Factors influencing quality of life in Moroccan postmenopausal women with osteoporotic vertebral fracture assessed by ECOS 16 questionnaire

<p>Abstract</p> <p>Objective</p> <p>The aim of the study was to evaluate factors influencing quality of life (QOL) in Moroccan postmenopausal women with osteoporotic vertebral fracture assessed by the Arabic version of ECOS 16 questionnaire.</p> <p>Methods</p> <p>357 postmenopausal women were included in this study. The participants underwent bone mineral density (BMD) measurements by DXA of the lumbar spine and the total hip as well as X-ray examination of the thoraco-lumbar spine to identify subclinical vertebral fractures. Patients were asked to complete a questionnaire on clinical and sociodemographic parameters, and osteoporosis risk factors. The Arabic version of the ECOS16 (Assessment of health related quality of life in osteoporosis questionnaire) was used to assess quality of life.</p> <p>Results</p> <p>The mean age was 58 ± 7.8 years, and the mean BMI was 28.3 ± 4.8 kg/m². One hundred and eight women (30.1%) were osteoporotic and 46.7% had vertebral fractures. Most were categorized as Grade1 (75%). Three independent factors were associated with a poor quality of life: low educational level (p = 0,01), vertebral fracture (p = 0,03), and history of peripheral fracture (p = 0,006). Worse QOL was observed in the group with vertebral fracture in all domains except "pain": Physical functioning (p = 0,002); Fear of illness (p = 0,001); and Psychosocial functioning (p = 0,007). The number of fractures was a determinant of a low QOL, as indicated by an increased score in physical functioning (p = 0,01), fear of illness (p = 0,007), and total score (p = 0,01) after adjusting on age and educational level. Patients with higher Genant score had low QOL in these two domains too (p = 0,002; p = 0,001 respectively), and in the total score (p = 0,01) after adjusting on age and educational level.</p> <p>Conclusion</p> <p>Our current data showed that the quality of life assessed by the Arabic version of the ECOS 16 questionnaire is decreased in post menopausal women with prevalent vertebral fractures, with the increasing number and the severity of vertebral fractures.</p

Dynamic evaluation of circulating mirna profile in egfr‐ mutated nsclc patients treated with egfr‐tkis

Background: Resistance to EGFR‐TKIs constitutes a major challenge for the management of EGFR‐mutated NSCLC, and recent evidence suggests that deregulation of specific microRNAs (miRNAs) may influence resistance to targeted agents. In this retrospective study, we explored the role of specific plasmatic miRNAs (miR‐21, miR‐27a and miR‐181a) as a surrogate for predicting EGFR‐TKI performance in EGFR‐mutated NSCLC patients. Methods: Plasma samples of 39 advanced EGFR‐mutated NSCLC patients treated with EGFR‐TKIs were collected at different points in time and miRNA levels were assessed by RT‐PCR. Results: Higher basal values of miR‐21 were reported in patients who achieved a partial/complete response (PR/CR) compared to those with stability/progression of disease (SD/PD) (p = 0.011). Along the same line, patients who experienced a clinical benefit lasting at least six months displayed higher basal levels of circulating miR‐21 (p = 0.039). However, dynamic evaluation of miRNA values after two months from the start of EGFR‐TKI treatment showed that patients who experienced SD had an increase in miR‐21 levels (Fold Change [FC] = 2.6) compared to patients achieving PR/CR (p = 0.029). The same tendency was observed for miR‐27a (FC = 3.1) and miR‐181a (FC = 2.0), although without reaching statistical significance. Remarkably, preclinical studies showed an increase in miR‐21 levels in NSCLC cells that became resistant after exposure to EGFR‐TKIs. Conclusions: Our study provides interesting insights on the role of circulating miRNAs, in particular miR‐21, and their dynamic change over time in predicting EGFR‐TKI response in EGFR‐mutated NSCLC

3-(6-Phenylimidazo [2,1-b][1,3,4]thiadiazol-2-yl)-1HIndole derivatives as new anticancer agents in the treatment of pancreatic ductal adenocarcinoma

A new series of imidazo[2,1-b][1,3,4]thiadiazole derivatives was efficiently synthesized and screened for their in vitro antiproliferative activity on a panel of pancreatic ductal adenocarcinoma (PDAC) cells, including SUIT-2, Capan-1 and Panc-1. Compounds 9c and 9l, showed relevant in vitro antiproliferative activity on all three pre-clinical models with half maximal inhibitory concentration (IC50) ranging from 5.11 to 10.8 μM, while the compounds 9e and 9n were active in at least one cell line. In addition, compound 9c significantly inhibited the migration rate of SUIT-2 and Capan-1 cells in the scratch wound-healing assay. In conclusion, our results will support further studies to increase the library of imidazo [2,1-b][1,3,4] thiadiazole derivatives for deeper understanding of the relationship between biological activity of the compounds and their structures in the development of new antitumor compounds against pancreatic diseases

PO-042 Targeting hypoxic pancreatic cancer cells with glucose conjugated lactate dehydrogenase inhibitor NHI-Glc-2

Introduction Pancreatic ductal adenocarcinoma (PDAC) is an abysmal disease with a 5 year survival rate of merely 8%. The tumour microenvironment is one of the factors contributing to PDAC chemoresistance. More specifically, the hypoxic tumour cores and the metabolic switch to aerobic glycolysis (e.g. the Warburg effect), contribute to the lack of drug response. Interestingly, two glycolysis components glucose transporter 1 (GLUT-1) and lactate dehydrogenase A (LDH-A) are overexpressed in PDAC. The latter, LDH-A, is also correlated with prognosis in metastatic PDAC. N-Hydroxyindole-based LDH-A inhibitors (NHI-1 and NHI-2) have shown a synergistic effect in hypoxic PDAC cells when combined with gemcitabine. A glucose conjugated NHI-Glc-2 was designed to exploit the GLUT-1 overexpression in PDAC cells and in the present study we evaluated whether this novel compound further improved the pharmacological effect of LDH-A inhibitors. Material and methods The effect of NHI-Glc-2 on cell growth is tested in our primary PDAC cancer cell cultures, characterised for their hypoxic signature and LDH-A/GLUT-1 expression levels by next-generation sequencing. Inhibition of cell and tumour growth was evaluated by the SRB assay, 3D spheroid-cultures and with an orthotopic bioluminescent in vivo model. Additionally, LDH-A enzyme activity inhibition and the effect on the glycolytic rate by NHI-Glc-2 were assessed by spectrophotometry and with the Seahorse XF analyzer, respectively. Results and discussions NHI-Glc-2 is capable of inhibiting PDAC cell growth in, especially in hypoxia, in nanomolar range and shows a synergistic effect with gemcitabine. In 3D cultures NHI-Glc-2 disrupts spheroid integrity, and preliminary in vivo studies show promising results. Conclusion Lactate dehydrogenase A is a viable target in PDAC, and the novel LDH-A inhibitor showed improved pharmacological effect in normoxic and hypoxic PDAC cells compared to NHI-1 and NHI-2. Moreover, this compound displays a synergistic cytotoxic activity with gemcitabine, offering an innovative tool in hypoxic tumours