Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.310
Filtrar
5.
World Neurosurg ; 132: 219-222, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31491579

RESUMO

BACKGROUND: Lynch syndrome (LS) is a cancer-predisposing condition resulting from germline mutations in deoxyribonucleic acid mismatch repair genes. Patients are at high risk for a multitude of tumors, but no reports of undifferentiated sellar carcinomas have previously been described. CASE DESCRIPTION: A 56-year-old female with LS due to MSH2 and MSH6 mutations presented with panhypopituitarism and a sellar mass. She was initially diagnosed with pituitary apoplexy and treated nonoperatively. The mass self-resolved. The mass recurred 2 years later, and she underwent endoscopic endonasal biopsy demonstrating an undifferentiated carcinoma of the sella with MSH2 and MSH6 loss. The tumor was negative for pituitary markers and weakly positive for p63. The patient further developed lung and bone metastases and was treated with radiation and chemotherapy. CONCLUSIONS: This is the first report of an undifferentiated carcinoma of the sella. Our patient harbored a diagnosis of LS and demonstrated local tumor recurrence and aggressive systemic progression. Patients with LS should undergo close follow-up and active surveillance to detect and treat these aggressive lesions in a timely manner.


Assuntos
Carcinoma/complicações , Neoplasias Colorretais Hereditárias sem Polipose/complicações , Neoplasias Hipofisárias/complicações , Neoplasias Ósseas/secundário , Carcinoma/patologia , Carcinoma/cirurgia , Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Terapia Combinada , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Biópsia Guiada por Imagem , Neoplasias Pulmonares/secundário , Pessoa de Meia-Idade , Proteína 2 Homóloga a MutS/genética , Recidiva Local de Neoplasia , Procedimentos Neurocirúrgicos/métodos , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/cirurgia , Tomografia Computadorizada por Raios X
6.
Rev. bras. cir. plást ; 34(3): 399-404, jul.-sep. 2019. tab
Artigo em Inglês, Português | LILACS | ID: biblio-1047163

RESUMO

Introdução: A Úlcera de Marjolin é definida como a malignização de cicatrizes, geralmente, crônicas, decorrentes de diversos tipos de lesão, sendo mais comum lesões por queimaduras. Métodos: Foi realizado levantamento bibliográfico nas plataformas BVS, PubMed, SciELO e Cochrane, tendo como critério de inclusão estudos publicados nos últimos 5 anos, que envolvem a espécie humana, disponíveis na web nos idiomas inglês ou português. Resultados: Analisados um total de 31, dos quais apenas 6 compuseram a amostra final. Discussão: As úlceras de Marjolin são encontradas em cicatrizes antigas de queimaduras, podem ocorrer em qualquer local, sendo mais comuns em membros superiores e inferiores. O diagnóstico inicia-se com a suspeita clínica baseada em características das lesões: lesões ulcerativas crônicas que não cicatrizam, com bordas elevadas e endurecidas e odor desagradável, podendo apresentar descarga purulenta. Esse só pode ser efetivado, entretanto, por meio do histopatológico da lesão. O período de latência entre a injúria da lesão e a sua malignização é, em média, de 30 a 35 anos. O tratamento deve ser individualizado, uma vez que depende de diversos fatores. Contudo, considera-se o padrão ouro a excisão cirúrgica. Conclusão: O conhecimento dos profissionais de saúde acerca dessa condição faz-se imprescindível para o melhor prognóstico do paciente. De modo que possíveis casos de malignização não tenham o seu diagnóstico subestimado, permita a terapêutica adequada à minimização das recidivas, e medidas profiláticas sejam efetivadas, no que tange à prevenção da queimadura e à minoração de fatores de risco para a malignização.


Introduction: Marjolin's ulcer is defined as a malignancy within scars that is usually chronic and results from several lesion types, with burn injuries being the most common. Methods: A bibliographic survey was conducted of the Virtual Health Library, PubMed, Scientific Electronic Library Online, and Cochrane databases using the inclusion criteria of studies published in the last 5 years, human studies, and published in English or Portuguese. Results: A total of 31 studies were analyzed, of which only 6 were included in the final sample. Discussion: Marjolin's ulcer is found in old burn scars and can occur anywhere, but it is more common in the upper and lower limbs. The diagnosis begins with the clinical suspicion based on lesion characteristics: chronic unhealed ulcerative lesions with high and hardened edges, an unpleasant odor, and purulent discharge. However, the diagnosis can only be made histopathologically. The latency period between injury and malignancy is 30­35 years. Although treatment should be individualized since it depends on several factors, surgical excision is considered the gold standard. Conclusion: Knowledge about this condition is essential to better patient prognosis and prevent underestimation of possible cases of malignancy, allowing for appropriate therapy to minimize recurrence and enabling prophylactic measures to prevent burn injury and reduce risk factors for malignancy.


Assuntos
Humanos , Feminino , Adulto , História do Século XXI , Úlcera Cutânea , Cirurgia Plástica , Cicatrização , Queimaduras , Queimaduras por Corrente Elétrica , Carcinoma , Úlcera Cutânea/cirurgia , Cirurgia Plástica/efeitos adversos , Cirurgia Plástica/métodos , Queimaduras/cirurgia , Queimaduras/complicações , Carcinoma/cirurgia , Carcinoma/complicações
7.
Anticancer Res ; 39(8): 4449-4454, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366543

RESUMO

BACKGROUND/AIM: Prostate multiparametric magnetic resonance imaging (mpMRI) is the reference imaging modality for extraprostatic extension of disease (EPE) assessment. We aimed to compare the diagnostic accuracy of different abbreviated MRI protocols to the standard prostate mpMRI in the identification of EPE of PCa. PATIENTS AND METHODS: Fifty patients were retrospectively enrolled. Dual-pulse (dpMRI) and biparametric (bpMRI) abbreviated protocols were obtained from mpMRI. The performance of two experienced radiologists and two radiology residents was correlated with a reference standard and compared. Inter and intra-reader agreements were evaluated. RESULTS: All protocols were strongly correlated to the reference standard (p≤0.001). A significant difference was found between dpMRI and mpMRI (p=0.009), no differences emerged between bpMRI and mpMRI (p=0.27). All readers showed moderate agreement (ĸ=0.47, ĸ=0.50 and ĸ=0.53 for dpMRI, bpMRI and mpMRI, respectively). Intra-reader agreement was good (all ĸ values ≥0.70). CONCLUSION: Only bpMRI showed similar diagnostic performance to mpMRI, thus appearing as a feasible alternative to the standard protocol for EPE detection.


Assuntos
Carcinoma/diagnóstico por imagem , Imagem por Ressonância Magnética , Próstata/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Idoso , Carcinoma/complicações , Carcinoma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Próstata/patologia , Prostatectomia , Neoplasias da Próstata/complicações , Neoplasias da Próstata/patologia , Estudos Retrospectivos
8.
Saudi Med J ; 40(8): 815-819, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31423519

RESUMO

OBJECTIVES: Abnormal uterine bleeding (AUB) is a leading cause of hysterectomies, the cause of which is usually diagnosed with preoperative endometrial sampling. We planned this study to assess the accuracy of diagnosing the histologic patterns of endometrium in the preoperative sample in reference to the final histologic diagnosis in hysterectomy. METHODS: We retrospectively reviewed medical charts between January 2011 and December 2015 at a tertiary hospital in Saudi Arabia and identified 43 cases of AUB with complete documentation. The histologic diagnoses were classified into normal and benign pathology group (N/B), or carcinoma and hyperplasia category (Ca/H). Measures of validity were used to compare endometrial sampling histological diagnoses to diagnoses following hysterectomy and Cohen's kappa to assess for agreement between the 2 modalities. Results: The median age of all patients was 49 years. Preoperative histologic examination showed 53.8% sensitivity, 90% specificity, 70% positive predictive values and 81.8% negative predictive values, 30.1%  false positive rates and 18.2% false negative rates. The agreement between preoperative and postoperative histologic diagnoses was moderate (79.1%, k=0.469). Conclusion: The accuracy of preoperative histologic examination was moderate. Our findings recommend cautious clinical decision making and limiting hysterectomy to women who do not respond to other therapeutic measures.


Assuntos
Carcinoma/patologia , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/patologia , Endométrio/patologia , Menorragia/patologia , Metrorragia/patologia , Adulto , Idoso , Carcinoma/complicações , Carcinoma/diagnóstico , Carcinoma/cirurgia , Tomada de Decisão Clínica , Hiperplasia Endometrial/complicações , Hiperplasia Endometrial/diagnóstico , Hiperplasia Endometrial/cirurgia , Neoplasias do Endométrio/complicações , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/cirurgia , Endometrite/complicações , Endometrite/diagnóstico , Endometrite/patologia , Endometrite/terapia , Reações Falso-Positivas , Feminino , Humanos , Histerectomia , Menorragia/etiologia , Menorragia/terapia , Metrorragia/etiologia , Metrorragia/terapia , Pessoa de Meia-Idade , Pólipos/complicações , Pólipos/diagnóstico , Pólipos/patologia , Pólipos/terapia , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
9.
J Coll Physicians Surg Pak ; 29(9): 888-890, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31455489

RESUMO

Acanthosis nigricans is a skin disease characterised by symmetric velvety hyperpigmented, verrucous plaques of the intertriginous surfaces of the axilla, neck, inframammary, and mucocutaneous regions. Malignant acanthosis nigricans is a paraneoplastic phenomenon most commonly associated with gastric adenocarcinoma. Tripe palms, florid cutaneous papillomatosis and oral involvement along with generalised acanthosis nigricans are the features which are highly suggestive of internal malignancy. This case report describes a rare case of a patient who presented with combination of malignant acanthosis nigricans, tripe palms, florid cutaneous papillomatosis and oral involvement associated with undifferentiated malignant neoplasm of hepatic bile ducts.


Assuntos
Acantose Nigricans/etiologia , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/diagnóstico , Ductos Biliares Intra-Hepáticos , Carcinoma/complicações , Carcinoma/diagnóstico , Acantose Nigricans/patologia , Humanos , Masculino , Pessoa de Meia-Idade
10.
J Mol Neurosci ; 69(2): 235-245, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31201657

RESUMO

Cancer pain induced by pancreatic carcinoma is one of the most common symptoms and is difficult to endure, especially in the advanced stage. Evidence suggests that mast cells are recruited and degranulate in enteric disease-related visceral hypersensitivity. However, whether mast cells promote the visceral pain induced by pancreatic carcinoma remains unclear. Here, using toluidine blue staining and western blotting, we observed that mast cells were dramatically recruited to tissues surrounding pancreatic carcinoma, but not inside the carcinoma in patients with severe visceral pain. The levels of mast cell degranulation products, including tryptase, histamine, and nerve growth factor, were significantly increased in pericarcinoma tissues relative to their levels in normal controls, as evidenced by enzyme-linked immunosorbent assay. We determined that systemic administration of mast cell secretagogue compound 48/80 exacerbated pancreatic carcinoma-induced visceral hypersensitivity in a male BALB/c nude mouse model as assessed by measuring the hunching behavior scores and mechanical withdrawal response frequency evoked by von Frey stimulation. In contrast, the mast cell stabilizer ketotifen dose-dependently alleviated pancreatic cancer pain. In addition, we observed incomplete development of abdominal mechanical hyperalgesia and hunching behavior in mast cell-deficient mice with pancreatic carcinoma. However, ketotifen did not further attenuate visceral hypersensitivity in mast cell-deficient mice with carcinoma. Finally, we confirmed that intraplantar injection of pericarcinoma supernatants from BALB/c nude mice but not mast cell-deficient mice caused acute somatic nociception. In conclusion, our findings suggest that mast cells contribute to pancreatic carcinoma-induced visceral hypersensitivity through enrichment and degranulation in pericarcinoma tissues. The inhibition of mast cell degranulation may be a potential strategy for the therapeutic treatment of pancreatic carcinoma-induced chronic visceral pain.


Assuntos
Dor do Câncer/tratamento farmacológico , Carcinoma/complicações , Degranulação Celular , Mastócitos/metabolismo , Neoplasias Pancreáticas/complicações , Dor Visceral/tratamento farmacológico , Adulto , Animais , Dor do Câncer/etiologia , Feminino , Histamina/metabolismo , Antagonistas dos Receptores Histamínicos H1/farmacologia , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Humanos , Cetotifeno/farmacologia , Cetotifeno/uso terapêutico , Masculino , Mastócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Fator de Crescimento Neural/metabolismo , Secretagogos/farmacologia , Secretagogos/uso terapêutico , Triptases/metabolismo , Dor Visceral/etiologia
11.
Saudi Med J ; 40(5): 440-446, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31056619

RESUMO

OBJECTIVE: To evaluate the molecular subtypes of Mammary Paget's disease (MPD) and the associated breast carcinomas. METHODS: This retrospective study was carried out at King Khalid University Hospital and King Faisal Specialist Hospital, Riyadh, Saudi Arabia. Data from MPD patient cases from January 2010 to June 2016 were reviewed. The molecular subtypes were determined based on estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) expression with immunohistochemical staining. The relative frequencies of the luminal A and B, HER2-enriched and basal-like molecular subtypes were calculated and compared for MPD and the associated breast carcinomas. Results: Among 22 patients with MPD, HER2-enriched was the most frequently occurring molecular subtype and was observed in 11 (50%) patients. Mammary Paget's disease was classified as basal-like in 5 (22.7%) patients, and luminal A and B were each detected in 3 (13.6%) patients. The molecular subtype of MPD corresponded with the subtype of the associated breast carcinoma in 18 out of 20 patients (90%). CONCLUSIONS: The HER2-enriched subtype is the most frequently occurring molecular subtype in MPD. The molecular subtype of the associated breast carcinoma is usually similar to that of MPD. The molecular subtypes vary between MPD associated breast carcinoma and overall breast carcinoma. The HER2-enriched subtype is the most frequently occurring subtype of MPD associated breast carcinoma, while luminal subtypes are more common in overall breast carcinoma.


Assuntos
Expressão Gênica , Doença de Paget Mamária/classificação , Doença de Paget Mamária/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/complicações , Carcinoma/complicações , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Doença de Paget Mamária/complicações , Doença de Paget Mamária/metabolismo , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptores Estrogênicos/genética , Receptores Estrogênicos/metabolismo , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo , Estudos Retrospectivos
12.
Osteoporos Int ; 30(7): 1511-1519, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30972448

RESUMO

Diagnosis of parathyroid carcinoma on histological examination is challenging. Thousands of differentially expressed lncRNAs were identified on the microarray data between parathyroid cancer and adenoma samples. Four lncRNAs were significantly dysregulated in further validation. The "lncRNA score" calculated from these lncRNAs differentiated parathyroid carcinomas from adenomas. LncRNAs serve as biomarkers for parathyroid cancer diagnosis. INTRODUCTION: Diagnosis of parathyroid carcinoma (PC) on histological examination is challenging. LncRNA profile study was conducted to find diagnostic biomarkers for PC. METHODS: LncRNA arrays containing 91,007 lncRNAs as well as 29,857 mRNAs were used to assess parathyroid specimen (5 carcinomas and 6 adenomas). Bioinformatics analyses were also conducted to compare the microarray results between parathyroid carcinomas and adenomas (PAs). Differentially expressed lncRNAs of 11 PCs and 31 PAs were validated by real-time quantitative PCR. RESULTS: On the microarray data between PC and PA samples (fold change ≥ 2, P < 0.05), 1809 differentially expressed lncRNAs and 1349 mRNAs also were identified. All carcinomas were clustered in the same group by clustering analysis using dysregulated lncRNAs or mRNAs. Four lncRNAs (LINC00959, lnc-FLT3-2:2, lnc-FEZF2-9:2, and lnc-RP11-1035H13.3.1-2:1) identified were significantly dysregulated in further RT-PCR validation. The global "lncRNA score" calculated from the lncRNAs above also differentiated parathyroid carcinomas from adenomas. CONCLUSIONS: LncRNA profiling shows distinct differentially expressed lncRNAs in parathyroid neoplasm. They may play a key role in parathyroid cancer and serve as potential biomarkers to distinguish parathyroid cancers from parathyroid adenomas.


Assuntos
Adenoma/genética , Carcinoma/genética , Neoplasias das Paratireoides/genética , RNA Longo não Codificante/genética , Adenoma/complicações , Adenoma/diagnóstico , Adulto , Idoso , Carcinoma/complicações , Carcinoma/diagnóstico , Diagnóstico Diferencial , Feminino , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Estudo de Associação Genômica Ampla/métodos , Humanos , Hiperparatireoidismo Primário/etiologia , Hiperparatireoidismo Primário/genética , Masculino , Pessoa de Meia-Idade , Neoplasias das Paratireoides/complicações , Neoplasias das Paratireoides/diagnóstico , RNA Mensageiro/genética , RNA Neoplásico/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos
13.
J Pak Med Assoc ; 69(4): 600, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31000873

RESUMO

Metastatic calcification relates to abnormal calcification resulting from hypercalcaemia in otherwise normal tissues. Hypercalcaemia can occur secondary to chronic renal failure, hyperparathyroidism, hypervitaminosis D, and metastatic neoplasms. Specific symptoms are often lacking, but calcification may be a marker of disease severity and its chronicity. We present cases with different patterns of soft tissue calcification on Tc99m MDP bone scan.


Assuntos
Calcinose/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Parede Torácica/diagnóstico por imagem , Idoso , Neoplasias Ósseas/complicações , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Calcinose/etiologia , Carcinoma/complicações , Carcinoma/diagnóstico por imagem , Carcinoma/secundário , Feminino , Humanos , Hipercalcemia/complicações , Falência Renal Crônica , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Cintilografia , Compostos Radiofarmacêuticos , Medronato de Tecnécio Tc 99m
15.
BMJ Case Rep ; 12(3)2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30826777

RESUMO

Orbit is an unusual and rare site for metastases from cancer. The most frequent site of a primary malignancy to metastasise to the orbit is the breast, followed by the lung. The malignant mixed mullerian tumour is a rare uterine and cervical carcinoma and accounts for <5% of uterine cancers. It is the primary tumour of the uterus, and de novo involvement of the cervix itself is extremely rare. We report the first case of cervical carcinoma with mixed mullerian aetiology to be associated with orbital metastasis and eventually leading to blindness and death.


Assuntos
Cegueira/etiologia , Carcinoma/secundário , Doenças Orbitárias/etiologia , Neoplasias Orbitárias/secundário , Neoplasias do Colo do Útero/patologia , Carcinoma/complicações , Evolução Fatal , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Orbitárias/complicações
17.
Med Sci Sports Exerc ; 51(7): 1387-1395, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30724848

RESUMO

INTRODUCTION: Cancer cachexia is characterized by loss of muscle mass and function. Increased protein catabolism, inflammation, impaired anabolism, and mitochondrial function markedly contribute to the pathogenesis of this syndrome. Physical activity has been suggested as a useful tool to prevent or at least delay the onset and progression of cancer-induced muscle wasting. Two main types of exercise can be adopted, namely, resistance and endurance training. The present study is aimed to investigate the effectiveness of a combined (resistance + endurance) exercise protocol in preventing/reverting cancer-induced muscle wasting. METHODS: Mice bearing the C26 colon carcinoma have been used as a model of cancer cachexia. They have been exposed to combined exercise training during 6 wk (4 before tumor implantation, 2 during tumor growth). Climbing a 1-m ladder inclined at 85° has been used for resistance training, while aerobic (endurance) exercise has been carried out on the same day using a motorized wheel. RESULTS: In C26-bearing mice, both muscle mass and strength are improved by combined training, while just the latter increased in exercised healthy animals. Such a pattern is associated with modulations of two markers of autophagy, namely, LC3B-I/II ratio, increased in sedentary tumor hosts and reduced in exercised C26-bearing mice, and p62, steadily increased in both sedentary and trained tumor-bearing animals. Finally, combined training is not able to modify PGC-1α protein levels, but it improves succinate dehydrogenase activity, both reduced in the muscle of the C26 hosts. CONCLUSION: The data reported in the present study show that combined training improves muscle mass and function in the C26 hosts, likely modulating autophagy and improving mitochondrial function; these observations suggest that combined exercise might become part of a multimodal approach to treat cancer cachexia.


Assuntos
Caquexia/prevenção & controle , Carcinoma/complicações , Neoplasias do Colo/complicações , Atrofia Muscular/prevenção & controle , Condicionamento Físico Animal/métodos , Animais , Autofagia/fisiologia , Caquexia/etiologia , Carcinoma/metabolismo , Neoplasias do Colo/metabolismo , Modelos Animais de Doenças , Humanos , Masculino , Camundongos Endogâmicos BALB C , Proteínas Associadas aos Microtúbulos/metabolismo , Mitocôndrias Musculares/metabolismo , Proteínas Musculares/metabolismo , Atrofia Muscular/etiologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Distribuição Aleatória , Treinamento de Resistência , Succinato Desidrogenase/metabolismo
18.
Mol Pain ; 15: 1744806918823477, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30799695

RESUMO

Aggressive breast cancer subtypes utilize system xc-, a membrane antiporter, to import cystine for glutathione synthesis and maintenance of redox homeostasis, in turn releasing glutamate as a metabolic pro-nociceptive by-product. Metastatic breast cancers establish themselves at distal sites including bone, where changes in extracellular glutamate levels contribute to cancer-induced bone pain. We previously established that stearically blocking system xc- activity with sulfasalazine delays the onset of nociceptive behaviours and that xCT, the functional antiporter subunit, is positively regulated by signal transducer and activator of transcription 3 (STAT3). In the current investigation, a murine xenograft cancer-induced bone pain model was applied to examine whether pharmacological inhibition of phosphorylated STAT3 (pSTAT3) induces changes in nociception. A high glutamate-releasing, xCT/pSTAT3 over-expressing human breast cancer cell line was selected for injection into the distal epiphysis of the right femur of female nude mice. A 14-day regimen of intraperitoneal injections with either vehicle or the novel STAT3 inhibitor DR-1-55 commenced three weeks after initial intrafemoral bone injection. Nociceptive behaviours were temporally monitored by automated von Frey, dynamic weight bearing and open-field testing for the duration of the study, beginning at the baseline. Prior to sacrifice and at ethical end point, tumour-induced osteolytic lesions were radiographically assessed. Treatment with DR-1-55 significantly delayed the onset and severity of spontaneous and induced nociceptive behaviours, also decreasing human SLC7A11 ( xCT) mRNA levels in tumour-bearing limbs without altering osteolysis. In addition, two pro-inflammatory cytokines released by this cell line, interleukin 6 and interleukin 1ß, were also down-regulated at the mRNA level in response to DR-1-55 treatment in vivo, with lower human interleukin 6 levels detected in the host circulation. This study demonstrates that targeting pSTAT3 may be a viable therapeutic means to manage cancer-induced bone pain, alone or in combination with stearic system xc- blockers.


Assuntos
Osso e Ossos/patologia , Dor do Câncer/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Nociceptividade/fisiologia , Fator de Transcrição STAT3/metabolismo , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/complicações , Neoplasias Ósseas/tratamento farmacológico , Neoplasias da Mama/complicações , Dor do Câncer/etiologia , Dor do Câncer/terapia , Carcinoma/complicações , Linhagem Celular Tumoral/patologia , Citocinas/sangue , Citocinas/genética , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Comportamento Exploratório/fisiologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Hiperalgesia/tratamento farmacológico , Hiperalgesia/etiologia , Masculino , Camundongos , Camundongos Nus , Nociceptividade/efeitos dos fármacos , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/genética , Suporte de Carga/fisiologia , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Mol Pain ; 15: 1744806919831909, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30700204

RESUMO

Descending nociceptive modulation from the supraspinal structures has an important role in cancer-induced bone pain (CIBP). Midbrain ventrolateral periaqueductal gray (vlPAG) is a critical component of descending nociceptive circuits; nevertheless, its precise cellular and molecular mechanisms involved in descending facilitation remain elusive. Our previous study has shown that the activation of p38 MAPK in vlPAG microglia is essential for the neuropathic pain sensitization. However, the existence of potential connection between astrocytes and c-Jun N-terminal kinase (JNK) pathway in CIBP has not yet been elucidated. The following study examines the involvement of astrocyte activation and upregulation of p-JNK in vlPAG, using a CIBP rat model. Briefly, CIBP was mimicked by an intramedullary injection of Walker 256 mammary gland carcinoma cells into the animal tibia. A significant increase in expression levels of astrocytes in the vlPAG of CIBP rats was observed. Furthermore, stereotaxic microinjection of the astrocytic cytotoxin L-α-aminoadipic acid decreased the mechanical allodynia as well as established and reversed the astrocyte activation in CIBP rats. A significant increase in expression levels of p-JNK in astrocytes in vlPAG of CIBP rats was also observed. Moreover, the intrathecal administration of JNK inhibitors SP600125 reduced the expression of glial fibrillary acidic protein, while microinjection of the SP600125 decreased the mechanical allodynia of CIBP rats. These results suggested that CIBP is associated with astrocyte activation in the vlPAG that probably participates in driving descending pain facilitation through the JNK MAPK signaling pathway. To sum up, these findings reveal a novel site of astrocytes modulation of CIBP.


Assuntos
Astrócitos/patologia , Dor do Câncer/patologia , Regulação Neoplásica da Expressão Gênica/fisiologia , MAP Quinase Quinase 4/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Substância Cinzenta Periaquedutal/patologia , Animais , Antracenos/farmacologia , Peso Corporal/efeitos dos fármacos , Neoplasias Ósseas/complicações , Neoplasias Ósseas/patologia , Antígeno CD11b/metabolismo , Dor do Câncer/etiologia , Carcinoma/complicações , Carcinoma/patologia , Linhagem Celular Tumoral , Inibidores Enzimáticos/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/metabolismo , Hiperalgesia/etiologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Substância Cinzenta Periaquedutal/metabolismo , Fosfopiruvato Hidratase/metabolismo , Ratos , Ratos Sprague-Dawley
20.
Mult Scler Relat Disord ; 30: 119-122, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30771577

RESUMO

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system (CNS). A typical finding on spinal magnetic resonance imaging (MRI) of NMOSD is longitudinally extensive transverse myelitis (LETM). However, patients with NMOSD presenting with short-segment transverse myelitis (STM) during myelitis attacks associated with breast cancer are uncommon. We report a case of a 35-year-old woman with STM and left eye optic neuritis. The patient was positive for serum aquaporin-4 antibodies (AQP4-IgG), and a biopsy of the left breast showed invasive ductal carcinoma. The patient was diagnosed with NMOSD and breast malignancy. This is the first report of a patient with NMOSD whose spinal MRI showed STM and serum test showed that the patient's AQP4-IgG was positive and complicated by breast cancer. This case improves our understanding of the association between NMOSD and cancer and raises the question of whether it was a coincidental occurrence. It is important to search for extensive malignancies in patients presenting with atypical MRI or no reaction to traditional therapies.


Assuntos
Anticorpos/líquido cefalorraquidiano , Aquaporina 4/imunologia , Neoplasias da Mama/líquido cefalorraquidiano , Carcinoma/líquido cefalorraquidiano , Mielite Transversa/sangue , Adulto , Neoplasias da Mama/complicações , Neoplasias da Mama/diagnóstico por imagem , Carcinoma/complicações , Carcinoma/diagnóstico por imagem , Feminino , Humanos , Imagem por Ressonância Magnética , Mielite Transversa/complicações , Mielite Transversa/diagnóstico por imagem , Medula Espinal/diagnóstico por imagem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA