Measurement of ATP6V1C1 expression in brush cytology samples as a diagnostic and prognostic marker in oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity. Brush cytology has reemerged as a molecular tool for diagnosing this cancer. ATP6V1C1, one of the main genes regulating V-ATPase activity, has been implicated in metastasis and multiple drug resistance. The aim of this study was to measure ATP6V1C1 expression levels in OSCC and to evaluate the value of this test in the diagnosis and prognosis of OSCC. RESULTS: The differences in ATP6V1C1 expression between patients and controls were statistically significant (Mann-Whitney U test = 26, p < 0.001). Receiver operating characteristic (ROC) curve analysis showed an area under the curve of 0.9476, with the following diagnostic indices: sensitivity, 81.25%, specificity, 93.75%; accuracy, 87.50%; positive predictive value, 92.86%; negative predictive value, 83.33%; positive likelihood ratio, 30; and negative likelihood ratio, 0.06. MATERIAL AND METHODS: Patients with OSCC and a control group of healthy individuals were studied. The clinical and demographic variables analyzed included age, sex, smoking, tumor location and tumor stage. Brush cytology samples were obtained using a cytology brush and analyzed by real-time quantitative polymerase chain reaction for ATP6V1C1 expression. CONCLUSIONS: It was confirmed that ATP6V1C1 levels were significantly higher in patients with OSCC than in healthy controls, with expression increasing with higher tumor stage. ROC analysis showed that the measurement of ATP6V1C1 expression levels is a highly sensitive and specific diagnostic method.

Multidrug resistance in oral squamous cell carcinoma: The role of vacuolar ATPases.

Resistance to chemotherapy agents is the main reason for treatment failure in patients with cancer. Multidrug resistance (MDR) is the primary mechanism that leads to the acquisition of the multiresistant phenotype through the overexpression of drug efflux transporters such as the P-glycoprotein (Pgp), encoded by the MDR1 gene, at the plasma membrane. Other molecules that have been implicated in drug resistance include multidrug resistance-associated proteins, glutathione S-transferase-pi, and DNA topoisomerase II. These molecules, however, cannot fully explain MDR in oral squamous cell carcinoma. Vacuolar ATPase (V-ATPase), which is largely responsible for regulating acidity in the microenvironment of solid tumors (and hence interfering with the absorption of chemotherapy drugs), seems to be the most important molecule involved in MDR in such tumors. Specific V-ATPase inhibitors, thus, may be useful, not only as coadjuvants in antitumor treatments but also as a mechanism for controlling resistance to antitumor drugs.

RANK/RANKL/OPG role in distraction osteogenesis.

Distraction osteogenesis is a fundamental pillar for craniomaxillofacial reconstruction processes. Nonetheless, although the clinical, biomechanical, and histologic changes associated with distraction osteogenesis have been widely described, this is not the case with the molecular mechanisms that regulate bone synthesis in the interfragmentary gap resulting from the gradual separation of bone segments. Recent studies have attributed a decisive role to the RANK/RANKL/OPG system in regulating bone metabolism and osteoclastogenesis. Receptor activator of nuclear factor kappa beta (RANK), belonging to the tumor necrosis factor superfamily, is present in the osteoclasts. It promotes osteoclastogenesis when it binds to RANK ligand (RANKL), which is produced by the osteoblasts and other stromal cells. Osteoprotegerin (OPG) acts as a decoy receptor by binding to RANKL and preventing RANK signaling. Osteoclast activation is thus blocked and apoptosis induced. The aim of this review is to analyze the influence of the RANK/RANKL/OPG system on the bone healing and remodeling processes that occur in distraction osteogenesis, with a view to possibly developing molecular mechanisms that stimulate bone regeneration and inhibit resorption, thereby improving the clinical outcome for distraction osteogenesis.

V-ATPase inhibitors and implication in cancer treatment.

Acidity is one of the main features of the tumors. The V-ATPase is the primary responsible for the control of tumor microenvironment by proton extrusion to the extracellular medium. The acid environment favors tissue damage, activation of destructive enzymes in the extracellular matrix, the acquisition of metastatic cell phenotypes as well as increasing the destructive capacity. The application of specific inhibitors of V-ATPases, can decrease the acidity of tumor and may allow the reduction of tumor metastasis, acting on the survival of tumor cells and prevent the phenomena of chemoresistance. Among the most important inhibitors can be distinguished benzolactone enamides (salicylihalamide), lobatamide A and B, apicularen, indolyls, oximidine, macrolactone archazolid, lobatamide C, and cruentaren. The latest generation of inhibitors includes NiK12192, FR202126, and PPI SB 242784. The purpose of this paper is to describe the latest advances in the field of V-ATPase inhibitors, describe further developments related to the classic inhibitors, and discuss new potential applications of these drugs in cancer treatment.

Palatal approach for maxillary alveolar distraction.

PURPOSE: The purpose of this report was to describe a surgical technique for performing alveolar distraction in the upper jaw via a palatal approach. PATIENTS AND METHODS: To illustrate this technique we report 2 clinical cases in which palatal-approach alveolar distraction was used to rectify insufficient alveolar rim height. The first case involves a 50-year-old man with atrophy of the alveolar rim in the posterior upper jaw. From the palatal side, a transport segment pedicled to the vestibular mucosa was cut, and 2 Lead System distractors (Leibinger, Kalamazoo, MI) were placed. The second case involves a 23-year-old woman with a bone defect in the alveolar rim in the premaxillary sector of the upper jaw. Again, from the palatal side, a transport segment pedicled to the vestibular mucosa was cut, and a single Lead System distractor was placed. RESULTS: In both cases the height of the alveolar rim was successfully increased by 8 mm, allowing placement of three 12-mm implants in case 1, and two 12-mm implants in case 2. CONCLUSIONS: We recommend a palatal approach and intraosseous distractors for alveolar distraction in the upper jaw.