Molecular genetics and the assessment of human cancers

1999 ◽  
Vol 1 (8) ◽  
pp. 1-19
Author(s):  
Carlos Caldas ◽  
Paul D.P. Pharoah
Keyword(s):  
Clinical Care ◽  
Molecular Genetic ◽  
Large Body ◽  
Clinical Staging ◽  
Genetic Profile ◽  
Molecular Fingerprint ◽  
Genetic Changes ◽  
Rigorous Evaluation ◽  
Human Cancers ◽  
Genetic Technologies

The past 20 years have seen rapid advances in the understanding of the biology of human cancers, and a large body of evidence now supports the idea that accumulated genetic changes underlie the development of neoplasia. In this article, we have reviewed the current research into the genetic bases of cancer and discussed the potential clinical applications of recent advances, with particular reference to the possibility of using molecular genetic tests for pre-symptomatic screening, clinical diagnosis and clinical staging. The possibility that the genetic profile of a tumour, its ‘molecular fingerprint’, will improve the ability of oncologists to predict tumour behaviour and thus help to determine optimum treatment has also been considered. Although the potential for the application of molecular genetic technologies is enormous, these technologies have yet to be subjected to rigorous evaluation in a clinical setting, and much work needs to be done before they are adopted for use in routine clinical care.

scholarly journals Contrasting Medical and Legal Standards of Evidence: A Precision Medicine Case Study

2016 ◽  
Vol 44 (1) ◽  
pp. 194-204 ◽  
Author(s):  
Gary E. Marchant ◽  
Kathryn Scheckel ◽  
Doug Campos-Outcalt
Keyword(s):  
Precision Medicine ◽  
New Technologies ◽  
Clinical Care ◽  
Large Body ◽  
Standard Of Care ◽  
Genetic Profile ◽  
Legal Standards ◽  
Standards Of Evidence ◽  
The Individual

As the health care system transitions to a precision medicine approach that tailors clinical care to the genetic profile of the individual patient, there is a potential tension between the clinical uptake of new technologies by providers and the legal system's expectation of the standard of care in applying such technologies. We examine this tension by comparing the type of evidence that physicians and courts are likely to rely on in determining a duty to recommend pharmacogenetic testing of patients prescribed the oral anti-coagulant drug warfarin. There is a large body of inconsistent evidence and factors for and against such testing, but physicians and courts are likely to weigh this evidence differently. The potential implications for medical malpractice risk are evaluated and discussed.

scholarly journals Molecular genetic changes in kidney tissue in patients with COVID-19

2021 ◽  
Vol 8 (3) ◽  
pp. 45-51
Author(s):  
G. A. Demyashkin ◽  
A. M. Mingazov ◽  
E. A. Kaprina ◽  
V. I. Shchekin ◽  
P. V. Shegay
Keyword(s):  
Protein Complexes ◽  
Molecular Genetic ◽  
Genetic Material ◽  
Kidney Tissue ◽  
Control Group ◽  
Genetic Profile ◽  
Genetic Changes ◽  
Genes Encoding ◽  
Favorable Conditions ◽  
High Degree

Purpose of the study. Assessment of the molecular genetic profile of cytological processes in the kidney tissue of patients with COVID‑19.Material and methods. Kidney fragments from patients with confirmed COVID‑19 (n = 96) were studied by real-time polymerase chain reaction to determine the expression of SARS-CoV‑2 viral RNA and genes encoding protein complexes: ACE‑2 and Furin. Results. In patients affected by COVID‑19, the presence of coronavirus genetic material in kidney tissue was recorded, as well as increased expression of ACE‑2 (7.49 ± 0.27, p < 0.01) and Furin 2.0 times (8.59 ± 0.65, p < 0.01,) compared with the control group (3.9 ± 0.48, p < 0.01 and 4.2 ± 0.8, p < 0.01, respectively), which creates favorable conditions for the invasion of SARS-CoV‑2.Conclusion. According to the results of RT-PCR for SARS-CoV‑2, assessment of the expression of ACE‑2 and Furin, it is possible with a high degree of probability to assert about the viral load and the vulnerability of the kidneys, since these proteins are informative markers of viral damage. Elderly people with increased vulnerability to SARS-CoV‑2.

PREDICTIVE VALUE OF THE DYNAMIC DETERMINATION OF CIRCULATING TUMOR DNA ON PFS IN PATIENTS WITH EGFR MUTATED NSCLC, WITH OSIMERTINIB THERAPY

2020 ◽  
Vol 66 (2) ◽  
pp. 135-142
Author(s):  
Fedor Moiseenko ◽  
Mariya Stepanova ◽  
Nikita Volkov ◽  
Albina Zhabina ◽  
A. Myslik ◽  
...  
Keyword(s):  
Predictive Value ◽  
Molecular Genetic ◽  
Predictive Marker ◽  
Circulating Tumor Dna ◽  
Qualitative Assessment ◽  
Genetic Profile ◽  
T790m Mutation ◽  
Rare Mutations ◽  
Effect Of Therapy ◽  
Pcr Method

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.

A bigger brain for a more complex environment

2020 ◽  
Vol 31 (8) ◽  
pp. 803-816
Author(s):  
Umberto di Porzio
Keyword(s):  
Human Brain ◽  
Cognitive Abilities ◽  
Molecular Genetic ◽  
Adult Size ◽  
Genetic Changes ◽  
Cultural Challenges ◽  
Birth Canal ◽  
Newborn Brain ◽  
Neuronal Interactions ◽  
The Brain

AbstractThe environment increased complexity required more neural functions to develop in the hominin brains, and the hominins adapted to the complexity by developing a bigger brain with a greater interconnection between its parts. Thus, complex environments drove the growth of the brain. In about two million years during hominin evolution, the brain increased three folds in size, one of the largest and most complex amongst mammals, relative to body size. The size increase has led to anatomical reorganization and complex neuronal interactions in a relatively small skull. At birth, the human brain is only about 20% of its adult size. That facilitates the passage through the birth canal. Therefore, the human brain, especially cortex, develops postnatally in a rich stimulating environment with continuous brain wiring and rewiring and insertion of billions of new neurons. One of the consequence is that in the newborn brain, neuroplasticity is always turned “on” and it remains active throughout life, which gave humans the ability to adapt to complex and often hostile environments, integrate external experiences, solve problems, elaborate abstract ideas and innovative technologies, store a lot of information. Besides, hominins acquired unique abilities as music, language, and intense social cooperation. Overwhelming ecological, social, and cultural challenges have made the human brain so unique. From these events, as well as the molecular genetic changes that took place in those million years, under the pressure of natural selection, derive the distinctive cognitive abilities that have led us to complex social organizations and made our species successful.

scholarly journals Chronic Alcohol Use Induces Molecular Genetic Changes in the Dorsomedial Thalamus of People with Alcohol-Related Disorders

2021 ◽  
Vol 11 (4) ◽  
pp. 435
Author(s):  
Andreas-Christian Hade ◽  
Mari-Anne Philips ◽  
Ene Reimann ◽  
Toomas Jagomäe ◽  
Kattri-Liis Eskla ◽  
...  
Keyword(s):  
Alcohol Use ◽  
Molecular Genetic ◽  
Brain Structures ◽  
Thalamic Nuclei ◽  
Genetic Changes ◽  
Molecular Changes ◽  
Gabaergic Neurotransmission ◽  
And Control ◽  
Upregulated Genes

The Mediodorsal (MD) thalamus that represents a fundamental subcortical relay has been underrepresented in the studies focusing on the molecular changes in the brains of subjects with alcohol use disorder (AUD). In the current study, MD thalamic regions from AUD subjects and controls were analyzed with Affymetrix Clariom S human microarray. Long-term alcohol use induced a significant (FDR ≤ 0.05) upregulation of 2802 transcripts and downregulation of 1893 genes in the MD thalamus of AUD subjects. A significant upregulation of GRIN1 (glutamate receptor NMDA type 1) and FTO (alpha-ketoglutarate dependent dioxygenase) was confirmed in western blot analysis. Immunohistochemical staining revealed similar heterogenous distribution of GRIN1 in the thalamic nuclei of both AUD and control subjects. The most prevalent functional categories of upregulated genes were related to glutamatergic and GABAergic neurotransmission, cellular metabolism, and neurodevelopment. The prevalent gene cluster among down-regulated genes was immune system mediators. Forty-two differentially expressed genes, including FTO, ADH1B, DRD2, CADM2, TCF4, GCKR, DPP6, MAPT and CHRH1, have been shown to have strong associations (FDR p < 10−8) with AUD or/and alcohol use phenotypes in recent GWA studies. Despite a small number of subjects, we were able to detect robust molecular changes in the mediodorsal thalamus caused by alcohol emphasizing the importance of deeper brain structures such as diencephalon, in the development of AUD-related dysregulation of neurocircuitry.

Molecular Genetic Changes in Alveolar Soft Part Sarcoma

1998 ◽  
Vol 18 (6) ◽  
pp. 529-543
Author(s):  
Agnes S. Chan ◽  
Jeremy A. Squire ◽  
Paul Thorner ◽  
Maria Zielenska
Keyword(s):  
Soft Part ◽  
Molecular Genetic ◽  
Alveolar Soft Part Sarcoma ◽  
Genetic Changes

scholarly journals Molecular genetic changes in gastric carcinoma

2021 ◽  
Vol 6 ◽  
pp. 30-46
Author(s):  
Juhi Singh ◽  
Puneet Kumar ◽  
Khushi Verma ◽  
Satyender Kumar Tiwary ◽  
Gopeshwar Narayan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Carcinoma ◽  
Wide Spectrum ◽  
Molecular Genetic ◽  
Survival Rates ◽  
High Throughput Analysis ◽  
Genetic Changes ◽  
Genetic Level ◽  
New Biomarkers

Gastric cancer remains highly prevalent and accounts for a notable proportion of global cancer mortality and this is associated with poor survival rates. Understanding the molecular genetic changes of gastric carcinoma may offer an insight into its pathogenesis helps in identifying new biomarkers, aid prognostication, and novel treatment targets. Over a past few decades, advances in technology and high throughput analysis have improved understanding of the molecular genetic aspects of gastric cancer. In this article, hierarchy of the changes at genetic and molecular level including several aspects which are heterogenous and represents a wide spectrum such as tumor suppressor genes, oncogenes, cellcycle regulators, apoptosis, cell-adhesion molecules, loss of heterozygosity, microsatellite instability, and epigenetic changes. The classification of gastric carcinoma at molecular and genetic level as well as hereditary gastric carcinoma is elaborated. The molecular genetic aspects regarding pathogenesis, changes and aberrations of all genes and pathways which are involved in gastric cancer are addressed in this review.

scholarly journals Metabolic and molecular-genetic changes in the liver during carbon tetrachloride intoxication

2020 ◽  
Vol 99 (9) ◽  
pp. 996-1000
Author(s):  
Denis O. Karimov ◽  
Tatyana G. Kutlina ◽  
Guzel’ F. Mukhammadiyeva ◽  
Yana V. Valova ◽  
Samat S. Baygildin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Blood Serum ◽  
Pearson Correlation ◽  
Molecular Genetic ◽  
Experimental Studies ◽  
Pcr Amplification ◽  
Statistical Processing ◽  
Male Rats ◽  
Clinical Test ◽  
Genetic Changes

Introduction. Toxic hepatitis (TH) is a complex and multifaceted disease, the development of which is mediated by a complex of biochemical and molecular genetic interactions. The current understanding of the pathogenesis of TH and, as a consequence, its treatment is based on standardization of the phenotype of the disease, often without taking into account metabolic disorders within the cells. Material and methods. experimental studies were performed on white outbred male rats weighing 200-220 g. A 50% solution of TCM was used as a toxicant. Biochemical studies were performed on a laboratory medical photometer “Stat Fax 3300” using clinical test kits and control materials manufactured by Vector-Best LLC. Liver tissue for histological examination was subjected to the standard histological procedure and paraffin embedding. Sections 5-7 μm thick were stained with hematoxylin-eosin. Gene expression analysis was performed using real-time PCR amplification on a RotorGene instrument (QIAGEN). Statistical processing of experimental data was performed using the Pearson correlation coefficient and one-way analysis of variance (ANOVA). The results were considered reliable at p <0.05. Results. As a result of the analysis of the correlation of the expression of the studied genes and the level of biochemical parameters, it was found that the correlation of the expression of the Nfe2l2 and Gstm1 genes was r = 0.812 (p = 0.0001). The dynamics of gene expression of Chek, Gstm1, Gstp1, Nfe2l2, had a negative correlation with the level of AST activity in blood serum. And the expression of the genes Chek, Gclc, Gstm1, Nfe2l2, Ripk, Sod1 with an index of ALT activity in the blood serum. After 72 hours, the expression of almost all of the studied genes became multidirectional. And the correlation between indices is often not determined. An analysis of the relationship between the level of cytolysis enzymes and the correlation level of the studied genes showed that after 72 hours the correlation was observed in the Gstm1, Hmox, and Sod1 genes with the levels of AST and ALT.

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