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1.
Support Care Cancer ; 31(9): 552, 2023 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-37658917

RESUMO

PURPOSE: Chemotherapy-induced taste alteration is a side effect that can result in malnutrition and reduced quality of life in cancer patients. However, the underlying causes of this phenomenon remain unclear, and evidence-based treatments have not been established. This study focused on patients' subjective symptoms of taste alterations aimed to explore how the sensitivity to basic tastes changes due to anticancer agents and how alterations in one taste perception are associated with changes in other tastes during chemotherapy. METHODS: A cross-sectional questionnaire-based interview survey was conducted on 215 patients undergoing chemotherapy. The subjective sensitivity to each basic taste was assessed using a visual analog scale, and the incidence of taste alterations due to different chemotherapy regimens was calculated. Multivariate logistic regression analysis was performed to determine whether there were associations between changes in one taste sensitivity and changes in other taste sensitivities. RESULTS: Approximately half (49.5%) of the patients experienced chemotherapy-induced taste alterations. An analysis of subjective changes in basic tastes revealed that the salt and umami taste systems were more sensitive to chemotherapy than other taste systems. Patients with altered sensitivity to sweet taste were significantly more likely to report altered sensitivity to salt, bitter, and sour tastes. Moreover, umami-salt and bitter-sour taste sensitivities were significantly related to each other. CONCLUSION: This study suggests that changes in subjective sensitivities to one basic taste during chemotherapy may be accompanied by changes in other tastes in specific combinations. Considering taste associations in dietary guidance may help improve the nutritional status of cancer patients experiencing taste alterations due to chemotherapy.


Assuntos
Antineoplásicos , Disgeusia , Neoplasias , Percepção Gustatória , Inquéritos e Questionários , Disgeusia/induzido quimicamente , Estudos Transversais , Neoplasias/tratamento farmacológico , Antineoplásicos/efeitos adversos , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais
2.
J Clin Periodontol ; 50(11): 1520-1529, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37666748

RESUMO

AIM: To retrospectively investigate the relationship between the CD4+ T-cell counts at baseline and the efficacy of the initial periodontal treatment of patients undergoing treatment for human immunodeficiency virus (HIV) infection using the periodontal inflamed surface area (PISA). MATERIALS AND METHODS: Thirty-three patients with chronic periodontitis who had undergone periodontal examination at baseline and after the initial periodontal treatment were enrolled. PISA was calculated from the periodontal probing depth and bleeding on probing, and the ratio of PISA after treatment to that at baseline (PISA response ratio) was calculated. Groups with a response ratio of <1 and ≥1 were defined as the improvement and the non-improvement groups, respectively. RESULTS: PISA after the initial periodontal treatment significantly decreased compared with that at baseline (p < .05). A weak negative correlation was found between the PISA response ratio and CD4+ T-cell counts at baseline (p < .05). The CD4+ T-cell counts at baseline were significantly higher in the improvement group than in the non-improvement group (p < .05). Multivariate analysis revealed that the CD4+ T-cell counts at baseline was an independent factor that affects the PISA (p < .05). CONCLUSIONS: The higher the CD4+ T-cell counts at baseline in patients undergoing treatment for HIV infection, the more effective the initial periodontal treatment.

3.
Pathol Int ; 73(8): 367-372, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37401869

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/patologia
4.
BMC Oral Health ; 23(1): 159, 2023 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-36934261

RESUMO

BACKGROUND: Dysgeusia is a relatively early symptom of zinc deficiency, and zinc replacement is effective in treating dysgeusia. The administration of zinc acetate hydrate (ZAH) was approved in 2017 for patients with hypozincemia in Japan. This retrospective study was conducted to explore the efficacy and safety of ZAH administration in patients with hypozincemia-induced dysgeusia. METHODS: Patients with hypozincemia-induced dysgeusia who visited our hospital from May 2013 to December 2019 were included in this study. ZAH (zinc content; 50 mg/day) was administered to 42 patients for 24 weeks. The taste test was performed using the filter paper disk method, and the total cognitive thresholds of the left and right chorda tympani regions were used. Changes in taste function, serum zinc and copper levels, and copper/zinc ratio were analyzed. A total of 28 patients who received polaprezinc (PPZ, zinc content; 34 mg/day) for 24 weeks, who were prescribed until ZAH was approved, were registered as controls. RESULTS: Serum zinc levels at 12 and 24 weeks after ZAH or PPZ administration were higher than those before administration. These levels were significantly higher in the ZAH-treated group than in the PPZ-treated group. However, serum copper levels did not significantly change before and after administration. In the taste test, the taste thresholds for the acidity and salty at 12 and 24 weeks after ZAH administration were significantly decreased compared to before administration. In contrast, in the PPZ group, the taste thresholds for the acidity and salty were significantly decreased 24 weeks after administration. CONCLUSIONS: ZAH (50 mg/day) administration was effective in improving the gustatory sensitivity of patients with dysgeusia and hypozincemia 12 weeks after administration without affecting the serum copper level. ZAH was also more effective than PPZ.


Assuntos
Disgeusia , Acetato de Zinco , Humanos , Disgeusia/induzido quimicamente , Disgeusia/tratamento farmacológico , Acetato de Zinco/uso terapêutico , Estudos Retrospectivos , Cobre/uso terapêutico , Zinco/uso terapêutico
5.
Pathol Int ; 72(7): 371-375, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35596702

RESUMO

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/genética
6.
Carcinogenesis ; 40(10): 1288-1297, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31074490

RESUMO

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 Metaloproteinase
7.
Biochem Biophys Res Commun ; 497(3): 876-882, 2018 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-29477844

RESUMO

Cleft lip and palate is the most common congenital anomaly in the orofacial region. Autogenous iliac bone graft, in general, has been employed for closing the bone defect at the alveolar cleft. However, such iliac bone graft provides patients with substantial surgical and psychological invasions. Consequently, development of a less invasive method has been highly anticipated. Stem cells from human exfoliated deciduous teeth (SHED) are a major candidate for playing a significant role in tissue engineering and regenerative medicine. The aim of this study was to elucidate the nature of bone regeneration by SHED as compared to that of human dental pulp stem cells (hDPSCs) and bone marrow mesenchymal stem cells (hBMSCs). The stems cells derived from pulp tissues and bone marrow were transplanted with a polylactic-coglycolic acid barrier membrane as a scaffold, for use in bone regeneration in an artificial bone defect of 4 mm in diameter in the calvaria of immunodeficient mice. Three-dimensional analysis using micro CT and histological evaluation were performed. Degree of bone regeneration with SHED relative to the bone defect was almost equivalent to that with hDPSCs and hBMSCs 12 weeks after transplantation. The ratio of new bone formation relative to the pre-created bone defect was not significantly different among groups with SHED, hDPSCs and hBMSCs. In addition, as a result of histological evaluation, SHED produced the largest osteoid and widely distributed collagen fibers compared to hDPSCs and hBMSCs groups. Thus, SHED transplantation exerted bone regeneration ability sufficient for the repair of bone defect. The present study has demonstrated that SHED is one of the best candidate as a cell source for the reconstruction of alveolar cleft due to the bone regeneration ability with less surgical invasion.


Assuntos
Regeneração Óssea , Polpa Dentária/citologia , Células-Tronco Mesenquimais/citologia , Transplante de Células-Tronco , Dente Decíduo/citologia , Processo Alveolar/patologia , Processo Alveolar/fisiologia , Diferenciação Celular , Células Cultivadas , Humanos , Transplante de Células-Tronco Mesenquimais , Procedimentos de Cirurgia Plástica , Medicina Regenerativa , Alicerces Teciduais/química , Dente Decíduo/transplante
8.
Pathol Int ; 68(1): 31-35, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29131467

RESUMO

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/genética
9.
Pathol Int ; 67(7): 365-369, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28543986

RESUMO

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 Saúde
10.
Odontology ; 105(1): 116-121, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27262724

RESUMO

The aim of this study was to examine the effect of 16 amino acids of the N-terminal region of human ameloblastin (16N-AMBN) synthetic peptide, on the proliferation and differentiation of MC3T3-E1 cells and bone regeneration. While 16N-AMBN did not affect the proliferation, it induced mRNA expression of type I collagen, alkaline phosphatase (ALP), bone sialoprotein, and osteocalcin. 16N-AMBN also stimulated ALP activity and promoted mineralized nodule formation. On the other hand, these activities were inhibited by anti-16N-AMBN antibody. Treatment of rat calvarial bone defects with 16N-AMBN resulted in almost complete healing compared to that of the control treatments. These findings suggest that 16N-AMBN may be applicable for regeneration therapy of bone defects.


Assuntos
Regeneração Óssea/efeitos dos fármacos , Proteínas do Esmalte Dentário/fisiologia , Fosfatase Alcalina/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Colágeno Tipo I/metabolismo , Humanos , Sialoproteína de Ligação à Integrina/metabolismo , Osteocalcina/metabolismo , Ratos , Crânio/cirurgia , Cicatrização/efeitos dos fármacos
11.
Mol Med Rep ; 29(3)2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38275130

RESUMO

Keratoameloblastoma (KA) and solid variant of odontogenic keratocyst (SOKC) are rare odontogenic lesions, and their relationship and differences are unclear. The present study described a case that started as an odontogenic keratocyst (OKC) and transformed to SOKC/KA upon recurrence. Briefly, a 26­year­old man presented with swelling in the right cheek and was referred to the Department of Oral and Maxillofacial surgery, Hiroshima University Hospital (Hiroshima, Japan). At the initial visit, unicystic bone permeation was observed extending from the right canine to the molar, maxillary sinus and nasal cavity. After the biopsy, the patient underwent excisional surgery and was diagnosed with OKC. Thereafter, the lesion recurred six times over a period of 13 years and showed different histopathological features from those of the primary lesion, all consisting of numerous cysts with keratinization, which were diagnosed as SOKC/KA. The Ki­67 positivity rate was ~10%, which was higher than that of the primary lesion, but there was no atypia. Genetic analysis of the recurrent lesion revealed mutations in adenomatous polyposis coli and Kirsten rat sarcoma viral oncogene homolog. This case originated from OKC, and the morphological features of OKC and KA were mixed upon recurrence, supporting the commonality and association between the two. However, multiple mutations different from those of OKC and ameloblastoma were detected, suggesting an association of SOKC/KA with increased proliferative activity and a high recurrence rate.


Assuntos
Ameloblastoma , Cistos Odontogênicos , Masculino , Humanos , Adulto , Ameloblastoma/diagnóstico , Ameloblastoma/genética , Ameloblastoma/cirurgia , Cistos Odontogênicos/diagnóstico , Cistos Odontogênicos/cirurgia , Cistos Odontogênicos/genética , Mutação , Biópsia , Osso e Ossos/patologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-38679502

RESUMO

OBJECTIVE: Extranodal extension (ENE) is an important prognostic factor in oral squamous cell carcinoma (OSCC). This study aimed to evaluate the clinical significance of stratifying minor or major ENE in OSCC. STUDY DESIGN: This retrospective cohort study included 75 patients who had undergone neck dissection for OSCC and were classified as pN+. ENE was measured using hematoxylin-eosin-stained specimens and stratified into major (ENEma, >2 mm) and minor (ENEmi, ≤2 mm) by distance. Their association with survival, locoregional relapse, and distant metastases were assessed. RESULTS: Of 49 patients with pathological ENE, 23 had ENEmi, and 26 had ENEma. The 5-year overall survival (OS) was 38%, 66%, and 76% in the ENEma, ENEmi, and no ENE groups, respectively. Compared with no ENE, ENEma was associated with significantly decreased 5-year cumulative OS and disease-specific survival. ENEma was a risk factor for decreased OS (HR: 2.54, 95% CI: 1.04-6.18, P = .040) in the multivariable Cox regression analysis, and was associated with distant metastasis. CONCLUSION: In patients with OSCC, ENEma is associated with a significantly poorer prognosis; therefore stratifying ENE is clinically relevant. ENEma may increase the risk of distant metastasis; therefore, new treatment modalities that contribute to distant metastasis control are required.


Assuntos
Carcinoma de Células Escamosas , Extensão Extranodal , Neoplasias Bucais , Esvaziamento Cervical , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Neoplasias Bucais/terapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Idoso , Prognóstico , Extensão Extranodal/patologia , Recidiva Local de Neoplasia/patologia , Adulto , Fatores de Risco , Estadiamento de Neoplasias , Idoso de 80 Anos ou mais
13.
Stem Cell Rev Rep ; 20(1): 347-361, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37917410

RESUMO

Mesenchymal stem cells (MSCs) have gained significant attention in cell therapies due to their multipotency and immunomodulatory capacities. The transcriptional co-activators YAP/TAZ, central to the mechanotransduction system in MSCs, dominantly direct MSCs lineage commitment. However, their role in immunomodulation remains elusive. Accordingly, this present study aimed to investigate the role of mechanotransducer YAP/TAZ and their binding target transcriptional factor, TEAD, in the immunomodulatory capacities of human bone marrow-derived MSCs. Reducing YAP/TAZ activity by altering the matrix stiffness, disrupting the F-actin integrity with chemical inhibitors, or using siRNAs increased the expression of immunomodulatory genes, such as TSG-6 and IDO, upon TNF-α stimulation. Similarly, transfection of TEAD siRNA also increased the immunomodulatory capacities in MSCs. RNA-seq analysis and inhibition assays demonstrated that the immunomodulatory capacities caused by YAP/TAZ-TEAD axis disruption were due to the NF-κB signaling pathway activation. Then, we also evaluated the in vivo anti-inflammatory efficacy of MSCs in a dextran sulfate sodium (DSS)-induced mice colitis model. The administration of human MSCs transfected with TEAD siRNA, which exhibited enhanced immunomodulatory properties in vitro, significantly ameliorated inflammatory bowel disease symptoms, such as body weight loss and acute colon inflammation, in the DSS-induced mice colitis model. Our findings underscore the mechanosignaling YAP/TAZ-TEAD axis as a regulator of MSCs immunomodulation. Targeting these signaling pathways could herald promising MSCs-based therapies for immune disorders.


Assuntos
Colite , Células-Tronco Mesenquimais , Proteínas de Sinalização YAP , Animais , Humanos , Camundongos , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Colite/metabolismo , Imunomodulação , Mecanotransdução Celular , RNA Interferente Pequeno/metabolismo , Transativadores/genética , Transativadores/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Proteínas com Motivo de Ligação a PDZ com Coativador Transcricional/metabolismo , Fatores de Transcrição de Domínio TEA/metabolismo
14.
Cancer Res Commun ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38954773

RESUMO

The comprehensive genomic analysis of the head and neck squamous cell carcinoma (HNSCC) oncogenome revealed the frequent loss of p16INK4A (CDKN2A) and amplification of cyclin D1 (CCND1) genes in most HPV negative HNSCC lesions. However, cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have shown modest effects in the clinic. The aberrant activation of PI3K/mTOR pathway is highly prevalent in HNSCC, and recent clinical trials have shown promising clinical efficacy of mTOR inhibitors (mTORi) in the neoadjuvant and adjuvant settings but not in advanced HNSCC patients. By a kinome-wide CRISPR/Cas9 screen, we identified cell cycle inhibition as a synthetic lethal target for mTORi. Combination of mTORi and palbociclib, a CDK4/6 specific inhibitor, showed strong synergism in HNSCC-derived cells in vitro and in vivo. Remarkably, we found that adaptive increase in cyclin E1 (CCNE1) expression upon palbociclib treatment underlies the rapid acquired resistance to this CDK4/6 inhibitor. Mechanistically, mTORi inhibits the formation of eIF4G-CCNE1 mRNA complexes, with the consequent reduction in mRNA translation and CCNE1 protein expression. Our findings suggest that mTORi reverts the adaptive resistance to palbociclib. This provides a multimodal therapeutic option for HNSCC by co-targeting mTOR and CDK4/6, which in turn may halt the emergence of palbociclib resistance.

15.
Sci Rep ; 14(1): 11114, 2024 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750118

RESUMO

Oral bacteria are known to be associated with perioperative complications during hospitalization. However, no presented reports have clarified the relationship of oral bacterial number with medical costs for inpatients. The Diagnosis Procedure Combination (DPC) database system used in Japan provides clinical information regarding acute hospital patients. The present study was conducted to determine the association of oral bacterial numbers in individual patients treated at a single institution with length of hospital stay and medical costs using DPC data. A total of 2369 patients referred by the medical department to the dental department at Hiroshima University Hospital were divided into the low (n = 2060) and high (n = 309) oral bacterial number groups. Length of hospital stay and medical costs were compared between the groups, as well as the associations of number of oral bacteria with Charlson comorbidity index (CCI)-related diseases in regard to mortality and disease severity. There was no significant difference in hospital stay length between the low (24.3 ± 24.2 days) and high (22.8 ± 20.1 days) oral bacterial number groups. On the other hand, the daily hospital medical cost in the high group was significantly greater (US$1456.2 ± 1505.7 vs. US$1185.7 ± 1128.6, P < 0.001). Additionally, there was no significant difference in CCI score between the groups, whereas the daily hospital medical costs for patients in the high group treated for cardiovascular disease or malignant tumors were greater than in the low number group (P < 0.05). Multivariate regression analysis was also performed, which showed that oral bacterial number, age, gender, BMI, cardiovascular disease, diabetes, malignant tumor, and hospital stay length were independently associated with daily hospitalization costs. Monitoring and oral care treatment to lower the number of oral bacteria in patients affected by cardiovascular disease or cancer may contribute to reduce hospitalization costs.


Assuntos
Hospitalização , Tempo de Internação , Humanos , Feminino , Masculino , Japão/epidemiologia , Idoso , Tempo de Internação/economia , Pessoa de Meia-Idade , Hospitalização/economia , Boca/microbiologia , Bases de Dados Factuais , Idoso de 80 Anos ou mais , Custos Hospitalares , Carga Bacteriana , Bactérias/isolamento & purificação , Bactérias/classificação , Custos de Cuidados de Saúde , Adulto
16.
Head Neck ; 45(11): 2829-2838, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37675788

RESUMO

BACKGROUND: Mass lesions occurring under the oral mucosal epithelium are often small and difficult to diagnose; however, intraoral ultrasonography can delineate these lesions. We aimed to investigate the features of submucosal mass lesions in the oral cavity using intraoral ultrasonography. METHODS: Fifty patients with hemangioma, irritation fibroma, mucous cyst, lipoma, and pleomorphic adenoma were included. Age, site, largest diameter, thickness, marginal morphology type, border type, internal echo posterior echo, and internal or peripheral Doppler images of the lesions were recorded. RESULTS: The hemangiomas were internally hypoechoic and exhibited a cord-like structure; irritation fibromas, mainly internally isoechoic; mucous cysts, hypoechoic; and the lipomas appeared as homogeneous, isoechoic, or hyperechoic images with unclear borders. Pleomorphic adenomas were surrounded by a single hypoechoic zone, suggesting a thick capsular structure, were predominantly isoechoic internally, and appeared as cyst-like hypoechoic images. CONCLUSIONS: The features of the lesions were identified and delineated using intraoral ultrasonography.


Assuntos
Adenoma Pleomorfo , Cistos , Hemangioma , Lipoma , Humanos , Ultrassonografia/métodos , Epitélio/patologia , Lipoma/diagnóstico por imagem , Lipoma/patologia
17.
J Int Med Res ; 51(7): 3000605231187819, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37480276

RESUMO

Resin components, such as methyl methacrylate (MMA) can cause allergic contact dermatitis (ACD). Allergic reactions to resin are usually delayed. Only a few studies have reported dental resin allergy with acute symptoms. Here, a case of ACD with acute facial swelling after dental treatment using resin material is reported. A 55-year-old woman with a history of periungual inflammation when using gel nail polish had repeated episodes of facial swelling after dental treatment with resin material. The resin temporary crown was removed, and symptoms were alleviated with antihistamines and corticosteroids. With the suspicion of resin allergy, skin tests were performed. Patch testing revealed positive reactions to self-adhesive resin cement (primer and polymerized), self-curing acrylic resin (liquid and polymerized), 2-hydroxyethyl methacrylate (2-HEMA), and ethylene glycol dimethacrylate (EGDMA), whereas the prick test was negative for all allergens. Complement C4 and C1 inhibitor activity were reference values in the tests for hereditary angioedema. Based on these findings, the patient was diagnosed with ACD to 2-HEMA and EGDMA. Since diagnosis, no similar symptoms have been observed in subsequent dental treatment with non-resin materials. The use of dental resin materials may cause ACD with an acute reaction. This report alerts dentists who routinely use resin materials.


Assuntos
Hipersensibilidade , Feminino , Humanos , Pessoa de Meia-Idade , Metacrilatos/efeitos adversos , Inflamação , Resinas Acrílicas/efeitos adversos
18.
Physiol Behav ; 267: 114224, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37148986

RESUMO

OBJECTIVES: The causes of hypogeusia include zinc deficiency, systemic illness, and consumption of drugs. Notably, patients with oral cavity diseases such as oral candidiasis and salivary gland hypofunction may present with risk factors that remain unreported. Hence, this study aimed to investigate the relationship between age, sex, smoking status, serum zinc concentration, oral candidiasis, saliva volume, and taste function in patients with hypogeusia. SUBJECTS AND METHODS: Overall, 335 participants who complained of taste abnormalities underwent a taste test. Based on the recognition threshold value, the participants were classified as normal individuals (recognition threshold of 1 and 2) and patients with hypogeusia (recognition threshold of ≥3). The clinical characteristics, including resting saliva volume (RSV) and stimulated saliva volume (SSV), were compared, and a multivariate logistic regression analysis focusing on RSV was performed. RESULTS: Patients with hypogeusia had a lower RSV than normal individuals for all tastes, but not for SSV. Based on the results of regression analysis, RSV was identified as an independent predictor of hypogeusia for salty and bitter tastes. Moreover, the proportion of patients with decreased RSV increased as the number of taste qualities exceeding the reference recognition threshold increased. Furthermore, a decrease in RSV was associated with an increase in the recognition threshold for salty and bitter tastes. CONCLUSIONS: Based on the results of the present study, moisturizing the oral cavity may be useful against hypogeusia.


Assuntos
Ageusia , Candidíase Bucal , Humanos , Ageusia/etiologia , Saliva , Estudos Retrospectivos , Candidíase Bucal/complicações , Paladar , Fatores de Risco , Zinco , Limiar Gustativo
19.
Pharmaceutics ; 15(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36678795

RESUMO

Tumor angiogenesis is essential for tumor progression. The inhibition of tumor angiogenesis is a promising therapy for tumors. Bovine lactoferrin (bLF) has been reported as an anti-tumor agent. However, bLF effects on tumor angiogenesis are not well demonstrated. This study evaluated the inhibitory effects of bLF on tumor angiogenesis in vivo and in vitro. Herein, tumor endothelial cells (TECs) and normal endothelial cells (NECs) were used. Proliferation, migration, tube formation assays, RT-PCR, flow cytometry, Western blotting, siRNA experiments and immunoprecipitation were conducted to clarify the mechanisms of bLF-induced effects. CD-31 immunoexpression was examined in tumor tissues of oral squamous cell carcinoma mouse models with or without Liposomal bLF (LbLF)-administration. We confirmed that bLF inhibited proliferation/migration/tube formation and increased apoptosis in TECs but not NECs. TNF receptor-associated factor 6 (TRAF6), p-p65, hypoxia inducible factor-α (HIF-1α) and vascular endothelial growth factor (VEGF) were highly expressed in TECs. In TECs, bLF markedly downregulated VEGF-A, VEGF receptor (VEGFR) and HIF-1α via the inhibition of p-p65 through binding with TRAF6. Since NECs slightly expressed p-p65, bLF-TRAF-6 binding could not induce detectable changes. Moreover, orally administrated LbLF decreased CD31-positive microvascular density only in TECs. Hence, bLF specifically suppressed tumor angiogenesis through p-p65 inhibition by binding to TRAF6 and suppressing HIF-1α activation followed by VEGF/VEGFR down-regulation. Collectively, bLF can be an anti-angiogenic agent for tumors.

20.
Dent J (Basel) ; 11(2)2023 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-36826194

RESUMO

The presence of a supernumerary tooth is one of the most common dental anomalies, and surgical treatment is often required to address this anomaly. Moreover, it may lead to malocclusion, and long-term follow-up is important to monitor its status. A 4-year-and-11-month-old boy was referred to our hospital for dental caries treatment. At 5 years and 5 months of age, a radiographic examination showed a supernumerary tooth (first supernumerary tooth) near the permanent maxillary left central incisor, and it was extracted 6 months later. Eighteen months after the extraction of the first supernumerary tooth, a new supernumerary tooth (second supernumerary tooth) was detected in the same region, which was extracted when the patient was aged seven years and seven months. Seven months later, another supernumerary tooth (third supernumerary tooth) was detected and extracted immediately. However, the permanent maxillary left central incisor did not erupt spontaneously even after 6 months. Therefore, surgical exposure was performed, and the central incisor erupted into the oral cavity. This report describes our experience with this patient with three metachronous supernumerary teeth and their management until the eruption of the permanent tooth. This report highlights the importance of long-term follow-up after supernumerary tooth extraction until the permanent teeth in that region have erupted completely.

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