RESUMO
Abstract As the treatment of infectious and parasitic diseases improved, the prevalence of these conditions declined. However, with the expansion of the use of immunobiologicals, opportunistic infections have emerged, especially under atypical presentations. The present study reports the case of a patient treated with infliximab for Crohn's disease, who presented diarrhea, weight loss, abdominal pain, fever, and subcutaneous erythematous nodules that evolved with spontaneous fluctuation and ulceration. With the finding of alcohol-resistant bacilli and Mycobacterium tuberculosis DNA in a cutaneous fragment, through polymerase chain reaction, the diagnosis of gummatous tuberculosis was confirmed, probably secondary to hematogenous dissemination from an intestinal focus.
Assuntos
Humanos , Tuberculose Cutânea/diagnóstico , Tuberculose Cutânea/induzido quimicamente , Tuberculose Cutânea/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Sífilis , Pele , Infliximab/efeitos adversosRESUMO
As the treatment of infectious and parasitic diseases improved, the prevalence of these conditions declined. However, with the expansion of the use of immunobiologicals, opportunistic infections have emerged, especially under atypical presentations. The present study reports the case of a patient treated with infliximab for Crohn's disease, who presented diarrhea, weight loss, abdominal pain, fever, and subcutaneous erythematous nodules that evolved with spontaneous fluctuation and ulceration. With the finding of alcohol-resistant bacilli and Mycobacterium tuberculosis DNA in a cutaneous fragment, through polymerase chain reaction, the diagnosis of gummatous tuberculosis was confirmed, probably secondary to hematogenous dissemination from an intestinal focus.
Assuntos
Doença de Crohn , Sífilis , Tuberculose Cutânea , Doença de Crohn/tratamento farmacológico , Humanos , Infliximab/efeitos adversos , Pele , Tuberculose Cutânea/induzido quimicamente , Tuberculose Cutânea/diagnóstico , Tuberculose Cutânea/tratamento farmacológicoRESUMO
Medullary thyroid carcinoma (MTC) is a rare type of tumor that originates from thyroid C cells and accounts for 2-4% of all malignant thyroid neoplasms. MTC may occur sporadically or be inherited, as part of the MEN 2 syndrome. Germline mutations of the RET (REarranged during Transfection) proto-oncogene cause hereditary cancer, whereas somatic RET mutations and, less frequently, RAS mutations have been described in sporadic MTC samples. Since early surgery with complete resection of tumor mostly determines the likelihood of attaining cure for MTC, the broader use of RET genetic screening has dramatically changed the prognostic of gene carriers in hereditary MTC. Nevertheless, despite recent advances, the management of advanced, progressive MTC remains challenging. The multikinase inhibitors (MKI), vandetanib and cabozantinib, were approved for the treatment of progressive or symptomatic MTC, and several other compounds have exhibited variable efficacy. Although these drugs have been shown to improve progression-free survival, no MKI has been shown to increase the overall survival. As these drugs are nonselective, significant off-target toxicities may occur, limiting achievement of the required TK-specific inhibition. Recently, next-generation small-molecule TKI has been developed. These TKI are specifically designed for highly potent and selective targeting of oncogenic RET alterations, making them promising drugs for the treatment of advanced MTC. Here, we summarize the current understanding of the intracellular signaling pathways involved in MTC pathogenesis as well as the therapeutic approaches and challenges for the management of advanced MTC, focusing on targeted molecular therapies.
Assuntos
Carcinoma Neuroendócrino , Neoplasias da Glândula Tireoide , Antineoplásicos/uso terapêutico , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/metabolismo , Carcinoma Neuroendócrino/terapia , Genótipo , Humanos , Imunoterapia , Terapia de Alvo Molecular , Fenótipo , Inibidores de Proteínas Quinases/uso terapêutico , Proto-Oncogene Mas , Transdução de Sinais , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/terapiaRESUMO
O mastocitoma é o segundo tumor mais comum no cão, sendo caracterizado pela proliferação desordenada de mastócitos na pele. O tratamento envolve a ressecção cirúrgica, quimioterapia e radioterapia. Recentemente, novos protocolos de tratamento têm sido desenvolvidos, como a utilização de inibidores de receptores de tirosina-quinase. Com o conhecimento do genoma e a evolução de metodologias em genética molecular, os fármacos com alvo molecular específico constituem uma modalidade terapêutica promissora contra o câncer, no futuro. Além de estarem envolvidos no ciclo celular normal, alguns estudos sugerem que os receptores de tirosina-quinase têm participação fundamental nos processos neoplásicos. Dessa forma, algumas estratégias, como o desenvolvimento de anticorpos antirreceptores de tirosina-quinase e as pequenas moléculas inibidoras de receptor de tirosina-quinase, têm sido desenvolvidas na tentativa de inibir o desenvolvimento tumoral. O objetivo da presente revisão é descrever o uso dos inibidores de tirosina-quinase no tratamento de mastocitoma em cães.
The mast cell tumor (MCT) is the second most common type of tumor in dogs. It is characterized by uncontrolled proliferation of mast cells in the skin. Treatment involves surgical resection, chemotherapy and radiotherapy. Recently, new treatment protocols have been developed, such as the use of tyrosine kinase inhibitors. With the increasing knowledge about the genome and the evolution of methods in molecular genetics, drugs with specific molecular targets are surely going to become promising therapeutic modalities in the near future. Besides being involved in the normal cell cycle, some studies suggest that tyrosine kinases have a fundamental role in neoplastic processes. Therefore, some strategies such as the development of antibodies anti-receptors for tyrosine kinases and small-molecule tyrosine kinase receptor inhibitors have been developed in an attempt to inhibit tumor development. The purpose of this review is to describe the use of tyrosine kinase inhibitors in the treatment of mast cell tumors in dogs.
El mastocitoma es el segundo tumor mas frecuente en perros, caracterizándose por la proliferación desordenada de mastocitos en la piel. El tratamiento abarca la resección quirúrgica, la quimio y la radioterapia. Recientemente, se han desarrollado nuevos protocolos de tratamiento, como los inhibidores de receptores de tirosina-quinasa. Una vez conocido el genoma y teniendo en cuenta la evolución de diferentes metodologías en genética molecular, en el futuro, los fármacos con acción molecular específica se convertirán, seguramente, en una alternativa terapéutica promisora en el tratamiento contra el cáncer. Según algunas investigaciones, los receptores de tirosina-quinasa, además de estar relacionados al ciclo celular normal, tienen una participación fundamental en los procesos neoplásicos. Así es que algunas estrategias terapéuticas, como el desarrollo de anticuerpos anti receptores de tirosina-quinasa y pequeñas moléculas inhibidoras del receptor de tirosina-quinasa, se han desarrollado en un intento de inhibir el desarrollo tumoral. El objetivo de la presente revisión bibliográfica es describir el uso de los inhibidores de tirosina-quinasa en el tratamiento del mastocitoma en perros.
Assuntos
Animais , Cães , Mastocitoma Cutâneo/patologia , Neoplasias/patologia , Tratamento Farmacológico , Cães/classificaçãoRESUMO
O mastocitoma é o segundo tumor mais comum no cão, sendo caracterizado pela proliferação desordenada de mastócitos na pele. O tratamento envolve a ressecção cirúrgica, quimioterapia e radioterapia. Recentemente, novos protocolos de tratamento têm sido desenvolvidos, como a utilização de inibidores de receptores de tirosina-quinase. Com o conhecimento do genoma e a evolução de metodologias em genética molecular, os fármacos com alvo molecular específico constituem uma modalidade terapêutica promissora contra o câncer, no futuro. Além de estarem envolvidos no ciclo celular normal, alguns estudos sugerem que os receptores de tirosina-quinase têm participação fundamental nos processos neoplásicos. Dessa forma, algumas estratégias, como o desenvolvimento de anticorpos antirreceptores de tirosina-quinase e as pequenas moléculas inibidoras de receptor de tirosina-quinase, têm sido desenvolvidas na tentativa de inibir o desenvolvimento tumoral. O objetivo da presente revisão é descrever o uso dos inibidores de tirosina-quinase no tratamento de mastocitoma em cães.(AU)
The mast cell tumor (MCT) is the second most common type of tumor in dogs. It is characterized by uncontrolled proliferation of mast cells in the skin. Treatment involves surgical resection, chemotherapy and radiotherapy. Recently, new treatment protocols have been developed, such as the use of tyrosine kinase inhibitors. With the increasing knowledge about the genome and the evolution of methods in molecular genetics, drugs with specific molecular targets are surely going to become promising therapeutic modalities in the near future. Besides being involved in the normal cell cycle, some studies suggest that tyrosine kinases have a fundamental role in neoplastic processes. Therefore, some strategies such as the development of antibodies anti-receptors for tyrosine kinases and small-molecule tyrosine kinase receptor inhibitors have been developed in an attempt to inhibit tumor development. The purpose of this review is to describe the use of tyrosine kinase inhibitors in the treatment of mast cell tumors in dogs.(AU)
El mastocitoma es el segundo tumor mas frecuente en perros, caracterizándose por la proliferación desordenada de mastocitos en la piel. El tratamiento abarca la resección quirúrgica, la quimio y la radioterapia. Recientemente, se han desarrollado nuevos protocolos de tratamiento, como los inhibidores de receptores de tirosina-quinasa. Una vez conocido el genoma y teniendo en cuenta la evolución de diferentes metodologías en genética molecular, en el futuro, los fármacos con acción molecular específica se convertirán, seguramente, en una alternativa terapéutica promisora en el tratamiento contra el cáncer. Según algunas investigaciones, los receptores de tirosina-quinasa, además de estar relacionados al ciclo celular normal, tienen una participación fundamental en los procesos neoplásicos. Así es que algunas estrategias terapéuticas, como el desarrollo de anticuerpos anti receptores de tirosina-quinasa y pequeñas moléculas inhibidoras del receptor de tirosina-quinasa, se han desarrollado en un intento de inhibir el desarrollo tumoral. El objetivo de la presente revisión bibliográfica es describir el uso de los inhibidores de tirosina-quinasa en el tratamiento del mastocitoma en perros.(AU)
Assuntos
Animais , Cães , Neoplasias/patologia , Mastocitoma Cutâneo/patologia , Tratamento Farmacológico , Cães/classificaçãoRESUMO
Apoptosis is an essential physiological process of elimination of destined cells during the development and differentiation or after damage from external stresses such as ionizing radiation or chemotherapeutic agents. Disruption of apoptosis is proved to cause various diseases including cancer. Among numerous molecules involved in diverse anti- or pro-apoptotic signaling pathways, NF-kappaB is one of the key factors controlling anti-apoptotic responses. Its anti-apoptotic effect is thought to be mediated through not only transcriptional activation of dependent genes but also by crosstalking with the JNK pathway. Oncogenic proteins such as Ret/PTC, Ras and BRAF can induce NF-kappaB activation making it an important change in thyroid cancer. A number of specific or non-specific NF-kappaB inhibitors have been tried to take over the cascade in in vitro and in vivo experiments. These agents can induce massive apoptosis especially in combination with radio- or chemotherapy. Current results suggest that the inhibition of the NF-kappaB may be a promising strategy for advanced thyroid cancer treatment but further investigations are warranted to develop specific and clinically effective NF-kappaB inhibitors in future.
A apoptose é um processo fisiológico essencial destinado a eliminar células durante o desenvolvimento e diferenciação ou após danos decorrentes de estresses externos com a radiação ionizante ou agentes quimioterápicos. Distúrbios na apoptose têm sido demonstrados como causadores de várias doenças, incluindo câncer. Entre as inúmeras moléculas envolvidas nas várias vias de sinalização anti- ou pró-apoptoticas, NF-kapaB é um dos fatores-chave que controlam as respostas anti-apoptóticas. Acredita-se que seu efeito anti-apoptótico seja mediado não apenas pela ativação transcricional de genes dependentes mas também por crosstalking com a via JNK. Proteínas oncogênicas como Ret/PTC, Ras e BRAF podem induzir ativação de NF-kapaB promovendo importante transformação no câncer da tireóide. Uma série de inibidores específicos e não-específicos do NF-kapaB tem sido usada em experimentos in vitro e in vivo procurando inibir a cascata. Esses agentes podem induzir apoptose maciça especialmente em combinação com radio ou quimioterapia. Resultados atuais sugerem que a inibição de NF-kapaB pode ser uma estratégia promissora no tratamento do câncer da tireóide avançado, mas novas investigações são necessárias para desenvolver inibidores específicos e clinicamente efetivos do NF-kapaB.