RESUMO
Ghost cell odontogenic carcinoma (GCOC) is an extremely rare intraosseous malignant odontogenic tumor with prominent ghost cell keratinization and dentinoid formation. Here, we present the first case of GCOC arising in dentinogenic ghost cell tumor (DGCT), peripheral. The patient was a man in his 60s with an exophytic mass in the anterior part of lower gingiva. The resected tumor measured 4.5 cm in maximum diameter. Histologically, the nonencapsulated tumor proliferated in the gingiva without bone invasion. It was predominantly composed of ameloblastoma-like nests and islands of basaloid cells with ghost cells and dentinoid in the mature connective tissue, suggesting DGCT, peripheral. As minor components, sheets of atypical basaloid cells and ameloblastic carcinoma-like nests with pleomorphism and high proliferative activity (Ki-67 labeling index up to 40%) consistent with malignancy were identified. CTNNB1 mutation and ß-catenin nuclear translocation were observed in both benign and malignant components. Final diagnosis was GCOC arising in DGCT, peripheral. GCOC shows similar histological features to DGCT. In this unique case without invasion, the cytological atypia and high proliferative activity supports the diagnosis of malignant transformation from DGCT.
Assuntos
Ameloblastoma , Carcinoma , Neoplasias Maxilomandibulares , Tumores Odontogênicos , Masculino , Humanos , Tumores Odontogênicos/patologia , Transformação Celular Neoplásica/patologiaRESUMO
BACKGROUND: Polymorphous adenocarcinoma is a common intraoral minor salivary gland carcinoma in Western countries but is extremely rare in Japan. The current study aimed to characterize the clinicopathological features and status of molecular alterations of polymorphous adenocarcinoma-associated genes, such as PRKD1/2/3, ARID1A, and DDX3X, in a large cohort of Japanese patients with polymorphous adenocarcinoma. METHODS: We examined the cases of 36 Japanese patients with salivary gland polymorphous adenocarcinoma and 26 cases involving histopathological mimics. To detect gene splits, fluorescence in situ hybridization was carried out for polymorphous adenocarcinoma-associated genes. Additionally, we applied a SNaPshot multiplex assay to identify PRKD1 hotspot mutations. RESULTS: This study revealed the indolent clinical course of polymorphous adenocarcinoma with a high 10-year overall survival rate (92.9%), accompanied by occasional local recurrences and cervical lymph node metastasis (23.3%). Twenty cases (55.6%) of polymorphous adenocarcinoma (but none of the mimics) exhibited alterations in at least one polymorphous adenocarcinoma-associated gene. Rearrangement of polymorphous adenocarcinoma-associated genes and PRKD1 E710D were identified in 17 (47.2%) and 4 (11.1%) cases, respectively; one case showed coexisting PRKD3 split and PRKD1 E710D. In the multivariate analysis, high clinical stage (p = 0.0005), the presence of prominent nucleoli (p = 0.0003), and ARID1A split positivity (p = 0.004) were independent risk factors for disease-free survival. CONCLUSION: Japanese patients with polymorphous adenocarcinoma showed clinicopathological features similar to those reported in Western countries. This study disclosed that polymorphous adenocarcinoma-associated genetic alterations were common and specific findings in polymorphous adenocarcinomas. The diagnostic role and possible prognostic significance of polymorphous adenocarcinoma-associated genetic alterations in polymorphous adenocarcinomas were suggested.
Assuntos
Adenocarcinoma , Neoplasias das Glândulas Salivares , Adenocarcinoma/patologia , Biomarcadores Tumorais/genética , Humanos , Hibridização in Situ Fluorescente , Japão , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares/patologiaRESUMO
Non-sebaceous lymphadenoma is a rare benign salivary gland tumor comprised of non-sebaceous epithelial cells and lymphoid tissue. Although its clinicopathological features have been described, its histogenesis and genetic background have not yet been elucidated. MAML2 rearrangement and the resultant CRTC1/3-MAML2 fusion gene are well-known specific genetic changes in mucoepidermoid carcinoma. Here, we present a case of lymphoepithelial tumor characterized by histomorphology of the non-sebaceous lymphadenoma and CRTC1-MAML2 fusion gene. The patient was an 83-year-old woman with an 8-year history of a solid, well-circumscribed tumor in the parotid gland. Histologically, the tumor was surrounded by thin fibrous connective tissue and was composed of tubular-cystic and solid nests of epithelial cells equally distributed in the lymphoid tissue. The histological features were suggestive of non-sebaceous lymphadenoma. Although the histomorphology was not consistent with mucoepidermoid carcinoma, a diagnosis of non-sebaceous lymphadenoma-like mucoepidermoid carcinoma was made based on the presence of the CRTC1-MAML2 fusion gene. The histological features alone could not establish the diagnosis, and ancillary molecular analysis was required.
Assuntos
Carcinoma Mucoepidermoide , Neoplasias das Glândulas Salivares , Idoso de 80 Anos ou mais , Carcinoma Mucoepidermoide/diagnóstico , Carcinoma Mucoepidermoide/genética , Carcinoma Mucoepidermoide/patologia , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Proteínas Nucleares/genética , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologia , Transativadores/genéticaRESUMO
Inverted ductal papilloma (IDP) is one of the least common benign papillary/cystic neoplasms of the salivary duct system, being characterized histologically by florid hyperplasia of duct-type epithelial cells into a cystic lumen near the orifice with occasional endophytic growth of the surface squamous epithelium along the terminus of the affected excretory duct. Given its rarity, the exact etiology of IDP remains to be defined. We herein present the first evidence of oncogenic HRAS mutation in a case of oral IDP. This finding, together with the frequent and specific BRAF mutations in sialadenoma papilliferum reported in the recent literature, supports an active role of the MAP-kinase cascade in the pathogenesis of benign papillary neoplasms of terminal duct origin.
Assuntos
Biomarcadores Tumorais/genética , Papiloma Invertido/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Neoplasias das Glândulas Salivares/genética , Idoso de 80 Anos ou mais , Feminino , Humanos , Mutação , Papiloma Invertido/diagnóstico , Papiloma Invertido/patologia , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/patologiaRESUMO
Diagnostic utility of a homeobox transcription factor, engrailed homeobox 1 (En1) in the histopathology of salivary gland neoplasms was studied. The expression of En1 was immunohistochemically examined in 51 cases of adenoid cystic carcinoma (AdCC) and 143 cases of other salivary gland neoplasms. In all 51 AdCCs, En1 was expressed in 30-100% of tumor cells. In eight of nine polymorphous adenocarcinomas (PACs), En1 was expressed in 40-100% of tumor cells. Less than 5% of tumor cells expressed En1 in three of 12 epithelial-myoepithelial carcinomas, one of 17 basal cell adenomas (BCAs), and one of 34 pleomorphic adenomas (PAs). Among 55 other carcinoma cases, 1-30% of tumor cells expressed En1 in three salivary duct carcinomas (SDCs) ex PA. None of the myoepitheliomas and Warthin tumors expressed En1. When the cut-off value of the percentage of En1-expressing cells was set to 25%, all 51 AdCCs, eight of nine PACs and one SDC ex PA were En1-positive and the others were En1-negative. En1 is expressed consistently in AdCCs, frequently in PACs, but rarely in other salivary gland neoplasms. En1 is a possible diagnostic marker for AdCC and PAC in the histopathology of salivary gland neoplasms.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Adenoide Cístico/diagnóstico , Proteínas de Homeodomínio/metabolismo , Neoplasias das Glândulas Salivares/diagnóstico , Adenoma/diagnóstico , Adenoma/metabolismo , Adenoma/patologia , Adenoma Pleomorfo/diagnóstico , Adenoma Pleomorfo/metabolismo , Adenoma Pleomorfo/patologia , Carcinoma Adenoide Cístico/metabolismo , Carcinoma Adenoide Cístico/patologia , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Curva ROC , Neoplasias das Glândulas Salivares/metabolismo , Neoplasias das Glândulas Salivares/patologia , Sensibilidade e EspecificidadeRESUMO
AIMS: Minor salivary gland tumours showing a predominant papillary-cystic structure are rare, and constitute a mixture of various types of neoplasm; thus, the histopathological assessment of these tumours poses a significant diagnostic challenge. We aimed to delineate the histological characteristics of these tumours and further mutational aspects with a particular focus on sialadenoma papilliferum (SP) and intraductal papillary mucinous neoplasm (IPMN). METHODS AND RESULTS: We retrieved 28 papillary-cystic tumours of the minor salivary glands, and performed histological re-evaluation and mutation analyses of several key oncogenes. The histological classifications were as follows: SP (n = 10), SP-like intraductal papillary tumour (SP-IPT) (n = 2), IPMN (n = 9), intraductal papilloma, cystadenoma, and cystadenocarcinoma (two, three and two respectively). Whereas SP typically consisted of a combination of exophytic squamous epithelium and endophytic intraductal papillary infoldings, SP-IPT lacked the exophytic component. SP and SP-IPT frequently harboured BRAF V600E mutations (75.0%), which were identified in both squamous and ductal components. IPMN was characterised by a well-demarcated cystic lesion filled exclusively with a papillary proliferation of mucinous cells and a high rate of AKT1 E17K mutations (88.9%). Intraductal papillomas were unilocular cystic lesions with intraluminal papillary growth of bland columnar cells. In contrast, both cystadenomas and cystadenocarcinomas showed a multicystic appearance with a papillary configuration. Cystadenocarcinomas invaded the surrounding tissue and were composed of markedly atypical tumour cells. CONCLUSION: The appropriate interpretation of histological findings and specific genetic alterations (e.g. BRAF V600E and AKT1 E17K in SP and IPMN) would be useful for the correct diagnosis of minor salivary gland papillary-cystic tumours.
Assuntos
Cistadenocarcinoma/genética , Cistadenoma/genética , Papiloma Intraductal/genética , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas c-akt/genética , Neoplasias das Glândulas Salivares/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Substituição de Aminoácidos , Cistadenocarcinoma/classificação , Cistadenocarcinoma/diagnóstico , Cistadenocarcinoma/patologia , Cistadenoma/classificação , Cistadenoma/diagnóstico , Cistadenoma/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Mutação , Papiloma Intraductal/classificação , Papiloma Intraductal/diagnóstico , Papiloma Intraductal/patologia , Neoplasias das Glândulas Salivares/classificação , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares Menores/patologiaRESUMO
This study investigated a method using loop-mediated isothermal amplification (LAMP) for the rapid detection of cnm-positive Streptococcus mutans (S. mutans) associated with cerebral microhemorrhage. LAMP amplified the cnm gene plasmid vector, but not human or microbial genomic DNA. The cnm DNA of the cnm-positive S. mutans strain was detected in saliva without DNA extraction after 1 day of culture. This method resulted in a cnm-positive rate of 26.4% in 102 samples, which was higher than that obtained with conventional PCR. In conclusion, LAMP may be used for the detection of cnm-positive S. mutans in a large number of samples.
Assuntos
Adesinas Bacterianas/análise , Proteínas de Transporte/análise , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Saliva/microbiologia , Streptococcus mutans/isolamento & purificação , HumanosRESUMO
Liposarcoma (LS) is the most common soft-tissue sarcoma. Dedifferentiated liposarcoma (DDLS) shows more aggressive biological behavior than that of well-differentiated liposarcoma (WDLS), so advanced therapeutic agents based on molecular mechanism are urgently needed. Here we show that tissue inhibitors of metalloproteinases (TIMPs) from TIMP-1 to TIMP-4 are differently expressed and regulate yes-associated protein (YAP)/transcriptional co-activator with PDZ binding motif (TAZ) in LS. Database analysis showed high TIMP-1 expression in DDLS patients correlating with poor prognosis, but high TIMP-4 expression in WDLS patients with better prognosis. Stable TIMP-1 knockdown inactivated YAP/TAZ and inhibited proliferation, colony formation and migration in DDLS cells, which was rescued by a constitutive active YAP. However, stable overexpression of TIMP-1 showed the opposite in WDLS cells. Stable TIMP-4 knockdown activated YAP/TAZ and promoted proliferation and migration in WDLS cells, which was suppressed by YAP/TAZ inhibitor (verteporfin) or knockdown of YAP/TAZ. Recombinant TIMP-4 showed opposite results in DDLS cells. These results indicate that dedifferentiation in LS shifts the expression of TIMPs from type 4 to type 1, inducing more aggressive behavior and poor prognosis through YAP/TAZ activation, which can be prognostic markers and therapeutic targets for LS patients.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Biomarcadores Tumorais/metabolismo , Lipossarcoma/mortalidade , Recidiva Local de Neoplasia/mortalidade , Inibidor Tecidual de Metaloproteinase-1/metabolismo , Inibidores Teciduais de Metaloproteinases/metabolismo , Fatores de Transcrição/metabolismo , Aciltransferases , Proteínas Adaptadoras de Transdução de Sinal/genética , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Lipossarcoma/metabolismo , Lipossarcoma/patologia , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Prognóstico , Transdução de Sinais , Taxa de Sobrevida , Inibidor Tecidual de Metaloproteinase-1/genética , Inibidores Teciduais de Metaloproteinases/genética , Fatores de Transcrição/genética , Células Tumorais Cultivadas , Proteínas de Sinalização YAP , Inibidor Tecidual 4 de MetaloproteinaseRESUMO
OBJECTIVE: This study aimed to assess the frequency of KRAS mutation and its association with the presence of the MAPK/ERK signaling pathway proteins in adenomatoid odontogenic tumors. STUDY DESIGN: Paraffin-embedded tissue samples from nine cases of adenomatoid odontogenic tumor were used. Genomic DNA was extracted from each sample; in one case, genetic mutations in 50 cancer-associated genes were examined by next-generation sequencing. Hotspot mutations in the RAS family were analyzed by Luminex assay using the remaining eight cases. Subsequently, immunohistochemistry for KRAS, CRAF, BRAF, EGFR, ERK, MEK, and BRAFV600E was performed. RESULTS: A KRAS G12D missense mutation was detected in the DNA sequence of the tumor cells, but it was not detected in the stromal tissue. KRAS G12V and KRAS G12R mutations were detected in two and four cases, respectively. For immunohistochemistry, all the cases were EGFR, KRAS, BRAF, CRAF positive, one case was ERK negative,and one case was MEK and ERK negative, all the other remaining cases were MEK and ERK positive. CONCLUSION: KRAS mutation at codon 12 and the presence of MAPK/ERK pathway proteins were detected suggesting their association with tumorigenesis of adenomatoid odontogenic tumors.
Assuntos
Ameloblastoma/genética , Ameloblastoma/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Adolescente , Adulto , Criança , Pré-Escolar , Receptores ErbB/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas B-raf/metabolismo , Proteínas Proto-Oncogênicas c-raf/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Adulto JovemRESUMO
Central mucoepidermoid carcinoma (MEC) poses a diagnostic challenge because of its rarity and histological overlap with glandular odontogenic cyst (GOC). In MEC of both salivary glands and jaws, MAML2 arrangement has been well known as the specific gene alteration. We report a case of central MEC arising from GOC diagnosed by MAML2 fusion gene. A 57-year-old male presented a multilocular cystic lesion in left molar region of the mandible. Histopathologically, multiple cysts lined by thin cuboidal or non-keratinized squamous epithelium with small duct-like structures, mucous cells and ciliated cells were present. It was diagnosed as GOC. The recurrent lesion after nine years showed the proliferation of many cystic and solid nests composed of epidermoid, mucous and intermediated cells. Nested PCR revealed CRTC3-MAML2 fusion gene in the recurrent lesion, but not in the primary one. Similarly, MAML-2 rearrangement by FISH analysis was positive in the recurrent lesion, while negative for the primary one, thus confirming the diagnosis of central MEC arising from GOC. Analysis of MAML2 rearrangement can be used as a supportive evidence to distinguish central MEC from GOC.
Assuntos
Carcinoma Mucoepidermoide/patologia , Neoplasias Mandibulares/patologia , Cistos Odontogênicos/patologia , Carcinoma Mucoepidermoide/genética , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/patologia , Proteínas de Ligação a DNA/genética , Humanos , Masculino , Doenças Mandibulares/patologia , Neoplasias Mandibulares/genética , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Transativadores , Fatores de Transcrição/genéticaRESUMO
OBJECTIVE: Primordial odontogenic tumour (POT) is a rare benign mixed epithelial and mesenchymal odontogenic tumour. POT is composed of dental papilla-like tissue covered with cuboidal to columnar epithelium that resembles to inner and outer enamel epithelium of the enamel organ without dental hard tissue formation. The aim of this study was to examine pathogenesis of POT based on tumourigenesis and odontogenesis. SUBJECTS AND METHODS: Six cases of POT were submitted for study. DNA analysis and transcriptome analysis were performed by next-generation sequencing. Expression of amelogenin, ameloblastin and dentin sialophosphoprotein (DSPP) was examined by immunohistochemistry. RESULTS: There were no gene mutations detected in any of analysed 151 cancer- and 42 odontogenesis-associated genes. Enamel protein-coding genes of Amelx, Ambn and Enam, and dentin protein-coding genes of Col1a1, Dspp, Nes and Dmp1 were expressed, whereas expression of dentinogenesis-associated genes of Bglap, Ibsp and Nfic was negative or very weak suggesting inhibition of dentin formation in POT after odontoblast differentiation. Immunoreactivity of amelogenin, ameloblastin and DSPP was detected in POT. CONCLUSIONS: Pathogenesis of POT is considered to be genetically different from other odontogenic tumours. It is suggested that inhibition of enamel and dentin formation in POT is due to defects in dentin formation process.
Assuntos
Carcinogênese/genética , DNA de Neoplasias/análise , Odontogênese/genética , Tumores Odontogênicos/genética , Adolescente , Amelogenina/genética , Amelogenina/metabolismo , Carcinogênese/metabolismo , Criança , Pré-Escolar , Colágeno Tipo I/genética , Cadeia alfa 1 do Colágeno Tipo I , Proteínas do Esmalte Dentário/genética , Proteínas do Esmalte Dentário/metabolismo , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Sialoproteína de Ligação à Integrina/genética , Masculino , Fatores de Transcrição NFI/genética , Nestina/genética , Osteocalcina/genética , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Sialoglicoproteínas/genética , Sialoglicoproteínas/metabolismoRESUMO
Primordial odontogenic tumor (POT) is a rare lesion in the jaw which has been included as a new entity of benign mixed epithelial and mesenchymal odontogenic tumour in the latest World Health Organization (WHO) classification (2017). Only seven cases have been reported. It typically occurs in the posterior mandible. We report an additional case of POT in the maxilla of an 8-year-old girl presenting with an asymptomatic buccal enlargement. A well-defined, unilocular, radiolucent lesion was observed radiographically. Histologically, the tumor was mostly composed of loose fibrous connective tissue resembling dental papilla and a single layer of columnar epithelium covering the periphery of the tumor. In part, cords or nests of epithelium were present in the mesenchyme close to the periphery. Nestin, a marker of odontogenic ectomesenchyme, was positive in the mesenchymal tumor cells. We finally diagnosed the lesion as POT considering the possibility of other odontogenic tumors like ameloblastic fibroma or developing odontoma as a differential diagnosis. The patient shows no recurrence after 16 months. This case is the first report from Japan using this novel diagnosis POT after it was recognized and defined in the latest WHO classification.
Assuntos
Tumores Odontogênicos/diagnóstico por imagem , Criança , Tomografia Computadorizada de Feixe Cônico , Diagnóstico Diferencial , Epitélio/diagnóstico por imagem , Epitélio/patologia , Feminino , Humanos , Japão , Maxila/diagnóstico por imagem , Maxila/patologia , Dente Molar/diagnóstico por imagem , Dente Molar/patologia , Tumores Odontogênicos/classificação , Tumores Odontogênicos/patologia , Dente Decíduo/diagnóstico por imagem , Dente Decíduo/patologia , Organização Mundial da SaúdeRESUMO
Epithelial cell rests of Malassez (ERM) are quiescent epithelial remnants of the Hertwig's epithelial root sheath (HERS) that are involved in the formation of tooth roots. ERM cells are unique epithelial cells that remain in periodontal tissues throughout adult life. They have a functional role in the repair/regeneration of cement or enamel. Here, we isolated odontogenic epithelial cells from ERM in the periodontal ligament, and the cells were spontaneously immortalized. Immortalized odontogenic epithelial (iOdE) cells had the ability to form spheroids and expressed stem cell-related genes. Interestingly, iOdE cells underwent osteogenic differentiation, as demonstrated by the mineralization activity in vitro in mineralization-inducing media and formation of calcification foci in iOdE cells transplanted into immunocompromised mice. These findings suggest that a cell population with features similar to stem cells exists in ERM and that this cell population has a differentiation capacity for producing calcifications in a particular microenvironment. In summary, iOdE cells will provide a convenient cell source for tissue engineering and experimental models to investigate tooth growth, differentiation, and tumorigenesis.
Assuntos
Odontogênese , Ligamento Periodontal/citologia , Células-Tronco Adultas , Diferenciação Celular , Separação Celular , Células Cultivadas , Células Epiteliais , Perfilação da Expressão Gênica , HumanosRESUMO
Epithelial-myoepithelial carcinoma (EMC) is a rare salivary gland tumor with a low-grade malignancy, and EMC with high-grade histopathological features is exceedingly rare. Furthermore, EMC with intracellular mucin is also extremely rare. We report an uncommon case of a high-grade EMC of the parotid gland with mucous cell differentiation in a 66-year old Japanese woman who noticed a right palpable parotid mass increasing in size within a one-year period. The cytological specimen showed a focally biphasic structure and included isolated or discohesive piled-up clusters with hyaline globules surrounded by neoplastic cells with nuclear atypia. The gross examination revealed a relatively well-demarcated, multinodular gray-whitish and solid mass. Histologically, the tumor consisted of variably sized solid nests or trabeculae with central necrosis and increased mitotic activity, and invaded into adjacent skeletal muscles. Immunohistochemically, the biphasic ductal and myoepithelial differentiation of this tumor confirmed the diagnosis of high-grade EMC. Furthermore, numerous small nests with d-PAS and alcian blue-positive mucous cells predominated in about 5% of the whole tumor, and these mucous cells were encompassed by neoplastic myoepithelial cells. We should recognize this variant of EMC because we can't rule out the possibility of EMC even in the presence of mucous cells.
Assuntos
Mioepitelioma/patologia , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Parotídeas/patologia , Idoso , Biópsia por Agulha Fina , Diferenciação Celular , Feminino , Células Caliciformes/patologia , Humanos , Mioepitelioma/cirurgia , Neoplasias Epiteliais e Glandulares/cirurgia , Glândula Parótida/patologia , Glândula Parótida/cirurgia , Neoplasias Parotídeas/cirurgiaRESUMO
Chemotherapy and radiation in addition to surgery has proven useful in a number of different cancer types, but the effectiveness in normal tissue cannot be avoided in these therapies. To improve the effectiveness of these therapies selectively in cancer tissue is important for avoiding side effects. Early mitotic inhibitor 1 (Emi1) is known to have the function to inhibit anaphase-promoting complex/cyclosome ubiquitin ligase complex, which ubiquitylates the cell cycle-related proteins. It recently has been shown that Emi1 knockdown prevents transition from S to G2 phase by down-regulating geminin via anaphase-promoting complex/cyclosome activation. At present, anticancer drugs for targeting DNA synthesis to interfere with rapidly dividing cells commonly are used. As Emi1 depletion interferes with completion of DNA synthesis in cancer cells, we thought that Emi1 knockdown might enhance the sensitivity for anticancer agents. Here, we confirmed that Emi1 siRNA induced polyploidy for preventing transition from S to G2 phase in several cancer cell lines. Then, we treated Emi1 depleted cells with doxorubicin. Interestingly, increased apoptotic cells were observed after doxorubicin treatment in Emi1 siRNA-treated cancer cells. In addition, Emi1 depletion enhanced the sensitivity of x-ray irradiation in cancer cells. Importantly, synergistic effect of Emi1 knockdown in these combination therapies was not observed in normal cells. These results suggest that Emi1 siRNA can be a useful tool for enhancing of sensitivity of cancer cells to anticancer reagents and radiation.
Assuntos
Antibióticos Antineoplásicos/farmacologia , Proteínas de Ciclo Celular/metabolismo , Doxorrubicina/farmacologia , Proteínas F-Box/metabolismo , Tolerância a Radiação , Proteína da Polipose Adenomatosa do Colo/metabolismo , Antígenos CD , Apoptose/efeitos dos fármacos , Caderinas/genética , Caderinas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Proteínas Cdc20 , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Dano ao DNA , Resistencia a Medicamentos Antineoplásicos , Proteínas F-Box/genética , Expressão Gênica , Técnicas de Silenciamento de Genes , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Poliploidia , RNA Interferente Pequeno/genéticaRESUMO
Matrix metalloproteinases (MMPs) are extracellular zinc-dependent endopeptidases involved in the degradation and remodeling of extracellular matrix in physiological and pathological processes. MMPs also have a role in cell proliferation, migration, differentiation, angiogenesis, and apoptosis. We previously identified cancer invasion-related factors by comparing the gene expression profiles between parent and the highly invasive clone of cancer cells. Matrix metalloproteinase-13 (MMP-13) was identified as a common up-regulated gene by cancer invasion-related factors. Although MMP-13 slightly promoted tumor invasion, we found that MMP-13 was involved in tumor angiogenesis. Conditioned medium from MMP-13-overexpressing cells promoted capillary formation of immortalized human umbilical vein endothelial cells. Furthermore, treatment with recombinant MMP-13 protein enhanced capillary tube formation both in vitro and in vivo. MMP-13-promoted capillary tube formation was mediated by activation of focal adhesion kinase and ERK. Interestingly, MMP-13 promoted the secretion of VEGF-A from fibroblasts and endothelial cells. By immunohistochemical analysis, we found a possible correlation between MMP-13 expression and the number of blood vessels in human cancer cases. In summary, these findings suggest that MMP-13 may directly and indirectly promote tumor angiogenesis.
Assuntos
Metaloproteinase 13 da Matriz/metabolismo , Neovascularização Patológica , Animais , Linhagem Celular Tumoral , Fibroblastos/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Imuno-Histoquímica/métodos , Masculino , Metástase Neoplásica , Estrutura Terciária de Proteína , RNA Interferente Pequeno/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/química , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Ameloblastic carcinoma is a rare, odontogenic, malignant tumor that has features of ameloblastoma in addition to cytologic atypia with or without metastasis. It is classified as primary type; secondary type, intraosseous; and secondary type, peripheral according to the World Health Organization classification of 2005. Ameloblastic carcinoma, secondary type, is extremely rare, and few cases have been reported in the English-language literature. The authors report a case of ameloblastic carcinoma, secondary type, arising at the mandible in a 17-year-old Japanese boy.
Assuntos
Neoplasias Mandibulares/patologia , Tumores Odontogênicos/patologia , Tumores Odontogênicos/secundário , Adolescente , Povo Asiático , Transformação Celular Neoplásica , Evolução Fatal , Humanos , Japão , Neoplasias Pulmonares/secundário , Masculino , Neoplasias Mandibulares/cirurgia , Recidiva Local de Neoplasia , Tumores Odontogênicos/cirurgia , Neoplasias da Base do Crânio/secundárioRESUMO
The purpose of the present study was to indicate that patients with anti-centromere antibodies (ACA) also experience ocular/oral dryness like patients with anti-Ro/SSA and/or anti-La/SSB antibodies (anti-SSA/SSB). A total of 80 patients with subjective ocular and/or oral dryness were classified into two groups, namely, anti-SSA/SSB-positive (anti-SSA/SSB [+]) group and ACA-positive (ACA [+]) group. The degree of ocular and oral dryness in ACA (+) patients is similar to that in anti-SSA/SSB (+) patients. On histopathological examination of the labial glands, the area of fibrosis was significantly larger in the ACA (+) group than in the anti-SSA/SSB (+) group. Thus, ACA (+) patients should be examined for Sjögren's syndrome.
Assuntos
Síndrome de Sjogren , Xerostomia , Anticorpos Antinucleares , Proteínas Cromossômicas não Histona , Humanos , Síndrome de Sjogren/diagnósticoRESUMO
Synovial chondromatosis (SC) is a rare benign disease involving multifocal generation of ectopic cartilage in the synovial tissue. Herein, we report two cases of SC in the temporomandibular joint: a 38-year-old woman (patient 1) and 39-year-old woman (patient 2). Both patients had trismus, jaw joint noises, and jaw-opening pain in the temporomandibular joint. Cone-beam computed tomography (CT) and magnetic resonance imaging (MRI) in patient 1 showed multiple calcified loose bodies around the right mandibular condyle. In addition, CT and MRI in patient 2 showed multiple calcified loose bodies around the left mandibular condyle and temporal bone perforation. Following establishing a diagnosis of SC, both patients underwent tumor resection via open surgery. In immunohistochemical examinations of the resected tissues, tumor cells showed intense nuclear staining with labeled anti-Gli1 antibody. Gene sequencing revealed that both patients had a homozygous mutation in the Gli1 gene (rs2228226 G>C). In conclusion, we suggest that the Gli1 gene (rs2228226 G>C) may be involved in the etiology of SC.
Assuntos
Condromatose Sinovial , Corpos Livres Articulares , Proteína GLI1 em Dedos de Zinco , Adulto , Condromatose Sinovial/diagnóstico por imagem , Condromatose Sinovial/genética , Condromatose Sinovial/cirurgia , Feminino , Humanos , Corpos Livres Articulares/complicações , Corpos Livres Articulares/cirurgia , Imageamento por Ressonância Magnética , Mutação , Articulação Temporomandibular , Proteína GLI1 em Dedos de Zinco/genéticaRESUMO
We report a palatal mucoepidermoid carcinoma (MEC) with unusual pathological features showing salivary duct cyst-like architecture, varied epithelial linings (excretory duct, mucous goblet cell, and apocrine epithelium phenotypes), scarce luminal tumor plaques, and a large intraluminal oncocytic polyp. To our knowledge, such a unicystic variant of MEC with pedicled oncocytic proliferation in the lumen is unprecedented in the literature. In this particular case, the microscopic diagnosis of MEC is problematic because of the large number of potential mimics.