Genomics is changing personal healthcare and medicine: the dawn of iPH (individualized preventive healthcare)

This opinion piece focuses on the convergence of information technology (IT) in the form of personal monitors, especially smart phones and possibly also smart watches, individual genomic information and preventive healthcare and medicine. This may benefit each one of us not only individually but also society as a whole through iPH (individualized preventive healthcare). This shift driven by genomic and other technologies may well also change the relationship between patient and physician by empowering the former but giving him/her also much more individual responsibility

Genomics of COVID-19: molecular mechanisms going from susceptibility to severity of the disease

The current COVID-19 pandemic (https://www.who. int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19%2D%2 D-11-march-2020) has highlighted the importance of science and medicine, specifically public health, in our modern societies. Countries have taken different approaches to the pandemic. Science and medicine will play an important role in our way forward. Specifically, genetics and genomics will be central in discovering variations in virus strains and their impact on patients’ susceptibility, progression, and outcome. Additionally, the human and zoonotic hosts’ ability to fend off the virus and the severity of disease in patients will have genomic elements. Furthermore, the question of long-term immunity to COVID-19 will likely have a genomic basis which should be investigated. Some of these genetic and genomic investigations will undoubtedly be suitable for publication in Human Genomics. We, therefore, expressly welcome submissions of manuscripts on such subjects to the thematic series on the “Genomics of COVID-19: molecular mechanisms going from susceptibility to severity of the disease.” As citizen-scientists, we also have a responsibility toward society as citizens first and foremost but also specifically as scientists working on improving the lives of all humans. Political aspects of the COVID-19 pandemic and its origins can and should not be ignored as the needs of all humans: rich and poor, various ethnicities, rural vs. urban, different health and political systems, etc. These aspects, if fitting within the scope of the journal, will also be considered for publication in this thematic series in Human Genomi

COVID-19 2022 update: transition of the pandemic to the endemic phase

COVID-19, which is caused by the SARS-CoV-2, has ravaged the world for the past 2 years. Here, we review the current state of research into the disease with focus on its history, human genetics and genomics and the transition from the pandemic to the endemic phase. We are particularly concerned by the lack of solid information from the initial phases of the pandemic that highlighted the necessity for better preparation to face similar future threats. On the other hand, we are gratified by the progress into human genetic susceptibility investigations and we believe now is the time to explore the transition from the pandemic to the endemic phase. The latter will require worldwide vigilance and cooperation, especially in emerging countries. In the transition to the endemic phase, vaccination rates have lagged and developed countries should assist, as warranted, in bolstering vaccination rates worldwide. We also discuss the current status of vaccines and the outlook for COVID-19

COVID-19 update: the first 6 months of the pandemic

The COVID-19 pandemic is sweeping the world and will feature prominently in all our lives for months and most likely for years to come. We review here the current state 6 months into the declared pandemic. Specifically, we examine the role of the pathogen, the host and the environment along with the possible role of diabetes. We also firmly believe that the pandemic has shown an extraordinary light on national and international politicians whom we should hold to account as performance has been uneven. We also call explicitly on competent leadership of international organizations, specifically the WHO, UN and EU, informed by science. Finally, we also condense successful strategies for dealing with the current COVID-19 pandemic in democratic countries into a developing pandemic playbook and chart a way forward into the future. This is useful in the current COVID-19 pandemic and, we hope, in a very distant future again when another pandemic might arise

COVID-19 one year into the pandemic: from genetics and genomics to therapy, vaccination, and policy

COVID-19 has engulfed the world and it will accompany us all for some time to come. Here, we review the current state at the milestone of 1 year into the pandemic, as declared by the WHO (World Health Organization). We review several aspects of the on-going pandemic, focusing first on two major topics: viral variants and the human genetic susceptibility to disease severity. We then consider recent and exciting new developments in therapeutics, such as monoclonal antibodies, and in prevention strategies, such as vaccines. We also briefly discuss how advances in basic science and in biotechnology, under the threat of a worldwide emergency, have accelerated to an unprecedented degree of the transition from the laboratory to clinical applications. While every day we acquire more and more tools to deal with the on-going pandemic, we are aware that the path will be arduous and it will require all of us being community-minded. In this respect, we lament past delays in timely full investigations, and we call for bypassing local politics in the interest of humankind on all continents

Identification of genomic aberrations in hemangioblastoma by droplet digital PCR and SNP microarray highlights novel candidate genes and pathways for pathogenesis

Background: The genetic mechanisms underlying hemangioblastoma development are still largely unknown. We used high-resolution single nucleotide polymorphism microarrays and droplet digital PCR analysis to detect copy number variations (CNVs) in total of 45 hemangioblastoma tumors. Results: We identified 94 CNVs with a median of 18 CNVs per sample. The most frequently gained regions were on chromosomes 1 (p36.32) and 7 (p11.2). These regions contain the EGFR and PRDM16 genes. Recurrent losses were located at chromosome 12 (q24.13), which includes the gene PTPN11. Conclusions: Our findings provide the first high-resolution genome-wide view of chromosomal changes in hemangioblastoma and identify 23 candidate genes: EGFR, PRDM16, PTPN11, HOXD11, HOXD13, FLT3, PTCH, FGFR1, FOXP1, GPC3, HOXC13, HOXC11, MKL1, CHEK2, IRF4, GPHN, IKZF1, RB1, HOXA9, and micro RNA, such as hsa-mir-196a-2 for hemangioblastoma pathogenesis. Furthermore, our data implicate that cell proliferation and angiogenesis promoting pathways may be involved in the molecular pathogenesis of hemangioblastoma

Elevated NLR May Be a Feature of Pediatric Brain Cancer Patients

Pediatric brain tumors are the most common solid tumor type and the leading cause of cancer-related death in children. The immune system plays an important role in cancer pathogenesis and in the response to immunotherapy treatments. T lymphocytes are key elements for the response of the immune system to cancer cells and have been associated with prognosis of different cancers. Neutrophils on the other hand, which secrete pro-angiogenic and anti-apoptotic factors, enhance the ability of tumor cells to grow and develop into metastases. We conducted a retrospective study of 120 pediatric brain cancer patients and 171 elective pediatric patients hospitalized in Dana Children's Hospital and Sheba Medical Center. Data on age, sex, treatment, lymphocyte, neutrophil, and monocyte count were collected from routinely performed preoperative blood tests. Neutrophil-to-lymphocyte ratio (NLR), and the lymphocyte-to-monocyte ratio (LMR) were calculated and significance was determined by paired T test. p < 0.05 was considered as statistically significant. NLR was significantly higher in the pediatric brain cancer patients. The high NLR in pediatric brain cancer patients is the result of a combination of low lymphocytes and high neutrophils. Both of these factors can have a role in cancer development and propagation and also in response to therapy

Comparison of transcriptional responses in liver tissue and primary hepatocyte cell cultures after exposure to hexahydro-1, 3, 5-trinitro-1, 3, 5-triazine

BACKGROUND: Cell culture systems are useful in studying toxicological effects of chemicals such as Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), however little is known as to how accurately isolated cells reflect responses of intact organs. In this work, we compare transcriptional responses in livers of Sprague-Dawley rats and primary hepatocyte cells after exposure to RDX to determine how faithfully the in vitro model system reflects in vivo responses. RESULTS: Expression patterns were found to be markedly different between liver tissue and primary cell cultures before exposure to RDX. Liver gene expression was enriched in processes important in toxicology such as metabolism of amino acids, lipids, aromatic compounds, and drugs when compared to cells. Transcriptional responses in cells exposed to 7.5, 15, or 30 mg/L RDX for 24 and 48 hours were different from those of livers isolated from rats 24 hours after exposure to 12, 24, or 48 mg/Kg RDX. Most of the differentially expressed genes identified across conditions and treatments could be attributed to differences between cells and tissue. Some similarity was observed in RDX effects on gene expression between tissue and cells, but also significant differences that appear to reflect the state of the cell or tissue examined. CONCLUSION: Liver tissue and primary cells express different suites of genes that suggest they have fundamental differences in their cell physiology. Expression effects related to RDX exposure in cells reflected a fraction of liver responses indicating that care must be taken in extrapolating from primary cells to whole animal organ toxicity effects

Insulin-like growth factor-binding protein-2 promotes prostate cancer cell growth via IGF-dependent or -independent mechanisms and reduces the efficacy of docetaxel

Background: The development of androgen independence, chemo-, and radioresistance are critical markers of prostate cancer progression and the predominant reasons for its high mortality. Understanding the resistance to therapy could aid the development of more effective treatments. Aim: The aim of this study is to investigate the effects of insulin-like growth factor-binding protein-2 (IGFBP-2) on prostate cancer cell proliferation and its effects on the response to docetaxel. Methods: DU145 and PC3 cells were treated with IGFBP-2, insulin-like growth factor I (IGF-I) alone or in combination with blockade of the IGF-I receptor or integrin receptors. Cells were also treated with IGFBP-2 short interfering ribonucleic acid with or without a PTEN (phosphatase and tensin homologue deleted on chromosome 10) inhibitor or docetaxel. Tritiated thymidine incorporation was used to measure cell proliferation and Trypan blue cell counting for cell death. Levels of IGFBP-2 mRNA were measured using RT-PCR. Abundance and phosphorylation of proteins were assessed using western immunoblotting. Results: The IGFBP-2 promoted cell growth in both cell lines but with PC3 cells this was in an IGF-dependent manner, whereas with DU145 cells the effect was independent of IGF receptor activation. This IGF-independent effect of IGFBP-2 was mediated by interaction with β-1-containing integrins and a consequent increase in PTEN phosphorylation. We also determined that silencing IGFBP-2 in both cell lines increased the sensitivity of the cells to docetaxel. Conclusion: The IGFBP-2 has a key role in the growth of prostate cancer cells, and silencing IGFBP-2 expression reduced the resistance of these cells to docetaxel. Targeting IGFBP-2 may increase the efficacy of docetaxel.7 page(s

Loss of PTEN expression is associated with IGFBP2 expression, younger age, and late stage in triple-negative breast cancer

© American Society for Clinical Pathology. Objectives: To investigate the association between PTEN loss and IGFBP2 expression in a series of triple-negative breast cancers and to relate this expression to basal cytokeratin expression and clinicopathologic features. Methods: One hundred and one formalin-fixed and paraffin-processed triple-negative breast cancer cases from the University of Malaya Medical Centre were tested immunohistochemically for cytokeratins 5/6 and 14, PTEN, and IGFBP2. The resulting slides were scored for proportion and intensity of staining. Results: Loss of tumor nuclear and cytoplasmic staining for PTEN occurred in 48.3% of cases and was significantly associated with younger age at diagnosis (47 years compared with 57 years in those without PTEN loss; P = .005). Independent predictors of PTEN loss were late stage at presentation ( P = .026), cytokeratin 5/6 positivity ( P = .028), and IGFBP2 expression ( P = .042). High levels of IGFBP2 expression were seen in 32% of cases; an independent predictor of high levels was cytokeratin 14 negativity ( P = .005). PTEN loss and high levels of IGFBP2 expression were associated with poorer survival, but neither of these trends was significant. Conclusions: PTEN loss is a frequent event in triple-negative breast cancers and is significantly associated with younger age at onset of breast cancer, late stage, and IGFBP2 expression