scholarly journals Dissecting Molecular Features of Gliomas: Genetic Loci and Validated Biomarkers

2020 ◽  
Vol 21 (2) ◽  
pp. 685 ◽  
Author(s):  
Antonietta Arcella ◽  
Fiona Limanaqi ◽  
Rosangela Ferese ◽  
Francesca Biagioni ◽  
Maria Antonietta Oliva ◽  
...  
Keyword(s):  
Somatic Mutations ◽  
Genetic Diagnosis ◽  
Tumor Development ◽  
Cost Effective ◽  
Circulating Tumor Dna ◽  
Copy Number Variations ◽  
Disease Classification ◽  
Individual Risk ◽  
Molecular Features ◽  
Increased Risk

Recently, several studies focused on the genetics of gliomas. This allowed identifying several germline loci that contribute to individual risk for tumor development, as well as various somatic mutations that are key for disease classification. Unfortunately, none of the germline loci clearly confers increased risk per se. Contrariwise, somatic mutations identified within the glioma tissue define tumor genotype, thus representing valid diagnostic and prognostic markers. Thus, genetic features can be used in glioma classification and guided therapy. Such copious genomic variabilities are screened routinely in glioma diagnosis. In detail, Sanger sequencing or pyrosequencing, fluorescence in-situ hybridization, and microsatellite analyses were added to immunohistochemistry as diagnostic markers. Recently, Next Generation Sequencing was set-up as an all-in-one diagnostic tool aimed at detecting both DNA copy number variations and mutations in gliomas. This approach is widely used also to detect circulating tumor DNA within cerebrospinal fluid from patients affected by primary brain tumors. Such an approach is providing an alternative cost-effective strategy to genotype all gliomas, which allows avoiding surgical tissue collection and repeated tumor biopsies. This review summarizes available molecular features that represent solid tools for the genetic diagnosis of gliomas at present or in the next future.

Molecular features encoded in the ctDNA reveal heterogeneity and predict outcome in high-risk aggressive B-cell lymphoma

Blood ◽  
2021 ◽  
Author(s):  
Leo Meriranta ◽  
Amjad Alkodsi ◽  
Annika Pasanen ◽  
Maija Lepistö ◽  
Parisa Mapar ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Liquid Biopsy ◽  
Residual Disease ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Circulating Tumor Dna ◽  
Prognostic Information ◽  
Molecular Features ◽  
Increased Risk

Inadequate molecular and clinical stratification of the patients with high-risk diffuse large B-cell lymphoma (DLBCL) is a clinical challenge hampering the establishment of personalized therapeutic options. We studied the translational significance of liquid biopsy in a uniformly treated trial cohort. Pretreatment circulating tumor DNA (ctDNA) revealed hidden clinical and biological heterogeneity, and high ctDNA burden determined increased risk of relapse and death independently of conventional risk factors. Genomic dissection of pretreatment ctDNA revealed translationally relevant phenotypic, molecular, and prognostic information that extended beyond diagnostic tissue biopsies. During therapy, chemorefractory lymphomas exhibited diverging ctDNA kinetics, whereas end-of-therapy negativity for minimal residual disease characterized cured patients and resolved clinical enigmas, including false residual PET positivity. Furthermore, we discovered fragmentation disparities in the cell-free DNA that characterize lymphoma-derived ctDNA and, as a proof-of-concept for their clinical application, utilized machine learning to show that end-of-therapy fragmentation patterns predict outcome. Altogether, we have discovered novel molecular determinants in the liquid biopsy that can non-invasively guide treatment decisions.

Therapeutic options in male osteoporosis

2013 ◽  
Vol 22 (04) ◽  
pp. 271-276 ◽  
Author(s):  
P. Farahmand ◽  
J. D. Ringe
Keyword(s):  
Risk Factors ◽  
Vitamin D ◽  
Public Health Problem ◽  
Male Osteoporosis ◽  
Individual Risk ◽  
Modes Of Action ◽  
Increased Risk ◽  
Study Results ◽  
Long Term Treatment ◽  
Male Patients

SummaryOsteoporosis in men is increasingly recognized as an important public health problem but affected patients are still under-diagnosed and -treated. As in women the diagnostic and therapeutic strategy has to be adapted to the individual case. In the practical management it is very important to detect possible causes of secondary osteoporosis, to explain the possibilities of basic therapy counteracting individual risk factors and communicate that osteoporosis is a chronic disease and adherence to a long-term treatment is crucial. In established severe osteoporosis a careful analgesic therapy is important to avoid further bone loss related to immobility. In elderly men with increased risk of falling insufficient Vitamin D supply or impaired activation of Vitamin D due to renal insufficiency must be taken into consideration. Specific medications available today for the treatment of male osteoporosis comprise among antiresorptive drugs the bis phosphonates alendronate, risedronate and zoledronic acid. Denosumab, the first biological therapy is approved for men with androgen deprivation therapy for prostate cancer. An important advantage of this potent antiresorptive drug is the increased adherence due to the comfortable application by sixmonthly subcutaneous injections. Study results from the 2-year multi-center randomized controlled ADAMO-Study will very soon allow the use of denosumab in all types of male osteoporosis. Teriparatide, the 34 N-terminal amino acid sequence of parathyroid hormone was approved for men with osteoporosis as an anabolic agent based on proven efficacy by different studies. Among drugs with other modes of action the D-hormone pro-drug alfacalcidol can be used in men alone or in combination with the advantage of pleiotropic effects on calcium absorption, parathyroids, bone and muscle. Recently also Strontium-ranelate was approved for male patients with the limitation to exclude men with clinical relevant cardiovascular risk factors. In general the possibilities to treat male osteoporosis have considerably improved during recent years. Today there is a choice of a spectrum of drugs from mild to strong potency with different modes of action on bone turnover to design strategies for individual male patients.

ASSESSMENT OF THE PLATELET COUNT IN THE PREGNANT WOMEN IN IGIMS, PATNA, BIHAR

2020 ◽  
Vol 4 (2) ◽  
Author(s):  
Tanwi Singh ◽  
Anshuman Sinha
Keyword(s):  
Platelet Count ◽  
Pregnant Women ◽  
Screening Test ◽  
Low Cost ◽  
Medical Science ◽  
Cost Effective ◽  
Platelet Indices ◽  
Increased Risk ◽  
Low Platelet Count ◽  
Severity Of The Disease

The major risk associated with low platelet count in pregnancy is the increased risk of bleeding during the childbirth or post that. There is an increased blood supply to the uterus during pregnancy and the surgical procedure requires cutting of major blood vessels. Women with thrombocytopenia are at increased risk of losing excessive blood. The risk is more in case of caesarean delivery as compared to vaginal delivery. Hence based on above findings the present study was planned for Assessment of the Platelet Count in the Pregnant Women in IGIMS, Patna, Bihar. The present study was planned in Department of Pathology, Indira Gandhi Institute of Medical Science, Patna, Bihar, India. The present study was planned from duration of January 2019 to June 2019. In the present study 200 pregnant females samples received for the platelet estimation were enrolled in the present study. Clinically platelet indices can be a useful screening test for early identification of preeclampsia and eclampsia. Also platelet indices can assess the prognosis of this disease in pregnant women and can be used as an effective prognostic marker because it correlates with severity of the disease. Platelet count is a simple, low cost, and rapid routine screening test. Hence the data generated from the present study concludes that platelet count can be used as a simple and cost effective tool to monitor the progression of preeclampsia, thereby preventing complications to develop during the gestational period. Keywords: Platelet Count, Pregnant Women, IGIMS, Patna, Bihar, etc.

ctDNA as a prognostic factor in operable colon cancer patients: a systematic review and meta-analysis

2020 ◽  
Author(s):  
Emre Yekedüz ◽  
Elif Berna Köksoy ◽  
Hakan Akbulut ◽  
Yüksel Ürün ◽  
Güngör Utkan
Keyword(s):  
Colon Cancer ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Circulating Tumor Dna ◽  
Random Effects Model ◽  
Inverse Variance ◽  
Increased Risk ◽  
Significant Step ◽  
Tumor Dna

Aim: Using circulating tumor DNA (ctDNA) instead of historical clinicopathological factors to select patients for adjuvant chemotherapy (ACT) may reduce inappropriate therapy. Material & methods: MEDLINE was searched on March 31, 2020. Studies, including data related to the prognostic value of ctDNA in the colon cancer patients after surgery and after ACT, were included. The generic inverse-variance method with a random-effects model was used for meta-analysis. Results: Four studies were included for this meta-analysis. ctDNA-positive colon cancer patients after surgery and ACT had a significantly increased risk of recurrence compared with ctDNA-negative patients. Conclusions: ctDNA is an independent prognostic factor, and this meta-analysis is a significant step for using ctDNA instead of historical prognostic factors in the adjuvant setting.

scholarly journals Hypoplastic Myelodysplastic Syndromes: Just an Overlap Syndrome?

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 132
Author(s):  
Bruno Fattizzo ◽  
Fabio Serpenti ◽  
Wilma Barcellini ◽  
Chiara Caprioli
Keyword(s):  
Bone Marrow ◽  
Aplastic Anemia ◽  
Clonal Selection ◽  
Cytotoxic T Cells ◽  
Immunosuppressive Treatment ◽  
Young Patients ◽  
Suppressor Cells ◽  
Molecular Alterations ◽  
Molecular Features ◽  
Increased Risk

Myelodysplasias with hypocellular bone marrow (hMDS) represent about 10–15% of MDS and are defined by reduced bone marrow cellularity (i.e., <25% or an inappropriately reduced cellularity for their age in young patients). Their diagnosis is still an object of debate and has not been clearly established in the recent WHO classification. Clinical and morphological overlaps with both normo/hypercellular MDS and aplastic anemia include cytopenias, the presence of marrow hypocellularity and dysplasia, and cytogenetic and molecular alterations. Activation of the immune system against the hematopoietic precursors, typical of aplastic anemia, is reckoned even in hMDS and may account for the response to immunosuppressive treatment. Finally, the hMDS outcome seems more favorable than that of normo/hypercellular MDS patients. In this review, we analyze the available literature on hMDS, focusing on clinical, immunological, and molecular features. We show that hMDS pathogenesis and clinical presentation are peculiar, albeit in-between aplastic anemia (AA) and normo/hypercellular MDS. Two different hMDS phenotypes may be encountered: one featured by inflammation and immune activation, with increased cytotoxic T cells, increased T and B regulatory cells, and better response to immunosuppression; and the other, resembling MDS, where T and B regulatory/suppressor cells prevail, leading to genetic clonal selection and an increased risk of leukemic evolution. The identification of the prevailing hMDS phenotype might assist treatment choice, inform prognosis, and suggest personalized monitoring.

scholarly journals HiCancer: accurate and complete cancer genome phasing with Hi-C reads

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Weihua Pan ◽  
Desheng Gong ◽  
Da Sun ◽  
Haohui Luo
Keyword(s):  
Copy Number ◽  
Somatic Mutations ◽  
Copy Number Variations ◽  
Cancer Genome ◽  
Structural Variations ◽  
Genome Map ◽  
Linkage Information ◽  
Suboptimal Solution ◽  
Allelic Copy Number ◽  
Very High

AbstractDue to the high complexity of cancer genome, it is too difficult to generate complete cancer genome map which contains the sequence of every DNA molecule until now. Nevertheless, phasing each chromosome in cancer genome into two haplotypes according to germline mutations provides a suboptimal solution to understand cancer genome. However, phasing cancer genome is also a challenging problem, due to the limit in experimental and computational technologies. Hi-C data is widely used in phasing in recent years due to its long-range linkage information and provides an opportunity for solving the problem of phasing cancer genome. The existing Hi-C based phasing methods can not be applied to cancer genome directly, because the somatic mutations in cancer genome such as somatic SNPs, copy number variations and structural variations greatly reduce the correctness and completeness. Here, we propose a new Hi-C based pipeline for phasing cancer genome called HiCancer. HiCancer solves different kinds of somatic mutations and variations, and take advantage of allelic copy number imbalance and linkage disequilibrium to improve the correctness and completeness of phasing. According to our experiments in K562 and KBM-7 cell lines, HiCancer is able to generate very high-quality chromosome-level haplotypes for cancer genome with only Hi-C data.

scholarly journals An Artificial-Intelligence-Discovered Functional Ingredient, NRT_N0G5IJ, Derived from Pisum sativum, Decreases HbA1c in a Prediabetic Population

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1635
Author(s):  
Sweeny Chauhan ◽  
Alish Kerr ◽  
Brian Keogh ◽  
Stephanie Nolan ◽  
Rory Casey ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Pisum Sativum ◽  
Cost Effective ◽  
Glycated Haemoglobin ◽  
Glucose Regulation ◽  
Functional Ingredient ◽  
Effective Manner ◽  
Human Skeletal Muscle Cells ◽  
Increased Risk

The prevalence of prediabetes is rapidly increasing, and this can lead to an increased risk for individuals to develop type 2 diabetes and associated diseases. Therefore, it is necessary to develop nutritional strategies to maintain healthy glucose levels and prevent glucose metabolism dysregulation in the general population. Functional ingredients offer great potential for the prevention of various health conditions, including blood glucose regulation, in a cost-effective manner. Using an artificial intelligence (AI) approach, a functional ingredient, NRT_N0G5IJ, was predicted and produced from Pisum sativum (pea) protein by hydrolysis and then validated. Treatment of human skeletal muscle cells with NRT_N0G5IJ significantly increased glucose uptake, indicating efficacy of this ingredient in vitro. When db/db diabetic mice were treated with NRT_N0G5IJ, we observed a significant reduction in glycated haemoglobin (HbA1c) levels and a concomitant benefit on fasting glucose. A pilot double-blinded, placebo controlled human trial in a population of healthy individuals with elevated HbA1c (5.6% to 6.4%) showed that HbA1c percentage was significantly reduced when NRT_N0G5IJ was supplemented in the diet over a 12-week period. Here, we provide evidence of an AI approach to discovery and demonstrate that a functional ingredient identified using this technology could be used as a supplement to maintain healthy glucose regulation.

scholarly journals Genomic alterations caused by HPV integration in a cohort of Chinese endocervical adenocarcinomas

2021 ◽  
Author(s):  
Wenhui Li ◽  
Wanjun Lei ◽  
Xiaopei Chao ◽  
Xiaochen Song ◽  
Yalan Bi ◽  
...  
Keyword(s):  
Copy Number ◽  
Somatic Mutations ◽  
Hpv Infection ◽  
Copy Number Variations ◽  
Cervical Adenocarcinoma ◽  
Structural Variations ◽  
Driver Genes ◽  
Genetic Changes ◽  
Genomic Changes ◽  
Whole Exome

AbstractThe association between human papillomavirus (HPV) integration and relevant genomic changes in uterine cervical adenocarcinoma is poorly understood. This study is to depict the genomic mutational landscape in a cohort of 20 patients. HPV+ and HPV− groups were defined as patients with and without HPV integration in the host genome. The genetic changes between these two groups were described and compared by whole-genome sequencing (WGS) and whole-exome sequencing (WES). WGS identified 2916 copy number variations and 743 structural variations. WES identified 6113 somatic mutations, with a mutational burden of 2.4 mutations/Mb. Six genes were predicted as driver genes: PIK3CA, KRAS, TRAPPC12, NDN, GOLGA6L4 and BAIAP3. PIK3CA, NDN, GOLGA6L4, and BAIAP3 were recognized as significantly mutated genes (SMGs). HPV was detected in 95% (19/20) of patients with cervical adenocarcinoma, 7 of whom (36.8%) had HPV integration (HPV+ group). In total, 1036 genes with somatic mutations were confirmed in the HPV+ group, while 289 genes with somatic mutations were confirmed in the group without HPV integration (HPV− group); only 2.1% were shared between the two groups. In the HPV+ group, GOLGA6L4 and BAIAP3 were confirmed as SMGs, while PIK3CA, NDN, KRAS, FUT1, and GOLGA6L64 were identified in the HPV− group. ZDHHC3, PKD1P1, and TGIF2 showed copy number amplifications after HPV integration. In addition, the HPV+ group had significantly more neoantigens. HPV integration rather than HPV infection results in different genomic changes in cervical adenocarcinoma.

Prevalence and prognostic impact of somatic mutations in patients with heart failure and reduced ejection fraction

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D.J Vazquez Andres ◽  
A Hernandez Vicente ◽  
M Diez Diez ◽  
M Gomez Molina ◽  
A Quintas ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Somatic Mutations ◽  
Myocardial Dysfunction ◽  
Study Endpoint ◽  
Prognostic Impact ◽  
Reduced Ejection Fraction ◽  
Increased Risk ◽  
Patients With Heart Failure

Abstract Introduction Somatic mutations in hematopoietic cells are associated with age and have been associated with higher mortality in apparently healthy adults, especially due to atherosclerotic disease. In animal models, somatic mutations are associated with atherosclerosis progression and myocardial dysfunction, especially when gene TET2 is affected. Preliminary clinical data, referred to ischemic heart failure (HF), have associate the presence of these acquired mutations with impaired prognosis. Purpose To study the prevalence of somatic mutations in patients with heart failure with reduced ejection fraction (HFrEF) and their impact on long-term prognosis. Methods We studied a cohort of elderly patients (more than 60 years old) hospitalized with HFrEF (LVEF&lt;45%). The presence of somatic mutations was assessed using next generation sequencing (Illumina HiSeq 2500), with a mutated allelic fraction of at least 2% and a panel of 55 genes related with clonal hematopoiesis. Patients were followed-up for a median of three years. The study endpoint was a composite of death or readmission for worsening HF. Kaplan-Meier analysis (log-rank test) and Cox proportional hazards regression models were performed adjusting for age, sex and LVEF. Results A total of 62 patients (46 males (74.2%), age 74±7.5 years) with HFrEF (LVEF 29.7±7.8%) were enrolled in the study. The ischemic etiology was present in 54% of patients. Somatic mutations in Dnmt3a or Tet2 were present in 11 patients (17.7%). No differences existed in baseline characteristics except for a higher prevalence of atrial fibrillation in patients with somatic mutations (70% vs. 40%, p=0.007). During the follow-up period, 40 patients (64.5%) died and 38 (61.3%) had HF re-admission. The KM survival analysis for the combined event is shown in Figure 1. Compared with patients without somatic mutations and after adjusting for covariates, there was an increased risk of adverse outcomes when the somatic mutations were present (HR 3.6, 95% CI [1.6, 7.8], p=0.0014). This results remains considering death as a competing risk (Gray's test p=0.0097) and adjusting for covariates (HR = 2.21 95% CI [0.98, 5], p=0.0556). Conclusions Somatic mutation are present in patients with HFrEF and determine a higher risk of adverse events in the follow-up. Further studies are needed to assess the clinical implications of these findings. Figure 1 Funding Acknowledgement Type of funding source: None

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