Cancer Initiation,Progression and Resistance: Are Phytocannabinoids from Cannabis sativa L. Promising Compounds?

Cannabis sativa L. is a source of over 150 active compounds known as phytocannabinoids that are receiving renewed interest due to their diverse pharmacologic activities. Indeed, phytocannabinoids mimic the endogenous bioactive endocannabinoids effects through activation of CB1 and CB2 receptors widely described in the central nervous system and peripheral tissues. All phytocannabinoids have been studied for their protective actions towards different biological mechanisms, including inflammation, immune response, oxidative stress that, altogether, result in an inhibitory activity against the carcinogenesis. The role of the endocannabinoid system is not yet completely clear in cancer, but several studies indicate that cannabinoid receptors and endogenous ligands are overexpressed in different tumor tissues. Recently, in vitro and in vivo evidence support the effectiveness of phytocannabinoids against various cancer types, in terms of proliferation, metastasis, and angiogenesis, actions partially due to their ability to regulate signaling pathways critical for cell growth and survival. The aim of this review was to report the current knowledge about the action of phytocannabinoids from Cannabis sativa L. against cancer initiation and progression with a specific regard to brain, breast, colorectal, and lung cancer as well as their possible use in the therapies. We will also report the known molecular mechanisms responsible for such positive effects. Finally, we will describe the actual therapeutic options for Cannabis sativa L. and the ongoing clinical trials.     

Existence and multiplicity of solutions for a nonlinear Neumann problem

We consider a Neumann problem of the type -εΔu+F ^′(u(x))=0 in an open bounded subset Ω of R ⁿ , where F is a real function which has exactly k maximum points. Using Morse theory we find that, for ε suitably small, there are at least 2k nontrivial solutions of the problem and we give some qualitative information about them. Received: October 30, 1999 Published online: December 19, 2001     

Chiral recognition in aqueous solutions. Preferential configurations of α-aminoacids bearing substituted alkyl chains at 25°C

Calorimetric measurements were carried out at 25°C on binary and ternary aqueous solutions containing L and D forms fo the following -aminoacids: tryptophan, cysteine, methionine, phenylalanine, histidine, threonine, and citrulline, which contain both hydrophilic and hydrophobic domains. Differences were found between the values of the homochiral and heterochiral pairwise enthalpic interaction coefficients for tryptophan, cysteine, and methionine. To the contrary, chiral recognition was not detected for phenylalanine, histidine, citrulline, and threonine. The data were interpreted in terms of a preferential configuration model. Chiral recognition is detected only when the interactions of the side chains in the homo- and heterochiral configurations are different. Chiral recognition disappears when a competition exists between zwitterion-zwitterion interactions and side chain-side chain interactions. In some cases, such as for citrulline, compensation effects can occur due to thermal contributions from different domains which mask chiral recognition.     

Is styrene planar in liquid phases?

The proton NMR spectra of two (13)C-labeled isotopomers of styrene dissolved in two liquid crystalline solvents have been obtained and analyzed to yield four sets each of 24 dipolar couplings. These couplings were then used to investigate the structure of the ring and the ene fragments of the molecule, and the position of the maximum, phi(0), in the ring-ene bond rotational probability distribution. To do this, the effect on the dipolar couplings of small-amplitude vibrational motion was taken into account using vibrational wave functions calculated by molecular orbital and density functional methods. It is concluded that the NMR data are consistent with the ring fragment, averaged over the ring-ene rotation, planar, while the ene fragment is not. The value of phi(0) is found to be 18.0 degrees +/-0.2 degrees for the two solutions, compared with a value of 27 degrees calculated by the molecular method MP2/6-31G(*).     

Constitution moleculaire d'α,ω-difluoropolydimethylsiloxanes equilibres obtenus par une reaction de redistribution

α,ω-Difluoropolydimethylsiloxanes F[(CH₃)₂SiO]_n(CH₃)₂SiF have been prepared by reaction of (CH₃)₂SiF₂ with cyclic dimethylsiloxanes [(CH₃)₂SiO]_n (n = 3 or 4). An equilibrium is reached in the redistribution of fluorine vs. oxygen atoms after ca. 24 h at 200°C or 15 days at 150°C when catalysed by AlCl₃. 16 equilibrated samples of varied (R = F/Si) overall compositions have been analysed by ¹H and ¹⁹F NMR and by VPC. The presence of rings has been established for the lower values of R. The molecular constitution of the equilibrated samples is described by a set of constants. The abundance of the end units

is slightly larger than expected from random distribution. The good resolution of the spectra permits the distinguishing of the 9th order of environment of the end units and the 5th order for the middle units and the verification that there is no preferential association among the building units, and thus the proportion of chains of various lengths obeys Flory's random distribution mode. The equilibrium molecular constitution of these α,ω-difluorosiloxanes is close to that of their dichloro analogs; the substitution of chlorine by fluorine atoms at the end of the chains thus appears to cause little perturbation. On the other hand, the kinetic evolution of the reaction appears to be different, since the first species which forms is always the pyro molecule

instead of long chains and large rings as in the case of the chloro analogs.     

Formation of a nanostructured layer on bioglass particles of different sizes immersed in tris-buffered solution. N2 adsorption and HR-TEM/EDS analysis

Morphological and structural variations of particles of Bioglass with two different grain sizes reacted in Tris-buffered solution were analyzed by means of N(2) adsorption/desorption at 77 K and HR-TEM/EDS. A remarkable increase in specific surface area (ssa) was observed after the first hour of dissolution. A plateau value corresponding to an increase of at least 2 orders of magnitude was reached after 2 days of dissolution. The ssa increase was faster for the smaller particle size sample, and the ratio between the ssa of the starting samples was not maintained during dissolution. Both micro- and mesopores were formed at different stages of the reaction for the two samples. Increasing ssa was also connected to the formation of a microcrystalline structure rich in Ca and P, as shown by TEM images. The segregation of both a SiO(2)-rich amorphous phase and a Ca/P-rich crystalline phase was observed after the first hour of dissolution. After 2 days of reaction, Ca/P-rich particles made of fine aciculate crystals were found either in close contact with SiO(2) particles or deposited on a small SiO(2)-rich core. A preliminary analysis of TEM data showed the formation, together with hydroxy carbonate apatite, of different types of calcium phosphates not detectable by powder X-ray diffraction.     

Purification of NAD glycohydrolase from Neurospora crassa conidia by a polyclonal immunoadsorbent.

NAD glycohydrolase from Neurospora crassa conidia was purified by affinity chromatography on a column of polyclonal antibodies bound to an agarose matrix. The procedure was easy, non-denaturating and suitable for repetitive use of the gel. The enzyme obtained appeared homogeneous by sodiumdodecyl sulphate-polyacrylamide gel electrophoresis.