Interleukin-11/gp130 upregulates MMP-13 expression and cell migration in OSCC by activating PI3K/Akt and AP-1 signaling.

Oral squamous cell carcinoma (OSCC) is an extremely common head and neck cancer with a poor 5-year survival rate, especially in cases of metastatic disease. Interleukin (IL)-11 reportedly promotes cell growth and the epithelial-mesenchymal transition process in metastasis. However, the molecular mechanisms of IL-11 in OSCC metastasis are unclear. This study found that IL-11 upregulates matrix metalloproteinase 13 (MMP-13) expression in OSCC via the IL-11 receptor alpha subunit/glycoprotein 130 receptors that activate phosphatidyl-inositol 3-kinase, Ak strain transforming, and activator protein 1 signaling, which subsequently enhance MMP-13-induced tumor metastasis. TIMER2.0 analysis revealed a positive correlation between MMP-13 and IL-11 levels (r = 0.454). Moreover, a strong positive association was observed between higher levels of IL-11 expression in OSCC tissue (p < 0.01), lymph node metastasis (p = 0.0154), and clinical disease stage (p = 0.0337). IL-11 knockdown suppressed the migration of OSCC cells (p < 0.05). The evidence indicates that IL-11 can serve as a new molecular therapeutic target in OSCC metastasis.

Circ_0002722-induced regulation of YAP promotes platinum resistance in oral squamous cell carcinoma: Implications for verteporfin therapy.

Oral squamous cell carcinoma (OSCC) poses a significant public health burden due to its high prevalence and poor prognosis. Platinum resistance is one of the major challenges in OSCC treatment. Yes-associated protein (YAP) has been identified as a pivotal player in OSCC tumorigenesis and progression. Circular RNA (circRNA) has been implicated in chemoresistance in various cancers by regulation the function of microRNA. Nevertheless, the specific mechanisms linking circRNA to YAP expression in OSCC remain poorly understood. In this study, we detected the YAP and circRNA hsa_circ_0002722 (circ_0002722) expression by western blot (WB) and quantitative polymerase chain reaction (qPCR). We found that YAP and circ_0002722 were up-regulated in platinum resistance in OSCC tissues. Furthermore, transfection of circ_0002722 siRNA into platinum-resistant cells revealed that circ_0002722 acted as a regulator of miR-1305, which influenced YAP expression and thereby affected platinum sensitivity. In vivo experiments corroborated the synergistic effects of cisplatin and verteporfin (a YAP inhibitor) in combating platinum resistance. Targeting YAP emerges as a promising therapeutic strategy for addressing platinum resistance in OSCC, with circ_0002722 serving as a potential therapy target and valuable diagnostic marker. These findings shed light on the underlying mechanisms of platinum resistance, paving the way for the development of effective treatment approaches.

Primary versus salvage intratympanic steroid treatment for idiopathic sudden sensorineural hearing loss.

Objective: The objective of this research is to compare primary and salvage intratympanic (IT) steroid treatments in terms of hearing outcomes in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). Methods: The patients were randomized into two (primary and salvage) groups. Both groups received systemic steroid treatment for 2 weeks. The primary group also received IT dexamethasone injection three times during the treatment period, whereas the salvage group received IT dexamethasone injection only if no or slight recovery was noted at the 2-week follow-up. If needed, salvage steroid injection was administered three times during the following 2 weeks. Hearing recovery was analyzed according to the modified American Academy of Otolaryngology-Head and Neck Surgery criteria. Results: The degrees of hearing improvement at the 3-month follow-up were similar in the two groups. Compared with baseline, the pure-tone average values and speech discrimination scores improved by 38.45 ± 21.95 dB HL and 34.32% ± 30.55%, respectively, in the primary group and 36.80 ± 22.33 dB HL and 31.87% ± 27.88%, respectively, in the salvage group (p = .762 and .659, respectively). In addition, the complete or partial hearing recovery rates were also similar in the primary and salvage groups (67.7% vs. 73.3%, respectively; p = .780). In the salvage group, 18 patients required no IT steroid injection because they recovered after systemic steroid treatment. Conclusion: Primary and salvage IT steroid treatments for ISSNHL led to similar outcomes. In summary, salvage IT steroid injection is recommended for patients with ISSNHL patients to prevent unnecessary IT injection. Level of evidence: 2.

The Chemokine CCL4 Stimulates Angiopoietin-2 Expression and Angiogenesis via the MEK/ERK/STAT3 Pathway in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is a common malignant tumor with a poor prognosis and is a major public health burden in Taiwan. Angiogenesis, the formation of new blood vessels, promotes tumor proliferation, maintenance, and metastasis. Angiopoietin 2 (Angpt2), a mitogen with a strong angiogenic effect, is highly specific to endothelial cells and a key player in angiogenesis. The inflammatory chemokine (C-C motif) ligand 4 (CCL4) is also important in the pathogenesis and progression of cancer. In this study, an analysis of records from The Cancer Genome Atlas (TCGA) database found higher CCL4 expression in oral cancer tissue than in normal healthy tissue. CCL4 treatment of oral cancer cells upregulated Angpt2 expression and stimulated mitogen-activated protein kinase kinase (MEK), extracellular signal-regulated kinase 1/2 (ERK), and signal transducer and activator of transcription 3 (STAT3) phosphorylation. Transfection of oral cancer cells with MEK, ERK, and STAT3 inhibitors and their small interfering RNAs inhibited CCL4-induced promotion of Angpt2 expression and angiogenesis. In a mouse model of OSCC, CCL4-treated cells promoted neovascularization in implanted Matrigel plugs, whereas inhibiting CCL4 expression suppressed Angpt2 expression and angiogenesis. CCL4 shows promise as a new molecular therapeutic target for inhibiting angiogenesis and metastasis in OSCC.

Free flap reconstruction for early stage tongue squamous cell carcinoma: surgical margin and recurrence.

BACKGROUND: To identify the difference of surgical margin and recurrence status of early stage tongue carcinoma via wide excision in a single institution with and without free flap reconstruction. OBJECTIVE: Survey whether the reconstruction methods for early tongue cancer affects disease control, survival outcomes. METHODS: This was a retrospective study and patients with early tongue cancer underwent surgery via tumor ablation with (group 1 = 56) or without free flap reconstruction (group 2 = 291). RESULTS: The percentage of patients with free margin less than 5 mm was higher in the group 2 than in group 1 (49.48% vs. 19.64%, p < .001), as the mean free margin was significantly larger in group 1 than in group 2 (7.88 mm vs. 5.68 mm; p < .001). Despite higher number of T2 stage patients in group 1 (89.29%), the group 1 resulted in a significant lower recurrence rate (p = .024). CONCLUSIONS: The utilization of free flap reconstruction for early stage tongue cancer achieved a large pathologic free margin and had relative lower recurrence and good survival rates.

A dual-mode highly efficient class-E stimulator controlled by a low-Q class-E power amplifier through duty cycle.

This paper presents the design flow of two high-efficiency class-E amplifiers for the implantable electrical stimulation system. The implantable stimulator is a high-Q class-E driver that delivers a sine-wave pulsed radiofrequency (PRF) stimulation, which was verified to have a superior efficacy in pain relief to a square wave. The proposed duty-cycle-controlled class-E PRF driver designed with a high-Q factor has two operational modes that are able to achieve 100% DC-AC conversion, and involves only one switched series inductor and an unchanged parallel capacitor. The measured output amplitude under low-voltage (LV) mode using a 22% duty cycle was 0.98 V with 91% efficiency, and under high-voltage (HV) mode using a 47% duty cycle was 2.95 V with 92% efficiency. These modes were inductively controlled by a duty-cycle detector, which can detect the duty-cycle modulated signal generated from the external complementary low-Q class-E power amplifier (PA). The design methodology of the low-Q inductive interface for a non-50% duty cycle is presented. The experimental results exhibits that the 1.5-V PA that consumes DC power of 14.21 mW was able to deliver a 2.9-V sine wave to a 500 Ω load. The optimal 60% drain efficiency of the system from the PA to the load was obtained at a 10-mm coupling distance.

In situ measurement of tissue impedance using an inductive coupling interface circuit.

In this work, a method of an inductive coupling impedance measurement (ICIM) is proposed for measuring the nerve impedance of a dorsal root ganglion (DRG) under PRF stimulation. ICIM provides a contactless interface for measuring the reflected impedance by an impedance analyzer with a low excitation voltage of 7 mV. The paper develops a calibration procedure involving a 50-Ω reference resistor to calibrate the reflected resistance for measuring resistance of the nerve in the test. A de-embedding technique to build the equivalent transformer circuit model for the ICIM circuit is also presented. A batteryless PRF stimulator with ICIM circuit demonstrated good accuracy for the acute measurement of DRG impedance both in situ and in vivo. Besides, an in vivo animal experiment was conducted to show that the effectiveness of pulsed radiofrequency (PRF) stimulation in relieving pain gradually declined as the impedance of the stimulated nerve increased. The experiment also revealed that the excitation voltage for measuring impedance below 25 mV can prevent the excitation of a nonlinear response of DRG.