Teanna
Anthony
BIOLOGICAL LITERATURE
Ultraviolet B Radiation-induced Skin Cancer in Mice Defective in the Xpc, Trp53, and Apex (HAP1) Genes: Genotype-specific Effects on Cancer Predisposition and Pathology of Tumors1
David L. Cheo, Lisiane B. Meira, Dennis K. Burns, Antonio M. Reis, Tony Issac, and Errol C. Friedberg
ARTICLES
In this article, the cell type specific effects of the deletion of the Rb gene within the murine retina were discussed. In certain cells of the human retina, the loss of the function of the retinoblastoma tumor suppressor gene makes the cells extremely sensitive. Retinoblastoma protein, or RB, is tumor suppressor protein that can lead to the development of several cancers if defected. The retinoblastoma in humans develop in early life and individuals that are heterozygous for the germ-line RB mutations have somatic mutations in the RB gene. In some humans, the inherited RB gene has a munt allele, which results in retinoblastoma causing the wild-type allele to lower the rate of tumorigenesis in cancers to be lost. Retinoblastoma are shown to develop within the first few years of life and in the human fetus as well. The Rb gene contains a product that is essential in regulating the cell cycle, apoptosis and terminal differentiation. Identifying the role of Rb in the development of different retinal cell types is an important factor in distinguishing the cause of retinoblastoma as well as the types of retinal cells that are prone to transformation. Past studies have shown that Rb-deficient retinas present to be tumorigenic. The loss of the function of Rb in embryonic retinas as closely related to the increased rate of apoptosis and suggests that this mutation causing the evasion of apoptosis is needed for the development for retinoblastoma. In the experiment performed in this article, the role of Rb was observed using conditional mutations of the Rb of mice. this study, the deletion of Rb resulting from a conditional mutation was implemented in the early progenitors of a mouse. By doing so, the cell type specific effects on the development of the retina resulting from Rb loss was characterized and reported to show that retinoblastoma develops when Rb and p130 are absent.
Frequent Nitric Oxide Synthase-2 Expression in Human Colon Adenomas: Implication for Tumor Angiogenesis and Colon Cancer Progression
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Ambs, Stefan, William G. Merriam, William P. Bennett, Emanuela Felley-Bosco, Mofolusara O. Ogunfusika, Sean M. Oser, Shawn Klein, Peter G. Shields, Timothy R. Billiar, and Curtis C. Harris.
Cell type specific effects of Rb deletion in the murine retina
David MacPherson,Julien Sage, Teresa Kim, Dennis Ho, Margaret E. McLaughlin, and Tyler Jacks
Mechanisms repair in Gram-positive bacteria
Lenhart JS, Pillon MC, Guarné A, Biteen JS, Simmons LA5
This article expresses the process of the biological pathway MMR that occurs in humans by examine the MMR process in Escherichia coli. MMR is DNA mismatch repair and is defined as a biological pathway responsible for correcting DNA base-base mismatches that occur during DNA replication, recombination or repair. Because of its significant similarities, the MMR process in Escherichia coli was examined to compare with the MMR process in humans to find the cause of defects in the process. By notating the defects within the pathway, plans to correct these errors can be made as well as benefits to making this system more effective in the body. The most important elements the article possessed were the breakdown of the pathway and the mechanisms that allow the pathway to function properly. MMR pathway is one of the most critical biological pathways in the body. MMR works by lowering the number of replication association errors; however, defects in this system can cause an increase in spontaneous generation rates that result in hereditary disease as well as cancerous diseases. E.coli is used to study MMR process because it mechanisms relate closely to the mechanisms of the MMR process found in eukaryotic MMR as well as humans. The MMR process in E.coli relies primarily on three protein components: MutS, MutL, and MutH. In E. coli, MutS is responsible for distinguishing base-base mismatches and insertion or deletion mismatches pairs. MutS is a homodimer that binds to the mismatch pair site. After the binding site is activated MutL enhances the function of MutS and finds and activate MutH. Defects in MutL are found to completely inhibit the function and effectiveness of the MMR pathway in E. coli. MutL also acts as a homodimer and has ATPase activity which is needed for ATP binding. MutH recognizes the hemimethylated dGATC sequence, which is the strand that contains the mismatches pair. A small cut or nick is then placed in the sequence by MutH and helicase gathers around the open space to unwind the mismatch pair from the sequence, which creates a gap. ExoI or ExoX then removes the mismatched pair and the gap in the sequence begins to undergo repair DNA resynthesize to correct the error. In the MMR process in humans, these proteins function the same or have similar properties. In the MMR process in humans, the protein component Mutsa functions as the MutH would in E.coli by recognizing the mismatch pair in the DNA sequence. MutLα is the component that regulates the termination of the mismatch pair and is required for the MMR process to occur. Lastly, MSH2 and MLH1 are the components involved in getting rid of the mismatched pair as well as DNA resynthesis. Research in the article showed that defects in the MMR pathway increased the mutation rates in genes that involved genes that had simple repeat sequence in coding regions. The article showed that there were specific areas in the DNA sequence that continuously had mutation errors that the MMR pathway did not correct. The area being studied was the defects in MMR in cancer-promoting mutations. In this study, the type II transforming growth factored-β receptor gene where these cells were MMR-deficient tumor cells in the patient that associated cancer.
In this article the increased NO production in human carcinoma cells inducing tumor angiogenesis and colon cancer progression were examined. The article explains how the increased expression of nitric oxide synthesis has shown to be present in human colon carcinoma cells as s well as in breast and central nervous system tumors. Nitric oxide is a bioactive agent that is involved in several signaling molecules that control functions such as vasodilation, neurotransmission, immune defense and metabolisms. Although Nitric oxide is an important factor within the mechanisms, high concentrations of nitric oxide is detrimental in the pathogenesis of many disorders such as cancer. There are three different forms of Nitric oxide: NOS 1, NOS2, and NOS3. NOS 1and NOS 3 are inducible forms of nitric oxide synthase and are not always expressed. NOS2 is an independent form of nitric oxide and are expressed frequently in carcinoma cells when produced at high volumes. The experiment performed in this article was used to observe cell types that express NOS from human carcinoma cells. Based on the results from the experiment, NOS activity was found in normal colon as well as in tumors; however, the in the adenoma cells of the normal colon, concentrations of NOS2 were relatively lower than those found in tumors of colon cancer. There were several test completed to confirm the results from the experiment such as Western Blot Analysis, RT-PRC sequencing, Histological Review of Tissue Samples and Immunohistochemical Staining, and Assay of NOS activity. The results from these showed that there was an increased NOS2 activity the tumor developing stage of carcinogenesis when compared to metastatic stage of carcinogenesis. Based on the results of the various tests, high concentrations of NOS2 were also noted in the blood vessels. This observation lead to the conclusion that increased volumes of NOS2 within the blood stream enable the blood vessels to grow, thus feeding the progression of the tumors. The data collected from the experiments in the article suggested that high concentration of NOS2 within carcinomas leads to the progression and angiogenesis of tumor formation.
•In this article, deficiencies in the DNA repair mechanisms nucleotide excision repair (NER) in relation to the development of the development of xeroderma pigmentosum was discussed. There are several different hereditary disorders, such as xeroderma pigmentosum that cause dysfunctions and mutations within the DNA repair mechanisms. XP is a disease that cause by a defect within the nucleotide excision repair mechanism. XP is characterized by the sensitivity to the DNA damaging effects of ultraviolet radiation. Different genetic complementation’s groups like (XP-A to XP-G) and XP-V forms have been distinguished in the disease. Recent studies have shown that mice with the XP gene are great models to research the gene. Within these mice, mutations are show to develop because of gene disruption. In these studies, Xpc generate mice have deficiencies in their NER repair mechanisms. These mice are also predisposed to UVB radiation- induced skin cancer, in which the skin cancer is more frequent in Xpc Trp53 double mutant. The p53 or Trp53 in mice, is the most common mutated gene in human cancers and is a target for mutation in for UVB radiation induced skin cancer. The p53 protein is important in many different cellular responses to DNA damage. Mechanisms that rely on p53 are demanded to inhibit cell cycle progression and activate apoptosis. When chemical or physical agents cause defects within the p53 gene cause DNA damage, these mechanisms cannot function properly. In the article, the increased exposure to UVB radiation-induced skin cancers in Xpc mice are compared with normal mice. The experiment conducted showed that Xpc Trp 53 double heterozygous mutant mice are more frequent to develop skin cancer than Trp53 single heterozygous mice. The results from the experiment show that Trp53 and the Xpc allele heterozygous conditions change the skin tumors when compared to differentiated forms in all Xpc genotypes.
In this article, the hallmarks of cancer and how they aid in the development of cancer were discussed. The hallmarks of cancer a set of organized characteristics of cancer, describing the factors that lead to the development of cancer. Several scientists have brainstormed the different methods, pathways, and mechanisms that lead to cancer development. The hallmarks that were created to described carcinogenesis are: self-sufficiency in growth signals, insensitivity to antigrowth signals, evading apoptosis, limitless replicative potential. Sustained angiogenesis, and tissue invasion and metastasis. self-sufficiency in growth signals hallmark explains the ability for cancer cells to grow without responding to growth signals. In cancer cells, growth signals are not required for their growth. Cancer cells are able to synthesize and secrete some of their own growth factors which reduces their dependency for the growth signals that normal cells use. The hallmark Insensitivity to Antigrowth Signals explains the ability of cancer cells to ignore anti growth signals. Normal cells have antigrowth signals that block proliferation by forcing cells out of the active proliferative cycle or induced to permanently stop their proliferation potential. Cancer cells evade these antiproliferative signals in order to continuously divide. Evading Apoptosis hallmark explains the ability for tumor cell populations to grow in number is based on their rate of attrition. Apoptosis is a process of cell death that uses a protein, p53, which induces apoptosis. Cancer cells can evade this apoptosis process because they are missing the p53 protein or they can inhibit the activity of the p53 protein by increase inhibitors of p53 or stopping its activators. The hallmark Limitless Replicative Potential explains the ability of cancer cells to continuously divide. Normal cells have a timer that keeps track of the number of times they divide and grow by using telomeres. Without telomeres, DNA would be loss and the chromosomes would get smaller and smaller. Cancer cells have to maintain all of their telomeres and do so by increasing the production of telomerase. Sustained Angiogenesis hallmark describes the ability of cancer cells to form new blood vessels, resulting in their growth rate to thrive. Angiogenesis is a process of developing new blood vessels. Cancer cells activate angiogenesis by changing the balance of angiogenesis induces and inhibitors in the surrounding cell environment. Cancer cells stop producing angiogenesis inhibitor such as thrombospondin, which is made by p53 gene. Since most cancer cells have a loss in p53 production, this inhibitor cannot be made, this allowing the tumors to be feed with blood vessels and grow. The hallmark Tissue Invasion and Metastasis explains the ability of cancer cells to invade other organs by migration. The ability of a cancer to metastasize enables the cancer cells to find new areas in the body where nutrients are everywhere, allowing the cancer to spread. Cancer cells lack the protein E-cadherin’s which exerts growth signals for contact inhibition that keeps cells that touch each other from growing. A dis-functioning E-cadherin protein allows invasive and metastatic phenotypes.