Oridonin inhibited epithelial-mesenchymal transition of laryngeal carcinoma by positively regulating LKB1/AMPK signaling.

Oridonin is the main bioactive component of Rabdosia rubescens, and its anticancer activity has been reported in a variety of cancers. However, the molecular mechanism of oridonin in laryngeal carcinoma remains unclear. In the present study, the cytotoxic effect of oridonin on laryngeal carcinoma Hep-2 and TU212 cell lines were initially detected by modified MTT assay. The results showed that oridonin had a dose-dependent anti-proliferative effect on laryngeal carcinoma Hep-2 and TU212 cells. Next, we found that oridonin significantly inhibited the migration and invasion of human laryngeal carcinoma Hep-2 and TU212 cell lines by wound healing assay and transwell assay. Subsequently, the results of quantitative real-time PCR assay and western blotting assay confirmed that oridonin upregulated the expression of E-cadherin while downregulated the expression of N-cadherin in a concentration-dependent manner at mRNA and protein levels. In addition, phosphorylation levels of liver kinase B1 (p-LKB1) and AMP-activated protein kinase (p-AMPK) were also elevated upon oridonin treatment. To further verify the role of LKB1/AMPK signaling pathway in laryngeal carcinoma, overexpression of LKB1 was constructed by plasmid transfection. The data exhibited that overexpression of LKB1 could further reinforce the increase of E-cadherin level and decrease of N-cadherin level mediated by oridonin. Additionally, AMPK inhibitor compound C could reverse anti-metastatic effect of oridonin on laryngeal carcinoma, and antagonise EMT expression. In contrast, AMPK activator AICAR presented the opposite effect. In conclusion, our study revealed that oridonin could remarkably reverse the epithelial-mesenchymal transition of laryngeal carcinoma by positively regulating LKB1/AMPK signaling pathway, which suggested that oridonin may be a potential candidate for the treatment of laryngeal carcinoma in the future.

Induction Toripalimab and Chemotherapy for Organ Preservation in Locally Advanced Laryngeal and Hypopharyngeal Cancer: A Single-Arm Phase II Clinical Trial.

PURPOSE: The aim of this study was to assess the efficacy, toxicities, and potential role of larynx preservation of induction chemotherapy combined with programmed cell death protein 1 (PD-1) inhibitor in locally advanced laryngeal and hypopharyngeal cancer. PATIENTS AND METHODS: This is a single-arm phase II study. Patients with histopathologically confirmed, resectable locally advanced laryngeal/hypopharyngeal squamous cell carcinoma and Eastern Cooperative Oncology Group Performance Status 0-1 were eligible. Three cycles of induction chemotherapy (paclitaxel 175 mg/m2 d1, cisplatin 25 mg/m2 d1-3) combined with PD-1 inhibitor (toripalimab 240 mg d0) were administered. Response assessment was performed after induction chemoimmunotherapy using RECIST 1.1 criteria. Patients with a complete/partial response of the primary tumor received concurrent chemoradiation, followed by maintenance therapy of toripalimab. Otherwise, patients were referred to surgery, followed by adjuvant (chemo) radiation and maintenance therapy of toripalimab. The primary endpoint is a larynx preservation rate at 3 months postradiation. RESULTS: Twenty-seven patients were enrolled. Most cases exhibited stage IV disease (81.5%), with T4 representing 37.0%. Five patients underwent pretreatment tracheostomy because of impaired larynx function. Overall response rate of induction chemoimmunotherapy was 85.2%. At 3 months postradiation, the larynx preservation rate was 88.9%. With a median follow-up of 18.7 months, the 1-year overall survival rate, progression-free survival rate, and larynx preservation rate were 84.7%, 77.6%, and 88.7%, respectively. When excluding those with pretreatment tracheostomy, the 1-year larynx preservation rate was 95.5%. Exploratory analysis revealed that relapse correlated with enrichment of RNA signature of hypoxia and M2 macrophage-associated genes. CONCLUSIONS: Induction toripalimab combined with chemotherapy provided encouraging activity, promising larynx preservation rate and acceptable toxicity in this cohort of extensively locally advanced laryngeal and hypopharyngeal cancer.

Betulinic acid inhibits the proliferation of human laryngeal carcinoma cells through reactive oxygen species-mediate mitochondrial apoptotic pathway.

Betulinic acid (BA), a natural pentacyclic triterpene, was extracted from the white birch tree, Triphyophyllum peltatum and the jujube tree. In a variety of human cancer cell lines, this substance displays anticancer properties. In this study, we examined how BA works to inhibit human laryngeal cancer growth. We discovered that BA minimally exhibited cytotoxicity in normal cells (human normal cell line GES-1), while remarkably inhibiting viability of AMC-HN-8, TU212, HEp-2 and M4e cells in a concentration-dependent manner. In AMC-HN-8 cancer cells, BA induced apoptosis, activated caspase-3/9/PARP, significantly reduced mitochondrial membrane potential (MMP), increased the expression of cytochrome C in the cytoplasm, transported Bax to the mitochondria, increased the production of reactive oxygen species (ROS), and the ROS scavenger N-acetylcysteine can reduce apoptosis. All data showed that BA triggered apoptosis via the mitochondrial pathway, in which ROS production was likely involved. The findings support the development of BA as a viable drug for the treatment of human laryngeal carcinoma.

A New Approach for Diagnosis and Surveillance of Infantile Subglottic Hemangioma in the Era of Propranolol Use: A Case Series.

OBJECTIVE: To report our institutional experience in diagnosing and surveilling patients with infantile subglottic hemangioma (SGH) using in-office flexible fiberoptic laryngoscopy (FFL) with video technology, without requiring operative endoscopy in the era of propranolol use. METHODS: A retrospective case series was conducted on 4 children diagnosed with SGH between 2016 and 2022 at our institution. RESULTS: Awake FFL with video technology provided adequate visualization of SGH lesions for diagnosis, without any complications. Serial examinations of the airway were performed in the outpatient setting and each SGH gradually regressed, with marked improvement in respiratory symptoms within 48 hours of oral propranolol initiation. CONCLUSION: Our findings showed that in select patients, FFL with video technology can successfully identify SGH lesions without general anesthesia exposure. FFL may be used as a low-risk screening tool for propranolol therapy initiation in some patients, but operative endoscopy should remain the gold standard procedure for others. By utilizing FFL in this manner, it is possible to diagnose SGH lesions and start propranolol therapy without exposing all patients to the risks of operative endoscopy.

Recent updates in laryngeal hemangioma management: a scoping review.

PURPOSE: To provide a comprehensive review of the current strategies in the management of laryngeal hemangiomas, with an aim to introduce a management algorithm that aligns with the variable clinical presentations and anatomical complexities of these lesions. METHODS: We conducted an extensive literature search across major databases using specific and general terms, combined with Boolean operators, to ensure comprehensiveness. Articles from January 2004 to August 2023 were included, with findings categorized by management approach. RESULTS: Laryngeal hemangiomas exhibit a spectrum of manifestations, ranging from asymptomatic lesions to those causing severe airway obstruction. Optimal management demands an individualized approach tailored to the patient's unique presentation and anatomical considerations. Diverse treatment modalities, each with distinct indications, advantages, and limitations, are explored. Notable highlights encompass the prominent role of Beta-blockers, notably Propranolol, in addressing problematic infantile hemangiomas, the nuanced efficacy of laser therapies contingent upon hemangioma type and depth, and the critical relevance of tracheotomy in emergencies. Novel approaches like transoral robotic surgery and transoral ultrasonic surgery, demonstrate promise in specific scenarios. We propose a management algorithm based on the complexity and presentation of laryngeal hemangiomas, emphasizing individualized treatment strategies, thereby addressing the unique challenges and nuances of each case. CONCLUSION: Laryngeal hemangioma management requires personalized approaches informed by diverse therapies, clinical expertise, and collaboration. The review introduces an algorithm spanning observation to advanced interventions, adapting to each case's complexity. Ongoing research promises innovative treatments.

Application of mPEG-CS-cRGD/Bmi-1RNAi-PTX nanoparticles in suppression of laryngeal cancer by targeting cancer stem cells.

Although surgery-based comprehensive therapy is becoming the main approach to treat laryngeal cancer, recurrence, metastasis, radiotherapy resistance and chemotherapy tolerance are still the main causes of death in patients. Targeted inhibition of laryngeal cancer stem cells has been considered as the consensus to cure laryngeal cancer. Our previous study has confirmed proto-oncogene Bmi-1 as a key regulator for self-renewal of laryngeal cancer stem cells. Targeted knockdown of Bmi-1 gene effectively inhibited the self-renewal and differentiation of laryngeal cancer stem cells, leading to the promoted sensitivity to chemotherapy including paclitaxel. However, due to off-target effects and quick degradation of the naked Bmi-1-RNAi small RNA oligo by nuclease in body fluids, it is urgently needed to develop a tumor-targeted delivery system with a protective shell. In this study, we designed and synthesized cRGD peptide-modified chitosan-polyethylene glycol slow-release nanoparticles (mPEG-CS-cRGD/Bmi-1RNAi-PTX) containing Bmi-1RNAi siRNA oligo and paclitaxel, which showed spherical in shape, 200 nm diameter in size, low cytotoxicity, strong DNA wrapping, resistance to nuclease degradation and high transfection efficiency to cells. Functional analysis indicated significant suppression of cell proliferation and migration and induction of apoptosis by the nanocomplex in laryngeal cancer cells in vitro. By application to the mouse model with laryngeal cancer, the nanocomplex inhibited tumor growth significantly in vivo. In addition, cRGD peptide, paclitaxel and Bmi-1 siRNA in the nanoparticles showed synergistic effects to suppress laryngeal cancer stem cells. In conclusion, this study not only developed a laryngeal tumor-targeted chemotherapeutic system, but also demonstrated a Bmi-1 RNAi-based chemotherapeutic strategy to inhibit cancer stem cells, having strong potential to treat laryngeal cancer patients suffering therapy resistance and/or tumor recurrence.

Effects of ceramide C2 application on human laryngeal carcinoma cells: a cell culture study.

OBJECTIVE: In the present study, we investigated the effects of Ceramide C2 application on human laryngeal carcinoma cells. MATERIALS AND METHODS: Human larynx epidermoid carcinoma HEp-2 (ATCC® CCL-23™) cells were purchased from the American Type Culture Collection (ATCC, USA). Human larynx epidermoid carcinoma HEp-2 cells were cultured in complete Dulbecco's Modified Eagle's Medium (DMEM) supplemented with fetal bovine serum (FBS) (10%) and penicillin/streptomycin (1%) in a CO2 (5%) incubator under standard cell culture conditions. Ceramide C2 was prepared, and further dilutions ranging from 3.13 to 100 µM were prepared in a fresh culture medium. Cells on 96 well plates were exposed to the prepared concentrations of ceramide C2 for 24 and 48 hours. Cytotoxicity evaluation was performed by MTT. Apoptosis profiles of HEp-2 cells were detected by annexin-V analysis. The activated caspases 3/7 on HEp-2 cells after ceramide C2 exposure were evaluated with flow cytometric analysis. The morphological changes on HEp-2 cells caused by ceramide C2 were evaluated by staining with phalloidine and acridine orange via confocal microscopy. For the Wound Healing Assay, HEp-2 cells were cultured in 6 well-plates until they became confluent. RESULTS: MTT cytotoxicity test findings revealed that the viability of human laryngeal carcinoma cells decreased with the increased application of ceramide C2 for 24 hours compared to untreated (control) cells. The highest growth inhibition by ceramide C2 for short-term application for 24 hours was detected at the highest concentration of ceramide C2 (100 µM). Annexin-V findings showed that 98.97 of HEp-2 cells were alive, and 1.63% were detected as early apoptosis for the control group. The results showed that ceramide C2 triggered apoptosis on HEp-2 cells with a percentage of total apoptotic cells of 61,40 compared to untreated HEp-2 cells. Cysteine proteases (caspases) 3/7 activation percentages of HEp-2 cells exposed to ceramide C2 for 24 hours were compared to control cells, and the morphology of HEp-2 cells was changed with clear apoptotic signs that underlined the cytotoxicity and pro-apoptotic activity of ceramide C2. Scratch Assay assessed the migration capability of HEp-2 cells before and after the exposure to ceramide C2. It showed that ceramide C2 reduced human laryngeal carcinoma cells' migration capability and proliferation for 24 hours. CONCLUSIONS: Based on all study findings, it can be considered that short-chain ceramide C2 exerted cytotoxicity on human laryngeal carcinoma cells in a dose and time-dependent manner and reduced the viability via inducing caspase-dependent apoptosis. The overall effect might be derived from the elevated intracellular ceramide levels by the exogenous application of ceramide C2. Consequently, it was concluded that ceramide C2 has good potential to cause cytotoxicity and apoptosis in human laryngeal carcinoma cells and, after deeper in vitro and in vivo investigations, can be a good candidate for designing anti-cancer drugs with high efficiency.

PD-1 Inhibitors combined with paclitaxel (Albumin-bound) and cisplatin for larynx preservation in locally advanced laryngeal and hypopharyngeal squamous cell carcinoma: a retrospective study.

BACKGROUND: laryngeal and hypopharyngeal squamous cell carcinoma (SCC) is a common head and neck cancer with significant impact on quality of life due to its crucial roles in vocalization, airway protection, and swallowing. This retrospective study aims to evaluate the efficacy and larynx organ preservation of neoadjuvant treatment with PD-1 inhibitors in combination with paclitaxel (Albumin-bound) and cisplatin for locally advanced laryngeal and hypopharyngeal SCC. METHODS: Medical records of consecutive patients diagnosed with histologically or cytologically confirmed locally advanced SCC of the larynx and hypopharynx, who received PD-1 inhibitor therapy at a single tertiary care center, were reviewed from January 1, 2019, to December 15, 2022. The patients were treated with a combination of PD-1 inhibitors, paclitaxel (Albumin-bound) 260mg/m2, and cisplatin 60mg/m2 (TP) as their first-line therapy. Survival outcomes, laryngectomy-free survival (LFS) rates and response rates were assessed. RESULTS: The study cohort comprised 156 patients, predominantly male, with a median age of 60.4 years. The estimated one-year overall survival (OS) rate was 94.1%, two-year OS rate was 82.5%, one-year progression-free survival (PFS) rate was 80.4%, and two-year PFS rate was 66.3%. The one-year LFS was 86.4%, and the two-year LFS rate was 73.0%. The overall response rate after TP + PD-1 inhibitors therapy was 88.5%. Common treatment-associated adverse events included rash, thyroid function abnormalities, myelosuppression, and colitis. CONCLUSION: Neoadjuvant therapy with PD-1 inhibitors in combination with paclitaxel (Albumin-bound) and cisplatin showed promising efficacy and tolerability for larynx preservation in locally advanced laryngeal and hypopharyngeal SCC. The high response rates and favorable survival outcomes suggest this approach as a potential treatment option. Prospective randomized controlled trials are needed to further validate these findings and establish the role of immunotherapy in larynx preservation.

Luteolin inhibits angiogenesis and enhances radiotherapy sensitivity of laryngeal cancer via downregulating Integrin ß1.

AIM: To demonstrate the role and mechanism of luteolin in radio-sensitization and angiogenesis of laryngeal cancer. METHODS: Firstly, we analyzed the cytotoxicity of Luteolin and radiation sensitive cytotoxicity through CCK8, and selected subsequent radiation doses and Luteolin concentrations. Next, we further analyzed the effects of Luteolin on radiation sensitivity and neovascularization of laryngeal cancer, and conducted CCK8, plate cloning, and angiogenesis experiments, respectively. At the same time, the effects of individual treatment and combination treatment on the expression of Integrin ß1 and VEGFA were analyzed through immunofluorescence analysis. We also analyzed the regulation of Integrin ß1 protein expression by Luteolin through Western blot. To investigate the mechanism of Integrin ß1, we transfected overexpressed and silenced Integrin ß1 vectors and analyzed the role of Integrin ß1 in Luteolin enhancing radiation sensitivity of laryngeal cancer by repeating the above experiments. We have also constructed an in vivo subcutaneous tumor transplantation model to further validate the cell experimental results. The expression of Integrin, KI67, VEGFA, and CD31 was analyzed through Western blot and immunohistochemistry experiments. RESULTS: Radiation inhibited cell proliferation and decreased Integrin ß1 expression, and increased the radiosensitivity through inhibiting cell proliferation, and inhibit angiogenesis during radiation. Overexpression of Integrin ß1 weakened radiotherapy sensitivity on the basis of cells treated with combined administration. Integrin ß1 is considered as the downstream molecule of luteolin, participating in radiosensitivity of luteolin to FaDu cells. Animal experiments also demonstrated that luteolin strengthened tumor suppression and anti-angiogenesis during radiation via Integrin ß1. CONCLUSION: In summary, our results manifested that radio-sensitivity effect of luteolin depended on downregulating Integrin ß1 in laryngocarcinoma.

A nationwide analysis of salvage surgery for laryngeal cancer in the elderly.

BACKGROUND: We aim to describe outcomes of elderly patients undergoing salvage surgery for laryngeal cancer and to characterize the interplay of age with various other factors in this growing population. METHODS: Using the National Cancer Database, we identified cases of salvage laryngectomy in patients who failed chemoradiation. An age cutoff of 70 years was used to separate subjects into two groups. Various factors were compared. RESULTS: Of the 825 patients included, 166 (20.1%) were elderly. Elderly patients had worse overall survival (p = 0.001), higher 30-day and 90-day mortality (p = 0.006, p < 0.001), and a longer length of stay (LOS) (p = 0.015). LOS over 1 week was associated with worse survival (p = 0.032). CONCLUSION: Elderly patients had worse overall perioperative survival than their younger counterparts. LOS and 30-day readmissions were associated with higher risk of mortality in this group. We provide a contemporary set of relevant information for head and neck cancer providers to consider in this growing population.

Validation of a prognostic model for predicting larynx preservation outcome (TALK score) in a Southern European population

Objective Larynx preservation is the current standard for locally advanced (LA) laryngeal/hypopharyngeal tumors, but not all patients respond as expected. TALK score model measures four variables (T-staging, albumin levels, liquor consumption and Karnofsky score) to determine which cases are best suited to preservation treatment scheme. We aimed to validate this prognostic model in a Southern European population. Methods We retrospectively evaluated 175 patients diagnosed from July 2008 to December 2015 with LA laryngeal/hypopharyngeal carcinoma and treated with a laryngeal preservation scheme comprising induction chemotherapy followed by concomitant chemotherapy and radiotherapy. We applied the TALK score model to predict larynx preservation rate. Results Of the 175 patients evaluated, 96.6% were men, 98.3% were smokers and 77.1% misused alcohol. Tumors were laryngeal 66.3% vs 33.7% in hypopharynx, and all were either stage III (37.7%) or stage IV (62.3%). TALK prognostic subgroups were: good risk 40.0%; intermediate risk 52.5%; and poor risk 7.5%. With a median follow-up of 40.1 months, larynx preservation rate, laryngectomy-free survival and overall survival at 3 years was 84.5%, 63.7% and 68.2%, respectively. Although TALK score was not predictive of 3-year larynx preservation rate (good risk 85.5%; intermediate risk 83.1%; poor risk 91.6%), it was predictive of 3-year overall survival (good risk 81.9%; intermediate risk 62.9%; poor risk 33.5%) and 3-year laryngectomy-free survival (good risk 75.6%; intermediate risk 59.6%; poor risk 30.7%) Conclusion TALK model could predict OS and laryngectomy-free survival, helping clinicians to decide which patients should avoid laryngeal preservation and undergo laryngectomy after diagnosis (AU)

Induction chemotherapy-based organ-preservation protocol improve the function preservation compared with immediate total laryngectomy for locally advanced hypopharyngeal cancer-Results of a matched-pair analysis.

BACKGROUND: We performed a paired analysis to compare the therapeutic effect between the induction chemotherapy-based organ-preservation approach and immediate total laryngectomy in hypopharyngeal squamous cell carcinoma patients requiring total laryngectomy. METHODS: 351 patients who were treated with organ-preservation approach were compared with 110 patients who were treated with total laryngectomy. The main measures and outcomes were progression-free survival (PFS), overall survival (OS), and larynx function preservation survival (LFPS). RESULTS: No statistical difference was observed for 3-, 5-, and 10-year PFS and OS in two groups. In the organ-preservation group, the 3-, 5-, and 10-year LFPS was 30.7%, 23.3%, and 16.6%, respectively. The LFPS of Stage III > Stage IV, N0 > N1 > N2 > N3, T2 > T3 > T4, CR > PR > SD > PD patients (all p values <0.05). CONCLUSIONS: Survival outcomes did not significantly differ between the two groups. The organ-preservation approach allowed more than 70% of the survivors to retain their larynx function.

Optimized radiotherapy treatment strategy for early glottic carcinoma.

The local control rates of T1 bulky and T2 glottic carcinoma treated via radiation therapy alone are unsatisfactory; thus, we aimed to evaluate the efficacy and safety of our treatment protocol for early glottic carcinoma. Patients with early glottic squamous cell carcinoma treated via radiation therapy from January 2007 to November 2019 were reviewed. Patients were treated with: 63-67.5 Gy/28-30 fractions of radiation therapy alone for T1 non-bulky; concurrent chemoradiotherapy with S-1 and 60 Gy/30 fractions for T1 bulky and T2 favorable; and concurrent chemoradiotherapy with high-dose cisplatin and 66-70 Gy/33-35 fractions for T2 unfavorable glottic carcinoma. Local failure rates were estimated using the cumulative incidence function, overall and disease specific survival rates were estimated using Kaplan-Meier analysis, and adverse events were evaluated. Eighty patients were analyzed; the median age was 69.5 (range, 26-90) years, the median follow-up time for survivors was 40.1 (range, 1.9-128.4) months, and the 3-year local failure, disease specific survival, and overall survival rates were 5.8%, 98.3%, and 94.4%, respectively. In T1 bulky and T2 cases, the local failure rate was significantly lower in the concurrent chemoradiotherapy than in the radiation therapy alone group. Grade 3 acute dermatitis and mucositis were noted in nine and four patients, respectively. There were no acute adverse events of Grade 4 or higher, or late adverse events of Grade 2 or higher. The treatment protocol was effective and well-tolerated; thus, the efficacy of concurrent chemoradiotherapy was suggested in T1 bulky and T2 cases.

Chitosomes Loaded with Docetaxel as a Promising Drug Delivery System to Laryngeal Cancer Cells: An In Vitro Cytotoxic Study.

Current delivery of chemotherapy, either intra-venous or intra-arterial, remains suboptimal for patients with head and neck tumors. The free form of chemotherapy drugs, such as docetaxel, has non-specific tissue targeting and poor solubility in blood that deters treatment efficacy. Upon reaching the tumors, these drugs can also be easily washed away by the interstitial fluids. Liposomes have been used as nanocarriers to enhance docetaxel bioavailability. However, they are affected by potential interstitial dislodging due to insufficient intratumoral permeability and retention capabilities. Here, we developed and characterized docetaxel-loaded anionic nanoliposomes coated with a layer of mucoadhesive chitosan (chitosomes) for the application of chemotherapy drug delivery. The anionic liposomes were 99.4 ± 1.5 nm in diameter with a zeta potential of -26 ± 2.0 mV. The chitosan coating increased the liposome size to 120 ± 2.2 nm and the surface charge to 24.8 ± 2.6 mV. Chitosome formation was confirmed via FTIR spectroscopy and mucoadhesive analysis with anionic mucin dispersions. Blank liposomes and chitosomes showed no cytotoxic effect on human laryngeal stromal and cancer cells. Chitosomes were also internalized into the cytoplasm of human laryngeal cancer cells, indicating effective nanocarrier delivery. A higher cytotoxicity (p < 0.05) of docetaxel-loaded chitosomes towards human laryngeal cancer cells was observed compared to human stromal cells and control treatments. No hemolytic effect was observed on human red blood cells after a 3 h exposure, proving the proposed intra-arterial administration. Our in vitro results supported the potential of docetaxel-loaded chitosomes for locoregional chemotherapy delivery to laryngeal cancer cells.

KRAS Mutation Reduces Thymoquinone Anticancer Effects on Viability of Cells and Apoptosis.

BACKGROUND: Cancer is a life-threatening condition with an economic burden on societies. Phytotherapy is rapidly taking place in cancer research to increase the success of treatment and quality of life. Thymoquinone (TQ) is the main active phenolic compound obtained from the essential oil of the Nigella sativa (black cumin) plant seed. For a long time, black cumin has been used traditionally for the remedy of different diseases because of its various biological effects. It has been shown that most of these effects of black cumin seeds are due to TQ. TQ became a popular research topic for phytotherapy studies for its potential therapeutic applications, and more research is going on to fully understand its mechanisms of action, safety, and efficacy in humans. KRAS is a gene that regulates cell division and growth. Monoallelic variants in KRAS result in uncontrollable cell division, leading to cancer development. Studies have shown that cancer cells with KRAS mutations are often resistant to certain types of chemotherapy and targeted therapies. OBJECTIVE: This study aimed to compare the effect of TQ on cancer cells with and without KRAS mutation to better understand the reason why TQ may have different anticancer effects in the different types of cancer cells. METHODS: TQ was investigated for its cytotoxic and apoptotic effects in laryngeal cancer cells (HEp-2) without KRAS mutation and compared to mutant KRAS-transfected larynx cancer cells and KRAS mutation-carrying lung cancer cells (A549). RESULTS: We showed that TQ has more cytotoxic and apoptotic effects on laryngeal cancer cells without KRAS mutation than in cells with mutation. CONCLUSION: KRAS mutations decrease the effect of TQ on cell viability and apoptosis, and further studies are needed to fully understand the relationship between KRAS mutations and thymoquinone effectiveness in cancer treatment.

Effect of CADM1 on TPF-induced chemotherapy in laryngeal squamous cell carcinoma.

OBJECTIVES: To explore the relationship between CADM1 expression and sensitivity to TPF-induced chemotherapy in laryngeal squamous cell carcinoma (LSCC) patients, then investigate its potential mechanisms. METHODS: Differential CADM1 expression was examined in chemotherapy-sensitive and chemotherapy-insensitive LSCC patient samples after TPF-induced chemotherapy using microarray analysis. Receiver operating characteristic (ROC) curve analysis and bioinformatics approaches were used to investigate the diagnostic value of CADM1. Small interfering RNAs (siRNAs) were used to knock down CADM1 expression in an LSCC cell line. Differential CADM1 expression was compared by qRT-PCR assays in 35 LSCC patients treated with chemotherapy, including 20 chemotherapy-sensitive and 15 chemotherapy-insensitive patients. RESULTS: Public database and primary patient data both suggest that CADM1 mRNA is expressed at lower levels in chemotherapy-insensitive LSCC samples, suggesting its potential usefulness as a biomarker. Knockdown of CADM1 with siRNAs led to decreased sensitivity of LSCC cells to TPF chemotherapy. CONCLUSIONS: Upregulation of CADM1 expression can alter the sensitivity of LSCC tumors to TPF induction chemotherapy. CADM1 is a possible molecular marker and therapeutic target for induction chemotherapy in LSCC patients.

Chidamide, a novel histone deacetylase inhibitor, inhibits laryngeal cancer progression in vitro and in vivo.

Although surgery is an important treatment for laryngeal cancer, surgery has a significant negative impact on the quality of life of patients, and many patients have poor tolerance to surgery. Therefore, alternative chemotherapeutic drugs are an important research hotspot. Chidamide is a histone deacetylase inhibitor that selectively inhibits the expression of type I and IIb histone deacetylases (1, 2, 3 and 10). It has a significant anticancer effect on a variety of solid tumours. This study verified the inhibitory effect of chidamide on laryngeal carcinoma. We conducted a variety of cellular and animal experiments to explore how chidamide inhibits the development of laryngeal cancer. The results showed that chidamide had significant antitumour activity against laryngeal carcinoma cells and xenografts and could induce cell apoptosis, ferroptosis and pyroptosis. This study provides a potential option for the treatment of laryngeal cancer.

Functionalized Sulfur-Containing Heterocyclic Analogs Induce Sub-G1 Arrest and Apoptotic Cell Death of Laryngeal Carcinoma In Vitro.

In this study, we speculate that the hydroxyl-containing benzo[b]thiophene analogs, 1-(3-hydroxybenzo[b]thiophen-2-yl) ethanone (BP) and 1-(3-hydroxybenzo[b]thiophen-2-yl) propan-1-one hydrate (EP), might possess antiproliferative activity against cancer cells. Hydroxyl-containing BP and EP show selectivity towards laryngeal cancer cells (HEp2), with IC50 values of 27.02 ± 1.23 and 35.26 ± 2.15 µM, respectively. The hydroxyl group present in the third position is responsible for the anticancer activity and is completely abrogated when the hydroxyl group is masked. BP and EP enhance the antioxidant enzyme activity and reduce the ROS production, which are correlated with the antiproliferative effect in HEp-2 cells. An increase in the BAX/BCL-2 ratio occurs during the BP and EP treatment and activates the caspase cascade, resulting in apoptosis stimulation. It also arrests the cells in the Sub-G1 phase, indicating the induction of apoptosis. The molecular docking and simulation studies predicted a strong interaction between BP and the CYP1A2 protein, which could aid in combinational therapy by enhancing the bioavailability of the drugs. BP and EP possess an antioxidant property with low antiproliferative effects (~5.18 µg/mL and ~7.8 µg/mL) as a standalone drug, therefore, they can be combined with other drugs for effective chemotherapy that might trigger the effect of pro-oxidant drug on healthy cells.

Benralizumab as an Adjuvant Therapy for Recurrent Laryngeal Papillomatosis.

Recurrent respiratory (RRP) or laryngeal papillomatosis is the result of human papillomavirus-mediated benign tumor growth on the larynx and is challenging to manage. Benralizumab is a monoclonal antibody targeted against the alpha subunit of the IL-5 receptor on eosinophils. A 61-year-old male patient presented with refractory RRP following multiple surgical excisions. His disease course improved substantially when benralizumab was added to his asthma regimen. There is no clear mechanistic role suggested for benralizumab directly treating RRP. This case may represent a novel application of benralizumab as an adjuvant treatment for patients with RRP and comorbid asthma. Laryngoscope, 133:863-865, 2023.

Asociación de hemangioma en zona cérvico facial y hemangioma subglótico en un neonato / Association of cervical-facial and subglottic hemangioma in neonates / Associação de hemangioma cervicofacial e subglótico em neonatos

Se presenta un neonato con hemangioma cérvico facial y posterior diagnóstico de hemangioma subglótico. Los hemangiomas en el período neonatal y los primeros meses de vida requieren una atención cuidadosa. Debido a su patrón de crecimiento y la futura aparición de nuevas lesiones, son considerados imprevisibles en esta etapa. Se encontró una fuerte asociación entre los hemangiomas difusos de localización cérvico facial y los hemangiomas sintomáticos de la vía aérea alta. El riesgo está relacionado con el grado de extensión de la afectación cutánea en un área que incluye la piel de la región mandibular, el mentón, el labio inferior y la parte anterior del cuello. Los hemangiomas infantiles requieren tratamiento cuando presentan riesgo vital y alteraciones funcionales, como compromiso de la vía aérea.

This is the case of a newborn with cervical hemangioma and a subsequent diagnosis of subglottic hemangioma. Hemangiomas in neonates and infants require careful attention. Due to their growth pattern and the potential appearance of new lesions, they are considered unpredictable at this stage. A strong link was found between diffuse cervical-facial and symptomatic upper airway hemangiomas. The risk is related to the extent of skin involvement in a given area, which might include the jaw, chin, lower lip, and front of the neck skin. Infant hemangiomas require treatment when they present life-threatening and functional alterations, such as airway compromise.

Relatamos o caso de um recém-nascido com hemangioma cervical com diagnóstico posterior de hemangioma subglótico. Hemangiomas em recém-nascidos e lactentes requerem atenção cuidadosa. Devido ao seu padrão de crescimento e ao potencial aparecimento de novas lesões, são considerados imprevisíveis nessa fase. Uma forte associação foi encontrada entre hemangiomas cervicofaciais difusos e hemangiomas sintomáticos das vias aéreas superiores. O risco está relacionado à extensão do envolvimento da pele da mandíbula, o queixo, o lábio inferior e a pele da frente do pescoço. Os hemangiomas infantis necessitam de tratamento quando apresentam alterações funcionais ou risco de vida, como comprometimento das vias aéreas.