A decade of outcomes and predictors of sac enlargement after endovascular abdominal aortic aneurysm repair using zenith endografts in a Japanese population.

PURPOSE: To present 10-year outcomes and risk factors for sac enlargement after endovascular aneurysm repair (EVAR) using the Zenith AAA Endovascular Graft (Cook, Inc, Bloomington, Indiana) in a Japanese population. MATERIAL AND METHODS: During the period 1999-2011, 127 patients underwent elective EVAR using Zenith endografts at a single institution. A retrospective investigation looked at initial rates of technical success and complications, 10-year rate of freedom from all-cause and aneurysm-related mortality, freedom from secondary intervention and sac enlargement, and risk factors for second intervention and sac enlargement. RESULTS: The median age of the patients was 78 years, and the median follow-up time was 43 months. The initial technical success rate was 98.4% (125 of 127 patients). Major adverse events occurred in 7 of 127 (5.5%) patients. Rates of freedom from all-cause and aneurysm-related mortality at 1, 3, 5, and 10 years were 95%, 87%, 77%, and 39% (all-cause mortality) and 100%, 100%, 99%, and 93% (aneurysm-related mortality). Rates of freedom from secondary intervention at 1, 3, 5, and 10 years were 97%, 91%, 88%, and 70%. Rates of primary freedom from sac enlargement at 1, 3, 5, and 10 years were 99%, 87%, 75%, and 67%. Multivariate analysis revealed aneurysm sac diameter as an independent risk factor for a secondary intervention. Preoperative sac diameter combined with an angulated short (AS) proximal neck was a risk factor for sac enlargement. CONCLUSIONS: The 10-year results of EVAR using Zenith endografts in a Japanese population were comparable to results from Western countries. Larger aneurysms and AS neck were predictors of sac enlargement after EVAR.

Synthesis of carbon fibers with branched nanographene sheets for electrochemical double layer capacitor application.

We demonstrate a one step technique to synthesis the carbon fibers (CNFs) with branched nanographene sheets by the pulsed discharge (PD) plasma chemical vapor deposition (CVD) process. Highly crystalline branched nanographene sheets were directly grown from the surface of the carbon fibers to obtain a three dimensional (3D) nanostructure. The growth process can be explained from the catalyst support growth of the CNFs, and subsequently nucleation and growth of the nanographene sheets from the crystalline surface of the CNF. The deposited nanostructured films with different pulse discharge were used as an electrode for electrochemical double-layer capacitors (EDLC). It is observed that the capacitance is dependent on the morphology of the electrode materials and an optimum capacitance is obtained with the branched nanographene on CNFs.

[Radiofrequency ablation for recurred renal cell carcinoma in the solitary kidney due to von Hippel-Lindau disease--indication and tip on how to prevent the thermal injury of the adjacent organs].

A 48-year-old female with the von Hippel-Lindau disease had the recurred renal cell carcinomas (RCCs) in the left remnant kidney after the right nephrectomy and partial resection of the left kidney due to the multiple RCCs. We performed radiofrequency ablation (RFA) under CT guidance for the treatment of that recurred tumor. As the tumors were adjacent to the descending colon, we injected the carbon dioxide gas (a dissection technique) during a radiofrequency ablation (RFA) procedure to displace the descending colon from the tumors. As a result, we were able to successfully achieve RFA for the recurred tumors without any complications including the intestinal thermal injury such as wall thickening or perforation. The patient survives well 5 months after RFA without the local recurrence. RFA in the solitary kidney is safe and effective treatment to preserve the remaining renal function, and the dissection technique using with carbon dioxide gas is also useful to avoid the thermal injury of the adjacent organs.

Cantharidin induces apoptosis of human multiple myeloma cells via inhibition of the JAK/STAT pathway.

Multiple myeloma is an incurable B-cell malignancy requiring new therapeutic strategies in clinical settings. Interleukin (IL)-6 signaling pathways play a critical role in the pathogenesis of multiple myeloma. The traditional Chinese medicine cantharidin (CTD) has been shown to inhibit cellular proliferation and induce apoptosis of various cancer cells. The aim of this study was to investigate the possibility of CTD as a novel therapeutic agent for the patients with multiple myeloma. We investigated the in vitro effects of CTD for its antimyeloma activity, and further examined the molecular mechanisms of CTD-induced apoptosis. CTD inhibited the cellular growth of human myeloma cell lines as well as freshly isolated myeloma cells in patients. Cultivation with CTD induced apoptosis of myeloma cells in a cell-cycle-independent manner. Treatment with CTD induced caspase-3, -8, and -9 activities, and it was completely blocked by each caspase inhibitor. We further examined the effect of CTD on the IL-6 signaling pathway in myeloma cells, and found that CTD inhibited phosphorylation of STAT3 at tyrosine 705 residue as early as 1 h after treatment and down-regulated the expression of the antiapoptotic bcl-xL protein. STAT3 directly bound and activated the transcription of bcl-xL gene promoter, resulting in the induction of the expression of bcl-xL in myeloma cells. The essential role of STAT3 in CTD effects was confirmed by transfection with the constitutively active and dominant negative form of STAT3 in U266 cells. In conclusion, we have demonstrated that CTD is a promising candidate to be a new therapeutic agent in signal transduction therapy.

Drug-induced pneumonitis detected earlier by 18F-FDG-PET than by high-resolution CT: a case report with non-Hodgkin's lymphoma.

Drug-induced pneumonitis is a serious and an unpredictable side effect of chemotherapy in patients with malignant lymphoma. We present the case of a 51-year-old man who developed drug-induced pneumonitis during chemotherapy for non-Hodgkin's lymphoma in which pneumonitis was detected earlier by 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) than by high-resolution computed tomography (HRCT). After five courses of chemotherapy, 18F-FDG-PET was performed for assessing residual lesions, and diffuse lung uptake was incidentally observed. No symptoms were present, and HRCT performed immediately following PET revealed no abnormalities. Mild dyspnea appeared 3 days after PET, and additional HRCT revealed patchy ground-glass opacities disseminated with the appearance of interlobular septum thickening. Drug-induced pneumonitis was finally diagnosed, and treatment was initiated. 18F-FDG-PET can be an imaging modality for detecting drug-induced pneumonitis at an extremely early stage in which HRCT is incapable of revealing any abnormal changes.

Hypermetabolic change as a possible predictive sign of a relapsed central nervous system lymphoma.

PURPOSE: A patient with abdominal lymphoma who had been in complete remission for 6 years presented with a 1-month history of dysarthria. The aim of our report is to discuss the discordance of the patient's results between magnetic resonance (MR) imaging and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET). MATERIALS AND METHODS: After the onset, FDG PET and brain MR imaging were performed. The FDG PET study included whole-body and brain scan. The MR study included pre- and postcontrast T1, T2, fluid-attenuated inversion recovery and diffusion-weighted sequences. RESULTS: Brain MR imaging showed a localized abnormal signal around the left Sylvian fissure in any sequence, although a postcontrast study exhibited poor enhancement in the lesion. Brain PET showed a widespread area of slightly increased uptake in the brain on the left side, which was quite inconsistent with the MR results. After 4 months, follow-up MR imaging revealed a widespread abnormal signal, with enhancing masses, in the hypermetabolic region. CONCLUSIONS: Hypermetabolic changes on FDG PET preceded signal changes on MR imaging, potentially suggesting that hypermetabolism occurred in the microscopic infiltration of lymphoma cells.

TEL/AML1 overcomes drug resistance through transcriptional repression of multidrug resistance-1 gene expression.

The t(12;21)(p12;q22) chromosomal aberration, which is frequently observed in pediatric precursor B-cell acute lymphoblastic leukemia (ALL), generates the TEL/AML1 chimeric gene and protein. TEL/AML1-positive ALL has a favorable prognosis, and one possible reason is that this subtype of ALL rarely shows drug resistance. AML1/ETO, another AML1-containing chimeric protein, has been shown to transcriptionally repress the activity of the multidrug resistance-1 (MDR-1) gene promoter; thus, we examined whether TEL/AML1 also represses MDR-1 gene expression, possibly preventing the emergence of multidrug resistance. In this study, we show that the TEL/AML1 protein binds to the consensus AML1 binding site in the MDR-1 promoter and transcriptionally represses its activity. Following transient transfection of TEL/AML1 protein into Adriamycin-resistant K562/Adr cells, we also demonstrate that TEL/AML1 can down-regulate the expression of P-glycoprotein, a product of the MDR-1 gene, and restore the chemosensitivity to the cells. Furthermore, we report that MDR-1 mRNA levels in leukemic cells obtained from TEL/AML1-positive ALL patients are lower than those from TEL/AML1-negative ALL patients. Thus, TEL/AML1 protein acts as a transcriptional repressor of MDR-1 gene expression, and although TEL/AML1 has been implicated in leukemogenesis, its effects on the MDR-1 gene may contribute to the excellent prognosis of TEL/AML1-positive ALL with current therapy.

[Clinical study of porous gelatin sphere (YM 670) in transcatheter arterial embolization].

A clinical study on the use of porous gelatin particles(sterile gelatin embolization material, YM 670, Gelpart) in transcatheter arterial embolization (TAE) was performed in patients with hepatocellular carcinoma, and the efficacy (embolization,anti-tumor effect, recanalization and operationality) and safety (tolerability) were studied. An additive agent comprising porous gelatin particles and low osmolarity contrast media was administered peripherally through a catheter into the hepatic artery proper of 63 patients with hepatocellular carcinoma. Good hepatic arterial embolization was confirmed in all cases (embolization: 100%), and a tumor necrosis effect was obtained in most cases (35/62 patients, 56.5%). Moreover, operationality was assessed as "highly easy to use" or "easy to use" in all cases. Frequencies of adverse events in which a relationship to TAE was not excluded and abnormalities of clinical laboratory data were high at 71.4% and 9 8.4%, respectively. The most common adverse reactions were pyrexia, abdominal pain, queasiness and blood pressure increase;abnormalities in clinical laboratory data included hepatic function with increased AST (GOT), increased ALT (GPT), decreased cholinesterase, increased LDH and increased total bilirubin. These adverse reactions and abnormalities in clinical laboratory data, however, were transient and attributed to the TAE procedure itself, and no adverse reactions related to YM 670 as an embolic material were observed. In addition, with regard to tolerability (safety), the treatment was assessed as suitable for use in all the present cases.

All-trans retinoic acid directly up-regulates thrombopoietin transcription in human bone marrow stromal cells.

OBJECTIVE: All-trans retinoic acid (ATRA) has been used as the first-line therapy for patients with acute promyelocytic leukemia (APL). We previously reported that ATRA increased serum thrombopoietin (TPO) levels accompanied by thrombocytosis during ATRA therapy for APL. In this study, we investigated the mechanism of transcriptional regulation of TPO gene by ATRA using human bone marrow stromal cells. PATIENTS AND METHODS: Real time reverse transcriptase polymerase chain reaction and Western blotting were performed to quantify TPO mRNA and protein levels in cells from the human bone marrow stromal cell line KM101. Luciferase-based reporter assay, electrophoretic mobility shift assay (EMSA), and chromatin immunoprecipitation (ChIP) assay were performed to identify a retinoic acid responsive element in the promoter region of TPO gene (TPO-RARE). RESULTS: TPO mRNA expression was up-regulated by approximately 2.9 times 8 hours after stimulation with 10(-6) M ATRA in KM101 cells. In contrast, ATRA did not alter TPO mRNA expression in cells from the human hepatoma cell line HepG2. Protein level of KM101 cells also was increased with 10(-6) M ATRA for 48 hours in KM101 cells. We found the synthesized RARalpha protein bound to [gamma-32P]-labeled TPO-RARE probe and its binding was competed by adding 200x amount of cold TPO-RARE probe by EMSA. In addition, [gamma-32P]-labeled TPO-RARE probe bound to KM101 nuclear protein extract was supershifted by anti-RARalpha antibody and modified by treatment with ATRA. The relative luciferase activity of TPO gene was increased by 2.2x and the histone H4 was acetylated through TPO-RARE after ATRA stimulation in KM101 cells by ChIP assay. CONCLUSION: These data support the direct up-regulation of TPO transcription by ATRA stimulation in human bone marrow stromal cells and propose one of the mechanisms of thrombocytosis during ATRA therapy for APL.

Decreased 18F-FDG uptake 1 day after initiation of chemotherapy for malignant lymphomas.

UNLABELLED: Several recent reports have described the judgment of chemotherapeutic effects on malignant lymphomas by use of (18)F-FDG PET as early as a few courses after the initiation of chemotherapy. However, the optimal timing of (18)F-FDG PET has yet to be clarified. Earlier (18)F-FDG PET, such as day 1 after chemotherapy, may be affected by inflammation or chemotoxicity in addition to chemotherapeutic effects, but the ways in which uptake is changed are as yet unclear. We therefore examined changes in (18)F-FDG PET results on day 1 after the initiation of chemotherapy for malignant lymphoma. METHODS: Twelve patients with non-Hodgkin's lymphoma were enrolled in this study. (18)F-FDG PET was performed before therapy to determine baseline results and then was repeated at day 1 and day 20 after the initiation of chemotherapy (just before the initiation of the second course of chemotherapy) and at the end of chemotherapy. We selected 1-9 regions of interest (ROIs) from each patient and calculated the corrected standardized uptake value (SUV(cor)) by subtracting the SUV of surrounding normal tissue for a semiquantitative analysis. From the ROIs in each patient, the representative SUV(cor) with the highest SUV(cor) at baseline was selected, and the mean representative SUV(cor)s for all 12 patients at baseline, day 1, day 20, and the end of chemotherapy were evaluated. Changes in the representative SUV(cor) were compared by use of paired t tests (2-tailed P values of <0.05 were considered statistically significant). RESULTS: All representative SUV(cor)s for each patient were lower on day 1 than at baseline, and the mean +/- SD representative SUV(cor) for all patients was significantly decreased from 10.7 +/- 7.9 at baseline to 5.8 +/- 5.8 at day 1 (P = 0.0002; paired t test). On day 20, the mean +/- SD SUV(cor) was 0.7 +/- 1.0, showing a further decrease from the value at day 1 (P = 0.01). Although the mean +/- SD SUV(cor) tended to decrease again to 0.4 +/- 0.7 by the end of chemotherapy compared with the value at day 20, no significant difference was identified (P = 0.37). CONCLUSION: (18)F-FDG uptake decreased as early as day 1 after the initiation of chemotherapy, indicating that (18)F-FDG PET for initial diagnosis or staging must be performed before the onset of chemotherapy, as scan results might already be severely compromised after the first day.

[Evaluation of lesions of malignant lymphoma using histograms of regional SUV].

We designed new evaluation method using histogram of regional standardized uptake value (SUV) of every pixels of box shape volume of interest (VOI) on 18F-FDG PET. We evaluate lung and liver of normal volunteers and also the lesions of 4 cases of patients with non Hodgikin's malignant lymphoma using this method. SUV of pixels of pretreatment lesions shows log-normal distribution, whereas SUV of lung and liver show normal shape distribution. The next day of chemotherapy, 2 cases of them showed changes of distribution pattern from long-normal to normal with decrease of component of higher SUV values. No remarkable changes of distribution pattern were observed on other 2 cases, whereas decrease of regional mean values and max values of SUV were observed. And these findings were continued to 3 weeks later. These findings suggest that regional evaluation using histograms of SUV gives additional and predictive information for tumor therapies soon after the end of course.

Gossypol induces apoptosis in multiple myeloma cells by inhibition of interleukin-6 signaling and Bcl-2/Mcl-1 pathway.

Multiple myeloma (MM) is a clonal plasma cell disorder affecting the immune system with various systemic symptoms. MM remains incurable even with high dose chemotherapy using conventional drugs, thus necessitating development of novel therapeutic strategies. Gossypol (Gos) is a natural polyphenolic compound extracted from cotton plants, and has been shown to possess anti-neoplastic activity against various tumors. Recent studies have shown that Gos is an inhibitor for Bcl-2 or Bcl-XL acting as BH3 mimetics that interfere interaction between pro-apoptotic BH3-only proteins and Bcl-2/Bcl-XL. Since most of the patients with MM overexpress Bcl-2 protein, we considered Gos might be a promising therapeutic agent for MM. We herein show that Gos efficiently induced apoptosis and inhibited proliferation of the OPM2 MM cell line, in a dose- and time-dependent manner. Gos induced activation of caspase-3 and cytochrome c release from mitochondria, showing mitochondrial dysfunction pathway is operational during apoptosis. Further investigation revealed that phosphorylation of Bcl-2 at serine-70 was attenuated by Gos treatment, while protein levels were not affected. In addition, Mcl-1 was downregulated by Gos. Interestingly, phosphorylation of JAK2, STAT3, ERK1/2 and p38MAPK was inhibited by Gos-treatment, indicating that Gos globally suppressed interleukin-6 (IL-6) signals. Moreover, JAK2 inhibition mimicked the effect of Gos in OPM2 cells including Bcl-2 dephosphorylation and Mcl-1 downregulation. These results demonstrated that Gos induces apoptosis in MM cells not only through displacing BH3-only proteins from Bcl-2, but also through inhibiting IL-6 signaling, which leads to Bcl-2 dephosphorylation and Mcl-1 downregulation.

The role of TC-PTP (PTPN2) in modulating sensitivity to imatinib and interferon-α in CML cell line, KT-1 cells.

T-cell protein tyrosine phosphatase (TC-PTP, also known as PTPN2) is a negative regulator of the JAK/STAT pathway. STAT5 is activated by BCR-ABL kinase and STAT1 is an important transcription factor for interferon (IFN)-α-induced signaling in chronic myeloid leukemia (CML). We used siRNA to delete TC-PTP in the CML cell line, KT-1, and examined changes in the sensitivity to imatinib and IFN-α. Suppression of TC-PTP induced activation of STAT5, leading to imatinib resistance, while prolonged phosphorylation of STAT1 was induced by IFN-α, triggering cell death in KT-1 cells. These findings suggest that TC-PTP modulates sensitivity to imatinib and IFN-α in CML.

Long-term outcome of transcatheter subsegmental and segmental arterial chemoemobolization using lipiodol for hepatocellular carcinoma.

PURPOSE: To clarify the efficacy of transcatheter hepatic sub-subsegmental, subsegmental, and segmental arterial chemoembolization using lipiodol (subseg/seg lip-TACE) for hepatocellular carcinoma (HCC), long-term outcomes of patients who had been treated using subseg/seg lip-TACE alone were retrospectively examined. MATERIALS AND METHODS: Subjects comprised 199 patients with HCC (T1/2/≥3=30/108/61; Child-Pugh A/B/C=115/52/32; Japan Integrated Staging [JIS] score≤1/2/≥3=88/64/47) who underwent subseg/seg lip-TACE using lipiodol mixed with an anticancer drug followed by injection of gelatin sponge particles. Each patient was followed-up every 3 months, and repeat subseg/seg lip-TACE and/or conventional lip-TACE was performed in cases showing recurrence. One-, 3-, 5-, 7-, and 10-year cumulative survival rates were calculated. Subgroup analyses were performed by stratifying the population according to T-factor, Child-Pugh classification, and JIS score. RESULTS: Median duration of follow-up was 3.8 years (range 0.2 to 16.4). Median overall survival was 3.8 years. One-, 3-, 5-, 7- and 10-year survival rates were 91.5, 66.1, 38.8, 20.3, and 9.4% for all patients, and 95.5, 76.9, 51.9, 27.9 and 20.4% for patients with JIS≤1, respectively. Significant survival differences were found across two subgroups of staging systems (T2 vs. T3≤[P=0.0012] and JIS score≤1 vs. 2 [P=0.0036]). CONCLUSION: This study demonstrated that subseg/seg lip-TACE is a feasible treatment for obtaining prolonged survival in patients with localized HCC showing rich vasculature. Outcomes are influenced by both tumor stage and liver function, as seen in the best prolonged survival in patients with JIS score≤1.

The gold compound auranofin induces apoptosis of human multiple myeloma cells through both down-regulation of STAT3 and inhibition of NF-κB activity.

Constitutive activation of NF-κB and STAT3 plays an important role in the cellular proliferation and survival of multiple myeloma cells. We first found that auranofin (AF), a coordinated gold compound, induced a significant level of cell cycle arrest at G1 phase and subsequent apoptosis of myeloma cells. Further, AF inhibited constitutive and IL-6-induced activation of JAK2 and phosphorylation of STAT3 followed by the decreased expression of Mcl-1. AF down-regulated the activation of NF-κB, and the combination of AF and a specific NF-κB inhibitor resulted in a marked decrease of Mcl-1 expression. These results suggest that AF inhibits both IL-6 induced-JAK/STAT pathway and NF-κB activation in myeloma cells.

Experimental study of poly-L-lactic acid biodegradable stents in normal canine bile ducts.

PURPOSE: This study was designed to clarify the advantages of biodegradable stents in terms of mucosal reaction and biodegradation after placement. We designed a biodegradable stent and assessed stent degradation and changes in the normal bile ducts of dogs. METHODS: The biodegradable stent is a balloon-expandable Z stent consisting of poly-L-lactic acid (PLLA) with a diameter of 6 mm and a length of 15 mm. We assessed four groups of three beagle dogs each at 1, 3, 6, and 9 months of follow-up. After evaluating stent migration by radiography and stent and bile duct patency by cholangiography, the dogs were sacrificed to remove the bile duct together with the stent. The bile duct lumen was examined macroscopically and histologically, and the stent degradation was examined macroscopically and by scanning electron microscopy (SEM). RESULTS: Bile duct obstruction was absent and none of the stents migrated. Macroscopic evaluation showed moderate endothelial proliferation in the bile ducts at the implant sites at 3 and 6 months and a slight change at 9 months. Slight mononuclear cell infiltration was histologically identified at all time points and epithelial hyperplasia that was moderate at 3 months was reduced to slight at 6 and 9 months. Stent degradation was macroscopically evident in all animals at 9 months and was proven by SEM in two dogs at 6 months and in all of them at 9 months. CONCLUSIONS: Our results suggest that PLLA bioabsorbable stents seems to be useful for implantation in the biliary system with further investigation.

Initial experience of branched endovascular graft for abdominal aortic aneurysm with complex anatomy of proximal neck: planning and technical considerations.

The purpose of this report was to demonstrate initial Japanese cases of abdominal aortic aneurysm (AAA) with complex anatomy of proximal neck treated using a Zenith fenestrated endograft with branched endovascular technique and to describe the device's design and technical considerations. Planning and sizing of endografts were performed using high-resolution computed tomography on a three-dimensional workstation. Branched endograft technique combined with reinforced fenestrated device and balloon-expandable stent graft was used in two patients because of challenging morphology for the fenestrated device with a bare stent. Successful exclusion of the aneurysm sac was achieved in both patients with antegrade perfusion in incorporated visceral vessels. Endovascular repair using a fenestrated device with graft material incorporating the visceral arteries is feasible. The combination of the reinforced fenestration and the balloon-expandable stent graft can provide an adequate sealing effect for the compromised anatomy. Initial and midterm results are reported with further follow-up and patient accrual.

Accuracy of centerline of flow measurement for sizing of the Zenith AAA endovascular graft and predictive factor for risk of inadequate sizing.

The purpose of this study was to evaluate the accuracy of centerline of flow (CLF) measurement for precise sizing of the Zenith AAA endovascular graft (Zenith) and to identify predictive factors of risk of inadequate endograft sizing. We analyzed 42 consecutive patients treated using the Zenith with pre- and postoperative multidetector CT between 2001 and 2007. Endograft sizing was retrospectively performed using CLF on a three-dimensional workstation. The following parameters were investigated: (a) change in distance from lowest renal artery to hypogastric artery between CLF on preoperative CT (CLFp) and CLF of graft path on postoperative CT (CLFg); (b) supposed success rate of adequate endograft length selection; and (c) predictive factors for significant alteration (>10 mm) between CLFp and CLFg. Median change in distance from lowest renal artery to hypogastric artery was 4 mm. CLFg was >10 mm shorter than CLFp in 10 of 84 limbs (12%). Multivariate analysis demonstrated tortuosity index (TI) of infrarenal abdominal aorta (p = 0.019), aneurysm diameter (p = 0.035), and ipsilateral side of the main body insertion (p = 0.042) as predictive factors of significant alteration between CLFp and CLFg. Adequate endograft length selection was achieved in 39 of 42 cases (93%). All three inadequate endograft length selections were associated with tortuous aorta (TI > 20 mm). In conclusion, distance calculations based on CLF measurement provided accurate length selection of the Zenith in the majority of cases. TI, aneurysm diameter, and ipsilateral side were predictive factors for significant alteration. The CLF and aortic measurements including the TI may allow for improved sizing for Zenith placements.

New therapeutic approaches to acute myeloid leukemia.

BACKGROUND: The heterogeneity of acute myeloid leukemia (AML) has been established by many new insights into the pathogenesis and treatment of patients with AML. Understanding the basic cellular and molecular pathogenesis of leukemic cells is vital to the development of new treatment approaches. OBJECTIVE/METHODS: To review progress until now with agents that are showing promise in the treatment of AML, we summarize the published preclinical and clinical trials that have been completed. RESULTS: Based on recent progress of investigations, more specifically targeted agents have been developed for the treatment of AML such as tyrosine kinase inhibitors, monoclonal antibodies, epigenetic agents, antiangiogenic agents, and farnesyl transferase inhibitors. CONCLUSION: In the future, in addition to performing therapeutic trials of these agents, it will be important to identify other highly specific therapeutic agents based on our evolving understanding of the biology of AML.