Hypopharyngeal Carcinoma Research Articles

Impact of cervical lymph node metastasis on transoral surgery for hypopharyngeal squamous cell carcinoma: A retrospective multicenter study.

Hypopharyngeal carcinoma is likely to spread to the lymph nodes, but there is no established strategy for management in transoral surgery. We compared oncologic and functional outcomes in a retrospective multicenter study of patients who underwent transoral surgery for hypopharyngeal carcinoma between 2015 and 2021. Two-hundred and thirty-two patients were included. Comparing patients with and without adjuvant radiotherapy, 3-year regional recurrence-free survival (RRFS) was not significantly different in pN2b and pN2c, but was significantly worse in pN3b without adjuvant radiotherapy. In patients without neck dissection, the 3-year RRFS was 85.6%, 76.8%, and 70.0% for T1, T2, and T3 primary lesions, respectively, and was significantly worse for T2 or higher (p = 0.035). In the absence of extracapsular invasion, regional control did not deteriorate without adjuvant therapy. If prophylactic neck dissection is not performed, careful follow-up is necessary if the primary lesion is T2 or greater.

Results and lessons learnt from the WISTERIA phase I trial combining AZD1775 with cisplatin pre- or post-operatively in head and neck cancer

BackgroundPre-clinical studies suggest AZD1775, a WEE1 kinase inhibitor, potentiates the activity of various chemotherapeutic agents.MethodsWISTERIA was a prospective, parallel two-group, open-label, dose-finding, phase I clinical trial. Eligible patients had histologically confirmed oral, laryngeal, or hypopharyngeal squamous cell carcinoma, ECOG performance status 0/1, and aged ≥18-to-≤70 years. Primary outcomes were adverse events and defining recommended dose and schedule of AZD1775 in combination with cisplatin in pre-operative (Group A), or with cisplatin/radiotherapy in post-operative (Group B) patients. Dose determination was guided by a modified time-to-event continual reassessment method (mTITE-CRM).ResultsBetween 30-Oct-2017 and 15-Jul-2019, nine patients were registered: Three into Group A and six into Group B. WISTERIA was closed early due to poor recruitment. Five dose-limiting toxicities (DLTs) were reported in four Group B patients. Seven serious adverse events were reported in four patients: One in Group A, and three in Group B. Three were related to treatment. No treatment-related deaths were reported.ConclusionsWISTERIA did not complete its primary objectives due to poor recruitment and toxicities reported in Group B. However, use of the novel mTITE-CRM improved flexibility in reducing accrual suspension periods and should be considered for future trials in complex patient populations.Clinical Trial RegistrationISRCTN76291951

Establishment and characterization of a novel hypopharyngeal squamous cell carcinoma cell line CZH1 with genetic abnormalities.

Hypopharyngeal squamous cell carcinoma (HPSCC) has the worst prognosis among head and neck squamous cell carcinomas. The lack of available tumor cell lines poses a significant obstacle to the development of efficient treatments for HPSCC. In this study, we successfully established a novel cell line, named CZH1, from the postcricoid region of a Chinese male patient with a T3N0M0 HPSCC. Short tandem repeat analysis confirmed the uniqueness of CZH1. The cell line was characterized by its phenotypes, biomarkers, and genetics. Importantly, CZH1 cells retained the typical features of epithelial malignancy, similar to the primary tumor tissue. Furthermore, CZH1 demonstrated a greater capacity for invasion and increased susceptibility to irradiation in comparison to FaDu, which is the most commonly used HPSCC cell line. Whole-exome sequencing analysis revealed that CZH1 cells had typical genomic features of HNSCC, including mutations of TP53 and amplifications of multiple transcripts. Therefore, our newly developed CZH1 cell line could serve as an efficient tool for the in vitro investigation of the etiology, pathogenesis, and preclinical treatment of HPSCC.

Combined average standard uptake value and rate constant can predict expression of EGFR in hypopharyngeal squamous cell carcinoma: A pilot study with integrated PET/MRI

PurposeTo investigate whether the quantitative multiparameters of 18F-FDG PET/MRI can predict expression of epidermal growth factor receptor (EGFR) of hypopharyngeal squamous cell carcinoma (HSCC). MethodsTwenty-one patients with HSCC confirmed by biopsy underwent neck integrated 18F-FDG PET/MRI and EGFR expression detection. Quantitative parameters derived from 18F-FDG PET, difusion-weighted imaging (DWI), and dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) were measured. The efficacies of quantitative multiparameters derived from 18F-FDG PET/MRI for predicting the expression of EGFR of HSCC were evaluated. ResultsThe patients were divided into positive expression group (PEG, n = 14) and negative expression group (NEG, n = 7). Mann-Whitney U nonparametric test showed that SUVmean and Kep had statistical difference between PEG and NPG, while other parameters had no statistical difference. Using 14.50 and 2.10 min−1 as the threshold values, areas under the curve (AUCs) for SUVmean and Kep were 0.786 with specificity of 92.9 % and sensitivity of 57.1 %. The combined use of SUVmean and Kep had better efficacy to evaluate the expression of EGFR with AUC of 0.980, sensitivity of 92.9 %, and specificity of 100.0 %. ConclusionCombined use of SUVmean and Kep showed good performance in predicting the expression of EGFR in HSCC. Integrated 18F-FDG PET/MRI enables simultaneous acquisition of SUVmean and Kep, so it represents as a powerful tool to noninvasively and repeatably evaluate the expression of EGFR during the management of HSCC.

Arterial Blood Gas Analysis in Patients with Stridor, and the Impact of Emergency Tracheostomy on It: A Tertiary Care Center Experience.

Comparative evaluation of arterial blood gas in patients with stridor, before and after emergency tracheostomy. The present prospective study was conducted in tertiary care Centre from February 2022 to June 2023 on 42 patients who presented with stridor and underwent emergency tracheostomy in our department. After proper history taking and clinical examination, nonsurgical cause of stridor was ruled out. Patients were then classified on the basis of location of cause of stridor (whether oropharyngeal, hypo-pharyngeal, supra-glottic, glottic or sub-glottic). Immediately an arterial blood gas (ABG) analysis was done, and emergency tracheostomy was performed. Following tracheostomy, ABG analysis was done immediately, after 12h and after 24h. The mean age of presentation of stridor in our study was 65.02 ± 3.23years, with male preponderance (Male: female ratio being 3.66:1). Most common etiology of stridor in our study was glottic carcinoma comprising 50%, and least common etiology of stridor was hypopharyngeal carcinoma, and subglottic stenosis comprising 2.4% each. There was statistically significant normalization of ABG in terms of pH, PO2, PCO2, HCO3. Mean pH, PO2, PCO2, and HCO3 before tracheostomy were 7.31, 74.8, 60.6, and 29.8 respectively. Mean pH, PO2, PCO2, HCO3, immediately after tracheostomy were7.38, 91.3, 48.4, and 27.4 respectively. After 12h of tracheostomy, mean pH, PO2, PCO2, HCO3 were 7.41, 95.4, 42.7, 25.3 respectively. Mean pH, PO2, PCO2, HCO3 24h after emergency tracheostomy were 7.441, 95.5, 42.8, 24.6 respectively. Emergency tracheostomy in stridor patients improves the acid base and ventilatory status, by relieving the obstruction as evidenced by statistically significant improvement in arterial blood gas values, and can be used as a diagnostic tool in upper airway obstruction.

Prophylactic pectoralis major flap to compensate for increased risk of pharyngocutaneous fistula in laryngectomy patients with low skeletal muscle mass (PECTORALIS): study protocol for a randomized controlled trial

BackgroundTotal laryngectomy (TL) is a surgical procedure commonly performed on patients with advanced laryngeal or hypopharyngeal carcinoma. One of the most common postoperative complications following TL is the development of a pharyngocutaneous fistula (PCF), characterized by a communication between the neopharynx and the skin. PCF can lead to extended hospital stays, delayed oral feeding, and compromised quality of life. The use of a myofascial pectoralis major flap (PMMF) as an onlay technique during pharyngeal closure has shown potential in reducing PCF rates in high risk patients for development of PCF such as patients undergoing TL after chemoradiation and low skeletal muscle mass (SMM). Its impact on various functional outcomes, such as shoulder and neck function, swallowing function, and voice quality, remains less explored. This study aims to investigate the effectiveness of PMMF in reducing PCF rates in patients with low SMM and its potential consequences on patient well-being.MethodsThis multicenter study adopts a randomized clinical trial (RCT) design and is funded by the Dutch Cancer Society. Eligible patients for TL, aged ≥ 18 years, mentally competent, and proficient in Dutch, will be enrolled. One hundred and twenty eight patients with low SMM will be centrally randomized to receive TL with or without PMMF, while those without low SMM will undergo standard TL. Primary outcome measurement involves assessing PCF rates within 30 days post-TL. Secondary objectives include evaluating quality of life, shoulder and neck function, swallowing function, and voice quality using standardized questionnaires and functional tests. Data will be collected through electronic patient records.DiscussionThis study’s significance lies in its exploration of the potential benefits of using PMMF as an onlay technique during pharyngeal closure to reduce PCF rates in TL patients with low SMM. By assessing various functional outcomes, the study aims to provide a comprehensive understanding of the impact of PMMF deployment. The anticipated results will contribute valuable insights into optimizing surgical techniques to enhance patient outcomes and inform future treatment strategies for TL patients.Trial registrationNL8605, registered on 11-05-2020; International Clinical Trials Registry Platform (ICTRP).

Machine learning model to preoperatively predict T2/T3 staging of laryngeal and hypopharyngeal cancer based on the CT radiomic signature.

To develop and assess a radiomics-based prediction model for distinguishing T2/T3 staging of laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) METHODS: A total of 118 patients with pathologically proven LHSCC were enrolled in this retrospective study. We performed feature processing based on 851 radiomic features derived from contrast-enhanced CT images and established multiple radiomic models by combining three feature selection methods and seven machine learning classifiers. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity were used to assess the performance of the models. The radiomic signature obtained from the optimal model and statistically significant morphological image characteristics were incorporated into the predictive nomogram. The performance of the nomogram was assessed by calibration curve and decision curve analysis. Using analysis of variance (ANOVA) feature selection and logistic regression (LR) classifier produced the best model. The AUCs of the training, validation, and test sets were 0.919, 0.857, and 0.817, respectively. A nomogram based on the model integrating the radiomic signature and a morphological imaging characteristic (suspicious thyroid cartilage invasion) exhibited C-indexes of 0.899 (95% confidence interval (CI) 0.843-0.955), fitting well in calibration curves (p > 0.05). Decision curve analysis further confirmed the clinical usefulness of the nomogram. The nomogram based on the radiomics model derived from contrast-enhanced CT images had good diagnostic performance for distinguishing T2/T3 staging of LHSCC. Accurate T2/T3 staging assessment of LHSCC aids in determining whether laryngectomy or laryngeal preservation therapy should be performed. The nomogram based on the radiomics model derived from contrast-enhanced CT images has the potential to predict the T2/T3 staging of LHSCC, which can provide a non-invasive and robust approach for guiding the optimization of clinical decision-making. • Combining analysis of variance with logistic regression yielded the optimal radiomic model. • A nomogram based on the CT-radiomic signature has good performance for differentiating T2 from T3 staging of laryngeal and hypopharyngeal squamous cell carcinoma. • It provides a non-invasive and robust approach for guiding the optimization of clinical decision-making.

Network pharmacology prediction and molecular docking-based strategy to explore the potential mechanism of Radix Astragali against hypopharyngeal carcinoma

To explore the anti-tumor effects of Radix Astragali on hypopharyngeal carcinoma and its mechanism. We have bioinformatically analyzed the potential targets of Radix Astragali and predicted the molecular mechanism of Radix Astragali treating of hypopharyngeal carcinoma. The binding process of the hub targets that could prolong the survival time of hypopharyngeal cancer patients with Radix Astragali was simulated by molecular docking. The results showed that 17 out of 36 hub targets could effectively improve the 5-year survival rate of hypopharyngeal cancer patients. Radix Astragali acts on hypopharyngeal carcinoma by regulating a signaling network formed by hub targets connecting multiple signaling pathways and is expected to become a drug for treating and prolonging hypopharyngeal carcinoma patients’ survival time.

Linc00662 sponges miR-15b-5p to promote hypopharyngeal squamous cell carcinoma progression by facilitating cancer stem cell-like phenotypes.

Background: Long non-coding RNAs (lncRNAs) are associated with multiple head and neck tumors and play important roles in cancer. This study explored the molecular mechanism of Linc00662 in hypopharyngeal squamous cell carcinoma (HSCC). Methods: Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect gene expression in HSCC tissues. The viability and proliferation of tumor cells were measured using CCK-8 assays. HSCC cell apoptosis was measured using flow cytometry and western blotting. Cell stemness was examined using the sphere formation assay. A xenograft tumor model was established to investigate the role of Linc00662 in vivo. Results: The expression level of Linc00662 in HSCC tissues was significantly higher than that in adjacent normal tissues. The expression of Linc00662 had no significant relationship with the tumor stage. Patients with high Linc00662 expression were found to have shorter overall survival than those with low Linc00662 expression. Linc00662 over-expression promoted cell viability and inhibited apoptosis. Using online databases and a dual luciferase reporter, miR-15b-5p was confirmed as a potential downstream sponge of Linc00662. Moreover, Linc00662 was negatively associated with miR-15b-5p in HSCC cells. Depletion of miR-15b-5p can reverse the function of Linc00662 in vivo and in vitro. Furthermore, Linc00662 promotes tumor growth, which was abolished by miR-15b-5p mimics. Importantly, the stemness of cancer stem cells was mediated by the Linc00662/miR-15b-5p axis. Conclusion: Patients with HSCC with high Linc00662 showed poor prognosis and high Linc00662 induced stemness of tumor cells by targeting miR-15b-5p. Linc00662 may serve as a novel diagnostic and target marker for head and neck squamous cell carcinoma.

Navigating diagnostic complexity: A case of giant cell tumour of tendon sheath of thumb in a patient with prior hypopharyngeal Carcinoma

Navigating diagnostic complexity: A case of giant cell tumour of tendon sheath of thumb in a patient with prior hypopharyngeal Carcinoma

A Case of Hypopharyngeal Carcinoma Long-term Success Achieved by Combination Therapy with Pembrolizumab Plus Chemotherapy After Failure of Pembrolizumab Monotherapy

A Case of Hypopharyngeal Carcinoma Long-term Success Achieved by Combination Therapy with Pembrolizumab Plus Chemotherapy After Failure of Pembrolizumab Monotherapy

2-Bromopalmitate inhibits malignant behaviors of HPSCC cells by hindering the membrane location of Ras protein.

Palmitoylation, which is mediated by protein acyltransferase (PAT) and performs important biological functions, is the only reversible lipid modification in organism. To study the effect of protein palmitoylation on hypopharyngeal squamous cell carcinoma (HPSCC), the expression levels of 23 PATs in tumor tissues of 8 HPSCC patients were determined, and high mRNA and protein levels of DHHC9 and DHHC15 were found. Subsequently, we investigated the effect of 2-bromopalmitate (2BP), a small-molecular inhibitor of protein palmitoylation, on the behavior of Fadu cells in vitro (50 μM) and in nude mouse xenograft models (50 μmol/kg), and found that 2BP suppressed the proliferation, invasion, and migration of Fadu cells without increasing cell apoptosis. Mechanistically, the effect of 2BP on the transduction of BMP, Wnt, Shh, and FGF signaling pathways was tested with qRT-PCR, and its drug target was explored with western blotting and acyl-biotinyl exchange assay. Our results showed that 2BP inhibited the transduction of the FGF/ERK signaling pathway. The palmitoylation level of Ras protein decreased after 2BP treatment, and its distribution in the cell membrane structure was reduced significantly. The findings of this work reveal that protein palmitoylation mediated by DHHC9 and DHHC15 may play important roles in the occurrence and development of HPSCC. 2BP is able to inhibit the malignant biological behaviors of HPSCC cells, possibly via hindering the palmitoylation and membrane location of Ras protein, which might, in turn, offer a low-toxicity anti-cancer drug for targeting the treatment of HPSCC.

Long-Term Treatment Outcomes of Hypopharyngeal Cancer Using Different Surgical Modalities

Background and Objectives In the present study, we evaluated the treatment results of hypopharyngeal squamous cell carcinoma (HPSCC) patients and analyzed the occurrence of secondary primary malignancies. Treatments were based on two different surgical modalities (conventional pharyngo-laryngectomy vs. transoral surgery). In addition, prognostic factors of the patients were evaluated.Subjects and Method We analyzed medical data of 232 patients diagnosed with HPSCC and underwent surgery at our hospital from January 2006 to December 2019.Results The 5-year recurrence-free survival was 67.2% for the stage I-II group and 64.9% for the stage III-IV group. The 5-year disease-specific survival was 78.2% for the stage I-II group and 54.5% for the stage III-IV group. N classification was significantly correlated with disease relapse and patient mortality. Patient age, sex, perineural invasion, extranodal extension, initial tumor stage, and early recurrence (within 6 months) were significantly associated with successful salvage treatment. The two surgical modalities did not yield different oncological outcomes. Secondary primary malignancies occurred most frequently in the esophagus, with no observed inferior survival rate in patients with second malignancies.Conclusion The 5-year survival rate for HPSCC patients who received surgical treatment was 78% for stage I-II and 54% for stage III-IV. While no difference in oncological outcome was observed based on surgical modality, the transoral surgery group showed better functional outcomes.

Caffeic acid phenethyl ester: Unveiling its potential as a potent apoptosis inducer for combating hypopharyngeal squamous cell carcinoma.

Hypopharyngeal squamous cell carcinoma (HSCC) is a relatively rare form of head and neck cancer that is notorious for its poor prognosis and low overall survival rate. This highlights the need for new therapeutic options for this malignancy. The objective of the present study was to examine the ability of caffeic acid phenethyl ester (CAPE), which is an active compound found in propolis, to combat HSCC tumor growth. CAPE exerted its tumor‑suppressive activity in HSCC cell lines through the induction of apoptosis. Mechanistically, the CAPE‑mediated apoptotic process was attributed to the perturbation of the mitochondrial membrane potential and the activation of caspase‑9. CAPE also modulated survivin and X‑linked inhibitor of apoptosis, which are potent members of the inhibitors of apoptosis protein family, either through transcriptional or post‑translational regulation, leading to HSCC cell line death. Therefore, the findings of the present study suggested that CAPE is an effective treatment alternative for HSCC via the stimulation of mitochondria‑dependent apoptosis.

Circ0005027 Acting as a ceRNA Affects the Malignant Biological Behavior of Hypopharyngeal Squamous Cell Carcinoma by Modulating miR-548c-3p/CDH1 Axis.

Hypopharyngeal squamous cell carcinoma (HSCC) is a malignant tumor of head and neck. It was verified that circ0005027 was downregulated in HSCC tissues. Here, we aimed to investigate the function and specific regulatory mechanism of circ0005027 in HSCC. Ten pairs tissues of HSCC and adjacent para-cancer were collected. Reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR) measured circ0005027, miR-548c-3p, and Cadherin 1 (CDH1) mRNA expression. CCK-8 analyzed cell proliferation viability. Flow cytometry assay detected cell cycle and apoptosis rate. Clonal formation assay measured the clonal ability. Transwell detected cell invasion ability. Western blot was performed to detect CDH1, LAST1, p-LAST1, MST1, p-MST1, YAP1, p-YAP1, TAZ and p-TAZ protein level. Dual-luciferase, RIP and RNA pull-down assay identified the target relationship among circ0005027, miR-548c-3p and CDH1. circ0005027 was decreased in tissues and FaDu cells of HSCC. Overexpression of circ0005027 inhibited cell viability, G1-S transition, clonal formation, and invasion and increased cell apoptosis. circ0005027 acted as a ceRNA and decreased circ0005027 enhanced the malignant process of FaDu cells through sponging miR-548c-3p and inhibiting CDH1 expression. Overexpression of CDH1 activated YAP1/TAZ pathway and inhibited the growth of HSCC in vitro. circ0005027 might act as a potential biomarker for the progression and prognosis prediction in HSCC by regulating miR-548c-3p/CDH1/ YAP1/TAZ signaling pathway.

Clinical analysis of retropharyngeal lymph node metastasis in patients with hypopharyngeal squamous cell carcinoma

Objective: To analyze the incidence and the related risk factors of retropharyngeal lymph node metastasis in patients with hypopharyngeal squamous cell carcinoma, evaluate the accuracy of preoperative enhanced CT in judging retropharyngeal lymph node metastasis, and investigate the impact of retropharyngeal lymph node metastasis on the prognosis. Methods: Retrospective analyses were made on 398 patients with hypopharyngeal squamous cell carcinoma who underwent surgery as the primary therapy and accepted retropharyngeal lymph node exploration and clearance during surgery in Shandong Provincial ENT Hospital from January 2014 to December 2019. Multivariate logistic regression analysis was used to clarify the related risk factors of retropharyngeal lymph node metastasis. Multivariate Cox regression analysis was used to investigate the impact of retropharyngeal lymph node metastasis on prognosis. The retropharyngeal lymph nodes of 218 cases with available preoperative enhanced CT images were evaluated by two experienced radiologists and compared with postoperative pathological results. Results: Retropharyngeal lymph node metastasis were confirmed in 54 of 398 (13.6%) cases according to postoperative pathology. The sensitivity and specificity of preoperative enhanced CT in the diagnosis of retropharyngeal lymph node metastasis were 34.6% and 91.1%, respectively, and the overall accuracy was 84.4%. Multivariate logistic regression analysis showed that the site of the primary lesion and pathological N stage were independent risk factors for retropharyngeal lymph node metastasis in hypopharyngeal squamous cell carcinoma. Patients with primary lesion located in the posterior wall of hypopharynx (OR=4.83, 95% CI: 1.27-18.40), N2 stage (OR=6.30, 95% CI: 2.25-17.67), and N3 stage (OR=26.89, 95% CI: 5.76-125.58) were prone to retropharyngeal lymph node metastasis. The 5-year overall survival rate of the 398 patients was 50.4%, and the 5-year disease-free survival rate was 48.3%. Multivariate Cox regression analysis showed that T stage, N stage, retropharyngeal lymph node metastasis, and radiotherapy were independent influencing factors for overall survival (T stage: HR=1.28, 95% CI: 1.06-1.54; N stage: HR=1.26, 95% CI: 1.14-1.40; retropharyngeal lymph node metastasis: HR=2.13, 95% CI: 1.47-3.08; radiotherapy: HR=0.54, 95% CI: 0.38-0.76) and disease-free survival of patients with hypopharyngeal squamous cell carcinoma (T stage: HR=1.26, 95% CI: 1.06-1.51; N stage: HR=1.25, 95% CI: 1.13-1.37; retropharyngeal lymph node metastasis: HR=2.24, 95% CI: 1.56-3.21; radiotherapy: HR=0.55, 95% CI: 0.40-0.77). Conclusions: Metastasis of retropharyngeal lymph nodes in hypopharyngeal squamous cell carcinoma is not rare. Enhanced CT is of low accuracy and limited value in diagnosing retropharyngeal lymph node metastasis. Primary lesions located in the posterior wall of the hypopharyngx, N2 stage, and N3 stage are independent high-risk factors for retropharyngeal lymph node metastasis. The prognosis of hypopharyngeal cancer patients with retropharyngeal lymph node metastasis is worse, and active surgical exploration and clearance can effectively reduce the mortality caused by retropharyngeal lymph node metastasis.

ESCO2 promotes hypopharyngeal carcinoma progression in a STAT1-dependent manner

BackgroundThe establishment of sister chromatid cohesion N-acetyltransferase 2 (ESCO2) is involved in the development of multiple malignancies. However, its role in hypopharyngeal carcinoma (HPC) progression remains uncharacterized.MethodsThis study employed bioinformatics to determine the ESCO2 expression in head and neck squamous cell carcinoma (HNSC) and normal tissues. In vitro cell proliferation, migration, apoptosis, and/or cell cycle distribution assays were used to determine the function of ESCO2 and its relationship with STAT1. Xenograft models were established in nude mice to determine ESCO2 in HPC growth in vivo. Co-immunoprecipitation/mass spectrometry (Co-IP/MS) was conducted to identify the potential ESCO2 binding partners.ResultsWe found that ESCO2 expression was elevated in HNSC tissues, and ESCO2 depletion suppressed tumor cell migration in vitro and inhibited tumor growth in vitro and in vivo. Co-IP/MS and immunoblotting assays revealed the interaction between ESCO2 and STAT1 in HPC cells. STAT1-overexpression compromised ESCO2-mediated suppressive effects on HPC cell proliferation, viability, and migration.ConclusionsThese findings suggest that ESCO2 is crucial in promoting HPC malignant progression through the STAT1 pathway and provides novel therapeutic targets for HPC treatment.

LncRNA HOXC-AS2 promotes the progression of hypopharyngeal cancer by binding to the P62 protein mediating the autophagy process.

Hypopharyngeal carcinoma is the most malignant type of head and neck squamous cell carcinoma, and lncRNAs play an important role in its formation and progression. However, the related specific mechanisms are rarely studied. lncRNAs closely associated with hypopharyngeal cancer were examined by lncRNA sequencing for in-depth exploration of the relationship between HOXC-AS2 and hypopharyngeal cancer pathogenesis. The mRNA expression of HOXC-AS2 and related genes was measured by qRT-PCR, and the biological function of HOXC-AS2 in hypopharyngeal carcinoma was demonstrated by gain- and loss-of-function experiments. RNA pulldown, RNA immunoprecipitation (RIP) and gene body truncation experiments and transcriptome sequencing were used to investigate the potential mechanism of HOXC-AS2 and its downstream genes, including P62, NF-KB and HMOX1. Finally, the biological function of HOXC-AS2 was confirmed in animal experiments. HOXC-AS2 and P62 expression was significantly upregulated in hypopharyngeal cancer tissues compared with normal hypopharyngeal tissues, while HMOX1 expression was decreased. Functionally, HOXC-AS2 overexpression can promote the viability, proliferation, migration and invasion of hypopharyngeal cancer cells and facilitate hypopharyngeal cancer progression. It was confirmed that HOXC-AS2 can bind to the P62 protein and activate the NF-KB signaling pathway, thereby affecting HMOX1 expression and regulating autophagy in hypopharyngeal cancer cells, ultimately regulating the formation and progression of hypopharyngeal cancer. In conclusion, our findings suggest that HOXC-AS2 regulates the progression of hypopharyngeal cancer by regulating autophagy and is abnormally highly expressed in hypopharyngeal cancer tissues. HOXC-AS2 may become a new target for the diagnosis and treatment of hypopharyngeal cancer.

A Review Concerning the Use of Etravirine and Darunavir in Translational Medicine

This comprehensive review explores two antiretroviral drugs, Etravirine (ETV) and Darunavir (DRV), a non-nucleoside reverse transcriptase inhibitor and a protease inhibitor, that are commonly used in human immunodeficiency virus (HIV) infection treatment, often in combination with each other. The pharmacokinetic properties of these drugs are covered as well as the clinical trials of these two drugs combined. This paper also delves into the possible repurposing of these two drugs for other diseases, with drug repurposing being a significant factor in addressing global health challenges. DRV was extensively studied for treating COVID-19, as well as other infections, such as candidiasis and cryptococcosis, while ETV proved to be efficient in hampering Zika virus brain infection. The focus on cancer repurposing is also explored, with the results revealing that ETV has a particular inhibitory effect on ovarian cancer in vitro and on cancer molecules, such as anterior gradient protein 2 homolog (AGR2) and casein kinase 1 (CK1ε), and that DRV has an in silico inhibitory effect on human lactate dehydrogenase A (LDHA) and induces the in vitro and in vivo inhibition of pepsin, consequent laryngopharyngeal reflux, and possible laryngeal and hypopharyngeal carcinomas. The significance of fresh methods of drug development is emphasized in this work, as is the enormous potential for new therapeutic uses of the antiretroviral drugs ETV and DRV in viral and non-viral disorders.

Single-cell RNA sequencing reveals pro-invasive cancer-associated fibroblasts in hypopharyngeal squamous cell carcinoma

BackgroundHypopharyngeal squamous cell carcinoma (HPSCC) has the worst prognosis among all head-and-neck cancers, and treatment options are limited. Tumor microenvironment (TME) analysis can help identify new therapeutic targets and combined treatment strategies.MethodsSix primary HPSCC tissues and two adjacent normal mucosae from six treatment-naïve patients with HPSCC were analyzed using scRNA-seq. Cell types were curated in detail, ecosystemic landscapes were mapped, and cell–cell interactions were inferred. Key results were validated with The Cancer Genome Atlas and cell biology experiments.ResultsMalignant HPSCC epithelial cells showed significant intratumor heterogeneity. Different subtypes exhibited distinct histological features, biological behaviors, and spatial localization, all affecting treatment selection and prognosis. Extracellular matrix cancer-associated fibroblasts (mCAFs) expressing fibroblast activation protein were the dominant CAFs in HPSCC tumors. mCAFs, constituting an aggressive CAF subset, promoted tumor cell invasion, activated endothelial cells to trigger angiogenesis, and synergized with SPP1+ tumor associated macrophages to induce tumor progression, ultimately decreasing the overall survival of patients with HPSCC. Moreover, the LAMP3+ dendritic cell subset was identified in HPSCC and formed an immunosuppressive TME by recruiting Tregs and suppressing CD8+ T cell function.ConclusionsmCAFs, acting as the communication center of the HPSCC TME, enhance the invasion ability of HPSCC cells, mobilizing surrounding cells to construct a tumor-favorable microenvironment. Inhibiting mCAF activation offers a new anti-HPSCC therapeutic strategy.Graphical 3rZBJkNLzDco4s_zE23WXSVideo