Ubiquitin-specific peptidase 10 attenuates the ferroptosis to promote thyroid cancer malignancy by facilitating GPX4 via elevating SIRT6.

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.

Retrospective, multicenter study of surgical treatment for carotid body tumors with or without preoperative embolization.

Background: Carotid 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. Methods: In 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. Results: Between 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%). Conclusion: There 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.

High expression of IGHG1 promotes breast cancer malignant development by activating the AKT pathway.

This study researched the exact function of IgG1 heavy chain (IGHG1) on breast cancer (BC) progression. IGHG1 level within BC and paired normal tissues was acquired in Gene Expression Profiling Interactive Analysis dataset. Meanwhile, this work harvested tumor and paired healthy tissues in 42 BC cases. siRNA targeting IGHG1 was transfected into BC cells. SC79 was used to treat the transfected BC cells. CCK-8 assay, clone formation experiment, BrdU assay, Transwell experiment and flow cytometry were carried out to measure the viability, colony formation, proliferation, invasion, and apoptosis of BC cells. Paclitaxel and cisplatin sensitivity of BC cells was evaluated by MTT assay. Real-time quantitative reverse transcription-polymerase chain reaction and Western-blot were performed for measuring mRNA and protein expression. The overexpressed IGHG1 indicated dismal BC survival. IGHG1 silencing attenuated the viability, invasion, proliferation, epithelial-mesenchymal transition, but enhanced the apoptosis of BC cells. IGHG1 silencing enhanced the paclitaxel and cisplatin sensitivity of BC cells. IGHG1 silencing suppressed the activity of the MEK, AKT, and ERK pathways. AKT agonist partially reversed the inhibition of IGHG1 silencing on BC cell malignant phenotype and resistance to paclitaxel and cisplatin. IGHG1 promotes the malignant development of BC by activating the AKT pathway. It may be an effective target for BC treatment.

[Analysis of clinical efficacy of C3 expanded half lamina excision combined with unilateral open-door laminoplasty for multiple segmental cervical spinal cord compression syndrome].

OBJECTIVE: To explore the clinical efficacy of C3 expanded half lamina excision combined with unilateral open door laminoplasty for multiple segmental cervical spinal cord compression syndrome. METHODS: The clinical data of 58 patients with multiple segmental cervical spinal cord compression syndrome underwent surgical treatment between September 2014 and May 2018 were retrospectively analyzed. There were 34 males and 24 females with a mean age of 64.4 years old (ranged from 46 to 78 years old). Among them, 28 cases received the surgery of C3 expanded half lamina excision combined with C4-C7 unilateral open-door laminoplasty (improvedgroup), and 30 cases received a single C3-C7 unilateral open-door laminoplasty (traditional group). Operation time, intraoperative blood loss, complications including C5 nerve root palsy and axial symptoms were compared between two groups. To evaluate the situation of the imaging indicators by measuring the space available for the spinal cord through cross sectional MRI of cervical spine at the narrowest segment of C3 (including intervertebral disc levels of C3, 4). Pre- and post-operative Japanese Orthopedic Association(JOA) score, Neck Disability Index(NDI) score, and improvement rate of neurological function, were recorded and analyzed between the two groups. RESULTS: All the patients were followed up for 12 to 18 months with an average of(14.5±1.8) months for improved group and (14.5±1.9) months for traditional group, and no significant difference was found between the two groups (P>0.05). There was no significant difference in intraoperative blood loss and C5 nerve root palsy between the two groups (P>0.05). The operation time (119±10) min vs (126±12) min and axial symptoms 7.1%(2/28) vs 26.6%(8/30) was significant difference between the two groups (P<0.05). Preoperative and postoperative space available for the spinal cord of C3 was (93.61±9.02) mm3 and (153.50±12.76) mm3 respectively, which was obtained obvious improvement in all patients(P<0.05). At the final follow up, JOA scores of improved group and traditional group were 14.36±1.70 and 14.03±1.82 respectively, and NDI scores were 10.36±2.55 and 12.47±3.46 respectively, there was significant difference between two groups (P<0.05). However, there was no significant difference between two groups for the improvement rate (68.36±0.12)%VS (65.01±0.12)%of neurological function(P>0.05). CONCLUSION: C3 expanded half lamina excision combined with unilateral open-door laminoplasty is an effective method to treat multiple segmental cervical spinal cord compression syndrome, for it can not only fully relieved spinal cord compression, but also achievedgood effect in preventing complications such as axial symptoms by reducing stripping of muscles from C2 spinous process.