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CMAJ : Canadian Medical Association... Jul 2023
Topics: Humans; Deglutition Disorders; Chest Pain; Thorax
PubMed: 37487618
DOI: 10.1503/cmaj.221673-f -
Nature Communications Aug 2023Immunotherapy combined with antiangiogenic targeted therapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for refractory...
Camrelizumab combined with apatinib in patients with first-line platinum-resistant or PD-1 inhibitor resistant recurrent/metastatic nasopharyngeal carcinoma: a single-arm, phase 2 trial.
Immunotherapy combined with antiangiogenic targeted therapy has improved the treatment of certain solid tumors, but effective regimens remain elusive for refractory recurrent/metastatic nasopharyngeal carcinoma (RM-NPC). We conducted a phase 2 trial to evaluate the safety and activity of camrelizumab plus apatinib in platinum-resistant (cohort 1, NCT04547088) and PD-1 inhibitor resistant NPC (cohort 2, NCT04548271). Here we report on the primary outcome of objective response rate (ORR) and secondary endpoints of safety, duration of response, disease control rate, progression-free survival, and overall survival. The primary endpoint of ORR was met for cohort 1 (65%, 95% CI, 49.6-80.4, n = 40) and cohort 2 (34.3%; 95% CI, 17.0-51.8, n = 32). Grade ≥ 3 treatment-related adverse events (TRAE) were reported in 47 (65.3%) of 72 patients. Results of our predefined exploratory investigation of predictive biomarkers show: B cell markers are the most differentially expressed genes in the tumors of responders versus non-responders in cohort 1 and that tertiary lymphoid structure is associated with higher ORR; Angiogenesis gene expression signatures are strongly associated with ORR in cohort 2. Camrelizumab plus apatinib combination effectiveness is associated with high expression of PD-L1, VEGF Receptor 2 and B-cell-related genes signatures. Camrelizumab plus apatinib shows promising efficacy with a measurable safety profile in RM-NPC patients.
Topics: Humans; Nasopharyngeal Carcinoma; Immune Checkpoint Inhibitors; Platinum; Nasopharyngeal Neoplasms; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37580352
DOI: 10.1038/s41467-023-40402-x -
Cell Death and Differentiation Mar 2024Cisplatin-based chemotherapy improves the control of distant metastases in patients with nasopharyngeal carcinoma (NPC); however, around 30% of patients fail treatment...
Cisplatin-based chemotherapy improves the control of distant metastases in patients with nasopharyngeal carcinoma (NPC); however, around 30% of patients fail treatment due to acquired drug resistance. Epigenetic regulation is known to contribute to cisplatin resistance; nevertheless, the underlying mechanisms remain poorly understood. Here, we showed that lysine-specific demethylase 5B (KDM5B) was overexpressed and correlates with tumor progression and cisplatin resistance in patients with NPC. We also showed that specific inhibition of KDM5B impaired the progression of NPC and reverses cisplatin resistance, both in vitro and in vivo. Moreover, we found that KDM5B inhibited the expression of ZBTB16 by directly reducing H3K4me3 at the ZBTB16 promoter, which subsequently increased the expression of Topoisomerase II- α (TOP2A) to confer cisplatin resistance in NPC. In addition, we showed that the deubiquitinase USP7 was critical for deubiquitinating and stabilizing KDM5B. More importantly, the deletion of USP7 increased sensitivity to cisplatin by disrupting the stability of KDM5B in NPC cells. Therefore, our findings demonstrated that USP7 stabilized KDM5B and promoted cisplatin resistance through the ZBTB16/TOP2A axis, suggesting that targeting KDM5B may be a promising cisplatin-sensitization strategy in the treatment of NPC.
Topics: Humans; Cell Line, Tumor; Cisplatin; Drug Resistance, Neoplasm; Epigenesis, Genetic; Jumonji Domain-Containing Histone Demethylases; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Nuclear Proteins; Promyelocytic Leukemia Zinc Finger Protein; Repressor Proteins; Ubiquitin-Specific Peptidase 7
PubMed: 38287116
DOI: 10.1038/s41418-024-01257-x -
Revista de Gastroenterologia de Mexico... 2023
Topics: Humans; Deglutition Disorders; Tomography, X-Ray Computed
PubMed: 38030418
DOI: 10.1016/j.rgmxen.2023.07.004 -
Clinical and Translational Medicine Sep 2023Super enhancers (SE) play pivotal roles in cell identity and diseases occur including tumorigenesis. The depletion of SE-associated lncRNA transcripts, also known as...
METTL3-stabilized super enhancers-lncRNA SUCLG2-AS1 mediates the formation of a long-range chromatin loop between enhancers and promoters of SOX2 in metastasis and radiosensitivity of nasopharyngeal carcinoma.
BACKGROUND
Super enhancers (SE) play pivotal roles in cell identity and diseases occur including tumorigenesis. The depletion of SE-associated lncRNA transcripts, also known as super-lncRNA, causes the activity of SE to be dysregulated.
METHODS
We screened and identified an elevated metastasis-associated SE-lncRNA SUCLG2-AS1 in nasopharyngeal carcinoma (NPC) using RNA-sequencing, real-time quantitative polymerase chain reaction (RT-qPCR) and bioinformatics. Western blotting, RT-qPCR, methylated RNA immunoprecipitation (MeRIP), RNA immunoprecipitation, chromatin immunoprecipitation, RNA pull-down and 3C (chromosome conformation capture assays) were used for mechanistic studies.
RESULTS
SUCLG2-AS1 was correlated with a poor prognosis. SUCLG2-AS1 promotes NPC cell invasion and metastasis while repressing apoptosis and radiosensitivity in vitro and in vivo. Mechanistically, high SUCLG2-AS1 expression occurred in an m6A-dependent manner. SUCLG2-AS1 was found to be located in the SE region of SOX2, and it regulated the expression of SOX2 via long-range chromatin loop formation, which via mediating CTCF (transcription factor) occupied the SE and promoter region of SOX2, thus regulating the metastasis and radiosensitivity of NPC.
CONCLUSIONS
Taken together, our data suggest that SUCLG2-AS1 may serve as a novel intervention target for the clinical treatment of NPC.
Topics: Humans; Chromatin; RNA, Long Noncoding; Nasopharyngeal Carcinoma; Promoter Regions, Genetic; Radiation Tolerance; Chromatin Immunoprecipitation; Nasopharyngeal Neoplasms; Methyltransferases; SOXB1 Transcription Factors
PubMed: 37658588
DOI: 10.1002/ctm2.1361 -
Ear, Nose, & Throat Journal Mar 2024There has been a subjective increase in the number of patients presenting for tonsil stones to our pediatric otolaryngology clinic. This may be related to frequent...
There has been a subjective increase in the number of patients presenting for tonsil stones to our pediatric otolaryngology clinic. This may be related to frequent viewing of videos on the social media application, TikTok, pertaining to tonsil stones.
Topics: Child; Humans; Palatine Tonsil; Tonsillitis; Social Media; Pharyngeal Diseases
PubMed: 34569296
DOI: 10.1177/01455613211038340 -
European Archives of... Jun 2024To discuss the different swallowing improvement surgeries that address one or more dysfunctional pharyngolaryngeal structures causing dysphagia. These surgeries reduce... (Review)
Review
PURPOSE
To discuss the different swallowing improvement surgeries that address one or more dysfunctional pharyngolaryngeal structures causing dysphagia. These surgeries reduce the risk of aspiration without sacrificing vocal function.
METHODS
We searched the PubMed database and used Google Scholar search engine to find studies discussing the different swallowing improvement surgeries. A manual search of references in selected articles and reviews was done as well. No chronologic limitation was set for the studies; however, only articles written in English and Japanese were considered. Due to the nature of this article, no particular inclusion or exclusion criteria were set when searching for studies to be used as references; however, all relevant studies were reviewed and agreed upon by the authors for inclusion in this review article.
RESULTS/DISCUSSION
Surgeries to improve swallowing function can be categorized into those that reinforce nasopharyngeal closure or pharyngeal contraction, improve laryngeal elevation or pharyngoesophageal segment opening, and those that improve vocal fold closure to protect the airway during swallowing. They are an effective alternative treatment that may significantly improve these patients' quality of life. Swallowing rehabilitation with the altered pharyngolaryngeal structures is required post-operatively to significantly improve patients' dysphagia.
CONCLUSIONS
Surgeries to improve swallowing function address specific dysfunctional sites involved in the swallowing mechanism. Choosing the most appropriate surgery for each patient requires knowledge of the pathophysiology for their dysphagia and detailed pre-operative work-up.
Topics: Humans; Deglutition; Deglutition Disorders; Larynx; Otorhinolaryngologic Surgical Procedures; Pharynx
PubMed: 38265461
DOI: 10.1007/s00405-024-08452-z -
Digestion 2024Esophageal motility disorders (EMDs) are caused by the impaired relaxation of the upper/lower esophageal sphincter and/or defective esophageal peristaltic contractions,... (Review)
Review
BACKGROUND
Esophageal motility disorders (EMDs) are caused by the impaired relaxation of the upper/lower esophageal sphincter and/or defective esophageal peristaltic contractions, resulting in dysphagia and noncardiac chest pain. High-resolution manometry (HRM) is essential for the diagnosis of primary EMD; however, the recognition of EMD and HRM by general practitioners in Japan is limited. This review summarizes the diagnosis of and treatment strategies for EMD.
SUMMARY
HRM is a specific test for the diagnosis of EMD, whereas endoscopy and barium swallow as screening tests provide characteristic findings (i.e., esophageal rosette and bird's beak sign) in some cases. It is important to note that manometric diagnoses apart from achalasia are often clinically irrelevant; therefore, the recently updated guidelines suggest additional manometric maneuvers, such as the rapid drink challenge, and further testing, including functional lumen imaging, for a more accurate diagnosis before invasive treatment. Endoscopic/surgical myotomy, pneumatic dilation, and botulinum toxin injections need to be considered for patients with achalasia and clinically relevant esophagogastric junction outflow obstruction.
KEY MESSAGE
Since the detailed pathophysiology of EMD remains unclear, their diagnosis needs to be cautiously established prior to the initiation of invasive treatment.
Topics: Humans; Esophageal Achalasia; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Sphincter, Lower; Manometry; Endoscopy, Gastrointestinal; Esophagogastric Junction
PubMed: 37634495
DOI: 10.1159/000533347 -
Cell Death & Disease Dec 2023Reprogramming of macrophages toward an M1 phenotype is a novel strategy to induce anticancer immunity. However, the regulatory mechanisms of M1 macrophage polarization...
Reprogramming of macrophages toward an M1 phenotype is a novel strategy to induce anticancer immunity. However, the regulatory mechanisms of M1 macrophage polarization and its functional roles in nasopharyngeal carcinoma (NPC) progression need to be further explored. Here we found that SPLUNC1 was highly expressed and responsible for M1 macrophage polarization. JAK/STATs pathway activation was involved in SPLUNC1-mediated M1 macrophage polarization. Importantly, regulation of SPLUNC1 in macrophages affected CM-mediated influence on NPC cell proliferation and migration. Mechanistically, USP7 deubiquitinated and stabilized TRIM24, which promoted SPLUNC1 expression via recruitment of STAT3 in M1 macrophages. Depletion of TRIM24 inhibited M1 macrophage polarization, which facilitated NPC cell growth and migration. However, over-expression of USP7 exhibited the opposite results and counteracted the tumorigenic effect of TRIM24 silencing. Finally, the growth and metastasis of NPC cells in vivo were repressed by USP7-induced M1 macrophage polarization via modulating TRIM24/SPLUNC1 axis. USP7 delayed NPC progression via promoting macrophage polarization toward M1 through regulating TRIM24/SPLUNC1 pathway, providing evidence for the development of effective antitumor immunotherapies for NPC.
Topics: Humans; Nasopharyngeal Carcinoma; Ubiquitin-Specific Peptidase 7; Macrophages; Nasopharyngeal Neoplasms; Macrophage Activation; Carrier Proteins
PubMed: 38129408
DOI: 10.1038/s41419-023-06368-w -
Disease burden, risk factors, and trends of lip, oral cavity, pharyngeal cancers: A global analysis.Cancer Medicine Sep 2023Lip, oral and pharyngeal cancers make up a small percentage of total cancer cases worldwide and have reported lower rates of cancer-related deaths globally in 2020, but...
BACKGROUND
Lip, oral and pharyngeal cancers make up a small percentage of total cancer cases worldwide and have reported lower rates of cancer-related deaths globally in 2020, but their 5-year survival rate in either early or advanced stages is different. The study evaluated the global incidence, mortality, risk factors, and temporal trends by age, gender, and geographical locations of lip, oral cavity, and pharyngeal cancer.
METHODS
Incidence and mortality rates were extracted from Cancer Incidence in Five Continents (CI5) volumes I-XI, the Nordic Cancer Registries (NORDCAN), the Surveillance, Epidemiology, and End Results (SEER) Program, and the WHO IARC mortality database. Joinpoint regression was used to calculate the Average Annual Percentage Change to examine trends.
RESULTS
The highest incidence rates were found in Melanesia and South-Central Asia and mortality rates were 8.2 and 7.5. Risk factors associated with incidence and mortality included HDI, tobacco use, alcohol consumption, poor diet, and chronic health conditions such as hypertension. Increasing trends of incidence and mortality were observed in females from Malta; males aged 50 and above from the United Kingdom, and females aged 50 and above from Slovakia reporting the largest increase.
CONCLUSIONS
Although global incidence and mortality trends reported an overall decrease, significant increases were found for older age groups and female subjects. Incidence increase may be due to the growing prevalence of lifestyle, metabolic risk factors, and HPV infections, especially in developed countries.
Topics: Male; Humans; Female; Aged; Lip; Pharyngeal Neoplasms; Risk Factors; Incidence; Cost of Illness; Registries; Global Health
PubMed: 37519070
DOI: 10.1002/cam4.6391