Ijeoma Unachukwu
PI: Dr. Kyle Murphy
Fall 2014 The Effect of CD44 Expression on Drug-Resistance and Cell Migration in the Zebra Fish Xenotransplant Model Abstract
Introduction
Xenotransplanting is an effective tool to look at the profileration and metastisi of cancer cells. Traditionally, xenotransplant experiments have been done in mice, but for this experient we used zebra fish. Xenotransplantation in mice can be timlely and costly and often times inefficient. Zebrafish on the other hand have can reproduce quicly and have similar systems to that of humans. One of the main benefits of using zebrafish a cancer xenotransplant model is that they do not develop an adaptive immune system until 14 days after post fertilization. This makes it possible for human cancer cells to survive when they are injected into the zebrafish embryos. (Evaluating human cancer cell metastasis in zebrafish Yong Teng, Xiayang Xie, Steven Walker, David T White, Jeff S Mumm and John K Cowell).Recent papers have already proven the similarities between human and zebrafish liver tumors at a molecular level. Also, studies have created carcinogen induced neoplasms that resemble human timors in zebra fish and they have metastasized. In every situation, human cancer cells and tissue have survived and proliferated in zebra fish provinf that it is a comparative tumor model. Not only can xenotransplanted zebrafish can support the normal development of the host and proliferation of transplanted human melanoma
Cancer, medically called ‘tumorigenesis’ (Thaker, Lutgendorf, & Sood, 2007, p.430) occurs when cells in the body orient themselves for malignant growth. Such cells show ‘self-sufficiency in growth signals’, are ‘insensitive to anti-growth signals’ and have ‘limitless replicative potential’ (Thaker, Lutgendorf, & Sood, 2007, p.430). Once a particular set of cells become malignant, the malignancy can spread to other set of cells in different organs due to ‘crosstalk’ between the affected cells and their surrounding ‘tissues’ and ‘micro-environments’(Thaker, Lutgendorf, & Sood, 2007, p.430).
In order to become cancerous a cell has many molecular changes that can occur including: tumor suppressor gene inactivation, oncogene activation, telomerase lengthening, ability to evade apoptosis, and angiogenesis (Mechanisms in Medicine, 2012). There are a few particular
Cancer occurs when cells in the human body create irregularities and start to duplicate at anomalous quick rates. The outcome is the development of tumors in or on the surface of the body and organs. Tumors might be generous (not destructive) or threatening (harmful). Since ordinary cell improvement and duplication is a moderate procedure which is well controlled, it is evident when cells duplicate so rapidly.
2013;90:118–126). Zebrafish are not only cost-efficient, but also easy to house. Therefore, they are considered ideal species for studying genetic mutations and molecular pathways (Ali S, et al.2012;228:272–283). Zebrafish are known to be social animals, which is an effective representation of human nature. Zebrafish also make very good research models to test for long-term stress disorders since they have the ability to show a wide variety of behavioral changes that can be observed in human
Cancer is listed as the second most common cause of death in western countries; particularly, in adults. Though it has a long antiquity, its prevalence and incidence today is pervasive and the war on cancer has not been promising. Malignant neoplasia is characterized by uncontrolled growth and the ability to metastasize or spread from the original site. Cancer results from mutations that promote cell proliferation and inhibit cell adhesion (metastasis). According to the National Cancer Institute (2016), “Cancer can also spread regionally,
Zebrafish (Danio rerio) are a popular freshwater fish that have been modified by researchers to produce several transgenic strains. The strain of transgenic zebrafish that express fluorescent colors have been given the name Glofish, for they contain different fluorescent proteins such as Green Fluorescent Protein (GFP), Red Fluorescent Protein (RFP), Yellow Fluorescent Protein (YFP), Blue Fluorescent Protein (BFP), or Purple Fluorescent Protein (PFP) (Vick, B. M., A. Pollak, C. Welsh, J. O. Liang, 2012). There are several benefits of using Glofish as a model to portray and understand inheritance patterns of transgenic genes. Glofish are small size in size, produce a high number of progeny, have similar genetic control to humans,
Ever since I was little, I’ve always been fascinated with everything aquatic. Seahorses, whales, fish, you name it, and I loved it. As a child, I begged my parents to no end for an aquarium, so I could have a little ocean of my own. Thankfully, one year, Santa finally pulled through, and I received the best Christmas present I can remember: my very own fish tank. Inside, it was filled with one of my favorite animals, zebrafish. Now although I knew I liked these little fish back then, it wasn’t until recently that I realized how truly fascinating these fish are. In fact, zebrafish prove to hold a treasure trove of information. This information has to potential to treat the sicknesses of millions of Americans. Today we will dive in to the basics
Genetic engineering allows biologists to manipulate an organism's genomes by utilizing biotechnology (Moulton, 2004 ). The Talimogene Laherparepvec virus, otherwise known as T-vec, is an oncolytic virus. A oncolytic virus, is a virus that destroys cancerous cells. The T-vec virus has recently had successful results for treating melanoma cancer. The virus originated from the herpes simplex virus 1 and has been genetically altered to help destroy cancer cells.The virus gets injected into the lesions, lesions are areas on or in the body that have been damaged . Not only does the virus destroy cancer cells, it also activities the immune system to attack the cancer cells. Many changes were done to diminish the virus, expand the selective for the cancer cells, and release the cytokine. The modifications that were implanted in the virus were, HSV-1 strain (JS1) which is the DNA set of the herpes virus, that increases the death of the tumour cells. To delete ICP34.5, that stops the HSV infection in the cells that are not tumorous, and will provide selective tumour duplication. As Well as the deletion of ICP47 that allows antigen presentation, an antigen is a substance that helps enable an immune response. Placing in the US11 will
Mice and rats have been the most common model organism that used for research. Recently, the zebrafish (Danio rerio) has emerged as one of the most popular animal model in different area of research such as developmental biology, genetics, and pharmacology (Liu et al., 2010; Eisen, 1996). Compared with other animal models, the zebrafish has numerous advantages that make them valuable as an animal model. The zebrafish has a small size (adult ~ 1- 1.5 inches long) and short generation time (about 3 months). In ideal condition, a female zebrafish can produce 100-200 eggs at weekly intervals, which can allow performing assays that required a large number of subjects. The zebrafish embryos undergo rapid external developmental within 2-4 days, and
As the world continues to suffer from these devastating diseases, researchers continue to find alternative therapeutic ways of addressing cancer treatment. It is on this premise that various immunotherapeutic alternatives have emerged and currently garnering the greatest level of attention and already raising hope throughout the world in addressing the treatment of NSCLC. However, this can no longer be viewed as a discovery but a wave in the medicine world that began in the 20th century. Various researchers have found the importance of the role of immune systems in fighting the growth of tumor caused by cancer cells. A study by Huncharek (2000) stated that specific immune boosters are capable of eliminating preclinical cancers. In contrast, Jermal et al. (2011) found that immunotherapy is an effective approach for the treatment of tumors that have already turned into solid. Similarly, the researchers highlighted that immunotherapy can be an effective approach to the treatment of melanoma as well as renal cell cancers (Lasalvia-Prisco, 2008). However, Jemal et al. (2011) noted that immunotherapy cannot achieve much in cancer treatment due to limitation brought about by the emission of immunosuppressive cytokines and subsequent loss of antigen expressions. Recent development in research studies on the immunotherapy approach to cancer treatment continues to elicit mixed reactions among researchers of medicinal ecology (Jadad et al., 1996). However, recent development in
This ability of malign cancer to make their way across basement membrane and into blood vessels is what makes cancer so fatal and impossible to be cure by surgery alone. The result of metastasis and invasion in normal tissue by cancer cells are often seen as one of the distinctive features of malignancy (Ruoslahti 1996). Even though the ability of invasion and metastasis are one of the hallmarks for cancer, these abilities are not unique to cancer cells as it can also occur during the early development stage of the embryo, in healthy organisms and in many noncancerous diseases (Mareel & Leroy 2003). It does not matter whenever the organism has developed benign or malign cancer, all cancer cells have the ability to disturb the normal cell cycle and threaten the survival of the organism.
Zebrafish (Danio rerio) have been used in developmental biology and molecular genetics studies, as well as in high-throughput screening for toxicity of chemicals (Hill et al., 2005). Among the several characteristics that make the zebrafish a useful animal model in research are: high fecundity; low maintenance costs in comparison with mammals; rapid embryogenesis; larvae transparency that allows the visualization of tissues in vivo; absorption of compounds from water, and the high degree of similarity with the human genome (Chakraborti et al, 2009).
The murine double minute 2 (MDM2) gene is a protein that was first discovered in 1992.Researchers discovered that the gene was responsible for transforming a line of healthy rodent cells into cancerous cells [1]. Further studies revealed that artificially manipulating the MDM2 gene to produce more of its proteins in strains of mice with reduced immune system resulted in the development of tumors in the connective tissues of these mice. Cultured cells are transmuted due to the overexpression of MDM2 cells. This phenomenon also results in the immortalization of primary fibroblasts in rodents. The transformed mouse cell line 3T3-DM includes three genes, one of which is the MDM2. The genes were situated on small, acentromeric, extrachromosomal
Despite the promise of such approaches, a number of difficulties remain to be overcome, the most important of which is the need for more efficient systems of gene delivery. No gene transfer system is 100% efficient, unless germ-line therapy is contemplated. During the past two decades, there have been major advances in our understanding of how cancer develops, proving that cancer has a genetic basis (2). A series of genetic abnormalities that accumulate in one cell may result in a pattern of abnormal clonal proliferation. Our growing understanding of the genetic basis of cancer offers new opportunities for the molecular prevention and treatment of cancer. There has been a
As new studies and determination for finding a treatment to cancer arise from all over the globe, the use of shark cartilage as an alternative medicine has been a reoccurring and hopeful treatment. For over a decade now, scientists and medical doctors have been using shark cartilage as a medicine to fight various types of cancer, most commonly brain tumors. As opposed to bones, sharks are composed of cartilage, a substance thought unable to contain cancer cells. Many patients choose to use this method of treatment, for it is natural and harms the body’s physical ability throughout treatment much less. As research continues, the use of shark cartilage is a rising alternative medicine being experimented on patients to find an ultimate cure for