Genetic profile of sports climbing athletes from three different ethnicities

Aim: study of the predictive value of determining ctDNA during treatment with osimertinib in patients with NSCLC with EGFR mutation. Methods: The study included patients with metastatic EG-FR-associated NSCLC, in whom, with progression against the background of 1st - 2nd generation TKIs, the T790M mutation was detected. Patients received osimertinib therapy 80 mg/ day, daily, until progression. Before treatment, and then every 2 months, whole blood was taken to conduct a qualitative assessment of ctDNA in dynamics by the RT-PCR method. Results: From 2016 to 2019 in St. Petersburg Clinical Scientific and Practical Center of Specialized Types of Medical Care (Oncology), 22 patients were identified T790M associated progression of EGFR NSCLC. 81.9% (18/22) are women, 18.1% (4/22) are men. The average age is 61.2 years (50-75). 1/22 had smoking experience for more than 30 years. The molecular genetic profile in 16 is represented by ex19del, 5 L858R, 1 -a combination of rare mutations G719S+S768I. The effect of therapy was evaluated in 20/22 patients. PR and SD were registered in 9/20 (45%) and 10/20 (50%) patients, respectively. Median PFS - 16.7 months (cI 95%, 11,4-22,0). In 12/22 patients was observed the disappearance of ctDNA T790M after 2 months of osimertinib therapy. PFS is 18,9 months (95% CI, 14,8-19,7), in patients with no mutation detected in the second month of treatment compared with the group of patients in which the ctDNA was determined (PFS 8.0 months) (CI 95%, 4,2-11,8) (p=0.015). Correlation analysis did not reveal any clinical factors associated with the disappearance of ctDNA. Conclusions: The disappearance of ctDNA in plasma after 2 months of treatment with osimertinib is associated with an increase in PFS and can be considered as a predictive marker in patients with metastatic NSCLC EGFR T790M.

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Immunogenetics of Celiac Disease: A Focus on Arab Countries

Current Molecular Medicine ◽

10.2174/1566524019666191024104930 ◽

2020 ◽

Vol 20 (4) ◽

pp. 275-285 ◽

Cited By ~ 1

Author(s):

Nadin Younes ◽

Salma Younes ◽

Ola. A. Alsharabasi ◽

Mohamed E. El Zowalaty ◽

Ibrahim Mustafa ◽

...

Keyword(s):

Celiac Disease ◽

Genetic Epidemiology ◽

Arab World ◽

Human Leukocyte ◽

Epidemiological Studies ◽

Arab Countries ◽

Global Perspective ◽

Genetic Profile ◽

Leukocyte Antigen ◽

Genetic And Environmental Factors

Celiac Disease (CD) is a complex immunogenic disease mainly triggered by gluten intake in genetically susceptible individuals with a prevalence of 1 in 100-300. CD results from the interplay between genetic and environmental factors. Genetic susceptibility is believed to play a prominent role in the pathogenicity of CD, mainly due to human leukocyte antigen (HLA)-related class II genes. Although CD is wellrecognized among Arab populations, there are few studies on the genetic epidemiology and prevalence of CD in the Arab countries. Therefore, the aim of this review was to highlight the importance of studying this disease in the Arab world in the context of a global perspective. Within the few studies published so far, it was found that Arab populations have a distinctive susceptibility genetic profile from other ethnic groups with the DQ2.5 and DQ8 genotypes that are considered the major genotypes that confer susceptibility among Arab patients with CD. Our findings will pave the way to perform further epidemiological studies that will help identify potential therapeutic targets against CD among Arab patients that are diagnosed with CD.

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Liver-Metabolizing Genes and Their Relationship to the Performance of Elite Spanish Male Endurance Athletes; a Prospective Transversal Study

Sports Medicine - Open ◽

10.1186/s40798-019-0227-7 ◽

2019 ◽

Vol 5 (1) ◽

Cited By ~ 1

Author(s):

David Varillas Delgado ◽

Juan José Tellería Orriols ◽

Carlos Martín Saborido

Keyword(s):

Binary Logistic Regression ◽

Endurance Performance ◽

Endurance Athletes ◽

Genetic Profile ◽

Glutathione S Transferase ◽

Binary Logistic Regression Model ◽

Genotypic Distribution ◽

Endurance Runner ◽

Cytochrome P450 Family ◽

First Time

Abstract Background The genetic profile that is needed to define an endurance athlete has been studied during recent years. The main objective of this work is to approach for the first time the study of genetic variants in liver-metabolizing genes and their role in endurance performance by comparing the allelic and genotypic frequencies in elite endurance athletes to the non-athlete population. Methods Genotypic and allelic frequencies were determined in 123 elite endurance athletes (75 professional road cyclists and 48 endurance elite runners) and 122 male non-athlete subjects (sedentary). Genotyping of cytochrome P450 family 2 subfamily D member 6 (CYP2D6 rs3892097), glutathione-S transferase mu isoform 1 (GSTM1), glutathione S-transferase pi (GSTP rs1695) and glutathione S-transferase theta (GSTT) genes was performed by polymerase chain reaction (PCR). The combination of the polymorphisms for the “optimal” polygenic profile has been quantified using the genotype score (GS). Results Statistical differences were found in the genetic distributions between elite endurance athletes and non-athletes in CYP2D6 (p < 0.001) and GSTT (p = 0.014) genes. The binary logistic regression model showed a favourable OR (odds ratio) of being an elite endurance runner against a professional road cyclist (OR: 2.403, 95% CI: 1.213–4.760 (p = 0.002)) in the polymorphisms studied. Conclusions Genotypic distribution of liver-metabolizing genes in elite endurance athletes is different to non-athlete subjects, with a favourable gene profile in elite endurance athletes in terms of detoxification capacity.

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HPA axis multilocus genetic profile score moderates the impact of interpersonal stress on prospective increases in depressive symptoms for offspring of depressed mothers.

Journal of Abnormal Psychology ◽

10.1037/abn0000316 ◽

2017 ◽

Vol 126 (8) ◽

pp. 1017-1028 ◽

Cited By ~ 12

Author(s):

Cope Feurer ◽

John E. McGeary ◽

Valerie S. Knopik ◽

Leslie A. Brick ◽

Rohan H. Palmer ◽

...

Keyword(s):

Depressive Symptoms ◽

Hpa Axis ◽

Genetic Profile ◽

Interpersonal Stress ◽

Profile Score ◽

Depressed Mothers ◽

The Impact

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BSCI-20. THERAPEUTIC TARGETING OF HLA-G IN BRAIN METASTASES

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz014.018 ◽

2019 ◽

Vol 1 (Supplement_1) ◽

pp. i5-i5

Author(s):

Sheila Singh ◽

Blessing Bassey-Archibong ◽

Nikoo Aghaei ◽

Agata Kieliszek ◽

Chitra Venugopal ◽

...

Keyword(s):

Brain Metastases ◽

Systemic Disease ◽

Human Leukocyte ◽

Genetic Profile ◽

Whole Brain Radiation ◽

Metastatic Cells ◽

Metastatic Process ◽

Xenograft Models ◽

Sphere Formation ◽

The Brain

Abstract Brain metastases (BM) are the most common brain tumor in adults, with an incidence ten times greater than that of primary brain tumors. The most common sources of BM in adult cancer patients include cancers of the lung, breast and melanoma, which together account for almost 80% of all BM. Current clinical modalities for BM include surgery, whole brain radiation therapy and stereotactic radiosurgery but these therapies still offer limited efficacy and reduced survival of only months in treated patients, emphasizing the need for novel BM research approaches and better therapeutic strategies. Our laboratory recently discovered that stem-like cells exist in patient-derived BM from lung, breast and melanoma cancers, which we termed “brain metastasis-initiating cells” or BMICs. Through clinically relevant human-mouse xenograft models established with these patient-derived BMICs, we captured lung, breast and melanoma BMICs at pre-metastasis – a key stage where circulating metastatic cells extravasate and initially seed the brain, prior to organization into micro-metastatic foci. Transcriptome analysis of pre-metastatic BMICs revealed a unique genetic profile and several genes commonly up-regulated among lung, breast and melanoma BM, including the non-classical human leukocyte class I antigen-G (HLA-G). Loss of HLA-G in lung, breast and melanoma BMICs using two HLA-G specific shRNAs attenuated sphere formation, migratory and tumor initiating abilities of lung, breast and melanoma BMICs compared to control BMICs. HLA-G knockdown also resulted in reduced phospho(p)-STAT3 expression in patient-derived BMICs suggesting a potential cooperative role between HLA-G and pSTAT3 in BM. Since HLA-G is highly expressed at the cell surface in control tumors, ongoing experiments are focused on developing HLA-G specific chimeric antigen receptor -T cells (CAR-Ts) and determining their efficacy in targeting lung-, breast- and melanoma-BM as blocking the brain metastatic process will markedly extend patient survival and ultimately transform a fatal systemic disease into a more treatable one.

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Genetic profile of two isolates of Trypanosoma evansi from southern Brazil with different parasitaemias

Biotemas ◽

10.5007/2175-7925.2014v27n3p73 ◽

2014 ◽

Vol 27 (3) ◽

pp. 73 ◽

Cited By ~ 2

Author(s):

Daniel Pereira Duarte ◽

Larissa Kaori Oide Komati ◽

Kaio César Simiano Tavares ◽

Cícera Regina Lazzarotto ◽

Éden Ramalho De Araújo Ferreira ◽

...

Keyword(s):

Trypanosoma Evansi ◽

Genetic Profile ◽

Southern Brazil

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Chemical-genetic profile analysis in yeast suggests that a previously uncharacterized open reading frame, YBR261C, affects protein synthesis

BMC Genomics ◽

10.1186/1471-2164-9-583 ◽

2008 ◽

Vol 9 (1) ◽

pp. 583 ◽

Cited By ~ 22

Author(s):

Md Alamgir ◽

Veronika Eroukova ◽

Matthew Jessulat ◽

Jianhua Xu ◽

Ashkan Golshani

Keyword(s):

Protein Synthesis ◽

Profile Analysis ◽

Open Reading Frame ◽

Genetic Profile ◽

Reading Frame ◽

Chemical Genetic

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Mutational landscape of EGFR-, MYC-, and Kras-driven genetically engineered mouse models of lung adenocarcinoma

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1613601113 ◽

2016 ◽

Vol 113 (42) ◽

pp. E6409-E6417 ◽

Cited By ~ 80

Author(s):

David G. McFadden ◽

Katerina Politi ◽

Arjun Bhutkar ◽

Frances K. Chen ◽

Xiaoling Song ◽

...

Keyword(s):

Lung Adenocarcinoma ◽

Mouse Models ◽

Cancer Progression ◽

Large Scale ◽

Human Cancer ◽

Genetically Engineered ◽

Model Systems ◽

Driver Mutations ◽

Genetic Profile ◽

Genetically Engineered Mouse Models

Genetically engineered mouse models (GEMMs) of cancer are increasingly being used to assess putative driver mutations identified by large-scale sequencing of human cancer genomes. To accurately interpret experiments that introduce additional mutations, an understanding of the somatic genetic profile and evolution of GEMM tumors is necessary. Here, we performed whole-exome sequencing of tumors from three GEMMs of lung adenocarcinoma driven by mutant epidermal growth factor receptor (EGFR), mutant Kirsten rat sarcoma viral oncogene homolog (Kras), or overexpression of MYC proto-oncogene. Tumors from EGFR- and Kras-driven models exhibited, respectively, 0.02 and 0.07 nonsynonymous mutations per megabase, a dramatically lower average mutational frequency than observed in human lung adenocarcinomas. Tumors from models driven by strong cancer drivers (mutant EGFR and Kras) harbored few mutations in known cancer genes, whereas tumors driven by MYC, a weaker initiating oncogene in the murine lung, acquired recurrent clonal oncogenic Kras mutations. In addition, although EGFR- and Kras-driven models both exhibited recurrent whole-chromosome DNA copy number alterations, the specific chromosomes altered by gain or loss were different in each model. These data demonstrate that GEMM tumors exhibit relatively simple somatic genotypes compared with human cancers of a similar type, making these autochthonous model systems useful for additive engineering approaches to assess the potential of novel mutations on tumorigenesis, cancer progression, and drug sensitivity.

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