Overexpression Case Study

Inflamed tissues from Ulcerative Colitis (UC) patients show increased oxidative and nitrosative damage, leading to accumulation of mutations and dysplastic progression27,28. Infiltrating leukocytes from these patients have increased ROS production in basal conditions and in response to different ligands29. Since TLR4 mediates ROS production in leukocytes22, it is easy to speculate that immune cells drive pro-tumorigenic effects of TLR4. However, bone marrow-transfer experiments in our lab demonstrate that non-immune TLR4 participates in development of neoplasia8. Furthermore, we have shown that epithelial TLR4 activation predisposes to colitis and CAC6. To understand the role of epithelial TLR4 in neoplasia, our research has focused on the

Therefore, the most notable P53-induced mechanisms in mediating this response are cell cycle arrest and apoptosis [18], which activation depends on the cellular context and the extent of damage [20].

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 is described as the abnormal growth of cells. Normal cells are replaced with abnormal cells in which their deoxyribonucleic acid (DNA) has been damaged or augmented (McCance & Huether, 2014). Cancer cells with their various DNA changes are characterized by growing uncontrollably, being immortal with an unlimited lifespan

Cancer is a disease caused by an uncontrolled division of abnormal cells. The DNA sequence in cells can be changed as a result of copying errors during replication. If these changes whatever their cause are left uncorrected, both growing and non-growing somatic cells might gain many mutations that they could no longer function. The relevance of DNA damage and repair to the generation of cancer was obvious when it was recognized that everything that causes cancer also cause a change in the DNA sequence. Tumor suppressor genes are protective genes and normally they limit cell growth by monitoring the speed of cell division, repair mismatched DNA and control when a cell dies. When a tumor suppressor gene is mutated cells grow

In current society, cancer is one of the most fatal and prevalent diseases to exist. However, new research being conducted on telomeres and telomerase provides insight on not only the aging process and mortality of cells, but also on how the idea of cell death connects to cancer cells. By gaining knowledge on the supposed immortality of cancer cells, researchers are acquiring a higher understanding of the subject, and attempting to work on alternate techniques to provide treatment for the illness. The connection between telomeres and cancer and the momentous discoveries being made on them is revolutionizing the world through potential current and future applications that have significant implications for cancer treatment, and society, the

To determine whether MGMT and ERCC1 DNA methylation is diagnostic of human cancer rectum, we detected the frequency of MGMT and ERCC1 methylation in 50 serious of primary cancer rectum samples and 43 benign rectum tumors by MSP. MGMT and ERCC1 were methylated for 13.9% and 18.6% in the benign tissue and for 4.7% and 7% in the blood, respectively. On the contrary, a methylation-positive pattern of MGMT and ERCC1 was observed for 80% and 74% of cancer rectum tissues and for 58% and 60% of the blood, respectively. The differences in the frequencies of MGMT and ERCC1 methylation pattern between rectum cancers and benign tumors was statistically significant (p<0.001 for each in the

As cancer becomes an increasingly threatening foe to human life, scientists strive to understand more about the disease. In the hope that they can improve detection and treatment, researchers study the formation, proliferation, and migration of cancerous cells. One such scientist, Dr. Kristi Neufeld, is faculty member at the University of Kansas and the Co-Leader of the Cancer Biology Program at the University of Kansas Cancer Center. She focuses her research on the effects of the APC and Musashi proteins on the development and progression of colon cancer.

p53 is the most studied tumor suppressor protein involved in the negative regulation of cell cycle and prevention of tumorigenesis . P53 induction usually occurs during cellular stresses like DNA damage or activation of other oncogenic proteins. P53 transcribes its target genes like p21,PUMA through p53 response element and halts the cell cycle until the stress is overcome, if not severely damaged cells are led to apoptosis (A9). Thus it is no wonder that most cancerous cells have either mutated p53 or completely lost it by deletion or inhibited by other factors. Tp53 gene is located in the 17p13 region , over a 20kbp region coding a 53 kDa protein. P53 protein comprises of N terminal transactivation domain, DNA binding domain and C terminal oligomerization domain (). Mutations in DBDs of p53 are most often found in cancers indicating prime role of DBD in p53 mediated tumor suppression. With advancement in p53 studies previously not conceived pleiotropic roles of p53 are coming into light. Along with the basic tumor suppressor activity, p53 it is also active in various cytoplasmic activities related to apoptosis, autophagy, physiological and pathological processes. P53 has been found to directly promote mitochondrial outer membrane permeabilisation leading to apoptosis (m1). It is also active in expressing pro-autophagy target genes (m2). However cytoplasmic wild type as well as

Additionally, p16 has been explained in the cytoplasm of some tumor cells where roles other than proliferation control might occur (24). Considering the data collected on the subject, it has been hypothesized that a function of p16 is a universal cancer suppressor, working to block numerous pro-neoplastic cell capabilities like invasion, proliferation, and angiogenesis. The p16 gene appears to be more than just a cell cycle progression regulator. Additional studies are needed to increase our understanding of its potential job in the progression of cancer and the development of cancer

It may be possible to correct an abnormality in a tumor suppressor gene such as P53 by inserting a copy of the wild-type gene; in fact, insertion of the wild-type P53 gene into P53-deficient tumor cells has been shown to result in the death of tumor cells (3). This has significant implications, since P53 alterations are the most common genetic abnormalities in human cancers. The over expression of an oncogene such as K-RAS can be blocked at the genetic level by integration of an antisense gene whose transcript binds specifically to the oncogene RNA, disabling its capacity to produce protein. Experiments in vitro and in vivo have demonstrated that when an antisense K-RAS vector is integrated into lung cancer cells that over express K-RAS their tumorigenicity is decreased (4).

The p53 is a vital tumour suppressor protein in humans which is important for cell cycle regulation. Ablation of the p53 protein causes the cell to proliferate infinitely that contributes to the development of tumours. Through the cell-autonomous program the cell-cycle arrest and apoptosis is caused by the presence of p53. The aim of the journal is to study cellular senescence program in hepatic stellate cells that is p53-dependent which is formed by dying hepatocytes which secret factors that influence the tissue microenvironment, preventing fibrosis, cirrhosis and liver cancer via promoting p53 senescent in these HSCs. The research objectives explain that fibrosis is limited through the p53-mediated senescence program by stopping HSC proliferation through cell-autonomous canonical senescence regulators and the non-cell-autonomous effects of SASP on ECM and immune surveillance. Currently there is a debate on the role p53 plays in HSCs which influences later stages of liver cancer and the research exhibits that through non-cell-autonomous mechanisms, p53 can inhibit cancer by manipulating the tissue microenvironment.

Indeed, it has been identified that PARs, in general, implicate in the activation of different cytokines in the cell, and mediate responses that are mainly leading to inflammation, pain, swelling, and redness. The Study done on the rat cortex by using PAR4 activating peptide showed that this PAR4 agonist (AP GYPGKF) raise the TNF-α expression which enhances inflammation in human cells. In addition to their pathological roles, PARs also have been recorded in mediating cancer progression. Different current studies identified that expression of PAR4 is highest in prostate cancer, and it also mediates the migration of colon cancer and hepatocellular carcinoma-derived cell lines [4]. However, in the cancer targeting strategy, some researchers use

In a study done by Ali Yousif et al Expressional profile of both markers (p16 and CK19) was different in same tumour. CK19 positivity was associated with age whereas p16 showed insignificant expression. The expres¬sion of P16 decreased while CK19 increased with the tumour grade.

Inflammation is generally an acute process that occurs in response to infection and tissue damage. This protective mechanism involves members of the innate immune system such as macrophages and neutrophils recognizing pathogen-associated molecular patterns (PAMPS) as well as damage-associated molecular patterns (DAMPs) and initiating mediators that increase vasodilation, edema and pain. Long-term inflammation can also occur and leads to a chronic state with conditions favorable for tissue damage and genomic lesions (1,2). Over time this genetic damage can lead to cancer. An example of chronic inflammation leading to cancer development can be seen in patients with ulcerative colitis.