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Prolonged survival of xenograft following an intrathymic injection of xeno tumor cells and a short course of immunosuppressive therapy
172
Abstracts
B-8.6 #227
PROLONGED SURVIVAL OF XENOGRAFT FOLLOWING AN INTRATHYMIC INJECTION OF XENO TUMOR CELLS AND A SHORT COURSE OF IMMUNOSUPPRESSIVE THERAPY. S. Vaidya, C Roorda, S Rajaraman and J Fish, Departments of Pathology and Surgery, UTMB, Galveston, TX. We demonstrate prolonged induction of donor-specific unresponsiveness toward tumor xenograft following a short course of immunosuppressive therapy and intrathymic (IT) transplantation of tumor cells in Balb/c mice. Six weeks old male Balb/c mice were divided into four groups. The animals in each group were challenged with 3 different doses (1.0 x 107, 1.5 X 107 or 2.5 X 107 cells) of human colon carcinoma HTC-116 cell line known to cause lethal tumors in nude mice. The group 1 mice received no other treatment except the tumor graft challenge in their back. The second group of animals were immunosuppressed by 3 injections of anti lymphocytes anti serum (ALS) of 0.3 ml each on days -8, -7 and -6 prior to the tumor cells challenge on day 0. The third group received IT injection of 3.5 to 5 X 106 tumor cells into each lobe of their thymi seven days prior to the tumor cell challenge. The group 4 animals received both ALS injection as the animals in group 2 and IT tumor cell transplant as in group 3. Seven days after IT transplant, these animals were challenged with 1,2,5,10,15 and 25 X 106 tumor cells in their back (10 animals in each category). Every animal in group 1, 2 and 3 promptly rejected its tumor graft which was confirmed by biopsy. Even in group 4, tumors grew only in animals that received the highest dose of tumor cell challenge (25 X 106 cells). By day 5, tumors grew to a size of 9mm X 12ram X 7mm. The tumor growth was still evident on day 7 post tumor challenge although signs of necrosis were present in a biopsy. The tumors were completely rejected by day 15. This study suggests that induction of transient unresponsiveness toward xenograft is possible by intrathymic grafting of tumor cells, but it requires added systemic immunosuppression.
B-9.1 #228
Organ Transplantation: Islamic Philosophy and Perspective. N Berka, GM Dunston, A ARm, G Macintosh, A Odeh, lmmunogenetics Laboratory, Howard University, Washington, DC. During the last two decades, ~emendous success in the field of transplantation, has raised many ethical issues on the use of organs from living and non-living persons. There have been many proposals addressing ethically "correct" organ programs and strategies. While some consideration has been given to the analyses of cultural and ethnic diversity as important factors in organ procurement, few studies have evaluated this issue from the perspective of major refigions philosophies and the religions dimension of organ donation. For example, despite the growth of Islam around the world and especially in the United States, there is no literature (educational material) written tbr Mnslim~ regarding organ donation which can result in improper and insensitive counseling for Muslim donors and recipients. The Islamic perspective on organ transplantation is derived from the Holy Qu'ran, the tradition of the Prophet Mohmnmed and is ordered by the following fundamental rules constructed to protect the person: 1. The hmn should be removed, 2. The need should outweigh the tbrbidden, 3. The lesser harm should be allowed to prevent greater harm, 4. Harm can be allowed upon an individual to prevent harm to society, 5. The extent of the need is determined by its' importance; and 6. With every difficulty there is a relief. The contemporary jurisprudence has concluded that it is permissible to transplant an organ or part of an organ (such as bone marrow or kidneys) from a living donor to another living recipient after observation of conditions for such donation, and when the medical ennsultancy is convinced beyond any doubt that the recipient would make use of that transplant. However, the will of a person is restricted in the Islamicjurisprudence by not bringing damage on his/herself voluntarily. Hence the donated orgms or part of the organ should not result in damage or malfunction in the body of the donor because of the sttrgical operation or otherwise. All appropriate and necessary tests and analyses to evaluate the advantages and disadvantages of that operation should be carried out before the transplant operation while observing the medical procedures. Thus, efforts to determine the compatibilityof donors and recipients based on HLA matching would be highly regarded by Muslims and should be explained. Also, the contemporary jurists concluded that it is permissible to remove an organ from a dead body, such as the eyes, bem't or kidneys, so as to be transplanted into the body of a living person. On condition that the one from whom an organ is removed has willed that during their life time, or permission has been obtained from the dead person's family, then there is no violation of dignity or sanctity of the dead body because the purpose behind this is the benefit of the riving people who have more consideration than the dead ones.
Abstracts
B-8.6 #227
PROLONGED SURVIVAL OF XENOGRAFT FOLLOWING AN INTRATHYMIC INJECTION OF XENO TUMOR CELLS AND A SHORT COURSE OF IMMUNOSUPPRESSIVE THERAPY. S. Vaidya, C Roorda, S Rajaraman and J Fish, Departments of Pathology and Surgery, UTMB, Galveston, TX. We demonstrate prolonged induction of donor-specific unresponsiveness toward tumor xenograft following a short course of immunosuppressive therapy and intrathymic (IT) transplantation of tumor cells in Balb/c mice. Six weeks old male Balb/c mice were divided into four groups. The animals in each group were challenged with 3 different doses (1.0 x 107, 1.5 X 107 or 2.5 X 107 cells) of human colon carcinoma HTC-116 cell line known to cause lethal tumors in nude mice. The group 1 mice received no other treatment except the tumor graft challenge in their back. The second group of animals were immunosuppressed by 3 injections of anti lymphocytes anti serum (ALS) of 0.3 ml each on days -8, -7 and -6 prior to the tumor cells challenge on day 0. The third group received IT injection of 3.5 to 5 X 106 tumor cells into each lobe of their thymi seven days prior to the tumor cell challenge. The group 4 animals received both ALS injection as the animals in group 2 and IT tumor cell transplant as in group 3. Seven days after IT transplant, these animals were challenged with 1,2,5,10,15 and 25 X 106 tumor cells in their back (10 animals in each category). Every animal in group 1, 2 and 3 promptly rejected its tumor graft which was confirmed by biopsy. Even in group 4, tumors grew only in animals that received the highest dose of tumor cell challenge (25 X 106 cells). By day 5, tumors grew to a size of 9mm X 12ram X 7mm. The tumor growth was still evident on day 7 post tumor challenge although signs of necrosis were present in a biopsy. The tumors were completely rejected by day 15. This study suggests that induction of transient unresponsiveness toward xenograft is possible by intrathymic grafting of tumor cells, but it requires added systemic immunosuppression.
B-9.1 #228
Organ Transplantation: Islamic Philosophy and Perspective. N Berka, GM Dunston, A ARm, G Macintosh, A Odeh, lmmunogenetics Laboratory, Howard University, Washington, DC. During the last two decades, ~emendous success in the field of transplantation, has raised many ethical issues on the use of organs from living and non-living persons. There have been many proposals addressing ethically "correct" organ programs and strategies. While some consideration has been given to the analyses of cultural and ethnic diversity as important factors in organ procurement, few studies have evaluated this issue from the perspective of major refigions philosophies and the religions dimension of organ donation. For example, despite the growth of Islam around the world and especially in the United States, there is no literature (educational material) written tbr Mnslim~ regarding organ donation which can result in improper and insensitive counseling for Muslim donors and recipients. The Islamic perspective on organ transplantation is derived from the Holy Qu'ran, the tradition of the Prophet Mohmnmed and is ordered by the following fundamental rules constructed to protect the person: 1. The hmn should be removed, 2. The need should outweigh the tbrbidden, 3. The lesser harm should be allowed to prevent greater harm, 4. Harm can be allowed upon an individual to prevent harm to society, 5. The extent of the need is determined by its' importance; and 6. With every difficulty there is a relief. The contemporary jurisprudence has concluded that it is permissible to transplant an organ or part of an organ (such as bone marrow or kidneys) from a living donor to another living recipient after observation of conditions for such donation, and when the medical ennsultancy is convinced beyond any doubt that the recipient would make use of that transplant. However, the will of a person is restricted in the Islamicjurisprudence by not bringing damage on his/herself voluntarily. Hence the donated orgms or part of the organ should not result in damage or malfunction in the body of the donor because of the sttrgical operation or otherwise. All appropriate and necessary tests and analyses to evaluate the advantages and disadvantages of that operation should be carried out before the transplant operation while observing the medical procedures. Thus, efforts to determine the compatibilityof donors and recipients based on HLA matching would be highly regarded by Muslims and should be explained. Also, the contemporary jurists concluded that it is permissible to remove an organ from a dead body, such as the eyes, bem't or kidneys, so as to be transplanted into the body of a living person. On condition that the one from whom an organ is removed has willed that during their life time, or permission has been obtained from the dead person's family, then there is no violation of dignity or sanctity of the dead body because the purpose behind this is the benefit of the riving people who have more consideration than the dead ones.