Virological and immunological connotations of apoptotic and anti-apoptotic forces in neoplasia.
Against the background of its earliest recognition, programmed cell death (PCD) or apoptosis (A) is presented in its fundamental biological contexts. Techniques of its demonstration are listed. Former original works of the authors encompass designs for genetically engineered oncolytic viruses. Presented here are observations on mesenchymal stromal cells of the bone marrow serving as feeder layers to chronic lymphocytic leukemia (CLL) cells (recently rediscovered elsewhere as subverted "nurse cells" protecting CLL cells from A). A-resistant human melanoma cells are shown to expropriate the Fas ligand to Fas receptor (CD95; APO-1) (FasL-->FasR) system for their autocrine growth loop not only in melanoma cells coexpressing CD95 and its ligand but also in CD95-positive melanoma cells undergoing divisions when exposed to CD95 ligand. Bi-directional A-induction is demonstrated upon the encounter of cytotoxic lymphocytes and targeted tumor cells as exemplified with lymphomas; and chemotherapy-induced A of malignant cells as exemplified by paclitaxel-induced PCD of Reed-Sternberg (RS) cells in a case of chemotherapy-resistant Hodgkin's disease (HD). A list of interventions capable of inducing A in tumor cells is provided. These interventions are of potential therapeutic value. The balance of apoptotic and anti-apoptotic forces in virally infected normal and malignant cells is discussed.
Sinkovics
J G
JG
Cancer Institute, St. Joseph's Hospital, 3001 W. Dr. Martin Luther King Jr. Blvd., Tampa, FL 33607-6387, USA. sinkovi.joseph@baycare.org
Horvath
J C
JC
D000255:Adenosine Triphosphate / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis; D001853:Bone Marrow / Q000473:pathology*; D002154:Calpain / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002462:Cell Membrane / Q000276:immunology / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000821:virology; D053222:Fas Ligand Protein; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000821:virology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000276:immunology* / Q000378:metabolism; D014721:Vesicular stomatitis Indiana virus / Q000378:metabolism; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor; D000255:Adenosine Triphosphate; D002154:Calpain; D020169:Caspases