Helical tomotherapy is an image-guided, intensity-modulated radiation therapy delivery system, a hybrid between a linear accelerator and a helical CT scanner. With its unique design features, tomotherapy has improved dose conformity and homogeneity of the target volumes, and conformal avoidance of the adjacent normal tissues. The daily pretreatment megavoltage computed tomography (MVCT) is a powerful tool used in image guided treatment delivery and patient setup verification. If anatomic changes occur during the course of treatment, MVCT images are utilized in correcting target volumes and constructing appropriate adaptive plans. Helical tomotherapy can be applied to more complicated cases, where conventional techniques find their limits: complex tumors with critical organ sparing, simultaneous irradiation of multiple targets, large volume and large superficial tumor irradiation, and recurrent tumor re-irradiation are a few examples. Tomothearpy may change the current paradigm in radiation oncology in the near future. Further studies regarding clinical implementation and treatment outcome of helical tomotherapy will be needed.
Chimera ; Humans ; Particle Accelerators ; Radiation Oncology ; Radiotherapy, Intensity-Modulated ; Tomography, Spiral Computed ; Treatment Outcome

BACKGROUND: Transplantation of solid organs has been increasing explosively. However, numerous problems remain unsolved, including the requirement for chronic immunosuppressive therapy and the shortage of donor organs. Recently one way to overcome this is bone marrow transplantation after total body irradiation. Especially though the dose of radiation used for conditioning is decreased, allogeneic bone marrow cells are engrafted and it can induce donor specific tolerance for allografting. The aim of this study is to develop a nonlethal conditioning approach to achieve donor chimerism and to confirm donor specific tolerance in C57BL/6 mice. METHODS: We performed experiments on C57BL/6 mice divided into three groups according to preparatory radiation dosage. C57BL/6 mice received sublethal dose of radiation and transplanted with bone marrow cells from BALB/c. The percentage of donor derived cells was analyzed by flow cytometry (FACS) and the donor specific tolerance for allografts was assessed by BALB/c skin grafts and so did it by mixed lymphocyte reaction (MLR) and cytotoxicity (CML) using spleen cells from chimeras (BALB/c->C57BL/6). RESULTS: Induction of alllogeneic donor chimerism occurred in 50%, 100%, 100% of animals irradiated with 6Gy, 7Gy, and 9Gy TBI, respectively. One hundred percent of chimeras with evidence of donor chimerism accepted skin allografts. Moreover, mixed chimeras exhibited donor specific tolerance in vitro as assessed by MLR and CML. CONCLUSION: This strategy induced the donor chimerism and exhibited the donor specific tolerance effect for skin allografting.
Allografts ; Animals ; Bone Marrow Cells ; Bone Marrow Transplantation ; Chimera ; Chimerism* ; Flow Cytometry ; Humans ; Immune Tolerance* ; Lymphocyte Culture Test, Mixed ; Mice ; Organ Transplantation* ; Radiation Dosage ; Skin ; Spleen ; Tissue Donors* ; Transplantation, Homologous ; Transplants* ; Whole-Body Irradiation

Bone marrow mesenchymal stromal cells (MSCs) have been implicated in the microenvironmental support of hematopoietic stem cells (HSCs) and often co-transplanted with HSCs to facilitate recovery of ablated bone marrows. However, the precise effect of transplanted MSCs on HSC regeneration remains unclear because the kinetics of HSC self-renewal in vivo after co-transplantation has not been monitored. In this study, we examined the effects of intrafemoral injection of MSCs on HSC self-renewal in rigorous competitive repopulating unit (CRU) assays using congenic transplantation models in which stromal progenitors (CFU-F) were ablated by irradiation. Interestingly, naive MSCs injected into femur contributed to the reconstitution of a stromal niche in the ablated bone marrows, but did not exert a stimulatory effect on the in-vivo self-renewal of co-transplanted HSCs regardless of the transplantation methods. In contrast, HSC self-renewal was four-fold higher in bone marrows intrafemorally injected with beta-catenin-activated MSCs. These results reveal that naive MSCs lack a stimulatory effect on HSC self-renewal in-vivo and that stroma must be activated during recoveries of bone marrows. Stromal targeting of wnt/beta-catenin signals may be a strategy to activate such a stem cell niche for efficient regeneration of bone marrow HSCs.
Animals ; Bone Marrow/metabolism/pathology ; Hematopoietic Stem Cell Mobilization ; *Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/pathology ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stem Cells/*metabolism/pathology ; Mice ; Mice, Inbred C57BL ; Radiation Chimera ; Regeneration ; Stem Cell Niche/metabolism/pathology ; Stromal Cells/*metabolism/pathology ; *Transplantation Conditioning ; beta Catenin/*metabolism