Search

Abstract Objectives To explore the efficacy of induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) in stage II nasopharyngeal carcinoma (NPC) treated with intensity‐modulated radiotherapy (IMRT). Methods Totally, 450 eligible patients with staged II NPC on the basis of the 8th edition of the AJCC/UICC TNM staging system were eventually included from January 2010 to September 2020. The one‐to‐one propensity score‐matched (1:1 PSM) analysis was employed to balance variables. We conducted univariate and multivariate analysis of survival to identify prognostic factors and demonstrated the findings in the matching cohort. Results In total, 141 pairs were selected by 1:1 PSM. IC + CCRT group in the matched data decreased 5‐year progression‐free survival (PFS, 75.5% vs. 88.0%, p = 0.032) and distant metastasis‐free survival (DMFS, 86.0% vs. 96.5%, p = 0.009). There was no significant difference in 5‐year overall survival (OS, 93.8% vs. 95.6%, p = 0.192) and locoregional relapse‐free survival (LRRFS, 87.1% vs. 94.3%, p = 0.169) compared with RT/CCRT. Multivariate analysis indicated that IC + CCRT was associated with significantly poor PFS (p = 0.024) and DMFS (p = 0.010). High neutrophil‐to‐lymphocyte ratio (>4.1) was negatively associated with OS (p = 0.034), PFS (p = 0.017) and DMFS (p = 0.001). Conclusion Adding IC to CCRT or IMRT alone has decreased PFS and DMFS, therefore, IC should not be recommended in stage II NPC patients. No significant differences in OS and LRRFS were observed in stage II disease.

Summary: Background: Induction chemotherapy regimens of docetaxel and cisplatin plus fluorouracil (TPF) are currently clinically used for patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) but have well-known side effects, such as myelosuppression and diarrhea. A docetaxel plus cisplatin (TP) regimen was developed to decrease the toxic effects induced by fluorouracil. In this trial, we assessed whether the TP induction chemotherapy regimen was noninferior to the TPF regimen. Methods: We performed an open-label, noninferiority, phase 3, multicentre, randomised, controlled trial at six centres in China. Eligible patients with NPC (stage III-IVA (excluding T3-4N0), Karnofsky's Performance Scoring ≥70) were randomly assigned (1:1) to receive either TP (docetaxel (75 mg per square meter, d1, intravenous infusion) and cisplatin (75 mg per square meter of body-surface area, d1, intravenous infusion)) or TPF (docetaxel (60 mg per square meter, d1, intravenous infusion) plus cisplatin (60 mg per square meter, d1, intravenous infusion) and 5-fluorouracil (600 mg per square meter, d1-d5, intravenous 120-hour infusion)) administered every 3 weeks for 3 cycles followed by concurrent chemoradiotherapy. The primary endpoint was failure-free survival at 2 years. Secondary endpoints included overall survival, safety, and treatment compliance. The trial was stopped early because of strong evidence for noninferiority (margin was -10%) of TP in failure-free survival. Efficacy analyses were performed in both the intention-to-treat and per-protocol trial populations and we included the patients who started treatment in each group for the safety analysis. The study was registered with chictr.org.cn, ChiCTR1800016337. Findings: Between June 1, 2018 and October 31, 2021, we randomly assigned 361 patients to the TP (n = 181) or TPF (n = 180) induction chemotherapy group. The 2-year failure-free survival was 91·3% (95% CI 86·2-96·4) in the TP group and 82·4% (84·8-88·9) in the TPF group (P = 0·029). Patients in the TPF group had a higher frequency of grade 1 or 2 neutropenia (53 (30·0%) vs. 28 (15·7%); P = 0·0010), grade 1 or 2 diarrhea (20 (11·3%) vs. 9 (5·1%); P = 0·032), and grade 3 or 4 neutropenia (43 (24·3%) vs. 25 (14·0%); P = 0·014) in the induction chemotherapy period. There was no treatment-related death. Interpretation: The preliminary results revealed that TP induction chemotherapy regimen was found to be clearly non-inferior compared to the TPF regimen in failure-free survival, with a lower frequency of neutropenia, anaemia and diarrhoea. The more convenient and beneficial survival regimen of the TP regimen should be recommended in patients with LA-NPC. Funding: This study was supported by grants from the Natural Science Foundation of Guangdong Province, China [grant number 2021A1515011182], Natural Science Foundation of Guangdong Province, China [grant number 2022A1515012272], National Natural Science Foundation of China [grant number 82072029] and National Natural Science Foundation of China [grant number 81903037].

BackgroundOncoprotein-Induced Transcript 3 Protein (OIT3) was identified as a liver-specific gene with abnormal expression in hepatocellular carcinoma (HCC). Herein, we aimed to examine the function and specific mechanism of OIT3 in HCC.MethodsBioinformatic analyses and tissue microarray via immunohistochemistry were used to validate the expression of OIT3 in HCC. The biofunctions of OIT3 in HCC were determined in vitro and in vivo. The mechanism was confirmed by RNA-Sequence and Western blotting. The uni- and multivariate analyses were used to identify the independent predictors for HCC.ResultsLow expression of OIT3 was observed in HCC and predicted a poor clinical outcome. Ectopic expression of OIT3 could inhibit the proliferation, migration, and invasion abilities of HCC cells. Mechanistically, OIT3 upregulated the expression of ALOX15 and CYP4F3, thus inducing arachidonic acid increase, ROS accumulation, and lipid peroxidation, and eventually causing ferroptosis. OIT3 was validated as a prognostic predictor for HCC patients.ConclusionsOur findings revealed a novel role of OIT3 in the process of tumorigenesis of HCC. OIT3 inhibited reproliferation, migration, and invasion of HCC cells by triggering ferroptosis, which indicates that OIT3 could serve as a potential biomarker in HCC.

BackgroundIn this trial, we aimed to assess the efficacy and safety of radiotherapy with nedaplatin or cisplatin in patients with locally advanced cervical cancer.MethodsWe conducted an open-label, non-inferiority, phase III, randomized, controlled trial. Eligible patients with stage IIB-IVA cervical carcinoma were randomly assigned to receive either nedaplatin or cisplatin for two cycles concurrently with radiotherapy. We reported the therapy-associated harms and survival. The study was registered with chictr.org.cn, number ChiCTR1800020527.ResultsWe randomly assigned 68 patients to nedaplatin-based or cisplatin-based concurrent chemoradiotherapy. Study treatment was stopped early after a data analysis found a higher number of patients suffered severe hematologic harms in the nedaplatin group than in the cisplatin group. Patients in the nedaplatin group had a significantly higher frequency of grade 3-4 neutropenia (19·4% vs. 13%; P < 0·001), severe thrombocytopenia (16·1% vs. 4·3%), and grade 1-2 anemia (51·6% vs. 43·5%) than patients in the cisplatin group. The 1-year PFS and OS in the nedaplatin and cisplatin groups were similar.ConclusionOur findings showed that nedaplatin-based concurrent chemoradiotherapy expressed remarkably higher severe hematologic harms which were mortal. Though the results were negative, the experiences and lessons we learned from it were important.

Background: Renal cell carcinoma (RCC) is a most common kidney malignancy, with atypical symptoms in the early stage and poor outcome in the late stage. Recently, emerging evidence revealed that some miRNAs play an essential role in the tumorigenesis and progression of RCC. Therefore, the aim of this study is that understand the detailed molecular mechanism of miR-23a-3p in RCC and identify its potential clinical value. Methods: In this study, RT-qPCR, wound scratch assay, cell proliferation assay, transwell assay and flow cytometry assay were performed to detect miR-23a-3p expression and its proliferation, migration and apoptosis in RCC. The bioinformatics analysis, RT-qPCR, western blot and luciferase reporter assay were performed to discern and examine the relationship between miR-23a-3p and its potential targets. Moreover, we analyzed the relationship between miR-23a-3p expression and clinicopathological variables or overall survival (OS) from 118 formalin-fixed paraffin-embedded RCC samples. Results: miR-23a-3p is significantly up-regulated in RCC tissue samples, RCC cell lines and the TCGA database. Upregulating miR-23a-3p enhances, while silencing miR-23a-3p suppresses cell viability, proliferation and mobility in ACHN and 786-O cell lines. Besides, overexpression of miR-23a-3p inhibits the cell apoptosis. Then our study further reveals that miR-23a-3p regulates tumorigenesis by targeting Proline-Rich Nuclear Receptor Coactivator 2 (PNRC2). Also, the cox proportional hazard regression analysis indicates that low expression of miR-23a-3p patients has a remarkable longer OS. Conclusions: Our results reveals that miR-23a-3p may not only serve as a new biomarker for prognosis but also serve as a new therapeutic strategy in the RCC treatment.

This article concerns the chemorepulsion system with nonlinear sensitivity and nonlinear secretion $$\displaylines{ u_t=\Delta u+\nabla\cdot(\chi u^m\nabla v),\quad x\in\Omega,\; t>0,\cr 0=\Delta v-v+u^\alpha,\quad x\in\Omega,\; t>0, }$$ under homogeneous Neumann boundary conditions, where $\chi>0$, m>0, $\alpha>0$, $\Omega\subset\mathbb{R}^n$ is a bounded domain with smooth boundary. The existence and uniform boundedness of a classical global solutions are obtained. Furthermore, it is shown that for any given $u_0$, if $\alpha>m$ or $\alpha\ge 1$, the corresponding solution (u,v) converges to $(\bar{u}_0,\bar{u}^\alpha_0)$ as time goes to infinity, where $\bar{u}_0:=\frac1{|\Omega|}\int_\Omega u_0dx$.

In the title complex, [Mn(C16H14N4O)(C2H5OH)2(H2O)](C6H2N3O7)2·2C2H5OH, the MnII ion is in a distorted octahedral coordination environment, defined by an MnN2O4 donor set. The 1,3-bis(benzimidazol-2-yl)-2-oxapropane ligand is tridentate. In the crystal structure, intermolecular N—H...O and O—H...O hydrogen bonds link the components into a three-dimensional network. The O atoms of one of the nitro groups are disordered over two sets of sites with refined occupancies of 0.577 (11) and 0.423 (11).

A key aspect of Knowledge fusion is Entity Matching. The objective of this study was to investigate how to identify heterogeneous expressions of the same real-world entity. In recent years, some representative works have used deep learning methods for entity matching, and these methods have achieved good results. However, the common limitation of these methods is that they assume that different attribute columns of the same entity are independent, and inputting the model in the form of paired entity records will cause repeated calculations. In fact, there are often potential relations between different attribute columns of different entities. These relations can help us improve the effect of entity matching, and can perform feature extraction on a single entity record to avoid repeated calculations. To use attribute relations to assist entity matching, this paper proposes the Relation-aware Entity Matching method, which embeds attribute relations into the original entity description to form sentences, so that entity matching is transformed into a sentence-level similarity determination task, based on Sentence-BERT completes sentence similarity calculation. We have conducted experiments on structured, dirty, and textual data, and compared them with baselines in recent years. Experimental results show that the use of relational embedding is helpful for entity matching on structured and dirty data. Our method has good results on most data sets for entity matching and reduces repeated calculations. [ABSTRACT FROM AUTHOR]

As influencing factors of genesis and progression in several types of human tumor, microRNAs (miRs) serves roles in the regulation of tumor cell viability, migration, and apoptosis. The present research aimed to investigate the association between the function of miR‑100‑5p and renal cell carcinoma (RCC). miR‑100‑5p expression was determined in RCC tissue and paired normal tissue samples using reverse transcription‑quantitative polymerase chain reaction. To assess the effects of miR‑100‑5p on cell viability, migration and apoptosis, multiple methods were used, including scratch wound assays, MTT assays, and flow cytometry. It was demonstrated that miR‑100‑5p was significantly upregulated in RCC tissue compared with in normal adjacent tissue samples. Furthermore, the viability and migration of 786‑O and, ACHN cells tranfected with miR‑100‑5p was significantly increased compared with the negative control group. In addition, miR‑100‑5p‑transfected 786‑O and ACHN cells demonstrated significantly reduced cellular apoptotic rates compared with the negative control group. To the best of our knowledge, the present study is the first to report an association between miR‑100‑5p and RCC. The results of the current study suggest that tumor oncogene miR‑100‑5p could be used as a diagnostic biomarker for RCC. [ABSTRACT FROM AUTHOR]

In recent years, accumulating evidence has demonstrated that microRNAs (miRs, miRNAs) may serve an important role in the occurrence and development of tumors. miR-23a-5p has been confirmed as an oncogene in numerous diseases through gene chip analysis. However, as the most common type of renal tumor, the expression and function of miR-23a-5p in renal cell carcinoma (RCC) remains unclear. In the present study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis, and Cell Counting Kit-8 (CCK-8), wound scratch, Transwell, MTT and flow cytometry assays were performed to investigate the role of miR-23a-5p in RCC. The expression of miR-23a-5p in RCC tissue samples was significantly higher compared with that in normal tissue samples (P<0.01). Furthermore, the expression of miR-23a-5p in RCC cell lines (786O, ACHN and Caki-1) was significantly higher compared with that in the human embryo kidney 293T cell line, as determined using RT-qPCR (P<0.001). In addition, the results revealed that the upregulation of miR-23a-5p promoted the proliferation, migration and invasion of RCC cells, and inhibited RCC cell apoptosis. The downregulation of miR-23a-5p resulted in the reversal of the results described above. Additionally, it was observed that the downregulation of miR-23a-5p significantly promoted ACHN and 786O cell viability (P<0.001). The results of the present study suggest that miR-23a-5p is an oncogene in the occurrence and development of RCC and may be a novel therapeutic target for RCC. [ABSTRACT FROM AUTHOR]