Читать книгу The Internet of Medical Things (IoMT) - Группа авторов - Страница 13

Lung cancer is known to be the number one cause of cancer deaths among all the cancer in both men and women in worldwide. According to a World Health Organization (WHO) survey, lung cancer caused 19.1 deaths per 100,000 in Malaysia, or 4,088 deaths per year (3.22% of all deaths) [1]. Moreover, there was a record of 1.69 million of deaths worldwide in 2015 due to lung cancer. Furthermore, a research in UK estimated that there will be 23.6 million of new cases of cancer worldwide each year by 2030 [1]. The main cause of lung cancer deaths is smoking. Almost 8% of people died because of it. Furthermore, the second reason is exposure to secondhand smoke. Thus, it is very clear that smoking is the leading risk factor for lung cancer. However, not everyone who got lung cancer is smokers as many people with lung cancer are former smokers while many others never smoked at all. Moreover, radiation exposure, unhealthy lifestyle, secondhand smoke, pollution of air, genetic markers, prolongs inhalation of asbestos, and chemicals as well as other factors can cause lung cancer non-smokers [2].

Furthermore, it seems that most lung cancer signs do not appear until the cancer has spread, although some people with early lung cancer do have symptoms. Generally, the symptoms of lung cancer are a cough that does not go away and instead gets worse, shortness of breath, chest pain, feeling tired or weak, new onset of wheezing, and some lung cancer can even cause syndrome [3]. On top of that, a number of tests can be conducted in order to look for cancerous cell such as X-ray image of lung that could disclose the abnormal mass or nodule, a CT scan to exhibit small lesions in the lungs which may not detected on X-ray, blood investigations, sputum cytology, and tissue biopsy [4]. Lung cancer treatments being carried out are adjuvant therapy which may include radiation, chemotherapy, targeted therapy, or immunotherapy.

Since they originate from the bronchi within the lungs, small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC) are the two main clinic pathological classes for lung cancer. They are also known as bronchogenic carcinomas because they arise from the bronchi within the lungs [4]. Lung cancer is believed to be arising after a series of continuous pathological changes (preneoplastic lesions) which very often discovered accompanying lung cancers as well as in the respiratory mucosa of smokers. Apart from that, the genes involved in lung cancer are epidermal growth factor receptor (EGFR), KRAS, MET, LKBI, BREF, ALK, RET, and tumor suppressor gene (TP53) [5]. The three most common genes in lung cancer are EGFR, KRAS, and TP53, and the structure of these genes is explored in thus study. EGFR is actually transmembrane protein that has cytoplasmic kinase movement and it transduces essential development factor motioning from the extracellular milieu to the cell. According to da Cunha Santos, more than 60% of NSCLCs expresses EGFR which has turned into an essential focus for the treatment of these tumors [6]. In addition, the KRAS mutation is the most widely recognized oncogene driver change in patients with NSCLC and presents a poor guess in the metastatic setting, making it an imperative focus for tranquilize advancement. It is difficult to treat patients with KRAS mutations since there is no targeted therapy yet [7]. Among the mutations, the most common mutation that found to occur in lung cancer is TP53 mutations and its frequency becomes greater with tobacco consumption [8]. In this study, three compounds (curcumin, ellagic acid, and quercetin) were used for docking with the three mutant proteins. Curcumin has excellent safety profile that focus on different infections with solid confirmation on molecule level. Thus, improvement in formulation criteria can aid in developing therapeutic drug [9]. Next, ellagic acid has the ability to bind with cancer cells to make them inactive and it is also effective to resist cancer in rats and mice according to a research [10]. Quercetin is a pigment from plant (flavonoid) which has anti-oxidant and anti-inflammatory effect. It has shown to inhibit the multiplication of cancer cells according to Pao-Chen Kuo et al. [11].

Bioinformatics is a multidisciplinary discipline that creates methods and software tools for storing, extracting, organizing, and interpreting biological data. To analyze biological data, a combination of bioinformatics and computer science, statistics, physics, chemistry, mathematics, and engineering is useful. Currently, this method is growing rapidly because it is cheap and quite faster than experimental approaches. Computational biology tools such as protein modeling (e.g., Swiss Model, Easy Modeller, and Modeller), molecular dynamic simulation (e.g., Gromacs and Amber), and docking (e.g., Autodock version 4.2, AutodockVina, Swissdock, and Haddock) helped design substrate-based drugs to study the interaction between the target proteins (cancer cell proteins) and ligand (phytocomponents).

The aim of conducting this research is to initiate three-dimensional (3D) models of lung cancer line proteins (EGFR, K-ras oncogene, and TP53) and to guesstimate their binding affinities with curcumin, ellagic acid, and quercetin via docking approach.