RESUMO
BACKGROUND Osteopontin (OPN) is a molecule expressed in numerous cancers including colorectal cancer (CRC) that correlates disease progression. The interaction of OPN that promotes CRC cell migration, invasion, and cancer stem-like cells (CSCs) have not been elucidated. Hence, we aimed to investigate the mechanisms that might be involved. MATERIAL AND METHODS Expression of OPN in tumor tissues derived from patients was monitored with real-time quantitative polymerase chain reaction and western blot. Wound healing and Transwell assay were used to test the differences in migration and invasion in an OPN enriched environment and OPN knockdown condition. Aldehyde dehydrogenase 1 (ALDH1) positive stem cells were isolated using fluorescence-activated cell sorting (FACS) following the protocol of the ALDEFLUOR™ kit. The expression of protein participation in the PI3K-Akt-GSK/3ß-ß/catenin pathway was detected by western blot. RESULTS OPN exhibited increased levels in CRC tumor tissue compared with non-tumor normal tissue and the high level of which correlated with lymphatic metastasis and late TNM stage. Additional rhOPN co-cultured low-expression CRC cells demonstrated more aggressive capability of proliferation, migration, and invasion. For knockdown of OPN in high-expression CRC cells, the bioactivities of proliferation, migration, and invasion were significantly inhibited. Interestingly, the percentage of ALDH1 labeled stem cells was dramatically decreased by OPN inhibition. The phosphorylation of PI3K-Akt-GSK/3ß-ß/catenin pathway was involved in the OPN signaling. Furthermore, Ly294002, a specific PI3K inhibitor, can reverse the promotion of bioactivities and stem cell proportion among rhOPN treated CRC cells. CONCLUSIONS OPN promoted cell proliferation, migration, and invasion, and was accompanied by upregulation of ALDH1-positive CSC in CRC through activation of PI3K-Akt-GSK/3ß-ß/catenin pathway.
Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Células-Tronco Neoplásicas/metabolismo , Osteopontina/metabolismo , Idoso , Apoptose/fisiologia , Diferenciação Celular/fisiologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Neoplasias Colorretais/patologia , Progressão da Doença , Feminino , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Células-Tronco Neoplásicas/patologia , Osteopontina/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Reação em Cadeia da Polimerase em Tempo Real/métodos , Transdução de Sinais , beta Catenina/metabolismoRESUMO
BACKGROUND: Large abdominal wall defect (LAWD) measures > 20 cm in width. LAWD can easily lead to intestinal necrosis, peritonitis, other complications, and even multiple organ dysfunction syndrome. Multiple intestinal fistulas are high-flow fistulas that can cause severe water-electrolyte imbalance and malnutrition, as well as inflammation, high metabolic status, and chronic intestinal failure caused by intestinal fluid corrosion in tissues around the orifice fistulas. CASE SUMMARY: This article summarizes the nursing experience of a patient with sigmoid carcinoma who has LAWD with multiple intestinal fistula due to repeated operations for postoperative complications. The key points of care: Scientific assessment of nutritional status, dynamic adjustment of nutritional support programmes, comprehensive adoption of enteral nutrition, parenteral nutrition and combined nutrition of enteral and parenteral; taking good care of abdominal wall defects and intestinal fistulas; continuous flushing of the abdominal drainage tube and low negative pressure drainage; prevention of venous thrombosis; strengthening of physical exercise; implementation of positive psychological interventions. CONCLUSION: After more than 7 months of careful care, the patient's physical fitness has been well recovered, local inflammation is well controlled, which wins the opportunity for the operation, and the postoperative recovery is good.
RESUMO
The aim was to evaluate the efficacy and safety between the watch-and-wait strategy (WW), radical surgery (RS), and local excision (LE) for rectal cancer with clinical complete response (cCR) after neoadjuvant radiotherapy (nCRT). We searched MEDLINE, EMBASE, the Cochrane Library, and clinical trials to compare WW with RS and LE for patients with cCR until March 2023 and collected the following data: local recurrence (LR), distant metastasis (DM), cancer-related death (CRD), overall survival (OS), and disease-free survival (DFS). In total, 2240 patients from 21 studies were included. Pairwise meta-analysis revealed no statistically significant differences between the three groups in terms of CRD and 2-, 3-, and 5-year OS (P < 0.05). The RS group was significantly better than the WW group in terms of the LR rate (odds ratio [OR] = 0.12, 95 % confidence interval [CI]: 0.06-0.21, P < 0.001, I2 = 0 %], 3-year DFS (OR = 1.56, 95 % CI: 1.10-2.21, P = 0.01, I2 = 38 %), and 5-year DFS (OR = 2.30, 95 % CI: 1.53-3.46, P < 0.001, I2 = 34 %). The results of network meta-analysis were also similar. After sensitivity analysis, the 5-year OS of the RS group was significantly better than that of the WW group (OR = 2.77, 95 % CI: 1.28-6.00, P = 0.009, I2 = 33 %). Nevertheless, neither regression analysis nor subgroup analysis provided meaningful results. However, the cumulative meta-analysis of LR, DM, and 3- and 5-year DFS revealed significant turning points (P < 0.05). Our meta-analysis recommends using the WW strategy for patients with cCR having poor underlying conditions and high surgical risk; however, there is a risk of higher LR and worse survival after 3 years.
Assuntos
Terapia Neoadjuvante , Neoplasias Retais , Humanos , Metanálise em Rede , Quimiorradioterapia , Conduta Expectante/métodos , Recidiva Local de Neoplasia , Neoplasias Retais/cirurgia , Resultado do TratamentoRESUMO
Gastric cancer (GC) is one of the most common malignancies of the digestive system. In diffusetype GC, differentiation is relatively poor, and the probability of distant metastasis and lymph node metastasis is high, resulting in poor clinical prognosis. The purpose of this study was to identify specific genes that can predict the prognosis of different types of GC. Differentially expressed genes (DEGs) were screened in the GSE62254 dataset obtained from the Gene Expression Omnibus using the 'limma' and 'survival' R packages. A total of 355 survivalrelated DEGs were selected according to specific screening criteria, of which 293 were associated with diffusetype GC and 62 with intestinaltype GC. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes were used for functional annotation and pathway enrichment analysis of DEGs. Using proteinprotein interaction networks and Cytoscape software, three hub genes were identified in diffusetype GCassociated DEGs, including angiotensinogen (AGT), CXC motif chemokine ligand 12 (CXCL12) and adrenoceptor ß2 (ADRB2). Immunohistochemical staining and reverse transcriptionquantitative PCR revealed that the expression levels of the three genes in diffusetype GC samples were upregulated compared with in intestinaltype GC samples. Kaplan Meier analysis indicated that a higher expression levels of these three hub genes were associated with a poorer prognosis of diffusetype GC. In summary, the present findings suggested that AGT, CXCL12 and ADRB2 might contribute to the progression of diffusetype GC, and could serve as potential biomarkers or therapeutic targets for this disease.