Sandra Martins

Increased expression of monocarboxylate transporters 1, 2, and 4 in colorectal carcinomas

Tumour cells are known to be highly glycolytic, thus producing high amounts of lactic acid. Monocarboxylate transporters (MCTs), by promoting the efflux of the accumulating acids, constitute one of the most important mechanisms in the maintenance of tumour intracellular pH. Since data concerning MCT expression in colorectal carcinomas (CRC) are scarce and controversial, the present study aimed to assess the expressions of MCT1, 2, and 4 in a well characterized series of CRC and assess their role in CRC carcinogenesis. CRC samples (126 cases) were analyzed for MCT1, MCT2, and MCT4 immunoexpression and findings correlated with clinico-pathological parameters. Expression of all MCT isoforms in tumour cells was significantly increased when compared to adjacent normal epithelium. Remarkably, there was a significant gain of membrane expression for MCT1 and MCT4 and loss of plasma membrane expression for MCT2 in tumour cells. Plasma membrane expression of MCT1 was directly related to the presence of vascular invasion. This is the larger study on MCT expression in CRC and evaluates for the first time its clinico-pathological significance. The increased expression of these transporters suggests an important role in CRC, which might justify their use, especially MCT1 and MCT4, as targets in CRC drug therapy.

Role of endoglin and VEGF family expression in colorectal cancer prognosis and anti-angiogenic therapies

Colorectal 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.

Gastric Cancer and Angiogenesis: Is VEGF a Useful Biomarker to Assess Progression and Remission?

Gastric 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.

Significance of glycolytic metabolism-related protein expression in colorectal cancer, lymph node and hepatic metastasis

BackgroundColorectal 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.MethodsExpressions of MCT1, MCT4, CD147 and GLUT1 were studied in human samples of CRC, lymph node and hepatic metastasis, by immunohistochemistry.ResultsAll 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.ConclusionThese 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.

Predictive Biomarkers in Colorectal Cancer: From the Single Therapeutic Target to a Plethora of Options

Colorectal cancer (CRC) is one of the most frequent cancers and is a leading cause of cancer death worldwide. Treatments used for CRC may include some combination of surgery, radiation therapy, chemotherapy, and targeted therapy. The current standard drugs used in chemotherapy are 5-fluorouracil and leucovorin in combination with irinotecan and/or oxaliplatin. Most recently, biologic agents have been proven to have therapeutic benefits in metastatic CRC alone or in association with standard chemotherapy. However, patients present different treatment responses, in terms of efficacy and toxicity; therefore, it is important to identify biological markers that can predict the response to therapy and help select patients that would benefit from specific regimens. In this paper, authors review CRC genetic markers that could be useful in predicting the sensitivity/resistance to chemotherapy.

Isolated splenic metastasis of colon cancer: a case report and literature review

Colorectal cancer (CRC) is a leading cause of death in the elderly and about 20% of these patients present metastasis at diagnosis, most often in the liver. Other common metastatic sites include: lung, bone and brain. Isolated splenic metastases are rare, and they are usually a sign of widespread disease. The authors report a case of the rare occurrence of synchronous isolated splenic metastasis, diagnosed by computed tomography in the preoperative staging of a patient with CRC.

Angiogenic factors: role in esophageal cancer, a brief review

Esophageal cancer has an aggressive behavior with rapid tumor mass growth and frequently poor prognosis; it is known as one of the most fatal types of cancer worldwide. The identification of potential molecular markers that can predict the response to treatment and the prognosis of this cancer has been subject of a vast investigation in the recent years. Among several molecules, various angiogenic factors that are linked to the tumor development, growth, and invasion, such as VEGF, HGF, angiopoietin-2, IL-6, and TGF-B1, were investigated. In this paper, the authors sought to review the role of these angiogenic factors in prognosis and hypothesize how they can be used as a treatment target.

Ki-67 Expression in CRC Lymph Node Metastasis Does Not Predict Survival

Colorectal 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.

Evaluation of quality parameters of rectal cancer surgery at the Coloproctology Unit of Hospital de Braga

INTRODUCTION: 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 treated with pressurized intraperitoneal aerosol chemotherapy: revising an option for peritoneal carcinomatosis

Aim: Gastric cancer is the cancer with the highest rate of peritoneal metastization and this type of spread is associated with a higher death rate compared to distant organ metastasis. The systemic chemotherapy has a minimal effect in peritoneal metastasis so new types of treatment have emerged. The authors revised the main studies done in pressurized intraperitoneal aerosol chemotherapy (PIPAC) and presented the main conclusions. Methods: A PubMed search was conducted focusing on PIPAC in gastric cancer. The MeSH database was searched with the terms: “Gastric cancer [MeSH] and intraperitoneal aerosol chemotherapy”. Results: Seven studies were analyzed. All the studies performed the technique with aerosol of doxorubicin and cisplatin. All cases were well tolerated, with minor adverse effects. Patients presented resolution of their abdominal symptoms and regression of macroscopic carcinomatosis. Cytoreductive surgery or hypertermic intraperitoneal chemotherapy could be performed in some patients with good response to PIPAC. The peritonitis caused by the chemotherapy was well tolerated. Conclusion: PIPAC can induce remission in end-stage and resistant disease with acceptable side effects, good safety levels for patients and health professionals, and quality of life improvement.