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[PMID]:27779297
[Au] Autor:Han KH; Kim MA; Park NH
[Ad] Endereço:Department of Obstetrics and Gynecology, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Republic of Korea.
[Ti] Título:Expression of aurora kinases: Predictor of tumor dissemination in uterine carcinosarcoma.
[So] Source:Histol Histopathol;32(7):717-724, 2017 Jul.
[Is] ISSN:1699-5848
[Cp] País de publicação:Spain
[La] Idioma:eng
[Ab] Resumo:Uterine carcinosarcoma is a rare, aggressive, and biphasic tumor. It comprises carcinomatous and sarcomatous components, and mitosis-associated factors are thought to discriminate these two lesions. Aurora kinases are mitotic enzymes that are highly expressed in uterine malignancies. To identify the clinical significance of aurora kinase expression, we performed immunohistochemistry on tissue microarrays using cores selected from areas with typical carcinomatous and sarcomatous characteristics. A total of 24 samples were included, from patients at Seoul National University Hospital diagnosed with uterine carcinosarcoma, and who undergone a staging operation between 1997 and 2012. Patients' clinical and pathological data were analyzed, and expression patterns of aurora kinases were investigated. Aurora kinases A and B were dominantly expressed in the cytoplasm, and phospho-aurora kinases A and B were expressed in the nuclei. Phospho-aurora kinase A and aurora kinase B showed significantly higher expression in the carcinomatous component (P=0.012 and 0.008). High expression of phospho-aurora kinase A was associated with lymphatic metastasis such as positive pelvic lymph node and omental involvement (P=0.012 and 0.037). Overexpression of aurora kinase B was related to vascular invasion (P=0.011). High expression of both phospho-aurora kinase A and aurora kinase B was a prognostic factor for progression-free survival in uterine carcinosarcoma (P=0.049). In conclusion, expression of aurora kinases is associated with bidirectional tumor dissemination into the lymphatic and hematogenous pathways. In addition, high expression of phospho-aurora kinase A and aurora kinase B is a predictor of progression-free survival. Therefore, inhibitors of aurora kinases might be a prospective therapeutic options for uterine carcinosarcoma.
[Mh] Termos MeSH primário: Aurora Quinases/biossíntese
Carcinossarcoma/enzimologia
Carcinossarcoma/patologia
Neoplasias Uterinas/enzimologia
Neoplasias Uterinas/patologia
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Aurora Quinase A/metabolismo
Aurora Quinase B/metabolismo
Aurora Quinases/genética
Biomarcadores Tumorais
Intervalo Livre de Doença
Feminino
Regulação Enzimológica da Expressão Gênica/genética
Regulação Neoplásica da Expressão Gênica/genética
Seres Humanos
Imuno-Histoquímica
Estimativa de Kaplan-Meier
Menopausa
Meia-Idade
Metástase Neoplásica/patologia
Estadiamento de Neoplasias
Valor Preditivo dos Testes
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); EC 2.7.11.1 (AURKA protein, human); EC 2.7.11.1 (AURKB protein, human); EC 2.7.11.1 (Aurora Kinase A); EC 2.7.11.1 (Aurora Kinase B); EC 2.7.11.1 (Aurora Kinases)
[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:161026
[St] Status:MEDLINE
[do] DOI:10.14670/HH-11-834


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[PMID]:28468189
[Au] Autor:Phan HNM; Hong YT; Hong KH
[Ad] Endereço:Department of Otolaryngology-HNS, Research Institute for Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Chonbuk, Korea.
[Ti] Título:Primary Carcinosarcoma of the Parotid Gland Mimicking as Parotid Abscess With Deep Neck Infection.
[So] Source:J Craniofac Surg;28(3):e210-e213, 2017 May.
[Is] ISSN:1536-3732
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Carcinosarcoma, true malignant mixed tumor, of the parotid is an extremely rare tumor. Pathologically, it is composed of malignant epithelial and malignant mesenchymal elements. The carcinosarcoma of the salivary glands comprised only 0.04% to 0.16% of all malignant salivary tumors with 65% occurring in the parotid gland. This tumor has an aggressive characteristic and is often regarded as a high-grade tumor with distant metastasis occurring in 54% of the patients. Patients usually present between 60 and 65 years of age and most series report no sex predominance. Radiologically, this tumor has a low attenuation center with a thick-enhancing wall and can be misdiagnosed deep neck infection in the parapharyngeal space. In this report, the authors report a patient of true malignant mixed tumor of the parotid gland mimicking as deep neck infection. Radiologic and histologic features including immunohistochemical results are discussed.
[Mh] Termos MeSH primário: Carcinossarcoma/diagnóstico
Glândula Parótida/diagnóstico por imagem
Neoplasias Parotídeas/diagnóstico
[Mh] Termos MeSH secundário: Abscesso/diagnóstico
Biópsia por Agulha Fina
Erros de Diagnóstico
Seres Humanos
Masculino
Meia-Idade
Pescoço
Tomografia Computadorizada por Raios X
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180126
[Lr] Data última revisão:
180126
[Sb] Subgrupo de revista:D
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.1097/SCS.0000000000003465


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[PMID]:28827101
[Au] Autor:Urrea YR; Epstein JI
[Ad] Endereço:The Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, MD 21231.
[Ti] Título:Sarcomatoid carcinoma associated with small cell carcinoma of the urinary bladder: a series of 28 cases.
[So] Source:Hum Pathol;67:169-175, 2017 Sep.
[Is] ISSN:1532-8392
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The association of sarcomatoid carcinoma (SC) with small cell carcinoma (SCC) has not been systematically studied. We identified 39 consult cases between 2001 and 2016 with available slides for review in 28 cases. There were 19 men and 9 women (mean age: 78 years [51-89]). In 26 (92.8%) cases, the sarcomatoid component had nonspecific malignant spindle cells, 4 (14%) chondrosarcoma, 2 (7%) myxoid sarcomatous, 1 (3.5%) osteosarcoma, and 1 (3.5%) rhabdomyosarcoma. The predominant component was SCC in 11 (39%) cases, urothelial carcinoma in 6 (21%), sarcomatoid in 3 (10%), and equal sarcomatoid and SCC in 8 (29%). There were 3 morphological groups: group 1 (18/28 [64%]) showed a gradual transition from SCC to other components; group 2 (5/28 [18%]) had an abrupt transition from SCC to other components; and in group 3 (5/28 [18%]), the SCC was separate from other components. In group 1, 12 (66%) cases of SCC showed a gradual transition to sarcomatoid areas; 3 (17%) to urothelial carcinoma; and 3 (17%) to multiple components including squamous cell carcinoma, urothelial carcinoma, and sarcomatoid. Mortality did not differ based on pathological groups. The 36-month actuarial risk of death was 64.3%. The multitude of different components in these tumors is further evidence of the remarkable ability of carcinoma of the bladder to show divergent differentiation with, in some cases, gradual transition between SCC and other elements including sarcomatoid. Greater recognition of this entity with chemotherapy targeted to the various histological elements may have important therapeutic implications.
[Mh] Termos MeSH primário: Carcinoma de Células Pequenas/patologia
Carcinossarcoma/patologia
Neoplasias da Bexiga Urinária/patologia
Urotélio/patologia
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Biomarcadores Tumorais/análise
Biópsia
Carcinoma de Células Pequenas/química
Carcinoma de Células Pequenas/tratamento farmacológico
Carcinoma de Células Pequenas/mortalidade
Carcinossarcoma/química
Carcinossarcoma/tratamento farmacológico
Carcinossarcoma/mortalidade
Bases de Dados Factuais
Diagnóstico Diferencial
Feminino
Seres Humanos
Imuno-Histoquímica
Masculino
Meia-Idade
Estadiamento de Neoplasias
Valor Preditivo dos Testes
Estudos Retrospectivos
Fatores de Tempo
Resultado do Tratamento
Neoplasias da Bexiga Urinária/química
Neoplasias da Bexiga Urinária/tratamento farmacológico
Neoplasias da Bexiga Urinária/mortalidade
Urotélio/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170823
[St] Status:MEDLINE


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[PMID]:28805821
[Au] Autor:Janouskova H; El Tekle G; Bellini E; Udeshi ND; Rinaldi A; Ulbricht A; Bernasocchi T; Civenni G; Losa M; Svinkina T; Bielski CM; Kryukov GV; Cascione L; Napoli S; Enchev RI; Mutch DG; Carney ME; Berchuck A; Winterhoff BJN; Broaddus RR; Schraml P; Moch H; Bertoni F; Catapano CV; Peter M; Carr SA; Garraway LA; Wild PJ; Theurillat JP
[Ad] Endereço:Institute of Oncology Research, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
[Ti] Título:Opposing effects of cancer-type-specific SPOP mutants on BET protein degradation and sensitivity to BET inhibitors.
[So] Source:Nat Med;23(9):1046-1054, 2017 Sep.
[Is] ISSN:1546-170X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:It is generally assumed that recurrent mutations within a given cancer driver gene elicit similar drug responses. Cancer genome studies have identified recurrent but divergent missense mutations affecting the substrate-recognition domain of the ubiquitin ligase adaptor SPOP in endometrial and prostate cancers. The therapeutic implications of these mutations remain incompletely understood. Here we analyzed changes in the ubiquitin landscape induced by endometrial cancer-associated SPOP mutations and identified BRD2, BRD3 and BRD4 proteins (BETs) as SPOP-CUL3 substrates that are preferentially degraded by endometrial cancer-associated SPOP mutants. The resulting reduction of BET protein levels sensitized cancer cells to BET inhibitors. Conversely, prostate cancer-specific SPOP mutations resulted in impaired degradation of BETs, promoting their resistance to pharmacologic inhibition. These results uncover an oncogenomics paradox, whereby mutations mapping to the same domain evoke opposing drug susceptibilities. Specifically, we provide a molecular rationale for the use of BET inhibitors to treat patients with endometrial but not prostate cancer who harbor SPOP mutations.
[Mh] Termos MeSH primário: Adenocarcinoma de Células Claras/genética
Carcinoma Endometrioide/genética
Carcinossarcoma/genética
Neoplasias do Endométrio/genética
Neoplasias Císticas, Mucinosas e Serosas/genética
Proteínas Nucleares/genética
Proteínas Nucleares/metabolismo
Neoplasias da Próstata/genética
Proteínas Serina-Treonina Quinases/metabolismo
Proteínas de Ligação a RNA/metabolismo
Proteínas Repressoras/genética
Fatores de Transcrição/metabolismo
[Mh] Termos MeSH secundário: Acetanilidas/farmacologia
Adenocarcinoma de Células Claras/metabolismo
Animais
Apoptose/efeitos dos fármacos
Azepinas/farmacologia
Carcinoma Endometrioide/metabolismo
Carcinossarcoma/metabolismo
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Cromatografia Líquida
Proteínas Culina/metabolismo
Resistência a Medicamentos Antineoplásicos
Neoplasias do Endométrio/metabolismo
Epigênese Genética
Feminino
Compostos Heterocíclicos com 3 Anéis/farmacologia
Seres Humanos
Immunoblotting
Imuno-Histoquímica
Imunoprecipitação
Masculino
Espectrometria de Massas
Camundongos Nus
Terapia de Alvo Molecular
Mutação
Transplante de Neoplasias
Neoplasias Císticas, Mucinosas e Serosas/metabolismo
Proteínas Nucleares/antagonistas & inibidores
Neoplasias da Próstata/metabolismo
Proteínas Serina-Treonina Quinases/antagonistas & inibidores
Proteínas de Ligação a RNA/antagonistas & inibidores
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Fatores de Transcrição/antagonistas & inibidores
Triazóis/farmacologia
Ubiquitinação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 ((+)-JQ1 compound); 0 (Acetanilides); 0 (Azepines); 0 (BRD3 protein, human); 0 (BRD4 protein, human); 0 (CUL3 protein, human); 0 (Cullin Proteins); 0 (Heterocyclic Compounds, 3-Ring); 0 (Nuclear Proteins); 0 (OTX015); 0 (RNA-Binding Proteins); 0 (Repressor Proteins); 0 (SPOP protein, human); 0 (Transcription Factors); 0 (Triazoles); EC 2.7.1.- (BRD2 protein, human); EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170815
[St] Status:MEDLINE
[do] DOI:10.1038/nm.4372


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[PMID]:28656498
[Au] Autor:Almond LM; Warfield AT; Desai A; Gourevitch D; Ford SJ
[Ad] Endereço:Midlands Abdominal and Retroperitoneal Sarcoma Unit (MARSU), University Hospitals Birmingham NHS Foundation Trust, Mindelsohn Way, Birmingham, B15 2TH, UK. mxa891@hotmail.com.
[Ti] Título:Biphasic malignant tumours of the abdominal cavity.
[So] Source:Int J Clin Oncol;22(4):635-640, 2017 Aug.
[Is] ISSN:1437-7772
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Carcinosarcomas (CS) are uncommon, highly aggressive, biphasic tumours consisting of both sarcomatous and carcinomatous elements. They appear to originate from a common cell of origin, either via transformation from a single premature precursor or conversion of a mature epithelial cell through an epithelial-mesenchymal transition. CS should be considered a unique cancer subtype with cells typically displaying diffuse mitotic activity and widespread atypical mitoses predisposing to early metastasis and a tendency to local recurrence following resection. This review addresses the pathophysiology of CS and discusses its presentation, natural history and management at a variety of sites within the abdominal cavity and retroperitoneum.
[Mh] Termos MeSH primário: Neoplasias Abdominais/patologia
Neoplasias Abdominais/terapia
Carcinossarcoma/patologia
Carcinossarcoma/terapia
[Mh] Termos MeSH secundário: Cavidade Abdominal/patologia
Carcinoma de Células Renais/epidemiologia
Carcinoma de Células Renais/fisiopatologia
Carcinoma de Células Renais/terapia
Transição Epitelial-Mesenquimal
Feminino
Seres Humanos
Neoplasias Renais/epidemiologia
Neoplasias Renais/fisiopatologia
Neoplasias Renais/terapia
Neoplasias Ovarianas/epidemiologia
Neoplasias Ovarianas/fisiopatologia
Neoplasias Ovarianas/terapia
Sarcoma/patologia
Sarcoma/terapia
Neoplasias Uterinas/epidemiologia
Neoplasias Uterinas/fisiopatologia
Neoplasias Uterinas/terapia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170629
[St] Status:MEDLINE
[do] DOI:10.1007/s10147-017-1153-7


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[PMID]:28652731
[Au] Autor:Horák D; Pustovyy VI; Babinskyi AV; Palyvoda OM; Chekhun VF; Todor IN; Kuzmenko OI
[Ad] Endereço:Department of Polymer Particles, Institute of Macromolecular Chemistry AS CR, Prague, Czech Republic.
[Ti] Título:Enhanced antitumor activity of surface-modified iron oxide nanoparticles and an α-tocopherol derivative in a rat model of mammary gland carcinosarcoma.
[So] Source:Int J Nanomedicine;12:4257-4268, 2017.
[Is] ISSN:1178-2013
[Cp] País de publicação:New Zealand
[La] Idioma:eng
[Ab] Resumo:Maghemite (γ-Fe O ) nanoparticles were obtained by coprecipitation of ferrous and ferric salts in an alkaline medium followed by oxidation; the nanoparticles were coated with poly( -dimethylacrylamide) (PDMA) and characterized by transmission electron microscopy, attenuated total reflection (ATR) Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering, thermogravimetric and elemental analyses, and magnetic measurements in terms of particle morphology, size, polydispersity, amount of coating, and magnetization, respectively. The effects of α-tocopherol (Toc) and its phenolic (Toc-6-OH) and acetate (Toc-6-Ac) derivatives on Fe release from γ-Fe O @PDMA, as well as from γ-Fe O and CuFe O nanoparticles (controls), were examined in vitro using 1,10-phenanthroline. The presence of tocopherols enhanced spontaneous Fe release from nanoparticles, with Toc-6-OH exhibiting more activity than neat Toc. All of the nanoparticles tested were found to initiate blood lipid oxidation in a concentration-dependent manner, as determined by analysis of 2-thiobarbituric acid reactive species. Wistar rats with Walker-256 carcinosarcoma (a model of mammary gland carcinosarcoma) received Toc-6-Ac, magnetic nanoparticles, or their combination per os, and the antitumor activity of each treatment was determined in vivo. γ-Fe O @PDMA nanoparticles exhibited increased antitumor activity compared to both commercial CuFe O particles and the antitumor drug doxorubicin. Moreover, increased antitumor activity was observed after combined administration of γ-Fe O @PDMA nanoparticles and Toc-6-Ac; however, levels of bilirubin, aspartate aminotransferase, and white bloods normalized and did not differ from those of the intact controls. The antitumor activity of the γ-Fe O nanoparticles strongly correlated with Fe release from the nanoparticles but not with nanoparticle-initiated lipid peroxidation in vitro.
[Mh] Termos MeSH primário: Carcinossarcoma/tratamento farmacológico
Compostos Férricos/química
Nanopartículas de Magnetita/química
Neoplasias Mamárias Experimentais/tratamento farmacológico
alfa-Tocoferol/administração & dosagem
[Mh] Termos MeSH secundário: Acrilamidas/química
Animais
Relação Dose-Resposta a Droga
Sistemas de Liberação de Medicamentos/métodos
Feminino
Nanopartículas de Magnetita/administração & dosagem
Microscopia Eletrônica de Transmissão
Ratos Wistar
Espectroscopia de Infravermelho com Transformada de Fourier
alfa-Tocoferol/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acrylamides); 0 (Ferric Compounds); 0 (Magnetite Nanoparticles); 0 (poly(N,N-dimethylacrylamide)); 1K09F3G675 (ferric oxide); H4N855PNZ1 (alpha-Tocopherol)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170628
[St] Status:MEDLINE
[do] DOI:10.2147/IJN.S137574


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[PMID]:28625393
[Au] Autor:Cuppens T; Depreeuw J; Annibali D; Thomas D; Hermans E; Gommé E; Trinh XB; Debruyne D; Moerman P; Lambrechts D; Amant F
[Ad] Endereço:KU Leuven - University of Leuven, Department of Oncology, Gynaecologic Oncology, B-3000 Leuven, Belgium.
[Ti] Título:Establishment and characterization of uterine sarcoma and carcinosarcoma patient-derived xenograft models.
[So] Source:Gynecol Oncol;146(3):538-545, 2017 Sep.
[Is] ISSN:1095-6859
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Uterine sarcomas (US) and carcinosarcomas (CS) are rare, aggressive cancers. The lack of reliable preclinical models hampers the search for new treatment strategies and predictive biomarkers. To this end, we established and characterized US and CS patient-derived xenograft (PDX) models. METHODS: Tumor fragments of US and CS were subcutaneously implanted into immunocompromised mice. Engrafted xenograft and original tumors were compared by means of histology, immunohistochemistry, whole-genome low-coverage sequencing for copy number variations, and RNA sequencing. RESULTS: Of 13 implanted leiomyosarcomas (LMS), 10 engrafted (engraftment rate of 77%). Also 2 out of 7 CS (29%) and one high-grade US (not otherwise specified) models were successfully established. LMS xenografts showed high histological similarity to their corresponding human tumors. Expression of desmin and/or H-caldesmon was detected in 8/10 LMS PDX models. We noticed that in CS models, characterized by the concomitant presence of a mesenchymal and an epithelial component, the relative distribution of the components is varying over the generations, as confirmed by changes in vimentin and cytokeratin expression. The similarity in copy number profiles between original and xenograft tumors ranged from 57.7% to 98.2% for LMS models and from 47.4 to 65.8% for CS models. Expression pattern stability was assessed by clustering RNA expression levels of original and xenograft tumors. Six xenografts clustered together with their original tumor, while 3 (all LMS) clustered apart. CONCLUSIONS: We present here a panel of clinically annotated uterine sarcoma and carcinosarcoma PDX models, which will be a useful tool for preclinical testing of new therapies.
[Mh] Termos MeSH primário: Carcinossarcoma/patologia
DNA de Neoplasias/análise
Modelos Animais de Doenças
Xenoenxertos/patologia
Leiomiossarcoma/patologia
RNA Neoplásico/análise
Neoplasias Uterinas/patologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Animais
Proteínas de Ligação a Calmodulina/análise
Carcinossarcoma/química
Carcinossarcoma/genética
Variações do Número de Cópias de DNA
Desmina/análise
Feminino
Expressão Gênica
Sobrevivência de Enxerto
Xenoenxertos/química
Seres Humanos
Leiomiossarcoma/química
Leiomiossarcoma/genética
Camundongos
Meia-Idade
Transplante de Neoplasias
Análise de Sequência de RNA
Transplante Heterólogo
Neoplasias Uterinas/química
Neoplasias Uterinas/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calmodulin-Binding Proteins); 0 (DNA, Neoplasm); 0 (Desmin); 0 (RNA, Neoplasm)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170620
[St] Status:MEDLINE


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[PMID]:28608929
[Au] Autor:Zhai Y; Wu R; Kuick R; Sessine MS; Schulman S; Green M; Fearon ER; Cho KR
[Ad] Endereço:Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.
[Ti] Título:High-grade serous carcinomas arise in the mouse oviduct via defects linked to the human disease.
[So] Source:J Pathol;243(1):16-25, 2017 Sep.
[Is] ISSN:1096-9896
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Recent studies have suggested that the most common and lethal type of 'ovarian' cancer, i.e. high-grade serous carcinoma (HGSC), usually arises from epithelium on the fallopian tube fimbriae, and not from the ovarian surface epithelium. We have developed Ovgp1-iCreER mice in which the Ovgp1 promoter controls expression of tamoxifen-regulated Cre recombinase in oviductal epithelium - the murine equivalent of human fallopian tube epithelium (FTE). We employed Ovgp1-iCreER mice to show that FTE-specific inactivation of several different combinations of tumour suppressor genes that are recurrently mutated in human HGSCs - namely Brca1, Trp53, Rb1, and Nf1 - results in serous tubal intraepithelial carcinomas (STICs) that progress to HGSC or carcinosarcoma, and to widespread metastatic disease in a subset of mice. The cancer phenotype is highly penetrant and more rapid in mice carrying engineered alleles of all four tumour suppressor genes. Brca1, Trp53 and Pten inactivation in the oviduct also results in STICs and HGSCs, and is associated with diffuse epithelial hyperplasia and mucinous metaplasia, which are not observed in mice with intact Pten. Oviductal tumours arise earlier in these mice than in those with Brca1, Trp53, Rb1 and Nf1 inactivation. Tumour initiation and/or progression in mice lacking conditional Pten alleles probably require the acquisition of additional defects, a notion supported by our identification of loss of the wild-type Rb1 allele in the tumours of mice carrying only one floxed Rb1 allele. Collectively, the models closely recapitulate the heterogeneity and histological, genetic and biological features of human HGSC. These models should prove useful for studying the pathobiology and genetics of HGSC in vivo, and for testing new approaches for prevention, early detection, and treatment. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/genética
Carcinoma in Situ/genética
Carcinossarcoma/genética
Neoplasias das Tubas Uterinas/genética
Tubas Uterinas/patologia
Neoplasias Císticas, Mucinosas e Serosas/genética
[Mh] Termos MeSH secundário: Animais
Biomarcadores Tumorais/metabolismo
Carcinoma in Situ/metabolismo
Carcinoma in Situ/patologia
Carcinossarcoma/patologia
Neoplasias das Tubas Uterinas/metabolismo
Neoplasias das Tubas Uterinas/patologia
Tubas Uterinas/metabolismo
Feminino
Genes BRCA1
Genes da Neurofibromatose 1
Genes do Retinoblastoma/genética
Genes p53
Predisposição Genética para Doença
Glicoproteínas/genética
Seres Humanos
Hiperplasia
Integrases/genética
Metaplasia
Camundongos Transgênicos
Mutação
Gradação de Tumores
Neoplasias Císticas, Mucinosas e Serosas/metabolismo
Neoplasias Císticas, Mucinosas e Serosas/patologia
PTEN Fosfo-Hidrolase/genética
Fenótipo
Regiões Promotoras Genéticas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (Glycoproteins); 0 (Ovgp1 protein, mouse); EC 2.7.7.- (Cre recombinase); EC 2.7.7.- (Integrases); EC 3.1.3.67 (PTEN Phosphohydrolase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170614
[St] Status:MEDLINE
[do] DOI:10.1002/path.4927


  9 / 2662 MEDLINE  
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[PMID]:28591030
[Au] Autor:Li BQ; Liu QF; Chang XY; Hu Y; Chen J; Guo JC
[Ad] Endereço:aDepartment of General Surgery bDepartment of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
[Ti] Título:Pancreatic carcinosarcoma mimics malignant intraductal papillary mucinous neoplasm: A rare case report and literature review.
[So] Source:Medicine (Baltimore);96(23):e6961, 2017 Jun.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Carcinosarcoma, an extremely rare pancreatic primary tumor, is characterized by coexistence of both carcinomatous and sarcomatous components. Due to its rarity, the clinical manifestation and imaging features have not been recognized. An accurate diagnostic method has not been available and a widely accepted guidelines instructing treatment has not been established. PATIENT CONCERNS: We present an uncommon case of pancreatic carcinosarcoma (PCS) which has been preoperatively diagnosed as pancreatic malignant intraductal papillary mucinous neoplasm. A radical resection, including total pancreatectomy (TP) and splenectomy, was performed. DIAGNOSIS: The diagnosis of PCS was confirmed by postoperative pathology. INTERVENTIONS: A radical resection, including TP and splenectomy, was performed. The patient was followed up by abdominal contrast-enhanced computed tomography scan and blood tumor marker examination. OUTCOMES: The patient is still alive and self-sufficient 7 months after the surgery. No evidence of tumor recurrence is found during follow-up. LESSONS: Although, until recently, there are no widely accepted guidelines instructing treatment for PCS, a radical resection is still a possible way. All the pancreatic neoplastic patients with high surgical risk should be transferred to a specialized high-volume pancreatic center to get precise preoperative evaluation, fine operation technique, and careful postoperative management.
[Mh] Termos MeSH primário: Adenocarcinoma Mucinoso/diagnóstico
Carcinoma Ductal Pancreático/diagnóstico
Carcinoma Papilar/diagnóstico
Carcinossarcoma/diagnóstico
Carcinossarcoma/cirurgia
Neoplasias Pancreáticas/diagnóstico
Neoplasias Pancreáticas/cirurgia
[Mh] Termos MeSH secundário: Carcinossarcoma/patologia
Diagnóstico Diferencial
Seres Humanos
Masculino
Meia-Idade
Pancreatectomia
Neoplasias Pancreáticas/patologia
Esplenectomia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE; REVIEW
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170706
[Lr] Data última revisão:
170706
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170608
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000006961


  10 / 2662 MEDLINE  
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[PMID]:28577885
[Au] Autor:Plante M; Stanleigh J; Renaud MC; Sebastianelli A; Grondin K; Grégoire J
[Ad] Endereço:Gynecologic Oncology Division, L'Hôtel-Dieu de Québec, Centre Hospitalier Universitaire de Québec, Laval University, Quebec City, Canada. Electronic address: marie.plante@crhdq.ulaval.ca.
[Ti] Título:Isolated tumor cells identified by sentinel lymph node mapping in endometrial cancer: Does adjuvant treatment matter?
[So] Source:Gynecol Oncol;146(2):240-246, 2017 Aug.
[Is] ISSN:1095-6859
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To evaluate the outcome and the role of adjuvant treatment in the management of patients with endometrial cancer and isolated tumor cells (ITCs) identified by SLN mapping. METHODS: This single center study identified all patients undergoing hysterectomy, salpingo-oophorectomy, lymphadenectomy and SLN mapping for endometrial cancer between November 2010 and December 2015. Data was prospectively collected. Progression-free survival was analyzed according to the Kaplan-Meier method and compared using the log-rank test. RESULTS: A total of 519 patients were included. Overall, 85 patients (16.4%) were found to have SLN metastases of which 43 (51%) were macrometastasis, 11 (13%) micrometastasis (MM) and 31 (36%) ITC. Eleven (35%) of patients with ITCs received adjuvant chemotherapy±whole pelvic radiation therapy (WPRT), 10 (32%) received WPRT, and 10 (32%) received either no adjuvant treatment or vault brachytherapy (VBT) only. ITC patients received significantly less chemotherapy (p=0.0001) and WPRT (p=0.007) compared to patients with macrometastasis. Of note, ITC were not considered node positive in our study. With a median follow-up of 29months (range: 0-67), the progression free survival (PFS) at 3-years for the ITC patients was 95.5%, similar to node negative (87.6%) and micrometastasis patients (85.5%), but statistically better than patients with macrometastasis (58.5%) (p=0.0012). Only 1/31 patient with ITC recurred (IB, 7cm carcinosarcoma) despite adjuvant treatments. None of the ITC patients with endometrioid histology recurred (0/28) and none of the ITC patients who did not receive adjuvant treatment or VBT recurred (0/10). CONCLUSIONS: Patients with endometrial cancer found to have SLN ITCs have an excellent outcome. The use of adjuvant treatment should be tailored to uterine factors and histology and not solely based on the presence of ITCs. Patients with ITCs and otherwise low-risk uterine disease probably derive little benefit from receiving additional treatments. More studies are needed to confirm our results.
[Mh] Termos MeSH primário: Adenocarcinoma de Células Claras/terapia
Carcinoma Endometrioide/terapia
Carcinossarcoma/terapia
Quimioterapia Adjuvante
Neoplasias do Endométrio/terapia
Micrometástase de Neoplasia/patologia
Neoplasias Císticas, Mucinosas e Serosas/terapia
Radioterapia Adjuvante
Linfonodo Sentinela/patologia
[Mh] Termos MeSH secundário: Adenocarcinoma de Células Claras/patologia
Adulto
Idoso
Idoso de 80 Anos ou mais
Braquiterapia
Carcinoma Endometrioide/patologia
Carcinossarcoma/patologia
Intervalo Livre de Doença
Neoplasias do Endométrio/patologia
Feminino
Seres Humanos
Histerectomia
Excisão de Linfonodo
Meia-Idade
Estadiamento de Neoplasias
Neoplasias Císticas, Mucinosas e Serosas/patologia
Ovariectomia
Prognóstico
Estudos Retrospectivos
Salpingectomia
Biópsia de Linfonodo Sentinela
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170724
[Lr] Data última revisão:
170724
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170605
[St] Status:MEDLINE



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