المؤلفون: Baoqing Chen, Shiliang Liu, Yujia Zhu, Ruixi Wang, Xingyuan Cheng, Biqi Chen, Mihnea P. Dragomir, Yaru Zhang, Yonghong Hu, Mengzhong Liu, Qiaoqiao Li, Hong Yang, Mian Xi

المصدر: Nature Communications, Vol 15, Iss 1, Pp 1-11 (2024)

مصطلحات موضوعية: Science

الوصف: Abstract The combination of toripalimab (an anti-PD-1 antibody) with definitive chemoradiotherapy (CRT) demonstrated encouraging efficacy against locally advanced esophageal squamous cell carcinoma (ESCC) in the EC-CRT-001 phase II trial (NCT04005170). The primary endpoint of this trial was the clinical complete response rate (cCR), and the secondary endpoints included overall survival (OS), progression-free survival (PFS), duration of response, and quality of life. The exploratory analyses of EC-CRT-001 include exploring the role of circulating tumor DNA (ctDNA) and blood-based tumor mutational burden (bTMB) in predicting the response and survival. In total, 118 blood and 35 tissue samples from 42 enrolled patients were included in the analyses. We found that ctDNA-negative patients achieved a higher cCR compared to those with detectable ctDNA during CRT (83%, 19/23 vs. 39%, 7/18; p = 0.008) or post-CRT (78%, 21/27 vs. 30%, 3/10; p = 0.017). Patients with detectable ctDNA during CRT had shorter PFS (p = 0.014). Similarly, patients with post-CRT detectable ctDNA had a significantly shorter PFS (p = 0.012) and worse OS (p = 0.004). Moreover, patients with high bTMB levels during CRT had prolonged OS (p = 0.027). In conclusion, ctDNA and bTMB have the potential to predict treatment efficacy and survival in ESCC treated with CRT and immunotherapy.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/5208618c38c443d3b5493d7559fed793Test

المؤلفون: Hui Jiang, Kanjiebubi Makelike, Baoqing Chen, Mian Xi, Qiaoqiao Li, Yonghong Hu, Yujia Zhu

المصدر: Radiation Oncology, Vol 18, Iss 1, Pp 1-14 (2023)

مصطلحات موضوعية: Esophageal cancer, Chemotherapy, Radiotherapy, Esophagus, Recurrence, Salvage treatment, Medical physics. Medical radiology. Nuclear medicine, R895-920, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract Background Definitive radiotherapy plus concurrent chemotherapy has been a standard treatment for esophagus patients who are unfit to undergo surgery. However, there are a variety of concurrent chemotherapy regimens with varying efficacy. In this phase II prospective study, we compared the efficacy and toxicity of DP (docetaxel and cisplatin) and PF (cisplatin and 5-fluorouracil) regimens with concurrent chemoradiotherapy (CCRT) in patients with esophageal squamous cell carcinoma (ESCC) and analyzed the 5-year overall survival (OS) and progression free survival (PFS). We also summarized the salvage treatments and late toxicities. Methods We enrolled 86 patients with clinical stage II-IVA from the Sun Yat-sen University Cancer Center. The patients were divided into two groups: PF group (41) and DP group (45). Statistics were analyzed using SPSS version 19.0. Results The 5-year OS rates were 62.9% ± 7.6% in PF group, and 52.7% ± 7.5% in DP group (P = 0.131), respectively. The 5-year PFS rates were 43.9% ± 7.8% for PF group, and 40.0% ± 7.3% for DP group (P = 0.398), respectively. Sixteen patients in the DP group and thirteen in the PF group received salvage treatment. For those patients with local residual or local recurrent disease, the median survival time after salvage treatment was 13.5 months and the 1, 2, and 3-year survival rates were 79.0%, 50.3%, and 43.1%, respectively. For all patients, thirteen (15.1%) had Grade 2 late cardiac toxicities. One patient had Grade 2 pleural effusion and required diuretic. Most patients with pneumonia are mild, and only one patient in PF group had Grade 2 pneumonia. One patient in the DP group developed tracheoesophageal fistula. Conclusions The 5-year follow-up confirmed that definitive CCRT with the DP regimen did not improve the treatment response, OS, or PFS in patients with ESCC compared to the PF regimen. The PF regimen remains the standard regimen for definitive CCRT for patients with locally advanced ESCC. Long-term follow-up also suggested that appropriate and active salvage treatment has a survival benefit for some patients, and late cardiopulmonary toxicities should be noticed during follow-up. Trial registration The trial was registered at https://clinicaltrials.govTest (ClinicalTrials.gov Identifier: NCT 02969473, October 2010).

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1748-717XTest

الوصول الحر: https://doaj.org/article/a2ebb54ab3994a21a4734a9ca630d8cfTest

المؤلفون: Hui Jiang, Qiaoqiao Li, Baoqing Chen, Mian Xi, Kanjiebubi Makelike, Shiliang Liu, Yonghong Hu, Yujia Zhu

المصدر: Cancer Medicine, Vol 12, Iss 14, Pp 15187-15198 (2023)

مصطلحات موضوعية: dose escalation, esophageal squamous cell carcinoma, nanoparticle albumin‐bound‐paclitaxel, phase I study, radiotherapy, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract Background This phase I study aimed to assess the safety, dose‐limiting toxicity (DLT), maximum tolerated dose (MTD) and preliminary effect of nanoparticle albumin‐bound (nab)‐paclitaxel in combination with concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Methods Patients with locally advanced ESCC who were ineligible or refused surgery were enrolled. Nab‐paclitaxel (60 mg/m2, 75 mg/m2, and 90 mg/m2) and cisplatin (25 mg/m2) were administered intravenously weekly on days 1, 8, 15, 22, and 29 on the basis of the 3 + 3 dose escalation method. The total dose of radiation was 50–64 Gy. The primary endpoint was the safety of chemotherapy. Results The study enrolled 12 patients across three dose levels. No treatment‐related deaths occurred. One patient in the 60 mg/m2 dose level occurred dose‐limiting Grade 3 febrile neutropenia. No DLT was found in the 90 mg/m2 dose level thus the MTD was not reached. The phase II study's recommended dose was 75 mg/m2 based on the available preclinical and clinical data including pharmacokinetics, pharmacodynamics, efficacy, and toxicity. The frequent hematologic toxicities were leukocytopenia (Grade 1–2 of 66.7% and Grade 3–4 of 33.3%), neutropenia (Grade 1–2 of 91.7% and Grade 3–4 of 8.3%). Nonhematologic toxicities were mild and manageable. Overall response rate (ORR) of all patients achieved 100%. Conclusions Weekly schedule of cisplatin and nab‐paclitaxel in combination with concurrent radiotherapy showed manageable toxicities and promising antitumor activity in patients with locally advanced ESCC. The recommended dose of nab‐paclitaxel for further studies is 75 mg/m2.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-7634Test

الوصول الحر: https://doaj.org/article/4fe0fa39b65d495c92d2f8902825346eTest

المؤلفون: Ruixi Wang, Xingyuan Cheng, Dongmei Chi, Shiliang Liu, Qiaoqiao Li, Baoqing Chen, Mian Xi

المصدر: Discover Oncology, Vol 14, Iss 1, Pp 1-16 (2023)

مصطلحات موضوعية: Methyladenosine, Esophageal squamous cell carcinoma, Prognostic biomarker, Treatment response, Immune cell infiltration, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract Background Esophageal squamous cell carcinoma (ESCC) is the most common esophageal malignancy, and RNA methylation has been reported to be involved in the tumorigenesis of ESCC. However, no study has explored methylation modifications in m1A and m7G as prognostic markers for survival prediction in ESCC. Methods Public gene-expression data and clinical annotation of 254 patients obtained from The Cancer Genome Atlas and the Gene Expression Omnibus databases were analyzed to identify potential consensus clusters of m1A and m7G modification-related genes. The RNA-seq of 20 patients in Sun Yat-Sen University Cancer Center was used as the validation set. Following screening for relevant differentially expressed genes (DEGs) and enrichment pathways were elucidated. DEGs were used to construct risk models using the randomForest algorithm, and the prognostic role of the models was assessed by applying Kaplan–Meier analysis. Extent of immune cell infiltration, drug resistance, and response to cancer treatment among different clusters and risk groups were also evaluated. Results Consensus clustering analysis based on m1A and m7G modification patterns revealed three potential clusters. In total, 212 RNA methylation-related DEGs were identified. The methylation-associated signature consisting of 6 genes was then constructed to calculate methylation-related score (MRScore) and patients were dived into MRScore-high and MRScore-low groups. This signature has satisfied prognostic value for survival of ESCC (AUC = 0.66, 0.67, 0.64 for 2-, 3-, 4- year OS), and has satisfied performance in the validation SYSUCC cohort (AUC = 0.66 for 2- and 3-year OS). Significant correlation between m1A and m7G modification-related genes and immune cell infiltration, and drug resistance was also observed. Conclusions Transcriptomic prognostic signatures based on m1A and m7G modification-related genes are closely associated with immune cell infiltration in ESCC patients and have important correlations with the therapeutic sensitivity of multiple chemotherapeutic agents.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2730-6011Test

الوصول الحر: https://doaj.org/article/ae5efcf2b5294ba5ad9a0ed0c8f276dfTest

المؤلفون: Andreas Untergasser, Jan Hellemans, Michael W. Pfaffl, Jan M. Ruijter, Maurice J. B. van denHoff, Mihnea P. Dragomir, Douglas Adamoski, Sandra Martha Gomes Dias, Rui Manuel Reis, Manuela Ferracin, Emmanuel Dias‐Neto, Ian Marsh, Mikael Kubista, Muller Fabbri, Ajay Goel, Ondřej Slabý, Erik Knutsen, Baoqing Chen, Massimo Negrini, Koshi Mimori, Martin Pichler, Maria Papatriantafyllou, Simone Anfossi, Thomas D. Schmittgen, Jim Huggett, Stephen Bustin, Jo Vandesompele, George A. Calin, for the HEROIC (tHe initiativE gRoup On qRT dIsClosure) Consortium

المصدر: Molecular Oncology, Vol 17, Iss 5, Pp 713-717 (2023)

مصطلحات موضوعية: accuracy, quantification, RNA, RT‐qPCR, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Accuracy and transparency of scientific data are becoming more and more relevant with the increasing concern regarding the evaluation of data reproducibility in many research areas. This concern is also true for quantifying coding and noncoding RNAs, with the remarkable increase in publications reporting RNA profiling and sequencing studies. To address the problem, we propose the following recommendations: (a) accurate documentation of experimental procedures in Materials and methods (and not only in the supplementary information, as many journals have a strict mandate for making Materials and methods as visible as possible in the main text); (b) submission of RT‐qPCR raw data for all experiments reported; and (c) adoption of a unified, simple format for submitted RT‐qPCR raw data. The Real‐time PCR Data Essential Spreadsheet Format (RDES) was created for this purpose.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1574-7891Test; https://doaj.org/toc/1878-0261Test

الوصول الحر: https://doaj.org/article/fc57157ea1114752966f2e759b70680fTest

المؤلفون: Rui Chen, Qianwen Liu, Qiaoqiao Li, Yujia Zhu, Lei Zhao, Shiliang Liu, Baoqing Chen, Mengzhong Liu, Yonghong Hu, Ting Lin, Jibin Li, Jiyang Chen, Yingxin Lv, Jianhua Fu, Mian Xi, Hong Yang

المصدر: EClinicalMedicine, Vol 62, Iss , Pp 102118- (2023)

مصطلحات موضوعية: Esophageal squamous cell carcinoma, Toripalimab, Neoadjuvant chemoradiotherapy, Pathological complete response, Safety, Medicine (General), R5-920

الوصف: Summary: Background: To evaluate the efficacy and safety of toripalimab combined with neoadjuvant chemoradiotherapy (NCRT) for locally advanced esophageal squamous cell carcinoma (ESCC). Methods: In this single arm, phase II trial, 44 ESCC patients were enrolled from December 2019 to July 2021 at Sun Yat-sen University Cancer Center (Guangzhou, China). All patients received concurrent radiotherapy (44 Gy in 20 fractions), chemotherapy (paclitaxel 50 mg/m2 and cisplatin 25 mg/m2 on days 1, 8, 15, and 22), and toripalimab (240 mg on days 1 and 22). Within 6–8 weeks of neoadjuvant treatment, patients underwent surgery. The results of the study patients were compared with those of 86 matched patients between July 2015 and March 2022. The primary endpoint was pathological complete response (pCR) rate, and the secondary endpoints were treatment-related adverse events and R0 rates. This trail was registered with ClinicalTrails.gov, NCT04006041. Findings: All patients received neoadjuvant treatment, and 42 completed esophagectomy. Of the 42 patients, 21 (50%; 95% CI 35–65) achieved pCR and 2 (5%) patients were ypT0N+. The R0 resection rate was 98% (41/42). Nine (20%) of 44 patients had grade 3/4 adverse events. Among the perioperative complications (n = 42), anastomotic leakage occurred in five cases (12%), tracheal fistula in three cases (7%), and postoperative death in one case (2%) due to tracheal fistula. Compared with the control cohort, the pCR rate of the study group was higher but without significant difference (50% vs. 36%, P = 0.19). Interpretation: Toripalimab combined with NCRT failed to show significantly better pCR rate than historical data. Nevertheless, considering the signs of efficacy and acceptable safety of this regimen, further evaluation in phase III randomized trials might be warranted. Funding: National Natural Science Foundation of China.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S258953702300295XTest; https://doaj.org/toc/2589-5370Test

الوصول الحر: https://doaj.org/article/521bf24d17c141f8a2da428e4bf25a53Test

المؤلفون: Ling Li, Jiajun Yu, Baoqing Chen, Ying Guo, Yufeng Yang

المصدر: Frontiers in Pharmacology, Vol 14 (2023)

مصطلحات موضوعية: abrocitinib, atopic dermatitis, dupilumab, meta-analysis, adolescents’, Therapeutics. Pharmacology, RM1-950

الوصف: Objective: This study aims to investigate the safety and efficacy of abrocitinib in treating moderate-to-severe AD in adolescents and adults.Methods: Pubmed, Cochrane, Embase, and Web of science data base were searched from inception to 9 August 2022. All randomized controlled trials (RCTs) evaluating the efficacy and safety of abrocitinib in moderate to severe AD were included in the meta-analysis.Results: This meta-analysis comprised 7 studies and found that 100 mg or 200 mg of abrocitinib significantly improved IGA {[RR = 2.44, 95% CI (1.93–3.08)] [RR = 3.16, 95% CI (2.52–3.96)]} and EASI-75{[RR = 2.18, 95%CI (1.78–2.67)] [RR = 3.04, 95%CI (2.22–4.16)]} responses compared to placebo. Following that, the population was divided into adolescent and adult groups. The abrocitinib improved IGA, EASI-75 responses, and it was still superior to placebo in both the adolescent and the adult groups. PP-NRS4 response index demonstrated that abrocitinib had a greater effect than placebo at 100 mg [RR = 2.22, 95% CI 1.80–2.72] and 200 mg [RR = 3.28, 95% CI 2.59–4.17]. Abrocitinib improved PSAAD, POEM, DLQI, CDLQI, and HADS more than a placebo.Conclusion: In conclusion, this meta-analysis preliminarily demonstrated that abrocitinib had higher efficacy and safety in the treatment of moderate-to-severe AD in adolescents and adults. In addition, abrocitinib could rapidly relieve itching, and effectively improve symptoms and signs, with a greater effect at the dosage of 200 mg than 100 mg.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fphar.2023.1154949/fullTest; https://doaj.org/toc/1663-9812Test

الوصول الحر: https://doaj.org/article/904004e3d6f04226bc0ccdda87b690d4Test

المؤلفون: BaoQing Chen, Mihnea P. Dragomir, Chen Yang, Qiaoqiao Li, David Horst, George A. Calin

المصدر: Signal Transduction and Targeted Therapy, Vol 7, Iss 1, Pp 1-20 (2022)

مصطلحات موضوعية: Medicine, Biology (General), QH301-705.5

الوصف: Abstract It is now well known that non-coding RNAs (ncRNAs), rather than protein-coding transcripts, are the preponderant RNA transcripts. NcRNAs, particularly microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are widely appreciated as pervasive regulators of multiple cancer hallmarks such as proliferation, apoptosis, invasion, metastasis, and genomic instability. Despite recent discoveries in cancer therapy, resistance to chemotherapy, radiotherapy, targeted therapy, and immunotherapy continue to be a major setback. Recent studies have shown that ncRNAs also play a major role in resistance to different cancer therapies by rewiring essential signaling pathways. In this review, we present the intricate mechanisms through which dysregulated ncRNAs control resistance to the four major types of cancer therapies. We will focus on the current clinical implications of ncRNAs as biomarkers to predict treatment response (intrinsic resistance) and to detect resistance to therapy after the start of treatment (acquired resistance). Furthermore, we will present the potential of targeting ncRNA to overcome cancer treatment resistance, and we will discuss the challenges of ncRNA-targeted therapy—especially the development of delivery systems.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2059-3635Test

الوصول الحر: https://doaj.org/article/f53841bc61ce490b838c6002f740738cTest

المؤلفون: Ting Wang, Asmitananda Thakur, Baoqing Chen

المصدر: BMC Pulmonary Medicine, Vol 21, Iss 1, Pp 1-6 (2021)

مصطلحات موضوعية: Bevacizumab, Lung cancer, Esophageal pleural fistula, Case report, Diseases of the respiratory system, RC705-779

الوصف: Abstract Background Esophageal pleural fistula (EPF) is a rare but fatal complication associated with bevacizumab use; however, cases reports of EPF caused by bevacizumab have not been previously published. Case presentation A 66-year-old male patient diagnosed with stage IV lung adenocarcinoma on April 24, 2020 received 6 cycles of platinum-containing dual chemotherapy combined with bevacizumab followed by three cycles of bevacizumab monotherapy. Five days before admission, he experienced chest tightness, dyspnea, and right chest pain. Bed-side X-ray examination revealed a massive right hydrothorax, and food was found in the extracted pleural effusion. EPF was further confirmed by upper gastrointestinal radiography after oral administration of iohexol. The patient underwent jejunostomy as the distal esophagus could not be identified on gastroscopy, and eventually died of septic shock on January 16, 2021. Conclusions It is necessary to pay attention to EPF during bevacizumab use in patients with or without risk factors.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1471-2466Test

الوصول الحر: https://doaj.org/article/fb6bc0fc80fa4d6f9d1ba67702b324f1Test

المؤلفون: Baoqing Chen, Chen Yang, Mihnea P. Dragomir, Dongmei Chi, Wenyan Chen, David Horst, George A. Calin, Qiaoqiao Li

المصدر: Therapeutic Advances in Medical Oncology, Vol 14 (2022)

مصطلحات موضوعية: Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Background: Proton pump inhibitors (PPIs) have been shown to regulate the gut microbiome and affect the response to immune checkpoint inhibitors (ICIs). Contradictory results on survival have been observed in patients concomitantly treated with ICIs and PPIs. We performed a systematic review and meta-analysis to determine the association between PPI use and survival outcomes in ICI-treated cancer patients. Methods: EMBASE, MEDLINE/PubMed, Cochrane Library databases, and major oncology conference proceedings were searched. Studies comparing overall survival (OS) and progression-free survival (PFS) between PPI-treated and PPI-free groups of ICI-treated cancer patients were included. Data regarding study and patient characteristics, ICI and PPI treatments, and survival outcomes were extracted. Hazard ratios (HRs) with 95% confidence interval (CI) were pooled using random effects models. Subgroup meta-analyses and meta-regressions were performed to explore possible factors of heterogeneity among the studies. Results: A total of 33 studies were included, comprising 7383 ICI- and PPI-treated patients and 8574 ICI-treated and PPI-free patients. The pooled HR was 1.31 (95% CI, 1.19–1.44; p

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1758-8359Test

الوصول الحر: https://doaj.org/article/075942607b924c9fab1c97b02e602288Test