Antitumor Activity of TRAIL Recombinant Adenovirus in Human Malignant Glioma Cells

Tumor necrosis factor-Related Apoptosis-Inducing Ligand (TRAIL) has been reported to specifically kill malignant cells but to be relatively nontoxic to normal cells. One of disadvantages to previous in vivo protocols was the need for large quantities of TRAIL recombinant protein to suppress tumor growth. To evaluate the antitumor activity and therapeutic value of the TRAIL gene, we constructed adenoviral vectors expressing the human TRAIL gene (Ad.hTRAIL) and transferred them into malignant glioma cells in vitro and tumors in vivo, as an alternative to recombinant soluble TRAIL protein. The results show that TRAIL-sensitive glioma cells infected Ad.hTRAIL undergo apoptosis through the production and expression of TRAIL protein. The in vitro transfer elicited apoptosis, as demonstrated by the quantification of viable or apoptotic cells and by the analysis of cleavage of poly (ADP-ribose) polymerase. Furthermore, in vivo administration of Ad.hTRAIL at the site of tumor implantation suppressed the outgrowth of human glioma xenografts in SCID mice. These results further define Ad.hTRAIL as an anti-tumor therapeutic and demonstrate its potential use as an alternative approach to treatment for malignant glioma.

Combined Chemotherapy and Radiotherapy versus Radiotherapy alone in the Management of Localized Angiocentric Lymphoma of the Head and Neck / 대한방사선종양학회지

PURPOSE: To clarify the clinical benefit derived from the combined modality therapy (CMT) consisting of chemotherapy (CT) and involved field radiotherapy (RT) for stage I and II angiocentric lymphomas of the head and neck. MATERIALS AND METHODS: Of 143 patients with angiocentric lymphoma of the head and neck treated at our hospital between 1976 and 1995, 104 patients (RT group) received involved field RT alone with a median dose of 50.4 Gy (range : 20-70 Gy), while 39 patients (CMT group) received a median 3 cycles (range : 1-6 cycles) of CT before involved field RT. The response rate, patterns of failure, complications, and survival data of the RT group were compared with those of the CMT group. RESULTS: Despite a higher response rate, local failure was the most common pattern of failure in patients of both groups. The patterns of failure, including the systemic relapse rate were not influenced by the addition of combination CT. Although both modalities were well tolerated by the majority of patients, aberrant immunologic disorders or medical illnesses, such as a hemophagocytic syndrome, sepsis, intractable hemorrhage, or the evolution of second primary malignancies were more frequently observed in patients of the CMT group. The prognosis of patients in the RT group was relatively poor, with a 5-year overall actuarial survival rate of 38% and disease-free survival rate of 32%, respectively. However, their clinical outcome was not altered by the addition of systemic CT. Achieving complete remission was the most important prognostic factor by univariate and multivariate analyses, but treatment modality was not found to be a prognostic variable influencing survival. Conclusions : Involved field RT alone for angiocentric lymphoma of the head and neck was insufficient to achieve an improved survival rate, but the addition of CT to involved field RT failed to demonstrate any therapeutic advantage over involved field RT alone.