Additive cytotoxic effects of radiation and mTOR inhibitors in a cervical cancer cell line

The PI3 K/AKT/mTOR signaling pathway is frequently activated in HPV-positive cervical squamous cell cancer (CC). This study investigated the biological effects of mTOR inhibitors associated with radiotherapy in a CC cell line (HeLa). A human keratinocyte cell line (HaCaT) was used as control. Temsirolimus, everolimus, resveratrol, curcumin and epigallocatechin gallate (EGCG) were the mTOR inhibitors assessed. The 50% cell cytotoxicity rate (CC₅₀) for each treatment was determined by MTT cell viability assay. Cells were pre-treated with mTOR inhibitors at CC₅₀ followed by radiotherapy (RT) at 2 Gy. Cell death profile after treatment with temsirolimus, resveratrol and curcumin was assessed with flow cytometry. Everolimus, temsirolimus, EGCG, resveratrol and curcumin were cytotoxic to HeLa. Radiation induced a statistically significant (p < 0.01) supra-additive cytotoxic effect in the cervical cancer cell line when combined with mTOR inhibitors. After a 24-h treatment, EGCG and resveratrol were more cytotoxic to HeLa cells than to HaCaT cells. After 48 h of treatment, resveratrol, curcumin and everolimus were more cytotoxic to HeLa cells when compared to HaCaT cells. After 24 h, temsirolimus induced late apoptosis or necrosis in HeLa cells. Based on these data, new studies with mTOR inhibitors as treatment options for cervical cancer are recommended, mainly combined to radiotherapy.     

Potentiation of anticancer-drug cytotoxicity by sea anemone pore-forming proteins in human glioblastoma cells.

The search for new drugs and treatment approaches is of particular importance for glioblastomas (GBMs), as with other types of malignant gliomas, as they are lethal without the available medical care. Current anticancer cocktails have failed to prolong survival beyond 1 year, in part owing to the natural resistance of GBM cells and to the toxic side effects of the available drugs. In many organisms, cell death can be induced by cytolysins, which are proteins that can form pores in biological membranes. Perhaps by facilitating drugs to enter into the cytosol, cytolysins might be used to increase the efficacy of conventional anticancer agents. Here, the cytotoxicity of two sea anemone pore-forming cytolysins, toxin Bc2, and equinatoxin (EqTx-II) were investigated. Toxin Bc2 and EqTx-II were cytotoxic against human U87 and A172 GBM cell lines either wild type or p53 mutant, a tumor suppressor frequently mutated in malignant gliomas. Moreover, noncytotoxic concentrations of Bc2 or EqTx-II potentiated the cytotoxicity induced by low dose concentrations of all classical chemotherapeutics agents tested: cytosine arabinoside, doxorubicin, and vincristine. In comparison with the cytotoxicity induced by each of these classical anticancer drugs alone, 10-300-fold less of the therapeutic drug was needed when combined with the cytolysins. These results are promising, since lower concentrations of chemotherapeutic drugs could reduce the adverse effects of chemotherapy.     

Analysis of the Ki-67 index in the vaginal epithelium of castrated rats treated with tamoxifen

OBJECTIVES:Vaginal atrophy and breast cancer are common conditions in postmenopausal women and tamoxifen is the standard endocrine treatment for hormone-sensitive tumors. The present study aimed to assess the effect of tamoxifen on Ki-67 protein expression in the vaginal epithelium of castrated rats.RESULTS:The mean index of Ki-67 expression in the rat vagina of groups I and II was 4.04±0.96 and 26.86±2.19, respectively (p<0.001).CONCLUSIONS:According to the results of the present study, tamoxifen, at the dose and treatment length used, induced a significant increase in the cell proliferation of the vaginal mucosa in castrated rats, as evaluated by Ki-67 protein expression.     

Factors Associated with Frailty Syndrome in Older Adults

The journal of nutrition, health & aging - Frailty is a common geriatric syndrome, characterized by a decrease in energy reserve and stress resistance, resulting in an accumulated decline of...     

Prevalence of morphometric vertebral fractures in old men and the agreement between different methods in the city of Recife,Brazil

Osteoporosis is relatively common in men and has a great impact on quality of life. Despite the importance of the subject, there are few studies regarding the prevalence of morphometric vertebral fractures in men and the associated risk factors. To determine the prevalence of morphometric vertebral fractures in elderly men by three different methods and the agreement between them, 234 asymptomatic men aged >60 years (mean age 69.4 ± 6.5 years) were evaluated using lateral thoracolumbar radiograph that were analyzed by two experienced radiologists according to semiquantitative (SQ) Genant and algorithm-based qualitative (ABQ) Jiang methods. A third senior radiologist adjudicated Genant’s method. The highest prevalence of fractures in ABQ Jiang and SQ Genant methods were 37.6 and 36.8 %, respectively (both examiner 2). The lowest prevalence rates were 26.5 % in ABQ Jiang method and 5.6 % in SQ Genant (both examiner 1). The prevalence found by the Genant adjudicated was 31.6 %. The agreement between the examiners were 69.2 % in ABQ Jiang method (κ 0.30; 95 % CI 0.17–0.43) and 65.5 % in SQ Genant (κ 0.09; 95 % CI 0.01–0.17). We evaluated skin phototype, waist circumference, hypertension, body mass index (BMI), history of fracture, calcium intake, serum 25 OHD and sun index. After multivariate regression analysis, we found that lower BMI (prevalence ratio = 1.41; p = 0.024; 95 % CI 1.05–2.03) and sun index (prevalence ratio = 1.45; p = 0.049; 95 % CI 1.01–1.95) were independently associated with morphometric vertebral fractures.