A 61-year-old woman presented with a 2-month history of non-painful left eye proptosis. Imaging studies showed a superotemporal mass in the left orbit with intracranial extension. Surgical excision of the orbitocranial mass was performed and histopathologic examination revealed metastatic papillary thyroid carcinoma. She subsequently underwent total thyroidectomy. Orbital metastasis from thyroid carcinoma is rare and can be the initial manifestation of occult disease in 63% of cases.

INTRODUCTION

Papillary thyroid cancer (PTC) is generally considered to be an indolent disease with relatively good prognosis. However, some studies have shown that the Filipino population has a higher risk for disease recurrence compared to non-Filipino patients and hence early identification and management during the follow-up period would be beneficial, especially those in whom risk factors for recurrence were identified.

This study aims to identify determinants for disease recurrence of patients with papillary thyroid carcinoma (as defined by the American Thyroid Association (ATA) guidelines 2015) diagnosed from January 1, 2013-December 31, 2017, seen at the University of Santo Tomas Hospital (USTH) outpatient endocrine clinic and underwent total thyroidectomy with or without radioactive iodine ablation therapy.

Retrospective review of outpatient medical records of 82 patients with PTC who underwent total thyroidectomy with or without radioactive iodine (RAI) therapy and achieved excellent response (ER) to therapy was performed. Baseline clinical profile such as age at diagnosis, sex, family history of thyroid cancer, family history of goiter, histopathology result, serial thyroglobulin (Tg), anti-thyroglobulin (anti-Tg) levels, whole body scan reports, neck ultrasound reports and RAI doses were collected. Logistic regression analysis was used to identify determinants to the development of worsening response.

Of the 82 patients, 18 (21.9%) developed worsening response to therapy. Predictors of poor outcomes identified from previous studies such as age, sex, extent of disease, size and multifocality of tumors, ATA risk classification and initial dynamic risk assessment, RAI therapy, level of thyroid-stimulating hormone (TSH) suppression were analyzed. After logistic regression analysis, there was no significant association between variables and progression to worsening response that were previously identified in other studies.

Even though no significant association between investigated variables and worsening response were identified in this study, previous studies with larger populations that had exhibited positive association should be considered and hence current Philippine guidelines for the management of PTC must still be applied.

Humans ; Early Detection of Cancer ; Endoscopy ; Esophageal Neoplasms/epidemiology* ; Risk Factors ; Mass Screening

Humans ; Parathyroid Neoplasms/genetics* ; Molecular Biology ; Parathyroid Glands

OBJECTIVE: To obtain detailed understanding on the gene regulation of natural compounds in altering prognosis of head and neck squamous cell carcinomas (HNSC). METHODS: Gene expression data of HNSC samples and peripheral blood mononuclear cells (PBMCs) of HNSC patients were collected from Gene Expression Omnibus (GEO). Differential gene expression analysis of GEO datasets were achieved by the GEO2R tool. Common differentially expressed gerres (DEGs) were screened by comparing DEGs of HNSC with those of PBMCs. The combination was further analyzed for regulating pathways and biological processes that were affected. RESULTS: Totally 110 DEGs were retrieved and identified to be involved in biological processes related to tumor regulation. Then 102 natural compounds were screened for a combination such that the expression of all 110 commonly DEGs was altered. A combination of salidroside, ginsenoside Rd, oridonin, britanin, and scutellarein was chosen. A multifaceted, multi-dimensional tumor regression was showed by altering autophagy, apoptosis, inhibiting cell proliferation, angiogenesis, metastasis and inflammatory cytokines production. CONCLUSIONS This study has helped develop a unique combination of natural compounds that will markedly reduce the propensity of development of drug resistance in tumors and immune evasion by tumors. The result is crucial to developing a combinatorial natural therapeutic cocktail with accentuated immunotherapeutic potential.
Humans ; Leukocytes, Mononuclear ; Head and Neck Neoplasms/drug therapy* ; Squamous Cell Carcinoma of Head and Neck/drug therapy* ; Immunotherapy ; Prognosis

Oral diseases, such as periodontitis, salivary gland diseases, and oral cancers, significantly challenge health conditions due to their detrimental effects on patient's digestive functions, pronunciation, and esthetic demands. Delayed diagnosis and non-targeted treatment profoundly influence patients' prognosis and quality of life. The exploration of innovative approaches for early detection and precise treatment represents a promising frontier in oral medicine. Exosomes, which are characterized as nanometer-sized extracellular vesicles, are secreted by virtually all types of cells. As the research continues, the complex roles of these intracellular-derived extracellular vesicles in biological processes have gradually unfolded. Exosomes have attracted attention as valuable diagnostic and therapeutic tools for their ability to transfer abundant biological cargos and their intricate involvement in multiple cellular functions. In this review, we provide an overview of the recent applications of exosomes within the field of oral diseases, focusing on inflammation-related bone diseases and oral squamous cell carcinomas. We characterize the exosome alterations and demonstrate their potential applications as biomarkers for early diagnosis, highlighting their roles as indicators in multiple oral diseases. We also summarize the promising applications of exosomes in targeted therapy and proposed future directions for the use of exosomes in clinical treatment.
Humans ; Exosomes ; Quality of Life ; Extracellular Vesicles ; Biomarkers ; Cell Communication ; Mouth Neoplasms

Existing studies have underscored the pivotal role of N-acetyltransferase 10 (NAT10) in various cancers. However, the outcomes of protein-protein interactions between NAT10 and its protein partners in head and neck squamous cell carcinoma (HNSCC) remain unexplored. In this study, we identified a significant upregulation of RNA-binding protein with serine-rich domain 1 (RNPS1) in HNSCC, where RNPS1 inhibits the ubiquitination degradation of NAT10 by E3 ubiquitin ligase, zinc finger SWIM domain-containing protein 6 (ZSWIM6), through direct protein interaction, thereby promoting high NAT10 expression in HNSCC. This upregulated NAT10 stability mediates the enhancement of specific tRNA ac⁴C modifications, subsequently boosting the translation process of genes involved in pathways such as IL-6 signaling, IL-8 signaling, and PTEN signaling that play roles in regulating HNSCC malignant progression, ultimately influencing the survival and prognosis of HNSCC patients. Additionally, we pioneered the development of TRMC-seq, leading to the discovery of novel tRNA-ac⁴C modification sites, thereby providing a potent sequencing tool for tRNA-ac⁴C research. Our findings expand the repertoire of tRNA ac⁴C modifications and identify a role of tRNA ac⁴C in the regulation of mRNA translation in HNSCC.
Humans ; DNA-Binding Proteins ; Head and Neck Neoplasms/genetics* ; N-Terminal Acetyltransferases ; RNA, Transfer ; Serine ; Signal Transduction ; Squamous Cell Carcinoma of Head and Neck

Wnt signaling are critical pathway involved in organ development, tumorigenesis, and cancer progression. WNT7A, a member of the Wnt family, remains poorly understood in terms of its role and the underlying molecular mechanisms it entails in head and neck squamous cell carcinoma (HNSCC). According to the Cancer Genome Atlas (TCGA), transcriptome sequencing data of HNSCC, the expression level of WNT7A in tumors was found to be higher than in adjacent normal tissues, which was validated using Real-time RT-PCR and immunohistochemistry. Unexpectedly, overexpression of WNT7A did not activate the canonical Wnt-β-catenin pathway in HNSCC. Instead, our findings suggested that WNT7A potentially activated the FZD7/JAK1/STAT3 signaling pathway, leading to enhanced cell proliferation, self-renewal, and resistance to apoptosis. Furthermore, in a patient-derived xenograft (PDX) tumor model, high expression of WNT7A and phosphorylated STAT3 was observed, which positively correlated with tumor progression. These findings underscore the significance of WNT7A in HNSCC progression and propose the targeting of key molecules within the FZD7/JAK1/STAT3 pathway as a promising strategy for precise treatment of HNSCC.
Animals ; Humans ; Squamous Cell Carcinoma of Head and Neck ; Carcinogenesis/genetics* ; Cell Transformation, Neoplastic ; Wnt Signaling Pathway ; Disease Models, Animal ; Head and Neck Neoplasms/genetics* ; Wnt Proteins ; Frizzled Receptors/genetics* ; Janus Kinase 1 ; STAT3 Transcription Factor

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism, and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.
Humans ; Carcinoma, Squamous Cell/metabolism* ; Squamous Cell Carcinoma of Head and Neck ; Mouth Neoplasms/metabolism* ; Immunosuppression Therapy ; Transforming Growth Factor beta ; Head and Neck Neoplasms ; Gene Expression Profiling ; Tumor Microenvironment

Objective: To identify in what phases in the treatment of head and neck cancer do delays happen at a tertiary hospital and to determine the association between the length of treatment delays and the oncologic outcomes (disease-free survival and overall survival) for patients with head and neck cancer. : Methods Design: Retrospective Cohort Study Setting: Tertiary National University Hospital Participants: Sixty-eight (68) patients who had surgery and adjuvant radiotherapy for invasive head and neck cancer at the Philippine General Hospital during the 5-year period of January 2014 to December 2019 were included in the initial consideration. Only 15 had survival data and were thus eligible for inclusion in this study. Results: The median treatment package time for head and neck cancers in our institution was 27.6 weeks or 193 days. The treatment package time statistically correlated with both overall survival, F(1,13)=12.952, p <0.005, R2=0.499, and disease-free survival, F(1-13)=12.823, p <0.005, R2= 0.497. However, the independent effects of other predictors such as time interval between first consult to histopathologic diagnosis, diagnosis to surgery, and surgery to post-operative radiotherapy, showed no statistically significant association with overall survival and disease free survival. Conclusion All study patients experienced treatment delays from diagnosis to surgery, and surgery to adjuvant radiation therapy, and in their total treatment package time. The positive correlation among treatment package time, and disease-free and overall survival in this study must be further investigated in order to elucidate the true effect of delays across time intervals in the treatment of head and neck cancer in the Philippine General Hospital. Every effort should be made towards timely management of these patients.
Head and Neck Neoplasms ; Radiotherapy ; Survival Rate ; Treatment Outcome ; Time-to-Treatment ; Surgery ; Disease-Free Survival ; Delayed Diagnosis ; Retrospective Studies ; Postoperative Care