The Institute for Molecular Medicine

The investigators will prospectively recruit 100 NSCLC patients. The cfDNA samples will be gathered before the surgery and postoperatively 4-6 weeks after surgery and at 6 and 12 months follow-up visits.
This study aims to investigate the role of ctDNA in NSCLC patients treated with curative intent surgery.
Preoperative ctDNA will be compared to primary tumor DNA to investigate the concordance of mutations and gained mutations from possible primary tumor cancer stem cell.
Preoperative ctDNA findings will be tested for associations with baseline characteristics as well as clinically important factors such as TNM stage, histopathological findings, and tumor volume.
The investigators aim to identify molecular residual disease (MRD) using multiple ctDNA samples after the surgery and search the associations with clinical recurrence and survival, with possible correlation to palliative chemotherapy response
Using multiple ctDNA samples, the investigators will gather information about tumor heterogeneity, diversity of disease genotypes, and dynamic changes in ctDNA.
If additional data from palliative immunotherapy (PD-L1 inhibitors) is available, the effect of this will be evaluated in the study.

P5.fi study - P4 together with a fifth 'P' and '.fi' for population health Finally Implemented in Finland - studies the value of returning genetic and metabolomic risk information in two diseases (coronary heart disease and type 2 diabetes) and one feature (venous thromboembolism). The hypothesis of the study is that 1) combining genetic and metabolic risk with traditional risk factors adds value to the personal risk assessment of these diseases, 2) such risk information can be provided to individuals using a web based user portal in an easily understandable and useful format, and 3) receiving genetic and metabolomic risk information has an effect on the health of the study participants.
The study is a continuation of FinHealth 2017 -study, which involved more than 7,000 Finns from around the country. The participants of FinHealth were invited to participate in P5.fi -study. The new research utilises information, samples, and measurements obtained in the FinHealth Study. Prospective clinical significance of selected genetic and metabolomic risk scores will be studied in 30.000 Finnish individuals. The study will analyze the genetic and metabolomic profile of the P5.fi participants and develop and test a protocol for returning them health related risk information. The impact of the intervention will by followed up by questionnaires and national health registers for five years.

The most frequent form of adult-onset mitochondrial disorders is mitochondrial myopathy, often manifesting with progressive external ophthalmoplegia (PEO), progressive muscle weakness and exercise intolerance. Mitochondrial myopathy is often caused by single heteroplasmic mitochondrial DNA (mtDNA) deletions or multiple mtDNA deletions, the former being sporadic and latter caused by mutations in nuclear-encoded proteins of mtDNA maintenance. Currently, no curative treatment exists for this disease. The investigators have previously observed that supplementation with an NAD+ precursor vitamin B3, nicotinamide riboside, prevented and delayed disease symptoms by increasing mitochondrial biogenesis in a mouse model for mitochondrial myopathy. Vitamin B3 exists in several forms: nicotinic acid (niacin), nicotinamide, and nicotinamide riboside, and it has been demonstrated to give power to diseased mitochondria in animal studies by increasing intracellular levels of NAD+, the important cofactor required for the cellular energy metabolism.
In this study, the form of vitamin B3, niacin, was used to activate dysfunctional mitochondria and to rescue signs of mitochondrial myopathy. Of the vitamin B3 forms, niacin, is employed, because it has been used in large doses to treat hypercholesterolemia patients, and has a proven safety record in humans. Phenotypically similar mitochondrial myopathy patients are studied, as the investigator's previous expertise indicates that similar presenting phenotypes predict uniform physiological and clinical responses to interventions, despite varying genetic backgrounds. Patients either with sporadic single mtDNA deletions or a mutation in a Twinkle gene causing multiple mtDNA deletions were recruited. In addition, for every patient, two gender- and age-matched healthy controls are recruited. Clinical examinations and collection of muscle biopsies are performed at the time points 0, 4 and 10 months (patients) or at 0 and 4 months (controls). Fasting blood samples are collected every second week until 4 months and thereafter every six weeks until the end of the study. The effects of niacin on disease markers, muscle mitochondrial biogenesis, muscle strength and the metabolism of the whole body are studied in patients and healthy controls.
The hypothesis is that an NAD+ precursor, niacin, will increase intracellular NAD+ levels, improve mitochondrial biogenesis and alleviate the symptoms of mitochondrial myopathy in humans.