imuvert and Alopecia

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

Topics: Administration, Topical; Alopecia; Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biological Products; Breast Neoplasms; Female; Humans; Immunologic Factors; Minoxidil; Rats

Chemotherapy-induced alopecia is a distressing problem to the cancer patient for which currently there is no effective preventive measure. Recently ImuVert, a biologic response modifier, has been shown to protect from cytarabine-induced alopecia in the young rat model, but not from alopecia induced by cyclophosphamide. In the present study, the rat model was used to examine the effect of N-acetylcysteine on the course of alopecia from cyclophosphamide and of ImuVert plus N-acetylcysteine on alopecia induced by cytarabine-cyclophosphamide combination. The following observations were made: (1) Cyclophosphamide-induced alopecia could be effectively prevented by N-acetylcysteine, administered parenterally or applied topically in liposomes. (2) Alopecia caused by the combination of cyclophosphamide and cytarabine could be prevented by the parenteral or topical administration of ImuVert plus N-acetylcysteine. The potential applicability of these observations to the clinical settings remains to be determined.

Topics: Acetylcysteine; Administration, Topical; Alopecia; Animals; Antineoplastic Combined Chemotherapy Protocols; Biological Products; Cyclophosphamide; Cytarabine; Immunologic Factors; Injections, Intraperitoneal; Injections, Subcutaneous; Random Allocation; Rats; Rats, Inbred F344; Rats, Inbred Strains

ImuVert, a biologic response modifier, and interleukin 1 (IL 1) have been shown to protect the young rat from alopecia induced by cytarabine (ARA-C). In the present study the inhibition by ARA-C of DNA synthesis in hair follicles (HFs) and the protective effect of ImuVert and IL 1 were investigated in vivo and in vitro. Both ImuVert and IL 1 were equally effective in protecting rats from ARA-C-induced alopecia. DNA synthesis in HFs isolated from ARA-C-treated animals was 10-20% of untreated controls. Follicles isolated from animals given either ImuVert or IL 1 before ARA-C exhibited normal DNA synthesis. In vitro, the incubation of normal rat HF with ARA-C resulted in 80% inhibition of [3H]-thymidine uptake. Preincubation of the follicles for 1 hr with IL 1 before the addition of ARA-C completely blocked the inhibition. Preincubation with imuVert, however, was less effective in blocking the inhibition from ARA-C.

Topics: Alopecia; Animals; Antineoplastic Agents; Biological Products; Cytarabine; DNA Replication; Dose-Response Relationship, Drug; Drug Antagonism; Hair; Immunologic Factors; In Vitro Techniques; Interleukin-1; Rats; Rats, Inbred Strains

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