Essay On Exosomes

Aim 2: To identify the proteins in the exosome of the metastatic cancer cells. The exosome or the secretory vesicle fraction will be concentrated from the extracellular media of metastatic, non-metastatic cancer cell and compare with the control cells. SILAC labelled proteomic analysis will be performed in the isolated exosomes to identify the proteins that are specific in metastatic cells.

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

Pancreatic cancer is one of the most deadliest cancers one can be afflicted with in the United States of America. Within one year of affliction, the survival rate is a mere twenty percent. Within five years of affliction, only six percent of patients will still be alive. Pancreatic cancer has long since been renowned for being caused by epigenetic changes in many cases. One subset of epigenetic a is DNA methylation which can suppress genes and prevent them from being transcribed. Aberrant DNA methylation increases the risk of metastatic pancreatic cancer by silencing tumor-suppressor microRNAs. Although methylation silencing can have disastrous effects, it can help by enabling scientists and doctors to recognize signs of pancreatic cancer early

Due to the low prevalence of disease, it is not deemed feasible to carry out population-based screening for PDAC (Brand et al., 2011). However, the successful implementation of screening strategies to enrich for individuals who remain high-risk candidates for development of PDAC, such as patients of new-onset diabetes mellitus and chronic pancreatitis, provides distinct opportunities for early disease detection (Kang et al., 2016; Hwang et al., 2015; Zhang et al., 2014). This may in turn improve the number of asymptomatic PDAC cases detected at a stage where curative therapy remains viable (Kang et al., 2016).

The 21st century has seen great progress in diagnosing and treating many types of cancers. Advancements in the medical field are helping more people discover their cancer earlier. Doctors are treating more Stage 1 and Stage 2 cancers than ever before. Survival rates are increasing due to early discoveries of tumors. In addition, better medicine and new technology has raised the survival rates of most cancers. More and more people are living beyond treatment and the number of survivors is only expected to increase as time continues.

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].

DICER expression was evaluated by immunohistochemistry in a large tissue microarray containing 87 serous and 39 non-serous ovarian tumors. DICER expression negatively correlated with node status and tumor grade. Low DICER expression in serous tumors was associated with poor overall survival. A similar trend was found for all tumors in the dataset but the analysis was not performed for specific histotypes. MicroRNA profiling in tumors with low DICER showed significant downregulation of many microRNA molecules compared to tumors with high DICER expression. Additionally, tumors with low DICER expression also had low estrogen receptor expression (19). On the other hand, Zhang et al (20) did not find any significant difference in DICER or DROSHA expression by QPCR or immunohistochemistry

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

The tumour stroma appears to be a major factor in tumour progression after initial tumour formation (Conklin and Keely, 2007). It initially protects against tumourigenesis; but neoplastic cells cause changes and recruit various other cell lines with a multitude of functions, forming a tumour micro-environment (TME). This is defined as “a heterogeneous population of cells consisting of the tumor bulk plus supporting cells” (Bussard et al., 2006). The tumour cells recruit the stroma cells and cause a reactive phenotype, known as tumor-associated stromal cells (TASCs).

Abstract: Increasing evidence suggests cell-to-cell communication is possible through extracellular RNAs (exRNAs). RNA (including mRNA, miRNA, or lincRNA) has, on many accounts, been found packaged inside extracellular vesicles (EVs) which may traverse through a variety of bodily fluids to be taken up by a recipient cell. The biological significance of exRNAs is largely unknown. However, preliminary studies suggest they may play a role in a variety of important biological processes, including stem cell maintenance, apoptosis, and cancer metastasis. Furthermore, there is much hope in eventually utilizing EVs as a drug delivery vector to supply damaged tissues with therapeutic RNAs. Such a system could overcome the immunological challenges associated with viral vectors. Advances in understanding the biology of exRNA transfer have been hindered by a lack of dynamic methods for detecting changes in RNA concentration in vivo. Northern blotting, microarray, and PCR based approaches are invasive, and sometimes lack sensitivity when dealing with small quantities of RNA. While evidence of their significance is growing, to date no exRNA has been shown to enter and function in a cell in vivo. To address these issues, I have been working on the development of a sensor system for detecting exogenous small RNAs. This molecular sensor will exploit the ability of microRNAs (miRNAs) to bind to, and repress, target

Sequencing the exome of the cancer patients’ tumour would identify whether the growth, is originally due to oncogenes or tumour suppressor genes and then the treatment can be tailored to treat the specific needs of the patient.

In the present study, we demonstrate the stimulatory roles of COX-2 and EP4 in human breast cancer progression and SLC induction via PI3K/AKT/NOTCH and WNT pathways, combining in vitro, in vivo, and in situ approaches. This work supports our previous studies, wherein we showed SLC stimulatory roles of COX-2 and EP4 in a murine breast cancer model [5]. The role of COX-2 in SLC induction has been hypothesized [42] and the roles of EP4 documented in human breast cancer cells [43]. We reported that COX-2/EP4 mediated induction of an oncogenic microRNA-526b was linked with SLC stimulation [19]. However, the mechanisms underlying COX-2/EP4 mediated SLC induction in human breast cancer remained unclear. In the present study, for the first time,

In breast cancer researchs it is have appeared that CSCs in this type of cancer are resistant to chemotherapy, radiotherapy, and hypoxia. Furthermore, the high tumorigenicity and invasiveness of CSCs are crucial to the occurrence, development, metastasis, and recurrence of breast cancer . Different LncRNAs including, HOTAIR , LncRNA ROR, LncRNA 00617, LncRNA SOX2OT and LncRNA-Hh have been showed that affect the characteristics of breast CSCs by influencing the Epithelial mesenchymal transition (EMT) -related signaling pathways [15, 16, 34-36].

Moreover, It has been suggested that cfDNA act as a ligand for Toll-like receptor 9 (TLR9) that may inhibit pro-apoptotic caspases by virtue of TLR9-dependent signaling [254]. This signifies a possible immunomodulatory role for cfDNA. These days cfDNA remains to be a hot topic and is widely used for a wide range of research and clinical purposes, including tumor genotyping, early cancer detection, patient prognosis, minimal residual disease monitoring, therapy evaluation, biomarker in transplant surgery for graft injury and prediction of allograft rejection [58, 255-267] . In recent years, multiple studies have demonstrated that patients with invasive tumors such as lung, breast, pancreas, colon, hepatocellular, ovarian, prostate, esophageal and melanoma generally have a high level of ctDNA in their plasma than in healthy individuals [268-273]. Several genomic studies of tumor mutations have analyzed ctDNA to quantify the tumor burden and to detect therapeutic resistance conferring mutations [216, 274-276]. Moreover, a correlation has been set up between the levels of non-mutated cfDNA and mutated cfDNA in circulation and the tumor stage [277, 278]. In addition to this, some studies have also found that mutated cfDNA can lead to therapeutic resistance in cancer several months prior to detection of

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.