CHAPTER TWO
LITERATURE REVIEWS ON BIOSENSORS AND RISK PERPECTION AND COMMUNICATIONS
1) INTRODUCTION
In time past, work relating to this project has been done. This Chapter aims at reviewing such works, compare research studies and provide a work base for this project. Cancer diagnosis is presently undergoing a paradigm shift with the integration of molecular biomarkers as part of a routine diagnostic panel. The molecular shift ranges from those comprising of the DNA, RNA, microRNAs (miRNAs) and proteins. The miRNAs were newly discovered as a small non-coding endogenous single-stranded RNAs that critically controls the development, invasion and metastasis of cancers [13]. MiRNAs are different with cancers; they are seen to have the potential to function as diagnostic markers for cancer. Also, the deregulating of the activities of miRNAs offers a novel cancer therapeutic approach that provides high throughput techniques for the identification of changed cellular molecules [13]. The application of miRNAs to a change of body specimens from blood to tissues has been beneficial and is valued in the clinical environment. Generally, the novel cancer diagnostic tools have extended their application as prognostic risk factors that are also targeted as a personalized medicine to individuals. Figure 5: Molecular diagnostic schema representing routine biological specimens and their molecular alterations [13]
It has been noted that delivering an early and accurate diagnosis in cancer
1. Introduction and Problem Statement: Cancer has a major societal impact in the United States and across the globe. In 2015, an estimated 1,658,370 new cases of cancer will be diagnosed in United States, and 589,430 people are estimated to die of the disease. Unfortunately, low cancer cell availability in human samples is a current barrier for early disease detection. There is an unmet medical need to improve methods of early cancer detection so that patients can receive treatment before cancer metastasizes to other areas of the body, resulting in better health outcomes.
This personalized approach is carried out using unique genetic and molecular biomarkers or signatures as epigenetic and the microenvironment play an essential role in the final manifestation of the malignant process
An abnormality in this process leads to a number of problems, including cancer. MicroRNAs are a type of RNA which inhibit the expression of genes and play a vital role in the development of cancer. Of notable interest is miR-378, as it increases tumor angiogenesis and growth and also enhances the survival of these cells, by decreasing the expression of tumor suppression genes like Sufu. A study testing human cell lines found that when Sufu expression levels were high, miR-378 expression levels were low, and when Sufu levels were low, miR-378 levels were high, showcasing that the two were negatively correlated. Because repression of Sufu can lead to rampant proliferation of cells, the inhibition of Sufu is essential in order for miR-378 to promote angiogenesis and increase cell
Biomarkers are natural indicators in the body that respond noticeably to the presence of disease. By measuring the responses of biomarkers, oncologists detect the cancerous cells before recommending expensive procedures, rather than immediately resorting to these procedures. One of these biomarkers that responds to the presence of cancerous cells is microRNA. MicroRNAs are molecules that are involved in the cell life cycle and therefore the progression of cancerous cells. A study in cancer patients was conducted to compare the accuracy of screening with microRNAs to screening with LDCT. Observing microRNAs did not prove to be as accurate at identifying cancer as LDCT, but since using microRNAs is a less expensive process, it can identify patients that should undergo LCDT testing. Screening with microRNA testing initially would decrease the number of patients paying for LCDT testing.
As such, it is important for the new doctor and patient to identify the poorly differentiated cancer cells that have the potential of spreading fast. This early recognition of this type of
The doctors could tell if the cells keep mutating or they stop, and they could see if the cancer cells spread out to the other parts of the body.
of new ways in how we can determined the cure of cancer and damage the
Over the past few decades, researchers have made significant advancements to the treatment and detection of cancers and similar diseases. However, these treatments have certain limitations due to cancer’s ever changing entity. If even an undetectable sliver of a tumor is left, it can mutate, multiply and wreak havoc once more. Cancer patients in remission usually face this unfortunate scenario. What’s worse is that the previous treatment is consistently compromised by the cancer’s new mutations. We are constantly chasing after cancer, it has been evading us at every turn and opportunity until now.
Hepatocellular carcinoma (HCC), a lethal liver cancer, has a very poor prognosis and is in dire need of novel targets to develop more effective treatments. The conventional treatment options of surgery and chemotherapy were limited to pre-metastatic HCC; however, a multi-kinase inhibitor, in addition to targeting other factors involved in development and progression of the disease showed promising results in advanced HCC [42]. LncRNAs such as HOTAIR, MALAT1, and H10 are dysregulated and have been suggested to play an essential role in HCC development whereas dysregulation affects proliferation, apoptosis, and metastasis. This is also true for gastric cancer, whereby dysregulation of lncRNAs- HOTAIR, HULC, and H19 are relatively linked to development, metastasis, and prognosis [43]. HCC is also characterized by aberrant expression of miRNAs. Respectively, upregulation and downregulation has been associated with invasion and metastasis, tumor progression, and drug resistance. Meng et al. proposed that aberrantly expressed miRNAs may regulate the expression of certain genes that control cell growth, migration, and invasion. In this study, the expression of miRNA in normal versus tumor tissue was investigated which led to the identification of overexpressed miR-21 in human HCC that could potentially serve as a target for regulating downstream events [44].
Cancer is a systemic disease that directly affects the region of onset and can metastasize to other sites, causing a variety of complications and loss of progressive organ function. The development of the disease may be initially slow or rapidly evolving, unavoidably affecting nutritional status (Santarpia et al., 2011). It is essentially a consequence of genetic mutations within a cell, which result in the proliferation of abnormal cells. Cancer represents a major global public health Problem. Worldwide, it accounts for 7.1 million deaths annually (12.6% of the global total); it is the leading cause of death in old age, with more than 70% of cancers occurring in those aged over 65 years (von Meyenfeldt, 2005). The World Health Organization
Therefore, patients can receive treatment before cancer metastasizes to other areas of the body, which is resulting in better health outcomes. The main challenge in circulating tumor cell (CTC) research is their detection, which requires the ability to detect one CTC out of almost 1 billion normal blood cells [2, 3]. Based on the known properties of tumor cells, several platforms for CTC detection have been developed. Such platforms can be classified into two major categories: (I) Immunochemistry-based methods, and (II) physical property-based methods. CELLSEARCHTM from Janssen Diagnostics is considered the most successful and the only FDA-approved platform for CTC detection in clinical practice in patients with breast, prostate, and colorectal cancers. Limitation of this method is the low yield of CTC capture from larger blood volume. Metastasis often involves epithelial-to-mesenchymal transition (EMT) of cells; thus, epithelial marker-dependent approaches may miss numerous CTCs that have low or absent epithelial marker expression. Isolation by size of epithelial tumor cells (ISET) [4] is another widely accepted size-based approach. This platform applies a specific membrane filter for tumor cell selection, because tumor cells are often larger and stiffer than blood cells. Main advantage of using membrane filter is that cells can be retained for further investigation. Nonetheless, the sizes of tumor cells may vary
The healthcare field is revolutionizing and always finding ways to make processes quick, effective, and conveniently accessible. An aspect of this revolution includes the use of diagnostic wearables. Wearables are positively impacting healthcare with the use of modern medicine and biotechnology, and healthcare professionals and patients are using them more readily. Being able to receive comprehensive real-time health information on one’s smartphone or smart watch allows patients to be able to track their health on a daily basis. These diagnostic devices are non-invasive and can transmit health information to physicians within seconds at any given time. These devices especially benefit senior citizens or patients living alone with chronic
Just after the Valadi’s discovery in 2007(59), various studies have been performed, in order to characterize exosomal miRNA as diagnostic biomarkers for cancers. In 2008, Taylor et al. reported that eight miRNAs, including miR-21, miR-141, miR-200a, miR-200c, miR-200b, miR-203, miR-205 and miR-214, previously demonstrated as diagnostic markers for ovarian cancer, were also present in serum exosomes, isolated from the ovarian cancer patients (74). In 2009, Rabinowits and collegues carried out a miRNA-profiling analysis on tumor biopsy specimen, exosomes isolated from lung adenocarcinoma patients and control subjects. They found a similar miRNA profile between exosomes and tumor biopsy samples from
Aim-3: To validate the automated mRNA FISH assay of ARv7, ETS gene fusion and PTEN on DeNovo’s JETTA™ microfluidic chip, Jetta 400 sample preparation system and Vanguard image processing system. Demonstrate the entire system capable of automated single cell mRNA FISH on CTCs using blood samples from patients with metastatic prostate cancer.
Aim of this project is to study opportunities and challenges of novel biosensor technology for cancer diagnosis/prognosis and how people perceive the technology in relation to the risk involve. Study shows the earlier cancer is been perceived in a person, there is a higher chance of there being a cure for it. Lately, most cancers are detected and diagnosed after it has fully grown. Hence, sensitive and accurate methods for early detection of relevant biomarkers for clinical diagnosis are of essence and need to be adopted by hospitals, clinics and also self-check by patient. Biosensors are devices intended to detect biological markers in the body, through the conversion of a biological sensing event to an electrical signal, which detects and analyse. This biosensor technology can potentially deliver fast and exact detection, dependable imaging of cancer cells, and observing of angiogenesis and cancer metastasis.