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[PMID]:29377909
[Au] Autor:Perdomo S; Anantharaman D; Foll M; Abedi-Ardekani B; Durand G; Reis Rosa LA; Holmila R; Le Calvez-Kelm F; Tajara EH; Wünsch-Filho V; Levi JE; Vilensky M; Polesel J; Holcatova I; Simonato L; Canova C; Lagiou P; McKay JD; Brennan P
[Ad] Endereço:International Agency for Research on Cancer (IARC), Lyon, France.
[Ti] Título:Genomic analysis of head and neck cancer cases from two high incidence regions.
[So] Source:PLoS One;13(1):e0191701, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We investigated how somatic changes in HNSCC interact with environmental and host risk factors and whether they influence the risk of HNSCC occurrence and outcome. 180-paired samples diagnosed as HNSCC in two high incidence regions of Europe and South America underwent targeted sequencing (14 genes) and evaluation of copy number alterations (SCNAs). TP53, PIK3CA, NOTCH1, TP63 and CDKN2A were the most frequently mutated genes. Cases were characterized by a low copy number burden with recurrent focal amplification in 11q13.3 and deletion in 15q22. Cases with low SCNAs showed an improved overall survival. We found significant correlations with decreased overall survival between focal amplified regions 4p16, 10q22 and 22q11, and losses in 12p12, 15q14 and 15q22. The mutational landscape in our cases showed an association to both environmental exposures and clinical characteristics. We confirmed that somatic copy number alterations are an important predictor of HNSCC overall survival.
[Mh] Termos MeSH primário: Neoplasias de Cabeça e Pescoço/epidemiologia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Cromossomos Humanos
Variações do Número de Cópias de DNA
Feminino
Neoplasias de Cabeça e Pescoço/genética
Seres Humanos
Incidência
Masculino
Meia-Idade
Análise de Sobrevida
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180130
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191701


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Svidzinski, Terezinha Inez Estivalet
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[PMID]:29262785
[Au] Autor:da Silva EM; Mansano ESB; Miazima ES; Rodrigues FAV; Hernandes L; Svidzinski TIE
[Ad] Endereço:Department of Medical Mycology, State University of Maringá, Av. Colombo, 5760, C.P, Maringá, PR, 87020-900, Brazil.
[Ti] Título:Radiation used for head and neck cancer increases virulence in Candida tropicalis isolated from a cancer patient.
[So] Source:BMC Infect Dis;17(1):783, 2017 Dec 20.
[Is] ISSN:1471-2334
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Studies have shown that radiation from radiotherapy increases the yeast colonization of patients. However it is not clear, if such radiation alters the yeast itself. The aim of the present study was therefore to report the direct impact of gamma radiation on Candida tropicalis. METHODS: C. tropicalis was obtained from a patient with a carcinoma, a suspension of this yeast containing 2.0 × 10 colony forming units per milliliter was prepared. It was submitted to gamma radiation dosage similar to that used in the treatment of head and neck cancer. After a cumulative dose of 7200 cGy some virulence attributes of C. tropicalis, including macro and micromorphological characteristics, adhesion and biofilm abilities, murine experimental infection and phagocytosis resistance were evaluated on irradiated and non-irradiated yeasts. RESULTS: After irradiation the colony morphology of the yeast was altered from a ring format to a smooth appearance in most colonies. Scanning electron microscopy revealed notable differences in the structures of both these colonies and the yeast cells, with the loss of pseudohyphae following irradiation and an increase in extracellular matrix production. The adherence and biofilm production of the yeast was greater following irradiation, both in terms of the number of yeasts and total biomass production on several abiotic surfaces and TR146 cells. The phagocytic index of the irradiated yeasts was not statistically different; however, the presence of cellular debris was detected in the kidneys of infected animals. Mice infected with irradiated yeasts developed an infection at the site of the yeast inoculation, although systemic infection was unchanged. CONCLUSIONS: Our findings show for the first time that C. tropicalis, one of the most important yeasts from colonization, which cause fatal candidemia in cancer patients, is affected by gamma irradiation, with changes to its virulence profile.
[Mh] Termos MeSH primário: Candida tropicalis
Candidíase Invasiva
Neoplasias de Cabeça e Pescoço
Radioterapia/efeitos adversos
Virulência/efeitos da radiação
[Mh] Termos MeSH secundário: Biofilmes
Candida tropicalis/patogenicidade
Candida tropicalis/efeitos da radiação
Neoplasias de Cabeça e Pescoço/complicações
Neoplasias de Cabeça e Pescoço/radioterapia
Seres Humanos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171222
[St] Status:MEDLINE
[do] DOI:10.1186/s12879-017-2879-6


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[PMID]:29400040
[Au] Autor:Lechien JR; Doyen J; Deleuze M; Khalife M; Saussez S
[Ti] Título:Giant metastasis invading pharyngeal wall, pterygo­maxillary space, submaxillary and parotid glands.
[So] Source:Rev Laryngol Otol Rhinol (Bord);136(4):167-8, 2015.
[Is] ISSN:0035-1334
[Cp] País de publicação:France
[La] Idioma:eng
[Mh] Termos MeSH primário: Carcinoma de Células Escamosas/patologia
Neoplasias de Cabeça e Pescoço/patologia
Neoplasias Primárias Desconhecidas/patologia
Faringe/patologia
Neoplasias das Glândulas Salivares/secundário
[Mh] Termos MeSH secundário: Feminino
Seres Humanos
Meia-Idade
Invasividade Neoplásica
Glândula Parótida/patologia
Glândula Submandibular/patologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180206
[St] Status:MEDLINE


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[PMID]:29400037
[Au] Autor:Estêvão R; Duarte H; Lopes F; Fernandes J; Monteiro E
[Ti] Título:Peptide receptor radionuclide therapy in head and neck paragangliomas ­ Report of 14 cases.
[So] Source:Rev Laryngol Otol Rhinol (Bord);136(4):155-8, 2015.
[Is] ISSN:0035-1334
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Background: Peptide receptor radionuclide therapy (PRRT) is a very promising treatment option in neuroendocrine tumours, with good results, but there are only few reports regar­ding its use in paragangliomas. Methods: The authors conduc­ted a retrospective study during the period of May 2011 to February 2014 in an Oncological Centre. Ten patients with jugular-tympanic paragangliomas and four with carotid body paragangliomas were treated with three cycles of Lutetium labelled peptide (177 Lu-DOTATATE). Treatment response was assessed with a PET-CT with 68 Ga-DOTANOC and clinical crite­ria. Results: Ten of the fourteen patients showed a decrea­se in the tumor standard uptake value (SUV) after treat­ment. 90% of patients with Jugulotympanic paraganglio­mas had symptomatic improvement or stabilization. Patients with carotid body paragangliomas and patients with a low uptake of 68 Ga-DOTANOC had a worse response to the treatment. The tumor SUV value was a predictor of treatment response [R= 0,64; F= 8,212; p= 0,014]. Conclusion: Peptide receptor radio­nuclide therapy can be a therapeutic option in selected cases of head and neck paragangliomas.
[Mh] Termos MeSH primário: Neoplasias de Cabeça e Pescoço/radioterapia
Lutécio/uso terapêutico
Paraganglioma/radioterapia
Radioisótopos/uso terapêutico
Compostos Radiofarmacêuticos/uso terapêutico
[Mh] Termos MeSH secundário: Adulto
Idoso
Feminino
Neoplasias de Cabeça e Pescoço/diagnóstico por imagem
Neoplasias de Cabeça e Pescoço/patologia
Seres Humanos
Masculino
Meia-Idade
Paraganglioma/diagnóstico por imagem
Paraganglioma/patologia
Tomografia Computadorizada com Tomografia por Emissão de Pósitrons
Estudos Retrospectivos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Lutetium-177); 0 (Radioisotopes); 0 (Radiopharmaceuticals); 5H0DOZ21UJ (Lutetium)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180206
[St] Status:MEDLINE


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[PMID]:29222650
[Au] Autor:Lowe NM; Bernstein JM; Mais K; Garcez K; Lee LW; Sykes A; Thomson DJ; Homer JJ; West CM; Slevin NJ
[Ad] Endereço:Translational Radiobiology Group, Division of Cancer Sciences, Manchester Academic Health Science Centre, NIHR Manchester Biomedical Research Centre, The Christie NHS Foundation Trust, University of Manchester, Wilmslow Road, Manchester, England, M20 4BX, UK. nataliemarielowe@gmail.com.
[Ti] Título:Taxane, platinum and 5-FU prior to chemoradiotherapy benefits patients with stage IV neck node-positive head and neck cancer and a good performance status.
[So] Source:J Cancer Res Clin Oncol;144(2):389-401, 2018 Feb.
[Is] ISSN:1432-1335
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:PURPOSE: The benefit of adding docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy to chemoradiotherapy (CRT) in head and neck squamous cell carcinoma (HNSCC) remains uncertain. We aimed to investigate whether ICT is well tolerated when given with prophylactic treatment against predicted adverse effects and which patients benefit most. METHODS: A single-centre audit identified 132 HNSCC patients with stage IVa/b neck node-positive disease, prescribed TPF followed by CRT. TPF involved three cycles of docetaxel (75 mg/m IV) and cisplatin (75 mg/m IV) on day 1 plus 5-FU (750 mg/m IV) on days 2-5. Planned CRT was 66 Gy in 30 fractions of intensity-modulated radiotherapy with concurrent cisplatin (100 mg/m IV) at the beginning of week 1 and 4 (days 1 and 22). All patients received prophylactic antibiotics and granulocyte colony-stimulating factor. RESULTS: Median follow-up was 39.5 months. 92.4% of patients completed three cycles of TPF; 95.5% of patients started chemoradiotherapy. Grade 3/4 adverse events were low (febrile neutropenia 3.0%), with no toxicity-related deaths. 3-year overall survival was 67.2%; disease-specific survival was 78.7%; locoregional control was 78.3%. Distant metastases rate was 9.8% (3.0% in those without locoregional recurrence). Good performance status (p = 0.002) and poor tumour differentiation (p = 0.018) were associated with improved overall survival on multivariate analysis. CONCLUSION: With prophylactic antibiotics and granulocyte colony-stimulating factor TPF was well tolerated with good survival outcomes. TPF should remain a treatment option for stage IV neck node-positive patients with a good performance status. The use of tumour grade to aid patient selection for TPF warrants investigation.
[Mh] Termos MeSH primário: Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
Carcinoma de Células Escamosas/tratamento farmacológico
Carcinoma de Células Escamosas/radioterapia
Neoplasias de Cabeça e Pescoço/tratamento farmacológico
Neoplasias de Cabeça e Pescoço/radioterapia
[Mh] Termos MeSH secundário: Adulto
Idoso
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
Carcinoma de Células Escamosas/patologia
Quimiorradioterapia
Cisplatino/administração & dosagem
Cisplatino/efeitos adversos
Esquema de Medicação
Feminino
Fluoruracila/administração & dosagem
Fluoruracila/efeitos adversos
Neoplasias de Cabeça e Pescoço/patologia
Seres Humanos
Quimioterapia de Indução
Metástase Linfática
Masculino
Meia-Idade
Estadiamento de Neoplasias
Estudos Retrospectivos
Taxoides/administração & dosagem
Taxoides/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Taxoids); 15H5577CQD (docetaxel); Q20Q21Q62J (Cisplatin); U3P01618RT (Fluorouracil)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171210
[St] Status:MEDLINE
[do] DOI:10.1007/s00432-017-2553-9


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[PMID]:29429177
[Au] Autor:Jiang L; Lou JL; Wang KJ; Fang MY; Fu ZF
[Ad] Endereço:Department of Head and Neck Surgery.
[Ti] Título:[Planned neck dissection in the treatment of locally advanced head and neck squamous cell carcinoma].
[So] Source:Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi;53(2):92-96, 2018 Feb 07.
[Is] ISSN:1673-0860
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:To investigate the value of planned neck dissection combined with induction chemotherapy and concurrent chemoradiotherapy in regional control and the outcome of locally advanced head and neck squamous cell carcinoma. A prospective randomized controlled study totally enrolled sixty-four patients of head and neck squamous cell carcinomas(include oropharynx, hypopharynx, and larynx) in stages â…£a-â…£b with lymph node metastase was were N2-N3. All patients firstly received 2-3 cycles of induction chemotherapy(ICT), then divided into two groups randomly, according to the efficacy of ICT. Group A(the study group) received planned neck dissection(PND) and concurrent chemoradiotherapy(CCRT). Group B(the control group) received concurrent chemoradiotherapy(CCRT). The differences in clinicopathologic features, local recurrence(LR), regional recurrence(RR), disease-free survival(DFS), and overall survival(OS) between the two groups were estimated. SPSS 19.0 software was used to analyze the data. Group A enrolled twenty-one patients, and group B enrolled forty-three patients.The follow-up of all patients were 4-55 months, median follow-up time was 22 months. In study group, two-year OS and DFS were 80.9% and 68.3%, respectively. In control group, two-year OS and DFS were 90.7% and 67.1%, respectively. There was no significant difference in gender( =0.215), age( =0.828), primary tumor site( =0.927), LR( =0.126), DFS( =0.710), and OS( =0.402) between the two groups, while the RR(χ(2)=5.640, <0.05) and distant metastasis(χ(2)=10.363, <0.01) showed significant differences between the two groups. The ICT+ PND+ CCRT treatment model has benefit on regional control of locally advanced head and neck squamous cell carcinoma.
[Mh] Termos MeSH primário: Carcinoma de Células Escamosas/terapia
Quimiorradioterapia/métodos
Neoplasias de Cabeça e Pescoço/terapia
Esvaziamento Cervical/métodos
[Mh] Termos MeSH secundário: Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Carcinoma de Células Escamosas/patologia
Carcinoma de Células Escamosas/cirurgia
Terapia Combinada
Intervalo Livre de Doença
Neoplasias de Cabeça e Pescoço/patologia
Neoplasias de Cabeça e Pescoço/cirurgia
Seres Humanos
Quimioterapia de Indução/métodos
Linfonodos
Metástase Linfática
Recidiva Local de Neoplasia
Estudos Prospectivos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180213
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.1673-0860.2018.02.003


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[PMID]:29429175
[Au] Autor:Peng Z; Wang ZX; Xie J; Wang LE; Liu Y; Gong SS
[Ad] Endereço:Department of Otorhinolaryngology Head and Neck Surgery, Beijing Friendship Hospital, Capital Medical University, Beijng 100050, China.
[Ti] Título:[Middle ear teratoma in infant: report of three cases and review of the literatures].
[So] Source:Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi;53(2):81-85, 2018 Feb 07.
[Is] ISSN:1673-0860
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:To summarize the clinical characteristics and therapeutic experiences of the middle ear teratoma in infants. Three cases of middle ear teratoma, from 2012-2015 in Beijing Friendship Hospital were analyzed. The three cases all developed slowly and presented unilateral otorrhea and hearing loss. Otoscopy showed the granulation tissue in the external ear canal. Audiological changes varied according to the degree of severity. Imaging features showed the pocket-like occupancy lesions in the Eustachian tube area. The temporal bone CT showed mass with soft tissue density usually involved in the mastoid and tympanic cavity. MRI showed mixed signal intense on both T1 and T2 weighted imaging. All the three cases received neoplasm resection of the middle ear. Only one case received tympanoplasty surgery at the same time. And all the pathology results displayed mature teratoma. The follow-up time was 17 to 54 months. MRI showed complete removal of the tumor. Teratoma are rare in the head and neck neoplasm. When the infants suffer from the unilateral otorrhea, hearing loss, and granulation tissue formed in the external ear canal, it should be vigilant for teratoma. The differential diagnosis is middle ear cholesteatoma, congenital first branchial cyst or fistula, and middle ear carcinoma. Temporal bone CT combined with MRI could improve the accuracy of diagnosis. It should be totally resection as soon as possible if there is no contraindication. Postoperative follow-up and imaging examination are necessary to eliminate tumor recurrence.
[Mh] Termos MeSH primário: Neoplasias da Orelha/cirurgia
Orelha Média
Teratoma
[Mh] Termos MeSH secundário: Branquioma
Surdez/etiologia
Diagnóstico Diferencial
Neoplasias da Orelha/complicações
Neoplasias da Orelha/diagnóstico por imagem
Orelha Média/diagnóstico por imagem
Tuba Auditiva/diagnóstico por imagem
Neoplasias de Cabeça e Pescoço
Seres Humanos
Lactente
Imagem por Ressonância Magnética
Processo Mastoide/diagnóstico por imagem
Recidiva Local de Neoplasia
Otoscopia
Osso Temporal/diagnóstico por imagem
Teratoma/complicações
Teratoma/diagnóstico por imagem
Teratoma/cirurgia
Tomografia Computadorizada por Raios X
Timpanoplastia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180213
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.1673-0860.2018.02.001


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[PMID]:29028221
[Au] Autor:Verma V; Simone CB; Mishra MV
[Ad] Endereço:Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NE; Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD.
[Ti] Título:Quality of Life and Patient-Reported Outcomes Following Proton Radiation Therapy: A Systematic Review.
[So] Source:J Natl Cancer Inst;110(4), 2018 Apr 01.
[Is] ISSN:1460-2105
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: As costs of cancer care rise, the importance of documenting value in oncology increases. Proton beam radiotherapy (PBT) has the potential to reduce toxicities in cancer patients, but is relatively expensive and unproven. Evaluating quality of life (QOL) and patient-reported outcomes (PROs) is essential to establishing PBT's "value" in oncologic therapy. The goal of this systematic review was to assess QOL and PROs in patients treated with PBT. Methods: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided systematic searches were conducted. The PubMed search engine was the primary data source, along with publications found from references of selected articles, and articles known to the authors published through 2017. Seventeen original investigations were found to have sufficient focus and relevance to be incorporated into the systematic review. Results: Studies of skull base (n = 1), brain (n = 1), head/neck (n = 1), lung (n = 1), breast (n = 2), prostate (n = 8), and pediatric (n = 3) malignancies treated with PBT that met eligibility criteria were included. QOL did not deteriorate during PBT for skull base and after PBT for brain tumors, respectively. PROs were higher for PBT than photon-based radiotherapy for both head/neck and lung cancer. Patient-reported breast cosmesis was appropriate after PBT and comparable to photon modalities. PBT in various settings of prostate cancer displayed an expected post-therapy decline; one study showed improved PROs (rectal urgency, bowel frequency) for PBT, and two others showed PROs/QOL comparable with other modalities. Pediatric studies demonstrated improvements in QOL during therapy, with additional increases thereafter. Conclusions: Based on limited data, PBT provides favorable QOL/PRO profiles for select brain, head/neck, lung, and pediatric cancers; measures for prostate and breast cancers were more modest. These results have implications for cost-effective cancer care and prudently designed QOL evaluation in ongoing trials, which are discussed. Future data could substantially change the conclusions of this review.
[Mh] Termos MeSH primário: Neoplasias/radioterapia
Medidas de Resultados Relatados pelo Paciente
Terapia com Prótons
Qualidade de Vida
[Mh] Termos MeSH secundário: Neoplasias Encefálicas/radioterapia
Neoplasias da Mama/radioterapia
Feminino
Neoplasias de Cabeça e Pescoço/radioterapia
Seres Humanos
Neoplasias Pulmonares/radioterapia
Masculino
Neoplasias da Próstata/radioterapia
Terapia com Prótons/efeitos adversos
Neoplasias da Base do Crânio/radioterapia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1710
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171014
[St] Status:MEDLINE
[do] DOI:10.1093/jnci/djx208


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[PMID]:28922779
[Au] Autor:Hanley CJ; Mellone M; Ford K; Thirdborough SM; Mellows T; Frampton SJ; Smith DM; Harden E; Szyndralewiez C; Bullock M; Noble F; Moutasim KA; King EV; Vijayanand P; Mirnezami AH; Underwood TJ; Ottensmeier CH; Thomas GJ
[Ad] Endereço:Cancer Sciences Unit, University of Southampton Faculty of Medicine, Southampton, UK; Genkyotex SA, Plan-les-Ouates, Switzerland; La Jolla Institute for Allergy and Immunology, La Jolla, CA.
[Ti] Título:Targeting the Myofibroblastic Cancer-Associated Fibroblast Phenotype Through Inhibition of NOX4.
[So] Source:J Natl Cancer Inst;110(1), 2018 Jan 01.
[Is] ISSN:1460-2105
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: Cancer-associated fibroblasts (CAFs) are tumor-promoting and correlate with poor survival in many cancers, which has led to their emergence as potential therapeutic targets. However, effective methods to manipulate these cells clinically have yet to be developed. Methods: CAF accumulation and prognostic significance in head and neck cancer (oral, n = 260; oropharyngeal, n = 271), and colorectal cancer (n = 56) was analyzed using immunohistochemistry. Mechanisms regulating fibroblast-to-myofibroblast transdifferentiation were investigated in vitro using RNA interference/pharmacological inhibitors followed by polymerase chain reaction (PCR), immunoblotting, immunofluorescence, and functional assays. RNA sequencing/bioinformatics and immunohistochemistry were used to analyze NAD(P)H Oxidase-4 (NOX4) expression in different human tumors. NOX4's role in CAF-mediated tumor progression was assessed in vitro, using CAFs from multiple tissues in Transwell and organotypic culture assays, and in vivo, using xenograft (n = 9-15 per group) and isograft (n = 6 per group) tumor models. All statistical tests were two-sided. Results: Patients with moderate/high levels of myofibroblastic-CAF had a statistically significant decrease in cancer-specific survival rates in each cancer type analyzed (hazard ratios [HRs] = 1.69-7.25, 95% confidence intervals [CIs] = 1.11 to 31.30, log-rank P ≤ .01). Fibroblast-to-myofibroblast transdifferentiation was dependent on a delayed phase of intracellular reactive oxygen species, generated by NOX4, across different anatomical sites and differentiation stimuli. A statistically significant upregulation of NOX4 expression was found in multiple human cancers (P < .001), strongly correlating with myofibroblastic-CAFs (r = 0.65-0.91, adjusted P < .001). Genetic/pharmacological inhibition of NOX4 was found to revert the myofibroblastic-CAF phenotype ex vivo (54.3% decrease in α-smooth muscle actin [α-SMA], 95% CI = 10.6% to 80.9%, P = .009), prevent myofibroblastic-CAF accumulation in vivo (53.2%-79.0% decrease in α-SMA across different models, P ≤ .02) and slow tumor growth (30.6%-64.0% decrease across different models, P ≤ .04). Conclusions: These data suggest that pharmacological inhibition of NOX4 may have broad applicability for stromal targeting across cancer types.
[Mh] Termos MeSH primário: Adenocarcinoma/tratamento farmacológico
Fibroblastos Associados a Câncer/patologia
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico
Carcinoma de Células Escamosas/tratamento farmacológico
Neoplasias Colorretais/química
Neoplasias Esofágicas/tratamento farmacológico
Neoplasias Pulmonares/tratamento farmacológico
Neoplasias Bucais/química
Miofibroblastos/patologia
NADPH Oxidases/antagonistas & inibidores
Neoplasias Orofaríngeas/química
[Mh] Termos MeSH secundário: Actinas/análise
Adenocarcinoma/química
Adenocarcinoma/genética
Adulto
Idoso
Idoso de 80 Anos ou mais
Animais
Fibroblastos Associados a Câncer/química
Fibroblastos Associados a Câncer/fisiologia
Carcinoma Pulmonar de Células não Pequenas/química
Carcinoma Pulmonar de Células não Pequenas/genética
Carcinoma de Células Escamosas/química
Carcinoma de Células Escamosas/genética
Contagem de Células
Transdiferenciação Celular/efeitos dos fármacos
Transdiferenciação Celular/genética
Neoplasias Colorretais/patologia
Progressão da Doença
Neoplasias Esofágicas/química
Neoplasias Esofágicas/genética
Feminino
Neoplasias de Cabeça e Pescoço/química
Neoplasias de Cabeça e Pescoço/tratamento farmacológico
Neoplasias de Cabeça e Pescoço/genética
Seres Humanos
Neoplasias Pulmonares/química
Neoplasias Pulmonares/genética
Masculino
Camundongos
Meia-Idade
Neoplasias Bucais/patologia
Miofibroblastos/química
NADPH Oxidase 4
NADPH Oxidases/análise
NADPH Oxidases/genética
Transplante de Neoplasias
Neoplasias Orofaríngeas/patologia
Fenótipo
Pirazóis/uso terapêutico
Piridinas/uso terapêutico
Interferência de RNA
Espécies Reativas de Oxigênio/metabolismo
Taxa de Sobrevida
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ACTA2 protein, human); 0 (Actins); 0 (GKT137831); 0 (Pyrazoles); 0 (Pyridines); 0 (Reactive Oxygen Species); EC 1.6.3.- (NADPH Oxidase 4); EC 1.6.3.- (NADPH Oxidases); EC 1.6.3.- (NOX4 protein, human)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170920
[St] Status:MEDLINE
[do] DOI:10.1093/jnci/djx121


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[PMID]:29429160
[Au] Autor:Zhao M; Wang YB; Yan YJ; Wang W; Ru GQ; He XL
[Ad] Endereço:Department of Pathology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, China.
[Ti] Título:[Clinicopathologic features of atypical spindle cell lipomatous tumor].
[So] Source:Zhonghua Bing Li Xue Za Zhi;47(2):99-104, 2018 Feb 08.
[Is] ISSN:0529-5807
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:To investigate the clinicopathologic characteristics, immunophenotype, differential and diagnostic features of atypical spindle cell lipomatous tumor (ASLT). Three cases of ASLT were collected from January 2010 to March 2017 at Zhejiang Provincial People's Hospital. The clinical and imaging features, histomorphology, immunophenotype and prognosis were analyzed. Fluorescence in situ hybridization (FISH) was used to detect MDM2 gene amplification, and relevant literature was reviewed. All three patients were adult males, aged 38, 43 and 54 years, respectively. One tumor originated in the subcutaneous soft tissue in the head and neck, one was located in the left primary bronchus and one in the latissimus dorsi muscle. Grossly, all three tumors were circumscribed and ranged from 4.0 to 5.8 cm in size. Microscopically, all showed a focally infiltrative front. These tumors were composed of variable proportions of spindle-shaped and adipocytic cells in a background of variable fibrous and edematous matrix. Scattered lipoblasts were easily seen. One tumor was composed predominately of spindle tumor cells, one of adipocytic cells, and one of equally mixed cell populations. The spindle tumor cells were generally bland-appearing with focal nuclear enlargement and hyperchromasia noted in one case. Mitosis was not seen in neither the spindle cells nor the adipocytic cells. By immunohistochemistry, diffuse and strong reactivity to CD34 of the spindle cells was noted in all cases, definite loss of Rb expression was noted in one of three cases, and S-100 protein was expressed only in the adipocytic cells. INI-1 was intact and Ki-67 index was 1% to 3%. All other markers including CDK4, MDM2, STAT6, SOX10, CD99, bcl-2, ß-catenin, CD117, GFAP, CK, EMA, SMA and desmin were negative. FISH of MDM2 was done in two cases, and both showed no amplification. The ASLT in the head and neck had two recurrences during 17 months of follow-up, whereas the tumor in the latissimus dorsi was free of disease during 33 months of follow-up. ASLT is a rare subtype of low-grade adipocytic neoplasm and is distinctive from atypical lipomatous tumor/well-differentiated liposarcoma. The histomorpholgy of ASLT has significant heterogeneity and forms a continuous spectrum. ASLT needs to be distinguished from a series of benign and malignant soft tissue tumors.
[Mh] Termos MeSH primário: Neoplasias Brônquicas/patologia
Neoplasias de Cabeça e Pescoço/patologia
Lipoma/patologia
Neoplasias Musculares/patologia
[Mh] Termos MeSH secundário: Adulto
Neoplasias Brônquicas/química
Neoplasias de Cabeça e Pescoço/química
Seres Humanos
Imuno-Histoquímica
Hibridização in Situ Fluorescente
Lipoma/química
Lipossarcoma/química
Lipossarcoma/patologia
Masculino
Meia-Idade
Neoplasias Musculares/química
Recidiva Local de Neoplasia
Proteínas S100/análise
Fator de Transcrição STAT6/análise
Músculos Superficiais do Dorso
beta Catenina/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CTNNB1 protein, human); 0 (S100 Proteins); 0 (STAT6 Transcription Factor); 0 (STAT6 protein, human); 0 (beta Catenin)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180213
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.0529-5807.2018.02.004



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