THE ONLINE SCIENCE DIGEST, INC.LETTERS/COMMENTARIES: Must be pertinent to a current concern/topic in Science, Education or Politics.ABSTRACTS: A brief summary of on-going, albeit preliminary, original research. Must include: 1) a reference that can be used as a link, within the text of the abstract, that reviews the area of research; 2) concluding sentence(s) as to the importance of the research to medicine. Submit Letters and Abstracts to: EDITOR. |
ABSTRACTS
The use of viruses to preferentially infect and kill cancer cells while not harming healthy cells has been studied for at least 50 years. Although early results were disappointing, recent advances in virology and molecular biology techniques have resulted in a revival of interest in the field. This method of cancer therapy is called the use of “oncolytic viruses”, since oncolytic refers to lysis or breakdown of cancer cells through the process of apoptosis. The use of viruses in this type of therapy is different from their use in gene therapy. In gene therapy, the virus is a delivery vehicle, needed to bring a corrective gene or chemotherapeutic agent into the cancer cell. This method is also different from the use of cancer vaccines, which stimulate the body’s natural immune response to destroy the cancer. In fact, an immune response to an oncolytic virus is undesirable, as the virus could be destroyed before it is able to infect the cancer cells. Researchers have developed many methods of oncolytic virus therapy. All methods involve the virus becoming active in cancer cells that have specific genetic and metabolic transformations. Since most cancers are the result of defective functioning of the p53 tumor suppressor gene, or activated ras or myc oncogenes, most of the research effort is focused in this area. The following are examples of promising treatments.
Adenoviruses are a group of many viruses that can cause a variety of respiratory and eye infections. In order to multiply, the adenovirus enters the cell, and takes steps that result in the activation of the cell cycle. The functioning of the cell cycle results in the replication of viral DNA. However, this “unscheduled” synthesis of foreign DNA activates the p53 gene, whose function is to maintain the integrity of the cell’s DNA. The p53 then acts to halt the cell cycle. If the DNA cannot be repaired, p53 initiates steps that results in apoptosis, or programmed cell death.
Lesions on the skin and mucous membranes of the mouth, face, eyes or genitalia characterize herpes simplex virus infection. Researchers have engineered a herpes simplex virus that is non-pathogenic by removal of the gene that codes for ICP34.5 protein. Interestingly, this engineered virus now infects malignant glioma (brain tumor) cells. It turns out that these cancer cells have an activated ras metabolic pathway that the virus uses as an alternate pathway to accomplish replication. The results of a Phase I clinical trial using this modified virus has recently been reported. 3 Although the primary objective of this trial was to study safety (no toxicity or major adverse effects were noted), there was evidence of inhibition of tumor progression and even tumor shrinkage.
Reovirus infections in humans are mild and restricted to the upper respiratory and gastrointestinal tracts, but in general, they are without symptoms. During basic research on the biology of reovirus infection, it was discovered that the Type 3 Dearing strain was capable of replicating in cells with an activated ras signaling pathway, while normal cells were unable to support the infection. It appears that the reovirus utilizes the Ras pathway in a similar manner as the modified herpes simplex virus discussed above. Activated ras oncogene occurs in about 30% of all human cancers, primarily in pancreatic, colorectal, lung and leukemias. Studies with mice have demonstrated that the reovirus is very effective in tumor regression, even with animals with an intact immune system. 2 Clinical trials with humans are sure to follow, given the many attractive features of this natural virus.
Vesicular stomatitis virus is nonpathogenic in humans. This virus has been of interest due to its extreme sensitivity to the antiviral actions of the interferons. Follow-up laboratory work demonstrated that the virus replicated in a majority of cancer cell lines. Balachandran and associates 1 conducted a series of experiments that involved implanting mice with tumors that were defective in p53 function, or transformed with activated myc or ras oncogenes. The virus markedly inhibited the growth of the tumors, while being virtually undetected in normal tissues. Another study indicated that the virus is able to migrate to sites distant from the site of inoculation to inhibit tumor growth. This experiment demonstrated that the virus could be capable of treating metastic cancers, and that an intact immune system of the animals does not have a detrimental effect on the virus’s action. This virus, therefore, holds great promise, as it is harmless to humans, and appears effective against a majority of cancers.
It is concluded that these different types of oncolytic viruses, and the viruses developed by the genetic engineering are helpful for the further study on the cancer treatment procedures using viruses. The other importance of these viruses is not completely studied, so such viruses constructs and manipulations are lead to a better treatment strategies of cancer.
Spectroscopy is the study of matter and its properties by investigating light, sound, or particles that are emitted, absorbed or scattered by the matter under investigation.It may also be defined as the study of the interaction between light and matter. Spectroscopy is often used in physical and analytical chemistry for the identification of substances through the spectrum emitted from them or absorbed in them. A device for recording a spectrum is a spectrometer.
Infrared spectroscopy is the subset of spectroscopy that deals with the Infrared part of the electromagnetic spectrum. This covers a range of techniques, with the most common type by far being a form of absorption spectroscopy. As with all spectroscopic techniques, it can be used to identify a compound and to investigate the composition of a sample.It may be either near,middle,far infrared.Far infrared is generally not used for biological purposes.Near infrared is used to study the overtunes and combinations of functional groups.Middle infrared is used to study the stretching and bending vibrations of functional groups.
Recently infrared spectroscopy is used in diagnosing diabates,cancer and also for bioreactor monitoring in fermentation technology. This technique is highly recomended for detection of blood glucose levels in diabateic patients which is highly advanced and time consuming than the conventional method of blood collection which is painfull to the patients all the time. This method employs a microdialysis membrane through a small scrapping of the adipose tissue. Microdialysis membrane collects the body fluids including blood at that particular area and this is connected to the spectrometer through fiber optic cable and spectrometer gives the blood glucose reading within no time.An artificial pancreas like method is developed where in this microdialysis membrane is connected to the insulin pump which pumps insulin into the abdomen based on the glucose levels detected by the biosensor connected to the microdialysis membrane.This kind of technique is being used in the western countries where all the food eaten by the diabetic patients is caluculated based on the calorific values of the food taken by them and correspondingly amount of insulin is pumped by the insulin pump.
The advantages of this method over the others is that here there is no requrement for sample preparartion, as in other methods, and it is less time consuming. This method would be more beneficial if this technology were brought to the attention of clinicians.
R.Saikrishna,. M.Sc., Centre for Biotechnology, AcharyaNagarjunaUniversity. NagarjunaNagar 522510, Guntur A.P INDIA
Herpesviruses are large double-stranded DNA-containing viruses that are highly disseminated throughout the animal kingdom. Members of the human herpesviruses include viruses that cause a variety of diseases ranging from a mild cold sore to severe lymphomas.
Initial envelopment of the virion takes place at the inner nuclear membrane. Subsequent to this step, two pathways have been suggested for final maturation of the virus and evidence in the literature exists for both. The first model states that capsids are enveloped at the inner nuclear membrane and translocate through the periplasmic space to the endoplasmic reticulum and enter the cell secretory pathway of which the golgi body is a primary component. The viruses aquire tegument proteins and glycoproteins which are processed into the mature forms during this translocation. Virions in vesicles then finally fuse to the plasma membrane to release infectious virus. The other model states that viruses undergo initial envelopment at the inner nuclear membrane but then fuse with the outer membrane to release naked capsids into the cytosol. These capsids are transported to the golgi or other cytoplasmic organelle where they aquire tegument proteins. Viruses eventually bud into these cytoplasmic vesicles which move to the cell surface where virions are released. Evidence in favor of the latter model include studies of the maturation of other alpha herpesviruses and the use of targeted glycoproteins which indicate that ER restricted glycoproteins are not incorporated into the mature virion. In addition, using a synchronous system of assembly, naked capsids have been shown to appear in the cytoplasm. The mode of virus maturation is contentious issue due to the conflicting evidence in the literature. The pathway that requires a virus to deenvelope and reenvelope at a cytoplasmic site seems at first glance to be an inefficient mode of maturation. However, this model may permit the virus to aquire the multitude of tegument proteins, which can be localized, throughout the cell. There is now a considerable body of evidence that favors this model including the data from in our laboratory.
The major practical significance that may result from the above studies is to identify targets that can be used for antiviral intervention. The virus uncoating and maturation pathways involve the participation of proteins from diverse structural families. Identification of the interactions that are critical for virus maturation and the uncoating of the virus genome will allow one to design antiviral compounds that interrupt this process and consequently virus replication. Since particle formation and uncoating are essential for the spread of most virus infections, it would be difficult for the virus to circumvent such an antiviral by mutation.
PRASHANT DESAI, DEPARTMENT OF PHARMCOLOGY/MOLECULAR SCIENCE, JHU, BALTIMORE, MD 21205.