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1.
BMJ Case Rep ; 14(2)2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33541994

RESUMO

An 86-year-old woman was referred to the otolaryngology clinic for a 1-year history of a painless, slow-growing neck mass. Physical examination showed a fixed, immobile right level II neck mass with normal vocal cord movement. MRI demonstrated a lobulated mass laterally displacing the carotid vessels, consistent with a schwannoma. Despite the pathognomonic radiographic findings for schwannoma, core needle biopsy of the mass was consistent with intramuscular myxoma (IM), which rarely presents in the head and neck region. After multiple years of slow growth with bulging into the pharynx, the patient ultimately underwent surgery to reduce the risk of airway compromise. The location of this IM together with its unusual imaging appearance is a unique finding in the head and neck and adds to the differential diagnoses for neck masses displacing the carotid sheath.


Assuntos
Diagnóstico Diferencial , Neoplasias Musculares , Mixoma/diagnóstico , Mixoma/patologia , Músculos do Pescoço/patologia , Neurilemoma/diagnóstico , Idoso de 80 Anos ou mais , Feminino , Humanos , Imagem por Ressonância Magnética , Neoplasias Musculares/diagnóstico , Neoplasias Musculares/patologia , Mixoma/cirurgia
2.
Minerva Med ; 111(4): 354-361, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33032395

RESUMO

INTRODUCTION: According to the Staging System of Barcelona Clinic Liver Cancer (BCLC), diaphragmatic invasion (DI) is generally considered to be a manifestation of advanced hepatocellular carcinoma (HCC) with nearly no cure. However, some studies have indicated that combined liver and diaphragmatic resection may be a reasonably safe treatment option for HCC patients with diaphragmatic invasion. In this article, we conduct a systematic review to compare the short- and long-term surgical outcomes between HCC patients without diaphragmatic involvement who underwent hepatectomy alone and HCC patients with diaphragmatic involvement who underwent combined liver and diaphragmatic resection. EVIDENCE ACQUISITION: PubMed, Web of Science, Embase and Cochrane library databases were searched. All related studies were checked. Hazard ratios (HR) with 95% confidence intervals were calculated for the comparison of cumulative overall survival (OS) and recurrence free survival (RFS). Odds ratios (OR) with 95% CI were calculated for the comparison of overall postoperative morbidity and mortality. EVIDENCE SYNTHESIS: Seven studies met the inclusion criteria were included. There was no significant difference between the single hepatectomy group and combined liver and diaphragmatic resection group in the overall survival and recurrence free survival. Subgroup analysis showed a statistically significantly higher overall survival in HCC patients with diaphragmatic fibrous adhesion (DFA) compared with the DI group. However, there was no statistically significant difference in OS between the DI group and the single hepatectomy group. CONCLUSIONS: For HCC patients with diaphragmatic involvement, combined liver and diaphragmatic resection might be considered no matter whether its diaphragmatic invasion or not.


Assuntos
Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Diafragma , Hepatectomia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Neoplasias Musculares/patologia , Neoplasias Musculares/cirurgia , Humanos , Invasividade Neoplásica
3.
J Cancer Res Ther ; 16(4): 900-902, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32930137

RESUMO

Objective: Aggressive fibromatosis (AF), also called desmoid tumor, is an uncommon soft-tissue neoplasm. Characteristically, it expands locally without metastatic potential. However, its tendency of relapse after curative resections has been well documented. Effective treatment options have been limited and there is a clear need for novel treatment strategies. Methods: We used combination therapy including multikinase tyrosine kinase inhibitor for treating AF. Results: We presented a case of an extra-abdominal AF who was successfully treated with meloxicam and sorafenib combination in our clinic. She tolerated this therapy well with only mild side effects. To our knowledge, this is the first case report of an extra-abdominal AF with a major partial response to sorafenib and meloxicam combination. Conclusion: Due to the favorable toxicity profile of sorafenib and meloxicam, this combination might be an effective treatment option for patients with locally aggressive and inoperable AF.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fibromatose Agressiva/tratamento farmacológico , Neoplasias Musculares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Anti-Inflamatórios não Esteroides/administração & dosagem , Feminino , Fibromatose Agressiva/diagnóstico por imagem , Fibromatose Agressiva/patologia , Humanos , Perna (Membro)/patologia , Imagem por Ressonância Magnética/métodos , Meloxicam/administração & dosagem , Neoplasias Musculares/diagnóstico por imagem , Neoplasias Musculares/patologia , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Inibidores de Proteínas Quinases/administração & dosagem , Sorafenibe/administração & dosagem , Resultado do Tratamento
5.
Sci Rep ; 10(1): 10952, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32616859

RESUMO

Muscle-invasive bladder cancer (MIBC) is a heterogeneous disease that often recurs despite aggressive treatment with neoadjuvant chemotherapy and (radical) cystectomy. Basal and luminal molecular subtypes have been identified that are linked to clinical characteristics and have differential sensitivities to chemotherapy. While it has been suggested that epigenetic mechanisms play a role in defining these subtypes, a thorough understanding of the biological mechanisms is lacking. This report details the first genome-wide analysis of histone methylation patterns of human primary bladder tumours by chromatin immunoprecipitations and next-generation sequencing (ChIP-seq). We profiled multiple histone marks: H3K27me3, a marker for repressed genes, and H3K4me1 and H3K4me3, which are indicators of active enhancers and active promoters. Integrated analysis of ChIP-seq data and RNA sequencing revealed that H3K4 mono-methylation demarcates MIBC subtypes, while no association was found for the other two histone modifications in relation to basal and luminal subtypes. Additionally, we identified differentially methylated H3K4me1 peaks in basal and luminal tumour samples, suggesting that active enhancers play a role in defining subtypes. Our study is the first analysis of histone modifications in primary bladder cancer tissue and provides an important resource for the bladder cancer community.


Assuntos
Biomarcadores Tumorais/genética , Cistectomia/métodos , Metilação de DNA , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Musculares/patologia , Neoplasias da Bexiga Urinária/patologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/classificação , Neoplasias Musculares/genética , Neoplasias Musculares/cirurgia , Invasividade Neoplásica , Prognóstico , Neoplasias da Bexiga Urinária/classificação , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/cirurgia
6.
Nat Commun ; 11(1): 3549, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32669548

RESUMO

Refractory metastatic rhabdomyosarcoma is largely incurable. Here we analyze the response of a child with refractory bone marrow metastatic rhabdomyosarcoma to autologous HER2 CAR T cells. Three cycles of HER2 CAR T cells given after lymphodepleting chemotherapy induces remission which is consolidated with four more CAR T-cell infusions without lymphodepletion. Longitudinal immune-monitoring reveals remodeling of the T-cell receptor repertoire with immunodominant clones and serum autoantibodies reactive to oncogenic signaling pathway proteins. The disease relapses in the bone marrow at six months off-therapy. A second remission is achieved after one cycle of lymphodepletion and HER2 CAR T cells. Response consolidation with additional CAR T-cell infusions includes pembrolizumab to improve their efficacy. The patient described here is a participant in an ongoing phase I trial (NCT00902044; active, not recruiting), and is 20 months off T-cell infusions with no detectable disease at the time of this report.


Assuntos
Imunoterapia Adotiva/métodos , Neoplasias Musculares/terapia , Recidiva Local de Neoplasia/terapia , Receptor ErbB-2/imunologia , Rabdomiossarcoma/terapia , Linfócitos T/transplante , Biópsia , Medula Óssea/patologia , Criança , Ensaios Clínicos Fase I como Assunto , Humanos , Masculino , Neoplasias Musculares/imunologia , Neoplasias Musculares/patologia , Recidiva Local de Neoplasia/imunologia , Receptores de Antígenos Quiméricos/imunologia , Indução de Remissão/métodos , Rabdomiossarcoma/imunologia , Rabdomiossarcoma/secundário , Linfócitos T/imunologia , Linfócitos T/metabolismo , Transplante Autólogo/métodos , Resultado do Tratamento
7.
Mol Carcinog ; 59(9): 1017-1027, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32529781

RESUMO

Bladder cancer (BCa) is an exophytic tumor that presents as either noninvasive confined to the mucosa (NMIBC) or invading the detrusor muscle (MIBC), and was recently further subgrouped into molecular subtypes. Arylamines, major BCa environmental and occupational risk factors, are mainly metabolized by the genetically polymorphic N-acetyltransferases 1, NAT1 and NAT2. In this study, we investigated the association between N-acetyltransferases genetic polymorphism and key MIBC and NMIBC tumor biomarkers and subtypes. A cohort of 250 males with histologically confirmed urothelial BCa was identified. Tumors were genotyped for NAT1 and NAT2 using real-time polymerase chain reaction (PCR), and characterized for mutations in TP53, RB1, and FGFR3 by PCR-restriction fragment length polymorphism. Pathology data and patients' smoking status were obtained from medical records. Pearson χ2 and Fisher exact tests were used to check for associations and interactions. Results show that NAT1 G560 A polymorphism is significantly associated with higher muscle-invasiveness (MIBC vs NMIBC; P = .001), higher tumor grade (high grade vs low grade; P = .011), and higher FGFR3 mutation frequency within the MIBC subgroup (P = .042; .027). NAT2 G857 A polymorphism is also found to be significantly associated with higher muscle-invasiveness (MIBC vs NMIBC; P = .041). Our results indicate that slow N-acetylation is a contributor to bladder carcinogenesis and muscle-invasiveness. These findings highlight NAT1 as a biomarker candidate in BCa and a potential target for drug development.


Assuntos
Arilamina N-Acetiltransferase/genética , Biomarcadores Tumorais/genética , Isoenzimas/genética , Neoplasias Musculares/patologia , Mutação , Polimorfismo Genético , Neoplasias da Bexiga Urinária/patologia , Arilamina N-Acetiltransferase/metabolismo , Biomarcadores Tumorais/metabolismo , Feminino , Seguimentos , Genótipo , Humanos , Isoenzimas/metabolismo , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/genética , Neoplasias Musculares/metabolismo , Invasividade Neoplásica , Prognóstico , Fatores de Risco , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo
8.
Cancer Imaging ; 20(1): 26, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32252816

RESUMO

BACKGROUND: The Vesical Imaging-Reporting and Data System (VI-RADS) was created in 2018, and a 5-point VI-RADS scoring system was proposed to determine whether the muscularis of the bladder has been infiltrated by tumor tissues. PURPOSE: To verify the accuracy of the VI-RADS scoring system in predicting muscle-invasive bladder cancer and to explore its value in clinical application. MATERIALS AND METHODS: A total of 220 patients with bladder cancer who underwent multiparameter magnetic resonance imaging from January 2017 to June 2019 were selected. Then, two radiologists with equivalent qualifications gave their diagnoses of bladder tumors on T2-weighted imaging, diffusion-weighted imaging and dynamic contrast enhanced imaging. Meanwhile, the bladder tumor was also scored on the basis of the VI-RADS system; for multifocal tumors, the highest tumor load was selected for scoring. Furthermore, the final pathological results of the patients were unknown during the imaging diagnosis and scoring. Next, the VI-RADS score was compared with the pathological results after surgery, and the ability of the VI-RADS score to assess the degree of muscularis infiltration was finally analyzed. RESULTS: A total of 220 patients were included in our study, including 194 males and 26 females. Among them, the pathological results were 113 cases of muscle-invasive bladder cancer and 107 cases of non-muscle-invasive bladder cancer. The results showed that there was a positive correlation between the pathological results and VI-RADS score (r = 0.821, P < 0.05). The area under the receiver operating characteristic curve of the VI-RADS score was 0.960 (95% CI: 0.937, 0.983). When the VI-RADS score was above 3, the sensitivity, specificity and accuracy of predicting muscle-invasive bladder cancer were 82.3, 95.3 and 88.64%, respectively. CONCLUSION: The VI-RADS scoring system has good diagnostic value in predicting the degree of tumor invasion and can be used to guide clinical decision-making and management.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Musculares/diagnóstico por imagem , Neoplasias da Bexiga Urinária/patologia , Idoso , Imagem de Difusão por Ressonância Magnética/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/patologia , Neoplasias Musculares/secundário , Curva ROC , Projetos de Pesquisa
9.
J Vasc Interv Radiol ; 31(6): 903-911, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32340861

RESUMO

PURPOSE: To characterize the utility of monitoring transcranial electrical motor evoked potentials (TCeMEPs) and somatosensory evoked potentials (SSEPs) for neural thermoprotection during musculoskeletal tumor ablations. MATERIALS AND METHODS: Retrospective review of 29 patients (16 male; median age, 46 y; range, 7-77 y) who underwent musculoskeletal tumor radiofrequency ablation (n = 8) or cryoablation (n = 22) with intraprocedural TCeMEP and SSEP monitoring was performed. The most common tumor histologies were osteoid osteoma (n = 6), venous malformation (n = 5), sarcoma (n = 5), renal cell carcinoma (n = 4), and non-small-cell lung cancer (n = 3). The most common tumor sites were spine (n = 22) and lower extremities (n = 4). Abnormal TCeMEP change was defined by 100-V increase above baseline threshold activation for a given myotome; abnormal SSEP change was defined by 60% reduction in baseline amplitude and/or 10% increase in latency. RESULTS: Abnormal changes in TCeMEP (n = 9; 30%) and/or SSEP (n = 5; 17%) occurred in 12 procedures (40%) and did not recover in 5 patients. Patients with unchanged TCeMEP/SSEP activities throughout the procedure (n = 18) did not have motor or sensory symptoms after the procedure; 3 (60%) with unrecovered activity changes and 2 (29%) with transient activity changes had new motor (n = 1) or sensory (n = 4) symptoms. Relative risk for neurologic sequelae for patients with unrecovered TCeMEP/SSEP changes vs those with transient or no changes was 7.50 (95% confidence interval, 1.66-33.9; P = .009). CONCLUSIONS: Abnormal activity changes of TCeMEP or SSEP during percutaneous ablative procedures correlate with postprocedural neurologic sequelae.


Assuntos
Neoplasias Ósseas/cirurgia , Criocirurgia , Potencial Evocado Motor , Potenciais Somatossensoriais Evocados , Monitorização Neurofisiológica Intraoperatória , Neoplasias Musculares/cirurgia , Traumatismos dos Nervos Periféricos/prevenção & controle , Ablação por Radiofrequência , Adolescente , Adulto , Idoso , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/patologia , Criança , Criocirurgia/efeitos adversos , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/diagnóstico por imagem , Neoplasias Musculares/patologia , Traumatismos dos Nervos Periféricos/diagnóstico , Traumatismos dos Nervos Periféricos/etiologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Valor Preditivo dos Testes , Ablação por Radiofrequência/efeitos adversos , Tempo de Reação , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Estimulação Transcraniana por Corrente Contínua , Resultado do Tratamento , Adulto Jovem
10.
Cancer Metastasis Rev ; 39(1): 303-320, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32086631

RESUMO

Melatonin is an indole produced by the pineal gland at night under normal light or dark conditions, and its levels, which are higher in children than in adults, begin to decrease prior to the onset of puberty and continue to decline thereafter. Apart from circadian regulatory actions, melatonin has significant apoptotic, angiogenic, oncostatic, and antiproliferative effects on various cancer cells. Particularly, the ability of melatonin to inhibit skeletomuscular sarcoma, which most commonly affects children, teenagers, and young adults, is substantial. In the past few decades, the vast majority of references have focused on the concept of epithelial-mesenchymal transition involvement in invasion and migration to allow carcinoma cells to dissociate from each other and to degrade the extracellular matrix. Recently, researchers have applied this idea to sarcoma cells of mesenchymal origin, e.g., osteosarcoma and Ewing sarcoma, with their ability to initiate the invasion-metastasis cascade. Similarly, interest of the effects of melatonin has shifted from carcinomas to sarcomas. Herein, in this state-of-the-art review, we compiled the knowledge related to the molecular mechanism of antimetastatic actions of melatonin on skeletomuscular sarcoma as in childhood and during adolescence. Utilization of melatonin as an adjuvant with chemotherapeutic drugs for synergy and fortification of the antimetastatic effects for the reinforcement of therapeutic actions are considered.


Assuntos
Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Melatonina/metabolismo , Neoplasias Musculares/metabolismo , Neoplasias Musculares/patologia , Adolescente , Animais , Criança , Humanos , Invasividade Neoplásica , Metástase Neoplásica , Transdução de Sinais
11.
J Am Acad Orthop Surg ; 28(13): e540-e549, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32097135

RESUMO

Melanoma is an aggressive form of skin cancer associated with significant morbidity and mortality. Although commonly seen in dermatologist clinics, orthopaedic surgeons must be aware of these lesions in various ways. The five common musculoskeletal manifestations of melanoma will be discussed as well as the epidemiology, pathogenesis, diagnosis, staging, treatment, and prognosis of melanoma. With an index of suspicion and awareness of melanoma, a thorough history and detailed physical examination are critical in establishing a diagnosis. An adequately performed biopsy will confirm the diagnosis and assist in determining prognosis. As ambassadors of health for the musculoskeletal system, orthopaedic surgeons may be the first practitioners to encounter a pigmented skin lesion. Acral pigmented lesions should prompt a concern for melanoma with appropriate subsequent steps for management to follow. Finally, it is important for every orthopaedic surgeon to consider disseminated melanoma in the differential diagnosis of a skeletal metastasis, a deep soft-tissue mass, or lymphadenopathy in a patient with a previous history of a melanotic lesion.


Assuntos
Neoplasias Ósseas/secundário , Melanoma/secundário , Neoplasias Musculares/secundário , Ortopedia , Neoplasias Cutâneas/patologia , Pele/patologia , Biópsia , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/patologia , Neoplasias Ósseas/terapia , Diagnóstico Diferencial , Humanos , Melanoma/diagnóstico , Melanoma/patologia , Melanoma/terapia , Neoplasias Musculares/diagnóstico , Neoplasias Musculares/patologia , Neoplasias Musculares/terapia , Cirurgiões Ortopédicos , Exame Físico , Prognóstico , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/terapia
12.
Adv Emerg Nurs J ; 42(1): 13-16, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32000186

RESUMO

Fibromatosis colli is a rare, usually self-limiting condition caused by a benign tumor in the sternocleidomastoid muscle. The tumor occurs most often during infancy and can be clinically associated with torticollis. Accurate diagnosis of fibromatosis colli is important to avoid unnecessary invasive interventions. Radiographic imaging is fundamental to differentiating this benign tumor from other causes of neck masses/swelling in infants. In this article, we discuss the case of a 4-month old child who presented with a head tilt and had imaging that favored a diagnosis of fibromatosis colli.


Assuntos
Fibroma/diagnóstico , Neoplasias Musculares/diagnóstico , Músculos do Pescoço/patologia , Feminino , Humanos , Lactente , Neoplasias Musculares/patologia
13.
J Vet Sci ; 21(1): e3, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31940682

RESUMO

A 12-year-old Warmblood mare was presented with an acute onset left hindlimb lameness associated with generalised soft tissue swelling of the entire limb and medial saphenous vein (MSV) thrombophlebitis. A presumptive diagnosis of extremity compartment syndrome (ECS) was made. Due to the clinical deterioration, emergency fasciotomy of the crural fascia and biopsy was performed. Histological and immunohistochemical examination of the samples confirmed a diagnosis of leiomyosarcoma likely originating from the tunica media of the MSV. This report is the first to describe an unique combination of ECS and thrombophlebitis associated with a leiomyosarcoma in a horse.


Assuntos
Síndromes Compartimentais/veterinária , Doenças dos Cavalos/diagnóstico , Coxeadura Animal/diagnóstico , Leiomiossarcoma/veterinária , Neoplasias Musculares/veterinária , Tromboflebite/veterinária , Animais , Biópsia/veterinária , Síndromes Compartimentais/diagnóstico , Síndromes Compartimentais/etiologia , Síndromes Compartimentais/patologia , Feminino , Doenças dos Cavalos/etiologia , Doenças dos Cavalos/patologia , Cavalos , Coxeadura Animal/etiologia , Coxeadura Animal/patologia , Leiomiossarcoma/diagnóstico , Leiomiossarcoma/etiologia , Leiomiossarcoma/patologia , Neoplasias Musculares/diagnóstico , Neoplasias Musculares/etiologia , Neoplasias Musculares/patologia , Coxa da Perna/patologia , Tromboflebite/diagnóstico , Tromboflebite/etiologia , Tromboflebite/patologia
14.
Biochem Biophys Res Commun ; 523(1): 135-139, 2020 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-31839218

RESUMO

Cancer cells are methionine (MET) and methylation addicted and are highly sensitive to MET restriction. The present study determined the efficacy of oral-recombinant methioninase (o-rMETase) and the DNA methylation inhibitor, decitabine (DAC) on restricting MET in an undifferentiated-soft tissue sarcoma (USTS) patient-derived orthotopic xenograft (PDOX) nude-mouse model. The USTS PDOX models were randomized into five treatment groups of six mice: Control; doxorubicin (DOX) alone; DAC alone; o-rMETase alone; and o-rMETase-DAC combination. Tumor size and body weight were measured during the 14 days of treatment. Tumor growth was arrested only in the o-rMETase-DAC condition. Tumors treated with the o-rMETase-DAC combination exhibited tumor necrosis with degenerative changes. This study demonstrates that the o-rMETase-DAC combination could arrest the USTS PDOX tumor suggesting clinical promise.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Liases de Carbono-Enxofre/metabolismo , Decitabina/farmacologia , Modelos Animais de Doenças , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Musculares/tratamento farmacológico , Sarcoma/tratamento farmacológico , Administração Oral , Animais , Antimetabólitos Antineoplásicos/administração & dosagem , Liases de Carbono-Enxofre/administração & dosagem , Terapia Combinada , Decitabina/administração & dosagem , Feminino , Humanos , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Neoplasias Musculares/patologia , Neoplasias Musculares/cirurgia , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/patologia , Neoplasias Experimentais/cirurgia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/metabolismo , Sarcoma/patologia , Sarcoma/cirurgia
15.
Am J Pathol ; 190(2): 442-452, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31843500

RESUMO

Pathologic downstaging (pDS) to neoadjuvant chemotherapy (NAC) is one of the most important predictors of survival in muscle-invasive bladder cancer (MIBC). The use of NAC is limited as pDS is only achieved in 30% to 40% of cases and predictive biomarkers are still lacking. We performed a comprehensive immunomolecular biomarker analysis to characterize the role of immune cells and inhibitory checkpoints, genome-wide frequencies of copy number alterations, mutational signatures in whole exome, and tumor mutational burden in predicting NAC response. Our retrospective study included 23 primary MIBC patients who underwent NAC, followed by radical cystectomy. pDS to NAC was a significant prognostic factor for better recurrence-free survival (P < 0.001), with a median time to recurrence of 41.2 versus 5.5 months in nonresponders. DNA damage repair alterations were noticed in 38.1% (n = 8), confirming a positive correlation with high tumor mutational burden (P = 0.007). Chromosomal 7p12 amplification, including the genes HUS1, EGFR, ABCA13, and IKZF1, predicted nonresponse in patients with a sensitivity, a negative predictive value, and a specificity of 71.4%, 87.5%, and 100%, respectively. Total count of CD3+ T cells/mm2 tumor was a significant predictor of NAC response. In conclusion, 7p12 amplification may predict nonresponse to NAC and worse survival in MIBC. Multicenter, prospective trials with sufficient statistical power may further fortify these findings.


Assuntos
Biomarcadores Tumorais/genética , Cromossomos Humanos Par 7/genética , Amplificação de Genes , Neoplasias Musculares/patologia , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/patologia , Neoplasias da Bexiga Urinária/patologia , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Aberrações Cromossômicas , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Musculares/tratamento farmacológico , Neoplasias Musculares/genética , Invasividade Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética
16.
Future Oncol ; 16(2): 4359-4368, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31823654

RESUMO

Immune checkpoint inhibitors have revolutionized the treatment of patients with metastatic urothelial carcinoma. In cisplatin-eligible muscle-invasive bladder cancer (MIBC), cisplatin-based neoadjuvant chemotherapy (NAC) before radical cystectomy improves overall survival. Tumor PD-L1 expression increases in MIBC after NAC, suggesting potential synergy in combining PD1/PD-L1 inhibitors with NAC. IDO1 is overexpressed in bladder cancer and is associated with poor outcomes. Linrodostat mesylate (BMS-986205) - a selective, potent, oral IDO1 inhibitor - combined with nivolumab has demonstrated safety and preliminary evidence of clinical activity in metastatic urothelial carcinoma. Here, we discuss the rationale and trial design of the ENERGIZE, a Phase III trial investigating the efficacy of NAC in combination with nivolumab with or without linrodostat followed by postsurgery nivolumab or nivolumab with linrodostat in cisplatin-eligible patients with MIBC. Clinical trial registration number: NCT03661320.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Musculares/tratamento farmacológico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Acetamidas/administração & dosagem , Biomarcadores Tumorais/metabolismo , Cisplatino/administração & dosagem , Método Duplo-Cego , Humanos , Neoplasias Musculares/patologia , Terapia Neoadjuvante , Invasividade Neoplásica , Nivolumabe/administração & dosagem , Prognóstico , Quinolinas/administração & dosagem , Taxa de Sobrevida , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
17.
Oncogene ; 39(6): 1302-1317, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31636388

RESUMO

Intratumoral heterogeneity in bladder cancer is a barrier to accurate molecular sub-classification and treatment efficacy. However, individual cellular and mechanistic contributions to tumor heterogeneity are controversial. We examined potential mechanisms of FOXA1 and PTEN inactivation in bladder cancer and their contribution to tumor heterogeneity. These analyses were complemented with inactivation of FOXA1 and PTEN in intermediate and luminal mouse urothelium. We show inactivation and reduced expression of FOXA1 and PTEN is prevalent in human disease, where PTEN and FOXA1 are downregulated by allelic loss and site-specific DNA hypermethylation, respectively. Conditional inactivation of both Foxa1 and Pten in intermediate/luminal cells in mice results in development of bladder cancer exhibiting squamous features as well as enhanced sensitivity to a bladder-specific carcinogen. In addition, FOXA1 is hypermethylated in basal bladder cancer cell lines, and this is reversed by treatment with DNA methyltransferase inhibitors. By integrating human correlative and in vivo studies, we define a critical role for PTEN loss and epigenetic silencing of FOXA1 in heterogeneous human disease and show genetic targeting of luminal/intermediate cells in mice drives squamous differentiation.


Assuntos
Carcinoma de Células Escamosas/patologia , Diferenciação Celular , Metilação de DNA , Fator 3-alfa Nuclear de Hepatócito/genética , Perda de Heterozigosidade , PTEN Fosfo-Hidrolase/genética , Neoplasias da Bexiga Urinária/patologia , Animais , Apoptose , Biomarcadores Tumorais , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Fator 3-alfa Nuclear de Hepatócito/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Neoplasias Musculares/genética , Neoplasias Musculares/metabolismo , Neoplasias Musculares/patologia , PTEN Fosfo-Hidrolase/metabolismo , Prognóstico , Células Tumorais Cultivadas , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo
18.
Gen Thorac Cardiovasc Surg ; 68(5): 546-548, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31201611

RESUMO

Intramuscular myxomas (IM) of the chest wall are extremely rare. We present the case of a 58-year-old African-American female who was initially diagnosed with having a chest wall lipoma. After re-evaluation, the lesion was consistent with an intercostal myxoma versus myxoid sarcoma. Preoperative imaging could not exclude malignancy. Given the diagnostic uncertainty, she underwent primary wide local resection and placement of polypropylene mesh for chest wall reconstruction. Histopathological examination revealed an intramuscular myxoma without sarcomatous changes arising from the 8th intercostal muscle bundle.


Assuntos
Lipoma/diagnóstico , Neoplasias Musculares/diagnóstico , Neoplasias Musculares/cirurgia , Mixoma/diagnóstico , Mixoma/cirurgia , Diagnóstico Diferencial , Erros de Diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Musculares/patologia , Mixoma/patologia , Parede Torácica
19.
Pan Afr Med J ; 37: 370, 2020.
Artigo em Francês | MEDLINE | ID: mdl-33796183

RESUMO

Fibratosis colli, or infantile pseudotumor of the sternocleidomastoid muscle, is a rare cause of benign cervical mass in newborns and infants. This study involved all patients admitted with cervical swelling and diagnosed with colli fibromatosis from March 2016 to February 2020. Five patients were retained. In all patients cervical swelling occurred in the first month of life. No patient had had obstetric trauma. The diagnosis of fibromatosis colli was based on ultrasound. All patients received medical treatment. Fibratosis colli is a relatively rare cause of cervical mass in newborns and infants.


Assuntos
Fibroma/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias Musculares/diagnóstico por imagem , Músculos do Pescoço/diagnóstico por imagem , Feminino , Fibroma/patologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Lactente , Masculino , Neoplasias Musculares/patologia , Músculos do Pescoço/patologia , Ultrassonografia
20.
Pan Afr Med J ; 37: 158, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33425191

RESUMO

Kaposi sarcoma (KS) is a cancer, characteristically manifesting as red or purple patches of abnormal tissue growing subcutaneously around the mouth, nose, and throat. Primary musculoskeletal KS is a never reported as skeletal muscles sarcomas are first differentials. Pertaining to the musculoskeletal system complicity of KS, African and classic KS lesions are inclined to manifest lesion in the peripheral skeleton. On the other hand AIDS-related KS routinely involves the maxillofacial bones and/or axial skeleton. KS distinguishably involves the tempo-parietal bones, paranasal sinus, hands and feet and other facial bones. Asymmetric involvement of the bones by KS is the rule. Though reported, involvement of the joints in KS is unusual. Skeletal muscle involvement has only sparingly been reported in AIDS-related KS patient. A primary KS of the skeletal muscle in an otherwise normal patient with no skin manifestations has never been reported thus far. The occurrence of KS in any atypical site may pose as difficulty to diagnose it. It is important for the radiologist to acquaintance with the spectrum of imaging manifestations of KS in various affected organs. Particularly in asymptomatic patients, lesions go unrecognized on routine imaging studies (e.g. KS on plain x-ray films) and clinicians are unwary of their existence. Awareness that KS can occur in any of these unusual locations may help avoid potential misdiagnosis with serious consequences (e.g. spinal cord compression) and/or mis-management.


Assuntos
Neoplasias Musculares/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Sarcoma de Kaposi/diagnóstico por imagem , Idoso , Humanos , Masculino , Neoplasias Musculares/patologia , Músculo Esquelético/patologia , Sarcoma de Kaposi/patologia
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