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1.
Neoplasma ; 69(5): 1041-1053, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35723199

ABSTRACT

Laryngeal squamous cell carcinoma (LSCC) is one of the most prevalent malignant diseases worldwide. LSCC patients suffer from a severe decline in life quality, due to the essential roles of the larynx in basic functions in the human body. The overarching goal of the present study is to explore whether exosome from M2 macrophages promotes LSCC by targeting glycolysis. In the current study, the expression of PDLIM2, an E3 ubiquitin ligase, in clinical samples was monitored by quantitative PCR and immunohistochemical examination. Extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were measured by the Seahorse machine. Cell proliferation was measured by using Cell Counting Kit-8. A luciferase assay was performed to verify the regulation of miRNA on its target gene. The results showed that PDLIM2 exhibited downregulation in LSCC clinical samples and was associated with stage and differentiation of tumors in patients. In FaDu cell line, PDLIM2 inhibited cell proliferation and glycolysis but promoted the ubiquitination of PFKL. Exosomes from M2-type macrophages delivered miR-222-3p into LSCC cells to suppress PDLIM2 expression, leading to the elevated expression of PFKL and enhanced glycolysis which accelerated the proliferation of FaDu cells. The findings from cultured cells were supported by a subcutaneous tumor growth model in nude mice. Collectively, our data provided a snapshot of the miR-222-3p/PDLIM2/PFKL axis in LSCC tumorigenesis, and in concert with the importance of TAM exosomes and glycolysis, could be potentially translated to LSCC clinics.


Subject(s)
Carcinoma, Squamous Cell , Exosomes , Head and Neck Neoplasms , Laryngeal Neoplasms , MicroRNAs , Adaptor Proteins, Signal Transducing , Animals , Carcinoma, Squamous Cell/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Gene Expression Regulation, Neoplastic , Glycolysis , Head and Neck Neoplasms/genetics , Humans , LIM Domain Proteins , Laryngeal Neoplasms/pathology , Macrophages , Mice , Mice, Nude , MicroRNAs/genetics , MicroRNAs/metabolism , Microfilament Proteins/genetics , Microfilament Proteins/metabolism , Squamous Cell Carcinoma of Head and Neck/genetics , Ubiquitin-Protein Ligases/genetics
2.
Audiol Neurootol ; 23(6): 309-315, 2018.
Article in English | MEDLINE | ID: mdl-30630184

ABSTRACT

OBJECTIVE: To explore the effectiveness and safety of round window niche drilling combined with intratympanic methylprednisolone injection for the salvage treatment of sudden sensorineural hearing loss (SSNHL) and its associated tinnitus after failed primary treatment. METHOD: SSNHL patients who showed a less than 10-dB improvement of pure-tone average after receiving standard systemic treatment and intratympanic steroid injection were enrolled. All included patients were randomly divided into two groups (control and study). Patients in the study group received round window niche drilling combined with daily intratympanic methylprednisolone for 7 times; the control group received only daily intratympanic methylprednisolone for 7 times. One month after treatment, the improvements of PTA, speech discrimination score (SDS), tinnitus and the incidence of adverse events were analyzed. RESULTS: 20 patients (10 for each group) were included in this study. The baseline between two groups showed no statistical significance. Patients in the study group experienced an average hearing improvement of 20.38 dB, SDS 19.3 compared with 2.1 dB and SDS 2.0 in the control group. None (0%) in the control group and 4 patients (40%) showed marked recovery, 5 patients (50%) showed slight improvement of hearing in the study group after 1 month. All patients in the study group showed significant recovery of tinnitus. Both tinnitus handicap inventory and a symptom visual analogue scale between two groups revealed statistical differences (p < 0.001, p = 0.002, respectively). None in the control and study groups experienced vertigo, infection and facial paralysis. CONCLUSION: Round window niche drilling increases the contact area and time of methylprednisolone. It is an effective and safe salvage therapy of idiopathic SSNHL and its induced tinnitus.


Subject(s)
Hearing Loss, Sudden/therapy , Injection, Intratympanic , Methylprednisolone/administration & dosage , Otologic Surgical Procedures/methods , Round Window, Ear/surgery , Salvage Therapy/methods , Adult , Audiometry, Pure-Tone , Auditory Threshold/drug effects , Combined Modality Therapy , Dexamethasone/administration & dosage , Drug Administration Schedule , Female , Humans , Infusions, Intravenous , Male , Middle Aged , Treatment Outcome , Visual Analog Scale
3.
Sci Rep ; 5: 16683, 2015 Dec 07.
Article in English | MEDLINE | ID: mdl-26639190

ABSTRACT

Acquired cholesteatoma is a chronic inflammatory disease characterized by both hyperkeratinized squamous epithelial overgrowth and bone destruction. Toll-like receptor (TLR) activation and subsequent inflammatory cytokine production are closely associated with inflammatory bone disease. However, the expression and function of TLRs in cholesteatoma remain unclear.We observed inflammatory cell infiltration of the matrix and prematrix of human acquired cholesteatoma, as well as dramatically increased expression of TLR4 and the pro-inflammatory cytokines TNF-α and IL-1ß. TLR2 exhibited an up-regulation that was not statistically significant. TLR4 expression in human acquired cholesteatoma correlated with disease severity; the number of TLR4-positive cells increased with an increased degree of cholesteatoma, invasion, bone destruction, and hearing loss. Moreover, TLR4 deficiency was protective against experimental acquired cholesteatoma-driven bone destruction and hearing loss, as it reduced local TNF-α and IL-1ß expression and impaired osteoclast formation by decreasing expression of the osteoclast effectors receptor activator of nuclear factor (NF)-κB ligand (RANKL) and tartrate-resistant acid phosphatase (TRAP). TLR2 deficiency did not relieve disease severity, inflammatory responses, or osteoclast formation. Moreover, neither TLR2 nor TLR4 deficiency had an effect on antimicrobial peptides, inducible iNOS,BD-2 expression or bacterial clearance. Therefore, TLR4 may promote cholesteatoma-induced bone destruction and deafness by enhancing inflammatory responses and osteoclastogenesis.


Subject(s)
Bone and Bones/pathology , Cholesteatoma/etiology , Inflammation/pathology , Toll-Like Receptor 4/metabolism , Adolescent , Adult , Aged , Animals , Bacteria/metabolism , Cell Count , Cholesteatoma/congenital , Cholesteatoma/pathology , Cholesteatoma/physiopathology , Cytokines/metabolism , Demography , Evoked Potentials, Auditory, Brain Stem , Female , Hearing Loss/pathology , Hearing Loss/physiopathology , Humans , Inflammation/complications , Inflammation Mediators/metabolism , Male , Mice, Inbred C57BL , Middle Aged , Osteoclasts/metabolism , Osteoclasts/pathology , Toll-Like Receptor 4/deficiency , Up-Regulation , Young Adult
4.
Article in English | MEDLINE | ID: mdl-24030443

ABSTRACT

AIM: To create an experimental model for the biomedical research of middle ear cholesteatoma. METHODS: Cholesteatoma was induced in the right ears of mice. An autologous meatal skin graft was implanted into the middle ear via the tympanic membrane followed by an intratympanic injection of Pseudomonas aeruginosa. Six weeks after surgery, the formation of acquired cholesteatoma was evaluated by macroscopic examination, CT scan, and histological analysis. The expressions of TNF-α, IL-1ß, and IL-6 were measured with real-time PCR. Auditory-evoked brain stem response was used for assessing the changes in hearing levels. RESULTS: None of the mice died during the modeling time. By the sixth postoperative week, cholesteatoma had successfully formed in 23 out of 25 mice, which equals a success rate of 92%. A CT scan revealed that the cholesteatoma was eroding the cochlea. Furthermore, histological analysis demonstrated a cystic structure covered by stratified squamous epithelium and keratin desquamation in the lamellae inside the cystic cavity in the bullae. All mice with experimentally induced cholesteatoma showed hearing impairment and an upregulated expression of TNF-α, IL-1ß, and IL-6. CONCLUSION: The present study successfully developed a mouse model of acquired middle ear cholesteatoma, which provides an extremely valuable tool for auditory and biomedical research. The modeling approach is technically easy and has a high success rate.


Subject(s)
Cholesteatoma, Middle Ear , Disease Models, Animal , Mice, Inbred C57BL , Pseudomonas Infections/surgery , Pseudomonas aeruginosa , Skin Transplantation/methods , Animals , Cholesteatoma, Middle Ear/microbiology , Cholesteatoma, Middle Ear/pathology , Cholesteatoma, Middle Ear/surgery , Cytokines/genetics , Evoked Potentials, Auditory, Brain Stem , Female , Hearing Disorders/microbiology , Hearing Disorders/pathology , Hearing Disorders/surgery , Injections, Intralymphatic , Mice , RNA, Messenger/metabolism , Transplantation, Autologous
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