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The pterygopalatine fossa and infratemporal fossa are often approached through an external incision because of their deep facial location, but this can present problems such as facial scarring and deformity. In schwannoma surgery, intraneural dissection is a useful surgical technique for achieving gross total resection while preserving the capsule, including the nerves. For appropriate enucleation and preservation of the functional nerve, it is indispensable to distinguish between the pseudocapsule and the tumor capsule. This case report presents a case of endonasal surgical intervention for an extracranial trigeminal schwannoma employing the tri-port approach and narrow-band imaging.
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OBJECTIVE: The objective of this study was to assess the utility of narrow-band imaging (NBI) for improving intraneural dissection during gross total resection of head and neck schwannoma. Specifically, we aimed to quantitatively evaluate whether NBI can enhance the identification of pseudocapsule and true capsule within the tumor. METHODS: Nine schwannoma surgery cases conducted between February 2018 and October 2022 were retrospectively analyzed. The surgical procedures followed established principles with a specific focus on utilizing NBI to distinguish between the pseudocapsule and true capsule. Intraneural dissection was performed by searching for a tumor surface with a fascicle-free window, followed by longitudinal incision of the pseudocapsule. NBI was used to distinguish between the pseudocapsule and true capsule. Surgical views were captured under both white light (WL) illumination and NBI for further analysis. The brightness and contrast of the pseudocapsule and true capsule were quantitatively measured using ImageJ and were compared. RESULTS: Under NBI, the pseudocapsule consistently appeared greenish-gray, whereas the true capsule exhibited a white appearance. Quantitative analysis revealed a statistically significant difference (p < 0.0001) in brightness between the pseudocapsule (mean grayscale value 52.1, 95%CI; 46.4-75.3) and true tumor capsule (mean grayscale value 120.8, 95%CI; 155.7-109.0) under NBI. Conversely, there was no statistically significant difference in the brightness of these structures under WL (p = 0.2067). NBI also showed significantly higher contrast between the two structures than did WL (contrast 73.6, 95%CI; 53.1-89.5 vs. 30.9, 95%CI; 1.0-47.5, p = 0.0034). Further spectral analysis revealed that the most substantial difference in brightness between the pseudocapsule and the true tumor capsule was observed in the red spectrum, with a difference in brightness of -0.6 (95%CI; -16.8-14.8) under WL and 83.5 (95%CI; 50.3-100.0) under NBI (p < 0.0001). CONCLUSION: NBI proved to be a valuable tool for enhancing the identification of pseudocapsule and true capsule during intraneural dissection in head and neck schwannoma surgery. The improved contrast and membrane visibility offered by NBI might have the potential to reduce postoperative neurological deficits and improve surgical outcomes. Further research is warranted to validate our findings and explore the broader applications of NBI in schwannoma surgery.
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BACKGROUND: Although immune checkpoint inhibitors (ICIs) are approved for the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), the response to ICIs remains unclear. AIMS/OBJECTIVES: To summarize the clinical outcomes of patients with HNSCC treated with nivolumab (Nivo) in our institution, and provide a basis for research on biomarkers that can predict the efficacy of ICIs. MATERIAL AND METHODS: Forty-four patients with R/M HNSCC who received Nivo (2017-2022) were retrospectively analysed. RESULTS: Despite the older age of this cohort (median age of 72 years), we observed favourable long-term outcomes, with an overall survival of 24.1 months, which could be attributed to our aggressive nutritional intervention. Older age, poor performance status (≥1), and higher Glasgow Prognostic Scores, reflecting the chronic inflammation and malnutrition of patients, were associated with poor prognoses, with hazard ratios for death of 2.63 (95% confidence interval [CI]; 1.07-6.46, p = .016), 3.50 (95% CI; 1.28-9.55, p = .001), and 2.69 (95% CI; 1.17-6.21, p = .029), respectively. Peripheral blood biomarker analysis revealed that systemic inflammation may negatively affect the efficacy of Nivo. CONCLUSIONS AND SIGNIFICANCE: Our results suggest that nutrition and inflammation must be the focus of future studies aiming to identify novel biomarkers.
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Neoplasias de Cabeça e Pescoço , Desnutrição , Humanos , Idoso , Nivolumabe/uso terapêutico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Desnutrição/complicações , Desnutrição/tratamento farmacológicoRESUMO
BACKGROUND: The CXCL12/CXCR4 axis plays a pivotal role in the progression of various malignancies, including oral squamous cell carcinoma (OSCC). In this study, we aimed to clarify the biological and clinical significance of CXCL12 in the tumor microenvironment of OSCCs. METHODS: Publicly available single-cell RNA-sequencing (RNA-seq) datasets were used to analyze CXCL12 expression in head and neck squamous cell carcinomas (HNSCC). Immunohistochemical analysis of CXCL12, α-smooth muscle antigen (α-SMA), fibroblast activation protein (FAP) and CD8 was performed in a series of 47 surgically resected primary tongue OSCCs. Human skeletal muscle cells were co-cultured with or without OSCC cells, after which CXCL12 expression was analyzed using quantitative reverse-transcription PCR. RESULTS: Analysis of the RNA-seq data suggested CXCL12 is abundantly expressed in stromal cells within HNSCC tissue. Immunohistochemical analysis showed that in grade 1 primary OSCCs, CXCL12 is expressed in both tumor cells and muscle cells. By contrast, grade 3 tumors were characterized by disruption of muscle structure and reduced CXCL12 expression. Quantitative analysis of CXCL12-positive areas within tumors revealed that reduced CXCL12 expression correlated with poorer overall survival. Levels of CXCL12 expression tended to inversely correlate α-SMA expression and positively correlate with infiltration by CD8+ lymphocytes, though these relations did not reach statistical significance. CXCL12 was significantly upregulated in muscle cells co-cultured with OSCC cells. CONCLUSION: Our results suggest that tongue OSCC cells activate CXCL12 expression in muscle cells, which may contribute to tumor progression. However, CXCL12 is reduced in advanced OSCCs due to muscle tissue destruction.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Neoplasias da Língua , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Neoplasias da Língua/genética , Língua , Músculo Esquelético/patologia , Prognóstico , Microambiente Tumoral , Quimiocina CXCL12/genética , Quimiocina CXCL12/metabolismoRESUMO
We previously showed that upregulation of adipocyte enhancer-binding protein 1 (AEBP1) in vascular endothelial cells promotes tumor angiogenesis. In the present study, we aimed to clarify the role of stromal AEBP1/ACLP expression in oral squamous cell carcinoma (OSCC). Immunohistochemical analysis showed that ACLP is abundantly expressed in cancer-associated fibroblasts (CAFs) in primary OSCC tissues and that upregulated expression of ACLP is associated with disease progression. Analysis using CAFs obtained from surgically resected OSCCs showed that the expression of AEBP1/ACLP in CAFs is upregulated by co-culture with OSCC cells or treatment with TGF-ß1, suggesting cancer-cell-derived TGF-ß1 induces AEBP1/ACLP in CAFs. Collagen gel contraction assays showed that ACLP contributes to the activation of CAFs. In addition, CAF-derived ACLP promotes migration, invasion, and in vivo tumor formation by OSCC cells. Notably, tumor stromal ACLP expression correlated positively with collagen expression and correlated inversely with CD8+ T cell infiltration into primary OSCC tumors. Boyden chamber assays suggested that ACLP in CAFs may attenuate CD8+ T cell migration. Our results suggest that stromal ACLP contributes to the development of OSCCs, and that ACLP is a potential therapeutic target.
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BACKGROUND: Tubarial glands (TGs) are a collection of unidentified salivary glands overlying the torus tubarius in the nasopharyngeal wall. Immunoglobulin G4-related disease (IgG4-RD) is a chronic fibroinflammatory state that often has multiple organ involvement. Involvement of the head and neck, especially the salivary glands, is common in IgG4-RD. AIMS/OBJECTIVES: This study aimed to elucidate the clinical significance of TGs in IgG4-RD. MATERIALS AND METHODS: We investigated the local findings of TGs in ten patients with IgG4-RD. RESULTS: Nasopharyngeal endoscopic examination revealed oedematous swelling of the nasopharyngeal wall surrounding the TGs, which improved after steroid treatment. Moreover, sonotubometry showed a stenotic pattern in three out of seven patients with IgG4-RD. CONCLUSIONS AND SIGNIFICANCE: TGs may be involved in IgG4-RD. The swollen TGs may be responsible for obstructive Eustachian tube dysfunction. Further studies are required to clarify the clinical significance and physiological roles of TGs in IgG4-RD.
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Doenças Autoimunes , Doença Relacionada a Imunoglobulina G4 , Humanos , Imunoglobulina G , Doença Relacionada a Imunoglobulina G4/complicações , Doença Relacionada a Imunoglobulina G4/diagnóstico , Glândulas Salivares , EsteroidesRESUMO
OBJECTIVE: In the elevation of the muco-perichondrium flap during septoplasty and septorhinoplasty, it is important to elevate the subperichondrial layer. When performing subperichondrial elevation of the flap, the surgeon uses differences in color tone to distinguish the perichondrium from cartilage; however, it is relatively difficult to understand these differences and to share them with assistants. Furthermore, the perichondrium at the caudal end adheres tightly to the cartilage, making it difficult to detach accurately the subperichondrial layer. Narrow band imaging (NBI) is an optical technology that facilitates detailed observation of microvessels in the mucosal surface layer. In this study, we investigated whether NBI is better than white light (WL) in accentuating differences in contrast between cartilage and perichondrium in the elevation of the muco-perichondrium flap during septoplasty and septorhinoplasty. METHODS: Twenty-six sides of 15 patients (the modified Killian approach was used in two patients, the hemitransfixion approach was used in seven patients, and open septorhinoplasty was used in six patients) with elevated muco-perichondrium flaps were studied under WL endoscopy and NBI. The brightness of the perichondrium and cartilage and the differences between the two tissues were compared between WL and NBI using ImageJ 1.53a. Next, the WL and NBI endoscopic images used for cartilage identification were divided into the three separate primary color channels of red, green, and blue, and the brightness of the perichondrium and cartilage were measured separately for each channel. RESULTS: Under WL, the perichondrium appeared reddish-white and the cartilage appeared white, whereas under NBI the perichondrium appeared greenish-gray, differentiating it from the white cartilage. The difference in brightness between the cartilage and perichondrium was significantly higher on NBI (grayscale difference 80.8 (SD 42.4)) than on WL imaging (grayscale difference 35.6 (SD 31.1)) (p<0.001). In the red channel, the difference in image intensity between cartilage and perichondrium was significantly higher on NBI than on WL imaging (Red WL grayscale difference -1.5 (SD 33.7), Red NBI grayscale difference 90.0 (SD 56.7); p<0.001). CONCLUSIONS: NBI is better than WL at accentuating the difference in contrast between cartilage and the perichondrium during the elevation of the muco-perichondrium flap during septoplasty and septorhinoplasty. The difference in the processing of red light between WL and NBI provides the largest contribution to the differentiation of cartilage from the perichondrium under WL and NBI. We believe that NBI can be usefully applied during septoplasty and septorhinoplasty to distinguish cartilage from the perichondrium with precision.
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Imagem de Banda Estreita , Rinoplastia , Cartilagem/diagnóstico por imagem , Humanos , Luz , Imagem de Banda Estreita/métodos , Retalhos CirúrgicosRESUMO
BACKGROUND: The p53 family p63 is essential for the proliferation and differentiation of various epithelial basal cells. It is overexpressed in several cancers, including salivary gland neoplasia. Histone deacetylases (HDACs) are thought to play a crucial role in carcinogenesis, and HDAC inhibitors downregulate p63 expression in cancers. METHODS: In the present study, to investigate the roles and regulation of p63 in salivary duct adenocarcinoma (SDC), human SDC cell line A253 was transfected with siRNA-p63 or treated with the HDAC inhibitors trichostatin A (TSA) and quisinostat (JNJ-26481585). RESULTS: In a DNA array, the knockdown of p63 markedly induced mRNAs of the tight junction (TJ) proteins cingulin (CGN) and zonula occuludin-3 (ZO-3). The knockdown of p63 resulted in the recruitment of the TJ proteins, the angulin-1/lipolysis-stimulated lipoprotein receptor (LSR), occludin (OCLN), CGN, and ZO-3 at the membranes, preventing cell proliferation, and leading to increased cell metabolism. Treatment with HDAC inhibitors downregulated the expression of p63, induced TJ structures, recruited the TJ proteins, increased the epithelial barrier function, and prevented cell proliferation and migration. CONCLUSIONS: p63 is not only a diagnostic marker of salivary gland neoplasia, but it also promotes the malignancy. Inhibition of HDAC and signal transduction pathways is, therefore, useful in therapy for p63-positive SDC cells.
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Of the schwannomas that arise from the parapharyngeal space, those in the high cervical region are particularly invasive, requiring mandibular dissection. Because these tumors are benign, however, excessive surgical invasion and postoperative neurological complications should be avoided. Postoperative dropout symptoms may be avoided by intracapsular extraction, including nerve integrity monitoring (NIM) and narrow-band imaging (NBI). Video laryngoscopy surgery is reported to be useful for transoral resection of pharyngeal and laryngeal tumors. This report describes the transoral removal of a giant schwannoma located in the high cervical region from a 74-years-old man using a surgical support device without mandibular dissection. The tumor was located on the right lateral pharyngeal wall and extended from the upper oropharynx to the hypopharynx while compressing the epiglottis to the skull base. No separation was observed between the internal jugular vein and the internal carotid artery. The tumor was diagnosed as a schwannoma with no malignancy on the basis of the histology of a core needle biopsy (CNB), and was completely and safely removed endoscopically using NIM and NBI, with no need for an external incision or mandibular dissection. This case illustrates that even a huge sympathetic schwannoma located in the parapharyngeal space at a high cervical position can be excised transorally using video-laryngoscopic surgery (TOVS) without mandibular dissection.
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Cirurgia Endoscópica por Orifício Natural/métodos , Neurilemoma/cirurgia , Espaço Parafaríngeo/cirurgia , Neoplasias Faríngeas/cirurgia , Idoso , Humanos , MasculinoRESUMO
In human head and neck squamous cell carcinoma (HNSCC), the invasion and metastatic properties of cancer cells are promoted by junctional adhesion moleculeA (JAMA) and claudin1; these are epithelial tight junction molecules regulated by histone deacetylases (HDACs) and transcription factor p63. HDAC expression is reportedly upregulated in HNSCC, and HDAC inhibitors suppress cancer cell proliferation by initiating proliferative arrest or apoptosis. However, little is known of the anticancer mechanisms of HDAC inhibitors in HNSCC. Thus, in the present study, the HNSCC Detroit 562 cell line and primary cultured HNSCC cells were treated with HDAC inhibitors to investigate their effects in HNSCC. Higher expression of p63, HDAC1, JAMA and claudin1 was observed in HNSCC tissues compared with the adjacent dysplastic regions. In Detroit 562 cells, treatment with trichostatin A (TSA), an inhibitor of HDAC1 and 6, downregulated the expression of p63, JAMA and claudin1, and upregulated that of acetylated tubulin; conversely, p63 knockdown resulted in the downregulation of JAMA and claudin1. Collectively, inhibiting HDAC suppressed the migration and invasiveness of cancer cells. In addition, treatment with TSA suppressed cancer cell proliferation via G2/M arrest, as well as upregulating p21 and downregulating cyclin D1 expression. TSA also downregulated the expression of epidermal growth factor receptor (EGFR) and phosphoERK1/2. p63 knockdown and treatment with an EGFR inhibitor induced G1 arrest and downregulated EGFR and phosphoERK1/2 levels, respectively. HDAC inhibition also suppressed the migration and invasiveness of primary cultured HNSCC cells. Collectively, the results of the present study indicate that HDAC inhibitors suppress the proliferation, migration and invasiveness of HNSCC by downregulating the p63mediated tight junction molecules JAMA and claudin1, and inducing p63 or p21mediated growth arrest.
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Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Junções Íntimas/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Idoso , Apoptose/efeitos dos fármacos , Moléculas de Adesão Celular/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Claudina-1/metabolismo , Feminino , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Inibidores de Histona Desacetilases/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Receptores de Superfície Celular/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Junções Íntimas/metabolismo , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genéticaRESUMO
Epithelial-derived thymic stromal lymphopoietin (TSLP) triggers dendritic cell (DC)-mediated Th2-type inflammatory responses and is a master switch for allergic inflammatory diseases. In the present study, the expression and induction of TSLP and the effects of TSLP on the tight-junctional barrier of human nasal epithelial cells (HNECs) have been investigated in order to elucidate the role of TSLP in allergic rhinitis. We have found high expression of TSLP in the epithelium from patients with allergic rhinitis with recruitment and infiltration of DCs. In vitro, TSLP is significantly produced in HNECs after treatment with a toll-like receptor 2 (TLR2) ligand, Pam(3)Cys-Ser-(Lys)(4), and a mixture of interleukin-1beta and tumor necrosis factor-alpha. Treatment with TSLP rapidly enhances the barrier function of cultured HNECs, together with an increase of tight-junction proteins claudin-1, -4, -7, and occludin. The nasal-epithelial-derived TSLP thus not only activates DCs but also preserves the epithelial barrier via the upregulation of tight-junction proteins, thereby regulating antigen sensitization during the early stage of allergic rhinitis.
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Claudinas/genética , Citocinas/metabolismo , Células Dendríticas/patologia , Proteínas de Membrana/genética , Mucosa Nasal/efeitos dos fármacos , Junções Íntimas/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Claudinas/metabolismo , Citocinas/genética , Citocinas/farmacologia , Humanos , Interleucina-1beta/farmacologia , Lipopeptídeos/farmacologia , Proteínas de Membrana/metabolismo , Mucosa Nasal/metabolismo , Ocludina , Rinite Alérgica Perene/patologia , Rinite Alérgica Perene/fisiopatologia , Junções Íntimas/metabolismo , Receptor 2 Toll-Like/antagonistas & inibidores , Fator de Necrose Tumoral alfa/farmacologia , Regulação para Cima , Linfopoietina do Estroma do TimoRESUMO
Rho-kinase inhibitor Y27632, which is a factor in conditional reprogramming culture, induces airway progenitor clone formation. To investigate whether Y27632 enhances airway progenitor cells in nasal epithelium, primary cultures of HNECs transfected with human telomerase reverse transcriptase (hTERT-HNECs) were treated with Y27632. In TERT-HNECs treated with Y27632 for 5 days, upregulation of p63, gap junction molecules Cx26, Cx30, Cx43, cytochrome P450 enzymes CYP2C9, CYP2C18, CYP39A1, CYP4B1, CYP2G1P, CYP4Z1, and KLF families KLF10 and KLF11 were observed compared to the control. Downregulation of tight junction molecules claudin-4, -7, and -23 was observed. Circumfential submembrane F-actin was also induced. The functions of gap junctional intercellular communication (GJIC) and the epithelial barrier were upregulated. Knockdown of p63 by siRNAs of TAp63 or ΔNp63 inhibited Cx26, Cx43 and CYP2C18, and induced claudin-1, and -4. Knockdown of KLF11 prevented p63 expression and enhancement of the epithelial barrier function by Y27632. In nasal mucosal tissues from patients with allergic rhinitis (AR), localized alteration of p63, KLF11, RhoA, Cx30 and claudin-4 was observed. Treatment with Y27632 in long-term culture induced airway progenitor cells via KLF11 in p63-positive human nasal epithelium. Airway progenitor cells of nasal epithelium induced by Y27632 is important in understanding upper airway disease-specific characteristics.
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The epithelium of upper respiratory tissues such as human nasal mucosa forms a continuous barrier via tight junctions, which is thought to be regulated in part through a protein kinase C (PKC) signaling pathway. To investigate the mechanisms of the regulation of PKC-mediated tight junction barrier function of human nasal epithelium in detail, primary human nasal epithelial cells were treated with the PKC activator 12-O-tetradecanoylophorbol-13-acetate (TPA). In primary human nasal epithelial cells, treatment with TPA led not only to activation of phosphorylation of PKC, myristoylated alanine-rich C kinase substrate, and mitogen-activated protein kinase but also expression of novel PKC-delta, PKC-theta, and PKC-epsilon. Treatment with TPA increased transepithelial electrical resistance, with tight junction barrier function more than 4-fold that of the control, together with up-regulation of tight junction proteins, occludin, zona occludens (ZO)-1, ZO-2 and claudin-1 at the transcriptional level. Furthermore, it affected the subcellular localization of the tight junction proteins and the numbers of tight junction strands. The up-regulation of barrier function and tight junction proteins was prevented by a pan-PKC inhibitor, and the inhibitors of PKC-delta and PKC-theta but not PKC-epsilon. In primary human nasal epithelial cells, transcriptional factors GATA-3 and -6 were detected by reverse transcription-polymerase chain reaction. The knockdown of GATA-3 using RNA interference resulted in inhibition of up-regulation of ZO-1 and ZO-2 by treatment with TPA. These results suggest that TPA-induced PKC signaling enhances the barrier function of human nasal epithelial cells via transcriptional up-regulation of tight junction proteins, and the mechanisms may contribute to a drug delivery system.
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Mucosa Nasal/fisiologia , Proteína Quinase C/fisiologia , Junções Íntimas/enzimologia , Transcrição Gênica/fisiologia , Células Cultivadas , Humanos , Mucosa Nasal/citologia , Mucosa Nasal/enzimologia , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C/genética , Transdução de Sinais/genética , Junções Íntimas/genética , Junções Íntimas/fisiologia , Transcrição Gênica/genéticaRESUMO
The human adenoid epithelium forms a continuous barrier against a wide variety of exogenous antigens. In this study, to elucidate the structures of the epithelial barrier in the human adenoid, including M-cells, we identified M-cells using an anti-cytokeratin 20 (Ck20) antibody and investigated expression of tight junction proteins in human adenoid epithelium in vivo and in vitro. In human adenoid epithelium and primary cultures, mRNAs of occludin, junctional adhesion molecule-A, ZO-1, and claudin-1, -4, -7, and -8 were detected by reverse transcription-polymerase chain reaction, whereas claudin-2 and -9 were expressed in vitro. In the epithelium in vivo, some Ck20-positive cells were randomly observed and indicated pocket-like structures, whereas Ck7 was positive in almost cells. Transmission electron microscopy revealed that Ck20-associated gold particles could be identified in M-like cells which had short microvilli and harboured the lymphocyte in the pocket-like structure. In primary cultures in vitro, Ck20-positive cells were also detected and had a function to take up fluorescent microparticles. In Ck20-positive cells in vivo and in vitro, expression of occludin, ZO-1, claudin-1 and -7 were observed at cell borders. These results indicate that the epithelial barrier of the human adenoid is stably maintained by expression of tight junction proteins in the epithelium including Ck20-positive M-like cells.
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Tonsila Faríngea/citologia , Tonsila Faríngea/metabolismo , Epitélio/metabolismo , Queratina-20/metabolismo , Proteínas de Membrana/metabolismo , Junções Íntimas/metabolismo , Tonsila Faríngea/ultraestrutura , Células Cultivadas , Criança , Pré-Escolar , Células Epiteliais/metabolismo , Células Epiteliais/ultraestrutura , Epitélio/ultraestrutura , Regulação da Expressão Gênica , Humanos , Proteínas de Membrana/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Junções Íntimas/ultraestruturaRESUMO
BACKGROUND/AIM: To analyze the clinical features and prevalence of synchronous and metachronous second primary malignancies (SPMs) in patients with hypopharyngeal squamous cell carcinoma (HSCC), their associated risk factors, and cause-specific mortality. PATIENTS AND METHODS: We retrospectively reviewed 136 patients treated with curative intent at our hospital. Statistical analyses were performed to determine factors predictive of SPM and cause-specific mortality. RESULTS: Sixty-three of 136 patients (46.3%) developed SPM; of these, 41 (30.1%) and 42 (30.9%) had synchronous and metachronous SPMs, respectively, with patient overlap. The most common site of synchronous and metachronous SPMs was the oesophagus (65.8% and 24.4%, respectively); the corresponding overall survival rates were 34.1% and 66.5%, respectively. Furthermore, heavy drinking was significantly correlated with synchronous SPM (p<0.001). CONCLUSION: Oesophageal cancer surveillance is recommended for patients with HSCC, especially heavy drinkers. Our findings may help identify and properly manage HSCC patients at high risk of SPMs.
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Carcinoma de Células Escamosas/patologia , Neoplasias Hipofaríngeas/patologia , Neoplasias Primárias Múltiplas/patologia , Segunda Neoplasia Primária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas , Carcinoma de Células Escamosas/complicações , Feminino , Humanos , Neoplasias Hipofaríngeas/complicações , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Múltiplas/complicações , Segunda Neoplasia Primária/complicações , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Análise de SobrevidaRESUMO
BACKGROUND: Carcinoma ex pleomorphic adenoma (CXPA) is a rare histologic subtype of lacrimal gland and submandibular gland cancer. Currently, there is no standard treatment for metastatic CXPA, although some case reports have explored the role of targeted agents in chemotherapy. A few histopathologic analyses have shown that some of these tumors overexpress human epidermal growth factor receptor-2 (HER2), suggesting a potential role for HER2-based therapy. We report here two cases of metastatic CXPA that were treated with trastuzumab-based chemotherapy (IRB approved) with rapid and significant responses. CASE REPORT 1: A 66-year-old male was diagnosed as HER2-positive CXPA of the right lacrimal gland with multiple bone and lymph node metastases. Combination chemotherapy with trastuzumab (Tmab) and nanoparticle albumin-bound paclitaxel (nabPTX) was initiated. A rapid response was confirmed, and after seven cycles of treatment, CR(complete response) was achieved. CASE REPORT 2: A 67-year-old female was diagnosed with HER2 positive CXPA of the right submandibular gland. Multiple pulmonary metastatic lesions were detected after surgery, and combination chemotherapy with Tmab and nab-PTX was initiated. A rapid partial response (PR) was confirmed, and she eventually became disease-free. CONCLUSION: In the absence of definitive clinical trials, which are unlikely to be performed due to the rarity of HER2-positive CXPA, therapeutic information must be obtained from case reports. Some reports, such as this one, have suggested a potential utility of trastuzumab-based chemotherapy.
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P63 is a regulator of cell-cell junction complexes in the epidermis. Claudin-4 is regulated via various factors in normal epithelial cells and diseases. We found that claudin-4 was directly regulated via p63 (TAp63 and ΔNp63) in human keratinocytes and nasal epithelial cells. In the epidermis of atopic dermatitis (AD), which contains ΔNp63-deficient keratinocytes, high expression of claudin-4 was observed. In primary keratinocytes, downregulation of ΔNp63 by treatment with short interfering RNA (siRNA)-p63 induced claudin-4 expression. In nasal epithelial cells in the context of rhinitis or nasal polyps, upregulation of TAp63 and downregulation of claudin-4 were observed. In primary nasal epithelial cells transfected with the human telomerase reverse transcriptase gene, knockdown of p63 by siRNAs induced claudin-4 expression. Taken together, these findings indicate that p63 is a negative regulator of claudin-4 expression. Understanding the regulation of claudin-4 via p63 in human epithelial cells may be important for developing therapies for allergies and drug delivery systems.
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Claudina-4/metabolismo , Células Epiteliais/metabolismo , Queratinócitos/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Claudina-4/genética , Regulação para Baixo , Humanos , Pólipos Nasais/genética , Pólipos Nasais/metabolismo , Rinite/genética , Rinite/metabolismo , Fatores de Transcrição/genética , Ativação Transcricional , Proteínas Supressoras de Tumor/genética , Regulação para CimaRESUMO
Accessory parotid gland tumors are clinically rare, and their management remains unclear. In this article, we describe our experience with 4 patients-2 males and 2 females, aged 13 to 66 years-who were diagnosed with an accessory parotid gland tumor. All patients presented with an asymptomatic midcheek swelling, and all underwent fine-needle aspiration biopsy, ultrasonography, computed tomography, and magnetic resonance imaging. A standard parotidectomy was performed on all patients. Postoperatively, 2 patients were found to have a malignant tumor, while the other 2 had a pleomorphic adenoma. No patient experienced any obvious facial nerve injuries postoperatively, and no recurrences were observed. We discuss the preoperative evaluation, treatment, and prognosis of these tumors, and we briefly describe the literature. The first choice of treatment for accessory parotid gland tumors is surgical resection. In our experience, a standard parotidectomy approach is safe and cosmetically appealing.
Assuntos
Adenoma Pleomorfo/patologia , Carcinoma de Células Acinares/patologia , Mioepitelioma/patologia , Glândula Parótida/anormalidades , Neoplasias Parotídeas/patologia , Adenoma Pleomorfo/diagnóstico por imagem , Adenoma Pleomorfo/cirurgia , Adolescente , Adulto , Idoso , Biópsia por Agulha Fina , Carcinoma de Células Acinares/diagnóstico por imagem , Carcinoma de Células Acinares/cirurgia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mioepitelioma/diagnóstico por imagem , Mioepitelioma/cirurgia , Glândula Parótida/diagnóstico por imagem , Glândula Parótida/cirurgia , Neoplasias Parotídeas/diagnóstico por imagem , Neoplasias Parotídeas/cirurgia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , UltrassonografiaRESUMO
Junctional adhesion molecule-A (JAM-A), which belongs to the IgG superfamily, is one of the tight junction molecules. JAM-A is dysregulated in various cancers and is closely associated with the invasion and metastasis of cancers such as breast cancer, lung cancer and pancreatic cancer. In the present study, we found a high expression of JAM-A in head and neck squamous cell carcinoma (HNSCC) as well as ß-catenin in immunohistochemistry. The expression of JAM-A and ß-catenin was of a low level in differentiation-induced cancer pearl regions of HNSCC. Real-time PCR showed the high expression of JAM-A mRNA through all differentiated stages (well, moderate, poor) of HNSCC. When we performed ELISA using the serum of HNSCC patients to measure plasma-soluble JAM-A, it was found to be higher in HNSCC patients than healthy subjects. These results indicate that JAM-A is one of the malignancy markers of HNSCC as well as ß-catenin in histopathology, and the plasma-soluble JAM-A may contribute to a serum diagnosis of HNSCC. JAM-A is a promising molecular target for diagnosis and therapy in HNSCC.
Assuntos
Carcinoma de Células Escamosas/genética , Moléculas de Adesão Celular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , RNA Neoplásico/genética , Receptores de Superfície Celular/genética , Junções Íntimas/metabolismo , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Moléculas de Adesão Celular/biossíntese , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Imuno-Histoquímica , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Superfície Celular/biossíntese , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
Inflammasomes, large protein complexes typically consisting of a Nod-like receptor (NLR), adapter protein apoptosis-associated speck-like protein containing CARD (ASC) and caspase-1, are postulated to be activated in response to danger signals arising from tumors. Inflammasomes are thought to have critical but contrasting roles through facilitating antitumor immunity and inducing oncogenic factors. However, the role and function of inflammasomes in oropharyngeal carcinoma remain unclear. We analyzed nine specimens of oropharyngeal squamous cell carcinoma (SCC) and determined the expression of NLRP3, ASC, interleukin (IL)-1ß, IL-18 and caspase-1 in the specimens with and without human papilloma virus (HPV) infection using immunohistochemistry, and analyzed the correlations between the altered expression of these proteins and clinicopathological factors of oropharyngeal SCC. We found strong expression of NLRP3, ASC, IL-1ß, IL-18 and caspase-1 in human oropharyngeal SCC and weak or no expression of these proteins in normal tonsils. Furthermore, the distribution of mindbomb E3 ubiquitin protein ligase 1 and inflammasome-associated proteins in oropharyngeal SCC was not significantly different; there was no correlation between the expression of inflammasome-associated proteins and HPV infection. These findings suggest that inflammasomes in oropharyngeal SCC play a key role through facilitating antitumor immunity and the possibility of new roles for inflammasomes in the oropharynx.