RESUMO
Colorectal cancer represents the fourth commonest malignancy, and constitutes a major cause of significant morbidity and mortality among other diseases. However, the chemical therapy is still under development. Angiogenesis plays an important role in colon cancer development. We developed HMQ18-22 (a novel analog of taspine) with the aim to target angiogenesis. We found that HMQ18-22 significantly reduced angiogenesis of chicken chorioallantoic membrane (CAM) and mouse colon tissue, and inhibited cell migration and tube formation as well. Then, we verified the interaction between HMQ18-22 and VEGFR2 by AlphaScreen P-VEGFR assay, screened the targets on angiogenesis by VEGF Phospho Antibody Array, validated the target by western blot and RNAi in lovo cells. We found HMQ18-22 could decrease phosphorylation of VEGFR2(Tyr(1214)), VEGFR1(Tyr(1333)), Akt(Tyr(326)), protein kinase Cα (PKCα) (Tyr(657)) and phospholipase-Cγ-1 (PLCγ-1) (Tyr(771)). Most importantly, HMQ18-22 inhibited proliferation of lovo cell and tumor growth in a human colon tumor xenografted model of athymic mice. Compared with normal lovo cells proliferation, the inhibition on proliferation of knockdown cells (VEGFR2, VEGFR1, Akt, PKCα and PLCγ-1) by HMQ18-22 decreased. These results suggested that HMQ18-22 is a novel angiogenesis inhibitor and can be a useful therapeutic candidate for colon cancer intervention.
Assuntos
Inibidores da Angiogênese/farmacologia , Benzamidas/farmacologia , Compostos de Bifenilo/farmacologia , Transdução de Sinais/efeitos dos fármacos , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Alcaloides/química , Alcaloides/farmacologia , Alcaloides/uso terapêutico , Inibidores da Angiogênese/uso terapêutico , Animais , Benzamidas/química , Benzamidas/uso terapêutico , Compostos de Bifenilo/química , Compostos de Bifenilo/uso terapêutico , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos , Camundongos Nus , Fosforilação/efeitos dos fármacos , Proteína Quinase C/antagonistas & inibidores , Proteína Quinase C/genética , Proteína Quinase C/metabolismo , Proteína Quinase C-alfa/antagonistas & inibidores , Proteína Quinase C-alfa/genética , Proteína Quinase C-alfa/metabolismo , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Transplante Heterólogo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genéticaRESUMO
Laryngeal mucosa-associated lymphoid tissue (MALT) lymphoma is rare, with only 25 cases reported in the literature. This report presents a case of laryngeal MALT lymphoma in a 35-year-old female with a 6-year history of progressively worsening hoarseness. MALT lymphoma was diagnosed based on biopsy and immunohistochemical analysis. The patient received two cycles of cyclophosphamide + epirubicin + vincristine + prednisone (CHOP) chemo therapy, which was ineffective. (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) showed (18)F-FDG accumulation in the larynx only and identified stage IE lymphoma. CHOP chemotherapy was terminated and the patient was treated with radiotherapy. After 3 months (total radiation dose 27 Gy), (18)F-FDG PET/CT scan showed that the laryngeal lesion was in complete remission. A review of the literature on the MEDLINE(®)/PubMed(®) databases regarding laryngeal MALT lymphoma and the use of PET/CT found that radiotherapy is the first-line treatment for stage I and II MALT lymphoma.