Molecular Biomarkers & Diagnosis

The cell cycle is under strict regulation. Cyclin-dependent kinases (CDKs) at the G1-S and G2-M checkpoints are positively regulated by cyclins and negatively regulated by CDK inhibitors. Oral squamous cell carcinoma (OSCC) is a common malignancy that is characterized by a high degree of local aggression and lymph node metastasis. We examined positive regulators of the cell cycle (cyclin A, cyclin B1, and cyclin D1), cell cycle inhibitors (p16, p21, p27, p53, and Rb), and the proliferation markers Ki-67 and topoisomerase IIA by immunohistochemistry in a tissue microarray, comprising 136 cases of OSCC. Expression of cyclin A, cyclin B1, cyclin D1, topoisomerase IIA, p53, and Rb was positively associated with Ki-67. Overexpression of cyclin D1 correlated with the presence of lymph node metastasis. Overexpression of cyclin A, cyclin D1, topoisomerase IIA, and Rb and downregulation of p21 and p27 were associated with reduced overall survival in OSCC patients. Cyclin A, p21 and p27, were implicated an independent prognostic factor, by multivariate analysis, in OSCC patients. In conclusion, cyclin A, cyclin D1, p21 and p27 expression can be a valuable marker of poor prognosis and tumor aggressiveness in OSCC.

Triple-negative breast cancers account for 10-17% of all breast carcinomas and there is considerable need for reliable prognostic markers to assist clinicians in making diagnostic and therapeutic management decisions. Altered ANXA7 (a novel pro-apoptotic tumor suppressor gene located on chromosome 10q21) protein levels are associated with a tumor-prone phenotype in knockout mouse model and prognostically challenging aggressive forms of prostate and breast cancer. So far, information is not available regarding the association of patient survival and ANXA7 expression in triple-negative breast cancers. Therefore, we used a retrospective prognostic tumor tissue microarray (TMA) technology in order to evaluate the ANXA7 immunoreactivity as a possible diagnostic and/ or prognostic marker of triple-negative breast cancer by immunoperoxidase assay using an ANXA7 monoclonal antibody. We report here that the expression of ANXA7 is significantly enhanced in triple-negative breast cancers and is associated with poor overall patient survival. We conclude that ANXA7 may be a new prognostic markers or a target for improving the treatment efficiency of patients with triple-negative breast cancers.

From a historical point of view, treatment of neoplastic disease can be considered one of the clearest example of the importance of combination strategies. In fact, a combination of surgery, radiotherapy and chemotherapy, is the best approach for the treatment of certain cancers such as breast cancer, ovarian and head and neck cancer. However, not only cancer may benefit from combination therapy. Tubercolosis is a classical example of this concept [1]. After the discovery of Streptomycin in 1944, a new era for the treatment of tubercolosis dawned with further detection of Isoniazid, the first oral mycobactericidal drug in 1952 and Rifamycins in 1957. Sanatoria closed and truly effective public health measures became possible. Treatment was also increasingly expanded to include those with latent tuberculous infections. Furthermore, the introduction of Rifampicin in 1970 revolutionized the treatment of tuberculosis as, with its use in the context of combination strategies, the therapy of this infectious disease changed. In fact, use of antituberculosis drugs in monotherapy, including those of first choice, is strictly proscribed, since it might be easy to select spontaneously resistant germs. For this reason, drug regimens include associations of 3 or more drugs, variously alternated in relation to the clinical and developmental stages of tuberculosis (Table 1). Another aim of using drugs in combination was to eliminate bacterial subpopulations in various stages of metabolic activity and at different locations.