Annotated Bibliography : Programmed Cell Death

The Onyx-015 is an oncolytic adenovirus that is similar to the H101 virus. The Onyx-015 is also used to treat head and neck cancers along with chemotherapy. This virus has been created in the US but has yet to be regulated by the government. During the trial period of the virus, there were 22 patients admitted into the trial that had head and neck cancers. In order to be admitted into the trial there were some conditions that had to be met. These conditions consists of, the life expectancy of the patient had to be 3 months, over the age of 18 years and have a Karnofsky performance greater than 60% [11]. The Karnofsky performance is a scale that states the health of a patient. In this case a performance greater than 60% indicates that they are able to care for themselves or may require occasional assistance [12]. Another important condition is that the tumor had to be in an area where there can be direct injections.

This article covers the Seneca Valley Virus (SVV-001) as a hopeful for an oncolytic treatment of certain cancer types. More specifically those with neuroendocrine properties such as rhabdomyosarcoma, Wilms tumor, glioblastoma, neuroblastoma, and adult small-cell lung cancer. Each of which effect smooth/skeletal muscle cells, kidneys/adrenal glands (mainly in children), astrocytes of the brain, nerve cells of a fetus, and lung cells in adults respectively. The virus was discovered by accident in a contaminated cell culture that contained bovine serum to promote growth. The virus was later discovered to be almost exclusively found in farm animals such as cows and pigs, due to the presence of neutralizing antibodies that were later to only ever have been found in one human sample. Just as important as that, the virus only targets the cells of the above-mentioned cancers/tumors, is a self-replicating RNA virus, and its inability to infect other cells in the body all come together to result in the lysis of these specific cancer cells. These properties alone give great hope for SVV-001 as a treatment for those infected by these diseases, and prompted for more research into its medicinal possibilities.

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.

In the article, "Mitosis Can Drive Cell Cannibalism Through Entosis", Joanne Durgen (et al.) suggests that cell division may cause living cells to engulf each other by invading another living cell. Although the word "cannibalism" sounds terrible, cell-eating-cell is very descriptive of what happens in this process and is shown that it may be beneficial in limiting tumor growth. Briefing over where entosis is found and what it does, what proteins regulate the entosis process, and possible beneficial characteristics in human cancer and chemotherapy in this article may give a better understanding of this microscopic process.

Adenoviruses are double stranded DNA viruses that lack an envelope. They are not a risk to humans and induce only mild upper respiratory infection or food poisoning. Non-pathogenicity is a great advantage to their use as vectors for gene transfer. They are composed of capsid and protein fibers in the surface that help them recognize and bind to membrane receptors of mammalian cells which belong to Coxsackie family (CAR), and the expression level of CAR is an important factor for the efficiency of infection. The virus in internalized by phagocytosis and goes to the endosome, which decomposes, the viral capsid disintegrates and the genetic material is released into the cytoplasm. The genetic material rarely integrates into the host genome. It

Autophagy gives cells with oxidizable substrate when nutrients become deficient. It can give protection against aging and a number of pathologies such as cancer, cardiac disease, diabetes, neurodegeneration, and infections. Autophagy principally plays an adaptive character to save organisms against various pathologies, including infections, cancer, and aging, neurodegeneration, and heart disease. A number of modern studies have stressed the importance of autophagy and the ubiquitin-proteasome in the pathogenesis of muscle declining in different types of inherited muscle problems.

GDEPT is a two-step treatment strategy where the gene that encodes a prodrug-activating nonendogenous enzyme is selectively transferred to target tissues. The most commonly used gene delivery vectors are cationic lipids, peptides, and viral vectors (i.e., retroviruses, adenoviruses, and adeno-associated viruses). Subsequently, inactive prodrug is delivered systemically and converted to its active cytotoxic drug by the nonendogenous enzyme expressed in the target tissues. The effectiveness of GDEPT depends on several factors, including level of enzyme expression at the target site, prodrug activation efficiency, and the capability of the active cytotoxic drug to diffuse into adjacent cells. The most frequently used enzyme/prodrug systems include

The cells of a multicellular organism are members of a highly-organized community. The number of cells in this community is regulated, not by controlling the rate of cell division, but also by controlling the rate of cell death. If cells are no longer needed, they commit suicide by activating an intracellular death program. This process is therefore called programmed cell death, although it is more commonly called apoptosis. Cell death plays a role in development and the process is called, morphogenesis, the biological process that causes an organism to develop its shape. It also plays a role in the maintenance

HBV DNA has been shown to become integrated within the chromosomes of infected hepatocytes, the integration of viral genetic material occuring in a critical location within the cellular genome. For example, integration of HBV DNA has been observed within the retinoic acid receptor alpha gene and within the human cyclin A gene, both playing crucial roles in cellular growth. However, in many if not most cases, the HBV DNA integration site does not appear to be in a critical location and the process appears to be random. Furthermore, the length and the components in the HBV DNA integrant varies considerably and the viral DNA may be rearranged, deleted or present in repeats. These findings suggest that it

Cancer occurrs by the production of multiple mutations in a single cell that causes it to proliferate out of control. Cancer cells often different from their normal neighbors by a host of specific phenotypic changes, such as rapid division rate, invasion of new cellular territories, high metabolic rate, and altered shape. Some of those mutations may be transmitted from the parents through the germ line. Others arise de novo in the somatic cell lineage of a particular cell. Cancer-promoting mutations can be identified in a variety of ways. They can be cloned and studied to learn how they can be controlled.

To overcome the drawback of classic -retroviral vectors mentioned above, the authors of this study proposed the use of self-inactivating (SIN) viruses as vectors for gene therapy. A SIN retrovirus is

These are the endogenous viruses and some individuals can have thousands of copies of these A-type viruses in their chromosomal DNA. B-type viruses have an eccentric core and the mammary tumor viruses exclusively possess this structure (Cloyd, M) . These viruses exist as endogenous and exogenous viruses and when expressed can cause mammary tumors. C-type viruses have a central electron core (Cloyd, M) . Most of the oncoviruses and endogenous viruses are C-type viruses. The D-type viruses have a rod-shaped core and consist primarily of lentiviruses (Cloyd, M) . HERVs are a subclass of a gene known as transposon. These genes can be packed and moved within the genome to serve a vital role in gene expression and regulation. HERVs have been grouped into three broad classes, based on the sequence similarities, which are broken into subgroups based on the specificity of their tRNA binding site. Class I HERVs are related to gamma retroviruses such as murine leukemia viruses (Griffiths, D). Class I includes the subgroups of HERV-W and HERV-H. Class II HERVs are related to beta retroviruses such as mammary tumor viruses and include several subtypes of HERV-K elements (Griffiths, D) . Class III HERVs are related to spumaretrovirueses and subgroups include HERV-L and HERV-S (Griffiths, D) . Class I and class III are the oldest groups, seen in primitive lineage, and class II includes those active most recently. HERVs

The role of autophagy poses as a highly conserved catabolic phenomena where cells undergoing stress develop a cytoplasmic crescent shaped phagophore that matures into an autophagosome. The autophagosome is involved in engulfing damaged organelles and long lived proteins in order to replenish the cellular energy content and building blocks for biosynthesis. The autophagy phenomenon always occurs to maintain the cellular homeostasis. But, under stress there is triggering of this autophagy event beyond its basal level. The most important breakthrough in our understanding of the molecular pathway of autophagy came from yeast genetic analysis where 35 Atg (Autophagy-related) genes were identified. Various types of Cellular stress sparks an

An oncolytic virus (OV) is a virus that preferentially infects and kills cancer cells. OVs posses the ability to selectively infect and replicate in cancer and associated endothelial cells and kill these cells in cancerous tissues while leaving normal tissues unharmed [1]. As the infected cancer cells are destroyed by lysis, they release new infectious virus particles to help destroy other cancer cells or the remaining tumor. The viruses achieve this by a number of mechanisms, including direct lysis, apoptosis, expression of toxic particles, shutdown of protein synthesis, as well as the induction of anti-tumoral immunity.

Kerr, Wyllie, and Currie first used the term apoptosis in a paper in 1972 to describe a morphologically distinct form of cell death, although certain components of the apoptosis concept had been described years previously. Our understanding of the mechanisms involved in the process of apoptosis in mammalian cells transpired from the investigation of programmed cell death that occurs during the development of the nematode Caenorhabditis elegans (Horvitz, 1999). In this organism 1090 somatic cells are generated in the formation of the adult worm, of which 131 of these cells undergo apoptosis or “programmed cell death.” These 131 cells die at particular points during the development process, which is invariant between worms, demonstrating the