RESUMO
A 56-year-old woman complaining of right lower abdominal pain was admitted to our hospital. An abdominal computed tomography showed the enlarged appendix tip and a high density area around the appendix to retroperitoneum. The patient was diagnosis with acute appendicitis and underwent emergency laparoscopic appendectomy. Histopathological findings of the resected specimens revealed a component with signet ring cell carcinoma morphology that was positive for neuroendocrine markers by immunohistochemical staining, which led to the diagnosis of goblet cell carcinoid(GCC)of appendix. GCC cells were found to infiltrate the surrounding serosa and Ly positive. An additional laparoscopic ileocecal resection with D3 dissection was performed. In the appendix GCC, additional resection is considered because the lymph node metastasis rate increases(SS/13%)as the depth of wall progresses. Appendiceal tumors including GCC may develop acute appendicitis and may be followed by additional resection. Therefore, it is important to consider how to deal with the first surgery.
Assuntos
Neoplasias do Apêndice , Apendicite , Apêndice , Tumor Carcinoide , Apendicectomia , Neoplasias do Apêndice/cirurgia , Apendicite/cirurgia , Apêndice/cirurgia , Tumor Carcinoide/cirurgia , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
A large number of antitumor drug delivery carriers based on passive targeting and/or active targeting have been developed. However, encapsulation of antitumor drugs into these drug carriers is often complicated, and antitumor activities of these targeting systems are not satisfactory. In the present study, we first prepared heptakis-6-folic acid (FA)-appended ß-cyclodextrin (ß-CyD) possessing two caproic acids between FA and a ß-CyD molecule as a spacer (Fol-c(2)-ß-CyD) and evaluated the potential as a novel tumor targeting carrier for antitumor drugs through a complexation. Fol-c(2)-ß-CyD formed an inclusion complex with doxorubicin (DOX) at a 1:1 molar ratio with a markedly high stability constant (>10(6) M(-1)). Cellular uptake of DOX was increased by the addition of Fol-c(2)-ß-CyD in KB cells, a folate receptor-α (FR-α)-positive cell line. Additionally, Fol-c(2)-ß-CyD increased in vitro antitumor activities of antitumor drugs such as DOX, vinblastine (VBL), and paclitaxel (PTX) in KB cells, but not in A549 cells, a FR-α-negative cell line. The complex of DOX with Fol-c(2)-ß-CyD markedly increased antitumor activity of DOX, not only after intratumoral administration but also after intravenous administration to mice subcutaneously inoculated Colon-26 cells, a FR-α-positive cell line. These findings suggest that Fol-c(2)-ß-CyD could be useful as a promising antitumor drug carrier.
Assuntos
Antineoplásicos/farmacologia , Portadores de Fármacos/química , Ácido Fólico/química , Neoplasias Experimentais/tratamento farmacológico , beta-Ciclodextrinas/química , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Caproatos/química , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Sistemas de Liberação de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Células KB , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
We reported that per-6-folic acid (FA)-appended ß-cyclodextrin (ß-CyD) possessing two caproic acids between FA and a ß-CyD molecule as a spacer (Fol-c2-ß-CyD) could be useful as a promising antitumor drug carrier. However, the effects of the cavity size and the spacer length on the carrier ability are not still known. In this study, we designed and evaluated the FA-appended three kinds of CyDs possessing a caproic acid as a spacer between FA and a CyD molecule (Fol-c1-CyDs) as a tumor targeting carrier for antitumor drugs. The stability constant of the Fol-c1-ß-CyD/doxorubicin (DOX) complex was much higher than those of Fol-c1-α-CyD and Fol-c1-γ-CyD at pH 7.3. Antitumor activity of DOX was increased by the complexation with Fol-c1-ß-CyD, but not with Fol-c1-α-CyD or Fol-c1-γ-CyD in KB cells, a folate receptor-α-positive cell line. Also, Fol-c1-ß-CyD increased antitumor activities of paclitaxel and vinblastine, but not 5-fluorouracil. Furthermore, Fol-c1-ß-CyD accelerated cellular uptake of DOX and inhibited its efflux from KB cells. The Fol-c1-ß-CyD/DOX complex showed much higher antitumor activity than DOX alone after intratumoral and intravenous administrations to tumor-bearing mice with a negligible change of the blood chemistry values. These findings suggest that Fol-c1-ß-CyD could be useful as a tumor-selective carrier for antitumor drugs.