Vereseerumi kasvajamarkerite kasutamine kliinilises praktikas

Vähi biomarkeri täpne definitsioon puudub. Tegemist on biomolekulidega, mida esineb nii veres, kudedes kui ka kehavedelikes. Neid biomolekule toodavad kasvajarakud või nende suurenenud tootmist mittekasvajalistes rakkudes saab seostada pahaloomulise kasvaja olemasoluga organismis. Vähi biomarkeritena on kasutusel geneetilised mutatsioonid, translokatsioonid ja geenide ekspressioonimustri muutused, mida uuritakse nii perifeerses veres kui ka kudedes. Vähi valguliste biomarkerite hulka kuuluvad hormoonid ja paljud erineva funktsiooniga valgud: ensüümid, glükoproteiinid, onkofetaalsed antigeenid ja retseptorid, mida uuritakse sagedamini verest.Artiklis on keskendutud just valguliste biomarkerite kasutamisele ning käsitletud neid kasvajamarkerite nimetuse all. Tegemist on kliinilises praktikas kõige rohkem kasutatud vähi biomarkeritega, mille tõlgendamisprobleemidega puutuvad kokku paljude erialade praktiseerivad arstid.Eesti Arst 2016; 95(9):597–60

Uusi suundi kasvajate energiametabolismi uuringutes

Genoomika kiire arengu käigus on selgunud, et selle valdkonna meetoditega ei ole võimalik erinevaid metabolismihäireid terviklikult kirjeldada ning täiendavalt on vaja kasutusele võtta teisi meetodeid rakuenergeetikast ning proteoomikast. Äärmiselt huvitavaks kujuneb selline süsteemsem käsitlus ulatuslike patoloogiliste muutustega maliigses koes. Eelmise sajandi alguses kirjeldas Otto Warburg efekti, kus tuumorirakkudes toimus eelistatult glükolüüs isegi normoksiatingimustes. Tema esmane arvamus, et just see asjaolu ongi raku maliigsuse allikas, lükati järgnevatel aastatel uute avastuste valguses ümber. Lisaks ulatuslikele rakuenergeetilistele ümberkorraldustele maliigse raku sees (nt kärbitud Krebsi-tsükkel, hingamisahela superkompleksid) on viimastel aastatel erinevate vähipaikmete juures korduvalt tõestatud ka kahe kompartmendi olemasolu, kus maliigne rakk allutab ümbritseva strooma enda jaoks vajalikke metaboliite tootma. Maliigsuse täpsem olemus, paremad ravimisihtmärgid ning -strateegiad võivad peituda just kasvajate süsteemsemate uuringute tulemustes. Eesti Arst 2013; 92(5):261–26

Ravimite rahastus Eestis – aeg muutusteks

Tööealise elanikkonna haigestumine on üks peamisi majanduskasvu peetumise allikaid globaalselt ning Eesti ei ole erand. Olukorra parandamisel on lisaks inimeste tervisekäitumisele ja meditsiinipersonali olemasolule kriitilise tähtsusega tänapäevase ravi kättesaadavus. Euroopas läbiviidud uuringu andmetel on 160 ravimist, mille Euroopa Ravimiamet on viimase 4 aasta jooksul heaks kiitnud, Eestis kättesaadavad vaid 41 ning aeg ravimi soodusravimite nimekirja arvamiseni on Eestis keskmiselt 599 päeva. Sellega jääb Eesti maha Euroopa Liidu keskmisest ja on pingereas tagapool mitmest meist majanduslikult nõrgemast riigist. Praegusele parimale teadmisele tuginedes on olukorra parandamiseks vaja uuendada Eesti tervisetehnoloogiate hindamise süsteemi ja siduda ravimitele soodustuse andmise piirmäärad majanduse arengu tasemega

Colorectal polyps increase the glycolytic activity

In colorectal cancer (CRC) energy metabolism research, the precancerous stage of polyp has remained rather unexplored. By now, it has been shown that CRC has not fully obtained the glycolytic phenotype proposed by O. Warburg and rather depends on mitochondrial respiration. However, the pattern of metabolic adaptations during tumorigenesis is still unknown. Understanding the interplay between genetic and metabolic changes that initiate tumor development could provide biomarkers for diagnosing cancer early and targets for new cancer therapeutics. We used human CRC and polyp tissue material and performed high-resolution respirometry and qRT-PCR to detect changes on molecular and functional level with the goal of generally describing metabolic reprogramming during CRC development. Colon polyps were found to have a more glycolytic bioenergetic phenotype than tumors and normal tissues. This was supported by a greater GLUT1, HK, LDHA, and MCT expression. Despite the increased glycolytic activity, cells in polyps were still able to maintain a highly functional OXPHOS system. The mechanisms of OXPHOS regulation and the preferred substrates are currently unclear and would require further investigation. During polyp formation, intracellular energy transfer pathways become rearranged mainly by increasing the expression of mitochondrial adenylate kinase (AK) and creatine kinase (CK) isoforms. Decreased glycolysis and maintenance of OXPHOS activity, together with the downregulation of the CK system and the most common AK isoforms (AK1 and AK2), seem to play a relevant role in CRC development

Precise, Genotype-First Breast Cancer Prevention : Experience With Transferring Monogenic Findings From a Population Biobank to the Clinical Setting

Although hereditary breast cancer screening and management are well accepted and established in clinical settings, these efforts result in the detection of only a fraction of genetic predisposition at the population level. Here, we describe our experience from a national pilot study (2018-2021) in which 180 female participants of Estonian biobank (of >150,000 participants in total) were re-contacted to discuss personalized clinical prevention measures based on their genetic predisposition defined by 11 breast cancer-related genes. Our results show that genetic risk variants are relatively common in the average-risk Estonian population. Seventy-five percent of breast cancer cases in at-risk subjects occurred before the age of 50 years. Only one-third of subjects would have been eligible for clinical screening according to the current criteria. The participants perceived the receipt of genetic risk information as valuable. Fluent cooperation of project teams supported by state-of-art data management, quality control, and secure transfer can enable the integration of research results to everyday medical practice in a highly efficient, timely, and well-accepted manner. The positive experience in this genotype-first breast cancer study confirms the value of using existing basic genomic data from population biobanks for precise prevention.Peer reviewe

Quality of life of palliative chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction treated with irinotecan combined with 5-fluorouracil and folinic acid: results of a randomised phase III trial

41st Annual Meeting of the American-Society-of-Clinical-Oncology -- MAY 13-17, 2005 -- Orlando, FLWOS: 000268881000007PubMed ID: 19568958The quality of life (QL) of advanced gastric cancer patients receiving irinotecan, folinic acid and 5-fluorouracil (5-FU) (IF arm) or cisplatin with 5-FU (CF arm) is presented. Patients with measurable or evaluable advanced gastric cancer received IF weekly for 6/7 weeks or CF q4 weeks. QL was assessed using the EORTC QLQ-C30 at baseline, subsequently every 8 weeks until progression and thereafter every 3 months until death. The QL data were analysed using several statistical methods including summary measures and pattern-mixture modelling. A total of 333 patients were randomised and treated (IF 170, CF 163). The time-to-progression for IF and CF was 5.0 and 4.2 months (P = 0.088), respectively. The overall compliance rates for QL questionnaire completion were 60 and 56% in the IF and CF arms, respectively. Significant treatment differences were observed for the physical functioning scale (P = 0.024), nausea\vomiting (P = 0.001) and EQ-5D thermometer (P = 0.020) in favour of the IF treatment arm. There was a trend in favour of IF over CF in time-to-progression. The IF group also demonstrated a better safety profile than CF and a better QL on a number of multi-item scales, suggesting that IF offers an alternative first-line platinum-free treatment option for advanced gastric cancer.Amer Soc Clin Onco

Mitochondrial Respiration in Human Colorectal and Breast Cancer Clinical Material Is Regulated Differently

International audienc