Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 550
Filtrar
2.
Gene ; 760: 145025, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32758582

RESUMO

Numerous cell lines for human alveolar rhabdomyosarcoma (ARMS) have been developed and are widely used to study biological processes of this myogenic cancer. The present study investigated the resemblance of commonly used ARMS cell lines to primary tumors in regards to gene expression. RNA-sequencing data was retrieved from published datasets for 4 commonly used ARMS cell lines and 35 ARMS primary tumors. The genes with most variable expression across primary tumors were used to calculate rank-based Spearman's correlation. The observed median correlations ranged from 0.36 to 0.61. RH-41 showed the highest median correlation while KYM-1 was the least correlated cell line. A significant number of genes dysregulated between tumors and non-tumors also exhibited similar expression patterns between tumors and cell lines, including The findings suggest that ARMS cell lines exhibit changes in gene expression compared to primary tumors and may not be completely representative of the disease process.


Assuntos
RNA Mensageiro/genética , Rabdomiossarcoma Alveolar/genética , Transcriptoma/genética , Linhagem Celular Tumoral , Bases de Dados Genéticas , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Modelos Biológicos , Rabdomiossarcoma Alveolar/metabolismo , Rabdomiossarcoma Alveolar/patologia , Rabdomiossarcoma Embrionário/genética , Rabdomiossarcoma Embrionário/metabolismo , Rabdomiossarcoma Embrionário/patologia , Análise de Sequência de RNA/métodos , Estatísticas não Paramétricas
3.
Am J Surg Pathol ; 44(6): 738-747, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31990691

RESUMO

DICER1 mutations (somatic or germline) are associated with a variety of uncommon neoplasms including cervical and genitourinary embryonal rhabdomyosarcoma (ERMS). We report a primary ovarian and 2 primary fallopian tube ERMS occurring in 60-, 13-, and 14-year-olds, respectively. The 3 neoplasms exhibited a similar morphologic appearance being polypoid and containing edematous hypocellular areas and hypercellular foci composed of small cells with scant cytoplasm exhibiting rhabdomyoblastic differentiation (desmin, myogenin, myoD1 positive). There was cellular cartilage in all cases and extensive foci of anaplasia, eosinophilic globules, and bone/osteoid in 1 case each. All 3 neoplasms exhibited DICER1 mutations; in 1 of the tubal cases, the patient had a germline mutation and in the other 2 cases, the DICER1 mutations were somatic. Accompanying DICER1 "second hits" were identified in all cases. In 2 of the neoplasms, SALL4-positive glandular structures were present which we speculate may represent an unusual primitive "metaplastic" phenomenon. Our study adds to the literature on ERMS at unusual sites associated with DICER1 mutations. ERMS arising at such sites, especially when they contain cartilage or bone/osteoid, are especially likely to be associated with DICER1 mutations. Pathologists should be aware of this as these may be the sentinel neoplasms in patients with DICER1 syndrome and confirming a germline mutation can facilitate the screening of the individual and affected family members for other neoplasms which occur in this syndrome.


Assuntos
RNA Helicases DEAD-box/genética , Neoplasias das Tubas Uterinas/genética , Síndromes Neoplásicas Hereditárias/genética , Neoplasias Ovarianas/genética , Rabdomiossarcoma Embrionário/genética , Ribonuclease III/genética , Adolescente , Neoplasias das Tubas Uterinas/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Mutação , Neoplasias Ovarianas/patologia , Rabdomiossarcoma Embrionário/patologia
4.
Urology ; 137: 173-177, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31945380

RESUMO

Rhabdomyosarcoma is the most common sarcoma diagnosed in childhood and adolescence, arising from the bladder/prostate in only 5%-10% of cases. Treatment-induced cytodifferention of tumor cells into mature rhabdomyoblasts has been reported following chemoradiation and is thought to suggest a more favorable outcome. We report a case of embryonal rhabdomyosarcoma of the bladder/prostate that exhibited extensive cytodifferentiation with downregulation of myogenin and MyoD1 gene expression in rhabdomyoblasts following treatment with chemoradiation therapy. The downregulation of myogenin and MyoD1 expression in rhabdomyoblasts following chemoradiation treatment has not previously been described in the literature and its significant remains uncertain.


Assuntos
Diferenciação Celular , Quimiorradioterapia , Proteína MyoD/genética , Miogenina/genética , Neoplasias da Próstata , Rabdomiossarcoma Embrionário , Neoplasias da Bexiga Urinária , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biópsia/métodos , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/efeitos da radiação , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Diagnóstico Diferencial , Regulação para Baixo , Expressão Gênica , Humanos , Imuno-Histoquímica , Lactente , Masculino , Proteína MyoD/análise , Miogenina/análise , Seleção de Pacientes , Prognóstico , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Rabdomiossarcoma Embrionário/diagnóstico por imagem , Rabdomiossarcoma Embrionário/genética , Rabdomiossarcoma Embrionário/patologia , Rabdomiossarcoma Embrionário/terapia , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia
5.
J Pediatr Adolesc Gynecol ; 33(2): 173-176, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31838154

RESUMO

BACKGROUND: Germline DICER1 mutations increase the risk of developing a wide variety of generally uncommon tumors. We describe a case of DICER1-related embryonal rhabdomyosarcoma (ERMS) of the uterine corpus in a prepubertal girl. CASE: A 10-year-old- girl with a history of cystic nephroma presented with a 3-week history of vaginal bleeding. A 3-cm mass filling the uterine cavity was detected, and histopathologic examination of hysteroscopy-guided biopsy samples revealed ERMS. Molecular genetic sequencing of the tumor sample revealed a DICER1 mutation. SUMMARY AND CONCLUSION: This report highlights the importance of screening for DICER1 mutations in the presence of the early-onset features of this syndrome, and extends the spectrum of DICER1-related tumors by showing the mutation in a case of ERMS of the uterine corpus.


Assuntos
Rabdomiossarcoma Embrionário/genética , Neoplasias Uterinas/genética , Quimioterapia Adjuvante/métodos , Criança , RNA Helicases DEAD-box , Feminino , Mutação em Linhagem Germinativa , Humanos , Histerectomia , Rabdomiossarcoma Embrionário/diagnóstico , Rabdomiossarcoma Embrionário/patologia , Rabdomiossarcoma Embrionário/terapia , Ribonuclease III , Hemorragia Uterina/etiologia , Neoplasias Uterinas/diagnóstico por imagem , Neoplasias Uterinas/patologia , Neoplasias Uterinas/terapia
6.
Urology ; 137: 168-172, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31794814

RESUMO

Neurofibromatosis-1 has a known increased risk of malignancy with rhabdomyosarcoma occurring in up to 6% of patients. Here we report on an 8-year-old male with a history of Neurofibromatosis-1 and previously treated stage 3, group III bladder/prostate embryonal rhabdomyosarcoma (diagnosed at 18 months old) who presented with penile swelling concerning for priapism. Imaging and subsequent biopsy confirmed embryonal rhabdomyosarcoma of the penile corporal bodies. Penile rhabdomyosarcoma is exceedingly rare, with less than 15 case reports in the literature. Our patient received chemoradiation per D9803 with organ preserving local control and is doing well 3 months after treatment.


Assuntos
Quimiorradioterapia/métodos , Recidiva Local de Neoplasia , Neurofibromatose 1 , Neoplasias Penianas , Priapismo/diagnóstico , Neoplasias da Próstata , Rabdomiossarcoma Embrionário , Neoplasias da Bexiga Urinária , Biópsia/métodos , Criança , Diagnóstico Diferencial , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neurofibromatose 1/patologia , Neurofibromatose 1/terapia , Neoplasias Penianas/diagnóstico , Neoplasias Penianas/tratamento farmacológico , Neoplasias Penianas/patologia , Neoplasias Penianas/radioterapia , Pênis/diagnóstico por imagem , Pênis/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Rabdomiossarcoma Embrionário/patologia , Rabdomiossarcoma Embrionário/terapia , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapia
7.
Pract Radiat Oncol ; 10(1): 53-58, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31629089

RESUMO

PURPOSE: In survivors of orbital embryonal rhabdomyosarcoma (ERMS), late effects include facial deformation and asymmetry. We sought to quantify orbital asymmetry in ERMS survivors and characterize the dose effect of radiation to the orbital bones. METHODS AND MATERIALS: We evaluated the most recent follow-up magnetic resonance imaging (MRI) in 17 children (≤21 years old) with stage 1 group III orbital ERMS treated with proton therapy between 2007 and 2018. For all patients, the orbital socket volumes were calculated and compared with the contralateral, unirradiated orbital socket. Patient age, orbital tumor quadrant, and the radiation dose delivered to the major orbital bones (maxillary, frontal, and zygomatic bones) were recorded and correlated with the orbital socket volume difference. RESULTS: The mean age at diagnosis was 5.4 years old (range, 1.1-9.7 years). All patients received a prescription dose of 45 GyRBE. The mean time interval between radiation and MRI was 2.9 years (range, 0.8-3.2 years). The mean age at most recent MRI was 8.4 years (range, 2.3-12.9 years). In 16 of 17 patients, the volume of the ipsilateral orbit was significantly smaller than the contralateral orbit on follow-up MRI (P ≤ .0001). In one patient with nonviable tumor in situ, the irradiated orbit was larger. The volume difference increased with follow-up time and did not correlate with age at treatment or age at MRI. A dose >40 GyRBE to all bones of the orbital rim was associated with a significant decrease in orbital volume (P < .05), but an isolated dose of >40 GyRBE to either the frontal, maxillary, or zygomatic bone was not. CONCLUSIONS: Despite the dosimetric precision of proton therapy, orbital asymmetry will develop after >40 GyRBE to multiple bones of the orbital rim. These data may be used to guide treatment planning and counsel patients on expected cosmesis.


Assuntos
Assimetria Facial/etiologia , Órbita/efeitos da radiação , Neoplasias Orbitárias/radioterapia , Terapia com Prótons/efeitos adversos , Lesões por Radiação/etiologia , Rabdomiossarcoma Embrionário/radioterapia , Criança , Pré-Escolar , Relação Dose-Resposta à Radiação , Assimetria Facial/diagnóstico por imagem , Assimetria Facial/prevenção & controle , Feminino , Seguimentos , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Órbita/diagnóstico por imagem , Órbita/patologia , Neoplasias Orbitárias/diagnóstico por imagem , Neoplasias Orbitárias/patologia , Tamanho do Órgão/efeitos da radiação , Terapia com Prótons/métodos , Lesões por Radiação/diagnóstico por imagem , Lesões por Radiação/prevenção & controle , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Rabdomiossarcoma Embrionário/diagnóstico por imagem , Rabdomiossarcoma Embrionário/patologia
8.
Clin Oncol (R Coll Radiol) ; 32(1): e27-e35, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31350181

RESUMO

AIMS: Embryonal and alveolar rhabdomyosarcoma (ERMS, ARMS) are subtypes of RMS that mainly occur in children, with relatively good outcomes. The incidence in adults is extremely low and survival is significantly worse compared with children. Data are scarce and literature generally combines all RMS subtypes, including pleomorphic RMS, which primarily occurs in adults and behaves more like undifferentiated pleomorphic sarcoma. The aim of this study was to evaluate patient and tumour characteristics, outcome and prognostic factors in adult patients with ERMS and ARMS. MATERIALS AND METHODS: All adult (18 years or older) ERMS and ARMS patients (presenting 1990-2016) were identified from a prospectively maintained database and were included in this analysis. RESULTS: Overall, 66 patients were included (42 men, 24 women). The median age at presentation was 28 years (range 18-71). The median overall survival for all ARMS (n = 42) and ERMS (n = 24) patients was 18 months, with a 5-year overall survival rate of 27%. Patients presenting with localised disease (n = 38, 58%) and metastatic disease (n = 25, 42%), had a 5-year overall survival rate of 36% and 11%, respectively. In univariate analysis we found alveolar subtype, fusion gene positivity, infiltrative tumour and metastatic presentation to be negative prognostic factors. CONCLUSION: Survival in adult ERMS and ARMS patients is poor and the current data may be useful in the design of trials with novel agents. Ideally, paediatric and adult oncologists should set up trials together to get a better understanding of biological, genetic and clinically relevant factors in this disease.


Assuntos
Rabdomiossarcoma Alveolar/epidemiologia , Rabdomiossarcoma Embrionário/epidemiologia , Neoplasias de Tecidos Moles/epidemiologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rabdomiossarcoma Alveolar/mortalidade , Rabdomiossarcoma Alveolar/patologia , Rabdomiossarcoma Embrionário/mortalidade , Rabdomiossarcoma Embrionário/patologia , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/patologia , Taxa de Sobrevida , Adulto Jovem
10.
Biosci Biotechnol Biochem ; 84(1): 63-75, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31462179

RESUMO

A natural isoquinoline alkaloid, berberine, has been known to exhibit anti-tumor activity in various cancer cells via inducing cell cycle arrest. However, it has not been investigated whether berberine and its analogs inhibit the growth of rhabdomyosarcoma (RMS), which is the most frequent soft tissue tumor in children. The present study examined the anti-tumor effects of berberine and palmatine on expansions of three human embryonal RMS cell lines; ERMS1, KYM1, and RD. Intracellular incorporation of berberine was relatively higher than that of palmatine in every RMS cell line. Berberine significantly inhibited the cell cycle of all RMS cells at G1 phase. On the other hand, palmatine only suppressed the growth of RD cells. Both of berberine and palmatine strongly inhibited the growth of tumorsphere of RD cells in three-dimensional culture. These results indicate that berberine derivatives have the potential of anti-tumor drugs for RMS therapy.Abbreviations: ARMS: alveolar rhabdomyosarcoma; ERMS: embryonal rhabdomyosarcoma; RMS: rhabdomyosarcoma.


Assuntos
Antineoplásicos/farmacologia , Alcaloides de Berberina/farmacologia , Berberina/farmacologia , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Rabdomiossarcoma Alveolar/patologia , Rabdomiossarcoma Embrionário/patologia , Antineoplásicos/química , Berberina/análogos & derivados , Berberina/química , Alcaloides de Berberina/química , Linhagem Celular Tumoral , Ciclina D1/genética , Inibidor de Quinase Dependente de Ciclina p57/genética , Avaliação Pré-Clínica de Medicamentos/métodos , Medicamentos de Ervas Chinesas/química , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica , Humanos , Antígeno Ki-67/genética , Conformação Molecular , Simulação de Acoplamento Molecular , Phellodendron/química , Rabdomiossarcoma Alveolar/metabolismo , Rabdomiossarcoma Embrionário/metabolismo
11.
Chem Biol Interact ; 312: 108813, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31494105

RESUMO

Rhabdomyosarcoma (RMS) is a pediatric tumor, which arises from muscle precursor cells. Recently, it has been demonstrated that Hippo Pathway (Hpo), a pathway that regulates several physiological and biological features, is involved in RMS tumorigenesis. For instance, an upregulation of the Hpo downstream effector Yes-Associated Protein 1 (YAP) leads to the development of embryonal rhabdomyosarcoma (eRMS) in murine activated muscle satellite cells. On the other hand, the YAP paralog transcriptional co-activator with PDZ-binding motif (TAZ) is overexpressed in alveolar rhabdomyosarcoma (aRMS) patients with poor survival. YAP and TAZ exhibit both cytoplasmic and nuclear functions. In the nucleus, YAP binds TEADs (TEA domain family members) factors and together they constitute a complex that is able either to activate the transcription of several genes such as MYC, Tbx5 and PAX8 or to maintain the stability of others like p73. Due to the key role of YAP and TAZ in cancer, the identification and/or development of new compounds able to block their activity might be an effective antineoplastic strategy. Verteporfin (VP) is a molecule able to stop the formation of YAP/TEAD complex in the nucleus. The aim of this study is to evaluate the action of VP on RMS cell lines. This work shows that VP has an anti-proliferative activity on all RMS cell lines analyzed. Depending on RMS cell lines, VP affects cell cycle differently. Moreover, VP is able to decrease YAP protein levels, and to induce the activation of apoptosis mechanism through the cleavage of PARP-1. In addition, Annexin V assay showed the activation of apoptosis and necrosis after VP treatment. In summary, the ability of VP to disrupt RMS cell proliferation could be a novel and valuable strategy to improve the therapeutic approaches in treating rhabdomyosarcoma.


Assuntos
Proliferação de Células/efeitos dos fármacos , Verteporfina/farmacologia , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Proteínas Nucleares/metabolismo , Poli(ADP-Ribose) Polimerase-1/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Rabdomiossarcoma Alveolar/metabolismo , Rabdomiossarcoma Alveolar/patologia , Rabdomiossarcoma Embrionário/metabolismo , Rabdomiossarcoma Embrionário/patologia , Fatores de Transcrição/metabolismo
12.
Lancet Oncol ; 20(11): 1566-1575, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31562043

RESUMO

BACKGROUND: For more than three decades, standard treatment for rhabdomyosarcoma in Europe has included 6 months of chemotherapy. The European paediatric Soft tissue sarcoma Study Group (EpSSG) aimed to investigate whether prolonging treatment with maintenance chemotherapy would improve survival in patients with high-risk rhabdomyosarcoma. METHODS: RMS 2005 was a multicentre, open-label, randomised, controlled, phase 3 trial done at 102 hospitals in 14 countries. We included patients aged 6 months to 21 years with rhabdomyosarcoma who were considered to be at high risk of relapse: those with non-metastatic incompletely resected embryonal rhabdomyosarcoma occurring at unfavourable sites with unfavourable age (≥10 years) or tumour size (>5 cm), or both; those with any non-metastatic rhabdomyosarcoma with nodal involvement; and those with non-metastatic alveolar rhabdomyosarcoma but without nodal involvement. Patients in remission after standard treatment (nine cycles of ifosfamide, vincristine, dactinomycin with or without doxorubicin, and surgery or radiotherapy, or both) were randomly assigned (1:1) to stop treatment or continue maintenance chemotherapy (six cycles of intravenous vinorelbine 25 mg/m2 on days 1, 8, and 15, and daily oral cyclophosphamide 25 mg/m2, on days 1-28). Randomisation was done by use of a web-based system and was stratified (block size of four) by enrolling country and risk subgroup. Neither investigators nor patients were masked to treatment allocation. The primary outcome was disease-free survival in the intention-to-treat population. Secondary outcomes were overall survival and toxicity. This trial is registered with EudraCT, number 2005-000217-35, and ClinicalTrials.gov, number NCT00339118, and follow-up is ongoing. FINDINGS: Between April 20, 2006, and Dec 21, 2016, 371 patients were enrolled and randomly assigned to the two groups: 186 to stop treatment and 185 to receive maintenance chemotherapy. Median follow-up was 60·3 months (IQR 32·4-89·4). In the intention-to-treat population, 5-year disease-free survival was 77·6% (95% CI 70·6-83·2) with maintenance chemotherapy versus 69·8% (62·2-76·2) without maintenance chemotherapy (hazard ratio [HR] 0·68 [95% CI 0·45-1·02]; p=0·061), and 5-year overall survival was 86·5% (95% CI 80·2-90·9) with maintenance chemotherapy versus 73·7% (65·8-80·1) without (HR 0·52 [95% CI 0·32-0·86]; p=0·0097). Toxicity was manageable in patients who received maintenance chemotherapy: 136 (75%) of 181 patients had grade 3-4 leucopenia, 148 (82%) had grade 3-4 neutropenia, 19 (10%) had anaemia, two (1%) had thrombocytopenia, and 56 (31%) had an infection. One (1%) patient had a grade 4 non-haematological toxicity (neurotoxicity). Two treatment-related serious adverse events occurred: one case of inappropriate antidiuretic hormone secretion and one of a severe steppage gait with limb pain, both of which resolved. INTERPRETATION: Adding maintenance chemotherapy seems to improve survival for patients with high-risk rhabdomyosarcoma. This approach will be the new standard of care for patients with high-risk rhabdomyosarcoma in future EpSSG trials. FUNDING: Fondazione Città della Speranza, Association Léon Berard Enfant Cancéreux, Clinical Research Hospital Program (French Ministry of Health), and Cancer Research UK.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclofosfamida/administração & dosagem , Quimioterapia de Manutenção , Rabdomiossarcoma Alveolar/tratamento farmacológico , Rabdomiossarcoma Embrionário/tratamento farmacológico , Vinorelbina/administração & dosagem , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Argentina , Brasil , Criança , Ciclofosfamida/efeitos adversos , Progressão da Doença , Intervalo Livre de Doença , Europa (Continente) , Feminino , Humanos , Israel , Quimioterapia de Manutenção/efeitos adversos , Quimioterapia de Manutenção/mortalidade , Masculino , Indução de Remissão , Rabdomiossarcoma Alveolar/mortalidade , Rabdomiossarcoma Alveolar/patologia , Rabdomiossarcoma Embrionário/mortalidade , Rabdomiossarcoma Embrionário/patologia , Medição de Risco , Fatores de Risco , Fatores de Tempo , Vinorelbina/efeitos adversos , Adulto Jovem
13.
Autops. Case Rep ; 9(3): e2019104, July-Sept. 2019. ilus
Artigo em Inglês | LILACS | ID: biblio-1017386

RESUMO

Rhabdomyosarcoma (RMS) is a rare solid tumor in childhood and adolescence. The higher incidence is predominant during the first two decades of life. According to the Intergroup RMS Study Group, the embryonal RMS (ERMS), botryoidal variant, constitutes a histological subtype characterized as a "grape-like" lesion of 2.0 cm to 9.5 cm. The treatment involves chemotherapy, surgery, and/or radiotherapy. We present the case of a 14-year-old female patient diagnosed with ERMS, botryoidal variant, which originated in the uterine cervix with vaginal externalization. The initial therapeutic approach comprised an initial prolapsed mass excision followed by Wertheim­Meigs surgery due to the tumor extension. No consensual protocol to ERMS treatment is found in the medical literature; however, a combined approach seems to offer a better result. The postoperative time period was uneventful and the patient followed an adjuvant therapy with vincristine, d-actinomycin, and cyclophosphamide. A comprehensive evaluation of the therapeutic options preserving the reproductive function­unfortunately not always possible­is part of a multi-disciplined care team concerning the pediatric patients.


Assuntos
Humanos , Feminino , Adolescente , Neoplasias do Colo do Útero/patologia , Rabdomiossarcoma Embrionário/patologia , Colo do Útero/anormalidades
14.
Pediatr Blood Cancer ; 66(11): e27952, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31397065

RESUMO

PURPOSE/OBJECTIVE(S): Bladder and prostate are unfavorable sites for rhabdomyosarcoma (B/P-RMS), and represent a challenging location for radiotherapy. MATERIALS/METHODS: Nineteen patients with B/P-RMS were enrolled on a prospective registry protocol (2008-2017) and treated with chemotherapy, proton beam therapy (PBT), and surgical resection (n = 8; 42%). Emphasis was given to treatment technique, disease-related outcomes, and toxicity associated with PBT. RESULTS: The majority of patients had bladder RMS (74%) of embryonal histology (95%), Group III (68%), and intermediate-risk disease by Children's Oncology Group (COG) risk stratification (89%). Seven patients (37%) had primary tumors >5 cm in size. All patients were treated according to COG protocols. With a median follow-up of 66.2 months, 5-year overall survival (OS) and progression-free survival (PFS) were 76%. Four patients (21%) experienced disease relapse, all presenting with local failure. The 5-year local control (LC) rate was 76%. Tumor size predicted LC, with 5-year LC for patients with >5 cm tumors being 43% versus 100% for those with ≤5 cm tumors (P = .006). Univariate analysis demonstrated an effect of tumor size on OS (tumor >5 cm, hazard ratio [HR] 17.7, P = .049) and PFS (HR 17.7, P = .049). Acute grade 2 toxicity was observed in two patients (11%, transient proctitis). Late grade 2+ toxicity was observed in three patients (16%; n = 1 grade 2 skeletal deformity; n = 3 transient grade 2 urinary incontinence; one patient experienced both). CONCLUSIONS: PBT for B/P-RMS affords promising disease-related outcomes with an acceptable toxicity profile. Higher local failure rates were observed for larger tumors, supporting dose-escalation components of ongoing RMS clinical trials.


Assuntos
Neoplasias da Próstata/radioterapia , Terapia com Prótons , Rabdomiossarcoma Embrionário/radioterapia , Neoplasias da Bexiga Urinária/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pré-Escolar , Terapia Combinada , Cistectomia , Feminino , Seguimentos , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Estadiamento de Neoplasias , Proctite/etiologia , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Prospectivos , Prostatectomia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Terapia com Prótons/efeitos adversos , Terapia com Prótons/métodos , Lesões por Radiação/etiologia , Sistema de Registros , Rabdomiossarcoma Alveolar/tratamento farmacológico , Rabdomiossarcoma Alveolar/patologia , Rabdomiossarcoma Alveolar/radioterapia , Rabdomiossarcoma Alveolar/cirurgia , Rabdomiossarcoma Embrionário/tratamento farmacológico , Rabdomiossarcoma Embrionário/patologia , Rabdomiossarcoma Embrionário/cirurgia , Risco , Carga Tumoral , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia , Incontinência Urinária/etiologia
15.
Urol J ; 17(5): 525-527, 2019 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-31328249

RESUMO

Traditionally, the standard treatment of bladder-prostate rhabdomyosarcoma (BP-RMS) is being implemented to be total cystoprostatectomy and urinary diversion. However, current multimodal treatment approaches emphasize the importance of bladder-sparing surgery. In this case series, it was aimed to indicate the results of the laparoscopic bladder-sparing approach of two pediatric patients with BP RMS. They have admitted to the emergency department due to acute urinary retention (AUR). The tumors located in the prostate causing AUR were detected by Magnetic resonance imaging (MRI) and the pathological diagnosis was confirmed by biopsy. The patients were managed in a prosperous manner by implementing laparoscopic surgery with the cause of detection of a significant decrease in the size as well as the enhancement pattern of the tumors following neoadjuvant chemotherapy. No urinary incontinence, tumor recurrence or metastasis was observed at 36 and 28 months follow-up in case 1 and case 2, respectively. Laparoscopic bladder-sparing approaches may have an advantage in patients with BP RMS to decrease morbidity and mortality related to radical surgery. To our knowledge, these are the first cases of laparoscopic bladder-sparing approach in the treatment of pediatric prostate-derived embryonal RMS (PDERMS).


Assuntos
Laparoscopia/métodos , Tratamentos com Preservação do Órgão/métodos , Próstata , Prostatectomia/métodos , Neoplasias da Próstata , Rabdomiossarcoma Embrionário , Bexiga Urinária , Biópsia/métodos , Pré-Escolar , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Terapia Neoadjuvante/métodos , Próstata/diagnóstico por imagem , Próstata/patologia , Próstata/cirurgia , Neoplasias da Próstata/complicações , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Rabdomiossarcoma Embrionário/complicações , Rabdomiossarcoma Embrionário/patologia , Rabdomiossarcoma Embrionário/cirurgia , Resultado do Tratamento , Retenção Urinária/diagnóstico , Retenção Urinária/etiologia
16.
Pathol Int ; 69(8): 488-495, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31328317

RESUMO

We herein report the case of a 2-year-old girl with neurofibromatosis type 1 (NF1), who presented with a 12-cm mass in the right retroperitoneum and underwent tumor resection. Histologically, the tumor was composed of two distinct components: one was teratoma, showing mature morphology; and the other was embryonal rhabdomyosarcoma. An interphase fluorescence in situ hybridization (FISH) analysis of the rhabdomyosarcoma component revealed the absence of isochromosome 12p. Although it is well known that rhabdomyosarcoma occurs in infantile NF1, and that rhabdomyosarcoma can arise from teratoma as a somatic-type malignancy, to the best of our knowledge, this is the first case of an infantile NF1 patient, who developed rhabdomyosarcoma within a retroperitoneal teratoma. The absence of chromosome 12p alteration suggests a possibility that the rhabdomyosarcoma occurred due to the NF1 background, not as a somatic-type malignancy of germ cell tumor.


Assuntos
Neoplasias Primárias Múltiplas/patologia , Neurofibromatose 1/patologia , Neoplasias Retroperitoneais/patologia , Rabdomiossarcoma Embrionário/patologia , Teratoma/patologia , Pré-Escolar , Feminino , Humanos , Neoplasias Primárias Múltiplas/diagnóstico , Neurofibromatose 1/diagnóstico , Neoplasias Retroperitoneais/diagnóstico , Rabdomiossarcoma Embrionário/diagnóstico , Teratoma/diagnóstico
17.
Sci Rep ; 9(1): 9211, 2019 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-31239476

RESUMO

Rhabdomyosarcomas (RMS) are rare and often lethal diseases. It is assumed that the tumor microenvironment (TME) of RMS exerts an immunosuppressive function, but there is currently no systematic analysis of the immune cells infiltrating sarcoma tissue. Focusing on two common types of RMS (alveolar [RMA] and embryonal [RME]), we performed a comprehensive immunohistochemical analysis of tumor-infiltrating immune cells in the TME. We performed a qualitative estimation of infiltrating immune cells in the tumor microenvironment by an experienced pathologist as well as a quantitative digital pathology analysis. We found that (1) manual and automatic quantification of tumor-infiltrating immune cells were consistent; (2) RME tumors showed a higher degree of immune cell infiltration than RMA tumors but (3) the number of tumor infiltrating lymphocytes was low compared to other solid tumor types; (4) microvascular density correlated with immune cell infiltration and (5) CD163 positive macrophages as well as CD54 positive microvessels were more often detected in RME than in RMA and correlated with patient overall and event free survival. Our systematic analysis provides a comprehensive view of the immune landscape of RMS which needs to be taken into account for developing immunotherapies for this rare type of cancer.


Assuntos
Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Biomarcadores Tumorais/metabolismo , Microvasos/imunologia , Receptores de Superfície Celular/metabolismo , Rabdomiossarcoma Embrionário/diagnóstico , Rabdomiossarcoma Embrionário/imunologia , Linfócitos B/imunologia , Linfócitos B/metabolismo , Antígeno B7-H1/metabolismo , Biópsia , Humanos , Microvasos/metabolismo , Prognóstico , Receptor de Morte Celular Programada 1/metabolismo , Rabdomiossarcoma Embrionário/metabolismo , Rabdomiossarcoma Embrionário/patologia
18.
Rev. esp. patol ; 52(2): 87-91, abr.-jun. 2019. ilus, graf
Artigo em Inglês | IBECS | ID: ibc-182694

RESUMO

We present a case of a nasal rhabdomyosarcoma (RMS) in a 27-year-old male with epistaxis and nasal obstruction due to a mass, which was subjected to prophylactic tumor embolization. However, histopathological study on the nasal biopsy was impossible due to necrotic changes. As blast cells were present in peripheral blood samples, a bone marrow biopsy was recommended in order to reach a definitive diagnosis. The possibility of an RMS in cases of bone marrow infiltration by a diffuse tumor constituted by small, round, blast-like cells mimicking acute leukemia should be assessed. Immunohistochemical staining in bone marrow biopsy and flow cytometry in aspirate samples may help to establish the diagnosis (CD45 negativity and CD56 positivity) and cytogenetic studies can be useful in identifying a RMS subtype. When clinically possible, it is desirable to await the results of the tumor immunophenotype and those of the primary mass or bone marrow biopsy to avoid possible errors of diagnosis and treatment


Se presenta el caso de un rabdomiosarcoma (RMS) en un varón de 27 años de edad con cuadro de epistaxis y obstrucción por masa nasal, que fue sometido a embolización tumoral profiláctica. El estudio en sangre periférica, fundamentalmente por la detección de células de apariencia blástica, recomendó biopsia de médula ósea que fue determinante para el diagnóstico, debido a que la embolización tumoral en la biopsia nasal, invalidó por cambios necróticos su estudio histopatológico. Se debe evaluar la posibilidad diagnóstica de un RMS, en casos de infiltración de médula ósea por un tumor difuso constituido por células pequeñas, redondas y similares a blastos que imitan una leucemia aguda. La tinción inmunohistoquímica en la biopsia de médula ósea y la citometría de flujo en muestras de aspirado, pueden ayudar a establecer el diagnóstico (negatividad CD45 y positividad CD56) y los estudios citogenéticos pueden ayudar a diferenciar el subtipo de RMS. Cuando sea clínicamente posible, se debe esperar a los resultados del inmunofenotipo celular del tumor y los de la masa primaria o la biopsia de la médula ósea, para así evitar posibles errores de diagnóstico y tratamiento


Assuntos
Humanos , Masculino , Adulto , Rabdomiossarcoma Embrionário/patologia , Neoplasias da Medula Óssea/patologia , Neoplasias da Medula Óssea/secundário , Metástase Neoplásica/patologia , Leucemia Mieloide Aguda/patologia , Diagnóstico Diferencial
19.
Skelet Muscle ; 9(1): 12, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-31113472

RESUMO

BACKGROUND: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in the pediatric cancer population. Survival among metastatic RMS patients has remained dismal yet unimproved for years. We previously identified the class I-specific histone deacetylase inhibitor, entinostat (ENT), as a pharmacological agent that transcriptionally suppresses the PAX3:FOXO1 tumor-initiating fusion gene found in alveolar rhabdomyosarcoma (aRMS), and we further investigated the mechanism by which ENT suppresses PAX3:FOXO1 oncogene and demonstrated the preclinical efficacy of ENT in RMS orthotopic allograft and patient-derived xenograft (PDX) models. In this study, we investigated whether ENT also has antitumor activity in fusion-negative eRMS orthotopic allografts and PDX models either as a single agent or in combination with vincristine (VCR). METHODS: We tested the efficacy of ENT and VCR as single agents and in combination in orthotopic allograft and PDX mouse models of eRMS. We then performed CRISPR screening to identify which HDAC among the class I HDACs is responsible for tumor growth inhibition in eRMS. To analyze whether ENT treatment as a single agent or in combination with VCR induces myogenic differentiation, we performed hematoxylin and eosin (H&E) staining in tumors. RESULTS: ENT in combination with the chemotherapy VCR has synergistic antitumor activity in a subset of fusion-negative eRMS in orthotopic "allografts," although PDX mouse models were too hypersensitive to the VCR dose used to detect synergy. Mechanistic studies involving CRISPR suggest that HDAC3 inhibition is the primary mechanism of cell-autonomous cytoreduction in eRMS. Following cytoreduction in vivo, residual tumor cells in the allograft models treated with chemotherapy undergo a dramatic, entinostat-induced (70-100%) conversion to non-proliferative rhabdomyoblasts. CONCLUSION: Our results suggest that the targeting class I HDACs may provide a therapeutic benefit for selected patients with eRMS. ENT's preclinical in vivo efficacy makes ENT a rational drug candidate in a phase II clinical trial for eRMS.


Assuntos
Benzamidas/uso terapêutico , Inibidores de Histona Desacetilases/uso terapêutico , Piridinas/uso terapêutico , Rabdomiossarcoma Embrionário/tratamento farmacológico , Adolescente , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Benzamidas/administração & dosagem , Sistemas CRISPR-Cas , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Reprogramação Celular/efeitos dos fármacos , Reprogramação Celular/genética , Criança , Pré-Escolar , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Histona Desacetilase 1/antagonistas & inibidores , Histona Desacetilase 1/genética , Inibidores de Histona Desacetilases/administração & dosagem , Humanos , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Piridinas/administração & dosagem , RNA-Seq , Rabdomiossarcoma Alveolar/tratamento farmacológico , Rabdomiossarcoma Alveolar/enzimologia , Rabdomiossarcoma Alveolar/patologia , Rabdomiossarcoma Embrionário/enzimologia , Rabdomiossarcoma Embrionário/patologia , Carga Tumoral/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/genética , Vincristina/administração & dosagem , Ensaios Antitumorais Modelo de Xenoenxerto
20.
PLoS One ; 14(4): e0214758, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30973903

RESUMO

Myo/Nog cells are identified by their expression of the skeletal muscle specific transcription factor MyoD and the bone morphogenetic protein inhibitor noggin, and binding of the G8 monoclonal antibody. Their release of noggin is critical for morphogenesis and skeletal myogenesis. In the adult, Myo/Nog cells are present in normal tissues, wounds and skin tumors. Myo/Nog cells in the lens give rise to myofibroblasts that synthesize skeletal muscle proteins. The purpose of this study was to screen human lens tissue, rhabdomyosarcoma cell lines, and tissue sections from rhabdomyosarcoma, Wilms and tumors lacking features of skeletal muscle for co-localization of antibodies to Myo/Nog cell markers and the lens beaded filament proteins filensin and CP49. Immunofluorescence localization experiments revealed that Myo/Nog cells of the lens bind antibodies to beaded filament proteins. Co-localization of antibodies to G8, noggin, filensin and CP49 was observed in most RC13 and a subpopulation of RD human rhabdomyosarcoma cell lines. Western blotting with beaded filament antibodies revealed bands of similar molecular weights in RC13 and murine lens cells. Human alveolar, embryonal, pleomorphic and spindle cell rhabdomyosarcomas and Wilms tumors contained a subpopulation of cells immunoreactive for G8, noggin, MyoD and beaded filaments. G8 was also co-localized with filensin mRNA. Staining for beaded filament proteins was not detected in G8 positive cells in leiomyosarcomas, squamous and basal cell carcinomas, syringocarciomas and malignant melanomas. Lens beaded filament proteins were thought to be present only in the lens. Myo/Nog-like cells immunoreactive for beaded filaments may be diagnostic of tumors related to the skeletal muscle lineage.


Assuntos
Proteínas de Transporte/metabolismo , Proteínas do Olho/metabolismo , Proteínas de Filamentos Intermediários/metabolismo , Proteína MyoD/metabolismo , Rabdomiossarcoma/patologia , Tumor de Wilms/patologia , Animais , Anticorpos Monoclonais/imunologia , Proteínas de Transporte/imunologia , Linhagem Celular , Proteínas do Olho/genética , Proteínas do Olho/imunologia , Humanos , Proteínas de Filamentos Intermediários/genética , Proteínas de Filamentos Intermediários/imunologia , Cristalino/citologia , Cristalino/metabolismo , Camundongos , Microscopia de Fluorescência , Proteína MyoD/imunologia , Rabdomiossarcoma/metabolismo , Rabdomiossarcoma Embrionário/metabolismo , Rabdomiossarcoma Embrionário/patologia , Tumor de Wilms/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...