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Biomedical subjects

J C Petricciani

Publications and source records attributed to J C Petricciani.

At least 37 records · Page 2Linked to original sources
PubMed1987

Risk of neoplastic transformation from cellular DNA: calculations using the oncogene model.

Based on a number of assumptions about oncogene size, frequency, biological integrity, and in vitro as well as in vivo transformation efficiency, estimates are made of the risk that the residual cellular DNA (rcDNA) contaminant in a biological product will cause a neoplastic transformation event. Using a statistical Poisson distribution approach, the probability of such an event is calculated to be at most 10(-6) assuming optimal in vitro conditions with 100 oncogene copies per cell and a 10 pg contaminant. More realistic assumptions using in vivo data suggest that the probability of a transformation event is at most 10(-9) assuming 100 oncogene copies per cell and a contaminant of 1 ng. Imperfections of the model and specific considerations of the human in vivo case are discussed.

Animals↗
PubMed1987

The approach used to establish the safety of veterinary vaccines produced in the BHK 21 cell line.

A unique feature of the BHK 21 system is that the hamster provides a readily available and extremely sensitive (5, 13) assay system for process validation assays (Table IV outlines a production control scheme) since only between 5 and 100 cells are needed for tumors to form. While it was argued on theoretical grounds that a transforming agent active in a target species would not necessarily induce transformation in hamsters, clinical evidence has shown that the tumorigenicity of BHK 21 cells is a whole cell phenomenon. The main points to be drawn from the work with BHK 21/13 cells are as follows: 1. Cell culture technology now allows standardized, safe, effective, economical, large-scale vaccine production. 2. Although intact BHK 21 cells have been shown to be tumorigenic in hamsters, which is the species of origin for the cell line, no tumorigenic activity has been demonstrated in a variety of other aspects. 3. Even in hamsters, BHK 21 cells must be intact to cause tumor growth, a condition which can easily be avoided in biologicals production. 4. Decisions on the acceptability of a cell like the BHK 21 line were made on the basis of multiple species studies and validation of the manufacturing process to show that the final product was free of biologically active contaminants.

Animals↗
PubMed1986

Comparison of the colony forming ability and invasive potential of six primate cell lines treated with retinoic acid.

Four human and two nonhuman primate cell lines were studied to determine their growth characteristics in soft agar, and for invasive characteristics in a muscle organ culture assay system. The cell lines ranged from normal human diploid to frankly tumorigenic in animal models. Additional studies were performed to assess the effects of retinoic acid (RA) on colony forming ability and invasion. The results showed a wide range of cloning efficiencies among the cell lines tested, as well as the degree of invasiveness. Of the soft agar growth parameters studied, colony growth index correlated best with invasion in the organ culture assay. RA significantly inhibited the growth of the tumor cells in soft agar, but failed to inhibit invasion in the organ culture assay although there was inhibition of surface proliferation. The data are consistent with the suggestion that cell proliferation and invasion are not necessarily linked characteristics.

Animals↗
PubMed1986

Biologicals and vaccines: regulatory perspectives.

The new biotechnology has opened the door to a very broad array of new pharmaceutical products which lend themselves to high degrees of purity and potency. From a regulatory point of view, the two basic questions of safety and efficacy are central to their approval for marketing. The kinds of safety tests which should be done on these new products will be discussed, as will the novel safety issues related to the use of abnormal mammalian cells as substrates for the production of some new drugs and biologicals. In addition, the relative need for efficacy studies will be discussed in the context of a genetically engineered product when the "natural" product has already been shown to be effective and is commercially available.

Antibodies, Monoclonal↗
PubMed1985

Tumorigenicity testing of primate cell lines in nude mice, muscle organ culture and for colony formation in soft agarose.

Primate neoplastic and finite cell lines were tested in one in vivo and two in vitro test systems: adult nude mice, muscle organ culture (MOC) and soft agarose (SA). Comparison of the sensitivity of the systems indicated that nude mice were inferior to either in vitro system: WI-38 VA13 (an SV40 transformed cell line) did not cause tumours in these animals yet it behaved as if it were neoplastic in MOC and formed colonies in SA. There was complete correlation between results obtained in MOC and SA. All cell lines which produced tumors in vivo were positive in both in vitro test systems. None of the lines which showed normal patterns in MOC and in SA was tumorigenic in nude mice. Since testing in vitro is simpler, faster, and is thought to be reliable, we recommend SA followed by MOC as the initial assays for determining tumorigenicity of cells.

Animals↗
PubMed1985

Licensed tests for antibody to human T-lymphotropic virus type III. Sensitivity and specificity.

Before the discovery of the etiologic agent of the acquired immunodeficiency syndrome (AIDS), substantial epidemiologic evidence suggested that the responsible agent could be transmitted by blood and blood products such as factor VIII. The Public Health Service and the Food and Drug Administration therefore took general steps to increase the safety of the blood supply. With the discovery of the human T-lymphotropic virus type III (HTLV-III) it became possible to test blood for evidence of infection using an antibody detection assay. Currently licensed tests to detect antibody to HTLV-III range in sensitivity between 93% and 99%, and all are above 99% in specificity. The Public Health Service has issued provisional recommendations regarding the voluntary use of the antibody tests to screen blood and plasma donations.

Antibodies, Viral↗
PubMed1985

Safety issues relating to the use of mammalian cells as hosts.

There has been increasing interest over the past decade in exploring the possibility of using continuous cell lines as substrates for the production of both old and new biological products. The recent introduction of hybridoma technology to produce monoclonal antibodies, and the use of lymphoblastoid cells to produce interferon has broadened the discussion even further because both of those cell substrates are frankly tumorigenic. More recently, recombinant DNA technology has expanded beyond bacterial cells to mammalian cells, some of which may also be tumorigenic. One of the major safety concerns in biologicals produced from other than normal cells relates to the possibility that one or more of the biological characteristics of abnormal cells might be transmitted through residual DNA in the biological product to the human recipients. The assessment of risk for a given product must ultimately be based on the totality of evidence available including generic data on DNA as well as specific pieces of information on the product itself. These issues are discussed in the context of attempting to identify those data elements for the product which are essential for making an assessment of risk, plus generic information which may help to put the risk of DNA into an overall biological perspective.

Animals↗
PubMed1984

Tumorigenicity of Vero cells.

One of the current criteria for evaluating the acceptability of cell lines for use in vaccine production is lack of tumorigenicity. Vero cells represent an example of a class of cells known as continuous cell lines. They were derived from African green monkey kidney, and their growth properties and culture characteristics have many advantages over other cell substrates for use in vaccine production. We have tested Vero cells for tumorigenicity in nude mice and in a human muscle organ culture system, and found a significant increase in their tumorigenic potential with increasing passage numbers. Cells at passage 232 and higher produced nodules in all nude mice inoculated. Histologically the nodules were well defined, anaplastic tumors, which exhibited some of the characteristics of renal adenocarcinomas. In about 6 to 8 days all of the nodules began to regress. Data were obtained that suggested an immune mechanism was the basis for the regression phenomenon.

Animals↗
PubMed1983

Human muscle: a model for the study of human neoplasia.

Human muscle (HM) was used in an organ culture system to study the growth of human tumor cells and to test an antitumor drug. The HM system mimicked the in vivo situation regarding the behavior of neoplastic versus normal cells in that tumor cells proliferated extensively and invaded, while normal cells showed only a limited proliferative potential and a limited invasion was observed with fibroblasts but not with epithelial cells. In addition, when human plasma (HP) was used in place of fetal bovine serum (FBS) and cell culture medium as a source of nutrients, the tumor cells displayed a more aggressive histopathologic pattern. The HM system, as illustrated by the 5-FU results, allows the direct visualization of the effect to an antitumor agent not only on tumor cell growth but also on a range of histopathologically evaluable characteristics of the interaction of tumor cells with the host tissue. The HM system provides for the first time an in vitro experimental model using easily accessible adult human tissue to study cancer and its treatment.

Cell Division↗
PubMed1983

An overview of safety and regulatory aspects of the new biotechnology.

New technology is producing new drugs and biologic products that present novel safety issues for the regulatory agencies. These products are produced using recombinant DNA or hybridoma techniques. Examples are growth hormone, antihemophilic factor, and interferon, produced by recombinant DNA. Very special proteins, namely, monoclonal antibodies, can be made by hybridoma technology that are extremely pure and potent. At present over two dozen in vitro monoclonal antibody products are approved by FDA and many more are expected. Regulating these products posed some new questions for the FDA, regarding the kinds of safety tests that should be done to establish reasonable levels of safety before clinical trials or marketing of these agents. The production methods are novel and thus require careful consideration to ensure that risks inherent in those methods do not cause disease when these products are administered to human subjects. A general overview of the regulatory safety issues of these new products is given.

Antibodies, Monoclonal↗