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

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

Bowen’s Disease, or squamous cell carcinoma in situ, is a premalignant skin condition characterized by atypical keratinocyte proliferation confined to the epidermis. It presents as scaly, erythematous plaque resembling benign disorders like eczema or psoriasis, complicating diagnosis. Early treatment is vital to prevent progression to invasive carcinoma.

A 60 year old female with prolonged sun exposure presented with a 17-year history of a solitary pinkish patch on her right lower abdomen. Initially non-pruritic and non-tender, the lesion gradually enlarged and thickened, developing into a pruritic plaque. She was treated with Mupirocin ointment without improvement. Three years thereafter, plaque showed hyperpigmentation, scaling, and increased pruritus. Self-treatment various topicals daily for one month was ineffective, prompting further evaluation. Physical examination revealed ill-defined hyperpigmented plaques with irregular borders, scaling, crusting, and hyperkeratosis on the right lower abdomen. A skin punch biopsy showed basketweave stratum corneum with scale crust, spongiotic epidermis with multiple atypical keratinocytes, and dermal infiltrates of atypical mononuclear cells, lymphohistiocytic cells, eosinophils, melanophages, dilated vessels, and extravasated erythrocytes. Diagnosis of in-situ squamous cell carcinoma. Treated with Imiquimod 5% cream three times weekly, achieving complete regression and no recurrence at six months.

Bowen’s Disease mainly affects older adults with significant sun exposure, aligning with higher incidence in chronically sun-damaged populations. Histopathology with atypical keratinocytes confined to the epidermis differentiates it from invasive carcinoma. Topical Imiquimod, an immune response modifier, effectively induced lesion regression by stimulating local cytokines. This case highlights the importance of early diagnosis and non-invasive treatment to prevent malignant progression.

This is a case of a 74-year-old female who previously worked as a Metro Manila Aide and presented with a solitary erythematous, well-demarcated mass with hyperkeratosis on the right zygomatic area. It started as a pea-sized erythematous papule three years prior without associated symptoms. The patient self-medicated with Ketoconazole + Clobetasol Propionate cream for five months without improvement. Two months before consultation, the lesion enlarged and developed yellow hyperkeratotic crusts. A biopsy revealed invasive squamous cell carcinoma (SCC). Complete excision with adequate margins was recommended. The patient underwent Mohs Micrographic Surgery and reconstruction with a rotational flap repair. Histopathology of the excised tissue confirmed squamous cell carcinoma. No tumor necrosis or lymphovascular invasion was identified, and all resection margins were clear. Post-surgical management included wound care and medications. The case emphasizes early intervention and histopathological evaluation in managing growths especially in cases where patients have not consulted and self medicated instead.

Squamous cell carcinoma (SCC) of the kidney is a rare malignancy and has a poor prognosis because it is usually detected and presents at an advanced stage of the disease. Due to lack of studies regarding its clinical course and its radiologic features, it is usually not detected and presents as an incidental finding in histopathologic results. This type of malignancy more often is related to Renal stones secondary to chronic infection, inflammation, and irritation. A 52-year-old Filipino woman was referred to this institution due to flank pain and constant weight loss. The authors administered antibiotics then performed simple nephrectomy on her. A pathologic examination revealed Squamous Cell Carcinoma with Sarcomatoid differentiation. Four months after the operation, patient was readmitted due to lowback pain and generalized weakness which led to a suspicion of a possibility of Bone Metastasis. Patient was offered further workups such as whole abdominal CT scan with contrast and other palliative treatments however she refused and opted to be discharged despite medical advice. Patient then died 2 weeks after being home against medical advice.
Carcinoma, Squamous Cell ; Staghorn Calculi

Xeroderma pigmentosum (XP) is a rare DNA repair disorder characterized by sensitivity to sunlight and predisposition to cutaneous malignancies. There are various types, including the Variant type, which does not manifest with acute sunburn reactions. This results to the development of multiple malignancies that are often discovered at late stages, making management more challenging. This is a case of a 54-year-old Filipino female presenting with multiple basal cell carcinomas (BCCs) on several areas of the face and advanced cutaneous squamous cell carcinoma (cSCC) on the right zygomatic area, treated with imiquimod 5% cream and external beam radiation therapy, respectively. There was an excellent response of the BCCs to imiquimod 5% cream and good tumoral response of the SCC to radiation therapy, with tolerable side effects, highlighting the use of these palliative treatment modalities for XP patients with multiple, unresectable, or difficult-to-treat cutaneous malignancies.

The efficacy of surgery alone for locally advanced esophageal squamous cell carcinoma (ESCC) is limited. In-depth studies concerning combined therapy for ESCC have been carried out worldwide, especially the neoadjuvant treatment model, including neoadjuvant chemotherapy (nCT), neoadjuvant chemoradiotherapy (nCRT), neoadjuvant chemotherapy combined with immunotherapy (nICT), neoadjuvant chemoradiotherapy combined with immunotherapy (nICRT), etc. With the advent of the immunity era, nICT and nICRT have attracted much attention from researchers. An attempt was thus made to take an overview of the evidence-based research advance regarding the neoadjuvant therapy of ESCC.
Humans ; Esophageal Squamous Cell Carcinoma/surgery* ; Neoadjuvant Therapy ; Esophageal Neoplasms/surgery* ; Chemoradiotherapy ; Esophagectomy

Recent advances in multimodality treatment offer excellent opportunities to rethink the paradigm of perioperative management for locally advanced esophageal squamous cell carcinoma. One treatment clearly doesn't fit all in terms of a broad disease spectrum. Individualized treatment of local control of bulky primary tumor burden (advanced T stage) or systemic control of nodal metastatic tumor burden (advanced N stage) is essential. Given that clinically applicable predictive biomarkers are still awaited, therapy selection guided by diverse phenotypes of tumor burden (T vs. N) is promising. Potential challenges regarding the use of immunotherapy may also boost this novel strategy in the future.
Humans ; Esophageal Squamous Cell Carcinoma/surgery* ; Carcinoma, Squamous Cell/pathology* ; Esophageal Neoplasms/pathology* ; Combined Modality Therapy ; Immunotherapy