Inhibition of telomerase activity preferentially targets aldehyde dehydrogenase-positive cancer stem-like cells in lung cancer

<p>Abstract</p> <p>Background</p> <p>Mortality rates for advanced lung cancer have not declined for decades, even with the implementation of novel chemotherapeutic regimens or the use of tyrosine kinase inhibitors. Cancer Stem Cells (CSCs) are thought to be responsible for resistance to chemo/radiotherapy. Therefore, targeting CSCs with novel compounds may be an effective approach to reduce lung tumor growth and metastasis. We have isolated and characterized CSCs from non-small cell lung cancer (NSCLC) cell lines and measured their telomerase activity, telomere length, and sensitivity to the novel telomerase inhibitor MST312.</p> <p>Results</p> <p>The aldehyde dehydrogenase (ALDH) positive lung cancer cell fraction is enriched in markers of stemness and endowed with stem cell properties. ALDH+ CSCs display longer telomeres than the non-CSC population. Interestingly, MST312 has a strong antiproliferative effect on lung CSCs and induces p21, p27 and apoptosis in the whole tumor population. MST312 acts through activation of the ATM/pH2AX DNA damage pathway (short-term effect) and through decrease in telomere length (long-term effect). Administration of this telomerase inhibitor (40 mg/kg) in the H460 xenograft model results in significant tumor shrinkage (70% reduction, compared to controls). Combination therapy consisting of irradiation (10Gy) plus administration of MST312 did not improve the therapeutic efficacy of the telomerase inhibitor alone. Treatment with MST312 reduces significantly the number of ALDH+ CSCs and their telomeric length <it>in vivo</it>.</p> <p>Conclusions</p> <p>We conclude that antitelomeric therapy using MST312 mainly targets lung CSCs and may represent a novel approach for effective treatment of lung cancer.</p

Dark Matter Searches Using NaI(Tl) at the Canfranc Underground Laboratory: Past, Present and Future

Sodium Iodide Thallium doped (NaI(Tl)) scintillation detectors have been applied to the direct searches for dark matter since the 1980s and have produced one of the most challenging results in the field-the observation by the DAMA/LIBRA collaboration of an annual modulation in the detection rate for more than twenty cycles. This result is very difficult to reconcile with negative results derived from other experiments using a large variety of target materials and detection techniques. However, it has been neither confirmed nor refuted in a model independent way up to the present. Such a model independent test of the DAMA/LIBRA result is the goal of the ANAIS-112 experiment, presently in the data taking phase at the Canfranc Underground Laboratory in Spain. ANAIS-112 design and operation leans on the expertise acquired at the University of Zaragoza in direct searches for Dark Matter particles using different targets and techniques and in particular using NaI(Tl) scintillation detectors for about thirty years, which are reviewed in the first section of this manuscript. In addition to presenting the status and more recent results of the ANAIS-112 experiment, open research lines, continuing this effort, will be presented

Radon Mitigation Applications at the Laboratorio Subterraneo de Canfranc (LSC)

The Laboratorio Subterraneo de Canfranc (LSC) is the Spanish national hub for low radioactivity techniques and the associated scientific and technological applications. The concentration of the airborne radon is a major component of the radioactive budget in the neighborhood of the detectors. The LSC hosts a Radon Abatement System, which delivers a radon suppressed air with 1.1 & PLUSMN;0.2 mBq/m(3) of Rn-222. The radon content in the air is continuously monitored with an Electrostatic Radon Monitor. Measurements with the double beta decay demonstrators NEXT-NEW and CROSS and the gamma HPGe detectors show the important reduction of the radioactive background due to the purified air in the vicinity of the detectors. We also discuss the use of this facility in the LSC current program which includes NEXT-100, low background biology experiments and radiopure copper electroformation equipment placed in the radon-free clean room

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery