Surgical treatment of orbital tumors in a single center: Analysis and results.

Background: Orbital tumors, arising within the bony orbit and its contents, present diverse challenges due to their varied origins and complex anatomical context. These tumors, classified as primary, secondary, or metastatic, are further subdivided into intraconal and extraconal based on their relationship with the muscle cone. This classification significantly influences surgical approach and management. This study highlights surgical experiences with orbital tumors, underscoring the importance of tailored surgical approaches based on the lesion's site and its proximity to the optic nerve. Methods: This retrospective study at the National Institute of Cancer's Head and Neck Department (2005-2014) analyzed 29 patients with orbital tumors treated with surgery, radiotherapy, chemotherapy, or combinations of them. Patient demographics, tumor characteristics, and treatment responses were evaluated using computed tomography (CT), magnetic resonance imaging, and positron emission tomography-CT imaging. Malignant tumors often required orbital exenteration and reconstruction, highlighting the study's commitment to advancing orbital tumor treatment. Results: 29 patients (18 females and 11 males, age 18-88 years, mean 53.5 years) with orbital tumors exhibited symptoms such as decreased vision and exophthalmos. Tumors included primary lesions like choroidal melanoma and secondary types like epidermoid carcinoma. Treatments varied, involving a multidisciplinary team for surgical approaches like exenteration, with follow-up from 1 to 9 years. Radiotherapy and chemotherapy were used for specific cases. Conclusion: Our study underscores the need for a multidisciplinary approach in treating orbital tumors, involving various surgical specialists and advanced technologies like neuronavigation for tailored treatment. The integration of surgery with radiotherapy and chemotherapy highlights the effectiveness of multidimensional treatment strategies.

Negative Regulation of Serine Threonine Kinase 11 (STK11) through miR-100 in Head and Neck Cancer.

BACKGROUND: Serine Threonine Kinase 11 (STK11), also known as LKB1, is a tumor suppressor gene that regulates several biological processes such as apoptosis, energetic metabolism, proliferation, invasion, and migration. During malignant progression, different types of cancer inhibit STK11 function by mutation or epigenetic inactivation. In Head and Neck Cancer, it is unclear what mechanism is involved in decreasing STK11 levels. Thus, the present work aims to determine whether STK11 expression might be regulated through epigenetic or post-translational mechanisms. METHODS: Expression levels and methylation status for STK11 were analyzed in 59 cases of head and neck cancer and 10 healthy tissue counterparts. Afterward, we sought to identify candidate miRNAs exerting post-transcriptional regulation of STK11. Then, we assessed a luciferase gene reporter assay to know if miRNAs directly target STK11 mRNA. The expression levels of the clinical significance of mir-100-3p, -5p, and STK11 in 495 HNC specimens obtained from the TCGA database were further analyzed. Finally, the Kaplan-Meier method was used to estimate the prognostic significance of the miRNAs for Overall Survival, and survival curves were compared through the log-rank test. RESULTS: STK11 was under-expressed, and its promoter region was demethylated or partially methylated. miR-17-5p, miR-106a-5p, miR-100-3p, and miR-100-5p could be negative regulators of STK11. Our experimental data suggested evidence that miR-100-3p and -5p were over-expressed in analyzed tumor patient samples. Luciferase gene reporter assay experiments showed that miR-100-3p targets and down-regulates STK11 mRNA directly. With respect to overall survival, STK11 expression level was significant for predicting clinical outcomes. CONCLUSION: This is, to our knowledge, the first report of miR-100-3p targeting STK11 in HNC. Together, these findings may support the importance of regulation of STK11 through post-transcriptional regulation in HNC and the possible contribution to the carcinogenesis process in this neoplasia.

Proliferation and apoptosis of HeLa cells induced by in vitro stimulation with digitalis.

In the HeLa tumor cell line, we studied the characteristics of the dual effect of digitalis compounds on cell growth (proliferation and death). In addition, we explored whether both effects occur by means of the same mechanism. HeLa cell cultures were exposed to increasing concentrations (0.01 nM-10 microM) of ouabain, strophantidin, digoxin, and digoxigenin at 24-96 h intervals. Cell growth in treated cultures was compared with cell growth under nontreated conditions. Additionally, we studied changes in nuclear morphology, as well as in genomic DNA degradation, cytochrome c release, and caspase-9 and -3 presence and processing induced by toxic concentrations of digitalis. Digitalis compounds increased HeLa cell number when exposed to concentrations <10 nM during a 48 h period. Ethacrynic acid (a nonsteroid inhibitor for Na+/K+-ATPase) did not induce cell growth at these concentrations. Digitalis concentrations >10 nM induced cell death in a concentration- and exposure period-dependent fashion. Changes in nuclear morphology, DNA fragmentation, mitochondrial cytochrome c release, and proteolytic processing of caspases-9 and -3, suggest apoptotic cell death. The IC50 for the inducing effect of apoptosis by ouabain at 96 h was 18 nM and corresponds with the IC50 for the Na+/K+-ATPase inhibition in HeLa cells. In conclusion, the dual effect of digitalis compounds on HeLa cells growth is concentration and time-dependent. The apoptosis-inducing effect correlates with inhibition of Na+/K+-ATPase. Proliferation does not appear to be mediated through this pathway. The apoptosis-induction pathway is possibly cytochrome c-dependent.