Browsing by Author "Martins, SF"
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- Clinicopathological correlation and prognostic significance of VEGF-A, VEGF-C, VEGFR-2 and VEGFR-3 expression in colorectal cancer.Publication . Martins, SF; Garcia, EA; Luz, MA; Pardal, F; Mesquita-Rodrigues, A; Filho, ALBACKGROUND: Colorectal cancer (CRC) is the third most common type of cancer and the fourth most frequent cause of cancer death. Literature indicates that vascular endothelial growth factor is a predominant angiogenic factor and that angiogenesis plays an important role in the progression of CRC. PATIENTS AND METHODS: The present series consisted of tissue samples obtained from 672 patients who had undergone large bowel resection between 2005 and 2010 at the Braga Hospital, Portugal. Archival paraffin-embedded CRC tissue and normal adjacent samples were used to build up tissue microarray blocks and VEGF-A, VEGF-C, VEGFR-2 and VEGFR-3 expression was immunohistochemically assessed. RESULTS: We observed an overexpression of VEGF-C in CRC when tumour cells and normal-adjacent tissue were compared (p=0.004). In tumour samples, VEGF-C-positive cases were associated with VEGFR-3 expression (p=0.047). When assessing the correlation between VEGF-A, VEGF-C, VEGFR-2 and VEGFR-3 expressions and the clinicopathological data, it was revealed that VEGF-A positive cases were associated with male gender (p=0.016) and well-differentiated tumours (p=0.001); VEGF-C with colon cancers (p=0.037), exophytic (p=0.048), moderately-differentiated (p=0.007) and T3/T4 (p=0.010) tumours; VEGFR-2 with invasive adenocarcinoma (p=0.007) and VEGFR-3 with the presence of hepatic metastasis (p=0.032). Overall survival curves for CRC were statistically significant for rectal cancer, VEGF-C expression and stage III (p=0.019) and VEGFR-3 expression and stage IV (p=0.047). CONCLUSION: Quantification of VEGF-A, VEGF-C, VEGFR-2 and VEGFR-3 expression seems to provide valuable prognostic information in CRC and the correlation with clinicopathological data revealed an association with characteristics that contribute to progression, invasion and metastasis leading to poorer survival rates and prognosis.
- Evaluation of quality parameters of rectal cancer surgery at the Coloproctology Unit of Hospital de BragaPublication . Pimenta de Castro, MA; Martins, SFINTRODUCTION: Rectal cancer (RC) represents 1/3 of all diagnosed colorectal cancers. After the creation of specialized units to treat RC, it became fundamental to establish criteria to assess the quality of the service. Objective: To evaluate the surgical treatment provided to RC patients at the Coloproctology Unit of Hospital de Braga (BH-CU) by means of quality parameters. METHODS: We conducted an observational cross-sectional descriptive study with a convenience sample of 149 patients undergoing surgical treatment in this unit, from January 1st, 2007 to June 30, 2010. RESULTS: We observed that the postoperative mortality rate (4%) and the global dehiscence rate (14.8%) were in accordance with recommended values. Sphincter sparing surgery rate (65.8%) was higher than the recommended minimum; however, more than 12 resected ganglia (36.6%) is inferior than what is recommended. The oncological results were analyzed by the local recurrence rate (6.7%) and the two-year survival rate (91.1%); both values are in accordance with literature. CONCLUSION: We conclude that the BH-CU surgical treatment has a quality level similar to that observed in literature.
- Gastric Cancer and Angiogenesis: Is VEGF a Useful Biomarker to Assess Progression and Remission?Publication . Macedo, F; Ladeira, K; Longatto-Filho, A; Martins, SFGastric cancer (GC) has high mortality owing to its aggressive nature. Tumor angiogenesis plays an essential role in the growth, invasion, and metastatic spread of GC. The aim of this work was to review the angiogenic biomarkers related to the behavior of GC, documented in the literature. A search of the PubMed database was conducted with the MeSH terms: "Stomach neoplasms/blood [MeSH] or stomach neoplasms/blood supply [MeSH] and angiogenic proteins/blood [Major]". A total of 30 articles were initially collected, and 4 were subsequently excluded. Among the 26 articles collected, 16 examined the role of vascular endothelial growth factor (VEGF), 4 studied endostatin, 3 investigated angiopoietin (Ang)-2, 2 studied the Ang-like protein 2 (ANGTPL2), and 1 each examined interleukin (IL)-12, IL-8, and hypoxia inducible factor. Regarding VEGF, 6 articles concluded that the protein was related to lymph node metastasis or distant metastases. Five articles concluded that VEGF levels were elevated in the presence of GC and decreased following tumor regression, suggesting that VEGF levels could be a predictor of recurrence. Four articles concluded that high VEGF levels were correlated with poor prognosis and lower survival rates. Ang-2 and ANGTPL2 were elevated in GC and associated with more aggressive disease. Endostatin was associated with intestinal GC. VEGF is the most extensively studied angiogenic factor. It is associated with the presence of neoplastic disease and lymph node metastasis. It appears to be a good biomarker for disease progression and remission, but not for diagnosis. The data regarding other biomarkers are inconclusive.
- Ki-67 Expression in CRC Lymph Node Metastasis Does Not Predict SurvivalPublication . Martins, SF; Amorim, R; Mota, SC; Costa, L; Pardal, F; Mesquita-Rodrigues, A; Longatto-Filho, AColorectal cancer is one of the most common malignancies and a leading cause of cancer death worldwide. Molecular markers may improve clinicopathologic staging and provide a basis to guide novel therapeutic strategies which target specific tumour-associated molecules according to individual tumour biology; however, so far, no ideal molecular marker has been found to predict disease progression. We tested Ki-67 proliferation marker in primary and lymph node metastasis of CRC. We observed a statistical significant difference between the positive rates of neoplastic cells positively stained by Ki-67 in both sites, with remarkable increased number of Ki-67 positive cells in primary tumor cells compared to cancer cells that invaded lymph nodes. We can speculate that the metastatic CRC in lymph node can be more resistant to the drugs that target cellular division.
- Ki-67 Expression in CRC Lymph Node Metastasis Does Not Predict SurvivalPublication . Martins, SF; Amorim, R; Coelho-Mota, S; Costa, L; Pardal, F; Mesquita-Rodrigues, A; Longatto-Filho, AColorectal cancer is one of the most common malignancies and a leading cause of cancer death worldwide. Molecular markers may improve clinicopathologic staging and provide a basis to guide novel therapeutic strategies which target specific tumour-associated molecules according to individual tumour biology; however, so far, no ideal molecular marker has been found to predict disease progression. We tested Ki-67 proliferation marker in primary and lymph node metastasis of CRC. We observed a statistical significant difference between the positive rates of neoplastic cells positively stained by Ki-67 in both sites, with remarkable increased number of Ki-67 positive cells in primary tumor cells compared to cancer cells that invaded lymph nodes. We can speculate that the metastatic CRC in lymph node can be more resistant to the drugs that target cellular division.
- Rational Identification of a Colorectal Cancer Targeting Peptide through Phage DisplayPublication . Ferreira, D; Silva, AP; Nobrega, FL; Martins, IM; Barbosa-Matos, C; Granja, S; Martins, SF; Baltazar, F; Rodrigues, LRColorectal cancer is frequently diagnosed at an advanced stage due to the absence of early clinical indicators. Hence, the identification of new targeting molecules is crucial for an early detection and development of targeted therapies. This study aimed to identify and characterize novel peptides specific for the colorectal cancer cell line RKO using a phage-displayed peptide library. After four rounds of selection plus a negative step with normal colorectal cells, CCD-841-CoN, there was an obvious phage enrichment that specifically bound to RKO cells. Cell-based enzyme-linked immunosorbent assay (ELISA) was performed to assess the most specific peptides leading to the selection of the peptide sequence CPKSNNGVC. Through fluorescence microscopy and cytometry, the synthetic peptide RKOpep was shown to specifically bind to RKO cells, as well as to other human colorectal cancer cells including Caco-2, HCT 116 and HCT-15, but not to the normal non-cancer cells. Moreover, it was shown that RKOpep specifically targeted human colorectal cancer cell tissues. A bioinformatics analysis suggested that the RKOpep targets the monocarboxylate transporter 1, which has been implicated in colorectal cancer progression and prognosis, proven through gene knockdown approaches and shown by immunocytochemistry co-localization studies. The peptide herein identified can be a potential candidate for targeted therapies for colorectal cancer.
- Role of endoglin and VEGF family expression in colorectal cancer prognosis and anti-angiogenic therapiesPublication . Martins, SF; Reis, RM; Mesquita-Rodrigues, A; Baltazar, F; Filho, ALColorectal cancer (CRC) is one of the cancer models and most of the carcinogenic steps are presently well understood. Therefore, successful preventive measures are currently used in medical practice. However, CRC is still an important public health problem as it is the third most common cancer and the fourth most frequent cause of cancer death worldwide. Nowadays, pathologic stage is a unique and well-recognized prognostic indicator, however, more accurate indicators of the biologic behavior of CRC are expected to improve the specificity of medical treatment. Angiogenesis plays an important role in the growth and progression of cancer but its role as a prognostic factor is still controversial. Probably the most important clinical implication of tumor angiogenesis is the development of anti-angiogenic therapy. The goal of this review is to critically evaluate the role of angiogenic markers, assessed by either endoglin-related microvessel density or expression of vascular endothelial growth factor family members in the CRC setting and discuss the role of these angiogenic markers in anti-angiogenic therapies.
- Role of endoglin and VEGF family expression in colorectal cancer prognosis and anti-angiogenic therapiesPublication . Martins, SF; Reis, RM; Rodrigues, AM; Baltazar, F; Filho, ALColorectal cancer (CRC) is one of the cancer models and most of the carcinogenic steps are presently well understood. Therefore, successful preventive measures are currently used in medical practice. However, CRC is still an important public health problem as it is the third most common cancer and the fourth most frequent cause of cancer death worldwide. Nowadays, pathologic stage is a unique and well-recognized prognostic indicator, however, more accurate indicators of the biologic behavior of CRC are expected to improve the specificity of medical treatment. Angiogenesis plays an important role in the growth and progression of cancer but its role as a prognostic factor is still controversial. Probably the most important clinical implication of tumor angiogenesis is the development of anti-angiogenic therapy. The goal of this review is to critically evaluate the role of angiogenic markers, assessed by either endoglin-related microvessel density or expression of vascular endothelial growth factor family members in the CRC setting and discuss the role of these angiogenic markers in anti-angiogenic therapie
- Significance of glycolytic metabolism-related protein expression in colorectal cancer, lymph node and hepatic metastasisPublication . Martins, SF; Amorim, R; Viana-Pereira, M; Pinheiro, C; Costa, RA; Silva, P; Couto, C; Alves, S; Fernandes, S; Vilaça, S; Falcão, J; Marques, H; Pardal, F; Rodrigues, M; Preto, A; Reis, RM; Longatto-Filho, A; Baltazar, FBACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies and a leading cause of cancer death worldwide. Most cancer cells display high rates of glycolysis with production of lactic acid, which is then exported to the microenvironment by monocarboxylate transporters (MCTs). The main aim of this study was to evaluate the significance of MCT expression in a comprehensive series of primary CRC cases, lymph node and hepatic metastasis. METHODS: Expressions of MCT1, MCT4, CD147 and GLUT1 were studied in human samples of CRC, lymph node and hepatic metastasis, by immunohistochemistry. RESULTS: All proteins were overexpressed in primary CRC, lymph node and hepatic metastasis, when compared with non-neoplastic tissue, with exception of MCT1 in lymph node and hepatic metastasis. MCT1 and MCT4 expressions were associated with CD147 and GLUT1 in primary CRC. These markers were associated with clinical pathological features, reflecting the putative role of these metabolism-related proteins in the CRC setting. CONCLUSION: These findings provide additional evidence for the pivotal role of MCTs in CRC maintenance and progression, and support the use of MCTs as biomarkers and potential therapeutic targets in primary and metastatic CRC.