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Summary - Screening 8 - Research seminar - Lung cancer
1.1 Lung cancer
Smoking, occupational exposures (asbestos, combustion fumes) and environmental exposure (passivesmoking, air pollution;).
Lung cancer is often diagnosed only in a metastatic stage.
- non-small cell lung cancer (NSCLC) 85%
- small cell lung carcinoma (SCLC) 15% - poorer prognosis in comparison with NSCLC
- primary tumor
- regional lymph nodes invasion
- distant metastases
Negative link between tumor stage and prognosis.
Treatment depends on stage and histology of the tumor, and also on the general stage of the patient.
Surgery, radiotherapy, chemoterapy, targeted therapy or combination of therapies.
Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. If left untreated, this growth can spread beyond the lung in a process called metastasis into nearby tissue or other parts of the body. Most cancers that start in lung, known as primary lung cancers, arecarcinomas that derive from epithelial cells. The main types of lung cancer are small-cell lung carcinoma (SCLC), also called oat cell cancer, and non-small-cell lung carcinoma (NSCLC). The most common symptoms are coughing (including coughing up blood), weight loss and shortness of breath.
1.2 Metabolomics/Nuclear magnetic resonace spectroscopy
Detects metabolomic responses to various stimuli, such as disease.
Targets small molecules/metabolites (fattyacids, amino acids, sugars;)
Metabolites are end products of cellular metabolism --> they are the closest to the phenotype
--> PROTEOME (enzyme)
--> METABOLOME (metabolism: substrate + enzyme => product, metabolite)
Interaction between host genome and environmental factors --> characteristic metabolomic profile of a body fluid
Generates metabolic phenotype of body fluids (plasma, serum, urine, ...). Gives information (detailed information on molecular structure) on a wide range of metabolites in a single measurement = METABOLIC SNAPSHOT.
1H is very abundant in organic molecules. 1H NMR measures H-atoms in metabolites.
H-containing molecules in a sample give 1H NMR spectrum.
You can identify components present in the sample. If you compare components present in cancer patients with components in controls, you can observe the difference between metabolites present. You can identify metabolites, that are specific for cancer.
1.3 Metabolomic reprogramming in cancer cells
- energy and nutrients (ATP, glucose, FA, AA;)
- growth factors and downstream signalling pathways
Cancer cell metabolism
Reorganized, to increase anabolic reactions linked to cell growth and cell proliferation.
- consumes glucose at a very high rate
- large increase in glycolysis
- secretes most of the glucose-derived carbon as lactate rather than oxidizing it completely via oxidative phosphorylation (faster?)
2 Early detection
There is an urgent need for effective tools, that would enable an early detection of lung cancer!!!
NMR analyses of the metabolic phenotype of blood plasma permit the early detection of lung cancer??
Many benefits of this technology, including its noninvasive nature and its capacity to identify malignant markers. In the coming years, MRS can be expected to follow the pattern of previous biomedical imaging technologies, advancing from a diagnostic method to a method for longitudinally tracking tumor changes and observing patient response to treatment. Research results and primary observation strongly suggest a promising future for MRS in the oncologic management of patients.
- examine which metabolites/biochemical pathways are involved in the development of lung cancer
- investigate whether metabolic changes in the blood correlate with metabolic changes on a PET/CT-scan
- investigate whether patients who do not react on specific therapy can be discriminated from patients who do react on that therapy by means of 1H-NMR spectroscopy