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1.
Mol Clin Oncol ; 18(4): 25, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36908979

RESUMO

Currently, there is a lack of evidence-based risk factors for the lateral cervical lymph node metastasis of papillary thyroid carcinoma (PTC). Thus, the risk factors and recurrence rate of lateral cervical lymph node metastasis were investigated in the present study for patients with PTC who underwent initial radical surgery. The data of 274 patients with PTC who underwent initial radical surgery over a 10-year period from January, 2009 to December, 2018 were retrospectively analyzed. By applying univariate analysis, lymphovascular invasion, venous invasion, extrathyroidal infiltration, paratracheal lymph node metastasis and tumor size were designated as significant risk factors for lateral cervical lymph node metastasis. As regards multivariate analysis, paratracheal lymph node metastasis and tumor size were identified as independent risk factors. The recurrence rate was higher in patients presenting with lateral cervical lymph node metastasis, and the disease-free survival rate was significantly lower in the patient group presenting with lateral cervical lymph node metastasis. On the whole, the present study demonstrated that paratracheal lymph node metastasis and tumor size were independent risk factors for lateral cervical lymph node metastasis.

2.
ORL J Otorhinolaryngol Relat Spec ; 85(2): 104-108, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36649679

RESUMO

INTRODUCTION: Papillary thyroid carcinoma is the most common endocrine malignancy and the most common type of thyroid cancer, accounting for approximately 85% of all thyroid cancer cases. It usually has a favorable course, with the 10-year survival rate exceeding 90%. However, the literature reports a recurrence rate of 7-23% after initial surgical treatment. It is important to consider medical treatment policies for this recurrence. METHODS: In this study, we examined the risk factors for the recurrence of papillary thyroid carcinoma. We treated 274 patients with thyroid papillary carcinoma at our hospital between 2009 and 2018. RESULTS: Recurrence occurred in 20 cases (7.3%). Lympho-vascular invasion and lateral cervical lymph node metastasis made significant independent contributions. CONCLUSION: The selection of the surgical mode should be based on the recurrence and after comprehensive consideration of the clinical features.


Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/cirurgia , Esvaziamento Cervical , Carcinoma Papilar/cirurgia , Carcinoma Papilar/secundário , Tireoidectomia , Metástase Linfática/patologia , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Linfonodos/patologia , Fatores de Risco , Recidiva Local de Neoplasia/patologia
3.
Chemistry ; 29(9): e202203162, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36372771

RESUMO

To stabilize SN 2 transition state-like penta-coordinate carbon species, triaryl-substituted cationic carbon compounds bearing a moderately flexible 7-6-7-ring skeleton with sulfur donors were synthesized and characterized. Electronic effects of para substituents (R=Cl, F, H, CH3 , SMe, OMe) of the two equatorial aryl groups bound to the cationic central carbon were investigated systematically along with a planar bidentate thioxanthene derivative. X-ray analysis on their solid-state structures showed that the parent (R=H), chloro-, fluoro- and methyl-derivatives were tetracoordinate carbon (sulfonium) structures, while the p-MeO and thioxanthenyl system were pentacoordinate carbocation structures. The Hammett substituent constants for the para substituents (σp + ) correlates well with the bonding in these compounds. The methylthio-derivative with intermediate Hammett substituent constants (p-MeS; σp + =-0.60) showed a tetracooridnate solid-state structure, though solution UV-Vis properties suggested the presence of a penta-coordinate structure. These findings amount to the first unambiguous solution evidence of the hypervalent apical 3c-4e interactions in pentacoordinate carbon compounds.

4.
Mol Clin Oncol ; 17(1): 116, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35747595

RESUMO

Reconstructive surgery using the free jejunum flap for locally advanced head and neck cancer is effective in preserving the swallowing function; however, it does not allow normal oral intake in all patients. A total of 47 patients underwent surgery at Nara Medical University between Jan 2010 and Dec 2019. The patients' ages ranged from 48 to 86 years. Sites were the hypopharynx (33 cases), larynx and cervical esophagus (5 cases each) and oropharynx (4 cases). Swallowing function was assessed using videofluorography, from the start of oral intake to discharge, as well as meal form at discharge. Lateral-retropharyngeal-lymph node dissection (LRPLND), preoperative radiation therapy, extended resection to the nasopharynx and incidence of stenosis in the jejuno-esophageal anastomosis were examined. Significant differences were revealed in the scores of pharyngeal residues of contrast medium and pharyngeal contraction, with and without preoperative radiotherapy. LRPLND did not affect swallowing function; dissection group cases had lower scores for soft palate elevation. Overall, resection extended to the nasopharynx, and the anastomosis method did not affect scores of swallowing function.

5.
Microb Drug Resist ; 28(3): 355-360, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34990283

RESUMO

The detection rate of extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales, microorganisms associated with health care settings, has significantly increased worldwide. Moreover, their community incidence has increased in several countries. In this study, we investigated the prevalence and genetic diversity of ESBL-producing Escherichia coli isolated from 547 nonduplicated stool specimens from healthy Japanese individuals, between 2015 and 2019. E. coli were isolated on deoxycholate-hydrogen sulfide-lactose (DHL) agar and identified by MALDI-TOF MS, ESBL were screened through disk diffusion method (cefotaxime with or without clavulanate), and genetic detection and genotyping were performed by PCR and DNA sequencing. Clonal similarities between ESBL-producing and nonproducing isolates were assessed by multilocus sequence typing (MLST). The prevalence of ESBL-producing E. coli was 9.7% (53/547). These bacteria harbored CTX-M genes, from which CTX-M-9 (31/53, 58.5%) and CTX-M-1 (13/53, 24.5%) groups were the predominant. The MLST analysis revealed that ST131 genotype prevailed within ESBL-producing E. coli (15/53), whereas ST95 (10/53) and ST73 (8/53) prevailed among non-ESBL producers, with ST131 being present in only four isolates. Overall, a high prevalence rate of CTX-M-type ESBL-producing E. coli was detected. CTX-M-9 group-producing ST131 predominated among healthy Japanese individuals, similar to that observed in hospital isolates. CTX-M-type ESBL may disseminate clonally among hospital patients and subsequently, within the community.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Adulto , Portador Sadio , Proteínas de Escherichia coli/genética , Feminino , Genes Bacterianos , Genótipo , Humanos , Japão , Masculino , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Adulto Jovem , beta-Lactamases/genética
6.
Mol Clin Oncol ; 16(1): 13, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34881033

RESUMO

Multiple endocrine neoplasia (MEN) with medullary thyroid carcinoma (MTC) is associated with rearranged during transfection (RET) mutations. The authors encountered four cases of MTC-related MEN type 2B (MEN2B) with RET codon M918T mutation in one family. Case 1 included a 19 year-old male diagnosed with MTC with lung metastases. Genetic testing revealed an RET codon M918T mutation, which indicated MEN2B. The patient responded partially to vandetanib and the disease has shown no progression in 25 months. Case 2 involved the mother of the patient in Case 1. She underwent total thyroidectomy (TT) when diagnosed with MTC-related MEN2B at 12 years of age, but was not counseled adequately. Cases 3 and 4 involved the sisters of the Case 1 patient and were assessed after Case 1 was diagnosed. Genetic testing revealed the same mutation. Case 3 was diagnosed with MTC and underwent TT. Case 4 was asymptomatic but underwent prophylactic TT; histopathologic examination revealed MTC tissue. Prophylactic TT prevented MTC from being detected at an advanced state. Genetic counseling is essential in treating MEN2B. The mother was uninformed about the genetic characteristics of MEN2B, delaying the detection of MTC in her children. The present study reaffirms the importance of family history and screening.

7.
Mol Clin Oncol ; 15(2): 158, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34194737

RESUMO

Laryngotracheal reconstruction is performed to treat locally advanced thyroid carcinoma invading the larynx and/or trachea. The reconstructive technique varies. The present report describes the case of a 71-year-old female patient who underwent surgery for thyroid carcinoma involving the larynx. Reconstructive surgical techniques were employed to maintain laryngeal structure and function. An anterolateral thigh flap with free rib cartilage grafts was used to compensate for laryngeal defects. Although a temporary tracheal stoma was constructed, it closed spontaneously after decannulation. Therefore, one-stage laryngeal reconstruction was accomplished. Post-operative histopathological examination revealed focal anaplastic changes in the lesion, which mainly consisted of papillary components. Post-operative positron emission tomography/computed tomography indicated early recurrence in the left side of the neck. Therefore, lenvatinib was started as adjuvant therapy. Complete response was observed with lenvatinib therapy. The patient was alive and had good laryngeal function 26 months after the operation. One-stage laryngeal reconstruction can reduce burden and improve quality of life in patients with thyroid carcinoma involving the larynx. Lenvatinib may be useful for treating early recurrence of anaplastic thyroid carcinoma after reconstructive surgery with a free flap.

8.
Mol Clin Oncol ; 15(3): 183, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34277002

RESUMO

Salivary gland carcinoma is a relatively rare disease of the head and neck. Although it frequently presents with distant metastases, few reports have been published on this subject. The present study investigated the prognosis of patients with distant metastases from salivary gland cancer. A total of 24 cases of salivary gland carcinoma with distant metastasis who were initially treated at the Department of Otolaryngology-Head and Neck Surgery of Nara Medical University during a 16-year period from August 2004 to July 2020 were included. The histopathological types included salivary duct carcinoma (8 cases), adenoid cystic carcinoma (6 cases), myoepithelial carcinoma (3 cases), Squamous cell carcinoma (2 cases), adenocarcinoma (2 cases), acinic cell carcinoma (2 cases) and mucoepidermoid carcinoma (1 case). A total of 18 patients had stage IV carcinoma, which represented the majority. Of all patients, ~80% developed distant metastases within 2 years of initial diagnosis. Survival rates after the appearance of distant metastases were 43.5% at 5 years and 14.5% at 10 years. The results of the current study revealed that no factors significantly influenced long-term prognosis after the development of distant metastases. In future, it may be necessary to re-examine these results in a larger sample size and standardise treatment methods as a result.

9.
Med Int (Lond) ; 1(5): 18, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-36698531

RESUMO

Total pharyngolaryngectomy with cervical esophagectomy (TPLCE) is an invasive procedure with various post-operative complications. Tracheal necrosis (TRN) is a fatal complication of TPLCE. The present study aimed to identify a surgical technique which may be used to prevent TRN. The post-operative complications of 48 patients who underwent TPLCE from January, 2010 to December, 2019 were retrospectively investigated. The incidence of TRN was examined and measures against TRN were reviewed. The results revealed that 3 patients (6%) experienced TRN within 1 week following surgery. In addition, 2 patients required the surgical debridement of the necrotic tissue and tracheoplasty. The other patient underwent conservative treatment. Stomal recurrence developed in 1 patient (2%). On the whole, the present study demonstrates that the incidence of TRN following TPLCE is lower than that observed in previous reports, and only one stomal recurrence was reported. Preserving the blood supply to the trachea is essential for the prevention of TRN. The eight surgical processes used herein effectively preserved the blood supply. Further investigations however, are necessary in order to confirm the present findings and to ensure effective measures are found with which to prevent TRN following TPLCE.

10.
Mol Clin Oncol ; 14(1): 1, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33235729

RESUMO

Anaplastic thyroid cancer (ATC) has a poor prognosis. ATC accounts for only 1-2% of all thyroid carcinomas, yet it is one of the most lethal neoplasms in humans. Notably, there are no established treatment protocols for ATC. The present study investigated the prognostic and predictive factors of ATC. A retrospective analysis was conducted on 17 patients with histologically confirmed ATC. The median overall survival of all patients was 3.8 months. In patients under the age of 70 years, the statistically significant prognostic factors indicating longer survival were the absence of distant metastasis and treatment by radical resection. Furthermore, in contrast to previous findings, tumor size and white blood cell count were not associated with ATC prognosis in the present cohort. Importantly, tracheostomy did not contribute to improvement of prognosis and should perhaps not be considered, when unnecessary, to preserve the patient's quality of life. Prognostic factors for ATC are critical to clinicians to enable them to determine which patients will benefit from aggressive treatment strategies, as opposed to supportive care.

11.
BMJ Case Rep ; 13(12)2020 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-33318283

RESUMO

Subglottic stenosis is a disease that causes dyspnoea by congenital or acquired stenosis of the cricoid cartilage and trachea. The cause of acquired subglottic stenosis varies. In this case, we present a case of idiopathic subglottic stenosis. Tracheotomies are performed in many cases, but they require long-term insertion of a tracheal cannula and make treatment difficult. In this case study, we performed a tracheoplasty by resection of the arch of cricoid cartilage and circumcision of the tracheal cartilage and implemented a cannula-free observation protocol.


Assuntos
Cartilagem Cricoide/cirurgia , Laringoestenose/cirurgia , Traqueia/cirurgia , Estenose Traqueal/cirurgia , Anastomose Cirúrgica/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica/métodos , Tomografia Computadorizada por Raios X
12.
Int J Infect Dis ; 98: 281-286, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32619765

RESUMO

OBJECTIVE: To provide data on the molecular characteristics of extended-spectrum ß-lactamase (ESBL)-producing Klebsiella pneumoniae clinical isolates in Japan. METHODS: A total of 100 clinical isolates of ESBL-producing K. pneumoniae collected throughout Japan between June and July 2018 were studied. ESBL genes were analyzed using PCR and DNA sequencing. Transferability of ESBL genes was investigated by conjugation experiments. Plasmid replicon types, virulence genes (rmpA, rmpA2, iucA, iroB, and peg-344) associated with hypervirulent K. pneumoniae (hvKp), and capsule types were detected using PCR. Genotyping was performed using multilocus sequence typing. RESULTS: All ESBL-producing isolates carried blaCTX-M genes. The most predominant CTX-M-type identified was CTX-M-15 (n=55). We identified 24 sequence types (STs) among the CTX-M-15 producers, with ST25 (n=8) being the most common. Most of the transconjugants carrying blaCTX-M-15 contained the FIIk replicon. Of the 100 ESBL-producing isolates, 31 were hvKp defined by the presence of the virulence genes. These ESBL-producing hvKp isolates belonged to eight STs (STs 23, 25, 36, 65, 86, 268, 412, and 4492), with five capsule types (K1, K2, K20, K57, and undefined). CONCLUSIONS: CTX-M-15 was the predominant ESBL among K. pneumoniae isolates from Japan. This study shows that ESBL-producing hvKp strains comprising various clones are emerging in Japan.


Assuntos
Proteínas de Bactérias/metabolismo , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/genética , beta-Lactamases/metabolismo , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana , Humanos , Japão , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Klebsiella pneumoniae/patogenicidade , Tipagem de Sequências Multilocus , Plasmídeos/genética , Plasmídeos/metabolismo , Reação em Cadeia da Polimerase , Virulência , beta-Lactamases/genética
13.
Ann Lab Med ; 40(1): 27-32, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31432636

RESUMO

BACKGROUND: Mutations in the quinolone resistance-determining regions (QRDRs) of Acinetobacter baumannii DNA gyrase (gyrA) and topoisomerase IV (parC) are linked to fluoroquinolone (FQ) resistance. We developed a mismatched PCR-restriction fragment length polymorphism (RFLP) assay to detect mutations in the gyrA and parC QRDRs associated with FQ resistance in A. baumannii. METHODS: Based on the conserved sequences of A. baumannii gyrA and parC, two primer sets were designed for mismatched PCR-RFLP to detect mutations in gyrA (codons 83 and 87) and parC (codons 80 and 84) by introducing an artificial restriction enzyme cleavage site into the PCR products. This assay was evaluated using 58 A. baumannii strains and 37 other Acinetobacter strains that have been identified by RNA polymerase ß-subunit gene sequence analysis. RESULTS: PCR amplification of gyrA and parC was successful for all A. baumannii strains. In 11 FQ -susceptible strains, the gyrA and parC PCR products were digested by the selected restriction enzymes at the site containing gyrA (codons 83 and 87) and parC (codons 80 and 84). PCR products from 47 FQ-resistant strains containing mutations in gyrA and parC were not digested by the restriction enzymes at the site containing the mutation. As for the non-baumannii Acinetobacter strains, although amplification products for gyrA were obtained for 28 strains, no parC amplification product was obtained for any strain. CONCLUSIONS: This assay specifically amplified gyrA and parC from A. baumannii and detected A. baumannii gyrA and parC mutations with FQ resistance.


Assuntos
Acinetobacter baumannii/genética , DNA Girase/genética , DNA Topoisomerase IV/genética , Farmacorresistência Bacteriana/genética , Reação em Cadeia da Polimerase/métodos , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Pareamento Incorreto de Bases , DNA Bacteriano/química , DNA Bacteriano/metabolismo , Fluoroquinolonas/farmacologia , Testes de Sensibilidade Microbiana , Mutação , Polimorfismo de Fragmento de Restrição , Análise de Sequência de DNA
14.
PLoS One ; 14(11): e0225210, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31721789

RESUMO

Almost all cases of carbapenemase-producing Enterobacteriaceae infections in Japan are caused by blaIMP-positive Enterobacteriaceae (especially blaIMP-6) and infections caused by other types of carbapenemase-producing Enterobacteriaceae are quite rare. We examined drug resistance genes co-harboring with blaIMP-6 and their inoculum size effects. We screened ß-lactamase genes, plasmid-mediated quinolone resistance (PMQR) genes, and aminoglycoside-modifying enzyme genes by PCR and performed sequencing for 14 blaIMP-6-positive Enterobacteriaceae. Further, all PMQR-positive isolates were submitted to conjugation and inoculum effect evaluation. Our data showed that 13 of the 14 isolates harbored CTX-M-2 and one co-harbored CTX-M-2 and CTX-M-1 as extended-spectrum ß-lactamases. All isolates carried one or more PMQRs; aac(6')-Ib-cr was the most prevalent (92.8%), and was followed by oqxA (64.3%), qnrS (50%), oqxAB (21.4%), and qnrB (14.3%). However, Klebsiella pneumoniae contains chromosomal OqxAB. Inoculum size effects were significant in all strains for meropenem, 13 strains for imipenem, 7 for levofloxacin, and 3 for amikacin. We observed that 11 of the experimental strains (100%), 8 strains (72.7%), and 1 strain showed inoculum size effects for meropenem, imipenem, and amikacin, respectively. However, four strains harbored qnr genes and two strains harbored qnr genes and QRDR mutations concurrently; no inoculum size effect was seen for levofloxacin. The blaIMP-6-positive Enterobacteriaceae that we studied was found to harbor at least one plasmid-mediated drug resistance gene. The inoculum size effect for carbapenems was thought to be mainly due to IMP-6-type metallo-ß-lactamase; however qnrB and qnrS also had a minimal impact on the inoculum size effect for levofloxacin.


Assuntos
Antibacterianos/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Infecções por Enterobacteriaceae/microbiologia , Enterobacteriaceae/genética , Plasmídeos/genética , Quinolinas/farmacologia , beta-Lactamases/biossíntese , Enterobacteriaceae/metabolismo , Genótipo , Humanos , Testes de Sensibilidade Microbiana , Fenótipo
15.
J Microbiol Methods ; 163: 105653, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31199937

RESUMO

Infection with cagA-positive Helicobacter pylori is associated with gastric cancer. Molecular techniques are vital for accurate H. pylori diagnosis. We developed a loop-mediated isothermal amplification (LAMP) for detecting the H. pylori cagA gene and evaluated its use for clinical diagnosis. A LAMP primer set was designed to recognize the homologous regions of cagA gene sequences of 6 H. pylori strains. LAMP sensitivity was evaluated with serial dilutions of H. pylori ATCC 43504 and fecal specimens; specificity was evaluated with H. pylori ATCC 49396 and CIP 104086. The LAMP sensitivity for H. pylori specimens was 10-1 cfu/tube (reaction time, 37 min), which was 10-fold more sensitive than polymerase chain reaction. LAMP was also highly sensitive and rapid for fecal specimens. It detected cagA gene from ATCC 49396 and CIP 104086. The findings suggest LAMP can be used for diagnosing and screening of H. pylori infections to decrease gastric cancer incidence.


Assuntos
Infecções por Helicobacter/diagnóstico , Helicobacter pylori/isolamento & purificação , Técnicas de Diagnóstico Molecular , Técnicas de Amplificação de Ácido Nucleico , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Fezes/microbiologia , Genes Bacterianos , Helicobacter pylori/genética , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos
16.
Oncol Rep ; 42(1): 436-442, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31059079

RESUMO

Identifying the key molecules that enhance chemo­ and radiosensitivity in head and neck squamous cell carcinoma (HNSCC) as well as reliable biomarkers for predicting recurrence and metastasis would be desirable to improve the prognosis of HNSCC. Previously, we have reported that Regenerating gene III (REG III) expression was associated with an improved survival rate for patients with HNSCC. In addition, resveratrol (3,4',5­trihydroxystilbene) significantly increased REG III expression in HNSCC cells, and significantly inhibited cell growth, enhanced chemo­ and radiosensitivity, and blocked the cancer invasion of HNSCC cells in vitro. In the present study, the effect of resveratrol on cancer progression in HNSCC was investigated in vivo using a xenograft nude mouse model. The results revealed that resveratrol increased the mRNA level of REG III in vivo, which was in agreement with our previous in vitro findings. Furthermore, REG III increased the antitumor effect of radiation or cisplatin in vivo, and resveratrol sensitized HNSCC to irradiation and cisplatin in vivo. These results indicated that resveratrol could increase the efficacy of cisplatin and irradiation through the REG III expression pathway, resulting in the inhibition of HNSCC progression in vivo.


Assuntos
Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Proteínas Associadas a Pancreatite/genética , Radiossensibilizantes/administração & dosagem , Resveratrol/administração & dosagem , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Regulação para Cima , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cisplatino/administração & dosagem , Cisplatino/farmacologia , Sinergismo Farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias de Cabeça e Pescoço/genética , Humanos , Masculino , Camundongos , Camundongos Nus , Radiossensibilizantes/farmacologia , Resveratrol/farmacologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Int J Oncol ; 49(4): 1553-1560, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27633858

RESUMO

Identification of reliable markers of chemo- and radiosensitivity and the key molecules that enhance the susceptibility of head and neck squamous cell carcinoma (HNSCC) to anticancer treatments is highly desirable. Previously, we have reported that regenerating gene (REG) â…¢ expression was such a marker associated with an improved survival rate for HNSCC patients. In the present study, we investigated the stimulators for induction of REG â…¢ expression using REG â…¢ promoter assay in HNSCC cells transfected with REG â…¢ promoter vector. We tested inflammatory cytokines, growth factors, polyphenols, PPARγ activator of thiazolidinediones, and histone deacetylase inhibitors, and found that 3,4',5-trihydroxy-trans-stilbene (resveratrol) significantly increased the REG â…¢ promoter activity and the mRNA levels of REG â…¢ in HNSCC cells. Moreover, we demonstrated the effect of resveratrol on cancer cell progression, such as cell proliferation, chemo­ and radiosensitivity and cancer invasion of HNSCC cells. Resveratrol significantly inhibited cell growth, enhanced chemo­ and radiosensitivity, and blocked cancer invasion of HNSCC cells. These data suggested that resveratrol could inhibit cancer progression through the REG â…¢ expression pathway in HNSCC cells.

18.
Oncol Rep ; 35(1): 261-6, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26498709

RESUMO

Epithelial-mesenchymal transition (EMT) is a key process involved in the invasion and metastasis of cancer cells. Furthermore, EMT can induce a cancer stem cell (CSC)-like phenotype in a number of tumor types. We demonstrated that Snail is one of the master regulators that promotes EMT and mediates cancer cell migration and invasion in many types of malignancies including head and neck squamous cell carcinoma (HNSCC). In the present study, we investigated the role of Snail in inducing and maintaining CSC-like properties through EMT in HNSCC. We established HNSCC cell lines transfected with Snail. Stem cell markers were evaluated with real-time RT-PCR and western blot analysis. CSC properties were assessed using sphere formation and WST-8 assays as well as chemosensitivity and chick chorioallantoic membrane in vivo invasion assays. Introduction of Snail induced EMT properties in HNSCC cells. Moreover, Snail-induced EMT maintained the CSC-like phenotype, and enhanced sphere formation capability, chemoresistance and invasive ability. These data suggest that Snail could be one of the critical molecular targets for the development of therapeutic strategies for HNSCC.


Assuntos
Carcinoma de Células Escamosas/patologia , Transição Epitelial-Mesenquimal , Neoplasias de Cabeça e Pescoço/patologia , Células-Tronco Neoplásicas/patologia , Fatores de Transcrição/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Células-Tronco Neoplásicas/metabolismo , Fatores de Transcrição da Família Snail , Carcinoma de Células Escamosas de Cabeça e Pescoço , Fatores de Transcrição/genética
19.
Int J Oncol ; 44(3): 693-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24365974

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is known to have a poor prognosis. The resistance to treatment and distant metastasis are important clinical problems in HNSCC. The epithelial-mesenchymal transition (EMT) is a key process in successful execution of many steps such as the invasion and metastasis for cancer cells. Snail is one of the master regulators that promote EMT in many types of malignancies including HNSCC. Recently, it has been shown that Snail-induced EMT could induce a cancer stem cell (CSC)­like phenotype in a number of tumor types. In this study, we investigated the role of Snail in inducing EMT properties and CSC-like phenotype in HNSCC. We established HNSCC cell lines transfected with Snail. E-cadherin was analyzed using western blot analysis and immunofluorescence staining. Cell migration and invasion were assessed using wound-healing assay and modified Boyden chamber assay, respectively. CSC markers of HNSCC, CD44 and aldehyde dehydrogenase 1 (ALDH1), were also evaluated with western blot analysis, and chemosensitivity was assessed with WST-8 assay. Introduction of Snail induced EMT properties in HNSCC cells and enhanced cell migration and invasion. Moreover, Snail-induced EMT gained CSC-like phenotype and was associated with increased chemoresistance. These results suggest that Snail could be one of the attractive targets for the development of therapeutic strategies in HNSCC.


Assuntos
Transição Epitelial-Mesenquimal/genética , Neoplasias de Cabeça e Pescoço/genética , Células-Tronco Neoplásicas/metabolismo , Fatores de Transcrição/genética , Família Aldeído Desidrogenase 1 , Caderinas/biossíntese , Linhagem Celular Tumoral , Cisplatino/administração & dosagem , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Receptores de Hialuronatos/biossíntese , Isoenzimas/biossíntese , Retinal Desidrogenase/biossíntese , Fatores de Transcrição da Família Snail
20.
Oncol Rep ; 30(4): 1593-600, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23917679

RESUMO

Thyroid cancer sometimes contains poorly differentiated components, which have the potential of invasion and metastasis. We evaluated the possible roles of heparin-binding EGF-like growth factor (HB-EGF), a member of the epidermal growth factor (EGF) family, in cell growth and invasion of thyroid cancer cells, and demonstrated that HB-EGF is not only a potent mitogen but also a chemotactic factor in the thyroid cancer cells 8305C and SW579. The HB-EGF-mediated chemotaxis was inhibited by neutralizing antibody against the EGF receptor (EGFR/HER1/ErbB1) or tyrphostin AG1478, a specific inhibitor of the EGFR tyrosine kinase. The HB-EGF mRNA and protein expression was also analyzed using RT-PCR and immunofluorescence methods, respectively. In addition, in clinical immunohistochemical study, increased expression of HB-EGF and its receptors, HER1 and EGFR4 (HER4/ErbB4), was observed in thyroid carcinoma cells. Our findings suggest that HB-EGF acts as a potent paracrine and/or autocrine chemotactic factor as well as a mitogen that mediates HER1 and/or HER4 in the invasion and metastasis of thyroid carcinoma cells, including poorly differentiated papillary carcinomas or undifferentiated/anaplastic carcinomas. These data may aid in the development of novel therapeutic strategies for thyroid cancer.


Assuntos
Receptores ErbB/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Metástase Neoplásica , Neoplasias da Glândula Tireoide/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Neutralizantes/imunologia , Linhagem Celular Tumoral , Proliferação de Células , Quimiotaxia/efeitos dos fármacos , Toxina Diftérica/farmacologia , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/biossíntese , Receptores ErbB/imunologia , Fator de Crescimento Semelhante a EGF de Ligação à Heparina , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Quinazolinas/farmacologia , RNA Mensageiro/biossíntese , Receptor ErbB-4 , Neoplasias da Glândula Tireoide/patologia , Tirfostinas/farmacologia
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