-
Romanian Journal of Morphology and... 2015Squamous cell tonsil carcinoma is the most frequent form of oropharyngeal cancer, representing 70-80% of the total of head and neck malignant tumors. Poor clinical...
Squamous cell tonsil carcinoma is the most frequent form of oropharyngeal cancer, representing 70-80% of the total of head and neck malignant tumors. Poor clinical symptoms make that 60-80% of patients with squamous cell tonsil carcinoma have a late diagnosis, in the third and fourth stages, when the tumor exceeds the organ limits, invading the pharyngeal wall or the tongue base, being associated with metastases in the laterocervical lymphatic ganglions. The tumor necrosis factor alpha (TNF-α) represents an important inflammation mediator associated to carcinogenesis and even to tumor progression. We evaluated the seric values of TNF-α in a group of patients with tonsil cancer in comparison to a group of patients with chronic tonsillitis, as well as the reaction of mastocytes and macrophages in the two types of tonsil lesions. Seric levels of TNF-α in squamous cell tonsil carcinoma were quite high, varying from 1000 to 2000 pg÷mL, and in four patients, with poorly differentiated tonsil carcinoma in the fourth stage, the TNF-α values varied from 2000 to 4000 pg÷mL. In the patients undergoing radiotherapy, the TNF-α seric levels were within normal limits. In chronic tonsillitis, the TNF-α seric level varied from 10 to 200 pg÷mL. There were not observed any significant differences between the two types of tonsil lesions, regarding the macrophages and mast cells density on the surface unit.
Topics: Adult; Aged; Carcinoma, Squamous Cell; Female; Gene Expression Regulation, Neoplastic; Humans; Inflammation; Macrophages; Male; Mast Cells; Middle Aged; Pharynx; Tonsillar Neoplasms; Tonsillitis; Tumor Necrosis Factor-alpha
PubMed: 25826493
DOI: No ID Found -
Advances in Clinical and Experimental... Jan 2021Hypopharyngeal cancer is one of the most frequent head and neck cancers and is associated with a poor prognosis because of recurrence and metastases. Therefore, there is...
BACKGROUND
Hypopharyngeal cancer is one of the most frequent head and neck cancers and is associated with a poor prognosis because of recurrence and metastases. Therefore, there is a need to improve the prognosis, which requires the identification of prognostic factors and elucidation of the mechanisms involved in tumor progression. Accumulated evidence has demonstrated that cluster of differentiation 147 (CD147) is strongly expressed in malignant tumors, including head and neck squamous cell carcinoma (HNSCC), and contributes to tumor progression.
OBJECTIVES
To investigate CD147-induced signaling pathways in HNSCC cells to evaluate the mechanisms of tumor progression mediated by CD147, and the association between CD147 expression in tumors and the survival rate of hypopharyngeal cancer patients.
MATERIAL AND METHODS
To determine the downstream signaling of CD147 in HNSCC, expression levels of phosphorylated AKT1, MEK1, p38 MAPK, STAT3, and NF-κB were evaluated using enzyme-linked immunosorbent assay (ELISA) in FaDu, a hypopharyngeal cell line, exposed to cyclophilin A, a CD147 ligand.
RESULTS
We found that hypopharyngeal cancer patients expressing CD147 showed a poor five-year overall survival (OS) of 11.1% compared with those without CD147 expression (43.0%) (p = 0.02). We confirmed that the expression of phosphorylated MEK and matrix metalloproteinase-9 (MMP-9), as well as cell invasion ability, were enhanced in hypopharyngeal cancer cells. In addition, this increased cell infiltration and enhancement of MMP-9 expression induced by CD147 were abolished by a MEK inhibitor.
CONCLUSIONS
These results suggest that CD147 can be a predictor of a poor prognosis, and that a CD147-induced MEK-mediated intracellular signaling pathway plays a crucial role in tumor progression in hypopharyngeal carcinoma.
Topics: Basigin; Cell Differentiation; Cell Line, Tumor; Humans; MAP Kinase Signaling System; Matrix Metalloproteinase 9; Mitogen-Activated Protein Kinase Kinases; Neoplasm Recurrence, Local; Pharyngeal Neoplasms; Prognosis; Signal Transduction; Squamous Cell Carcinoma of Head and Neck
PubMed: 33529506
DOI: 10.17219/acem/128228 -
International Journal of Cancer Nov 2017The possible role of dietary fiber in the etiology of head neck cancers (HNCs) is unclear. We used individual-level pooled data from ten case-control studies (5959 cases...
The possible role of dietary fiber in the etiology of head neck cancers (HNCs) is unclear. We used individual-level pooled data from ten case-control studies (5959 cases and 12,248 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium, to examine the association between fiber intake and cancer of the oral cavity/pharynx and larynx. Odds Ratios (ORs) and their 95% Confidence Intervals (CIs) were estimated using unconditional multiple logistic regression applied to quintile categories of non-alcohol energy-adjusted fiber intake and adjusted for tobacco and alcohol use and other known or putative confounders. Fiber intake was inversely associated with oral and pharyngeal cancer combined (OR for 5th vs. 1st quintile category = 0.49, 95% CI: 0.40-0.59; p for trend <0.001) and with laryngeal cancer (OR = 0.66, 95% CI: 0.54-0.82, p for trend <0.001). There was, however, appreciable heterogeneity of the estimated effect across studies for oral and pharyngeal cancer combined. Nonetheless, inverse associations were consistently observed for the subsites of oral and pharyngeal cancers and within most strata of the considered covariates, for both cancer sites. Our findings from a multicenter large-scale pooled analysis suggest that, although in the presence of between-study heterogeneity, a greater intake of fiber may lower HNC risk.
Topics: Adult; Aged; Alcohol Drinking; Carcinoma, Squamous Cell; Case-Control Studies; Dietary Fiber; Female; Head and Neck Neoplasms; Humans; Laryngeal Neoplasms; Male; Middle Aged; Pharyngeal Neoplasms; Risk Factors; Squamous Cell Carcinoma of Head and Neck; Nicotiana
PubMed: 28710831
DOI: 10.1002/ijc.30886 -
Virologica Sinica Apr 2015Nasopharyngeal carcinoma (NPC) is closely associated with Epstein-Barr virus (EBV) infection. EBV episomes are detected in almost all NPC cells. The role of EBV in NPC... (Review)
Review
Nasopharyngeal carcinoma (NPC) is closely associated with Epstein-Barr virus (EBV) infection. EBV episomes are detected in almost all NPC cells. The role of EBV in NPC pathogenesis has long been postulated but remains enigmatic. In contrast to infection of B lymphocytes, EBV infection does not directly transform nasopharyngeal epithelial cells into proliferative clones with malignant potential. EBV infection of normal pharyngeal epithelial cells is predominantly lytic in nature. Genetic alterations in premalignant nasopharyngeal epithelium, in combination with inflammatory stimulation in the nasopharyngeal mucosa, presumably play essential roles in the establishment of a latent EBV infection in infected nasopharyngeal epithelial cells during the early development of NPC. Establishment of latent EBV infection in premalignant nasopharyngeal epithelial cells and expression of latent viral genes, including the BART transcripts and BART-encoded microRNAs, are crucial features of NPC. Expression of EBV genes may drive further malignant transformation of premalignant nasopharyngeal epithelial cells into cancer cells. The difficulties involved in the establishment of NPC cell lines and the progressive loss of EBV epsiomes in NPC cells propagated in culture strongly implicate the contribution of host stromal components to the growth of NPC cells in vivo and maintenance of EBV in infected NPC cells. Defining the growth advantages of EBV-infected NPC cells in vivo will lead to a better understanding of the contribution of EBV infection in NPC pathogenesis, and may lead to the identification of novel therapeutic targets for NPC treatment.
Topics: Carcinogenesis; Carcinoma; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Host-Pathogen Interactions; Humans; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms
PubMed: 25910483
DOI: 10.1007/s12250-015-3592-5 -
European Journal of Epidemiology Apr 2016Food and nutrition play an important role in head and neck cancer (HNC) etiology; however, the role of carotenoids remains largely undefined. We explored the relation of...
Food and nutrition play an important role in head and neck cancer (HNC) etiology; however, the role of carotenoids remains largely undefined. We explored the relation of HNC risk with the intake of carotenoids within the International Head and Neck Cancer Epidemiology Consortium. We pooled individual-level data from 10 case-control studies conducted in Europe, North America, and Japan. The analysis included 18,207 subjects (4414 with oral and pharyngeal cancer, 1545 with laryngeal cancer, and 12,248 controls), categorized by quintiles of carotenoid intake from natural sources. Comparing the highest with the lowest quintile, the risk reduction associated with total carotenoid intake was 39 % (95 % CI 29-47 %) for oral/pharyngeal cancer and 39 % (95 % CI 24-50 %) for laryngeal cancer. Intakes of β-carotene equivalents, β-cryptoxanthin, lycopene, and lutein plus zeaxanthin were associated with at least 18 % reduction in the rate of oral and pharyngeal cancer (95 % CI 6-29 %) and 17 % reduction in the rate of laryngeal cancer (95 % CI 0-32 %). The overall protective effect of carotenoids on HNC was stronger for subjects reporting greater alcohol consumption (p < 0.05). The odds ratio for the combined effect of low carotenoid intake and high alcohol or tobacco consumption versus high carotenoid intake and low alcohol or tobacco consumption ranged from 7 (95 % CI 5-9) to 33 (95 % CI 23-49). A diet rich in carotenoids may protect against HNC. Persons with both low carotenoid intake and high tobacco or alcohol are at substantially higher risk of HNC.
Topics: Adult; Aged; Aged, 80 and over; Antioxidants; Carcinoma, Squamous Cell; Carotenoids; Case-Control Studies; Epidemiologic Studies; Europe; Female; Head and Neck Neoplasms; Humans; Japan; Middle Aged; Squamous Cell Carcinoma of Head and Neck; United States
PubMed: 25930054
DOI: 10.1007/s10654-015-0036-3 -
International Journal of Clinical... Jun 2024Salivary gland-type cancers (SGTCs) are histologically heterogeneous and can affect organs other than the salivary glands. Some tumors outside the salivary glands are...
BACKGROUND
Salivary gland-type cancers (SGTCs) are histologically heterogeneous and can affect organs other than the salivary glands. Some tumors outside the salivary glands are diagnosed on their unique histological characteristics. Comprehensive cross-organ studies on SGTCs are limited.
METHODS
We retrospectively analyzed the data of patients with salivary duct carcinoma (SDC), adenoid cystic carcinoma (AdCC), mucoepidermoid carcinoma (MEC), epithelial-myoepithelial carcinoma (EMC), acinic cell carcinoma (AcCC), and polymorphous adenocarcinoma (PAC) who visited our institution between 2009 and 2019. The primary tumor sites were classified into four categories; major salivary glands, head/neck (H/N) excluding (exc) major salivary glands (MSG) regions, broncho-pulmonary regions, and "others". H/N exc MSG was further divided into three subcategories, nasal/paranasal sinus, oral and pharynx/larynx.
RESULTS
We identified 173 patients with SGTCs, with SDC, AdCC, MEC, EMC, AcCC, and PAC accounting for 20%, 42%, 27%, 3%, 8%, and 1% of the cases, respectively. The most frequent primary site was the major salivary glands (64%), followed by H/N exc MSG regions (27%), broncho-pulmonary regions, and "others", thus non-salivary gland origins accounted for 9% of all cases. Patients with SDC, MEC, AcCC, or SGTC of the major salivary glands and broncho-pulmonary regions were more frequently treated by surgery. The overall survival time of the patients with MEC was significantly better than that of patients with SDC or EMC.
CONCLUSIONS
This cross-organ study highlights the clinical significance of SGTCs, underscoring the need for developing novel therapies for this rare disease entity.
Topics: Humans; Salivary Gland Neoplasms; Female; Male; Middle Aged; Retrospective Studies; Aged; Adult; Carcinoma, Mucoepidermoid; Carcinoma, Adenoid Cystic; Aged, 80 and over; Carcinoma, Acinar Cell; Young Adult; Adolescent; Adenocarcinoma; Salivary Glands
PubMed: 38492066
DOI: 10.1007/s10147-024-02505-3 -
Theranostics 2020Among head and neck squamous cell carcinomas (HNSCCs), hypopharyngeal squamous cell carcinoma (HPSCC) has the worst prognosis. Iron metabolism, which plays a crucial...
Among head and neck squamous cell carcinomas (HNSCCs), hypopharyngeal squamous cell carcinoma (HPSCC) has the worst prognosis. Iron metabolism, which plays a crucial role in tumor progression, is mainly regulated by alterations to genes and post-transcriptional processes. The recent discovery of the N6-methyladenosine (mA) modification has expanded the realm of previously undiscovered post-transcriptional gene regulation mechanisms in eukaryotes. Many studies have demonstrated that mA methylation represents a distinct layer of epigenetic deregulation in carcinogenesis and tumor proliferation. However, the status of mA modification and iron metabolism in HPSCC remains unknown. Bioinformatics analysis, sample analysis, and transcriptome sequencing were performed to evaluate the correlation between mA modification and iron metabolism. Iron metabolic and cell biological analyses were conducted to evaluate the effect of the mA reader YTHDF1 on HPSCC proliferation and iron metabolism. Transcriptome-wide mA-seq and RIP-seq data were mapped to explore the molecular mechanism of YTHDF1 function in HPSCC. YTHDF1 was found to be closely associated with ferritin levels and intratumoral iron concentrations in HPSCC patients at Sir Run Run Shaw Hospital. YTHDF1 induced-HPSCC tumorigenesis depends on iron metabolism . Mechanistically, YTHDF1 methyltransferase domain interacts with the 3'UTR and 5'UTR of TRFC mRNA, then further positively regulates translation of mA-modified TFRC mRNA. Gain-of-function and loss-of-function analyses validated the finding showing that TFRC is a crucial target gene for YTHDF1-mediated increases in iron metabolism. YTHDF1 enhanced TFRC expression in HPSCC through an mA-dependent mechanism. From a therapeutic perspective, targeting YTHDF1 and TFRC-mediated iron metabolism may be a promising strategy for HPSCC.
Topics: Adenosine; Animals; Antigens, CD; Carcinogenesis; Cell Line, Tumor; Cell Proliferation; Cohort Studies; Diffusion Magnetic Resonance Imaging; Disease-Free Survival; Gene Expression Regulation, Neoplastic; Humans; Hypopharyngeal Neoplasms; Hypopharynx; Iron; Male; Methylation; Mice; Neoplasm Recurrence, Local; RNA, Messenger; RNA-Binding Proteins; Receptors, Transferrin; Squamous Cell Carcinoma of Head and Neck; Xenograft Model Antitumor Assays
PubMed: 33204330
DOI: 10.7150/thno.51231 -
BMJ Case Reports Mar 2019The impact of metastasis to the retropharyngeal lymph node group is poorly understood because of the difficult access to the retropharyngeal space (RPS). In 20%-50% of...
The impact of metastasis to the retropharyngeal lymph node group is poorly understood because of the difficult access to the retropharyngeal space (RPS). In 20%-50% of surgically treated oropharyngeal, hypopharyngeal, and cervical oesophageal carcinomas, we can find metastases to the retropharyngeal lymph nodes (RPLNs). The use of a three-dimensional (3D)-imaging-guided navigation system to perform a biopsy for a suspicion of metastasis in an RPLN can provide advantages in terms of better precision and 3D orientation with protection of the surrounding critical structures. We report two cases of an open biopsy by transoral and transnasal approaches for a suspicion of metastasis in a retropharyngeal lymph node in two patients with oropharyngeal and pulmonary cancer, respectively, by using the 3D imaging-guided navigation system. In the both cases, the biopsies performed were very accurate and allowed to get a full histological analysis and diagnosis. The use of the navigation system as a means to perform biopsies in the soft tissue of the neck is rarely reported and up to date few reports can be found in the literature. This technique can provide multiple advantages when compared with other conventional methods. The procedure is simple, safe and minimally invasive.
Topics: Aged; Female; Humans; Image-Guided Biopsy; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Oropharyngeal Neoplasms; Pharynx
PubMed: 30890518
DOI: 10.1136/bcr-2018-227201 -
The Laryngoscope Jun 2021Long-term functional outcomes are poorly characterized for salvage laryngectomy. We identified predictors of esophageal stricture and swallowing function after salvage...
BACKGROUND
Long-term functional outcomes are poorly characterized for salvage laryngectomy. We identified predictors of esophageal stricture and swallowing function after salvage laryngectomy in a large cohort.
METHODS
A retrospective study of 233 patients who underwent salvage total laryngectomy for recurrent/persistent squamous cell carcinoma of the larynx or hypopharynx after radiation (XRT) or chemoradiation (CRT) was performed. Primary outcomes were esophageal dilation within 1 year, time to dilation, and gastrostomy tube dependence. Multivariate logistic and Cox regressions were used for statistical analysis.
RESULTS
Dilation was performed in 29.9% of patients. Dilation was twice as likely in patients with post-operative fistula compared to those without (Hazard Ratio (HR) 2.10, 95% Confidence Interval (CI) 1.06-4.13, P = .03). Every year between XRT/CRT and salvage was associated with 10% increase in dilation (HR 1.09, 95% CI 1.03-1.17, P = .01). No factors were associated with dilation by 1 year. About 10% of patients were at least partially gastrostomy tube-dependent 1 year post-operatively. At last follow-up (median 29 months), this rate was 13%. Patients with supraglottic recurrence had an increased risk of gastrostomy tube dependence at 1 year compared to glottic (OR 16.7, 95% CI 1.73-160, P = .02). For every 10 pack years pre-salvage, the OR of requiring tube feeds at last follow-up was 1.24 (95% CI 1.04-1.48, P = .02).
CONCLUSIONS
Fistula and pre-salvage smoking were associated with stricture post-salvage laryngectomy. No factors were associated with dilation by 1 year. Supraglottic recurrence and smoking were associated with gastrostomy tube dependence. These findings are important for pre-operative counseling prior to salvage laryngectomy.
LEVEL OF EVIDENCE
Level 4 Laryngoscope, 131:1229-1234, 2021.
Topics: Aged; Carcinoma, Squamous Cell; Constriction, Pathologic; Deglutition; Esophageal Fistula; Esophageal Stenosis; Female; Gastrostomy; Humans; Hypopharyngeal Neoplasms; Hypopharynx; Laryngeal Neoplasms; Laryngectomy; Larynx; Logistic Models; Male; Middle Aged; Neoplasm Recurrence, Local; Odds Ratio; Postoperative Complications; Postoperative Period; Proportional Hazards Models; Retrospective Studies; Salvage Therapy; Smoking; Time Factors; Treatment Outcome
PubMed: 33152117
DOI: 10.1002/lary.29215 -
European Journal of Nuclear Medicine... Jan 2023Head and neck squamous cell carcinomas (HNSCCs) are a molecularly, histologically, and clinically heterogeneous set of tumors originating from the mucosal epithelium of...
PURPOSE
Head and neck squamous cell carcinomas (HNSCCs) are a molecularly, histologically, and clinically heterogeneous set of tumors originating from the mucosal epithelium of the oral cavity, pharynx, and larynx. This heterogeneous nature of HNSCC is one of the main contributing factors to the lack of prognostic markers for personalized treatment. The aim of this study was to develop and identify multi-omics markers capable of improved risk stratification in this highly heterogeneous patient population.
METHODS
In this retrospective study, we approached this issue by establishing radiogenomics markers to identify high-risk individuals in a cohort of 127 HNSCC patients. Hybrid in vivo imaging and whole-exome sequencing were employed to identify quantitative imaging markers as well as genetic markers on pathway-level prognostic in HNSCC. We investigated the deductibility of the prognostic genetic markers using anatomical and metabolic imaging using positron emission tomography combined with computed tomography. Moreover, we used statistical and machine learning modeling to investigate whether a multi-omics approach can be used to derive prognostic markers for HNSCC.
RESULTS
Radiogenomic analysis revealed a significant influence of genetic pathway alterations on imaging markers. A highly prognostic radiogenomic marker based on cellular senescence was identified. Furthermore, the radiogenomic biomarkers designed in this study vastly outperformed the prognostic value of markers derived from genetics and imaging alone.
CONCLUSION
Using the identified markers, a clinically meaningful stratification of patients is possible, guiding the identification of high-risk patients and potentially aiding in the development of effective targeted therapies.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell; Retrospective Studies; Genetic Markers; Head and Neck Neoplasms; Prognosis; Risk Assessment
PubMed: 36161512
DOI: 10.1007/s00259-022-05973-9