TET1-TRPV4 Signaling Contributes to Bone Cancer Pain in Rats.

Bone cancer pain (BCP) is excruciating for cancer patients, with limited clinical treatment options and significant side effects, due to the complex and unclear pathogenesis of bone cancer pain. Peripheral sensitization in dorsal root ganglion (DRG) neurons is a recognized cellular mechanism for bone cancer pain. The pathological mechanism of chronic pain is increasingly being affected by epigenetic mechanisms. In this study, we unbiasedly showed that the DNA hydroxymethylase ten-eleven translocation 1 (TET1) expression was significantly increased in the L4-6 DRG of BCP rats and ten-eleven translocation 2 (TET2) expression did not change significantly. Notably, TET1 inhibition by intrathecal injection of Bobcat339 (a TET1 inhibitor) effectively relieved mechanical hyperalgesia in BCP rats. Peripheral sensitization in chronic pain relies on the activation and overexpression of ion channels on neurons. Here, we demonstrated that TRPV4, one of the transient receptor potential ion channel family members, was significantly elevated in the L4-6 DRG of BCP rats. In addition, TRPV4 inhibition by intrathecal injection of HC067047 (a TRPV4 inhibitor) also significantly attenuated mechanical hyperalgesia in BCP rats. Interestingly, we found that TET1 inhibition downregulated TRPV4 expression in the L4-6 DRG of BCP rats. As a result, these findings suggested that TET1 may contribute to bone cancer pain by upregulating TRPV4 expression in the L4-6 DRG of BCP rats and that TET1 or TRPV4 may become therapeutic targets for bone cancer pain.

The role of the genomic mutation signature and tumor mutation burden on relapse risk prediction in head and neck squamous cell carcinoma after concurrent chemoradiotherapy.

Personalized genetic profiling has focused on improving treatment efficacy and predicting risk stratification by identifying mutated genes and selecting targeted agents according to genetic testing. Therefore, we evaluated the role of genetic profiling and tumor mutation burden (TMB) using next-generation sequencing in patients with head and neck squamous cell carcinoma (HNSC). The relapse mutation signature (RMS) and chromatin remodeling mutation signature (CRMS) were explored to predict the risk of relapse in patients with HNSC treated with concurrent chemoradiotherapy (CCRT) with platinum-based chemotherapy. Patients in the high RMS and CRMS groups showed significantly shorter relapse-free survival than those in the low RMS and CRMS groups, respectively (p < 0.001 and p = 0.006). Multivariate Cox regression analysis showed that extranodal extension, CCRT response, and three somatic mutation profiles (TMB, RMS, and CRMS) were independent risk predictors for HNSC relapse. The predictive nomogram showed satisfactory performance in predicting relapse-free survival in patients with HNSC treated with CCRT.

Machine learning-based dynamic prediction of lateral lymph node metastasis in patients with papillary thyroid cancer.

Objective: To develop a web-based machine learning server to predict lateral lymph node metastasis (LLNM) in papillary thyroid cancer (PTC) patients. Methods: Clinical data for PTC patients who underwent primary thyroidectomy at our hospital between January 2015 and December 2020, with pathologically confirmed presence or absence of any LLNM finding, were retrospectively reviewed. We built all models from a training set (80%) and assessed them in a test set (20%), using algorithms including decision tree, XGBoost, random forest, support vector machine, neural network, and K-nearest neighbor algorithm. Their performance was measured against a previously established nomogram using area under the receiver operating characteristic curve (AUC), decision curve analysis (DCA), precision, recall, accuracy, F1 score, specificity, and sensitivity. Interpretable machine learning was used for identifying potential relationships between variables and LLNM, and a web-based tool was created for use by clinicians. Results: A total of 1135 (62.53%) out of 1815 PTC patients enrolled in this study experienced LLNM episodes. In predicting LLNM, the best algorithm was random forest. In determining feature importance, the AUC reached 0.80, with an accuracy of 0.74, sensitivity of 0.89, and F1 score of 0.81. In addition, DCA showed that random forest held a higher clinical net benefit. Random forest identified tumor size, lymph node microcalcification, age, lymph node size, and tumor location as the most influentials in predicting LLNM. And the website tool is freely accessible at http://43.138.62.202/. Conclusion: The results showed that machine learning can be used to enable accurate prediction for LLNM in PTC patients, and that the web tool allowed for LLNM risk assessment at the individual level.

Consistent administration of cetuximab is associated with favorable outcomes in recurrent/metastatic head and neck squamous cell carcinoma in an endemic carcinogen exposure area: a retrospective observational study.

BACKGROUND: This study aimed to analyze the clinical outcomes associated with patients with recurrent/metastatic head and neck squamous cell carcinoma (RM HNSCC) who received cetuximab-based chemotherapy in a real-world clinical setting. METHODS: Clinical data were extracted from RM HNSCC patients diagnosed between 2016 and 2019. Kaplan-Meier survival estimates and Cox proportional hazards model were used for survival analyses. RESULTS: Of 106 RM HNSCC patients (mean age = 55.1 years), 38.7% exhibited recurrent disease and 61.3% had metastatic disease. The majority of patients showed a habit of addictive substance use, including alcohol (67.0%), betel nuts (71.7%), or tobacco (74.5%). The primary tumor sites included the oral cavity (64.1%), hypopharynx (19.8%), and oropharynx (16.0%). The median number of cetuximab cycles for the 106 patients was 11 (2-24). The disease control rate (DCR) was 48.1%, and the overall response rate (ORR) was 28.3%. The median progression-free survival (PFS) and overall survival (OS) were 5.0 and 9.23 months, respectively. Patients treated with more than 11 cycles of cetuximab exhibited a longer median PFS and median OS than did patients treated with less than 11 cycles (median PFS: 7.0 vs. 3.0 months, p < 0.001; OS: 12.43 vs. 4.46 months, p = 0.001). Patients without previous concurrent chemoradiotherapy (CRT) had a better median PFS than did those with previous CRT (6.0 vs. 4.0 months, p = 0.046). Multivariable analysis revealed that perineural invasion and fewer cycles of cetuximab (<11 cycles) were independent risk factors associated with disease progression. In addition, the reduction in treatment cycles of cetuximab and advanced lymph node metastasis were independent prognostic factors predicting poorer overall survival. CONCLUSION: Our study provides important real-world data regarding cetuximab-containing treatment in RM HNSCC. Consistent administration of cetuximab could be associated with more favorable outcomes in RM HNSCC in endemic carcinogen exposure areas.

A Pilot Study for a Better Visibility in the 3D Laparoscopic Right Colectomy Surgery.

OBJECTIVE: The aim of this study was to investigate the feasibility of digital defog technique in 3D laparoscopic surgery for right colon cancer. METHODS: Fifty patients with right colon cancer were divided into digital defogging group and control group. The intraoperative image clarity, the surgeon's anxiety, the time of operation and the time of fog nursing were compared. RESULTS: The clarity of the video screen of the digital defogging group was significantly higher than that of the control group, and the degree of anxiety was significantly lower than that of the control group. The operative time was (136.4 ± 30.4) min in the digital defogging group, the operation time of the control group was (168.7 ± 32.7) min, and the difference was statistically significant (P < 0.05). The time of dehumidification was (4.8 ± 1.3) min in the digital defogging group and (16.3 ± 4.6) min in the control group, and the difference was statistically significant (P < 0.05). CONCLUSION: Digital defogging technology in the 3D laparoscopic right colon cancer surgery significantly improves the clarity of video images, reduces the surgeon due to screen clarity caused by anxiety, reduces the operation of right colon cancer time and reduces the time to fog care.

[Construction of Lentiviral Vector Over-Expressing MEG3 and Its Effect on XG-7 Cell Apoptosis].

OBJECTIVE: To construct a recombinant lentiviral expression vectors carrying MEG3 and to evaluate its effects on XG-7 cell apoptosis. METHODS: A full-length genomic fragment of human MEG3 was cloned from the pcDNA3.0-MEG3 packaging plasmid and was amplified by PCR. New restriction sites were introduced to be blunted with T4 DNA Ligase. The sequence of the amplified segments was sub-cloned into lentivirus expression vector pCDH-EF1-MCS-T2A-copGFP.The recombined lentiviral expression vector was transfected into 293T cells. FACS was used to detect the effect of MEG3 on XG-7 cell apoptosis after being infected by optimized MOI. RESULTS: The recombined lentiviral expression vector pCDH-EF1-MEG3-copGFP was constructed successfully. The results showed that pCDH-EF1-MEG3-copGFP could increase the mRNA expression of MEG3 dramatically, its transfection efficiency was more than 90%. The apoptosis rate in XG-7 cells (26.8±2.8%) was very significantly higher than that of the control group (P<0.01). CONCLUSION: The recombined lentiviral LncRNA expression vector targeting MEG3, pCDH-EF1-MEG3-copGFP, has been successfully constructed, the pCDH-EF1-MEG3-copGFP can induce the cell apoptosis in human myeloma cell lines. This study set up a basis to further explore the relationship between human myeloma cells and LncRNA-MEG3 gene.