RESUMO
INTRODUCTION: Multiple myeloma (MM) remains incurable due to high rates of relapse after various treatment regimens. WEE1 is a cell cycle related gene that regulates the G2/M checkpoint and promotes cell cycle suspension for consequent DNA repair. To date, there are clinical studies for the evaluation of WEE1 inhibitors in the treatment of solid tumors and studies on cell lines of non-MM hematological tumors. OBJECTIVES: To perform in vitro functional studies to verify the effect of the inhibition of WEE1 on MM cell lines viability and its potential as therapeutic target. MATERIAL AND METHODS: WEE1 expression was evaluated in 22 newly diagnosed MM patients and in four MM cell lines, RPMI-8226, U266 and SKO-007 and SK-MM2, by quantitative real-time PCR (qPCR). After treatment with the WEE1 inhibitor (MK-1775), with or without proteasome inhibitor (bortezomib) pretreatment, we assessed cell viability through Prestoblue functional test, microspheres formation in soft agar, and induction of apoptosis and cell cycle alterations by flow cytometry. RESULTS: All MM cell lines showed WEE1 expression by qPCR. RPMI-8226 and U266 showed a 50% reduction in cell viability after 24â¯h of incubation with MK-1775, at concentrations of 5⯵M and 20⯵M, respectively. SKO-007 showed dose and time dependence to this drug. Combination therapy with bortezomib and MK-1775 abolished the formation of soft agar microspheres in the RPMI-8226â¯cell line (also responsive to the use of both drugs) and U266, but SKO-007 was resistant to all drugs, isolated and combined. However, treatment of bortezomib followed by MK-1775 (sequential treatment) versus bortezomib alone showed statistically significant impact on cell lines total apoptosis: 88.8% vs 74.1% in RPMI-8222 (confirmed by cell cycle experiments); 92.5% vs 86.6% in U266; and 60.2% 30.9% on SKO-007 (pâ¯<â¯0.05). CONCLUSION: The sequential combination of bortezomib and WEE1 inhibitor, MK-1775, induced apoptosis in RPMI-8226, U266, and especially SKO-007â¯cell lines, more efficiently than the use of the same isolated drugs, highlighting its effect in inhibition of proliferation of tumor cells in MM cell lines. Our data suggest that WEE1 can figure as a MM target and that the sequential combination of bortezomib and MK-1775 may be explored in future clinical trials.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Bortezomib/farmacologia , Proteínas de Ciclo Celular/antagonistas & inibidores , Mieloma Múltiplo/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Proteínas Tirosina Quinases/antagonistas & inibidores , Pirazóis/farmacologia , Pirimidinonas/farmacologia , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
Gastric syphilis is an uncommon extracutaneous manifestation of syphilis, occurring in less than 1% of patients, presenting nonspecific clinical manifestations. In general, it occurs on secondary stage. The critical point is the recognition of the syphilitic gastric involvement, without which there may be incorrect diagnosis of malignancy of the digestive tract. In this report, a case of secondary syphilis with gastric involvement that had complete remission with benzathine penicillin will be described.
Assuntos
Gastropatias/diagnóstico , Sífilis/diagnóstico , Antibacterianos/uso terapêutico , Biópsia , Endoscopia Gastrointestinal , Humanos , Masculino , Pessoa de Meia-Idade , Penicilina G Benzatina/uso terapêuticoRESUMO
Abstract: Gastric syphilis is an uncommon extracutaneous manifestation of syphilis, occurring in less than 1% of patients, presenting nonspecific clinical manifestations. In general, it occurs on secondary stage. The critical point is the recognition of the syphilitic gastric involvement, without which there may be incorrect diagnosis of malignancy of the digestive tract. In this report, a case of secondary syphilis with gastric involvement that had complete remission with benzathine penicillin will be described.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Gastropatias/diagnóstico , Sífilis/diagnóstico , Penicilina G Benzatina/uso terapêutico , Biópsia , Endoscopia Gastrointestinal , Antibacterianos/uso terapêuticoRESUMO
Abstract Sarcoidosis is a disease which still has uncertain etiology. Possible environmental causes are cited in the literature, like organic and inorganic particles and infectious agents. Recent studies have demonstrated the occurrence of sarcoidosis in patients with chronic C hepatitis; however, this association remains without statistical or causal evidence. In this report a case of sarcoidosis associated with chronic hepatitis C will be described, with subcutaneous lesions, considered rare, and good response to treatment with colchicine and prednisone. The hepatitis C virus was isolated in sarcoid tissue and the association between the two diseases will be discussed.
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Sarcoidose/tratamento farmacológico , Prednisona/uso terapêutico , Colchicina/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Glucocorticoides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Sarcoidose/etiologia , Sarcoidose/patologia , Reação em Cadeia da Polimerase , Resultado do Tratamento , Hepatite C Crônica/complicaçõesRESUMO
Eccrine syringofibroadenoma is a rare benign adnexal neoplasm derived from cells of the acrosyringium of eccrine sweat glands. ESFA usually manifests as a solitary nodule on the extremities of elderly patients, but it may also present as papules, nodules or plaques. Its clinical appearance is nonspecific and malignant neoplasms should be considered in the differential diagnosis. However, histopathological findings are typical. The main treatment is surgical excision. In order to illustrate a typical presentation of the tumor, we report a case of solitary eccrine syringofibroadenoma, including the surgical treatment used and its result.
Assuntos
Glândulas Écrinas/patologia , Fibroadenoma/patologia , Neoplasias das Glândulas Sudoríparas/patologia , Siringoma/patologia , Idoso de 80 Anos ou mais , Tornozelo , Biópsia , Glândulas Écrinas/cirurgia , Feminino , Fibroadenoma/cirurgia , Humanos , Neoplasias das Glândulas Sudoríparas/cirurgia , Siringoma/cirurgia , Resultado do TratamentoRESUMO
Eccrine syringofibroadenoma is a rare benign adnexal neoplasm derived from cells of the acrosyringium of eccrine sweat glands. ESFA usually manifests as a solitary nodule on the extremities of elderly patients, but it may also present as papules, nodules or plaques. Its clinical appearance is nonspecific and malignant neoplasms should beconsidered in the differential diagnosis. However, histopathological findings are typical. The main treatment is surgical excision. In order to illustrate a typical presentation of the tumor, we report a case of solitary eccrine syringofibroadenoma, including the surgical treatment used and its result.
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