously, wounding activated the sucrose-cleaving enzymes of INVs, including acid INV (AI) and neutral INV (NI), and up-regulated the expressions of most encoding genes of INVs. In addition, treatment with INV activators accelerated the accumulation of phenolic antioxidants, while treatment with INV inhibitors suppressed this process, suggesting that the synthesis of phenolic compounds in wounded carrots is closely related to the availability of sugars. Our findings provide new insights into the regulation role of INV on the wound-induced accumulation of phenolic compounds in carrots, which may be helpful in using wounded plants to produce more phenolic antioxidants. [ABSTRACT FROM AUTHOR]

Circular RNAs (circRNAs) play vital regulatory roles in the development of ovarian cancer (OC). However, the functions of circRNA Atlastin GTPase 2 (circATL2) in paclitaxel (PTX) resistance of OC are still unclear. As a result, circATL2 was upregulated in PTX‐resistant OC tissues and cells. CircATL2 knockdown reduced IC50 of PTX, inhibited colony formation ability and promoted cell cycle arrest and apoptosis in PTX‐resistant OC cells. Silencing of circATL2 restrained PTX resistance in vivo. Furthermore, miR‐506‐3p could be targeted by circATL2 and miR‐506‐3p inhibition reversed the impacts of circATL2 knockdown on PTX resistance and cell progression in PTX‐resistant OC cells. NFIB was identified as the target of miR‐506‐3p. MiR‐506‐3p overexpression suppressed PTX resistance and malignant behaviors of PTX‐resistant OC cells, with NFIB elevation rescued the impacts. To summarize, circATL2 promoted the resistance of OC to PTX by sponging miR‐506‐3p to upregulate NFIB expression, providing a new sight in chemoresistance of OC. [ABSTRACT FROM AUTHOR]

Purpose: To assess whether the integration of PD-1 inhibitor with total neoadjuvant therapy (iTNT) can lead to an improvement in complete responses (CRs) and favors a watch-and-wait (WW) strategy in patients with proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC)., Patients and Methods: We conducted a prospective, multicenter, randomized, open-label, phase II trial using a pick-the-winner design. Eligible patients with clinical T3-4 and/or N+ rectal adenocarcinoma were randomly assigned to group A for short-course radiotherapy (SCRT) followed by six cycles of consolidation immunochemotherapy with capecitabine and oxaliplatin and toripalimab or to group B for two cycles of induction immunochemotherapy followed by SCRT and the rest four doses. Either total mesorectal excision or WW was applied on the basis of tumor response. The primary end point was CR which included pathological CR (pCR) after surgery and clinical CR (cCR) if WW was applicable, with hypothesis of an increased CR of 40% after iTNT compared with historical data of 25% after conventional TNT., Results: Of the 130 patients enrolled, 121 pMMR/MSS patients were evaluable (62 in group A and 59 in group B). At a median follow-up of 19 months, CR was achieved at 56.5% in group A and 54.2% in group B. Both groups fulfilled the predefined statistical hypothesis ( P < .001). Both groups reported a pCR rate of 50%. Respectively, 15 patients in each group underwent WW and remained disease free. The most frequent grade 3 to 4 toxicities were thrombocytopenia and neutropenia. Patients in group A had higher rate of cCR (43.5% v 35.6%) at restaging and lower rate of grade 3 to 4 thrombocytopenia (24.2% v 33.9%) during neoadjuvant treatment., Conclusion: The iTNT regimens remarkably improved CR rates in pMMR/MSS LARC compared with historical benchmark with acceptable toxicity. Up-front SCRT followed by immunochemotherapy was selected for future definitive study.

Objective: To investigate the potential effect of Lysimachia capillipes capilliposide (LCC) on the chemo sensitivity and the stemness of human ovarian cancer cells., Methods: Cell Counting Kit-8 (CCK8) was used to measure the IC 50 values. The apoptosis of cells was measured through flow cytometry. Evaluation of the stemness and differentiation markers was performed by the immunoblotting and the immunostaining assays. RNA-seq was performed through the Illumina HiSeq PE150 platform and differentially expressed genes (DEGs) were screened out through the bioinformation analysis. Overexpression or knockdown of Fos gene was achieved by shRNA transfection., Results: Pre-exposure of A2780T cells with 10 μg/mL LCC sensitized them to paclitaxel, of which the IC 50 value reduced from 8.644 μmol/L (95%CI: 7.315-10.082 μmol/L) to 2.5 μmol/L (95%CI: 2.233-2.7882 μmol/L). Exposure with LCC enhanced the paclitaxel-induced apoptosis and inhibited the colony formation of A2780T cells. LCC exposure reduced the expression of cancer stemness markers, ALDH1, Myd88 and CD44, while promoting that of terminal differentiation markers, NFATc1, Cathepsin K and MMP9. RNA-seq analysis revealed that the expressions of FOS and JUN were upregulated in LCC-treated A2780T cells. A2780T cells overexpressing Fos gene displayed increased paclitaxel-sensitivity and reduced cell stemness, and shared common phenotypes with LCC-treated A2780T cells., Conclusion: These findings suggested that LCC promoted terminal differentiations of ovarian cancer cells and sensitized them to paclitaxel through activating the Fos/Jun pathway. LCC might become a novel therapy that targets at cancer stem cells and enhances the chemotherapeutic effect of ovarian cancer treatments., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Tianjin Press of Chinese Herbal Medicines. Published by ELSEVIER B.V.)

Cancer stem cells (CSCs) are a cellular subpopulation accelerating cancer cell growth, invasion and metastasis and survival. After chemoradiotherapy, CSCs are enriched because of their survival advantages and lead to tumor relapse and metastasis. Elimination of CSCs is critically important for the radical treatment of human cancers. Long non-coding RNAs (lncRNAs) are a group of RNAs longer than 200 nucleotides and have no protein-coding potential. Aberrant expressions of lncRNAs are associated with human diseases including cancer. LncRNAs function as cancer biomarkers, prognostic factors and therapeutic targets. They induce cancer stemness by chromatin modification, transcriptional regulation or post-transcriptional regulation of target genes as a sponge or through assembling a scaffold complex. Several factors caused aberrant expressions of lncRNAs in CSCs such as genes mutations, epigenetic alteration and environmental stimuli. Targeting of lncRNAs has been demonstrated to significantly reverse the chemoradioresistance of CSCs. In this review, we have summarized the progress of studies regarding lncRNAs-mediated therapy resistance of CSCs and clarified the molecular mechanisms. Furthermore, we have for the first time analyzed the influences of lncRNAs on cell metabolism and emphasized the effect of tumor microenvironment on lncRNAs functions in CSCs. Overall, the thorough understanding of the association of lncRNAs and CSCs would contribute to the reversal of therapy resistance., Competing Interests: None., (AJCR Copyright © 2021.)