Neoplastic cells

Modem cancer therapy has been primarily dependent upon surgery, radiotherapy, chemotherapy, and hormonal therapy (72) (see Chemotherapeutics,anticancer Hormones Radiopharmaceuticals). Chemotherapeutic agents maybe able to retard the rate of growth, but are unable to eradicate the entire population of neoplastic cells without significant destmction of normal host tissue. This serious side effect limits general use. More recentiy, the immunotherapeutic approach to cancer has involved modification and exploitation of the cellular and molecular mechanisms in host defense, regulation of tissue proliferation, tissue differentiation, and tissue survival. The results have been more than encouraging. 

Vitamin A (retinol) and its naturally occurring and synthetic derivatives, collectively referred to as retinoids (chemical structure), exert a wide variety of profound effects in apoptosis, embryogenesis, reproduction, vision, and regulation of inflammation, growth, and differentiation of normal and neoplastic cells in vertebrates. 

The antimetabolites interfere with various metabolic functions of cells, thereby disrupting normal cell functions. They inactivate enzymes or alter the structure of DNA, changing the DNA s ability to replicate These drag are most effective in the treatment of rapidly dividing neoplastic cells. Examples of the antimetabolites include methotrexate and fluorouracil (Adrucil). 

The process, once initiated, is self-sustaining and may become more accelerated with time because the atrophy and intestinal metaplasia are progressive lesions and lead to further loss of parietal cells and incrased bacterial colonization of the mucosa. The initial mutations transform gastric cells into mature intestinal-type cells. Further superimposed mutations transform metaplastic cells into progressively dysplastic cells and eventually into neoplastic cells. This is a process of loss of differentiation which implies a multihit phenomenon which could be explained on the basis of continued formation of minute amounts of nitroso compounds over many years. 

Low-density lipoprotein 0.017-0.025 Delivery to neoplastic cells Methotrexate, anticancer agents... 

Obermuller-Jevic et al. (2003) comparison PrEC-non-neoplastic cells M -trans/5% cis isomers 0.5—5.0pM THF affected cell cycle, corrected for THF alone values 48 h medium changed every 24 h Lycopene uptake 3H thymidine incorporation for proliferation... 

Quackenbush, E., et al. Molecular doning of complementary DNAs encoding the heavy chain of the human 4F2 cell-surface antigen a type II membrane glycoprotein involved in normal and neoplastic cell growth. Proc. Natl. Acad. Sci. U. S. A. 1987, 84, 6526-6530. 

A number of cells, including cytotoxic T lymphocytes, NK cells, and mononuclear phagocytic cells, are endowed with cytotoxic abilities and thus mediate important immunosurveillance mechanisms against neoplastic cells and viral infections. In immune-compromised hosts, a correlation has been observed between low NK cell activity and morbidity [22-25] or the incidence and severity of upper respiratory tract infections [24],... 

Blood vessels penetrating tumors provide malignant cells with another point at which to enter the circulation. Evidence exists that in situation where cancers disseminate predominantly by the blood, the extent of metastasis depends upon the vasculature of the primary tumor. Thin-walled capillaries, especially those newly formed, provide poor resistance to invading cancer cells. Also, data from microscopy studies show that the endothelium of tumor vessels, particularly in areas of poor oxygenation, is often abnormal (Kl). These abnormalities may permit invasion by neoplastic cells (P3). Finally, tumors can spread by direct extension into body cavities such as pleural and peritoneal spaces. An example of this is the formation of peritoneal metastases from ovarian carcinoma. 

It now appears that both mechanical factors and finding a suitable environment are responsible for the preferred organ location of secondary growths. The relative importance of these factors is unknown and may vary depending on the type of tumor. Proctor (P4) has suggested that the initial dissemination of neoplastic cells is controlled mostly by mechanical factors, whereas later metastasis is determined more by appropriate environment. 

The SHE cell transformation assay at pH 6.7 is conducted to determine the ability of a test article to induce morphological transformation in cultured SHE cells. The SHE cell transformation assay is one of the most widely used cell transformation assays. The endpoints of this assay are related to the conversion of normal cells into preneoplastic or neoplastic cells. The assay provides a valuable tool in the process of assessment and evaluation of the carcinogenic potential of a test article.2 28... 

Bums, C. P., and Wagner, B. A., 1991, Heightened susceptibility of fish oil polyunsamrate-enriched neoplastic cells to ethane generation during Upid peroxidation, J. Lipid Res. 32 79-87. 

SMase activity (Mansat et al 1997) and downstream (by blocking the apoptotic effect of ceramide). However, the cross-talk between ceramides and DAG opens new intriguing avenues of research and may lead to better pharmacological maiupulation of key steps in the apoptosis/survival signaling cascade resulting in an increased chemosensitivity of neoplastic cells. 

Depletion of histone HI after covalent modification from chromatin is a key step in eukaryotic transcription (Lee et al, 1993 Juan et al, 1994 Rice and Allis, 2001). A comparison of the association of the antibiotic Mg + complexes with the normal and HI depleted chromatin suggests that smaller ligands, like anticancer drugs, have better accessibility for HI depleted chromatin compared to native chromatin. HI depleted chromatin is also more prone to aggregation upon association with the complex I of the antibiotic Mg + complexes. It is also less accessible to micrococcal nuclease. We propose that HI depleted chromatin is a better target of these antibiotics compared to native chromatin. This observation is particularly significant in case of neoplastic cells where most of the cell nuclei are transcriptionally active, and, therefore, contain HI depleted chromatin. 

An excess of zinc will cause problems in humans. Excessive doses can lead to biochemical control system damage, while doses slightly higher than optimal can cause disorders in iron and copper metabolism, resulting in incurable anemia, decrease in activity of zinc protein enzymes, and pancreas and kidney damage (Boularbah et ah, 1999 Seiler et ah, 1994). Increased levels of zinc have been observed in nuclei of neoplastic cells and in cases of acute dental caries, however its role in these diseases has not been explained. 

Neoplasms are, as we noted in Chapter 3, new growths. But they are new in several highly destructive ways. Normal processes of cell replication within tissues occur in orderly, well-controlled ways. Neoplastic cells replicate wildly, without apparent controls. The relationships between the various types of cells within an organ are, if the organ is to function properly, also orderly neoplastic cells, because of their disorderly replication patterns, can disrupt normal architecture and organ dysfunction can ensue. 

It has seemed pretty clear for several decades, from both studies in humans and in experimental settings, that carcinogenesis is a multistage process. At the broadest level, the process can be thought of as one in which a normal cell is first converted to a permanently deranged cell, which is called a neoplastic cell, and a second sequence in which the neoplastic cell develops into a tnmor, a neoplasm, that the pathologist can observe neoplastic conversion and neoplastic development. 

Transformation the conversion of normal cells into neoplastic cells. 

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