RESUMO
BACKGROUND: FOLFOX chemotherapy is widely used as an adjuvant treatment for advanced colon cancer. The duration of adjuvant chemotherapy is usually set to 6 months, which is based on a former study of 5-fluorouracil/leucovorin chemotherapy. However, the FOLFOX regimen is known to have complications, such as peripheral neuropathy. The aim of this study was to compare the survival rates and complications experienced by patients receiving either 4 or 6 months of FOLFOX chemotherapy. METHODS: Retrospective data analysis was performed for stage II and III patients who underwent radical resection of colon cancer. We compared the 5-year survival rates and the occurrence of complications in patients who completed only 8 cycles of FOLFOX chemotherapy with patients who completed 12 cycles of chemotherapy. RESULTS: Among 188 patients who underwent adjuvant FOLFOX chemotherapy for stage II or III colon cancer, 83 (44.1%) completed 6 months of FOLFOX chemotherapy and 64 (34.0%) patients discontinued after 4 months of chemotherapy. The 5-year overall survival and disease-free survival rates did not show a significant difference. Patients in the 6-month group had peripheral neuropathy more frequently (p = 0.028). CONCLUSIONS: Five-year overall and disease-free survival were not significantly different between the 2 groups. Large-scale prospective studies are necessary for the analysis of complications and survival rates.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neutropenia/etiologia , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Doenças do Sistema Nervoso Periférico/etiologia , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Many reports have shown the anticancer effects of iron deficient on cancer cells, but the effects of iron-chelators on gastric cancer have not been clearly elucidated. Recently, we reported that iron chelators induced an antiproliferative effect in human malignant lymphoma and myeloid leukemia cells. In the present study, we investigated the antitumor activity of these two iron-chelating agents, deferoxamine (DFO) and deferasirox (DFX), with gastric cancer cell lines, and their apoptosis-inducing effects as the potential mechanism. We found that iron chelators displayed significant antiproliferative activity in human gastric cancer cell lines, which may be attributed to their induction of G1 phase arrest and apoptosis. We also found that iron chelators induced reactive oxygen species (ROS) production, resulting in the activation of both c-Jun N-terminal kinase (JNK) and endoplasmic reticulum (ER) stress apoptotic pathways in gastric cancer cells. Taken together, our data suggest that iron chelators induced apoptosis in gastric cancer, involving ROS formation ER stress and JNK activation.
Assuntos
Apoptose/efeitos dos fármacos , Benzoatos/farmacologia , Desferroxamina/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Quelantes de Ferro/farmacologia , Neoplasias Gástricas/patologia , Triazóis/farmacologia , Biomarcadores Tumorais/metabolismo , Western Blotting , Proliferação de Células/efeitos dos fármacos , Deferasirox , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Microscopia Confocal , Estadiamento de Neoplasias , Prognóstico , Espécies Reativas de Oxigênio/metabolismo , Sideróforos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Células Tumorais CultivadasRESUMO
Bone morphogenetic proteins (BMPs) have been involved in metastatic progression and tumorigenesis of many cancer types. However, it remains unclear how BMP-2 contributes to the initiation and development of these cancers. Here, we investigated the role of BMP-2 in colon cancer stem cell (CSC) development from colon cancer cells. We also determined the effects of BMP-2 on CSC development and epithelial-mesenchymal transition (EMT) in human colon cancer cell lines HCT-116 and SW620. We found that BMP-2 enhanced sphere formation of colon cancer cells without serum. Also, BMP-2-induced spheres displayed up-regulation of stemness markers (CD133+ and EpCAM+) and increased drug resistance, hallmarks of CSCs. Importantly, expression of EMT activators p-Smad1/5 and Snail and N-cadherin was increased in the spheres' cells, indicating that BMP-2 signaling might result in CSC self-renewal and EMT. Furthermore, siRNA-mediated knockdown of signal transducer and activator of transcription 3 (STAT3) in HCT-116 cells reversed BMP-2-induced EMT and stem cell formation. Taken together, our results suggest that the BMP-2 induced STAT3-mediated induction of colon cancer cell metastasis requires an EMT and/or changes in CSC markers.
Assuntos
Proteína Morfogenética Óssea 2/genética , Neoplasias do Colo/genética , Células-Tronco Neoplásicas , Fator de Transcrição STAT3/genética , Antígeno AC133 , Antígenos CD/genética , Antígenos de Neoplasias/genética , Proteína Morfogenética Óssea 2/biossíntese , Moléculas de Adesão Celular/genética , Diferenciação Celular/genética , Movimento Celular/genética , Neoplasias do Colo/patologia , Molécula de Adesão da Célula Epitelial , Transição Epitelial-Mesenquimal/genética , Glicoproteínas/genética , Células HCT116 , Humanos , Metástase Neoplásica , Peptídeos/genética , Fator de Transcrição STAT3/biossíntese , Transdução de SinaisRESUMO
The colorectal cancer (CRC) patients with microsatellite instability (MSI) have distinct clinicopathological characteristics consisting of factors predicting positive and negative outcomes, such as a high lymph node harvest and poor differentiation. In this study, we measured the value of MSI as a prognostic factor after controlling for these discrepant factors. A total of 603 patients who underwent curative surgery for stages I to III colorectal cancer were enrolled. The patients were divided into microsatellite instability high (MSI-H) and microsatellite stable/microsatellite instability low (MSS/MSI-L) groups. Propensity score matching was used to match clinicopathological factors between the 2 groups. MSI-H patients had a high lymph node harvest (median: 31.0 vs 23.0, Pâ<â.001), earlier-stage tumors (Pâ<â.001), advanced T stage (89.3% vs 74.0%, Pâ=â.018), and poor differentiation (19.6% vs 2.0%, Pâ<â.001). Survival analysis showed better survival in the MSI-H group, but the difference was not statistically significant (Pâ=â.126). Propensity score matching was performed for significant prognostic factors identified by Cox hazard regression. After the matching, the survival difference by MSI status was estimated to be larger than before, and reached statistical significance (Pâ=â.045). In conclusion, after controlling for pathological characteristics, MSI-H could be a potent prognostic factor regarding patient survival.
Assuntos
Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Instabilidade de Microssatélites , Humanos , Linfonodos/patologia , Metástase Linfática , Estadiamento de Neoplasias , Prognóstico , Pontuação de Propensão , Modelos de Riscos Proporcionais , Análise de SobrevidaRESUMO
Recent studies have determined that inactivation of runtrelated transcription factor 3 (RUNX3) expression is highly associated with lymph node metastasis and poor prognosis in various types of cancer. However, the mechanism of RUNX3-mediated suppression of tumor metastasis remains unclear. Herein, we aimed to clarify the effect of RUNX3 on metastasis and angiogenesis in colorectal cancer (CRC). Firstly, we found that the reduction in expression of RUNX3 in CRC tissues when compared with tumor adjacent normal colon tissues, as indicated by reduced RUNX3 staining, was significantly correlated with tumor-node-metastasis (TNM) stage. Secondly, we demonstrated that RUNX3 overexpression inhibited CRC cell migration and invasion resulting from the upregulation of matrix metalloproteinase-2 (MMP-2) and MMP-9 expression. In contrast, the knockdown of RUNX3 reduced the inhibition of migration and invasion of CRC cells. Finally, we found that restoration of RUNX3 decreased vascular endothelial growth factor (VEGF) secretion and suppressed endothelial cell growth and tube formation in CRC cells. All in all, our findings may provide insight into the development of RUNX3 for CRC metastasis diagnostics and therapeutics.
Assuntos
Neoplasias Colorretais/genética , Subunidade alfa 3 de Fator de Ligação ao Core/genética , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/biossíntese , Neovascularização Patológica/genética , Fator A de Crescimento do Endotélio Vascular/biossíntese , Linhagem Celular Tumoral , Movimento Celular/genética , Neoplasias Colorretais/patologia , Subunidade alfa 3 de Fator de Ligação ao Core/biossíntese , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Invasividade Neoplásica/genética , Metástase Neoplásica , Estadiamento de Neoplasias , Neovascularização Patológica/patologia , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
Rectal foreign bodies are being detected more frequently, and their textures, sizes, shapes, and locations are critical considerations when removal and deciding on management plans. Many removal techniques have been described and various theories have been put forward to explain procedural mechanics. Here the authors report a case in which a transanal technique using a SILS port was successfully used.