predictive preventive personalized medicine
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BACKGROUND: Cancer management faces multiple obstacles, including resistance to current therapeutic approaches. In the face of challenging microenvironments, cancer cells adapt metabolically to maintain their supply of energy and precursor molecules for biosynthesis and thus sustain rapid proliferation and tumor growth. Among the various metabolic adaptations observed in cancer cells, the altered glucose metabolism is the most widely studied. The aberrant glycolytic modification in cancer cells has been associated with rapid cell division, tumor growth, cancer progression, and drug resistance. The higher rates of glycolysis in cancer cells, as a hallmark of cancer progression, is modulated by the transcription factor hypoxia inducible factor 1 alpha (HIF-1α), a downstream target of the PI3K/Akt signaling, the most deregulated pathway in cancer. AIM OF REVIEW: We provide a detailed overview of current, primarily experimental, evidence on the potential effectiveness of flavonoids to combat aberrant glycolysis-induced resistance of cancer cells to conventional and targeted therapies. The manuscript focuses primarily on flavonoids reducing cancer resistance via affecting PI3K/Akt, HIF-1α (as the transcription factor critical for glucose metabolism of cancer cells that is regulated by PI3K/Akt pathway), and key glycolytic mediators downstream of PI3K/Akt/HIF-1α signaling (glucose transporters and key glycolytic enzymes). KEY SCIENTIFIC CONCEPTS OF REVIEW: The working hypothesis of the manuscript proposes HIF-1α - the transcription factor critical for glucose metabolism of cancer cells regulated by PI3K/Akt pathway as an attractive target for application of flavonoids to mitigate cancer resistance. Phytochemicals represent a source of promising substances for cancer management applicable to primary, secondary, and tertiary care. However, accurate patient stratification and individualized patient profiling represent crucial steps in the paradigm shift from reactive to predictive, preventive, and personalized medicine (PPPM / 3PM). The article is focused on targeting molecular patterns by natural substances and provides evidence-based recommendations for the 3PM relevant implementation.
- MeSH
- flavonoidy MeSH
- fosfatidylinositol-3-kinasy metabolismus MeSH
- glukosa metabolismus MeSH
- individualizovaná medicína MeSH
- lidé MeSH
- nádorové mikroprostředí MeSH
- nádory * farmakoterapie metabolismus MeSH
- protoonkogenní proteiny c-akt * metabolismus MeSH
- signální transdukce MeSH
- transkripční faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Ačkoliv pokroky v chápání podstaty chorobných procesů v poznání příčin a v diagnostice směřují medicínu k její stále podrobnější „personalizaci“, vznikají i pochybnosti o míře její únosnosti z hlediska nákladů na zdravotní péči a její v současnosti používané systémy. K zdůrazňování nezbytnosti přijmout individuálnost nemoci každého pacienta přispěly úspěchy v analýze sekvence lidského genomu, možnost současného sledování aktivity téměř všech jeho genů, kterých bylo dosaženo prudkým rozvojem nových technologií. Zlepšená diagnostika je provázena i účinnější terapií, zvláště v oblasti farmakogenomiky a vývojem léků s větší schopností zasáhnout jednotlivé konkrétní cíle patologického procesu.
Personalized medicine has become declared to be a strategic goal of nearly all medical disciplines, a modern fashion of medicine, which corresponds to unexpected progress in knowledge of structure and sometimes also understanding the function of our genome. This was made possible by development of new technologies and methodological approaches, which led to improved and more detailed diagnostics and categorization of diseases Also pharmaceutical industry is producing many new drugs, but not all are effective as supposed, and sometimes also cause adverse reactions (ADR). To prevent uneffectiveness and ADR, preliminary genetic testing of patients seems to be necessary. Utility of personalized medicine is sometimes discussed from the point of view of supposed inevitable increase of cost and problems with its adoption by existing system of healthcare.
Cancer causes many deaths worldwide each year, especially due to tumor heterogeneity leading to disease progression and treatment failure. Targeted treatment of heterogeneous population of cells - cancer stem cells is still an issue in protecting affected individuals against associated multidrug resistance and disease progression. Nanotherapeutic agents have the potential to go beyond state-of-the-art approaches in overall cancer management. Specially assembled nanoparticles act as carriers for targeted drug delivery. Several nanodrugs have already been approved by the US Food and Drug Administration (FDA) for treating different cancer types. Phytochemicals isolated from plants demonstrate considerable potential for nanomedical applications in oncology thanks to their antioxidant, anti-inflammatory, anti-proliferative, and other health benefits. Phytochemical-based NPs can enhance anticancer therapeutic effects, improve cellular uptake of therapeutic agents, and mitigate the side effects of toxic anticancer treatments. Per evidence, phytochemical-based NPs can specifically target CSCs decreasing risks of tumor relapse and metastatic disease manifestation. Therefore, this review focuses on current outlook of phytochemical-based NPs and their potential targeting CSCs in cancer research studies and their consideration in the framework of predictive, preventive, and personalized medicine (3PM).
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Prediktivní genetika používá genetické testy k odhadu rizika u asymptomatických osob. Protože u multifaktoriálních onemocnění pracuje prediktivní genetická analýza se zjištěními, která dovolují širší výklad, má u jednoznačně podmíněných chorob (monogenních) s vysokou penetrací větší výpovědní hodnotu než u multifaktoriálních (polygenních) onemocnění s vysokou účastí faktorů prostředí. Na patogenezi většiny "civilizačních" (multifaktoriálních) onemocnění včetně diabetu se neúčastní odděleně dědičnost a faktory prostředí, ale zásadní roli hrají interakce mezi nimi. Nová klasifikace diabetu vychází z implementace nejen nových etiopatogenetických, ale i genetických výzkumů. Diabetes mellitus 1. typu (DM1T) je polygenní multifaktoriální choroba, genetická složka přináší asi polovinu rizika a negenetická složka druhou polovinu. Studium autoimunitního charakteru DM1T ve spojení s genetickou analýzou přinese v budoucnu i nové poznatky v predikci DM1T. Zmíněny jsou nové poznatky molekulární genetiky týkající se některých specifických typů diabetu. Problematika dědičnosti u diabetes mellitus 2. typu (DM2T) je ještě komplikovanější. Onemocnění má polygenní charakter a na fenotypu nemocného s DM2T se kromě významné účasti faktorů zevního prostředí uplatňují nejméně tři, ale možná desítky různých genetických variací. V současnosti se za nejvíce slibné jeví výsledky analýz na úrovni celého genomu. V současné době je reálným východiskem predikce a prevence DM2T současné pojetí prediabetu. Multifaktoriální, multimarkerový přístup, který vychází z pochopení nových patofyziologických faktorů DM2T, se snaží vytvořit "mapu" fyziologie prediabetu, a pokud se k těmto testům přiřadí sofistikované metody genetické předpovědi DM2T, postoupili bychom výrazně v metodice predikce diabetu. Zatím je však prediktivní genetika limitována interpretací genetické predispozice a individualizací míry rizika. Při interpretaci je nesporně nutná spolupráce s klinikem a výsledky genetických analýz nelze zatím nekriticky přeceňovat. Prediktivní medicína však nesporně naplňuje preventivní zaměření současné medicíny a genetická analýza je perspektivní diagnostickou metodou.
Predictive genetics uses genetic testing to estimate the risk in asymptomatic persons. Since in the case of multifactorial diseases predictive genetic analysis deals with findings which allow wider interpretation, it has a higher predictive value in expressly qualified diseases (monogenous) with high penetration compared to multifactorial (polygenous) diseases with high participation of environmental factors. In most “civilisation” (multifactorial) diseases including diabetes, heredity and environmental factors do not play two separate, independent roles. Instead, their interactions play a principal role. The new classification of diabetes is based on the implementation of not only ethiopathogenetic, but also genetic research. Diabetes mellitus type 1 (DM1T) is a polygenous multifactorial disease with the genetic component carrying about one half of the risk, the non‑genetic one the other half. The study of the autoimmune nature of DM1T in connection with genetic analysis is going to bring about new insights in DM1T prediction. The author presents new pieces of knowledge on molecular genetics concerning certain specific types of diabetes. Issues relating to heredity in diabetes mellitus type 2 (DM2T) are even more complex. The disease has a polygenous nature, and the phenotype of a patient with DM2T, in addition to environmental factors, involves at least three, perhaps even tens of different genetic variations. At present, results at the genom‑ wide level appear to be most promising. The current concept of prediabetes is a realistic foundation for our prediction and prevention of DM2T. A multifactorial, multimarker approach based on our understanding of new pathophysiological factors of DM2T, tries to outline a “map” of prediabetes physiology, and if these tests are combined with sophisticated methods of genetic forecasting of DM2T, this may represent a significant step in our methodology of diabetes prediction. So far however, predictive genetics is limited by the interpretation of genetic predisposition and individualisation of the level of risk. There is no doubt that interpretation calls for co‑ operation with clinicians, while results of genetic analyses should presently be not uncritically overestimated. Predictive medicine, however, unquestionably fulfills the preventive focus of modern medicine, and genetic analysis is a perspective diagnostic method.
- Klíčová slova
- genetic testing,
- MeSH
- diabetes mellitus MeSH
- genetická predispozice k nemoci MeSH
- genetické poradenství MeSH
- genetické testování MeSH
- lidé MeSH
- rizikové faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
... /ica, Georgi lskrov, and Rumen Štefanov -- Biobanking for Rare Diseases - Impact on Personalised Medicine ... ... Technologies for Gene Identification in Rare Diseases 33 -- Filippo Belcggia and Bernd Wollnik -- Personalized ... ... Medicine for Hereditary Deafness 47 -- Jessica Ordonez, Oscar Diaz-Horta. and Mustafa Tckin -- Mitochondrial ... ... Nikolajs Zeps and Chris Hemmings -- Adeno-Associated Virus Gene Therapy and Its Application to the Prevention ...
Advances in predictive, preventive and personalised medicine, ISSN 2211-3495 Vol. 6
xviii, 208 s. : il., tab. ; 24 cm
Abdominal aortic aneurysm (AAA) is often a hidden pathological process showing no clinical symptoms. Genetic burden, smoking, male gender, age > 65 years, and white race have been identified as the main risk factors. A regular screening program has been introduced but is, as yet, unclear and is not performed in most countries. Prostate cancer is the most frequent male malignant disease in Western countries. Prostate cancer is a disease of older age with a median primary diagnosis of over 60 years. In recent years, advanced imaging methods have been established as important diagnostic tools in prostate cancer diagnostics. The incidental detection of AAA during diagnostic imaging performed due to prostate cancer diagnosis could reveal some asymptomatic aneurysms. Using our experience, the incidental detection of AAA during 18F-fluoromethylcholine PET/CT imaging, performed due to the staging, follow-up, and restaging of the prostate cancer, was reworked into a regular tool of secondary prevention within the framework of personalized medicine strategies. Experience with this type of AAA detection is demonstrated by a cohort of 500 patients who underwent 18F-fluorometylcholine PET/CT examination due to the staging or restaging of prostate cancer. A total of 28 aneurysms were detected (26 aneurysms < 50 mm, 2 aneurysms > 50 mm). In 2 cases (diameter < 50 mm), serious complications were found (penetrating aortic ulcer). The detection and monitoring of AAA in patients undergoing 18F-fluorometylcholine PET/CT due to the prostate cancer offers the possibility of a secondary prevention of AAA, patient stratification, and common follow-up for both pathologies.
- Publikační typ
- časopisecké články MeSH
Multi-factorial mitochondrial damage exhibits a "vicious circle" that leads to a progression of mitochondrial dysfunction and multi-organ adverse effects. Mitochondrial impairments (mitochondriopathies) are associated with severe pathologies including but not restricted to cancers, cardiovascular diseases, and neurodegeneration. However, the type and level of cascading pathologies are highly individual. Consequently, patient stratification, risk assessment, and mitigating measures are instrumental for cost-effective individualized protection. Therefore, the paradigm shift from reactive to predictive, preventive, and personalized medicine (3PM) is unavoidable in advanced healthcare. Flavonoids demonstrate evident antioxidant and scavenging activity are of great therapeutic utility against mitochondrial damage and cascading pathologies. In the context of 3PM, this review focuses on preclinical and clinical research data evaluating the efficacy of flavonoids as a potent protector against mitochondriopathies and associated pathologies.
- MeSH
- antioxidancia farmakologie terapeutické užití MeSH
- cytoprotekce účinky léků MeSH
- flavonoidy farmakologie terapeutické užití MeSH
- individualizovaná medicína metody MeSH
- lidé MeSH
- mitochondriální nemoci diagnóza prevence a kontrola MeSH
- mitochondrie účinky léků metabolismus MeSH
- mitofagie účinky léků MeSH
- oxidační stres účinky léků MeSH
- prognóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Biobanks are an important compound of personalized medicine and strongly support the scientific progress in stratification of population and biomarker discovery and validation due to progress in personalized medicine. Biobanks are an essential tool for new drug discoveries and drug development. Biobanks play an important role in the whole process of patient prevention and prediction, follow-up, and therapy monitoring and optimalization. Biobanks have the specificity in that they cover multidisciplinary approach to the human health combining biological and medical approaches, as well as informative bioinformatics technologies, computationing, and modeling. The importance of biobanks has during the last decade increased in variety and capacity from small collections of samples to large-scale national or international repositories. Collected samples are population-based, disease-specific or rare diseases originating from a diverse profile of individuals. There are various purposes of biobanks, such as diagnostics, pharmacology, or research. Biobanks involve, store, and operate with specific personal information, and as a consequence, such a diversity of biobanking is associated with a broad spectrum of ethical and legal issues. Biobanks are an international phenomenon because any single country, state, or society at the moment is not able to cover all issues involving the whole biobank problematic. Biobanks have an enormous innovative potential in the whole process of biomedical research in the twenty-first century.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- MeSH
- individualizovaná medicína MeSH
- kongresy jako téma MeSH
- preventivní lékařství MeSH
- Publikační typ
- zprávy MeSH
