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1.
Int J Oral Maxillofac Surg ; 52(6): 621-629, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36470693

RESUMO

The aim of this study was to assess changes in the quality of life and psychological distress of patients with tongue cancer undergoing total/subtotal glossectomy (TG) or extended hemiglossectomy (HG) and free flap transfer. Differences between the two groups were compared using the Short Form 8-Item Health Survey (SF-8) and Hospital Anxiety and Depression Scale (HADS). Of the 43 patients with tongue cancer, 24 (56%) underwent TG and 19 (44%) underwent HG. The general health and social functioning scores in the SF-8 and depression in the HADS were significantly worse in the TG group than in the HG group at 12 months after surgery, indicating that patients in the TG group may experience social isolation and psychological distress, and have difficulty in employability even 12 months after surgery. In contrast, all items of the SF-8 in the HG group were nearly equal to those in the general population. Due to the extensive psychological impact on patients with tongue cancer who are planned for an extended resection, curative surgery with free flap transfer and multidisciplinary psychiatric support are essential to improve quality of life and manage psychological distress.


Assuntos
Retalhos de Tecido Biológico , Procedimentos de Cirurgia Plástica , Angústia Psicológica , Neoplasias da Língua , Humanos , Glossectomia , Neoplasias da Língua/cirurgia , Qualidade de Vida , Antebraço , Língua/cirurgia
2.
ACS Chem Biol ; 17(8): 2284-2295, 2022 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-35904259

RESUMO

N-Methylated amino acids (N-MeAAs) are privileged residues of naturally occurring peptides critical to bioactivity. However, de novo discovery from ribosome display is limited by poor incorporation of N-methylated amino acids into the nascent peptide chain attributed to a poor EF-Tu affinity for the N-methyl-aminoacyl-tRNA. By reconfiguring the tRNA's T-stem region to compensate and tune the EF-Tu affinity, we conducted Random nonstandard Peptides Integrated Discovery (RaPID) display of a macrocyclic peptide (MCP) library containing six different N-MeAAs. We have here devised a "pool-and-split" enrichment strategy using the RaPID display and identified N-methylated MCPs against three species of prokaryotic metal-ion-dependent phosphoglycerate mutases. The enriched MCPs reached 57% N-methylation with up to three consecutively incorporated N-MeAAs, rivaling natural products. Potent nanomolar inhibitors ranging in ortholog selectivity, strongly mediated by N-methylation, were identified. Co-crystal structures reveal an architecturally related Ce-2 Ipglycermide active-site metal-ion-coordinating Cys lariat MCP, functionally dependent on two cis N-MeAAs with broadened iPGM species selectivity over the original nematode-selective MCPs. Furthermore, the isolation of a novel metal-ion-independent Staphylococcus aureus iPGM inhibitor utilizing a phosphoglycerate mimetic mechanism illustrates the diversity of possible chemotypes encoded by the N-MeAA MCP library.


Assuntos
Transferases Intramoleculares , Fator Tu de Elongação de Peptídeos , Aminoácidos/química , Transferases Intramoleculares/metabolismo , Fator Tu de Elongação de Peptídeos/metabolismo , Biblioteca de Peptídeos , Peptídeos/química , Peptídeos Cíclicos/química , RNA de Transferência
3.
J Laryngol Otol ; 135(4): 297-303, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33785085

RESUMO

BACKGROUND: The prognosis of patients with advanced squamous cell carcinoma of the external auditory canal and middle ear has been improved by advances in skull base surgery and multidrug chemoradiotherapy during the last two decades. METHODS: Ninety-five patients with squamous cell carcinoma of the external auditory canal and middle ear who were treated between 1998 and 2017 were enrolled. The number of patients with tumour stages T1, T2, T3 and T4 was 15, 22, 24 and 34, respectively. Oncological outcomes and prognostic factors were retrospectively investigated. RESULTS: Among patients with T4 disease, invasion of the brain (p = 0.024), carotid artery (p = 0.049) and/or jugular vein (p = 0.040) were significant predictors of poor prognosis. The five-year overall survival rate of patients with at least one of these factors (T4b) was significantly lower than that of patients without these factors (T4a) (25.5 vs 65.5 per cent, p = 0.049). CONCLUSION: It is proposed that stage T4 be subclassified into T4a and T4b according to the prognostic factors.


Assuntos
Carcinoma de Células Escamosas/classificação , Neoplasias da Orelha/classificação , Estadiamento de Neoplasias/classificação , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Meato Acústico Externo/patologia , Neoplasias da Orelha/patologia , Orelha Média/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
4.
AJNR Am J Neuroradiol ; 40(12): 2045-2051, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31753834

RESUMO

BACKGROUND AND PURPOSE: Photodynamic therapy is a novel treatment that provides effective local control, but little is known about photodynamic therapy-induced changes on MR imaging. The aim of this study was to assess the utility of DWI and ADC in monitoring the response of malignant gliomas to photodynamic therapy. MATERIALS AND METHODS: Time-dependent changes in DWI and ADC values after photodynamic therapy were analyzed in a group that received photodynamic therapy in comparison with a group that did not. RESULTS: Twenty-four patients were enrolled (photodynamic therapy, n = 14; non-photodynamic therapy, n = 10). In all patients who received photodynamic therapy, linear high signals on DWI in the irradiated area were detected adjacent to the resection cavity and were 5-7 mm in depth from 1 day posttreatment and disappeared in about 30 days without any neurologic deterioration. The non-photodynamic therapy group did not show this change. The photodynamic therapy group had significantly lower ADC values from 1 day posttreatment (P < .001), which increased steadily and disappeared by 30 days. There was no decline or time-dependent change in ADC values in the non-photodynamic therapy group. CONCLUSIONS: The acute response of malignant gliomas to photodynamic therapy was detected as linear high signals on DWI and as a decrease in ADC values. These findings were asymptomatic and transient. Although the photodynamic therapy-induced acute response on MR imaging disappeared after approximately 30 days, it may be helpful for confirming the photodynamic therapy-irradiated area.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/terapia , Imagem de Difusão por Ressonância Magnética/métodos , Glioma/diagnóstico por imagem , Glioma/terapia , Adulto , Idoso , Feminino , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Neuroimagem/métodos , Fotoquimioterapia/métodos , Sensibilidade e Especificidade , Resultado do Tratamento
5.
Ann Hematol ; 98(9): 2131-2138, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31286196

RESUMO

The optimal dose, schedule, and other aspects of bendamustine plus rituximab treatment remain unclear for patients with relapsed or refractory follicular lymphoma (FL). Herein, we analyzed the efficacy of bendamustine combined with rituximab (RB-120) treatment for Japanese patients with relapsed or refractory FL. This phase II clinical trial included patients with relapsed or refractory FL who received 375 mg/m2 rituximab on day 1 and 120 mg/m2 bendamustine on days 2 and 3 every 28 days for up to 6 cycles. The primary endpoint was the overall response rate (ORR), and the secondary endpoints included the complete response (CR) rate, progression-free survival (PFS), overall survival (OS), and safety. Thirty-seven patients were enrolled in the trial (median age 62 years, range 42-75 years). All patients were previously treated with rituximab-containing chemotherapy, and 83.8% were previously treated with the R-CHOP regimen. A median of 5 cycles (range 1-6) and 48.6% of patients completed 6 cycles. The ORR was 91.9% (95% confidence interval [CI] 78.1-98.3%), with a CR rate of 86.5% (95% CI 71.2-95.5%). The 3-year PFS and OS were 70.9% (95% CI 52.3-83.3%) and 88.9% (95% CI 73.1-95.7%), respectively, with the median 39.5 months follow-up duration. The most-frequently observed grade 3/4 adverse events were hematologic: lymphopenia (95%) and neutropenia (70%). No treatment-related deaths were observed. RB-120 showed a good efficacy with equivalent toxicities, compared with the bendamustine 120 mg/m2 monotherapy. However, the problem of high drop-out incidences cannot be ignored.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma Folicular , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cloridrato de Bendamustina/administração & dosagem , Cloridrato de Bendamustina/efeitos adversos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Linfoma Folicular/tratamento farmacológico , Linfoma Folicular/mortalidade , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Neutropenia/mortalidade , Rituximab/administração & dosagem , Rituximab/efeitos adversos , Taxa de Sobrevida
7.
Int J Oral Maxillofac Surg ; 48(5): 644-650, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30609954

RESUMO

Patients with orofacial pain and discomfort often suffer from psychiatric disorders. However, few studies involving a large sample have examined the diagnostic results of patients with orofacial pain or discomfort in relation to psychiatric disorders. The purpose of this study was to summarize and clarify the characteristics and demographic data of 1202 patients attending the psychiatric liaison clinic at Aichi Gakuin University Hospital. Psychiatric diagnosis was performed by psychiatrists for all patients, based on the Diagnostic and Statistical Manual of Mental Disorders, fifth edition. Among the 1202 patients, 992 (82.5%) were female. The average age of the patients was 57.2±15.0years. The predominant broad categories of orofacial pain and discomfort seen were burning mouth syndrome (n=484, 40.3%), persistent idiopathic facial pain (n=258, 21.5%), and oral dysesthesia (n=215, 17.9%). The predominant broad categories of psychiatric diagnoses seen were somatic symptoms and related disorders (n=934, 77.7%) and depressive disorders (n=76, 6.3%). Among the 934 patients with somatic symptoms and related disorders, 678 had a somatic symptom disorder with predominant pain. The results confirmed that most patients with orofacial pain and discomfort were middle-aged and elderly women suffering from a somatic symptom disorder with predominant pain.


Assuntos
Síndrome da Ardência Bucal , Transtorno Depressivo , Transtornos Mentais , Adulto , Idoso , Dor Facial , Feminino , Humanos , Pessoa de Meia-Idade
8.
Andrology ; 6(1): 158-165, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29179259

RESUMO

Histone H3.5 (H3.5) is a newly identified histone variant highly expressed in the human testis. We have reported the crystal structure, instability of the H3.5 nucleosome and accumulation around transcription start sites, mainly in primary spermatocytes, but its role in human spermatogenesis remains poorly understood. Testicular biopsy specimens from 30 men (mean age: 35 years) with non-obstructive azoospermia (NOA) who underwent microdissection testicular sperm extraction and 23 men with obstructive azoospermia (OA) were included. An H3.5-specific mouse monoclonal antibody recognizing an H3.5-specific synthetic peptide was generated, and immunohistological staining for H3.5 and proliferating cell nuclear antigen (PCNA) was performed on Bouin's solution-fixed sections. Expression and localization of H3.5 were compared with patient background, germinal stage, and PCNA expression. In testes of patients with normal spermatogenesis, differentially expressed H3.5 was specifically localized in either spermatogonia or preleptotene/leptotene-stage primary spermatocytes, especially during germinal stages VI-X. In NOA testes, mRNA expression of H3.5 (H3F3C) was significantly reduced compared with other H3 histone family members, and expression of H3.5 was significantly lower than that in OA. Additionally, the number of H3.5-positive germ cells was higher in hypospermatogenesis or late maturation arrest than in early maturation arrest in NOA testes (p < 0.01). A significant positive correlation was observed between H3.5 and PCNA expression (p < 0.05) but not TUNEL-positive cells, and expression of H3.5 was enhanced after hCG-based salvage hormonal therapy. Different from other testis-specific histones, which are often expressed during the histone-to-protamine transition during meiosis, H3.5 was expressed mainly in immature germ cells. H3.5 may play roles in DNA synthesis, but not apoptosis, and its expression is regulated by gonadotropins, indicating that such epigenetic regulations are important in normal spermatogenesis and spermatogenic disorders.


Assuntos
Azoospermia/metabolismo , Histonas/metabolismo , Espermatogênese/fisiologia , Espermatozoides/metabolismo , Adulto , Histonas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
9.
Eur J Gynaecol Oncol ; 37(4): 581-583, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-29894091

RESUMO

Gynandroblastoma, an extremely rare ovarian tumour that usually consists of both Sertoli stromal cell and granulosa cell tumours, often produces both androgenic and estrogenic effects. The authors herein report a case of gynandroblastoma with the longest disease-free period reported to date. A 66-year-old woman without metrorrhagia or hirsutism presented with abdominal pain and slightly elevated serum estradiol levels. Her uterus was enlarged, and endometrial curettage performed to reduce endometrial thickness prior to laparotomy led to a diagnosis of atypical endometrial hyperplasia. She was diagnosed of ovarian tumour. The pathology report revealed that the right ovarian tumour was a "gynandroblastoma". Such lesions are classified as borderline malignant. Postoperative adjuvant therapy was not administered in this case because only a few recurrent or fatal cases have been reported. The lesion was classified as pTlaN0M0 according to Union for International Cancer Control (UICC). The patient is alive and has been disease-free for 77 months post-surgery.


Assuntos
Pós-Menopausa , Tumores do Estroma Gonadal e dos Cordões Sexuais/patologia , Idoso , Evolução Fatal , Feminino , Humanos , Estadiamento de Neoplasias , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/patologia , Tumores do Estroma Gonadal e dos Cordões Sexuais/cirurgia
11.
Oncogene ; 34(2): 199-208, 2015 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-24362523

RESUMO

POU5F1B (POU domain class 5 transcription factor 1B), a processed pseudogene that is highly homologous to OCT4, was recently shown to be transcribed in cancer cells, but its clinical relevance and biological function have remained unclear. We now show that POU5F1B, which is located adjacent to MYC on human chromosome 8q24, is frequently amplified in gastric cancer (GC) cell lines. POU5F1B, but not OCT4, was also found to be expressed at a high level in GC cell lines and clinical specimens. In addition, the DNA copy number and mRNA abundance for POU5F1B showed a positive correlation in both cancer cell lines and GC specimens. Overexpression of POU5F1B in GC cells promoted colony formation in vitro as well as both tumorigenicity and tumor growth in vivo, and these effects were enhanced in the additional presence of MYC overexpression. Furthermore, knockdown of POU5F1B expression with a short hairpin RNA confirmed a role for the endogenous pseudogene in the promotion of cancer cell growth in vitro and tumor growth in vivo. POU5F1B overexpression induced upregulation of various growth factors in GC cells as well as exhibited mitogenic, angiogenic and antiapoptotic effects in GC xenografts. Finally, amplification of POU5F1B was detected in 17 (12%) of 145 cases of GC and was a significant predictor of poor prognosis in patients with stage IV disease. In conclusion, we found that the POU5F1B pseudogene is amplified and expressed at a high level in, as well as confers an aggressive phenotype on, GC, and that POU5F1B amplification is associated with a poor prognosis in GC patients.


Assuntos
Fator 3 de Transcrição de Octâmero/genética , Pseudogenes , Neoplasias Gástricas/genética , Animais , Proliferação de Células/genética , Feminino , Amplificação de Genes , Dosagem de Genes , Células HEK293 , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fator 3 de Transcrição de Octâmero/biossíntese , Fenótipo , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia
12.
Bone Joint J ; 96-B(4): 555-61, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24692627

RESUMO

In 1999, we developed a technique for biological reconstruction after excision of a bone tumour, which involved using autografts of the bone containing the tumour treated with liquid nitrogen. We have previously reported the use of this technique in 28 patients at a mean follow up of 27 months (10 to 54). In this study, we included 72 patients who underwent reconstruction using this technique. A total of 33 patients died and three were lost to follow-up, at a mean of 23 months (2 to 56) post-operatively, leaving 36 patients available for a assessment at a mean of 101 months 16 to 163) post-operatively. The methods of reconstruction included an osteo-articular graft in 16, an intercalary in 13 and, a composite graft with prosthesis in seven. Post-operative function was excellent in 26 patients (72.2%), good in seven (19.4%), and fair in three (8.3%) according to the functional evaluation system of Enneking. No recurrent tumour occurred within the grafts. The autografts survived in 29 patients (80.6%), and the rates of survival at five and ten years were 86.1% and 80.6 %, respectively. Seven of 16 osteo-articular grafts (44%) failed because of fracture or infection, but all the composite and intercalary grafts survived. The long-term outcomes of frozen autografting, particularly using composite and intercalary grafts, are satisfactory and thus represent a good method of treatment for patients with a sarcoma of bone or soft tissue.


Assuntos
Neoplasias Ósseas/cirurgia , Transplante Ósseo/métodos , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/cirurgia , Adolescente , Adulto , Idoso , Transplante Ósseo/efeitos adversos , Criança , Feminino , Seguimentos , Congelamento , Sobrevivência de Enxerto , Humanos , Estimativa de Kaplan-Meier , Salvamento de Membro/métodos , Masculino , Pessoa de Meia-Idade , Nitrogênio , Osteossarcoma/cirurgia , Coleta de Tecidos e Órgãos/métodos , Transplante Autólogo/métodos , Resultado do Tratamento
13.
Oncogene ; 33(5): 643-52, 2014 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-23318426

RESUMO

Cancer stem cells (CSCs), a small and elusive population of undifferentiated cancer cells within tumors that drive tumor growth and recurrence, are believed to resemble normal stem cells. Although surrogate markers have been identified and compelling CSC theoretical models abound, actual proof for the existence of CSCs can only be had retrospectively. Hence, great store has come to be placed in isolating CSCs from cancers for in-depth analysis. On the other hand, although induced pluripotent stem cells (iPSCs) hold great promise for regenerative medicine, concern exists over the inadvertent co-transplantation of partially or undifferentiated stem cells with tumorigenic capacity. Here we demonstrate that the introduction of defined reprogramming factors (OCT4, SOX2, Klf4 and c-Myc) into MCF-10A nontumorigenic mammary epithelial cells, followed by partial differentiation, transforms the bulk of cells into tumorigenic CD44(+)/CD24(low) cells with CSC properties, termed here as induced CSC-like-10A or iCSCL-10A cells. These reprogrammed cells display a malignant phenotype in culture and form tumors of multiple lineages when injected into immunocompromised mice. Compared with other transformed cell lines, cultured iCSCL-10A cells exhibit increased resistance to the chemotherapeutic compounds, Taxol and Actinomycin D, but higher susceptibility to the CSC-selective agent Salinomycin and the Pin1 inhibitor Juglone. Restored expression of the cyclin-dependent kinase inhibitor p16INK4a abrogated the CSC properties of iCSCL-10A cells, by inducing cellular senescence. This study provides some insight into the potential oncogenicity that may arise via cellular reprogramming, and could represent a valuable in vitro model for studying the phenotypic traits of CSCs per se.


Assuntos
Reprogramação Celular , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células-Tronco Pluripotentes Induzidas/citologia , Glândulas Mamárias Humanas/citologia , Células-Tronco Neoplásicas/citologia , Animais , Neoplasias da Mama/patologia , Antígeno CD24/biossíntese , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células , Senescência Celular/efeitos dos fármacos , Inibidor p16 de Quinase Dependente de Ciclina/farmacologia , Dactinomicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Receptores de Hialuronatos/biossíntese , Fator 4 Semelhante a Kruppel , Fatores de Transcrição Kruppel-Like/metabolismo , Células MCF-7 , Glândulas Mamárias Humanas/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Naftoquinonas/farmacologia , Fator 3 de Transcrição de Octâmero/metabolismo , Paclitaxel/farmacologia , Proteínas Proto-Oncogênicas c-myc/metabolismo , Piranos/farmacologia , Fatores de Transcrição SOXB1/metabolismo , Esferoides Celulares/metabolismo
14.
Br J Cancer ; 109(5): 1100-8, 2013 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-23922113

RESUMO

BACKGROUND: Chemokines and chemokine receptors not only have significant roles in cancer metastasis and tumorigenesis but also act as antitumour agents. The interaction between the Crk-like adaptor protein (CrkL), which is encoded by the CRKL gene, and non-receptor tyrosine kinase c-ABL is reported to transform many cells into malignant cells. We examined the effects of CC chemokine receptor 7 (CCR7), CCR7 ligands and CrkL and c-ABL in lung adenocarcinoma. METHODS: One hundred and twenty patients with lung adenocarcinoma were included in this historical cohort analysis. We examined CCR7 and CCR7 ligands and CrkL and c-ABL mRNA expressions in surgically resected lung adenocarcinoma specimens and evaluated their contribution to prognosis, and the relationship with epidermal growth factor receptor (EGFR) and TP53 mutations. RESULTS: High CCR7 mRNA expressions indicated better prognoses than those of the groups with low CCR7 mRNA expressions (P=0.007, HR=2.00, 95% CI of ratio: 1.22 -3.31). In lung adenocarcinoma, CrkL and c-ABL mRNAs were related to CCR7 mRNA expression (P<0.0001). CrkL and c-ABL mRNA expressions were influenced by EGFR mutations. A high expression of CCL19 was a good prognostic factor of lung adenocarcinoma. CONCLUSION: We propose that CCR7 and CCL19 are clinically good prognostic factors and that CCR7 is strongly related to CrkL and c-ABL kinase mRNA expression in lung adenocarcinoma.


Assuntos
Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidade , Biomarcadores Tumorais/metabolismo , Quimiocina CCL19/biossíntese , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/mortalidade , Receptores CCR7/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Adenocarcinoma/cirurgia , Adenocarcinoma de Pulmão , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Quimiocina CCL19/genética , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Prognóstico , Proteínas Proto-Oncogênicas c-abl/genética , RNA Mensageiro/biossíntese , Receptores CCR7/genética , Taxa de Sobrevida , Proteína Supressora de Tumor p53/genética
15.
Sex Dev ; 7(6): 316-24, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23867162

RESUMO

The fate of the differentiating gonads in pejerrey Odontesthes bonariensis is determined by the environmental water temperature experienced by the larvae during the critical period of sex determination. We previously reported a link between apoptosis, temperature and sex differentiation in this species. To clarify this link, we subjected larvae to thermal and endocrine treatments between hatching and the onset of histological sex differentiation of the gonads and assessed the patterns of gonadal development and apoptosis by light microscopic histology and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) analysis, respectively. Apoptotic labeling was widespread among somatic cells of the anterior region of the right gonads of fish reared at the male-producing temperature (MPT) and part of the fish at the mixed sex-producing temperature prior to sex differentiation. In contrast, TUNEL-positive cells were rarely observed in gonads at the female-producing temperature (FPT). Administration of exogenous estrogen completely prevented MPT-induced masculinization, induced feminization and reduced gonadal apoptosis, whereas an aromatase inhibitor (fadrozole) induced TUNEL signals in the gonads of FPT-reared larvae. These results provide strong evidence that apoptosis in somatic cells in the right lobe of the gonads might play a key role in testicular differentiation in pejerrey and that estrogens are involved in the regulation of this process.


Assuntos
Apoptose , Peixes/crescimento & desenvolvimento , Hormônios Esteroides Gonadais/fisiologia , Gônadas/citologia , Diferenciação Sexual/fisiologia , Temperatura , Animais , Inibidores da Aromatase/farmacologia , Estrogênios/farmacologia , Estrogênios/fisiologia , Fadrozol/farmacologia , Feminino , Marcação In Situ das Extremidades Cortadas , Masculino , Diferenciação Sexual/efeitos dos fármacos , Testículo/crescimento & desenvolvimento
16.
J Oral Rehabil ; 40(5): 368-74, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23438017

RESUMO

Gender-related risk factors in the survival of transplanted teeth with complete root formation have not yet been identified. The purpose of this study was to investigate gender differences in tooth autotransplantation at dental clinics. We asked participating dentists to provide information on transplantations they had undertaken from 1 January 1990 to 1931 December 2010. The data were screened to exclude patients who underwent more than one transplantation, smokers or those whose smoking habits were unknown, patients under 30 or who were 70 years old and over, cases where the transplanted teeth had incomplete root formation or multiple roots and those with fewer than 20 present teeth post-operation. We analysed 73 teeth of 73 males (mean age, 47.2 years) and 106 teeth of 106 females (mean age, 45.3 years) in this study. The cumulative survival rate and mean survival time were calculated using the Kaplan-Meier method. The cumulative survival rate for males was 88.3% at the 5-year mark, 64.8% at 10 years and 48.6% at 15 years; for females, it was 97.2% at the 5-year mark, 85.9% at 10 years and 85.9% at 15 years. A log-rank test indicated the difference between males and females to be significant (P = 0.011). There was also a significant difference in the main causes for the loss of transplanted teeth: males lost more transplanted teeth due to attachment loss than females (P < 0.05). These results indicate that males require more attention during the autotransplantation process, particularly at the stage of pre-operation evaluation and that of follow-up maintenance.


Assuntos
Raiz Dentária/anatomia & histologia , Dente/transplante , Adulto , Idoso , Dente Pré-Molar/patologia , Dente Pré-Molar/transplante , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Masculino , Pessoa de Meia-Idade , Dente Molar/patologia , Dente Molar/transplante , Odontogênese/fisiologia , Perda da Inserção Periodontal/complicações , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Perda de Dente/etiologia , Transplante Autólogo , Resultado do Tratamento
17.
J Clin Pharm Ther ; 38(1): 62-7, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23057528

RESUMO

WHAT IS KNOWN AND OBJECTIVE: The increasing cost of drug research and development and the decreasing number of new drugs being launched are serious issues for pharmaceutical companies. Biomarkers for predicting drug effectiveness are regarded as useful tools for combating these trends. However, the extent to which these biomarkers actually help in improving drug development is unclear. Here, we investigated the efficiency of biomarker usage in oncology drug development by focusing on stratification markers. METHODS: Anti-tumour agents for which clinical studies were initiated between 1998 and 2009 were identified using commercially available data sources, and clinical trials registered in ClinicalTrials.gov were examined to identify the use of stratification marker. Phase transition probability for each clinical phase was calculated and analysed along with various other factors that may affect the efficiency of the development process. RESULTS AND DISCUSSION: Of 908 anti-tumour agents identified, 121 (13·3%) utilized stratification markers in their clinical studies. Phase I, II and III transition probabilities for all agents were 76·4%, 50·8% and 58·5%, respectively. Corresponding Phase I, II and III transition probabilities of agents developed with stratification markers of 90·4%, 69·0% and 85·0%, respectively, were significantly higher than those for agents without stratification markers. Orphan designation positively affected phase transition probabilities of agents without stratification markers in all phases, while it did not affect transition probabilities of agents with stratification markers, except for Phase II. This shows that stratification markers help improve the probability of success in the development of agents without orphan designation. WHAT IS NEW AND CONCLUSION: Stratification markers contribute to improving the efficiency of development of anti-cancer drugs. The majority of non-orphan drugs are still being developed without stratification markers. Finding reliable stratification markers for all drugs should improve the success rates in drug development.


Assuntos
Antineoplásicos/farmacologia , Biomarcadores/metabolismo , Desenho de Fármacos , Ensaios Clínicos como Assunto/métodos , Indústria Farmacêutica/métodos , Humanos , Neoplasias/tratamento farmacológico , Produção de Droga sem Interesse Comercial/métodos
18.
J Oral Rehabil ; 40(2): 112-8, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23134328

RESUMO

The aim of this study was to investigate risk factors with age in the long-term prognosis of autotransplantation of teeth with complete root formation at dental clinics. Participating dentists were asked to provide information on transplantations they had undertaken from 1 January 1990 to 31 December 2010. Data on a total of 708 teeth from 637 patients were collected. The data were screened to exclude patients who were under 25 or 70 years of age and over, those who were smokers or whose smoking habits were unknown, those whose transplanted teeth had incomplete root formation or multiple roots and those with fewer than 25 present teeth post-operation. The participants in this study were 71 men (74 teeth) and 100 women (107 teeth) ranging from 25 to 69 years of age. Third molars were used as donor teeth in 89·0% of the cases. The participants were divided into three age groups of 25-39, 40-54 and 55-69. Survival analysis was conducted using the Kaplan-Meier method, and a log-rank test revealed that there were no significant differences in age groups for men or women. Cox regression analysis indicated that the survival of transplanted teeth was not influenced by age. However, although not statistically significant, the clinical success rate was lower in the 55-69-year-old group than that in the younger groups. These results indicate that if suitable donor teeth are available and the conditions are right, autotransplantation is a viable treatment for missing teeth regardless of the age of the patient.


Assuntos
Raiz Dentária/crescimento & desenvolvimento , Dente/transplante , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Dente Serotino/transplante , Prognóstico , Modelos de Riscos Proporcionais , Transplante Autólogo
19.
J Nanosci Nanotechnol ; 12(6): 4883-6, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22905546

RESUMO

Metallic glass is one of the most attractive advanced materials, and many researchers have conducted various developmental research works. Metallic glass is expected to be used as a functional material because of its excellent physical and chemical functions such as high strength and high corrosion resistance. However, the application for small size parts has been carried out only in some industrial fields. In order to widen the industrial application fields, a composite material is preferred for the cost performance. In the coating processes of metallic glass with the conventional deposition techniques, there is a difficulty to form thick coatings due to their low deposition rate. Thermal spraying method is one of the potential candidates to produce metallic glass composites. Metallic glass coatings can be applied to the longer parts and therefore the application field can be widened. The gas tunnel plasma spraying is one of the most important technologies for high quality ceramic coating and synthesizing functional materials. As the gas tunnel type plasma jet is superior to the properties of other conventional type plasma jets, this plasma has great possibilities for various applications in thermal processing. In this study, the gas tunnel type plasma spraying was used to form the metallic glass coatings on the stainless-steel substrate. The microstructure and surface morphology of the metallic glass coatings were examined using Fe-based metallic glass powder and Zr-based metallic glass powder as coating material. For the mechanical properties the Vickers hardness was measured on the cross section of both the coatings and the difference between the powders was compared.


Assuntos
Cristalização/métodos , Vidro/química , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Nanoestruturas/química , Nanoestruturas/ultraestrutura , Gases em Plasma/química , Zircônio/química , Adsorção , Substâncias Macromoleculares/química , Conformação Molecular , Tamanho da Partícula
20.
J Oral Rehabil ; 39(11): 821-9, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22672336

RESUMO

The aim of this study was to investigate the risk factors affecting long-term prognosis of autotransplantation of third molars with complete root formation in males at dental clinics. Participating dentists were requested to provide information on transplantations they had undertaken from 1 January 1990 to 31 December 2010. Data on a total of 708 teeth from 637 patients were collected. After data screening and elimination, participants of this study consisted of 183 teeth of 171 males ranging from 20 to 72 years of age (mean age, 44·8 years). The cumulative survival rate was 86·0% at the 5-year mark, 59·1% at 10 years and 28·0% at 15 years. The mean survival time was 134·5 months, as calculated by the Kaplan-Meier method. Single factor analysis using the log-rank test showed that the following factors had significant influence (P < 0·05) on survival of transplanted teeth: periodontal disease as the reason for recipient site tooth extraction, fewer than 25 present teeth and Eichner index Groups B1 to C. Cox regression analysis examined five factors: age, smoking habit, recipient site extraction caused by periodontal disease, fewer than 25 present teeth and Eichner index. This analysis showed that two of these factors were significant: fewer than 25 present teeth was 2·63 (95% CI, 1·03-6·69) and recipient site extraction caused by periodontal disease was 3·80 (95% CI, 1·61-9·01). The results of this study suggest that long-term survival of transplanted teeth in males is influenced not only by oral bacterium but also by occlusal status.


Assuntos
Dente Serotino/transplante , Adulto , Fatores Etários , Idoso , Coroas , Dente Suporte , Cárie Dentária/etiologia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Perda da Inserção Periodontal/etiologia , Periodontite/complicações , Complicações Pós-Operatórias , Estudos Retrospectivos , Fatores de Risco , Tratamento do Canal Radicular , Reabsorção da Raiz/etiologia , Fatores Sexuais , Fumar , Análise de Sobrevida , Anquilose Dental/etiologia , Extração Dentária , Fraturas dos Dentes/etiologia , Raiz Dentária/lesões , Alvéolo Dental/cirurgia , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
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