Cancer Pathogenesis Of Cancer

Its locus is particularly amplified in these noted tumours leading to the progression of these cancers, it can be suppressed by p53 (tumour/ proliferation suppressor) which represses the EZH2 promoter, resulting inhibition of cell proliferation and invasion (Bracken, 2003; Xiao, 2011).

The purpose of this research was to determine the mechanisms in naked mole-rats that restricts cell proliferation and tumor formation. Contact inhibition is a mechanism observed where cell proliferation stops when two cells come in contact with one another. This process is caused by elevated levels of p27 cyclin-dependent kinase inhibitor which stops cells in the G1 phase from dividing. The cylcin-dependent kinase inhibitor p16 is also thought to regulate contact inhibition but its levels do not change in mice or human samples. Tumor-suppressor genes Rb and p53 are present in high concentration during contact inhibition to help control cell proliferation and apoptosis respectively. It was hypothesized that the naked mole-rats' cancer resistivity

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

One study by Shuijun Zhanga et al had shown the ABT-737 induced apoptosis of hepatocellular carcinoma cells (HCC) by the transcriptional repression of Myeloid cell leukemia 1 (Mcl-1). Shuijun Zhanga et a. had shown that NCTD could affect apoptosis by the modification of the B-cell lymphoma 2

For years people have been looking for a cure for the devastating disease of cancer. Cancer is the third highest killer in the US with over 2,500,000 victims per year. Oncologists and scientists around the country are researching all forms of cancer in an effort to understand, treat, and ultimately defeat this disease. Already there have been numerous advances in the field, such as chemotherapy and gene therapy. One advance has been the use of a cell process known as apoptosis. By harnessing this normal cell process, scientists hope to have found an effective way to combat cancer.

Mutations (for most cancers) must appear in both tumour suppressing genes and oncogenes for cancers to form. The tumour suppressing genes and oncogenes act in complementary fashion to one another; one pulls forward, and the other pushes back ensuring that the cell cycle occurs in a controlled manner (Sherr, 2004).

Under normal conditions, cells balance division and apoptosis, and these processes are accomplished and preserved by several biochemical “checkpoints” during the cell cycle2. When these checkpoints are affected, uncontrolled cellular proliferation and cancer can result. Two general classes of cancer genes are oncogenes and tumor suppressor genes. Oncogenes facilitate tumor formation by directly accelerating cell division, whereas tumor suppressor genes, when affected, allow uncontrolled growth that was normally suppressed2. Tumor suppressor gene loss usually affects a cell’s phenotype when both copies of the gene are lost, so null alleles can be present in a heterozygous state in cells without affecting cell and tissue phenotype. The loss of these genes can occur through genetic mutation or the epigenetic silencing of genes via promoter

Functional studies have demonstrated that combination of primary BRAF or NRAS driver genes together with additional genetic alterations such as deletion of CDKN2A or PTEN and inactivation of tumor protein p53 (TP53) tumor suppressor gene as a necessary event to bypass OIS79–82. High frequency BRAF mutation in concert with loss of function in tumor suppressors (PTEN, p53) and cell-cycle control genes (CDKN2A) has also been observed in ~40% human melanoma and most melanoma cell lines further highlighting the importance of co-operating pathways to fully form

Transformation-Related Protein 53, also known as TP53, is a tumor suppressor gene. It is named after its molecular mass. The gene was discovered by Arnold Levine, David Lane, and William Old in 1979 and was voted molecule of the year by science magazine in 1993. Although, it was not until 1989 that it was revealed to be a tumor suppressor gene. It was previously thought of as an oncogene. TP53 encodes for a protein, called p53 protein, that helps to regulate the cell cycle and inhibits mutations in the genome as well. Both of these functions help to conserve stability. One of the reasons for TP53’s high importance, and the extensive research on the gene, is its function to suppress cancer cells in multicellular organisms, including humans (Vijayaraj).

Being such a complex and important molecule, all of the functions of p53 are not yet understood. As such, much of the research conducted in the past few decades focuses on discovering new functions of p53 and the mechanisms behind them. Once discovered, these functions may be targeted as potential therapeutic approaches to cancer caused by p53 mutations.

The article then looks at the role, in solid tumours, of areas of low oxygen (hypoxia) in selecting for those cells that have mutations in the p53 tumour supressing gene. A common feature inside solid tumours is hypoxia and an increase of cell death. This happens because often the rate of growth in a solid tumour outstrips the supply of oxygen to the cells. The normal reaction of a group of cells, expressing the normal p53 gene, when exposed to an hypoxic region, is an increase in the rate of apoptosis. However, in a solid tumour there are many cells with many different types of mutations. In the battle against solid tumours, some tumours resistant to treatment have cropped up. The article takes a look at the role of hypoxia possibly selecting for those cells resistant to apoptosis.

It is thought that cancer cells in haematological cancers enhance the activity of the anti- apoptotic BCL-2 proteins in order to evade apoptosis and continue to proliferate uncontrollably. To understand the mechanism of apoptotic regulation we must first consider the mechanism by which apoptosis occurs. Apoptosis requires the release of cytochrome c from the mitochondrial intermembrane space to the cystol5. Cytochrome c then interacts with caspases (cysteine-aspartic proteases) which are then used to cleave other cellular proteins, which eventually leads to apoptosis of the cell. The anti-apoptotic BCL-2 proteins, such as BCL-2 and BCL-XL are thought to prevent the release of cytochrome c and AIF (apoptosis-inducing factor) into the cytoplasm and are known to bind to pro-caspases to prevent their activation by cytochrome c6. The exact mechanism by which this occurs is still unknown.

More than four thousands mutations of p53 genes have been identified in human tumors. p53 mutation in human skin cancers is consider to be unique mutation among other cancers mutations. p53 mutation in human skin cancers is mostly found to be C to T transitions. These transitions are located on dipyrimidine sites that are the specific target for UV radiation (Dumaz et. al, 1997). Alteration of tumor suppressor gene p53 will hinder p53 to repair damaged DNA or perform apoptosis as needed, which then results in precancerous cell (Madan et. al,

Dr Angeline Yek En Hui is a senior lecturer and cancer researcher at Newcastle University. Most of her publications in well-known journals such as Nature and Journal of Cancer are mainly centring the targeting therapies studies for cancers, mostly ovarian cancer and cervical cancer. Aiming to innovate new treatments for various cancers, she raised a team of 50 dedicated and responsible researchers and postgraduate students. In recent years, by the deep realizing and understanding about the involvement of BCL-2 family as an anti-apoptotic protein in the intrinsic apoptosis pathway which leads to cancer, her team start to focus particularly in investigating the effect of downregulating the BCL-2 which might

Cancer is one of the oldest genetic diseases known to man. Since the evolution of mitosis as a means for cell division and the development of multicellular eukaryotes - like humans and their biological progenitors - mutations in normal cell maturation and proliferation have resulted in various types of cancers, some benign but many of which exhibit great malignancy (Hajdu, 2011).