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Pharmacogenomics in colorectal cancer:current role in clinical practice and future perspectives

Journal of Cancer Metastasis and Treatment 2018年第1期4卷 146-170页

作者： Francesca Battaglin Alberto Puccini Madiha Naseem Marta Schirripa Martin DBerger Ryuma Tokunaga Michelle McSkane Taline Khoukaz Shivani Soni Wu Zhang Heinz-Josef Lenz Division of Medical Oncology Norris Comprehensive Cancer CenterKeck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA Medical Oncology Unit 1 Clinical and Experimental Oncology DepartmentVeneto Institute of Oncology IOV-IRCCSPadua 35128Italy Department of Medical Oncology University Hospital of BernBern 3010Switzerland

The treatment scenario of colorectal cancer(CRC)has been evolving in recent years with the introduction of novel targeted agents and new therapeutic strategies for the metastatic disease.An extensive effort has been directed to the identification of predictive biomarkers to aid patients selection and guide therapeutic choices.Pharmacogenomics represents an irreplaceable tool to individualize patients treatment based on germline and tumor acquired somatic genetic variations able to predict drugs response and risk of toxicities.The growing knowledge of CRC molecular characteristics and complex genomic makeup has played a crucial role in identifying predictive pharmacogenomic biomarkers,while supporting the rationale for the development of new drugs and treatment combinations.Clinical validation of promising biomarkers,however,is often an issue.More recently,a deeper understanding of resistance mechanisms and tumor escape dynamics under treatment pressure and the availability of novel technologies are opening new perspectives in this field.This review aims to present an overview of current pharmacogenomic biomarkers and future perspectives of pharmacogenomics in CRC,in an evolving scenario moving from a single drug-gene interactions approach to a more comprehensive genome-wide approach,comprising genomics and epigenetics.

关键词： Colorectal cancer pharmacogenomics RAS BRAF microsatellite instability dihydropyrimidine dehydrogenase UDP-Glucuronosyltrasferase A1 epidermal growth factor receptor vascular endothelial growth factor DNA methylation

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Yang-Mills Mass Gap Problem: A Possible Solution

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Journal of Applied Mathematics and Physics 2023年第6期11卷 1755-1794页

作者： Antonio puccini Health Ministry Naples Italy

As known, the spontaneous symmetry breaking (SSB) and the Brout-Englert-Higgs Mechanism (BEH-M) solved the Yang-Mills Mass Gap Problem. However, various mathematicians, even prestigious ones, consider the basic assumptions of the gauge theories to be wrong, as well as in conflict with the experimental evidence and in clear disagreement with the facts, distorting the physical reality itself. Likewise, these theories are mathematically inconsistent, adopting a mathematical structure somewhat complicated and arbitrary, which does not satisfy the strong demands for coherence. The weakest point of the gauge theories, in our opinion, consists in imposing that all the particles must be free of an intrinsic mass. On the contrary, even for the particle considered universally massless, i.e. the photon, our calculations show a dynamic-mass, a push-momentum (p) of 1.325 × 10-22 [g⋅cm/s]. With this work we try to provide a possible solution to the Yang-Mills Mass Gap Problem, but without taking into account the SSB, nor using the BEH-M. We try to provide a mathematical explanation for this phenomenon, considering that in the spectrum of the Yang-Mills theory, there is a mass gap, that is, the difference between the energy of the vacuum state and the first excited state is different from zero. In other words, the lightest of the particles predicted by the theory must have a strictly positive mass to explain the short range of strong nuclear forces. It is clear, indeed, that if we replaced this value with the null value of the photon inserted in the equations of the Perturbation Theory, the Quantum Fields Theory and the Yang-Mills theories, all divergences, that is all zeroes and infinities, would suddenly disappear. Consequently, the limits imposed by the SSB disappear so that there is no longer any need to deny the mass to the Nuclear Forces bosons, including the Yang-Mills b quantum.

关键词： Electromagnetic (EM) Quantum Fields Theory (QFT) Spontaneous Symmetry Breaking (SSB) Gluon (G) Photon (P)

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A monocenter retrospective study of serological,histological and genetic characteristics of celiac disease in Northern Central Italy

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Open Journal of Clinical Diagnostics 2013年第3期3卷 122-127页

作者： Stefania Lombardi Gloria Bertacca Isabella Giannelli Elena Bonomi Daniela Tornaboni Marco Culli Andrea Cavazzana Antonella puccini Paolo Franceschini Marco Friggeri SSD Immunologia Allergologia e Patologia Molecolare Azienda USL1 Massa e Carrara Massa Italy UO Anatomia Patologia Azienda USL1 Massa e Carrara Carrara Italy

Objective: To examine the seroprevalence, correlates and characteristics of Celiac disease (CD) in a population sample of a Northern Central Area of Italy, by a monocenter retrospective study. Methods: Between 2006 and 2010, serum samples of 9371 subjects (age range 6 months to 91 years) were screened for tissue transglutaminase IgA antibodies (IgA-tTG) by the Immunologia-Allergologia Unit of AUSL1 Massa-Carrara, an area with a population of approximately 150,000. Endomysial IgA antibodies (EMA), HLA typing and small-bowel biopsy were also performed when indicated. Results: Of the 9371 subjects, 269 (2.87%) had positive antibody tests. The population was divided into several age groups and the highest prevalence (5.63%) was found in the 6 months-3 years group. The prevalence of IgA-tTG positivity was double in females compared to males. All IgA-tTG positive patients that were genotyped carried HLA-DQ2 or DQ8, none was a5 positive only. In positive IgA-tTG sera, levels of IgA-tTG were significantly higher in EMA positive than in EMA negative sera (p in children and in adults. Ninety-five/269 IgA-tTG positive subjects underwent biopsy. IgA-tTG levels were different according to the histological degree of the lesion. When EMA were evaluated in IgA-tTG positive subjects the number of EMA negative sera was significantly higher in adults than in children. Conclusions: In summary, this study provides a monocenter retrospective analysis of serological, histological and genetic parameters of subjects with suspicion of CD in an area of Northern Central Italy from 2006 to 2010.

关键词： Celiac Disease Anti-Endomysium Antibodies Anti-Transglutaminase Antibodies Epidemiology HLA-DR

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