imuvert and Disease-Models--Animal

The goal is to provide an overview on the advances in protection against chemotherapy-induced alopecia (CIA).. The four major parts of this review are (a) overview of the hair follicle biology, (b) characteristics of CIA, (c) state-of-the-art animal models of CIA, and (d) experimental approaches on protection against CIA.. The hair follicle represents an unintended target of cancer chemotherapy. CIA is a significant side effect that compromises the quality of life of patients. Overcoming CIA represents an area of unmet needs, especially for females and children. Significant progresses have been made in the last decade on the pathobiology of CIA. The pharmacological agents under evaluation include drug-specific antibodies, hair growth cycle modifiers, cytokines and growth factors, antioxidants, cell cycle or proliferation modifiers, and inhibitors of apoptosis. Their potential applications and limitations are discussed.. Multiple classes of agents with different action mechanisms have been evaluated in animal CIA models. Most of these protective agents have activity limited to a single chemotherapeutic agent. In comparison, calcitriol and cyclosporine A have broader spectrum of activity and can prevent against CIA by multiple chemotherapeutic agents. Among the three agents that have been evaluated in humans, AS101 and Minoxidil were able to reduce the severity or shorten the duration of CIA but could not prevent CIA.

Topics: Alopecia; Animals; Antineoplastic Agents; Antioxidants; Apoptosis; Biological Products; Calcitriol; Disease Models, Animal; Fibroblast Growth Factors; Hair; Hair Follicle; Humans; Stem Cells

Alopecia (hair loss) is among the most distressing side effects of cancer chemotherapy. Little progress has been made, however, in its prevention or treatment, partly because of the lack of suitable experimental model. In recent work on the treatment of myelogenous leukemia in the rat, the following observations were made: (i) treatment of 8-day-old rats with cytosine arabinoside consistently produced alopecia, and (ii) ImuVert, a biologic response modifier derived from the bacterium Serratia marcescens, uniformly produced complete protection against the alopecia. In subsequent experiments, both cyclophosphamide and doxorubicin also produced alopecia in this model, and the doxorubicin-induced alopecia was prevented by treatment with ImuVert. The potential relevance of these observations to chemotherapy-induced alopecia in the clinical setting should be examined.

Topics: Alopecia; Animals; Biological Products; Cytarabine; Disease Models, Animal; Immunologic Factors; Leukemia, Experimental; Rats; Rats, Inbred F344; Skin

We have previously demonstrated that the successful transfer of rat chloroleukemia (Mia C51) cells to newborn rats is related to the host's inability to generate adequate levels of differentiation factor (DF). Thus, when the appropriate amount of DF was injected into rats bearing MIA C51 cells, the development of chloroleukemia was aborted. In the present study, we provide evidence that stimulation of endogenous differentiation activity (DA) production by the administration of a biologic response modifier (Imuvert) will like-wise abort the development of chloroleukemia. Imuvert at 50 micrograms/ml had no direct effect on growth, viability, or differentiation of MIA C51 cells. However, when monocytes from young rats or adult rats were stimulated with Imuvert in vivo or in vitro, there was significant increase in DA production. Treatment of young rats with Imuvert aborted the development of chloroleukemia from transplanted MIA C51 cells. It is concluded that stimulation of endogenous DA production may provide a potentially useful approach in the treatment of leukemia.

Topics: Animals; Antineoplastic Agents; Biological Factors; Biological Products; Cell Differentiation; Disease Models, Animal; Immunologic Factors; Leukemia, Myeloid; Monocytes; Rats