Non-steroidal anti-inflammatory drugs in cancer prevention and therapy

Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) can be regarded as an effective approach for cancer chemoprevention, as demonstrated by a bulk of clinical and experimental evidence. However, the clinical use of these drugs as chemopreventive agents is limited by many open questions about the optimal drug, dose, duration of therapy and knowledge about the mechanism(s) by which these drugs act. In particular, the recent data on cardiovascular toxicity of coxibs has posed some limitations on the use of NSAIDs for cancer chemoprevention in the general population. The situation is different in certain genetically susceptible subgroups, such as in individuals with genetic mutations associated with hereditary nonpolyposis colon cancer (HNPCC) or familiar adenomatous polyps (FAP) in whom lifetime risk increases up to 70-90% and in whom the benefit of a chemopreventive drug might justify its use even in the presence of adverse effects

Non-steroidal anti-inflammatory drugs in cancer prevention and therapy

Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) can be regarded as an effective approach for cancer chemoprevention, as demonstrated by a bulk of clinical and experimental evidence. However, the clinical use of these drugs as chemopreventive agents is limited by many open questions about the optimal drug, dose, duration of therapy and knowledge about the mechanism(s) by which these drugs act. In particular, the recent data on cardiovascular toxicity of coxibs has posed some limitations on the use of NSAIDs for cancer chemoprevention in the general population. The situation is different in certain genetically susceptible subgroups, such as in individuals with genetic mutations associated with hereditary nonpolyposis colon cancer (HNPCC) or familiar adenomatous polyps (FAP) in whom lifetime risk increases up to 70-90% and in whom the benefit of a chemopreventive drug might justify its use even in the presence of adverse effects

Serum sE-selectin levels and carcinoembryonic antigen mRNA-expressing cells in peripheral blood as prognostic factors in colorectal cancer patients

This study analyzed the possible prognostic value of presurgical serum soluble (s)E-selectin levels and/or carcinoembryonic antigen (CEA) mRNA positivity in predicting the disease-free survival of colorectal cancer (CRC) patients

Liquid biopsy in cervical cancer: Hopes and pitfalls

Cervical cancer (CC) is the fourth most common cancer in women worldwide, with about 90% of cancer-related deaths occurring in developing countries. The geographical influence on disease evolution reflects differences in the prevalence of human papilloma virus (HPV) infection, which is the main cause of CC, as well as in the access and quality of services for CC prevention and diagnosis. At present, the most diffused screening and diagnostic tools for CC are Papanicolaou test and the more sensitive HPV-DNA test, even if both methods require gynecological practices whose acceptance relies on the woman’s cultural and religious background. An alternative (or complimen-tary) tool for CC screening, diagnosis, and follow-up might be represented by liquid biopsy. Here, we summarize the main methodologies developed in this context, including circulating tumor cell detection and isolation, cell tumor DNA sequencing, coding and non-coding RNA detection, and exosomal miRNA identification. Moreover, the pros and cons of each method are discussed, and their potential applications in diagnosis and prognosis of CC, as well as their role in treatment mon-itoring, are explored. In conclusion, it is evident that despite many advances obtained in this field, further effort is needed to validate and standardize the proposed methodologies before any clinical use

Analysis of adenomatous polyposis coli gene in thyroid tumours.

Familial adenomatous polyposis (FAP) is known to be associated with neoplasia of various tissues, including thyroid carcinoma. Germline mutations of the tumour-suppressor gene APC, responsible for the predisposition to FAP, may therefore be involved in the pathogenesis of these tumours. In this report the structure of the APC gene has been investigated in 26 thyroid tumours, at different stages of dedifferentiation, that were surgically excised from patients with a negative history of FAP. Approximately 35% of the APC gene coding region, where most of the mutations are clustered, has been analysed by a combination of single-strand conformation polymorphism and direct sequencing. No significant alterations could be demonstrated in any sample examined. It is concluded that, at least in patients not affected by FAP, APC gene abnormalities do not seem to play a relevant role in the pathogenesis of thyroid carcinoma

Predictive value of VEGF gene polymorphisms for metastatic colorectal cancer patients receiving first-line treatment including fluorouracil, irinotecan, and bevacizumab

The aim of this study is to evaluate the influence of germline vascular endothelial growth factor (VEGF) gene polymorphisms (VGPs) on the efficacy of the anti-VEGF antibody bevacizumab (Bev) in metastatic colorectal cancer (MCRC) patients

Prognostic value of carcinoembryonic antigen and vascular endothelial growth factor tumor tissue content in colorectal cancer

This study was designed to assess the prognostic significance of the combined measurement of vascular endothelial growth factor (VEGF) and carcinoembryonic antigen (CEA) tissue content with respect to relapse-free and overall survival of patients with colorectal cancer (CRC)

Prognostic value of soluble P-selectin levels in colorectal cancer

Measurement of soluble (s) P-selectin levels has been proposed as a diagnostic tool for monitoring the clinical course of human neoplasms. Thus, our study was aimed at analyzing the role of sP-selectin in association with clinicopathological variables in 181 patients with primary (n =149) or metastatic (n = 32) colorectal cancer (CRC), 34 patients with benign diseases and 181 control subjects. The results obtained showed that sP-selectin levels were higher in patients with CRC compared either to patients with benign disease (p = 0.006) or controls (p = 0.003). No differences were observed between the latter and patients with benign diseases. Increased median sP-selectin levels were significantly associated with the presence of distant metastasis (68.2 ng/ml vs. 48.6 ng/ml, p = 0.002). Of interest, carcinoembryonic antigen (CEA) levels were independently associated to sP-selectin (regression coefficient = 0.28, p < 0.002). Cox's proportional hazards survival analysis of primary CRC patients demonstrated that beside the stage of disease sP-selectin levels had an independent prognostic role in predicting recurrent disease (HR = 2.22, p = 0.019) and mortality from CRC (HR = 3.44, p= 0.017). These results suggest that measurement of plasma sP-selectin might represent a prognostic indicator in the management of patients with CRC

Soluble CD40 ligand plasma levels in lung cancer

: Tumor-induced platelet activation may cause the release of various cytokines, including CD40 ligand (CD40L). Activation of the CD40/CD40L pathway in human tumors may result in thrombin generation, which is known to be involved in angiogenesis. Thus, we investigated whether soluble (s)CD40L levels are increased in patients with lung cancer as a result of platelet and/or coagulation activation. EXPERIMENTAL DESIGN: Citrated plasma samples were obtained from 120 patients with different stages and histotypes of lung cancer and 60 age- and sex-matched control subjects. sCD40L, sP-selectin (marker of platelet activation), prothrombin fragment 1 + 2, and thrombin-antithrombin III complex levels (both markers of coagulative activation) were measured in all samples. RESULTS: Patients with lung cancer had median sCD40L levels higher than in control subjects (0.46 versus 0.13 ng/ml; P < 0.0001), although correlation with the stage of disease was not evident. Nonetheless, sCD40L levels were significantly higher in squamous cancer compared with adenocarcinoma (0.75 versus 0.27 ng/ml; P < 0.05). Moreover, median sCD40L levels were higher in stage IV compared with nonmetastatic squamous lung cancer (1.02 versus 0.61 ng/ml; P < 0.05). sCD40L levels significantly correlated with sP-selectin (P < 0.001), prothrombin fragment 1 + 2 (P < 0.001), or thrombin-antithrombin III complex (P < 0.05) in squamous lung cancer, but only sP-selectin (P = 0.011) was independently related to sCD40L. CONCLUSIONS: These findings indicate that elevated sCD40L levels can be preferentially found in patients with advanced squamous cancer and provide evidence that increased levels of this cytokine are associated to the occurrence of in vivo platelet activatio

Prognostic significance of adiponectin levels in non-metastatic colorectal cancer

Circulating adiponectin levels are inversely correlated with the risk of colorectal cancer (CRC). This study was designed to evaluate the association between adiponectin levels and the clinicopathological variables of CRC and to analyze the possible prognostic value of adiponectin in predicting relapse-free survival