Screening of Promising Chemotherapeutic Candidates from Plants against Human Adult T-Cell Leukemia/Lymphoma (VI): Cardenolides from Asclepias curassavica.

In the course of our screening program for novel chemotherapeutic candidates from plants against adult T-cell leukemia/lymphoma, the extracts of Asclepias curassavica L. showed potent activity against MT-1 and MT-2 cells. Therefore, we attempted to isolate their active components. We identified a new cardenolide, 19-dihydrocalactinic acid methyl ester (1), along with 16 known cardenolides (2-17). Their structures were determined on the basis of spectroscopic data. Almost all of the isolated cardenolides inhibited the growth of both tumor cell lines. All the doubly linked cardenolides (11-17) except for 14 showed more potent activity than the other cardenolides. A comparison of the activities of 11, 14 and 16 revealed that the presence of hydroxy or acetoxy functional groups at C-16 led to a decrease in the activity. The 50% effective concentration (EC50) value of calotropin (11) against MT-2 cells was comparable to the potency of the clinical antineoplastic drug doxorubicin. The cytotoxic effect of 11 toward normal mononuclear cells obtained from the peripheral blood (PB-MNCs) was observed at a concentration 6 to 12 times higher than that used to induce growth inhibition against MT-1 and MT-2 cells. The proportions of annexin V-positive cells after 72 h of treatment with 11 were increased, indicating that it significantly induced apoptosis in MT-1 and MT-2 cells in a concentration-dependent manner. Cell cycle experiments demonstrated that 11 arrested MT-1 and MT-2 cells at the G2/M phase. Therefore, compound 11 may be a promising candidate for the treatment of adult T-cell leukemia/lymphoma.

Multi-institutional comparison of computer-based independent dose calculation for intensity modulated radiation therapy and volumetric modulated arc therapy.

PURPOSE: No multi-institutional studies of computer-based independent dose calculation have addressed the discrepancies among radiotherapy treatment planning systems (TPSs) and the verification programs for intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). We conducted a multi-institutional study to investigate whether ±5% is a reasonable action level for independent dose calculation for IMRT/VMAT. METHODS: In total, 477 IMRT/VMAT plans for prostate or head and neck (H&N) malignancies were retrospectively analyzed using a modified Clarkson-based commercial verification program. The doses from the TPSs and verification programs were compared using the mean ±1 standard deviation (SD). RESULTS: In the TPS-calculated dose comparisons for prostate and H&N malignancies, the sliding window (SW) technique (-2.5 ±â€¯1.8% and -5.3 ±â€¯2.6%) showed greater negative systematic differences than the step-and-shoot (S&S) technique (-0.3 ±â€¯2.2% and -0.8 ±â€¯2.2%). The VMAT dose differences for prostate and H&N malignancies were 0.9 ±â€¯1.8% and 1.1 ±â€¯3.3%, respectively. The SDs were larger for the H&N plans than for the prostate plans in both IMRT and VMAT. Such plans including more out-of-field control points showed greater systematic differences and SDs. CONCLUSIONS: This study will help individual institutions to establish an action level for agreement between primary calculations and verification for IMRT/VMAT. A local dose difference of ±5% at a point within the planning target volume (above -350 HU) may be a reasonable action level.