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Can microcalcifications' characteristics predict the risk of breast cancer metastasis to bone?

Journal of Cancer Metastasis and Treatment 2019年第4期4卷 31-37页

作者： Rita Bonfiglio Manuel Scimeca alessandro polidori Clara Nazzaro Giselda De Silva ElenaBonanno Department of Experimental Medicine University of Rome“Tor Vergata”Via Montpellier 1Rome 00133Italy Department of Biomedicine and Prevention University of Rome“Tor Vergata”Via Montpellier 1Rome 00133Italy San Raffaele University Via di Val Cannuta 247Rome 00166Italy Assing S.p.a Via Edoardo Amaldi 14Monterotondo 00015Italy Diagnostica Medica’&“Villa dei Platani” Neuromed GroupAvellino 83100Italy

Aim: To correlate the microcalcifications' characteristics, such as morphology and elemental compositions, with the occurrence of bone metastatic lesions at 5 years from diagnosis. Methods: In this retrospective study, we enrolled 70 patients from which we collected one breast biopsy each. From each biopsy, paraffin serial sections were obtained to perform histological classifications, immunohistochemical analyses and Energy Dispersive X-ray evaluation. Results: Microcalcifications analysis showed a significant association between the presence of calcium crystals made of magnesium substituted hydroxyapatite and the development of bone metastasis from 5 years from diagnosis. No significant association was observed by evaluation the morphological appearance of microcalcifications. Immunohistochemical analysis displayed a significant association between the expression of bone morphogenetic proteins 2 and pentraxin-3, two osteoblast induction factors, and the formation of bone metastatic lesions. Conclusion: Results here reported highlighted the possible use of breast microcalcifications as a negative prognostic marker of bone metastatic diseases. In particular, the association between elemental composition of breast microcalcifications and the formation of bone lesions can lay the foundation for the development of new in vivo diagnostic tools based on the analysis of microcalcifications and capable to predict the formation of bone metastasis.

关键词： Microcalcifications breast cancer bone metastasis breast osteoblast-like cells bone morphogenetic proteins 2 pentraxin-3

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Pharmacogenetic considerations for optimizing tacrolimus dosing in liver and kidney transplant patients

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World Journal of Gastroenterology 2013年第48期19卷 9156-9173页

作者： Alessio Provenzani Andrew Santeusanio Erin Mathis Monica Notarbartolo Manuela Labbozzetta Paola Poma Ambra Provenzani Carlo polidori Giovanni Vizzini Piera polidori Natale D'alessandro Department of Clinical Pharmacy Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT) 90127 Palermo Italy School of Pharmacy University of Pittsburgh Pittsburgh PA 15261 United States G. D’alessandro Department of Health Promotion Sciences Section of Pharmacology P Benigno University of Palermo 90127 Palermo Italy National Institute of Social Security (INPS) 90143 Palermo Italy School of Pharmacy University of Camerino 62032 Camerino Italy Department of Medicine Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT) 90127 Palermo Italy

The introduction of tacrolimus in clinical practice has improved patient survival after organ ***,despite the long use of tacrolimus in clinical practice,the best way to use this agent is still a matter of intense *** start of the genomic era has generated new research areas,such as pharmacogenetics,which studies the variability of drug response in relation to the genetic factors involved in the processes responsible for the pharmacokinetics and/or the action mechanism of a drug in the *** variability seems to be correlated with the presence of genetic *** is an attractive option especially for the initiation of the dosing of tacrolimus;also,unlike phenotypic tests,the genotype is a stable characteristic that needs to be determined only once for any given ***,prospective clinical studies must show that genotype determination before transplantation allows for better use of a given drug and improves the safety and clinical efficacy of that *** present,research has been able to reliably show that the CYP3A5 genotype,but not the CYP3A4 or ABCB1 ones,can modify the pharmacokinetics of ***,it has not been possible to incontrovertibly show that the corresponding changes in the pharmacokinetic profile are linked with different patient outcomes regarding tacrolimus efficacy and *** these reasons,pharmacogenetics and individualized medicine remain a fascinating area for further study and may ultimately become the face of future medical practice and drug dosing.

关键词： Pharmacogenetics Calcineurin inhibitors Tacrolimus Liver transplant Kidney transplant Single nucleotide polymorphisms CYP3A4 CYP3A5 ABCB1

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