RESUMO
Monocarboxylate transporter 1 (MCT1) inhibition is thought to block tumor growth through disruption of lactate transport and glycolysis. Here, we show MCT1 inhibition impairs proliferation of glycolytic breast cancer cells co-expressing MCT1 and MCT4 via disruption of pyruvate rather than lactate export. MCT1 expression is elevated in glycolytic breast tumors, and high MCT1 expression predicts poor prognosis in breast and lung cancer patients. Acute MCT1 inhibition reduces pyruvate export but does not consistently alter lactate transport or glycolytic flux in breast cancer cells that co-express MCT1 and MCT4. Despite the lack of glycolysis impairment, MCT1 loss-of-function decreases breast cancer cell proliferation and blocks growth of mammary fat pad xenograft tumors. Our data suggest MCT1 expression is elevated in glycolytic cancers to promote pyruvate export that when inhibited, enhances oxidative metabolism and reduces proliferation. This study presents an alternative molecular consequence of MCT1 inhibitors, further supporting their use as anti-cancer therapeutics.
Assuntos
Neoplasias da Mama/metabolismo , Regulação Neoplásica da Expressão Gênica , Transportadores de Ácidos Monocarboxílicos/genética , Proteínas Musculares/genética , Ácido Pirúvico/metabolismo , Simportadores/genética , Animais , Antineoplásicos/farmacologia , Transporte Biológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclo do Ácido Cítrico/efeitos dos fármacos , Ciclo do Ácido Cítrico/genética , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Perfilação da Expressão Gênica , Glicólise/efeitos dos fármacos , Glicólise/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Transportadores de Ácidos Monocarboxílicos/antagonistas & inibidores , Transportadores de Ácidos Monocarboxílicos/metabolismo , Proteínas Musculares/metabolismo , Fosforilação Oxidativa/efeitos dos fármacos , Pirimidinonas/farmacologia , Transdução de Sinais , Simportadores/antagonistas & inibidores , Simportadores/metabolismo , Tiofenos/farmacologia , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
In many cultures, the erect penis has been a symbol of masculine qualities. Because of this symbolism, a penis that is less than average size can cause insecurity or embarrassment. This series reports the authors' 18-year experience in the management of 60 men with a complaint of a small penis. For 44 of these 60 men, counseling was sufficient; the other 16 had surgery, and of these, 9 were satisfied with the result. Despite limitations, the authors conclude that those men who already achieve a penis length of no less than 7.5 cm (2.95 in) in erection, have only limited benefit from penis-enhancing surgery. This particular patient category should therefore be dissuaded from surgery.
Assuntos
Satisfação do Paciente , Doenças do Pênis/terapia , Ereção Peniana , Pênis/anatomia & histologia , Adolescente , Adulto , Imagem Corporal , Aconselhamento , Humanos , Masculino , Pessoa de Meia-Idade , Autoimagem , Adulto JovemRESUMO
Penis lengthening pills, stretch apparatus, vacuum pumps, silicone injections, and lengthening and thickening operations are available for men who worry about their penis size. Surgery is thus far the only proven scientific method for penile enlargement. In this article, we consider patient selection, outcome evaluation, and techniques applied. In our view, sexological counseling and detailed explanation of risks and complications are mandatory before any operative intervention.