The impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen treatment in breast cancer patients

Tamoxifen is a standard therapeutical treatment in patients with estrogen receptor positive breast carcinoma. However, less than 50% of estrogen receptor positive breast cancers do not respond to tamoxifen treatment whereas 40% of tumors that initially respond to treatment develop resistance over time. The underlying mechanisms for tamoxifen resistance are probably multifactorial but remain largely unknown. The primary aim of this study was to investigate the impact of PTEN tumor suppressor gene on acquiring resistance to tamoxifen by analyzing loss of heterozygosity (LOH) and immunohystochemical expression of PTEN in 49 primary breast carcinomas of patients treated with tamoxifen as the only adjuvant therapy. The effect of PTEN inactivation on breast cancer progression and disease outcome was also analyzed. Reduced or completely lost PTEN expression was observed in 55.1% of samples, while 63.3% of samples displayed LOH of PTEN gene. Inactivation of PTEN immunoexpression significantly correlated with the PTEN loss of heterozygosity, suggesting LOH as the most important genetic mechanism for the reduction or complete loss of PTEN expression in primary breast carcinoma. Most importantly, LOH of PTEN and consequential reduction of its immunoexpression showed significant correlation with the recurrence of the disease. Besides, our study revealed that LOH of PTEN tumor suppressor was significantly associated with shorter disease free survival, breast cancer specific survival and overall survival. In summary, our results imply that LOH of PTEN could be used as a good prognostic characteristic for the outcome of breast cancer patients treated with tamoxifen

Microanatomical study of replaced meniscus in the rabbit.

We investigated clinical and morphological characteristics of replaced menisci after the transplantation of deep frozen meniscal allografts. We replaced medial menisci (in 18 New Zealand white rabbits) by meniscal grafts obtained fro m other rabbits. These grafts were kept in a deep f reezer (3-5 weeks), thawed in sterile saline and transplanted. The menisci were removed and studied after 2 weeks (first group), 8 weeks (second group) and after 36 weeks (third gro u p ) . Menisci from non-operated, contralateral knees served as controls. The tissue of the menisci investigated was processed using several histological and histochemical methods and analyzed by light microscope. Transplanted meniscal allografts retained a normal gross appearance, healed f i rmly through fibrovascular tissue to the re c i p i e n t capsular tissue, and did not show macro s c o p i c pathological changes. At the histological evaluation, in the first group the collagen fibers were i r regularly oriented, with a low cellular population. In the second group, blood vessels were p resent, cellular repopulation and immature collagen fibers being observed. The third group had a more mature collagen tissue, with a significant cell repopulation. Deep-frozen meniscal allografts showed significant collagen remodeling with cellular and vascular ingrowth from the surro u n d i n g synovia. This suggests that used allografts function normally and protect underlying cartilage

Monomerizing alkali-metal 3,5-dimethylbenzyl salts with tris(N, N -dimethyl-2-aminoethyl)amine (MeTREN) : structural and bonding implications

The series of alkali-metal (Li, Na, K) complexes of the substituted benzyl anion 3,5-dimethylbenzyl (MeCHCH ) derived from 1,3,5-trimethylbenzene (mesitylene) have been coerced into monomeric forms by supporting them with the tripodal tetradentate Lewis donor tris(N,N-dimethyl-2-aminoethyl)amine, [N(CH CHNMe), MeTREN]. Molecular structure analysis by X-ray crystallography establishes that the cation-anion interaction varies as a function of the alkali-metal, with the carbanion binding to lithium mainly in a σ fashion, to potassium mainly in a π fashion, with the interaction toward sodium being intermediate between these two extremes. This distinction is due to the heavier alkali-metal forcing and using the delocalization of negative charge into the aromatic ring to gain a higher coordination number in accordance with its size. MeTREN binds the metal in a η mode at all times. This coordination isomerism is shown by multinuclear NMR spectroscopy to also extend to the structures in solution and is further supported by density functional theory (DFT) calculations on model systems. A MeTREN stabilized benzyl potassium complex has been used to prepare a mixed-metal ate complex by a cocomplexation reaction with tBuZn, with the benzyl ligand acting as an unusual ditopic σ/π bridging ligand between the two metals, and with the small zinc atom relocalizing the negative charge back on to the lateral CH arm to give a complex best described as a contacted ion pair potassium zincate

Co-complexation syntheses, structural characterization, and DFT studies of a novel series of polymeric alkali-metal tetraorganogallates

Exploring the co-complexation reactions between the gallium alkyl Ga(CH2SiMe3)(3) and alkali-metal alkyl MCH2SiMe3 (M = Li, Na, or K) using an arene/hexane solvent mixture has allowed the isolation of solvent-free alkali-metal tetraorganogallates [{MGa(CH2SiMe3)(4)}(infinity)] (M = Li, 1; Na, 2) and related benzene adduct [{(C6H6)(2)KGa-(CH2SiMe3)(4))(infinity)] (3). By combining X-ray crystallography, NMR spectroscopy, and DFT calculations, this study sheds new light on the constitution of these mixed-metal species. Xray crystallographic studies reveal that all gallates exhibit novel polymeric arrangements, with 1 and 2 sharing the same linear chain structure, made up exclusively of M-C and Ga-C bonds, whereas 3 displays a significantly more open structural motif, where the K and Ga atoms are connected by a single alkyl bridge and propagation occurs via weaker K center dot center dot center dot Me electrostatic interactions of a methyl from a SiMe3 group of an alkyl ligand from one monomer to the potassium from a neighboring monomeric unit. Multinuclear NMR spectroscopic studies suggest that in deuterated benzene solutions 1-3 exist as discrete solvent-separated ion-pair species where the alkali-metal is solvated by the arene solvent. DFT calculations show that while the infinite aggregation of these polymeric structures is key for thermodynamically favoring the formation of 1 and 2, in the case of 3 the solvation of unsaturated potassium by two molecules of benzene, via pi-electrostatic interactions, appears to be the major contributor to its overall stability