Current Pharmacogenomics and Personalized Medicine最新文献

{"title":"Factors Associated with Plasma Levels of Tamoxifen and its Main Metabolites in Mexican Patients with Breast Cancer","authors":"S. Romano, Miriam Morales, Angélica Aguilar, Susanna Medellín, R. Milán, José Cruz, José Zermeño, Alejandra Segarra","doi":"10.2174/1875692119666220830100021","DOIUrl":"https://doi.org/10.2174/1875692119666220830100021","url":null,"abstract":"\u0000\u0000Tamoxifen (TAM) is commonly prescribed as adjuvant therapy in women with estrogen receptor-positive breast cancer. Unfortunately, not all patients respond adequately to this drug. This variation in pharmacological response has been associated with different factors, including genetic polymorphisms of enzymes responsible for the metabolism of TAM.\u0000\u0000\u0000\u0000To determine the concentrations of tamoxifen (TAM) and its main metabolites in Mexican women with breast cancer and to evaluate its relationship with genetic, demographic and anthropometric characteristics.\u0000\u0000\u0000\u0000Eighty-four patients with a mean age of 49.3 (± 8.8) years were included in the study. Plasma concentrations of TAM and its metabolites N-desmethyl-tamoxifen (NDT), 4-hydroxy-tamoxifen (4HT) and endoxifen (END) were determined in predose for each patient. CYP2D6 * 4, * 10 and CYP3A5 * 3 genetic polymorphisms were characterized. Demographic, anthropometric, biochemical and clinical data were recorded for each patient.\u0000\u0000\u0000\u0000Plasma concentrations of 4HT and END were higher in the extensive metabolizer (EM) phenotype than in the intermediate metabolizer (IM) phenotype (p<0.05). The metabolic ratio (MR) [END+4HT]/[TAM+NDT] were lower in patients with the CYP2D6 IM phenotype than those with the EM phenotype (p= 0.014). Regarding anthropometric factors, a positive correlation was found for 4HT and END respect to age (R = 0.256 and 0.232, respectively). The body mass index (BMI) presented a statistically significant correlation with the concentrations of NDT (R=-0.351) and 4HT (R=-0.298).\u0000\u0000\u0000\u0000CYP2D6 phenotype, age and BMI could help to explain part of the interindividual variability of TAM plasma levels and its metabolites in the Mexican population.\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85981732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Tp53 Gene And Covid 19 Virus: A Correlation Analysis","authors":"L. C, K. P K","doi":"10.2174/1875692119666220617160537","DOIUrl":"https://doi.org/10.2174/1875692119666220617160537","url":null,"abstract":"\u0000\u0000To discover the most effective anti-cancer medicine for cancer patients who are infected with SARS-Cov-2.\u0000\u0000\u0000\u0000The correlation between TP53 and SARS-CoV-2 was discovered using biomolecular networking analysis.\u0000\u0000\u0000\u0000Cancer patients with TP53 gene mutations are more likely to be infected with the SARS-Cov-2 virus since it is the most frequently mutated tumor suppressor gene in human cancer. The main goal of this study is to discover the most effective and efficient anti-cancer therapy for patients with SARS-Cov-2 infection.\u0000\u0000\u0000\u0000Topp gene analysis was used to prioritize candidate genes based on molecular function, biological process, and pathway analysis. Biomolecular networking was carried out using Cytoscape 2.8.2. The Protein-protein Interaction network was used to identify the functionally associated proteins. Protein-Drug Interaction network was used to observe the molecular therapeutic efficiency of drugs. The network was further analyzed using Cytohubba to find the hub nodes. The molecular docking was used to study the protein-ligand interaction and the protein-ligand complex was further evaluated through molecular dynamic simulation to determine its stability.\u0000\u0000\u0000\u0000Functionally relevant genes were prioritized through Toppgene analysis. Through Cytohabba study it was found that the genes UBE2N, BRCA1, BARD1, TP53, and DPP4 was having a high degree and centrality score. The drugs 5-fluorouracil, Methotrexate, Temozolomide, Favipiravir, and Levofloxacin have a substantial association with the hub protei, according to protein-drug interaction analysis. Finally, a docking study revealed that 5-fluorouracil have the highest connection value and stability when compared to Methotrexate, Favipiravir, and Levofloxacin.\u0000\u0000\u0000\u0000The biomolecular networking study used to discover the link between TP53 and SARS-CoV-2 found that 5-fluorouracil, had a higher affinity for binding to TP53 and its related genes, such as UBE2N, BRCA1, RARD1, and SARS-CoV-2 specific DPP4. For cancer patients with TP53 gene mutations and covid 19 infection, these treatments were determined to be the most effective.\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81722922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacogenetics for improving efficacy and safety in drug development and for reducing costs in Alzheimer’s disease.","authors":"R. Cacabelos","doi":"10.2174/1875692119666220603154831","DOIUrl":"https://doi.org/10.2174/1875692119666220603154831","url":null,"abstract":"<jats:sec>\u0000<jats:title />\u0000<jats:p />\u0000</jats:sec>","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"1987 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86588991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computational Pathways Analysis and Personalized Medicine in HER2- Positive Breast Cancer","authors":"Maria Lui, D. Giosa, O. Romeo, A. Bitto","doi":"10.2174/1875692119666220407114044","DOIUrl":"https://doi.org/10.2174/1875692119666220407114044","url":null,"abstract":"\u0000\u0000The heterogeneity of some diseases, such as cancer, makes the decisions on therapeutic strategy very challenging. In this context, pathway analysis can support the identification of the best treatment and indeed prevent the issues arising from the trial and error process, in terms of best overall efficacy and lowest toxicity, ultimately saving time and resources. In a pathway, each gene is represented by a node and the pathway analysis can be performed using algorithms that interpolate data from different sources (i.e. sequencing, microarray, drug efficacy and interactions).\u0000\u0000\u0000\u0000The purpose of this study was to evaluate the effects of erbb2 amplification on HER2- positive breast cancer and to predict, with a pathway based computational approach, the efficacy of a therapy with Trastuzumab and Palbociclib, alone or in combination.\u0000\u0000\u0000\u0000One of the available and most integrated algorithms is PHENSIM that was used in this study to evaluate the gene dysregulations caused by the erbb2 amplification on its related pathways and the effects of Trastuzumab and Palbociclib on these deregulations. The effects have been estimated considering the drugs alone or in a combination therapy.\u0000\u0000\u0000\u0000A reduction of the number of pro-proliferative signals has been observed for both drugs alone or in combination. Regarding genes involved in MAPK signaling pathway, a total of 69 nodes were activated by the erbb2 mutation. A simulated treatment with Palbociclib reduced the number of activated genes down to 60, while with Trastuzumab the activated nodes were only 53. The combined therapy revealed an intriguing result providing a significant and remarkable reduction of the activated genes from 69 to 33.\u0000\u0000\u0000\u0000These results let us hypothesize that there could be an increased efficacy giving the combination therapy to subjects with HER2 positive breast cancer. Finally, pathway analysis could be specifically used to design clinical trials predicting the efficacy of combination therapies or untested drugs on a specific disease.\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81019927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Systematic Review of Decipher Genomic Classifier Risk Scores for Prostate Cancer in African-Americans","authors":"M. Rahimi, S. Greenfield","doi":"10.2174/1875692119666220309120918","DOIUrl":"https://doi.org/10.2174/1875692119666220309120918","url":null,"abstract":"\u0000\u0000Prostate Cancer (PCa) is a non-cutaneous malignancy in men, and Decipher being a genomic test, has gained increasing attention in estimating the risk of developing a recurrence or metastatic PCa disease in patients. Therefore, this study is focused on evaluating the association of Decipher score risk with recurrence of prostate cancer patients based on their medical, genetic predictors, and demographics (e.g., races) by conducting a systematic review. Moreover, the study has also assessed whether Decipher score risk can be a good predictor for prostate patients’ metastasis and prostate cancer-specific mortality in men and clinical decision-making regarding patient treatment recommendations.\u0000\u0000\u0000\u0000The research study has reviewed 74 research articles, and the systematic review results have been presented in the form of themes. The studies' review indicated that Decipher acts as a genomic metastasis signature to predict metastatic disease among patients and make better decisions about treating the disease. Moreover, this genomic test can also be used in conjunction with Magnetic Resonance Imaging (MRI) for identifying the lesions that may carry the biological potential for early metastases. Furthermore, this review also identified that treatment options for PCa might range from Adjuvant Radiation Treatment (ART) and Salvage Radiation Therapy (SRT) to Radical Prostatectomy (RP); however, the selection of treatment methodology depends upon the GC score and risk stratification.\u0000\u0000\u0000\u0000The results further suggested that the occurrence of PCa is two folds greater among African-Americans (AA) men as compared to non-AA men. Thus, the increasing incidence of PCa among AA and discrimination within AA's health and socio-economic conditions plays a significant role in treating AA. In this scenario, the Decipher test score plays an essential role in making treatment decisions.\u0000\u0000\u0000\u0000To conclude, further trials are still required for validating the Decipher biomarkers, and scientists should enhance the decipher test ability to be run on a patient's blood samples instead of tumor tissue, which will help patients use decipher as a screening test at the asymptomatic level.\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"83 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82153249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perspectives of Health Professionals Towards Neonatal Genetic Screening","authors":"T. A. Abeje","doi":"10.2174/1875692119666220225140848","DOIUrl":"https://doi.org/10.2174/1875692119666220225140848","url":null,"abstract":"\u0000\u0000After the completion of the human genome, the project has created opportunities of improving the diagnosis, prevention, and treatment of disease. However, limitations of health professionals (HPs), genetic knowledge, technological resources, and shortage of scientific researches prevent addressing genetic screening globally.\u0000\u0000\u0000\u0000To assess HPs knowledge, attitude, and future perspective towards neonatal genetic screening.\u0000\u0000\u0000\u0000The study was carried out in a cross-sectional survey. A simple random sampling technique was used to select health centers and health care, professionals. Questioners were used to assessing HPs knowledge, attitude, and future perspectives towards genetic disease screening.\u0000\u0000\u0000\u0000Among the total of 384 HPs, 79.7% and 20.3% had good and poor knowledge on the basic idea of genetic screening, respectively. Similarly, 92.4% and 7.6% of HPs had good and poor knowledge, respectively, on the parental history of genetic disease. Besides, 68.8% and 31.3% of HPs had good and poor knowledge on the possibility of treating genetic diseases. Lastly, 81.3% and 18.5% of HPs had a positive and negative attitude towards genetic screening.\u0000\u0000\u0000\u0000The majority of HPs were found good genetic knowledge and a positive attitude on the basic idea of genetic screening, parental history, and the possibility of treating genetic disease, respectively. However, the practice of genetic screening is not addressed in Ethiopia yet. Genetic HPs and non-genetic HPs have to be encouraging the concerned bodies including the governmental system to implement genetic screening in Ethiopia.\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83352392","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Alantolactone on Stemness Genes Expression in the Epithelial Mesenchymal Transition (EMT) in Breast Cancer","authors":"S. Aziz, Saiedeh Kashefi, N. Khalaji","doi":"10.2174/1875692119666220211154735","DOIUrl":"https://doi.org/10.2174/1875692119666220211154735","url":null,"abstract":"\u0000\u0000Background: To reduce the side effects of conventional chemotherapy drugs, new herbal\u0000remedies, such as alantolactone, can be used.\u0000\u0000Objective: We evaluated the association between stemness and EMT (epithelial-mesenchymal transition) process in triple-negative breast cancer cells treated with alantolactone that targets STAT3.\u0000\u0000Methods: The MDA-MB-231 cell line was used as one of the triple-negative breast cancer cell lines.\u0000MTT assay was used to evaluate cell viability and drug dose at three-time points of 24, 48, and 72\u0000hours, and three doses, i.e., 1, 0.1, and 0.01 mM of alantolactone were used to evaluate cellular behavior in proliferative and invasion pathways, respectively. A scratch test was also performed to evaluate\u0000the invasive power of cancer cells. Real-time PCR was used to evaluate the expression of regular\u0000genes by cancerous cell proliferation, STAT3 NANOG, SOX-2, and E-cadherin metastasis.\u0000\u0000Results: It was observed that increasing the dose of alantolactone increased cell apoptosis rate. The\u0000three doses selected for the cell culture study did not differ significantly from the control group regarding apoptosis-inducing abilities at desired time intervals. In the scratch test, the least amount of\u0000repair was seen at 1 mm. Expression of SOX-2, STAT3, and NANOG in the treated cells decreased\u0000with increasing dose of the drug, whereas expression of E-cadherin was found to be increased.\u0000\u0000Conclusion: Alantolactone through the STAT3 signaling pathway affects the expression of Ecadherin, NANOG, and SOX2 genes, inhibiting the EMT process and subsequent stemness, and may\u0000potentially be used in therapeutics for cancer patients.\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"34 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72583351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological and Pharmacogenomics Bases of Gastrointestinal and Some Long-Term Selective Serotonin Reuptake Inhibitors-Induced Adverse Effects","authors":"I. Badamasi, J. Stanslas","doi":"10.2174/1875692118666211105085901","DOIUrl":"https://doi.org/10.2174/1875692118666211105085901","url":null,"abstract":"\u0000\u0000\u0000Patients being treated with SSRIs who experience intolerable Adverse Effects (AEs) have a penchant for discontinuing treatment, inevitably jeopardizing any probability for treatment response. \u0000\u0000\u0000\u0000\u0000This study aims to identify the Single Nucleotide Polymorphisms (SNPs) that are associated with certain AEs of SSRI treatment in Major Depression Disorder (MDD).\u0000\u0000\u0000\u0000\u0000Patients with the short (SS) genotype (44 base pair deletion) and those with the long along with guanine substitution (LgLg - 44 base pair insertion with rs25531- guanine substitution variant) of the serotonin transporter gene (STG) have substantially been reported with a higher incidence of AEs to SSRI. While variants of glutamate receptor ionotropic genes have been found to be linked with different domains of sexual dysfunction, polymorphisms of 5-HT2A gene - rs6311 (G > A), the long allele (L) of STG, rs6295 (C > G) polymorphism of HTR1A and polymorphism rs1160351 (A > C) of MAM domain-containing glycosyl-phosphatidyl inositol anchor 2 (MDGA2) gene have also been found to be associated with sexual dysfunction. The rs4680 (G>A; Val > Met) polymorphism of catechol-O-methyltransferase (COMT), AA genotype of rs18532 polymorphism of tryptophan hydroxylase, the rs6318 (C > G) polymorphism of the serotonin receptor 2C (HTR2C), and S allele of STG were found to be associated with weight gain following SSRI treatment. The sanctity of these results is limited by the inability of some researchers to replicate these association findings.\u0000\u0000\u0000\u0000\u0000\u0000This review highlights a number of polymorphisms associated with some of the key AEs encountered in SSRI treatments. Standardized study designs in pharmacogenomic evaluations hold great promise for replication of association findings. \u0000\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"79 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76653812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is There Still a Role for Sulfonylureas in Type 2 Diabetes?","authors":"B. Tomlinson, Paul Chan, C. Lam","doi":"10.2174/1875692118666211021164840","DOIUrl":"https://doi.org/10.2174/1875692118666211021164840","url":null,"abstract":"<jats:sec>\u0000<jats:title />\u0000<jats:p />\u0000</jats:sec>","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72712088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Phytochemical Extracts on Cytokine Gene Expression","authors":"E. Mashkina, A. Alkhaddour","doi":"10.2174/1875692118666210923142013","DOIUrl":"https://doi.org/10.2174/1875692118666210923142013","url":null,"abstract":"\u0000\u0000In the last century, nutritional supplements have shown a wide spectrum of biochemical effects, most notably about immunomodulation and countering inflammation.\u0000\u0000\u0000\u0000This study investigates the impact of phytochemical compounds that are present in different quantities of pomegranate, grape seeds and garlic extracts on the expression of inflammatory (IL1β and IL6) and anti-inflammatory (IL10) genes, the effects of polymorphisms in these genes on this response.\u0000\u0000\u0000\u0000Human peripheral blood leukocyte cultures were treated with pomegranate (1.2% or 2.4%), garlic (0.5% or 1.2%), or grape seed (1.2% or 2.4%) extracts. Gene expression was assessed with real-time polymerase chain reaction (PCR). Polymorphisms of the cytokine genes were analyzed using allele-specific PCR.\u0000\u0000\u0000\u0000Pomegranate extract (2.4%) reduced the transcription of IL1β by 16-fold in comparison to control. The expression of IL6 relative to the control after the addition of grape seed extract (1.2%) was reduced by 100-fold. The grape seeds extract (1.2%) showed the effect of increasing transcription for IL10 compared to the control. The level of IL1β transcription in culture with garlic extract depends on the genotype of the cell for -31T>C polymorphism (r = 0.67 p = 0.03). There is correlation between polymorphism -174G>C and level gene expression IL6 (r=-0.66, p = 0.04) after adding grape seeds extract.\u0000\u0000\u0000\u0000The phytochemical compounds in pomegranate extracts and grape seed extracts play the role of anti-inflammatory by decreasing the gene expression of IL1β, IL6 and increasing the transcription of IL10.\u0000","PeriodicalId":11056,"journal":{"name":"Current Pharmacogenomics and Personalized Medicine","volume":"165 3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86704952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}