In recent years, studies of cancer development and recurrence have been influenced by the cancer stem cells (CSCs)/cancer-initiating cells (CICs) hypothesis. According to this, cancer is sustained by ...highly positioned, chemoresistant cells with extensive capacity of self renewal, which are responsible for disease relapse after chemotherapy. Growth of cancer cells as three-dimensional non-adherent spheroids is regarded as a useful methodology to enrich for cells endowed with CSC-like features. We have recently reported that cell cultures derived from malignant pleural effusions (MPEs) of patients affected by adenocarcinoma of the lung are able to efficiently form spheroids in non-adherent conditions supplemented with growth factors. By expression profiling, we were able to identify a set of genes whose expression is significantly upregulated in lung tumor spheroids versus adherent cultures. One of the most strongly upregulated gene was stearoyl-CoA desaturase (SCD1), the main enzyme responsible for the conversion of saturated into monounsaturated fatty acids. In the present study, we show both by RNA interference and through the use of a small molecule inhibitor that SCD1 is required for lung cancer spheroids propagation both in stable cell lines and in MPE-derived primary tumor cultures. Morphological examination and image analysis of the tumor spheroids formed in the presence of SCD1 inhibitors showed a different pattern of growth characterized by irregular cell aggregates. Electron microscopy revealed that the treated spheroids displayed several features of cellular damage and immunofluorescence analysis on optical serial sections showed apoptotic cells positive for the M30 marker, most of them positive also for the stemness marker ALDH1A1, thus suggesting that the SCD1 inhibitor is selectively killing cells with stem-like properties. Furthermore, SCD1-inhibited lung cancer cells were strongly impaired in their in vivo tumorigenicity and ALDH1A1 expression. These results suggest that SCD1 is a critical target in lung cancer tumor-initiating cells.
Unilateral and solid-state nuclear magnetic resonance (NMR) analyses were performed on a parchment fragment of the Dead Sea Scroll (DSS). The analyzed sample belongs to the collection of ...non-inscribed and nontreated fragments of known archaeological provenance from the John Rylands University Library in Manchester. Therefore, it can be considered as original DSS material free from any contamination related to the post-discovery period. Considering the paramount significance of the DSS, noninvasive approaches and portable
in situ
nondestructive methods are of fundamental importance for the determination of composition, structure, and chemical–physical properties of the materials under study. NMR studies reveal low amounts of water content associated with very short proton relaxation times,
T
1
, indicating a high level of deterioration of collagen molecules within scroll fragments. In addition,
13
C cross-polarization magic-angle-spinning (CPMAS) NMR spectroscopy shows characteristic peaks of lipids whose presence we attribute to the production technology that did not involve liming. Extraction with chloroform led to the reduction of both lipid and protein signals in the
13
C CPMAS spectrum indicating probable involvement of lipids in parchment degradation processes. NMR absorption and relaxation measurements provide nondestructive, discriminative, and sensitive tools for studying the deterioration effects on the organization and properties of water and collagen within ancient manuscripts.
Fig
The state of deterioration of a Dead Sea scroll fragment was studied by means of
1
H and
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C solid state NMR and proton
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relaxation measurements
We report a measurement of the energy spectrum of cosmic rays above 2.5×1018 eV based on 215030 events. New results are presented: at about 1.3×1019 eV, the spectral index changes from ...2.51±0.03(stat)±0.05(syst) to 3.05±0.05(stat)±0.10(syst), evolving to 5.1±0.3(stat)±0.1(syst) beyond 5×1019 eV, while no significant dependence of spectral features on the declination is seen in the accessible range. These features of the spectrum can be reproduced in models with energy-dependent mass composition. The energy density in cosmic rays above 5×1018 eV is 5.66±0.03(stat)±1.40(syst)×1053 erg Mpc-3.
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