Vitamin D Compounds PRI-2191 and PRI-2205 Enhance Anastrozole Activity in Human Breast Cancer Models

1,25-Dihydroxycholecalciferol, the hormonally active vitamin D₃ metabolite, is known to exhibit therapeutic effects against breast cancer, mainly by lowering the expression of estrogen receptors and aromatase activity. Previously, the safety of the vitamin D active metabolite (24R)-1,24-dihydroxycholecalciferol (PRI-2191) and 1,25(OH)₂D₃ analog PRI-2205 was tested, and the in vitro activity of these analogs against different cancer cell lines was studied. We determined the effect of the two vitamin D compounds on anastrozole (An) activity against breast cancer based on antiproliferative activity, ELISA, flow cytometry, enzyme inhibition potency, PCR, and xenograft study. Both the vitamin D active metabolite and synthetic analog regulated the growth of not only estrogen receptor-positive cells (T47D and MCF-7, in vitro and in vivo), but also hormone-independent cancer cells such as SKBR-3 (HER-2-positive) and MDA-MB-231 (triple-negative), despite their relatively low VDR expression. Combined with An, PRI-2191 and PRI-2205 significantly inhibited the tumor growth of MCF-7 cells. Potentiation of the antitumor activity in combined treatment of MCF-7 tumor-bearing mice is related to the reduced activity of aromatase by both An (enzyme inhibition) and vitamin D compounds (switched off/decreased aromatase gene expression, decreased expression of other genes related to estrogen signaling) and by regulation of the expression of the estrogen receptor ERα and VDR.     

Thick film NO2 Sensor

 Thick film technology was used to manufacture a solid-state electrochemical nitrogen dioxide sensor. The prepared sensor has a linear dependence of electromotive force that is based in the NO₂ concentration level. This paper presents discussion on a thick-film sensor that has a much smaller dimension and shorter response time as compared to typical ceramic solid-state electrochemical devices. Received: 26 February 1996/Accepted: 27 June 1996     

The prognostic value of NCAM, p53 and cyclin D1 in resected non-small cell lung cancer

Expression of the neural cell adhesion molecule, NCAM, in frozen sections has been associated with decreased postoperative survival in non-small cell lung carcinoma. Of the various isoforms of NCAM described, the highly sialylated isoform plays a role in the migration of embryonal cells from the neural crest and is expressed by highly malignant tumours such as small cell lung carcinomas. We investigated the clinical significance of expression of this NCAM isoform as a prognostic factor in a series of 96 non-small cell lung carcinomas resected with curative intent. We also evaluated the effect of microwave pre-treatment of formalin-fixed, paraffin-embedded sections on the NCAM immunostaining and related the outcome to the postoperative clinical course of disease. In addition, in an attempt to extend our search for possible molecular markers of unfavourable prognosis in lung cancer, we evaluated increased immunostaining for p53 and cyclin D1 in the same series. We did not find a significant relation between expression of NCAM or its highly sialylated isoform and the length of postoperative survival. The numbers of positive cases (9 and 14, respectively) were relatively low. Increased p53 and cyclin D1 immunostaining (50 and 55 of the 96 tumours) failed to show a significant relation with postoperative survival. In our material, tumour stage was the only significant prognostic factor.     

Current Diagnosis and Treatment Options for Cutaneous Adnexal Neoplasms with Follicular Differentiation

Neoplasms derived from follicular tissue are extremely rare. Clinically, they are reported as non-symptomatic, slow-growing nodules. These lesions are mainly benign, but the malignant type can occur. Mainly middle-aged people (50–60 years of age) are affected. These carcinomas are mainly localized on the head and neck or torso. They can be locally aggressive and infiltrate surrounding tissue and metastasize to regional lymph nodes. In the minority of cases, distant metastases are diagnosed. Quick and relevant diagnosis is the basis of a treatment for all types of tumors. The patient’s life expectancy depends on multiple prognostic factors, including the primary tumor size and its mitotic count. Patients should be referred to a specialized skin cancer center to receive optimal multidisciplinary treatment. This article tries to summarize all the information that is currently available about pathogenesis, diagnosis, and treatment methods of follicular tumors.     

Solubility and Aggregation of Selected Proteins Interpreted on the Basis of Hydrophobicity Distribution

Protein solubility is based on the compatibility of the specific protein surface with the polar aquatic environment. The exposure of polar residues to the protein surface promotes the protein’s solubility in the polar environment. The aquatic environment also influences the folding process by favoring the centralization of hydrophobic residues with the simultaneous exposure to polar residues. The degree of compatibility of the residue distribution, with the model of the concentration of hydrophobic residues in the center of the molecule, with the simultaneous exposure of polar residues is determined by the sequence of amino acids in the chain. The fuzzy oil drop model enables the quantification of the degree of compatibility of the hydrophobicity distribution observed in the protein to a form fully consistent with the Gaussian 3D function, which expresses an idealized distribution that meets the preferences of the polar water environment. The varied degrees of compatibility of the distribution observed with the idealized one allow the prediction of preferences to interactions with molecules of different polarity, including water molecules in particular. This paper analyzes a set of proteins with different levels of hydrophobicity distribution in the context of the solubility of a given protein and the possibility of complex formation.     

Microstructure and Mechanical Properties of the Ductile Al–Ti–Mo–Nb–V Refractory High Entropy Alloys

Metallurgical and Materials Transactions A - A number of non-equimolar refractory high entropy alloys (RF HEAs) from the Al–Ti–Mo–Nb–V system are synthesized, with the...     

Novel conventional and chelating anion exchange resins with amino ligands for sorption of silver

ABSTRACT

The polymeric resins containing diethylenetriamine, tetraethylenepentamine, 2-(diethylamino)ethanol, 1-methylimidazole, and 1,2-dimethylimidazole ligands have been synthesized from vinylbenzyl chloride-divinylbenzene copolymers and used in the removal of Ag(I) from chloride solution. The best Ag(I) sorption was reached in the case of 1-methylimidazole resin. Resins retain their capacity towards Ag(I) in five consecutive sorption/desorption cycles. The resins with imidazole ligands were highly selective for Ag(I) from synthetic chloride solution and they did not sorb chloride complexes of Cu(II). Additionally, the recovery of Ag(I) was tested from real chloride solution coming from leaching of the copper concentrate from Lubin Concentrator (KGHM Polska Mied? S.A.).     

Hybrid Model of High Speed Machining Centre Headstock

A hybrid high-speed machining centre headstock model based on two computation methods: the finite element method and the finite difference method is presented. The model allows one to calculate precisely the headstock's indices on the basis of which its optimal operating characteristics can be determined. The presented modelling methods allow one to evaluate a design from thermal, stiffness and durability points of view. By way of illustration, the behaviour of three machining centre headstocks with: an electrospindle on rolling bearings, a conventional spindle and an electrospindle on aerostatic bearings are modelled using the hybrid model.