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1.
Exp Dermatol ; 33(3): e15049, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38509717

RESUMO

Extramammary Paget disease (EMPD) is a rare skin cancer mainly found in areas rich in apocrine sweat glands. Since the effective treatments for advanced and/or metastasized EMPD are limited, there is an urgent need to develop novel therapeutic approaches. Nectin cell adhesion molecule 4 (NECTIN4) is highly expressed in cancers and considered to be a promising therapeutic target. NECTIN4 is also expressed in EMPD, but its role and the efficacy of NECTIN4-targeted therapy in EMPD remain unclear. This study investigated the potential of NECTIN4 as a novel therapeutic target for EMPD. NECTIN4 expression was immunohistochemically analysed in EMPD patients' primary (118 samples) and metastatic (21 samples) lesions. Using an EMPD cell line, KS-EMPD-1, the effects of NECTIN4 inhibition on cell proliferation and migration were investigated. NECTIN4 was expressed in primary and metastatic EMPD lesions, and the H-score of NECTIN4 staining was significantly higher in metastatic lesions than in primary ones. Knockdown of NECTIN4 significantly inhibited cell proliferation and affected cell migration. The cytotoxic effects of NECTIN4-targeted antibody-drug conjugate (ADC) were further evaluated, revealing a significant decrease in EMPD cell viability. In conclusion, NECTIN4 is a potential therapeutic target and NECTIN4-targeted ADC is promising as a therapeutic option for EMPD.


Assuntos
Neoplasias , Doença de Paget Extramamária , Humanos , Doença de Paget Extramamária/tratamento farmacológico , Doença de Paget Extramamária/patologia , Epiderme/metabolismo , Moléculas de Adesão Celular
2.
Support Care Cancer ; 31(12): 707, 2023 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-37979045

RESUMO

PURPOSE: Oral mucositis (OM) is a side effect associated with cancer treatment. Hangeshashinto (HST), a Kampo medicine, was originally prescribed to treat diarrhea, gastritis, and stomatitis. Several reports have described the effects of HST for OM induced by chemotherapy in patients with gastric or colorectal cancer. In this study, the effects of HST for prevention of OM were investigated in patients undergoing hematopoietic stem cell transplantation (HSCT). METHODS: Thirty patients scheduled to receive allogeneic grafts were enrolled from July 2020 to December 2021. They were randomly assigned to two groups and instructed to wash their mouth using HST dissolved in saline solution or using only saline solution three times a day. The observation period was from the initiation date of the conditioning regimen to the date of engraftment, and the end point was the incidence of OM. RESULTS: Eighteen patients developed OM, the most severe of which was Grade (G)3. There was no significant difference in the incidence of OM between the HST group and the control group. However, a negative correlation tended to be observed between the duration using HST use and the duration of OM (G2-3: P = 0.027, G3: P = 0.047). CONCLUSIONS: The present study demonstrated that HST use did not clearly inhibit onset of OM but showed a tendency to inhibit OM exacerbation. However, further studies are necessary to fully understand the effects of HST on OM in patients undergoing HSCT. TRIAL REGISTRATION: This study was registered in the Japan Registry of Clinical Trials on 7 May 2020 (jRCTs071200012).


Assuntos
Transplante de Células-Tronco Hematopoéticas , Estomatite , Humanos , Solução Salina/efeitos adversos , Estomatite/induzido quimicamente , Estomatite/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Incidência , Condicionamento Pré-Transplante/efeitos adversos
3.
Clin Pract ; 12(5): 723-733, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36136869

RESUMO

(1) Background: To what extent is information manipulation by doctors acceptable? To answer this question, we conducted an exploratory study aimed at obtaining basic data on descriptive ethics for considering this issue. (2) Methods: A self-administered questionnaire survey was conducted on a large sample (n = 3305) of doctors. The participants were queried on (1) whether they consider that information manipulation is necessary (awareness), (2) whether they have actually manipulated information (actual state), and (3) their ethical tolerance. (3) Result: The response rate was 28.7%. Sixty percent of the doctors responded that information manipulation to avoid harm to patients is necessary (awareness), that they have actually manipulated information (actual state), and that information manipulation is ethically acceptable. (4) Conclusion: While the present survey was conducted among doctors in Japan, previous studies have reported similar findings in the United States and Europe. Based on our analysis, we hypothesize that a relationship of trust between patients and medical personnel is crucial and that information manipulation is not needed when such a relationship has been established.

4.
BMC Med Ethics ; 23(1): 92, 2022 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-36096840

RESUMO

BACKGROUND: The Act Regarding the Promotion of the Appropriate Supply of Hematopoietic Stem Cells for Transplant regulates only how public banks store and provide umbilical cord blood (UCB) for research or transplantation. Japan had no laws to regulate how the private banks manage the procedures, harvesting, preparation, and storage of such blood. As a result, the status of UCB distribution remains unknown. We conducted a survey to investigate the current status of UCB storage and provision to private biobanks by Japanese institutions that handle childbirth. METHODS: Questionnaire forms were mailed to 3,277 facilities handling childbirth that were registered in the Japan Council for Quality Health Care website. RESULTS: Of the 1,192 institutions handling childbirth that participated in the survey (response rate: 36.7%), 34.4% responded that they currently provide UCB to private biobanks, while 16.1% of facilities did so in the past. Moreover, some institutions currently provide or formerly provided UCB to medical treatment facilities (2.6%), research institutions (5.9%), companies (2.2%), or overseas treatment facilities, research institutions, or companies (0.3%). A certain number of institutions handling childbirth did not even provide explanations or obtain consent when the UCB was harvested from private bank users. CONCLUSIONS: This is the first study to determine the status of UCB provision to private banks by Japanese institutions handling childbirth. Future studies will need to examine in detail how institutions handling childbirth provide explanations to private bank users and UCB providers as well as how these institutions obtain consent.


Assuntos
Bancos de Sangue , Sangue Fetal , Bancos de Espécimes Biológicos , Parto Obstétrico , Feminino , Humanos , Japão , Gravidez
5.
Eur J Dermatol ; 32(2): 181-186, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-35866909

RESUMO

Background: Sebaceous carcinoma and sweat gland carcinoma (malignant tumours with apocrine and eccrine differentiation) are rare malignant adnexal tumours that differentiate toward sebaceous glands and eccrine and apocrine glands, respectively. Because of the rarity of these malignancies, standard treatments for advanced disease have yet to be established. The outcomes of patients with systemic metastasis remain poor, highlighting the need for novel treatment strategies. Nectin cell adhesion molecule 4 (NECTIN4) and its antibody-drug conjugate, enfortumab vedotin, have attracted attention as potential treatments for solid tumours. Objectives: To examine the potential use of NECTIN4-target therapy for sebaceous and sweat gland carcinoma. Materials & Methods: We immunohistochemically investigated NECTIN4 expression in 14 sebaceous carcinoma samples and 18 sweat gland carcinoma samples, and examined whether NECTIN4-targeted therapy could be applied to these cancers. Results: We found strong and frequent expression of NECTIN4 in both cancers. All tumours exhibited positive staining at least in a part of the lesion, and the mean H-score, a semiquantitative score ranging from 0 to 300, was 259.4 for sebaceous carcinoma and 253.1 for sweat gland carcinoma. Conclusion: Our results suggest that both sebaceous carcinoma and sweat gland carcinoma could be potentially treated with NECTIN4-targeted antibody-drug conjugates, such as enfortumab vedotin.


Assuntos
Carcinoma de Apêndice Cutâneo , Moléculas de Adesão Celular/metabolismo , Neoplasias Cutâneas , Neoplasias das Glândulas Sudoríparas , Glândulas Apócrinas/patologia , Carcinoma de Apêndice Cutâneo/patologia , Humanos , Neoplasias Cutâneas/patologia , Neoplasias das Glândulas Sudoríparas/patologia
6.
Sci Rep ; 12(1): 11545, 2022 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-35799050

RESUMO

A drug holiday of 3 months does not promote separation of sequestra and is not correlated with treatment outcomes after surgical therapy in osteoporosis patients who receive antiresorptive agents and who have medication-related osteonecrosis of the jaw. Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse effect of antiresorptive agents alone or in combination with immune modulators or antiangiogenic medications, in the absence of radiation exposure to the head and neck region. The effectiveness of surgical treatment for MRONJ has been reported, but the timing of the operation remains controversial. The purpose of this study was to clarify whether preoperative drug holidays of antiresorptive agents promote sequestrum separation and improve treatment outcomes in patients who receive low doses of antiresorptive agents. This retrospective study included 173 patients who received low-dose antiresorptive agents and underwent surgical therapy. The effects of a drug holiday on the separation of sequestra and treatment outcomes were analyzed using logistic and Cox regression analyses. Multivariate analysis revealed that administration of an antiresorptive agent for more than 4 years, a high number of lymphocytes, and an extensive osteolytic area were significantly correlated with separation of sequestra, but drug holiday did not promote sequestrum separation. Furthermore, a drug holiday of 90, 120 or 180 days did not show any improvement in treatment outcomes. The drug holiday of the antiresorptive agents for the treatment of MRONJ is unnecessary, and surgical therapy should be performed early.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Osteoporose , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/tratamento farmacológico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/cirurgia , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/uso terapêutico , Humanos , Osteoporose/induzido quimicamente , Osteoporose/complicações , Osteoporose/tratamento farmacológico , Preparações Farmacêuticas , Estudos Retrospectivos , Resultado do Tratamento
7.
Artigo em Inglês | MEDLINE | ID: mdl-35742679

RESUMO

Although maxillary sinusitis often occurs in patients with medication-related osteonecrosis of the jaw (MRONJ) of the upper jaw, there have been few reports on the treatment and outcomes for maxillary sinusitis associated with maxillary MRONJ. This study aimed to retrospectively investigate the treatment outcomes of maxillary sinusitis in patients with MRONJ of the upper jaw. There were 34 patients diagnosed with maxillary MRONJ and sinusitis by preoperative computed tomography who underwent surgery in our institution between January 2011 and December 2019. Age, sex, primary disease, stage of MRONJ, class and administration period of an antiresorptive agent, corticosteroid administration, preoperative leukocyte count and serum albumin level, periosteal reaction, sinusitis grade, maxillary sinus surgical procedure, and treatment outcomes of MRONJ and sinusitis were examined. There were 7 male and 27 female patients (average age, 74.7 years). Complete healing of MRONJ was obtained in 29 of 34 patients (85.3%). Maxillary sinusitis resolved or improved in 21 patients (61.8%) but did not change or worsen in 13 patients (38.2%). We found that complete resection of necrotic bone with intraoperative irrigation of the maxillary sinus may provide good treatment outcomes for maxillary sinusitis associated with MRONJ, although our findings were not statistically significant owing to the small number of patients.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Sinusite Maxilar , Idoso , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico por imagem , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/cirurgia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento
8.
Sci Rep ; 12(1): 10188, 2022 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-35715518

RESUMO

Elevated numbers of candida in the oral cavity often lead to oral candidiasis development in patients undergoing radiotherapy for oral or oropharyngeal cancer. This study aimed to verify the effect of miconazole mucoadhesive tablets on suppression of oral candida infection during radiotherapy. For this preliminary interventional study, miconazole mucoadhesive tablets were attached to the oral mucosa for 14 days from when grade 2 oral mucositis appeared in patients with oral or oropharyngeal cancer receiving radiotherapy, and the incidence of oral candidiasis was investigated. Various clinical factors were examined; univariate and multivariate Cox regression analyses were performed to investigate and compare the efficacy of this drug in preventing oral candidiasis with results of our previous study as historical control. Miconazole mucoadhesive tablets were administered to 18 patients, and oral candidiasis was observed in one patient (5.6%) after treatment completion. Among 144 historical control patients, 43 (29.9%) developed oral candidiasis. Multivariate Cox regression showed that miconazole mucoadhesive tablets significantly reduced oral candidiasis development during radiotherapy (p = 0.049, Hazard ratio 0.136, 95% confidence interval 0.019-0.994). This preliminary study suggests the efficacy of miconazole mucoadhesive tablets in preventing oral candidiasis in oral or oropharyngeal cancer patients treated with radiotherapy.Trial registration: Japan Registry of Clinical Trials (jRCT), jRCTs071190023. Registered 3 September, 2019.


Assuntos
Candidíase Bucal , Candidíase , Neoplasias Orofaríngeas , Antifúngicos/uso terapêutico , Candidíase/tratamento farmacológico , Candidíase Bucal/tratamento farmacológico , Candidíase Bucal/etiologia , Candidíase Bucal/prevenção & controle , Humanos , Miconazol/uso terapêutico , Neoplasias Orofaríngeas/induzido quimicamente , Neoplasias Orofaríngeas/tratamento farmacológico , Neoplasias Orofaríngeas/radioterapia , Comprimidos
9.
Support Care Cancer ; 30(9): 7241-7248, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35587291

RESUMO

PURPOSE: To retrospectively investigate whether apical lesion, alveolar bone loss, probing pocket depth, or local infectious symptoms were associated with the onset of medication-related osteonecrosis of the jaw (MRONJ) in patients treated with high-dose antiresorptive agents who did not undergo tooth extraction. METHODS: The study included 92 patients receiving high-dose antiresorptive agent therapy who had teeth with apical lesion ≧ 3 mm, alveolar bone loss ≧ 1/2, probing pocket depth ≧ 4 mm, or local infection symptoms such as swelling, pain, and pus discharge, but did not undergo tooth extraction. Univariate and multivariate Cox regression analyses were performed to determine the relationship between each variable and MRONJ onset. RESULTS: MRONJ developed in 15 of 92 patients (35 of 404 teeth) from 74 to 1883 days (median, 383 days) after the first visit. Multiple Cox regression analysis revealed that a lower number of teeth, diabetes, increased leukocyte count, administration of antiresorptive agents for 180 days or more, local infection symptoms, apical lesion ≧ 3 mm, and probing pocket depth ≧ 4 mm were significantly correlated with the development of MRONJ. CONCLUSION: It is recommended that teeth with apical lesion ≧ 3 mm, probing pocket depth ≧ 4 mm, or local infection symptoms are extracted before or as early as possible after beginning of medication in cancer patients receiving high-dose antiresorptive agent therapy to prevent the development of MRONJ.


Assuntos
Perda do Osso Alveolar , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Neoplasias , Perda do Osso Alveolar/induzido quimicamente , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/tratamento farmacológico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/epidemiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/uso terapêutico , Humanos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Estudos Retrospectivos , Fatores de Risco
10.
Artigo em Inglês | MEDLINE | ID: mdl-35457491

RESUMO

It is controversial as to whether the withdrawal of antiresorptive (AR) agents is necessary while treating medication-related osteonecrosis of the jaw (MRONJ). In this study, we investigated whether a drug holiday promoted sequestrum separation and improved the surgical outcomes of MRONJ patients with malignant tumors, who were undergoing high-dose AR therapy. In total, we included 103 MRONJ patients with malignant tumors as their primary disease who underwent surgery at Nagasaki University Hospital or Kansai Medical University Hospital from January 2009 to December 2020. We recorded the patients' age, sex, primary disease, MRONJ stage, type and administration period of the AR agent, presence of diabetes, corticosteroid use, drug holiday period, white blood cell count, serum albumin, serum creatinine, outcomes, and computed tomography findings. The relationships between a drug holiday and sequestrum separation, and between a drug holiday and outcome, were analyzed. Drug holidays of 60, 90, and 120 days were not significant factors of sequestrum separation and did not influence patients' surgical outcomes as per the univariate and multivariate analyses. MRONJ patients with cancer as their primary disease should be operated upon immediately and without drug holidays if their general condition permits surgery.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Neoplasias , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/cirurgia , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/administração & dosagem , Difosfonatos/efeitos adversos , Humanos , Neoplasias/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
11.
Curr Treat Options Oncol ; 23(4): 578-593, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35312963

RESUMO

OPINION STATEMENT: Nectin-4 is a tumor-associated antigen that is highly expressed on various cancer cells, and it has been further proposed to have roles in tumor development and propagation ranging from cellular proliferation to motility and invasion. Nectin-4 blockade reduces tumor proliferation and induces apoptosis in several malignancies. Nectin-4 has been used as a potential target in antibody-drug conjugate (ADC) development. Enfortumab vedotin, an ADC against Nectin-4, has demonstrated efficacy against solid tumor malignancies. Enfortumab vedotin has received US Food and Drug Administration approval for treating urothelial cancer. Furthermore, the efficacy of ADCs against Nectin-4 against solid tumors other than urothelial cancer has been demonstrated in preclinical studies, and clinical trials examining the effects of enfortumab vedotin are ongoing. Recently, Nectin-4 was reported to be highly expressed in several skin cancers, including malignant melanoma, cutaneous squamous cell carcinoma, and extramammary Paget's disease, and involved in tumor progression and survival in retrospective studies. Nectin-4-targeted therapies and ADCs against Nectin-4 could therefore be novel therapeutic options for skin cancers. This review highlights current knowledge on Nectin-4 in malignant tumors, the efficacy of enfortumab vedotin in clinical trials, and the prospects of Nectin-4-targeted agents against skin cancers.


Assuntos
Anticorpos Monoclonais , Carcinoma de Células Escamosas , Moléculas de Adesão Celular , Imunoconjugados , Terapia de Alvo Molecular , Neoplasias Cutâneas , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Moléculas de Adesão Celular/antagonistas & inibidores , Humanos , Imunoconjugados/farmacologia , Imunoconjugados/uso terapêutico , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias Urológicas/tratamento farmacológico
12.
Sci Rep ; 12(1): 4031, 2022 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-35256687

RESUMO

Angiosarcoma is a rare, life-threatening soft tissue sarcoma with malignant endothelial cells that is mainly found in the skin. Multidisciplinary approaches are used to treat patients with unresectable metastasized lesions; considering the cellular origin of angiosarcoma, anti-angiogenic therapy has also been used recently. However, these treatments have limited efficacy, and the survival rate remains low. Thus, more effective treatments need to be developed. Nectin cell adhesion molecule 4 (NECTIN4) is highly expressed in malignant tumors and promotes tumor progression. Thus, NECTIN4 is expected to be a novel therapeutic target for cancer. However, the significance of NECTIN4 in angiosarcoma remains unknown. Using immunohistochemistry, we investigated NECTIN4 expression in 74 tissue samples from angiosarcoma patients, finding variable NECTIN4 expression. In addition, we investigated NECTIN4 expression and function in human angiosarcoma cell lines. NECTIN4 expression was higher in angiosarcoma cells than normal endothelial cells, and angiosarcoma cells were sensitive to monomethyl auristatin E, the cytotoxic part of a NECTIN4-targetting antibody-drug conjugate. NECTIN4 knockdown inhibited the proliferation and angiogenesis of angiosarcoma cells, and Src kinase signaling was shown to be involved in NECTIN4 function, at least in part. NECTIN4-targeted therapy has the potential to be a novel treatment strategy for angiosarcoma.


Assuntos
Moléculas de Adesão Celular , Hemangiossarcoma , Neoplasias Cutâneas , Quinases da Família src , Moléculas de Adesão Celular/imunologia , Moléculas de Adesão Celular/metabolismo , Células Endoteliais/metabolismo , Hemangiossarcoma/irrigação sanguínea , Hemangiossarcoma/tratamento farmacológico , Hemangiossarcoma/metabolismo , Humanos , Imunoconjugados/farmacologia , Nectinas , Neovascularização Patológica/tratamento farmacológico , Neoplasias Cutâneas/irrigação sanguínea , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/metabolismo , Quinases da Família src/metabolismo
13.
J Clin Med ; 11(3)2022 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-35160059

RESUMO

Sebaceous carcinoma and sweat gland carcinoma (malignant tumors with apocrine and eccrine differentiation) are rare malignant skin adnexal tumors that differentiate toward sebaceous gland and eccrine and apocrine glands, respectively. Owing to the rarity of these carcinomas, standard treatments for advanced disease have not been established. Because the prognosis of patients with systemic metastasis is poor, a new treatment for these diseases is eagerly desired. Trophoblast cell surface antigen 2 (TROP2) and sacituzumab govitecan, an antibody-drug conjugate of TROP2, have attracted attention in the treatment of various solid tumors. In the current study, we immunohistochemically investigated TROP2 expression in 14 sebaceous carcinoma and 18 sweat gland carcinoma samples and found strong and relatively homogeneous TROP2 staining in both cancer types. The mean Histoscore, a semi-quantitative scoring ranging from 0 (negative) to 300, was 265.5 in sebaceous carcinoma and 260.0 in sweat gland carcinoma. These observations directly suggest that both sebaceous carcinoma and sweat gland carcinoma could be potentially treated with TROP2-targeted antibody-drug conjugates such as sacituzumab govitecan.

14.
BMJ Open ; 12(1): e056781, 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35039301

RESUMO

INTRODUCTION: This is a randomised, multi-centre, open-label, phase II study to evaluate the efficacy of betamethasone valerate ointment on radiation-induced oral mucositis in patients with head and neck cancer undergoing concomitant radiotherapy with cisplatin or cetuximab. METHODS AND ANALYSIS: The trial will take place at seven hospitals in Japan. Patients will be randomised (1:1) into betamethasone and control groups after the occurrence of grade 1 oral mucositis. In the betamethasone group, patients will use betamethasone valerate ointment five times a day, in addition to usual oral hygiene guidance. The primary endpoint is the incidence and onset time of grade 3 oral mucositis. The secondary endpoints are the incidence and onset time of grade 2 oral mucositis, incidence and onset time of oral candidiasis, completion of radiation therapy and adverse events. Target accrual is 102 patients with a two-sided type I error rate of 5% and 80% power to detect an 80% risk reduction in the incidence of grade 3 oral mucositis. ETHICS AND DISSEMINATION: This study was approved by the Clinical Research Review Board of Nagasaki University (No. CRB20-009). All participants will be required to provide written informed consent. Findings will be disseminated through scientific and professional conferences and peer-reviewed journal publication. The datasets generated during the study will be available from the corresponding author on reasonable request. TRIAL REGISTRATION NUMBER: jRCTs071200013.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Lesões por Radiação , Estomatite , Valerato de Betametasona/uso terapêutico , Ensaios Clínicos Fase II como Assunto , Neoplasias de Cabeça e Pescoço/complicações , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Estudos Multicêntricos como Assunto , Pomadas/uso terapêutico , Neoplasias Orofaríngeas/radioterapia , Lesões por Radiação/etiologia , Lesões por Radiação/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Estomatite/tratamento farmacológico , Estomatite/etiologia , Estomatite/prevenção & controle
15.
Sci Rep ; 11(1): 17226, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446755

RESUMO

Tooth extraction has been avoided since it has been considered a major risk factor for medication-related osteonecrosis of the jaw (MRONJ). However, MRONJ may also develop from tooth that is an infection source. This study aimed to clarify whether tooth extraction is a risk factor for the development of MRONJ in cancer patients receiving bone-modifying agents (BMAs). This retrospective observational study included 189 patients (361 jaws) from two hospitals. The risk factors of MRONJ were identified by comparing patient characteristics between those who did and did not develop MRONJ. Furthermore, the effect of tooth extraction during BMA therapy was analyzed after adjusting for confounding factors using the propensity score matching method. MRONJ occurred in 33 patients jaws. A longer duration of BMA administration, fewer number of teeth, presence of symptoms of local infection, and infected teeth were independent risk factors of MRONJ. However, tooth extraction during BMA therapy did not increase the risk. Propensity score matching analysis showed that tooth extraction significantly lowered the risk of MRONJ development. Teeth that can be an infection source increases the risk of MRONJ, and thus, they need to be extracted even during BMA administration.


Assuntos
Denosumab/uso terapêutico , Arcada Osseodentária/patologia , Neoplasias/tratamento farmacológico , Osteonecrose/diagnóstico , Extração Dentária/métodos , Ácido Zoledrônico/uso terapêutico , Idoso , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Denosumab/efeitos adversos , Feminino , Humanos , Arcada Osseodentária/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias/patologia , Osteonecrose/induzido quimicamente , Pontuação de Propensão , Estudos Retrospectivos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Ácido Zoledrônico/efeitos adversos
16.
Int J Mol Sci ; 22(14)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34299325

RESUMO

Extramammary Paget's disease (EMPD) is a rare skin cancer arising in the apocrine gland-rich areas. Most EMPD tumors are dormant, but metastatic lesions are associated with poor outcomes owing to the lack of effective systemic therapies. Trophoblast cell surface antigen 2 (Trop2), a surface glycoprotein, has drawn attention as a potential therapeutic target for solid tumors. Sacituzumab govitecan, an antibody-drug conjugate of Trop2, has recently entered clinical use for the treatment of various solid cancers. However, little is known about the role of Trop2 in EMPD. In this study, we immunohistochemically examined Trop2 expression in 116 EMPD tissue samples and 10 normal skin tissues. In normal skin, Trop2 was expressed in the epidermal keratinocytes, inner root sheaths, and infundibulum/isthmus epithelium of hair follicles, eccrine/apocrine glands, and sebaceous glands. Most EMPD tissues exhibited homogeneous and strong Trop2 expression, and high Trop2 expression was significantly associated with worse disease-free survival (p = 0.0343). These results suggest the potential use of Trop2-targeted therapy for EMPD and improve our understanding of the skin-related adverse effects of current Trop2-targeted therapies such as sacituzumab govitecan.


Assuntos
Antígenos de Neoplasias/biossíntese , Moléculas de Adesão Celular/biossíntese , Doença de Paget Extramamária/metabolismo , Neoplasias Cutâneas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/farmacologia , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/metabolismo , Glândulas Apócrinas/metabolismo , Biomarcadores Tumorais , Camptotecina/análogos & derivados , Camptotecina/farmacologia , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Feminino , Expressão Gênica/genética , Regulação da Expressão Gênica/genética , Folículo Piloso/metabolismo , Humanos , Imunoconjugados/farmacologia , Queratinócitos/metabolismo , Masculino , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Doença de Paget Extramamária/tratamento farmacológico , Doença de Paget Extramamária/genética , Doença de Paget Extramamária/patologia , Glândulas Sebáceas/metabolismo , Pele/metabolismo , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia
17.
Biomedicines ; 9(4)2021 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-33808400

RESUMO

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, and its incidence is rising because of the aging population. Nectin cell adhesion molecule 4 (NECTIN4) is involved in the progression of tumors and has attracted interest as a potential therapeutic target. However, little is known about the expression and significance of NECTIN4 in cSCC. The aim of this study was to determine the expression and function of NECTIN4 in cSCC. Immunohistological NECTIN4 expression was investigated in tissues from 34 cSCC patients. Using an A431 human SCC cell line, the role of NECTIN4 in the regulation of cell-cell attachment and migration and proliferation was assessed. NECTIN4 was expressed in most cSCC tissues and on the plasma membrane of A431 cells. Silencing of NECTIN4 prevented cell-cell attachment and induced the expression migration-related molecules, leading to an increase in cell migration. Knockdown of NECTIN4 downregulated extracellular signal-regulated kinase signaling, decreased cyclin D1 expression, and inhibited cell proliferation. These results show that NECTIN4 is expressed in cSCC and functions in the regulation of cell-cell interactions, as well as in the migration and proliferation of SCC cells. NECTIN4-targeted therapy may serve as a novel and promising treatment for cSCC.

18.
Curr Treat Options Oncol ; 22(3): 20, 2021 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-33558987

RESUMO

OPINION STATEMENT: In the era of molecular targeted therapy, the accurate detection of BRAF mutation in melanoma has become increasingly important. With the advances of molecular analyses and immunohistochemistry, the presence of BRAF mutational heterogeneity in melanoma has been widely recognized. Although most patients with melanoma have a homogeneous BRAF mutation status because the BRAF mutation occurs at an early stage of melanoma development and acts as a driver gene mutation, BRAF mutational heterogeneity does exist, among different tumor sites of a single patient (intertumor heterogeneity) and/or even within a single tumor (intratumor heterogeneity). To summarize the published reports, about 10% of melanoma patients may show intertumorally discordant BRAF status and about 15% of BRAF-mutated melanomas may have intratumor BRAF heterogeneity, although the reported results vary strikingly among the studies and methods used. Considering the BRAF heterogeneity of melanoma, a single biopsy from a single tumor may not be sufficient to uncover the entire BRAF status of a patient. Multiple samples from different sites may be preferable to assess the indication of BRAF/MEK inhibitors, as recommended by the current clinical guidelines. The impact of BRAF heterogeneity on patient survival or the response to treatment with BRAF/MEK inhibitors is an interesting issue, but requires further investigation.


Assuntos
Biomarcadores Tumorais , Heterogeneidade Genética , Melanoma/etiologia , Melanoma/metabolismo , Proteínas Proto-Oncogênicas B-raf/genética , Animais , Análise Mutacional de DNA , Gerenciamento Clínico , Suscetibilidade a Doenças , Regulação Neoplásica da Expressão Gênica , Humanos , Melanoma/diagnóstico , Melanoma/terapia , Técnicas de Diagnóstico Molecular , Mutação , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , Proteínas Proto-Oncogênicas B-raf/metabolismo
19.
J Dent Sci ; 16(1): 96-100, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33384784

RESUMO

BACKGROUND/PURPOSE: Bioadhesive barrier-forming oral liquid, is a recently developed medical material for the management of pain caused by oral mucositis associated with cancer radiotherapy or chemotherapy. The purpose of this study was to evaluate the effectiveness of this liquid in relieving pain resulting from radiation-induced oral mucositis in patients with head and neck cancer. MATERIALS AND METHODS: This randomized, crossover trial investigated the analgesic effects of bioadhesive barrier-forming oral liquid using dexamethasone ointment as a control. Fifteen patients with mild or moderate pain due to radiation-induced oral mucositis were randomly assigned to two groups. Group A applied dexamethasone ointment once on day 1, had a wash-out period on day 2, and used bioadhesive barrier-forming oral liquid once on day 3. Conversely, group B used bioadhesive barrier-forming oral liquid on day 1, had a wash-out period on day 2, and applied dexamethasone ointment once on day 3. The effectiveness in relieving pain was compared between the two groups. RESULTS: One patient reported nausea immediately after the application of bioadhesive barrier-forming oral liquid and was therefore excluded from the analysis. Dexamethasone ointment and bioadhesive barrier-forming oral liquid relieved pain in 85.7% and 71.4% patients, respectively (p = 0.682). Nine patients wished to continue dexamethasone ointment after the study, while only five wished to continue bioadhesive barrier-forming oral liquid. CONCLUSION: Our findings suggest that the analgesic effect of bioadhesive barrier-forming oral liquid is comparable or inferior to that of dexamethasone ointment in patients with radiation-induced oral mucositis. Further studies are needed to verify these findings.

20.
J Dent Sci ; 16(1): 154-159, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33384792

RESUMO

BACKGROUND/PURPOSE: TThe bone cavities after extirpation of cysts or tumor of the jawbone requires the insertion of gauze containing various antibiotics/antiseptics to minimize the risk of pain, bleeding, and surgical site infection (SSI). However, there have been few reports on the efficacy of topical administration of antibiotics/antiseptics to an open wound of the jawbone. To compare the inhibitory effects of topical povidone-iodine gel and tetracycline ointment on the jawbone wound bacterial growth after extirpation of cyst or tumor. MATERIALS AND METHODS: This is a preliminary, randomized controlled, open-labeled trial. Eighteen patients were randomly assigned into two groups. In povidone-iodine (PI) group, gauze mixed with povidone-iodine gel was inserted into the bone cavity wound, and in tetracycline (TC) group gauze mixed with tetracycline ointment was inserted after extirpation of cyst or tumor of the jaw bone. In both groups, gauze was removed 48 h after surgery, and examined by bacterial culture and real-time polymerase chain reaction (PCR) using primers detecting total bacteria and MRSA. RESULTS: The topical application of tetracycline ointment was superior to that of povidone-iodine gel concerning inhibitory effects of total bacteria and methicillin-resistant Staphylococcus aureus (MRSA). CONCLUSION: This preliminary study suggests that the insertion of gauze mixed with tetracycline ointment is recommended for bone wounds after extirpation of cyst or tumor of the oral cavity.

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