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Adenomatous ductal proliferation/hyperplasia (ADP/H) is a rare hyperplastic condition of the salivary gland. It is mostly associated with other salivary gland pathologies such as tumors and inflammations, and is incidentally found in tissue sections during histopathological examinations of those diseases. Herein, we report a case of ADP/H in the parotid gland not associated with any other pathological lesions, and present a review of the literature on this condition. A 60-year-old Japanese female complained of swelling on the left side of parotid region. Clinical examination revealed a swelling on the lower lobe of the left parotid gland. The lesion was firm but non-tender and was not attached to adjacent structures. A clinical diagnosis of benign salivary gland tumor was reached, and surgical excision was performed under general anesthesia. Histopathological examination revealed an intact parotid gland capsule with isomorphic and basaloid cells within scanty cytoplasm. In addition, an admixture of hyperplasia and proliferation of the intercalated ducts, the presence of zymogen granules, the absence of solid nests, and a peripheral palisaded arrangement of the cells were observed. Based on these findings, a diagnosis of ADP/H was confirmed. ADP/H is a non-tumorous lesion; therefore, tumor involvement should be ruled out before the diagnosis is reached.
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Carcinoma Ductal/diagnóstico , Glándula Parótida/diagnóstico por imagen , Neoplasias de las Glándulas Salivales/diagnóstico , Carcinoma Ductal/diagnóstico por imagen , Carcinoma Ductal/cirugía , Femenino , Humanos , Hiperplasia , Persona de Mediana Edad , Glándula Parótida/cirugía , Neoplasias de las Glándulas Salivales/diagnóstico por imagen , Neoplasias de las Glándulas Salivales/cirugíaRESUMEN
Carcinoma follows a course of multiple changes that are affected by several important factors, with epigenetic silencing of the promoter gene being one of them. A series of studies have suggested that epigenetic changes in the anti-aging gene Klotho may be one of the emerging areas of concern in the study of carcinogenesis. We hypothesized that epigenetic silencing of Klotho due to hypermethylation of DNMT3a may be one of the causes of carcinoma in the oral and maxillofacial region. In this study, we analyzed the immunohistochemical expressions of Klotho and DNMT3a in tissues obtained from oral dysplasia and oral squamous cell carcinoma. Our results showed increased immune expression of DNMT3a, and decreased expression of Klotho in cells of the cancer tissues when compared with those in the dysplasia and healthy control samples. Chi-square tests complemented by adjusted residual analysis revealed significantly higher number of Klotho-positive and DNMT3a-negative cases in healthy controls, Klotho-negative and DNMT3a-negative cases in ODL, and Klotho-negative and DNMT3a-positive cases in OSCC when compared with the other types among the three groups (X 2 = 46.66, p < 0.001). Thus, downregulation of Klotho may be associated with the overexpression of DNMT3a in cancer tissues.
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Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , ADN (Citosina-5-)-Metiltransferasas/metabolismo , Glucuronidasa/metabolismo , Neoplasias de la Boca/metabolismo , Neoplasias de la Boca/patología , Adulto , Anciano , Anciano de 80 o más Años , ADN Metiltransferasa 3A , Femenino , Humanos , Inmunohistoquímica , Proteínas Klotho , Masculino , Persona de Mediana EdadRESUMEN
INTRODUCTION: Hypoglossal nerve palsy (HNP) can be caused by nerve damage from the central nerve to a peripheral nerve, and individuals with multiple factors could be predisposed to HNP. We report a case of isolated unilateral HNP after orthognathic surgery. CASE PRESENTATION: A 56-year-old Japanese woman complained of jaw distortion and malocclusion. She had undergone a Le Fort I osteotomy and bilateral sagittal split ramus osteotomy (BSSRO) under general anesthesia in August 2021. On postoperative day 3, she experienced tongue motility, and when the tongue protruded forward, the tongue tip shifted to the right, and swelling of the right lateral pharyngeal wall was observed. An additional blood test revealed increased antibody titer levels (40×), cytomegalovirus IgG EIA titer (16.9 U/mL), HSV-IgG EIA titer (40 U/mL), and EBV-viral capsid antigen (VCA) IgG EIA titer (1.4 U/mL). We administered valacyclovir hydrochloride 1000 mg/day for 7 days, prednisolone (PSL) 60 mg/day, mecobalamin 1500 µg/day, and adenosine triphosphate (ATP) disodium hydrate 300 mg/day. A neurological examination revealed no central lesions, and we continued the patient's tongue-function training and oral hygiene guidance. The tongue apex deviation was resolved approx. 3 months postoperatively. DISCUSSION: There are no major reports on the etiology of HNP after orthognathic surgery. The possibility of HNP triggered by endotracheal intubation or through packing gauze under general anesthesia and viral infection cannot be ruled out. CONCLUSION: Clinicians should be aware of the possibility of unilateral HNP following orthognathic surgery.
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BACKGROUND/AIM: The incidence and mortality rates of prostate cancer have been increasing worldwide. Although prostate cancer cells grow slowly in the local original site, once the cancer cells spread to distant organs they grow rapidly and show very aggressive features. Cortactin is a protein that regulates the actin cytoskeleton and plays crucial roles in cancer metastasis. Up-regulated cortactin is correlated with the metastatic capacity of prostate cancer cells. AHCC®, a standardized extract of cultured Lentinula edodes mycelia, has been previously reported to have cortactin-down-regulating effects on human pancreatic cancer cells. In the present study, the effects of AHCC® treatment on cortactin levels in prostate cancer cells was evaluated. MATERIALS AND METHODS: LNCaP.FGC, DU145, and PC-3 are human prostate cancer cell lines. LNCaP.FGC is well differentiated, androgen-dependent, and poorly metastatic. DU145 is less differentiated, androgen-independent, and moderate metastatic. PC-3 is less differentiated, androgen-independent, and highly metastatic. The effects of AHCC® treatment on cortactin levels in prostate cancer cells was evaluated by western blot. RESULTS: In vitro AHCC® treatment decreased cortactin levels in LNCaP.FGC and DU145 cells but did not change those in PC-3 cells. CONCLUSION: AHCC® treatment down-regulated cortactin expression in poor and moderate metastatic LNCaP.FGC and DU145 cells but showed no effect on cortactin expression in the highly metastatic PC-3 cells. Further studies are required to elucidate the mechanism of the resistance to AHCC® treatment in highly metastatic PC-3 cells.
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Neoplasias de la Próstata , Hongos Shiitake , Masculino , Humanos , Cortactina , Andrógenos , Neoplasias de la Próstata/tratamiento farmacológico , Extractos VegetalesRESUMEN
Fresh compact bone, the candidate graft material for bone regeneration, is usually grafted for horizontal bone augmentation. However, the dense calcified structure inhibits the release of growth factors and limits cellular and vascular perfusion. We aimed to create mechano-chemically altered dense skull bone by ultrasonic treatment, along with partial demineralization using commercially available acidic electrolyzed water (AEW). The parietal skull bone of an 11-month-old Wistar rat was exposed and continuously treated with a piezoelectric ultrasonic scaler tip for 1 min, using AEW (pH 2.3) or distilled water (DW, pH 5.6) as irrigants. Treated parietal bone was removed, cut into plates (5 × 5 × 1 mm3), grafted into the back subcutaneous tissues of syngeneic rats, and explanted at 1, 2, and 3 weeks. AEW bone showed an irregular surface, deep nano-microcracks, and decalcified areas. SEM-EDS revealed small amounts of residual calcium content in the AEW bone (0.03%) compared to the DW bone (0.86%). In the animal assay, the AEW bone induced bone at 2 weeks. Histomorphometric analysis showed that the area of new bone in the AEW bone at 2 and 3 weeks was significantly larger. This new combination technique of AEW-demineralization with ultrasonic treatment will improve the surface area and three-dimensional (3D) architecture of dense bone and accelerate new bone synthesis.
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INTRODUCTION: Vertical maxillary excess, a common orthodontic problem that leads to long faces and open bites, can be repositioned with a Le Fort I osteotomy. However, the Le Fort I osteotomy poses the risk of a variety of complications including descending palatine artery (DPA) injury. Although several Le Fort I osteotomy modifications were reported to avoid complications associated with this osteotomy, only a few of such studies were conducted in Japan, and details remain scarce. PATIENTS AND METHODS: We performed a literature review regarding modifications of Le Fort I osteotomies, including Le Fort I with a horseshoe osteotomy, modified horseshoe osteotomy, unilateral horseshoe osteotomy, pyramidal osteotomy, and U-shaped osteotomy. We identified eight relevant studies conducted in Japan; one study did not provide the number of patients examined. The 77 patients (seven studies) with vertical maxillary excess who underwent orthognathic surgery were ≥17 years old. DISCUSSION: There were no severe complications after the modified Le Fort I osteotomies. The postoperative maxillary changes obtained by the conventional horseshoe, modified horseshoe, unilateral type of horseshoe, pyramidal, and U-shaped osteotomies were nearly repositioned to the planned position and remained stable for ≥12 months post-surgery. CONCLUSION: Our review indicates that preserving the DPA can lower the incidence of intra- and post-operative complications. Each modification of the Le Fort I osteotomy (i.e., conventional horseshoe, modified horseshoe, unilateral horseshoe, pyramidal, and U-shaped osteotomy) has its respective advantages and indications.
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BACKGROUND: Clavicle fractures (CF) after radical neck dissection (RND) for oral cancer are rare but are thought to occur as a result of myotonia and decreased blood supply to the muscles around the clavicle after RND. The current report presents a rare case of a non-neoplastic pathological CF after RND, and discusses the role of imaging examinations for the timely detection of CF. CASE REPORT: An 82-year-old Japanese man underwent RND followed by chemotherapy without radiotherapy for secondary metastasis of the right cervical lymph node after resection of tongue cancer. Computed tomography at 6 months after RND revealed a fracture with bone destruction in the proximal end of the right clavicle. He had no history of trauma at the site of the fracture and no symptoms. The possibility of bone metastasis of the clavicle was considered; however, the bone destruction had not advanced 6 years after the discovery of the fracture. The CF was thus finally considered to be a side effect of RND, rather than metastasis. CONCLUSION: CF is a rare complication following treatment for head and neck cancer but can be caused by neck dissection. Regular imaging examinations, including the clavicular region, are therefore needed before and after surgery to ensure the timely detection of CF.
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Disección del Cuello , Neoplasias de la Lengua , Anciano de 80 o más Años , Clavícula/diagnóstico por imagen , Humanos , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/cirugía , Metástasis Linfática , Masculino , Neoplasias de la Lengua/diagnóstico por imagen , Neoplasias de la Lengua/tratamiento farmacológico , Neoplasias de la Lengua/cirugíaRESUMEN
BACKGROUND/AIM: Cancer is the most fatal disease worldwide whose most lethal characteristics are invasion and metastasis. Hepatocellular carcinoma (HCC) is one of the most fatal cancers worldwide. HCC often shows encapsulation, which is related to better prognosis. In this study, proteomic analysis of HCC tissues with and without encapsulation was performed, in order to elucidate the factors which play important roles in encapsulation. MATERIALS AND METHODS: Five HCC tissues surrounded by a capsule and five HCC tissues which broke the capsule were obtained from patients diagnosed with HCC who underwent surgical liver resection. Protein samples from these tissues were separated by two-dimensional gel electrophoresis (2-DE), and the protein spots whose expression was different between encapsulated and non-encapsulated HCC tissues were identified through gel imaging analysis software. The selected protein spots were analyzed and identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: Two-DE analysis showed 14 spots whose expression was different between encapsulated and non-encapsulated HCC tissues. Of these, 9 were up-regulated and 5 were down-regulated in HCC tissues without encapsulation. The validation by Western blot confirmed that leucine aminopeptidase 3 (LAP3) and phosphoenolpyruvate carboxykinase mitochondrial (PCK2) were up-regulated significantly in HCC tissues with a capsule, compared to HCC tissues that broke the capsule. CONCLUSION: These findings suggest that LAP3 and PCK2 could be factors responsible for the maintenance of encapsulation in HCC tissues.
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Carcinoma Hepatocelular/metabolismo , Leucil Aminopeptidasa/metabolismo , Neoplasias Hepáticas/metabolismo , Fosfoenolpiruvato Carboxiquinasa (ATP)/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Femenino , Humanos , Leucil Aminopeptidasa/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Masculino , Fosfoenolpiruvato Carboxiquinasa (ATP)/genética , Pronóstico , Proteómica , Regulación hacia ArribaRESUMEN
We reported an extremely rare case regarding intraosseous clear cell variant of mucoepidermoid carcinoma in maxilla.
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AHCC®, a standardized extract of cultured Lentinula edodes mycelia, enhances the therapeutic effects and reduces the adverse effects of chemotherapy. Our previous study reported that treatment with AHCC® downregulated the expression levels of tumor-associated proteins in the gemcitabine-resistant pancreatic cancer cell line, KLM1-R. However, to the best of our knowledge, the role of AHCC® in the inhibition of cell migration remains unexplored. Cortactin (CTTN), an actin nucleation-promoting factor, has been reported to be upregulated and correlated with migration, invasion and metastasis in pancreatic cancer cells. The present study aimed to investigate the effects of AHCC® on cell migration and the protein expression level of CTTN in KLM1-R cells. The Gene Expression Profiling Interactive Analysis (GEPIA2), an online bioinformatics platform, was used to analyze CTTN mRNA expression levels in pancreatic cancer tissues compared with normal pancreatic tissues. CTTN mRNA expression and its association with clinicopathological characteristics were assessed by using the GEPIA2 platform. Next, the effects of AHCC® on KLM1-R cell migration were investigated by in vitro wound-healing assay. The KLM1-R cells were treated with AHCC® at a concentration of 10 mg/ml for 48 h. Western blotting was performed on of cell lysates with anti-CTTN or anti-actin antibodies to assess the protein expression levels of CTTN. Bioinformatics analysis indicated that the mRNA expression level of CTTN increased in pancreatic cancer tissues. The increased mRNA expression levels of CTTN were inversely associated with clinicopathological characteristics, including disease stages and prolonged patient survival times. The administration of 10 mg/ml AHCC® significantly inhibited KLM1-R cells migration compared with controls. The protein expression levels of CTTN were significantly reduced in AHCC®-treated KLM1-R cells, whereas actin expression was not affected. The downregulation of CTTN indicated the anti-metastatic potential of AHCC® in pancreatic cancer cells. Overall, AHCC® may have the potential to be a complementary and alternative therapeutic approach in treating pancreatic cancer.
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INTRODUCTION: Mucoceles are mucous extravasation phenomena resulting from spontaneous ductal rupture or, less commonly, a traumatic cutting of a salivary excretory duct. Occasionally, the appearance of a mucocele closely resembles a neoplastic lesion, and it can be difficult to diagnose. PRESENTATION OF CASE: A 74-year-old Japanese male patient was referred to our clinic with painless swelling related to the upper right canine-premolar area. Preoperative imaging of the lesion revealed that it was fluid-filled and the histopathological biopsy suggested a myxoid tumor. We excised the lesion with the patient under general anesthesia, using safety margins based on the histology of the biopsy specimen to reach the definitive diagnosis and treatment. The final pathological diagnosis was a mucocele in the vicinity with an aberrant small salivary gland. Follow-up visits showed complete healing of the epithelium, and no recurrence has been observed during the subsequent 30 months. DISCUSSION: In cases with a difficult definitive diagnosis based on medical history, diagnostic imaging and pathological examination, it is important to proceed carefully with the possibility of a tumor in mind. CONCLUSION: This case emphasizes that some mucous cysts are challenging for clinicians in terms of diagnosis and treatment due to an uncommon presentation.
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INTRODUCTION: Masticatory muscle tendon-aponeurosis hyperplasia (MMTAH) is a new clinical entity that presents mainly with trismus due to hyperplasia of the masseter aponeurosis and temporalis muscle tendon. However, the etiological factors of this disease are unknown; it is often mistreated as temporomandibular joint disorder (TMD). PRESENTATION OF CASE: We report a 32-year-old female patient complaining of bilateral pain in her jaw and difficulty opening her mouth. She was first diagnosed as TMD and treated with a splint; however, her symptoms did not improve. Clinical examination revealed a square mandible, tenderness in the left and right temporalis muscles and masseter muscles, and tenderness along the anterior border of the masseter muscle. Her maximum mouth-opening was 30 mm. Short TI inversion recovery magnetic resonance imaging showed areas of low intensity at the anterior border of the masseter muscle and around the coronoid process where the temporalis muscle tendon attaches. Consequently, the diagnosis made based on the clinical and radiographic findings was MMTAH. Bilateral coronoidectomy was performed, followed by a rehabilitation program for six months. The maximum opening was maintained at 48 mm two years after the operation. DISCUSSION: MMTAH was treated as type 1 TMD until it was recognized as a new disease at the conference for the Japanese Society for Oral and Maxillofacial Surgeons. Since then, many clinicians have become aware of this particular condition, and different treatment modalities have been proposed. CONCLUSION: Clinicians should consider MMTAH as a differential diagnosis when the patient's chief complaint is gradually decreasing mouth-opening.
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BACKGROUND: Bee pollen (BP) has a broad range of beneficial effects on health. The aim of this study was to examine the effect of BP on the oral environment, including the microbiome and antimicrobial peptides. METHODS: C57BL/6J mice were randomly divided into two groups: control and BP. The BP group was fed with a 5% BP diet for 1 month. Swabs from the oral and buccal mucosa and samples of the intestinal stool were collected. Genomic DNA was extracted and the microbiome was analyzed via 16S rRNA sequencing. RESULTS: BP inhibited the growth of P. gingivalis at a concentration of >2.5%. The metagenomic study showed that the abundance of genus Lactococcus was significantly elevated in the oral and intestinal microbiomes of the BP group when compared to those of the control group. Significant alterations in alpha and beta diversity were observed between the oral microbiomes of the two groups. The mRNA levels of beta-defensin-2 and -3 were significantly upregulated in the buccal mucosa of the BP group. CONCLUSION: A BP diet may have a beneficial effect on oral and systemic health by modulating the bacterial flora and antimicrobial peptides of the oral cavity. Further investigations are needed to clarify how a BP diet affects overall human health.
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BACKGROUND: Betel quid chewing is known as a crucial risk factor for oral diseases such as periodontal diseases, oral cancer, and precancerous lesions in Southeast Asian countries. Although abnormal oral bacterial flora may be linked to betel quid related-oral diseases such as oral cancer, precancerous lesions, and periodontal diseases, little information is available on alterations of their oral flora thus far. To identify these alterations, we analyzed the oral flora in betel quid chewers (BQC) and non-chewers (NC) in Sri Lanka. METHODS: Samples obtained from buccal swabs of BQC and NC were analyzed with a next generation sequencer. Data were processed and analyzed using the QIIME software package. Mann-Whitney U test and Permutational multivariate analysis of variance were used for statistical analyses. P values < 0.05 were considered to be statistically significant. RESULTS: In BQC, the proportion of periodontal pathogens including Actinomyces, Tannerella, and Prevotella was higher than that in NC (P < 0.05), while the proportion of cariogenic pathogens including Streptococcus, Lautropia, and Actinobacillus was lower than that in NC (P < 0.05). A statistically significant difference in Shannon index and PD Whole tree was observed between BQC and NC (P < 0.05). PCoA analysis detected different clusters in BQC and NC (P < 0.05). CONCLUSION: The results suggested that betel quid chewing significantly altered oral flora. Adequate oral health care may help prevent BQC from developing bacterial pathogen-related oral diseases.
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Areca/efectos adversos , Boca/microbiología , Adulto , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Análisis por Conglomerados , ADN Bacteriano/genética , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Masculino , Enfermedades Periodontales/microbiología , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Sri LankaRESUMEN
INTRODUCTION: Temporomandibular disorders (TMD) are diseases of the temporomandibular joint and masticatory muscles, and are often difficult to be diagnosed because they have various symptoms, pathological conditions and causes. PRESENTATION OF CASE: Herein, we report a 78-year-old male referred to our hospital with a diagnosis of TMD and presenting with facial asymmetry, marked deviation to the right side on vertical mandibular movement and complaints of abnormal perception at the right oral and buccal region. Past medical history revealed that he had undergone a right intracranial trigeminal schwannoma resection 9 years prior. Computed tomography (CT) showed disuse atrophy of the right side of 4 masticatory muscles and 2 suprahyoid muscles controlled by the motor component of the mandibular division (V3) of the trigeminal nerve (TGN). Together with the neurosurgeon, we confirmed that there was no recurrence of the tumor and explained to the patient that the oral and maxillofacial symptoms are after-effects of the operation, and we provided oral hygiene instructions and coordinated cleaning of the inside of the oral cavity. DISCUSSION: Although it is difficult to compare treatment methods from case to case, we believe that in our case, the patient's understanding of the cause of his discomfort contributed significantly to the improvement of his quality of life. CONCLUSION: We experienced a case of masticatory muscle disuse atrophy during long-term follow-up after resection of intracranial trigeminal schwannoma. Further studies are needed to develop the diagnostic and therapeutic protocols for disuse atrophy.
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BACKGROUND: DNA hypermethylation of tumor suppressor genes is observed in precancerous lesions and oral cancer of individuals with the habits of betel quid (BQ) chewing. SIRT1 has been identified as playing a role in the maintenance of epithelial integrity, and its alteration is often related to carcinogenesis. However, the methylation and transcription status of SIRT1 in patients with BQ chewing-related oral cancer has not been investigated. We examined the methylation status of SIRT1 in paraffin-embedded tissue samples of oral squamous cell carcinoma (OSCC) obtained from BQ chewing and non-chewing patients and in tissue samples from healthy control subjects. In addition, we examined whether the hypermethylation of SIRT1 followed by its transcriptional downregulation in the human gingival epithelial cells could be caused by arecoline, a major component of BQ. Furthermore, we investigated the methylation status of SIRT1 in smear samples of macroscopically healthy buccal mucosa from subjects with a habit of BQ chewing. RESULTS: SIRT1 was significantly hypermethylated in tissue samples of OSCC from BQ chewers and non-chewers than in oral mucosa from healthy control subjects. Results also showed that the hypermethylation level of SIRT1 was significantly higher in OSCC of patients with BQ chewing habits than in those of non-chewing habits (p < 0.05). Our in vitro model showed that hypermethylation is followed by downregulation of the transcriptional level of SIRT1 (p < 0.05). The methylation levels of SIRT1 in the smear samples obtained from BQ chewing individuals were significantly higher than those in the samples obtained from individuals that did not chew BQ. The duration of BQ chewing habits was correlated positively to the frequency of SIRT1 hypermethylation (p < 0.05). CONCLUSIONS: Our results suggest that DNA hypermethylation of SIRT1 is involved in the occurrence of oral cancer in BQ chewing patients and that hypermethylation in the oral mucosa of BQ chewers could be a predictive marker for the occurrence of malignant transformation. This is the first report that showed DNA hypermethylation in clinically healthy oral epithelium of BQ chewers. Our study shows evidence that DNA hypermethylation may be an early event of oral carcinogenesis prior to observable clinical changes.
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Areca/efectos adversos , Arecolina/genética , Carcinoma de Células Escamosas/genética , Metilación de ADN/genética , Sirtuina 1/genética , Adulto , Anciano , Biomarcadores , Estudios de Casos y Controles , Transformación Celular Neoplásica/genética , Células Epiteliales/metabolismo , Femenino , Regulación de la Expresión Génica/genética , Humanos , Masculino , Masticación/fisiología , Persona de Mediana Edad , Mucosa Bucal/patología , Neoplasias de la Boca/patología , Valor Predictivo de las PruebasRESUMEN
Secretory carcinoma (SC) of the salivary gland was recently added to the fourth edition of the World Health Organization classification of head and neck tumors. Some salivary tumors, including acinic cell carcinoma, have been reclassified as SC. Most of these tumors are located on the parotid gland with very few cases reported in the minor salivary glands of the buccal mucosa. Herein, we present a case of SC of buccal mucosa, which appeared clinically as a benign lesion in a 54-year-old Japanese female patient. Histopathologically, the tumor cells presented with an eosinophilic cytoplasm with microcytic structure along with eosinophilic secretory material and hemosiderin deposit. Immunohistochemical staining revealed strongly positive staining for S100, vimentin, and mammaglobin and negative staining for DOG-1. The tumor was finally diagnosed as secretory carcinoma of the buccal mucosa. We present a review of the medical literature of SC arising from minor salivary glands. We found only 15 cases of SC of buccal mucosa out of 63 cases of SC in the minor salivary glands. They showed good prognoses and only one case of SC in the buccal mucosa exhibited local recurrence and lymph node metastases.
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BACKGROUND: Oral squamous cell carcinoma and the most common oral pre-malignancies appear to be related to the habit of betel-quid chewing in Sri Lanka. Although hypermethylation of the tumour suppressor genes in oral cancer have been well documented, little information has been available concerning hypermethylation in oral pre-cancerous lesions. In the present study, we investigated the hypermethylation of p14, p15 and p16 in pre-cancerous lesions including epithelial dysplasia and submucous fibrosis. METHODS: All samples were obtained from patients with a betel-quid chewing habit in Sri Lanka. Sixty-four patients were clinically diagnosed with leukoplakia, and histopathologically diagnosed with mild or severe dysplasia. Ten patients were diagnosed with submucous fibrosis without epithelial dysplasia. CpG island hypermethylation was assessed by a methylation-specific PCR method. Immunohistochemical staining was performed using anti-p53 antibodies. RESULTS: A high frequency of hypermethylation of p14, p15 and p16 was detected in the pre-cancerous lesions, although no hypermethylation was found in normal epithelium. The frequency of hypermethylation was higher than that of positive staining for p53 mutation except in the case of p16 in mild dysplasia. No significant correlation was observed between p53-positive reactions and hypermethylation in any lesions. The hypermethylation was highly detectable even in p53-negative lesions, suggesting that hypermethylation of p14, p15 and p16 occur regardless of whether the lesions have p53 mutations or not. CONCLUSIONS: The present study indicates that hypermethylation may be involved in the pathogenesis of oral pre-cancerous lesions associated with betel-quid chewing in Sri Lanka.
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Areca/efectos adversos , Inhibidor p15 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Metilación de ADN/genética , Neoplasias de la Boca/patología , Lesiones Precancerosas/patología , Proteína p14ARF Supresora de Tumor/genética , Alelos , Islas de CpG/genética , Citosina/metabolismo , Epitelio/patología , Genes p16 , Genes p53/genética , Humanos , Leucoplasia Bucal/genética , Leucoplasia Bucal/patología , Neoplasias de la Boca/genética , Mutación/genética , Fibrosis de la Submucosa Bucal/genética , Fibrosis de la Submucosa Bucal/patología , Lesiones Precancerosas/genética , Sri Lanka , Proteína p53 Supresora de Tumor/genética , Uracilo/metabolismoRESUMEN
BACKGROUND/AIM: We have previously reported that treatment of pancreatic cancer cells with active hexose-correlated compound (AHCC), an extract of a basidiomycete mushroom, decreases the levels of tumor-associated proteins including heat-shock protein 27 (HSP27), heat shock factor 1 (HSF1) and sex-determining region Y-box 2 (SOX2). The transmembrane glycoprotein, CUB domain-containing protein 1 (CDCP1) has been reported to be up-regulated in various cancers, and be associated with invasion and metastasis. The aim of this study was to examine the effect of AHCC on the expression of CDCP1 in KLM1-R cells. MATERIALS AND METHODS: Gemcitabine-resistant pancreatic cancer cells (KLM1-R) were treated with AHCC (10 mg/ml) for 48 h. Western blot analysis of cell extracts with anti-CDCP1 or anti-actin antibodies was performed to assess the expression of CDCP1. RESULTS: Expression of CDCP1 was reduced by AHCC treatment of KLM1-R cells, whereas expression of actin was not affected. The ratio of intensities of CDCP1/actin in AHCC-treated KLM1-R cells was significantly suppressed (p<0.05) compared to untreated cells. CONCLUSION: AHCC down-regulated CDCP1 expression and inhibited the malignant progression of pancreatic cancer cells.
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Antígenos CD/biosíntesis , Moléculas de Adhesión Celular/biosíntesis , Proteínas de Neoplasias/biosíntesis , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/metabolismo , Polisacáridos/farmacología , Actinas/biosíntesis , Antígenos de Neoplasias , Western Blotting , Línea Celular Tumoral , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Regulación hacia Abajo/efectos de los fármacos , Resistencia a Antineoplásicos , Humanos , GemcitabinaRESUMEN
Betel quid chewing is implicated in the high prevalence of oral cancer in Southeast Asian countries. One of the major components of betel quid is arecoline. In the present study, in order to characterize the association between chronic arecoline stimulation and carcinogenesis the expression level of matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 mRNA in human gingival epithelial progenitor cells (HGEPs) stimulated with arecoline was assessed. The HGEPs were alternated between 3 days of incubation with arecoline (50 µg/ml), and 3 days without arecoline, for up to 30 days. The expression levels of the MMPs and TIMPs in the cells stimulated with arecoline were evaluated by reverse transcription-quantitative polymerase chain reaction at 18 and 30 days. The expression of MMP-9 mRNA in the experimental group was significantly increased compared with in the control group (P<0.01). No significant differences in the expression of MMP-2, TIMP-1 or TIMP-2 mRNA were observed between the experimental and control groups. Using an MMP-9 activity assay, the levels of MMP-9 activity in the experimental group were demonstrated to be significantly higher than in the control group (P<0.05). To investigate associated cellular signaling pathways, PDTC [a nuclear factor (NF)-κB/inhibitor of NF-κB (IκB) inhibitor], PD98059 [a mitogen-activated protein kinase kinase (MAPKK)1 and MAPKK2 inhibitor], SB203580 (a p38 MAPK inhibitor) and 5,15-DPP [a signal transduction and activator of transcription (STAT) 3 inhibitor] were used. All inhibitors decreased the extent of MMP-9 upregulation induced by stimulation with arecoline. Based on the data, it is hypothesized that MMP-9 activity may be involved in the pathological alterations of oral epithelium induced by betel quid chewing, and that the NF-κB/IκB, MAPK, p38 MAPK and STAT3 signaling pathways may be involved in the production of MMP-9 induced by betel quid chewing.