Background Gastric cancer (GC) is a leading cause of cancer-related deaths worldwide. Understanding the molecular mechanisms of GC metastasis is crucial for improving patient survival outcomes. Methods RNA sequencing and analysis were performed on tissue samples from primary and lymph node metastatic lesions of gastric cancer. Differential gene analysis and functional pathway analysis were conducted. Immune infiltrating environment and protein expression levels were evaluated using immunohistochemistry. Cell experiments were conducted to investigate the role of CCL21 in GC metastasis. Results ACTG2, CNN1, DES, MUC6, and PGC were significantly upregulated in primary tumor cells, while CCL21, MS4A1, CR2, CLDN11, and FDCSP were significantly upregulated in metastatic tumor cells. Functional pathway analysis revealed enrichment in pathways related to immune response. CLDN11 and CCL21 were found to play important roles in promoting gastric cancer metastasis. Cell experiments confirmed the role of CCL21 in promoting GC cell growth and metastasis. CCL21 is highly expressed in GC tissues and binds to CCR7, leading to upregulation of CLDN11. This results in GC-lymph node metastasis and abnormal activation of immune cells (B cells and CD4 + T cells). Conclusion Inhibition of CCL21 and CLDN11 proteins may be a promising strategy for treating GC and preventing lymph node metastasis. These findings provide specific molecular markers for early lymph node metastases of GC, which can aid in developing treatment strategies and predicting patient prognosis.
PURPOSE:Ubiquitin-specific peptidase 10 (USP10) has been found to have oncogenic activity in several human tumors. This study first revealed the exact function of USP10 on the progression of thyroid cancer (THCA) by researching its effect on the ferroptosis.METHODS:USP10 expression in THCA patients was analyzed by online data analysis and in 75 THCA cases was scrutinized by real-time quantitative reverse transcription-polymerase chain reaction and Western blot. Influence of USP10 on the viability, colony formation, migration and invasion of THCA cells was demonstrated by cell counting kit-8, colony formation, wound healing and Transwell invasion assays. Effect of USP10 on the Erastin-induced ferroptosis in THCA cells was evaluated by detecting the ferroptosis-related indicators. Intrinsic mechanism of USP10, glutathione peroxidase 4 (GPX4) and sirtuin 6 (SIRT6) in regulating THCA progression was identified. In vivo xenograft experiment was implemented.RESULTS:USP10 was abundantly expressed in THCA patients, linking to poor outcome. USP10 overexpression enhanced the viability, colony formation, migration and invasion of THCA cells. USP10 mitigated the Erastin-induced ferroptosis in THCA cells, decreased the levels of iron, Fe2+ , malondialdehyde, lipid reactive oxygen species, reduced mitochondrial superoxide level, and increased mitochondrial membrane potential. USP10 facilitated the expression of ferroptosis suppressor GPX4 by elevating SIRT6. Loss of USP10 repressed the in vivo growth of THCA cells.CONCLUSION:USP10 might attenuate the ferroptosis to promote thyroid cancer malignancy by facilitating GPX4 via elevating SIRT6. It might be novel target for the treatment of THCA.
Tripartite motif-containing 29 (TRIM29) has been found to be involved in the regulation of cancer progression and its function varies depending on the type of cancer. However, the role of TRIM29 in cholangiocarcinoma has yet to be revealed. This study initially explored the role of TRIM29 in cholangiocarcinoma. TRIM29 expression in cholangiocarcinoma cells were scrutinized by quantitative real-time reverse transcription polymerase chain reaction and Western blot. The function of TRIM29 on cholangiocarcinoma cell viability, proliferation, migration and sphere formation abilities were studied by cell count kit-8, clone formation, Transwell and sphere formation assays. TRIM29 effect on the expression of proteins associated with epithelial-mesenchymal transition and cancer stem cell characteristics were researched by Western blot. TRIM29 effect on MAPK and β-catenin pathway activity was researched through Western blot. TRIM29 was overexpressed in cholangiocarcinoma cells. TRIM29 silencing mitigated the viability, proliferation, migration and sphere formation abilities of cholangiocarcinoma cells, increased E-cadherin expression and decreased the expression of N-cadherin, Vimentin, CD33, Sox2 and Nanog proteins in cholangiocarcinoma cells. The loss of TRIM29 suppressed the expression of p-MEK1/2/MEK1/2 and p-ERK1/2/ERK1/2 in cholangiocarcinoma cells. The inhibition of the MAPK and β-catenin signaling pathways abrogated the promotion of TRIM29 on cholangiocarcinoma cell viability, proliferation, migration, EMT, and cancer stem cell characteristics. TRIM29 plays an oncogenic role in cholangiocarcinoma. It may promote the malignancy of cholangiocarcinoma via inducing the activation of the MAPK and β-catenin pathways. Thus, TRIM29 may aid in the creation of innovative treatment strategies for cholangiocarcinoma.
颈动脉体瘤(carotid body tumor,CBT)是一种相对罕见的疾病,大部分起源自颈动脉分叉处的化学细胞感受器,临床少见。目前CBT的治疗以手术切除为主,但其解剖位置特殊,病灶血供丰富,导致手术难度大,放化疗等治疗方法亦有报道。本综述从CBT的发病机制、临床表现、临床分型、治疗等方面予以总结。
BackgroundCarotid body tumor (CBT) is the most common head and neck paraganglioma. Whether preoperative embolization benefits CBT patients who will receive surgical resection is still controversial.MethodsIn this multi-center retrospective study, we collected data from patients with CBT who received surgical treatment without (group A) or with preoperative embolization (group B) from 2011 to 2019. The primary outcome was the rate of death or stroke after 3 years of follow-up. The secondary outcomes of the study were length of operation (LOO), intraoperative blood loss (IBL), length of stay (LOS), rate of recurrence, and rate of cranial nerve (CN) injuries. Descriptive statistics were used to analyze the demographics, clinical characteristics, complications, and follow-up results of the patients.ResultsBetween January 2011 and October 2019, 261 consecutive patients (107 male and 154 female) entered analysis. After 3 years of follow-up, no patient died in both groups. Only three patients with stroke were detected: 2/226 (0.9%) in group A vs. 1/35 (2.9%) in group B (p = .308). The LOO in group A was 132.6 ± 64.6 min compared with 152.9 ± 40.4 min in group B (p = .072). IBL in group A was 375.4 ± 497.8 ml compared with 448.0 ± 270.8 ml in group B (p = .400). LOS in group A was 8.3 ± 2.0 days compared with 7.4 ± 1.7 days in group B (p = .016). Seventy-two CN injuries were detected: 65/226 (28.8%) in group A vs. 7/35 (20.0%) in group B (p = .281). There were 65 temporary CN injuries (59 in group A vs. 6 in group B) (p = .254) and seven permanent CN injuries (6 in group A vs. 1 in group B) (p = .945). Three most frequently injured cranial nerves were the pharyngeal branch and superior laryngeal nerve (12.3%), recurrent laryngeal nerve (7.7%) and vagus nerve (7.3%).ConclusionThere was insufficient evidence to support the efficacy of preoperative embolization. CBT resection alone had a similar rate of stoke, recurrence, and CN injuries when compared with CBT resection with preoperative arterial embolization. Meanwhile, CBT resection alone did not increase LOO and IBL.
Objective To evaluate arterial covered stent used in the resection of complex carotid body tumor (CBT) and postoperative adverse events. Methods Twelve patients with CBT Shamblin type Ⅱ 3 cases and type Ⅲ 9 cases from 2018 to 2020 who underwent intraoperative combined arterial covered stent reconstruction (4 cases) or prereconstruction of internal carotid artery (8 cases) were included in this study. Statistics and analysis were done for general clinical data, intraoperative evaluation and postoperative adverse events. Results The operation was successful for all 12 cases. Average operative time was (160±55) min and blocking time was (25±6) min during carotid artery reconstruction. There was without need to block during internal carotid artery prereconstruction. Intraoperative bleeding was (342±101) mL. It was shown by follow-up one year later that there were 2 cases of temporary nerve injury and 1 case of postoperative covered stent obstruction. Both permanent nerve injury and transient ischemic attack were not found. Conclusions Stent graft used to reconstruct during operation or prereconstruction of internal carotid artery in CBT Shamblin type Ⅱ and type Ⅲ could reduce vascular injury, shorten blocking time of carotid artery, and lower adverse events. However, the treatment remained to be studied with large-sample controlled trial.