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Πέμπτη 10 Φεβρουαρίου 2022

USP47 stabilizes BACH1 to promote the Warburg effect and non-small cell lung cancer development via stimulating Hk2 and Gapdh transcription

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Am J Cancer Res. 2022 Jan 15;12(1):91-107. eCollection 2022.

ABSTRACT

Increasing studies demonstrated that ubiquitination plays a crucial part in the pathogenesis of non-small cell lung cancer (NSCLC), and targeted adjustment of the deubiquitination enzymes is a potential means for cancer treatment. However, the role of ubiquitin carboxyl-terminal hydrolase 47 (USP47) in NSCLC is still unclear. Here, we show that USP47 was upregulated in NSCLC clinical tissues and greatly related to advanced tumor stages and survival rate. Functional experimental results showed that USP47 promoted the cell proliferation in vitro and tumor growth in vivo. And the overexpression of USP47 promoted the glycolysis capacity of lung cancer cells. Mechanistic investigations showed that USP47 promoted NSCLC development, which depends a lot on directly binding to and deubiquitination of the basic leucine zipper transcription factor 1 (BACH1, BTB an d CNC homology 1). BACH1 was also significantly overexpressed in primary NSCLC tissues and positively correlated with the expression of USP47. The promotion of USP47 on the Warburg effect and NSCLC progression was mediated by the deubiquitination of BACH1 and the downstream transcriptional regulation of hexokinase 2 (Hk2) and glyceraldehyde-phosphate dehydrogenase (Gapdh). Therefore, targeting USP47/BACH1 axis might offer a new way to inhibit the progression of NSCLC.

PMID:35141006 | PMC:PMC8822287

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Evaluation of Surgical Margin Status in Patients With Salivary Gland Cancer

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This cohort study evaluates the association of surgical margin status with use of postoperative radiotherapy and survival in patients with salivary gland cancer.
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The clinicopathological and prognostic significances of LATS1 expression in breast cancer

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Histol Histopathol. 2022 Feb 10:18433. doi: 10.14670/HH-18-433. Online ahead of print.

ABSTRACT

AIM: Large tumor suppressor gene 1 (LATS1) belongs to the PKA/PKG/PKC serine/threonine kinase subfamily of the Hippo signaling pathway and inactivates nuclear co-activators YAP1 and WWTR1 by phosphorylation. This study aimed to discern the clinicopathological and prognostic significances of LATS1 expression in breast cancer.

METHODS: We examined LATS1 expression in breast carcinogenesis and compared it with clinicopathological parameters and survival information of breast cancer patients using immunohistochemistry, western blotting, RT-PCR, and bioinformatics analysis.

RESULTS: LATS1 expression was downregulated in breast cancer at both mRNA and protein levels (P<0.05). LATS1 mRNA expression was negatively correlated with young age, nodal metastasis status, TNM staging, ER and PR expression, TP53 mutation, aggressive subtypes (TNBC and HER2+ vs. luminal), and poor survival (P<0.05). Its protein expression was negatively linked to patient age, T stage, N stage, histological grade, PR status, and unfavorable prognosis (P<0.05). There was a positive correlationship between nuclar and cytoplasmic LATS1 expression in breast cancer (P<0.05).

CONCLUSIONS: The downregulation of LATS1 expression plays a vital role in the carcinogenesis and progression of breast cancer. Thus, LATS1 loss was employed to indicate the aggressive behaviors and poor prognosis of breast cancer.

PMID:35142365 | DOI:10.14670/HH-18-433

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Secondary Syphilis Presenting as Recurrent Oral Mucocutaneous Lesions

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Ear Nose Throat J. 2022 Feb 10:1455613221078179. doi: 10.1177/01455613221078179. Online ahead of print.

NO ABSTRACT

PMID:35142533 | DOI:10.1177/01455613221078179

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Τετάρτη 9 Φεβρουαρίου 2022

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The cover image is based on the Education A novel method to reconstruct right recurrent laryngeal nerve by transforming into nonrecurrent laryngeal nerve: The end-to-free vagal laryngeal branch end anastomosis by Yu-Long Wang et al., https://doi.org/10.1002/hed.26942.


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Long-term outcome of patients treated with antithyroid drugs, radioactive iodine or surgery for persistent or relapsed Graves' disease

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Br J Surg. 2022 Feb 7:znab474. doi: 10.1093/bjs/znab474. Online ahead of print.

ABSTRACT

BACKGROUND: The aim of this study was to compare long-term mortality, morbidity, and cumulative healthcare costs between antithyroid drugs, radioactive iodine, and surgical treatment for patients with persistent or relapsed Graves' disease.

METHODS: Data on patients with persistent or relapsed Graves' disease between 2006 and 2018 were retrieved from the Hong Kong Hospital Authority. Haza rd ratios (HRs) estimated by Cox proportional hazards regression models were used to compare the risks of all-cause mortality, cardiovascular disease, atrial fibrillation, psychological disease, Graves' ophthalmopathy, and cancer across treatment groups. The 10-year healthcare cost and change in co-morbidity status were also estimated.

RESULTS: Over a median follow-up of 79 months (22 636 person-years), a total of 3443 patients (antithyroid drug 2294, radioactive iodine 755, surgery 394) were analysed. Compared with antithyroid drug treatment, surgery was associated with significantly lower risks of all-cause mortality (HR 0.40, 95 per cent c.i. 0.36 to 0.45), cardiovascular disease (HR 0.54, 0.48 to 0.60), atrial fibrillation (HR 0.11, 0.09 to 0.14), psychological disease (HR 0.85, 0.79 to 0.92), Graves' ophthalmopathy (HR 0.09, 0.08 to 0.10), and cancer (HR 0.56, 0.50 to 0.63). Patients who underwent surgery also had a lower risk of all outcome events than those in the radio active iodine group. The 10-year direct cumulative healthcare cost was €14 754 for surgery compared with €17 390 for antithyroid drugs, and €17 918 for the radioactive iodine group.

CONCLUSION: Patients who underwent surgery for persistent or relapsed Graves' disease had lower risks of all-cause mortality and analysed morbidities. The 10-year cumulative healthcare cost in the surgery group was lowest among the three treatment alternatives.

PMID:35136950 | DOI:10.1093/bjs/znab474

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Reductive rhinoplasty principles applied to the curative treatment of different nasal diseases

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Eur Arch Otorhinolaryngol. 2022 Feb 9. doi: 10.1007/s00405-022-07287-w. Online ahead of print.

ABSTRACT

PURPOSE: Reductive rhinoplasty is generally intended as a facial plastic procedure aiming for functional and aesthetic outcomes in patients affected by nasal dysmorphism and/or obstruction. However, when applied to different pathologies of the nasal pyramid it holds great potentialities, beyond the solo cosmetic and functional objectives.

METHODS: We retrospectively analyzed preoperative conditions, surgical charts, and postoperative results of patients who underwent reductive rhinoplasty for different nasal diseases at our Institution.

RESULTS: Principles and techniques of reductive rhinoplasty were described in the different possible applications to the treatment of nasal disease, from nasal septal perforation to benign and malignant diseases of the nose.

CONCLUSIONS: Reductive rhinoplasty showed to play a crucial role in the curative purpose of different nasal diseases, representing a versatile tool in the expert hand of rhinoplasty surgeons who approach them.

LEVEL OF EVIDENCE: N/A.

PMID:35138440 | DOI:10.1007/s00405-022-07287-w

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Τρίτη 8 Φεβρουαρίου 2022

Benign paroxysmal positional vertigo: is hypothyroidism a risk factor for recurrence?

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Acta Otorhinolaryngol Ital. 2022 Feb 7. doi: 10.14639/0392-100X-N1775. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the relationship between risk of Benign Paroxysmal Positional Vertigo (BPPV) recurrence and hypothyroidism treated with hormone replacement therapy (HRT).

METHODS: 797 patients with idiopathic BPPV were divided into two groups: 250 patients with recurrence of BPPV (R-BPPV) and 547 patients without recurrence (NR-BPPV). Regarding patients with thyroid disease on HRT, we collected serum test results of thyroidstimulating hormone (TSH), free triiodothyronine f-T3, free thyroxine f-T4, thyroglobulin antibodies (TG-Ab) and thyroid peroxidase antibodies (TPO-Ab).

RESULTS: Hypothyroidism in long-term HRT was found in 61/250 (24.4%) patients of the RBPPV group vs 79/547 (14.4%) of the NR-BPPV-group (p = 0.0006). Hashimoto thyroiditis (HT) was associated with recurrence (p < 0.0001). A significant correlation was found between recurrence and level of serum TPO-Ab (p = 0.0117) and TG-Ab (p = 0.0025), but not with mean serum TSH, f-T3 and f-T4.

CONCLUSIONS: We assume that patients with hypothyroidism in HRT have an increased risk of BPPV recurrence, which is particularly strong for patients with HT and positive thyroid antibodies, suggesting an association between autoimmunity and recurrent vertigo.

PMID:35129542 | DOI:10.14639/0392-100X-N1775

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Quantification of near-infrared fluorescence imaging with indocyanine green in free flap breast reconstruction

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J Plast Reconstr Aesthet Surg. 2022 Jan 14:S1748-6815(22)00003-1. doi: 10.1016/j.bjps.2021.12.004. Online ahead of print.

ABSTRACT

BACKGROUND: One of the complications of free flap breast reconstruction is the occurrence of skin and fat necrosis. Intra-operative use of near-infrared (NIR) fluorescence imaging with Indocyanine Green (ICG) has the potential to predict these complications. In this study, the quantification of the fluorescence intensity measured in free flap breast reconstruction was performed to gain insight into the perfusion patterns observed with ICG NIR fluorescence imaging.

METHODS: ICG NIR fluorescence imaging was performed in patients undergoing free flap breast reconstruction following mastectomy. After completion of the arterial and venous anastomosis, 7.5 mg ICG was administered intravenously. The fluorescence intensity over time was recorded using the Quest Spectrum Platform®. Four regions of interest (R OI) were selected based on location and interpretation of the NIR fluorescence signal: (1) The perforator, (2) normal perfusion, (3) questionable perfusion, and (4) low perfusion. Time-intensity curves were analyzed, and two parameters were extracted: Tmax and Tmax slopes.

RESULTS: Successful ICG NIR fluorescence imaging was performed in 13 patients undergoing 17 free flap procedures. Region selection included 16 perforators, 17 normal perfusions, 8 questionable perfusions, and 5 low perfusion ROIs. Time-intensity curves of the perforator ROIs were comparable to the ROIs of normal perfusion and demonstrated a fast inflow. No outflow was observed for the ROIs with questionable and low perfusion.

CONCLUSION: This study provides insight into the perfusion patterns observed with ICG NIR fluorescence imaging in free flap breast reconstruction. Future studies should correlate quantitative parameters with clinical perfusion assessment and outcome.

PMID:35131194 | DOI:10.1016/j.bjps.2021.12.004

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Predicting outcomes from sentinel node biopsy for melanoma in the UK: Is the MIA nomogram the answer?

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J Plast Reconstr Aesthet Surg. 2022 Jan 21:S1748-6815(22)00031-6. doi: 10.1016/j.bjps.2022.01.017. Online ahead of print.

NO ABSTRACT

PMID:35131192 | DOI:10.1016/j.bjps.2022.01.017

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Depleting hsa_circ_0000567 suppresses acquired gefitinib resistance and proliferation of lung adenocarcinoma cells through regulating the miR-377-3p / ZFX axis: an in vitro and in vivo study

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Histol Histopathol. 2022 Feb 8:18431. doi: 10.14670/HH-18-431. Online ahead of print.

ABSTRACT

BACKGROUND: Circular RNAs (circRNAs) expression profile has been reported in lung adenocarcinoma (LUAD) cells resistant to gefitinib, and hsa_circ_0000567 was abnormally upregulated. However, its precise role in gefitinib resistance remains unclarified.

METHODS: Levels of hsa_circ_0000567, microRNA (miR)-377-3p and zinc finger protein X-linked (ZFX) were detected by real-time quantitative PCR. Direct attachment was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation assay. Gefitinib resistance was measured by MTT assay, colony formation assay, flow cytometry, western blotting, and xenograft in mice.

RESULTS: Expression of hsa_circ_0000567 was upreguated in human gefitinib-resistant human LUAD tissues and cells (HCC827/GR and PC9/GR). Clinically, higher hsa_circ_0000567 correlated with advanced tumor burden. Blo ckage of hsa_circ_0000567 suppressed cell viability, half maximal inhibitory concentration (IC₅₀) value, colony formation ability, and expression of Bcl-2 and proliferating cell nuclear antigen (PCNA) in HCC827/GR and PC9/GR cells under gefitinib treatment or not, accompanied with enhanced apoptosis rate and Bax expression. In vivo, tumor growth of PC9/GR cells untreated and treated with gefitinib was restrained by silencing hsa_circ_0000567. miR-377-3p was directly regulated by hsa_circ_0000567, and then targeted ZFX. Similar to hsa_circ_0000567 knockdown, overexpressing miR-377-3p inhibited chemoresistance in genitinib-resistant LUAD cells in vitro, whereas, depleting miR-377-3p was able to promote gefitinib resistance in spite of hsa_circ_0000567 knockdown. Moreover, restoring ZFX abrogated miR-377-3p-mediated chemosensitivity in genitinib-resistant LUAD cells in vitro.

CONCLUSION: The hsa_circ_0000567/miR-377-3p/ZFX axis might contribute to acquired gefitinib resistanc e in LUAD cells both in vitro and in vivo, suggesting hsa_circ_0000567 as a novel therapeutic target in treatment of gefitinib-resistant LUAD.

PMID:35133000 | DOI:10.14670/HH-18-431

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