Nano zinc Oxide-Ruthenium (III) complex of novel coumarin derivative: Synthesis, Characterization, DNA Cleavage, anticancer and bioimaging activities.

The uniqueness of nanofunctionalized metal complexes would play a prominent role in medicinal chemistry, especially in cancer chemotherapy. Among the metal based chemotherapeutic drugs, ruthenium complexes exhibit different oxidation states, lower toxicity and remarkable antitumor activities than other anticancer drugs. In this investigation bioactive ruthenium(III) complex has been synthesized from novel coumarin derivative and it is functionalized with nanostructured zinc oxide (ZnO) under well defined condition. An octahedral geometry is proposed for the ruthenium complex based on analytical and spectrochemical characterization techniques (UV, FT-IR and NMR). The g|| and g⊥ values obtained from the ESR spectrum indicated high symmetry and octahedral field around ruthenium ion. The XRD patterns of all synthesized compounds explicit average particle sizes are nanometer range. The morphology and particle size of Nano ZnO-Ru(III) complex is also confirmed by using SEM and TEM analysis. The nanofunctionalized material exhibited enhanced fluorescence emissions at 674 nm and 681 nm. The evaluation of DNA cleavage study indicated compounds were effectively cleaved supercoiled pUC18 DNA by gel electrophoresis method. The examinations of in-vitro anticancer activities of compounds were studied against human breast (MCF-7) and leukemia (K-562) cancer cell lines. The ruthenium complex showed greater effect against MCF-7 with < 10 IC50 value. Nowadays, the cell imaging property of nanofunctionalized materials receive more attention. The fluorescence microscopic images of Nano ZnO-Ru(III) complex displayed higher luminescence at 100 µg/ mL against L6 rat skeletal muscle cell line.

Analysis of radiotherapy in 1054 patients with primary central nervous system lymphoma treated from 1985 to 2009.

AIMS: Data on primary central nervous system lymphoma that had been collected through surveys for four consecutive periods between 1985 and 2009 were analysed to evaluate outcomes according to treatment. MATERIALS AND METHODS: All had histologically proven disease and had received radiotherapy. No patients had AIDS. Among 1054 patients, 696 died and 358 were alive or lost to follow-up. The median follow-up period for surviving patients was 37 months. RESULTS: For all patients, the median survival time was 24 months; the 5 year survival rate was 25.8%. Patients treated with methotrexate-based chemotherapy and radiation had a higher 5 year survival rate (43%) than those treated with radiation alone (14%) and those treated with non-methotrexate chemotherapy plus radiation (20%), but differences in relapse-free survival were smaller among the three groups. The 5 year survival rate was 25% for patients treated with whole-brain irradiation and 29% for patients treated with partial-brain irradiation (P = 0.80). Patients receiving a total dose of 40-49.9 Gy had a higher 5 year survival rate (32%) than those receiving other doses (21-25%, P = 0.0004) and patients receiving a whole-brain dose of 30-39.9 Gy had a higher 5 year survival rate (32%) than those receiving ≥40 Gy (13-22%, P < 0.0005). Patients receiving methotrexate-based chemotherapy and partial-brain radiotherapy (≥30 Gy) had a 5 year survival rate of 49%. CONCLUSIONS: The optimal total and whole-brain doses may be in the range of 40-49.9 and <40 Gy, respectively, especially in combination with chemotherapy. Patients receiving partial-brain irradiation had a prognosis similar to that of those receiving whole-brain irradiation. With methotrexate-based chemotherapy, partial-brain radiotherapy may be worth considering for non-elderly patients with a single tumour.

Radiation therapy for primary vaginal carcinoma.

Brachytherapy plays a significant role in the management of cervical cancer, but the clinical significance of brachytherapy in the management of vaginal cancer remains to be defined. Thus, a single institutional experience in the treatment of primary invasive vaginal carcinoma was reviewed to define the role of brachytherapy. We retrospectively reviewed the charts of 36 patients with primary vaginal carcinoma who received definitive radiotherapy between 1992 and 2010. The treatment modalities included high-dose-rate intracavitary brachytherapy alone (HDR-ICBT; two patients), external beam radiation therapy alone (EBRT; 14 patients), a combination of EBRT and HDR-ICBT (10 patients), or high-dose-rate interstitial brachytherapy (HDR-ISBT; 10 patients). The median follow-up was 35.2 months. The 2-year local control rate (LCR), disease-free survival (DFS), and overall survival (OS) were 68.8%, 55.3% and 73.9%, respectively. The 2-year LCR for Stage I, II, III and IV was 100%, 87.5%, 51.5% and 0%, respectively (P = 0.007). In subgroup analysis consisting only of T2-T3 disease, the use of HDR-ISBT showed marginal significance for favorable 5-year LCR (88.9% vs 46.9%, P = 0.064). One patient each developed Grade 2 proctitis, Grade 2 cystitis, and a vaginal ulcer. We conclude that brachytherapy can play a central role in radiation therapy for primary vaginal cancer. Combining EBRT and HDR-ISBT for T2-T3 disease resulted in good local control.

Head and neck tumors: assessment of perfusion-related parameters and diffusion coefficients based on the intravoxel incoherent motion model.

BACKGROUND AND PURPOSE: IVIM MR imaging provides perfusion and diffusion information with a single diffusion-weighted MR image. We determined whether PP and D differ among various types of head and neck tumors. MATERIALS AND METHODS: The study cohort included 123 head and neck tumors: 30 SCCs, 28 benign and 20 malignant SG tumors, 36 lymphomas, and 9 schwannomas. The D and PP values were determined by using b-values of 0, 500, and 1000 s/mm(2) based on the IVIM model. RESULTS: The PP values (lymphomas, 0.09 ± 0.04; SCCs, 0.15 ± 0.04; and malignant SG tumors, 0.22 ± 0.07) and D values (0.47 ± 0.07 × 10(-3) mm(2)/s, 0.82 ± 0.17 × 10(-3) mm(2)/s, and 1.03 ± 0.16 × 10(-3) mm(2)/s, respectively) were significantly different among the malignant tumors (P < .01). These values were also significantly different between pleomorphic adenomas (0.13 ± 0.02 and 1.44 ± 0.39 × 10(-3) mm(2)/s) and Warthin tumors (0.19 ± 0.04 and 0.73 ± 0.22 × 10(-3) mm(2)/s) (P < .001). The PP values of malignant SG tumors were significantly different from those of pleomorphic adenomas (P = .001) and the D values of the malignant SG tumors were significantly different from those of pleomorphic adenomas (P = .002) and Warthin tumors (P = .007). Schwannomas had large PP (0.23 ± 0.08) and D values (1.26 ± 0.20 × 10(-3) mm(2)/s), greatly overlapping those of some SG tumor types. CONCLUSIONS: Head and neck tumors had distinctive PP and D values by using IVIM MR imaging.

Efficacy of diffusion-weighted imaging for the differentiation between lymphomas and carcinomas of the nasopharynx and oropharynx: correlations of apparent diffusion coefficients and histologic features.

BACKGROUND AND PURPOSE: ADCs may help distinguish benign from malignant head and neck diseases. We sought to evaluate the effectiveness of ADC for differentiating between carcinomas and lymphomas of the nasopharynx and oropharynx. MATERIALS AND METHODS: We retrospectively compared the ADCs between 24 histologically proved lymphomas and 32 carcinomas, including 8 NPCs and 7 lymphomas of the nasopharynx, and 24 SCCs and 17 lymphomas of the oropharynx. ADCs were determined on tumor-by-tumor (overall ADCs) and pixel-by-pixel (ADC mapping) bases by using 2 b-values (500 and 1000 s/mm(2)). RESULTS: Lymphomas and oropharyngeal SCCs had unique histologic features in terms of keratinization, cell attenuation, stromal areas, and necrosis and had distinctive ADCs (0.503 ± 0.099 × 10(-3) mm(2)/s for lymphomas and 0.842 ± 0.164 × 10(-3) mm(2)/s for SCCs). However, NPCs and lymphomas were similar in terms of these histologic features, exhibiting comparable ADCs (0.567 ± 0.057 × 10(-3) mm(2)/s for NPCs and 0.528 ± 0.094 × 10(-3) mm(2)/s for lymphomas). Poorly and moderately differentiated SCCs with homogeneous T2 signals were indistinguishable from lymphomas on conventional MR images; however, ADCs of these SCC subtypes were significantly larger than those of lymphomas. ADC mapping profiles with respect to percentage of tumor areas of extremely low, intermediate, and high ADC levels were well-correlated with the histologic features of lymphomas, NPCs, and different types of SCCs. CONCLUSIONS: The effectiveness of ADC-based differentiation between lymphomas and carcinomas of the nasopharynx and oropharynx depends on their histologic characteristics.

Multiparametric MR imaging of sinonasal diseases: time-signal intensity curve- and apparent diffusion coefficient-based differentiation between benign and malignant lesions.

BACKGROUND AND PURPOSE: The sinonasal region is a platform for a broad spectrum of benign and malignant diseases, and image-based differentiation between benign and malignant diseases in this area is often difficult. Here, we evaluated multiparametric MR imaging with combined use of TICs and ADCs for the differentiation between benign and malignant sinonasal tumors and tumorlike diseases. MATERIALS AND METHODS: TICs obtained from dynamic contrast-enhanced MR imaging and ADCs were analyzed on a lesion-by-lesion (overall TIC and ADC) and pixel-by-pixel (TIC and ADC mapping) basis in patients with benign (n = 21) or malignant (n = 23) sinonasal tumors and tumorlike diseases. The TICs were semiautomatically classified into 5 distinctive patterns (flat, slow uptake, rapid uptake with low washout ratio, rapid uptake with high washout ratio, and miscellaneous). ADCs were determined by using b-values of 500 and 1000 s/mm(2). RESULTS: Malignant sinonasal tumors had small (<25%) areas of the type 1 flat TIC profile as determined by pixel-by-pixel TIC analysis and large (≥50%) areas of low or extremely low ADCs (≤1.2 × 10(-3) mm(2/)s) as determined by ADC mapping. Consequently, stepwise classification on the basis of TICs and ADCs successfully (at 100% accuracy) discriminated malignant from benign sinonasal diseases in the present patient cohort. CONCLUSIONS: Multiparametric MR imaging by using TICs and ADCs may help differentiate benign and malignant sinonasal diseases.

Apparent diffusion coefficient mapping for sinonasal diseases: differentiation of benign and malignant lesions.

BACKGROUND AND PURPOSE: CT and MR imaging features of benign and malignant sinonasal lesions are often nonspecific. Therefore, we evaluated the ADC-based differentiation of these lesions. MATERIALS AND METHODS: We retrospectively assessed ADCs of 61 patients with histologically proved sinonasal tumors and tumorlike lesions: 19 benign lesions, 28 malignant tumors, and 14 inflammatory lesions. Overall ADCs and percentages of total tumor area with extremely low, low, intermediate, or high ADCs (ADC mapping) were determined by using 2 b-values (500 and 1000 s/mm(2)). RESULTS: ADCs of malignant tumors (0.87 ± 0.32 × 10(-3) mm(2)/s) were significantly lower than those of benign (1.35 ± 0.29 × 10(-3) mm(2)/s, P < .0001) and inflammatory (1.50 ± 0.50 × 10(-3) mm(2)/s, P = .0002) lesions. On ADC mapping, percentages of total tumor area within malignant tumors having extremely low or low ADCs were significantly (P < .0001) greater than those within benign and inflammatory lesions. Cutoff points for ADC mapping (≥78% of tumor areas having extremely low or low ADCs) effectively differentiated benign or inflammatory lesions and malignant tumors with 75% sensitivity, 94% specificity, 85% accuracy, and 91% positive and 82% negative predictive values, respectively. ADCs also effectively discriminated lymphomas and SCCs from other malignant tumors. CONCLUSIONS: ADC mapping may be an effective MR imaging tool for the differentiation of benign/inflammatory lesions from malignant tumors in the sinonasal area.

Diffusion-weighted MR imaging of ameloblastomas and keratocystic odontogenic tumors: differentiation by apparent diffusion coefficients of cystic lesions.

BACKGROUND AND PURPOSE: Ameloblastomas and keratocystic odontogenic tumors are major aggressive odontogenic tumors in the maxillomandibular regions, but the differentiation between these 2 tumors is frequently ineffective based on only conventional CT and MR imaging findings. Here, we evaluated diffusion-weighted MR imaging for the differentiation of these 2 odontogenic tumors. MATERIALS AND METHODS: We prospectively studied 9 patients with ameloblastoma and 7 patients with keratocystic odontogenic tumor using diffusion-weighted MR imaging. Apparent diffusion coefficients (ADCs) of the nonenhancing and solid lesions in these tumors were determined with use of 2 b factors (500 and 1000). RESULTS: Two types of nonenhancing lesions were identified; one with high signal intensity on fat-suppressed T2-weighted images (type A) and the other with low or intermediate intensity (type B). The type A nonenhancing lesions were observed in all the ameloblastomas, but they were evident in only 2 keratocystic odontogenic tumors. It is interesting to note that the ADCs of the nonenhancing lesions in the ameloblastomas were significantly higher than those of the nonenhancing lesions in the keratocystic odontogenic tumors (2.48 +/- 0.20 x 10(-3) mm(2)/s vs 1.13 +/- 0.56 x 10(-3) mm(2)/s; P < .001). The ADCs of the solid lesions in the ameloblastomas (1.39 +/- 0.15 x 10(-3) mm(2)/s) were significantly lower than those of the nonenhancing lesions in the ameloblastomas and were similar to those of the nonenhancing lesions in the keratocystic odontogenic tumors. CONCLUSION: ADC determination may be used as an adjunct tool for differentiation between ameloblastomas and keratocystic odontogenic tumors.

MR imaging criteria for the prediction of extranodal spread of metastatic cancer in the neck.

BACKGROUND AND PURPOSE: The presence of extranodal spread in metastatic nodes significantly affects treatment planning and prognosis of the patient with head and neck cancer. We attempted to evaluate the predictive capability of MR imaging for the extranodal spread in the neck. MATERIALS AND METHODS: We retrospectively studied MR images from 109 patients with histologically proved metastatic nodes, of which 39 were positive for extranodal spread. We assessed 47 extranodal spread-positive and 130 extranodal spread-negative metastatic nodes by using the following MR imaging findings as the possible criteria for extranodal spread: 1) nodal size (short-axis diameter); 2) obliterated fat spaces between the metastatic node and adjacent tissues, such as the muscles and skin on T1-weighted images ("vanishing border" sign); 3) the presence of high-intensity signals in the interstitial tissues around and extending from a metastatic node on fat-suppressed T2-weighted images ("flare" sign); and 4) an irregular nodal margin on gadolinium-enhanced T1-weighted images ("shaggy margin"). Multivariate logistic regression analysis was conducted to identify independent predictive criteria for extranodal spread. RESULTS: Nodal size, shaggy margin, and flare sign criteria were independent and significant MR imaging findings suggestive of extranodal spread in the metastatic nodes. We obtained 77% sensitivity and 93% specificity with the flare sign, 65% sensitivity and 99% specificity with the shaggy margin, and 80% sensitivity and 85% specificity with the size criterion (cutoff point = 16 mm). CONCLUSION: Fat-suppressed T2-weighted and gadolinium-enhanced T1-weighted images are useful for the detection of extranodal spread in metastatic nodes in the neck.

MR imaging of labial glands.

BACKGROUND AND PURPOSE: The labial salivary gland is a site of occurrence of tumors and cysts, and it serves as the biopsy site for the diagnosis of Sjögren syndrome. However, its imaging features have not been well understood. Here we attempted to depict the labial gland by high-resolution MR imaging. MATERIALS AND METHODS: The labial glands from 89 patients without Sjögren syndrome, 14 patients with Sjögren syndrome, and 3 patients with tumor or cyst of the lips were imaged by using a 1.5T MR imager with a 47- or 110-mm surface coil. RESULTS: The upper and lower labial glands consisted of 1-3 layers of gland clusters, each of which had high signal intensity on T1-weighted and fat-suppressed T2-weighted images and was readily enhanced after gadolinium injection. The posterior parts of the glands were thicker than the anterior parts. The gland areas in the lower lips (186 +/- 64 mm(2) in women and 192 +/- 68 mm(2) in men) were greater than those in the upper lips (140 +/- 46 mm(2) in women and 162 +/- 66 mm(2) in men). We did not find any significant age-related changes or sex differences in the gland area. The labial gland areas were smaller in the patients with Sjögren syndrome than in patients without Sjögren syndrome, though the difference was significant only in the upper lips (104 +/- 53 mm(2)). CONCLUSION: This is the first report describing imaging features of the labial salivary glands. High-resolution MR imaging can readily delineate the labial glands.

Apparent diffusion coefficient mapping of salivary gland tumors: prediction of the benignancy and malignancy.

BACKGROUND AND PURPOSE: Preoperative prediction of tumor malignancy is clinically very important, because this information strongly influences the surgical plan. We evaluate the preoperative apparent diffusion coefficient (ADC) maps of benign and malignant salivary gland tumors. MATERIALS AND METHODS: High-resolution MR imaging was performed on 31 patients with benign or malignant salivary gland tumors; ADC maps of the tumors were also obtained. Surface coils of 47 or 110 mm diameter were used to improve the image resolution. The ADCs were compared with histologic features of the excised tumors. RESULTS: The ADC maps effectively depicted the histologic features of the salivary gland tumors, such as presence of cancer cells, myxomatous tissues, fibrosis, necrosis, cyst formation, and lymphoid tissues. The ADC maps showed that more frequent areas with high ADCs (> or = 1.8 x 10(-3) mm(2)/s) were significantly greater in benign tumors than in malignant tumors. The sensitivity and specificity for high ADC occupying fewer than 5% of the area of a tumor was 89% and 100%, respectively, resulting in 97% accuracy, 100% positive predictive value, and 96% negative predictive value. CONCLUSION: The ADC may provide preoperative tissue characterization of the salivary gland tumors.

Effects of glycine betaine on bone marrow death and intestinal damage by gamma rays and carbon ions.

In this study, we investigated the effects of glycine betaine (GB) on bone marrow death and intestinal damage by gamma rays or carbon ions. C(3)H/He female mice received an i.p.-injection of GB before or after whole-body irradiation with gamma rays or 50 keV microm(-1) carbon ions. The irradiated mice were observed to determine the mortality for 30 days after exposure. Mice were also killed at 3.5 days after the exposure to determine the intestinal damage. The numbers of crypts per transverse circumference were counted using a microscope. For the bone marrow death, GB (93 mg GB per mouse) significantly (p < 0.05) increased the percentage survival for both radiations. For the intestinal damage, GB (93 mg GB per mouse) significantly (p < 0.05) increased the crypt survival for gamma rays, but not for carbon ions. GB might be a potential protector against normal tissue damage as a side effect in radiotherapy.

Turbo short tau inversion recovery imaging for metastatic node screening in patients with head and neck cancer.

BACKGROUND AND PURPOSE: A rapid and sensitive MR imaging technique would be beneficial for screening of metastatic nodes in the neck. We preliminarily evaluated the coronal MR imaging with a turbo short tau inversion recovery (STIR) sequence for that purpose. METHODS: The coronal turbo STIR imaging (repetition time [TR]/echo time [TE]/inversion time [TI] = 3850 ms/20 or 80 ms/180 ms) and axial fat-suppressed spectral presaturation with inversion recovery (SPIR) T2-weighted imaging (fsT2WI) (TR/TE = 3500 ms/80 ms) were performed on 29 patients with head and neck cancer. We obtained coronal turbo STIR images and axial fsT2WI of the necks. The section thickness, intersection gap, matrix size, and field of view were the same in both techniques. The diagnostic ability for metastatic nodes was assessed at each neck level by using various cutoff size criteria. The nodal involvement was confirmed by histologic examination. RESULTS: The image acquisition time for the whole neck by coronal turbo STIR and axial fsT2WI techniques was approximately 2 minutes and 4 minutes, respectively. When the size criteria (cutoff sizes of short axis diameter were 8 mm at level I and 5 mm at levels II and III) were used, the STIR imaging yielded compromised diagnostic ability having 100% sensitivity and 100% negative predictive value (NPV). fsT2WI technique yielded 100 sensitivity and 100% NPV by using cutoff sizes of 6 mm at levels I and II and 5 mm at level III. CONCLUSION: Coronal STIR imaging provided a rapid screening technique for cervical metastatic nodes and could be a diagnostic tool before detailed MR studies of the neck.

Telomerase inhibition with a novel G-quadruplex-interactive agent, telomestatin: in vitro and in vivo studies in acute leukemia.

The telomerase complex is responsible for telomere maintenance and represents a promising neoplasia therapeutic target. Recently, we have demonstrated that treatment with a G-quadruplex-interactive agent, telomestatin reproducibly inhibited telomerase activity in the BCR-ABL-positive leukemic cell lines. In the present study, we investigated the mechanisms of apoptosis induced by telomerase inhibition in acute leukemia. We have found the activation of caspase-3 and poly-(ADP-ribose) polymerase in telomestatin-treated U937 cells (PD20) and dominant-negative DN-hTERT-expressing U937 cells (PD25). Activation of p38 mitogen-activated protein (MAP) kinase and MKK3/6 was also found in telomestatin-treated U937 cells (PD20) and dominant-negative DN-hTERT-expressing U937 cells (PD25); however, activation of JNK and ASK1 was not detected in these cells. To examine the effect of p38 MAP kinase inhibition on growth properties and apoptosis in telomerase-inhibited cells, we cultured DN-hTERT-expressing U937 cells with or without SB203580. Dominant-negative-hTERT-expressing U937 cells stopped proliferation on PD25; however, a significant increase in growth rate was observed in the presence of SB203580. Treatment of SB203580 also reduced the induction of apoptosis in DN-hTERT-expressing U937 cells (PD25). These results suggest that p38 MAP kinase has a critical role for the induction of apoptosis in telomerase-inhibited leukemia cells. Further, we evaluated the effect of telomestatin on the growth of U937 cells in xenograft mouse model. Systemic intraperitoneal administration of telomestatin in U937 xenografts decreased tumor telomerase levels and reduced tumor volumes. Tumor tissue from telomestatin-treated animals exhibited marked apoptosis. None of the mice treated with telomestatin displayed any signs of toxicity. Taken together, these results lay the foundations for a program of drug development to achieve the dual aims of efficacy and selectivity in vivo.

A multidisciplinary treatment strategy that includes high-dose chemotherapy for metastatic retinoblastoma without CNS involvement.

The prognosis of patients with metastatic retinoblastoma is poor with conventional chemotherapy and radiation. Since retinoblastoma is highly chemosensitive, dose-escalation of chemotherapeutic agents with stem cell support should be promising. We report our experience with high-dose chemotherapy (HDC) and autologous stem cell transplantation (SCT) in patients with metastatic retinoblastoma. Five patients with metastatic retinoblastoma underwent HDC with autologous SCT following conventional chemotherapy and local radiation therapy. Stem cells (bone marrow in four and peripheral blood stem cells in one) were collected after marrow involvement was cleared. Melphalan was a key drug in all patients, and was administered in combination with other agents such as cisplatin, cyclophosphamide, carboplatin or thiotepa. Three patients are currently alive disease-free at 113, 107 and 38 months, respectively, from the time of SCT. They had no central nervous system (CNS) involvement. The two patients who died of disease had CNS involvement. No long-term sequelae of HDC have been noted. Our treatment strategy using HDC appears to be effective for treating metastatic retinoblastoma without CNS involvement.

A G-quadruplex-interactive agent, telomestatin (SOT-095), induces telomere shortening with apoptosis and enhances chemosensitivity in acute myeloid leukemia.

Telomerase, the ribonucleoprotein enzyme maintaining the telomeres of eukaryotic chromosomes, is up-regulated in the vast majority of human neoplasias but not in normal somatic tissues. Therefore, the telomerase complex represents a promising universal therapeutic target in cancer. Telomeric G-rich single-stranded DNA can adopt in vitro an intramolecular quadruplex structure, which has been shown to inhibit telomerase activity. We examined G-quadruplex interactive agent, telomestatin (SOT-095), for its ability to inhibit the proliferation of human leukemia cells, including freshly obtained leukemia cells. Telomere length was determined by either the terminal restriction fragment method or flow-FISH, and apoptosis was assessed by flow cytometry. Moreover, chemosensitivity was examined in telomestatin-treated U937 cells before ultimate telomere shortening. Treatment with telomestatin reproducibly inhibited telomerase activity in U937 and NB4 cells followed by telomere shortening. Enhanced chemosensitivity toward daunorubicin and cytosine-arabinoside was observed in telomestatin-treated U937 cells, before ultimate telomere shortening. Telomere shortening associated with apoptosis by telomestatin was evident in some freshly obtained leukemia cells from acute myeloid leukemia patients, regardless of sub-types of AML and post-myelodysplasia AML. These results suggest that disruption of telomere maintenance by telomestatin limits the cellular lifespan of AML cells, as well. However, in a minority of AML patients apoptosis was not evident, thus indicating that resistant mechanism might exist in some freshly obtained AML cells. Therefore, further investigation of telomestatin as a therapeutic agent is warranted.