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[A Case of Descending Colon and Rectal Cancer with Acute Myeloid Leukemia Performed Robot‒Assisted Hartmann's Procedure].

Gan To Kagaku Ryoho 2021 Apr;48(4):599-601

Dept. of Gastroenterological Surgery, Hirosaki University Graduate School of Medicine.

The case is a 68‒year‒old male, who had been diagnosed with acute myeloid leukemia(AML)prior to rectal cancer surgery, was referred to our hospital for treatment in July 2019. We planned to treat the AML first, and then the colorectal cancer. After completion of 1 course of CAG therapy(cytarabine, aclarubicin, G‒CSF), his white blood cell count increased sufficiently, so he underwent a robot‒assisted Hartmann operation in October. Read More

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Clinical Characteristics and Optimal Therapy of Acute Myeloid Leukemia with Myelodysplasia-related-changes: A Retrospective Analysis in a Cohort of Chinese Patients.

Turk J Haematol 2021 May 3. Epub 2021 May 3.

Qingdao University Medical College, Affiliated Yantai Yuhuangding Hospital, Department of Hematology, Yantai, China.

Objective: This study aimed to investigate the clinical characteristics of acute myeloid leukemia with myelodysplasia-related-changes (AML-MRC) according to the 2016 WHO classification and the preferred therapy of patients with AML-MRC and aged 60-75 years.

Materials And Methods: We retrospectively analyzed the differences of clinical data between 190 patients with AML-MRC and 667 patients with AML not otherwise specified (AML-NOS). And we compared different therapeutic regimens among patients with AML-MRC and aged 60-75 years. Read More

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Early T-Cell Precursor Acute Lymphoblastic Leukemia and T/Myeloid Mixed Phenotype Acute Leukemia Possess Overlapping Characteristics and Both Benefit From CAG-Like Regimens and Allogeneic Hematopoietic Stem Cell Transplantation.

Transplant Cell Ther 2021 Feb 28. Epub 2021 Feb 28.

National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China; Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China. Electronic address:

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) and T-lymphoid/myeloid mixed phenotype acute leukemia (T/M-MPAL) are closely related entities and remain a therapeutic challenge. In this study, we characterized the clinical features of 43 ETP-ALL and 41 T/M-MPAL patients and compared clinical outcomes and safety between cytarabine, aclarubicin, and granulocyte colony-stimulating factor (CAG)-like regimens in 34 patients and conventional ALL regimens in 50 patients. In our series, ETP-ALL and T/M-MPAL showed similar biological characteristics, immunophenotypes, genomic alterations, and outcomes. Read More

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February 2021

Carbonyl reduction pathway in hepatic in vitro metabolism of anthracyclines: Impact of structure on biotransformation rate.

Toxicol Lett 2021 May 10;342:50-57. Epub 2021 Feb 10.

Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9 St., 30-638, Kraków, Poland.

Carbonyl reduction biotransformation pathway of anthracyclines (doxorubicin, daunorubicin) is a significant process, associated with drug metabolism and elimination. However, it also plays a pivotal role in anthracyclines-induced cardiotoxicity and cancer resistance. Herein, carbonyl reduction of eight anthracyclines, at in vivo relevant concentrations (20 μM), was studied in human liver cytosol, to describe the relationship between their structure and metabolism. Read More

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Multiple keratoacanthomas in a patient with myelodysplastic syndrome.

Lancet Haematol 2021 01 22;8(1):e94. Epub 2020 Dec 22.

Department of Dermatology and Venereology, Peking University First Hospital, Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, China. Electronic address:

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January 2021

Drug repurposing using transcriptome sequencing and virtual drug screening in a patient with glioblastoma.

Invest New Drugs 2021 Jun 12;39(3):670-685. Epub 2020 Dec 12.

Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 5512, Mainz, Germany.

Background Precision medicine and drug repurposing are attractive strategies, especially for tumors with worse prognosis. Glioblastoma is a highly malignant brain tumor with limited treatment options and short survival times. We identified novel BRAF (47-438del) and PIK3R1 (G376R) mutations in a glioblastoma patient by RNA-sequencing. Read More

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[Comparison of the Curative Efficacy of Elderly Patients with High-Risk MDS and MDS-Transformed AML between Decitabine Combined with Low-Dose CEG Regimen and Decitabine Combined with Low-Dose CAG Regimen].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2020 Dec;28(6):1991-1997

Department of Hematology, First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China.

Objective: To evaluate the efficacy of decitabine combined with low-dose CEG regimen (DCEG) and decitabine combined with low-dose CAG regimen (DCAG) in the treatment of elderly patients with MDS and MDS-transformed acute myeloid leukemia (AML).

Methods: A prospective study was conducted in 7 medical centers, 45 patients with MDS (≥ 60 years old) and MDS-transformed AML from October 2016 to January 2019 were enrolled, with the median age of 68.5 years old. Read More

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December 2020

Rational approach toward COVID-19 main protease inhibitors via molecular docking, molecular dynamics simulation and free energy calculation.

Sci Rep 2020 10 19;10(1):17716. Epub 2020 Oct 19.

Department of Biomedical Sciences, College of Medicine, Chosun University, Gwangju, 501-759, Republic of Korea.

In the rapidly evolving coronavirus disease (COVID-19) pandemic, repurposing existing drugs and evaluating commercially available inhibitors against druggable targets of the virus could be an effective strategy to accelerate the drug discovery process. The 3C-Like proteinase (3CL) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as an important drug target due to its role in viral replication. The lack of a potent 3CL inhibitor and the availability of the X-ray crystal structure of 3CL (PDB-ID 6LU7) motivated us to perform computational studies to identify commercially available potential inhibitors. Read More

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October 2020

Doxorubicin and Aclarubicin: Shuffling Anthracycline Glycans for Improved Anticancer Agents.

J Med Chem 2020 11 16;63(21):12814-12829. Epub 2020 Oct 16.

Leiden Institute of Chemistry, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.

Anthracycline anticancer drugs doxorubicin and aclarubicin have been used in the clinic for several decades to treat various cancers. Although closely related structures, their molecular mode of action diverges, which is reflected in their biological activity profile. For a better understanding of the structure-function relationship of these drugs, we synthesized ten doxorubicin/aclarubicin hybrids varying in three distinct features: aglycon, glycan, and amine substitution pattern. Read More

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November 2020

New insights into the activities and toxicities of the old anticancer drug doxorubicin.

FEBS J 2020 Oct 6. Epub 2020 Oct 6.

Department of Cell and Chemical Biology, ONCODE Institute, Leiden University Medical Centre LUMC, The Netherlands.

The anthracycline drug doxorubicin is among the most used-and useful-chemotherapeutics. While doxorubicin is highly effective in the treatment of various hematopoietic malignancies and solid tumours, its application is limited by severe adverse effects, including irreversible cardiotoxicity, therapy-related malignancies and gonadotoxicity. This continues to motivate investigation into the mechanisms of anthracycline activities and toxicities, with the aim to overcome the latter without sacrificing the former. Read More

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October 2020

Alkaloid-based regimen is beneficial for acute myeloid leukemia resembling acute promyelocytic leukemia with NUP98/RARG fusion and RUNX1 mutation: A case report.

Medicine (Baltimore) 2020 Oct;99(40):e22488

Department of Hematology, Cancer Center, the First Hospital of Jilin University, Changchun.

Rationale: Some acute myeloid leukemia (AML) patients present with features mimicking the classical hypergranular subtype of acute promyelocytic leukemia (APL) but without the typical promyelocytic leukemia/retinoic acid receptor α (PML/RARα) rearrangement. Herein, we report an AML patient resembling APL but with nucleoporin 98/retinoid acid receptor gamma gene (NUP98/RARG) fusion transcript and Runt-related transcription factor 1 (RUNX1) mutation.

Patient Concerns: An 18-year-old male presented at the hospital with a diagnosis of AML. Read More

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October 2020

Chidamide, decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor (CDCAG) in patients with relapsed/refractory acute myeloid leukemia: a single-arm, phase 1/2 study.

Clin Epigenetics 2020 09 1;12(1):132. Epub 2020 Sep 1.

Department of Hematology-Oncology, International Cancer Center, Shenzhen University General Hospital, Shenzhen University Health Science Center, Shenzhen, China.

Background: Epigenetic mechanisms play an important role in the chemoresistance of acute myeloid leukemia (AML). The clinical response to epigenetic modifier-based chemotherapy in patients with relapsed/refractory AML (r/r AML) is unclear. This multicenter clinical trial evaluated the safety and efficacy of epigenetic modifiers (chidamide and decitabine) in combination with aclarubicin, cytarabine, and granulocyte colony-stimulating factor (G-CSF) in patients with r/r AML. Read More

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September 2020

Cladribine with Granulocyte Colony-Stimulating Factor, Cytarabine, and Aclarubicin Regimen in Refractory/Relapsed Acute Myeloid Leukemia: A Phase II Multicenter Study.

Oncologist 2020 11 21;25(11):e1663-e1670. Epub 2020 Sep 21.

Department of Hematological Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China.

Lessons Learned: Studies targeting cladribine in combination with granulocyte colony-stimulating factor, low-dose cytarabine, and aclarubicin (C-CAG) regimen in relapsed and refractory acute myeloid leukemia (R/R AML) are limited. The complete remission rate after two cycles of C-CAG regimen was 67.6%, and 1-year overall survival and disease-free survival rates were 59. Read More

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November 2020

Uncoupling DNA damage from chromatin damage to detoxify doxorubicin.

Proc Natl Acad Sci U S A 2020 06 17;117(26):15182-15192. Epub 2020 Jun 17.

Department of Cell and Chemical Biology, ONCODE Institute, Leiden University Medical Center, 2333 ZC Leiden, The Netherlands;

The anthracycline doxorubicin (Doxo) and its analogs daunorubicin (Daun), epirubicin (Epi), and idarubicin (Ida) have been cornerstones of anticancer therapy for nearly five decades. However, their clinical application is limited by severe side effects, especially dose-dependent irreversible cardiotoxicity. Other detrimental side effects of anthracyclines include therapy-related malignancies and infertility. Read More

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CAG regimen for refractory or relapsed adult T-cell acute lymphoblastic leukemia: A retrospective, multicenter, cohort study.

Cancer Med 2020 08 3;9(15):5327-5334. Epub 2020 Jun 3.

Department of Hematology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang, China.

Adult patients with relapsed or refractory T-cell acute lymphoblastic leukemia (R/R-T-ALL) have extremely poor prognosis, representing an urgent unmet medical need. Finding an optimal salvage regimen to bridge transplantation is a priority. The CAG (cytarabine, aclarubicin, and G-CSF) regimen was initially used by one group in China, showing unexpectedly promising results in 11 R/R-T-ALL patients. Read More

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[Clinical outcome of CAG regimen in 26 children with aucte myeloid leukemia].

Zhonghua Xue Ye Xue Za Zhi 2019 07;40(7):594-596

Pediatric Blood Diseases Centre, Institute of Haematology and Blood Diseases Hospital, CAMS & PUMC, Tianjin 300020, China.

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Decitabine in combination with low-dose cytarabine, aclarubicin and G-CSF tends to improve prognosis in elderly patients with high-risk AML.

Aging (Albany NY) 2020 04 1;12(7):5792-5811. Epub 2020 Apr 1.

Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing 210029, Jiangsu Province, China.

We evaluated the risk status and survival outcomes of 125 elderly acute myeloid leukemia (AML) patients treated with decitabine in combination with low-dose cytarabine, aclarubicin, and G-CSF (D-CAG). The risk status was evaluated by determining the frequency of recurring gene mutations using next-generation sequencing (NGS) analysis of 23 selected genes and cytogenetic profiling of bone marrow samples at diagnosis. After a median follow-up of 12 months (range: 2-82 months), 86 patients (68. Read More

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Hypereosinophilia (HE) in acute myeloid leukemia (AML) with normal karyotype: A report of two cases.

Niger J Clin Pract 2020 Jan;23(1):116-119

Department of Hematology, Affiliated Changzhou Second Hospital of Nanjing Medical University, Changzhou, Jiangsu, China.

We present two rare cases of hypereosinophilia (HE) in acute myeloid leukemia with normal karyotype (NK-AML) at diagnosis. The first case is a 29-year-old female who presented with HE. On evaluation, she was found to have NK-AML. Read More

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January 2020

Relapsed/refractory early T-cell precursor acute lymphoblastic leukemia was salvaged by venetoclax plus HAG regimen.

Ann Hematol 2020 Feb 26;99(2):395-397. Epub 2019 Dec 26.

Department of Hematology, The First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou, 310003, Zhejiang, China.

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February 2020

Directed Biosynthesis of Iso-aclacinomycins with Improved Anticancer Activity.

Org Lett 2020 01 12;22(1):150-154. Epub 2019 Dec 12.

State Key Laboratory of Bio-organic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis , Shanghai Institute of Organic Chemistry , University of Chinese Academy of Sciences (CAS), CAS, Shanghai 200032 , China.

A four-enzyme catalyzed hydroxy regioisomerization of anthracycline was integrated into the biosynthetic pathway of aclacinomycin A (ALM-A), to generate a series of iso-ALMs via directed combinatorial biosynthesis combined with precursor-directed mutasynthesis. Most of the newly acquired iso-ALMs exhibit obviously (1-5-fold) improved antitumor activity. Therefore, we not only developed iso-ALMs with potential as clinical drugs but also demonstrated the utility of this tailoring tool for modification of anthracycline antibiotics in drug discovery and development. Read More

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January 2020

A retrospective study of the correlation of in vitro chemosensitivity using ATP-TCA with patient clinical outcomes in acute myeloid leukemia.

Cancer Chemother Pharmacol 2020 03 25;85(3):509-515. Epub 2019 Oct 25.

Department of Clinical Pharmacology, The First Affiliated Hospital of Soochow University, Suzhou, China.

Purpose: To evaluate the predictive value of the in vitro chemosensitivity using ATP-TCA method to compare the clinical efficacy of patients with AML.

Methods: Bone marrow or peripheral blood samples were collected from 65 patients with AML, and the in vitro chemosensitivity of four drugs (cytarabine/idarubicin/decitabine/aclacinomycin) was measured by an ATP-tumor chemosensitivity assay.

Results: Aclacinomycin and cytarabine had the highest chemosensitivity rates (66. Read More

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[Research Advances on Combination Strategies of Demethylating Agents for Elderly Acute Myeloid Leukemia--Review].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2019 Aug;27(4):1339-1343

Department of Hematology,Peking University International Hospital,Beijing

Abstract   Demethylating agents (HMAs) hold an important status in therapy for elderly acute myeloid leukemia, who are not eligible for intensive chemotherapy (ICT). Beyond the edge of monotherapy, domestic and foreign scholars have carried out a lot of studies on combination strategies, such as HMAs with low-intensity therapy (G-CSF, low-dose cytarabine and aclarubicin, CAG), with targeted therapy (BCL-2 inhibitor), with immunotherapy (immune checkpoint inhibitors, ICI), and with other epigenetic therapys (isocitrate dehydrogenase or histonedeacetylase inhibitor). Some of these researches have obtained positive results and discussed the mechanisms of combination strategies besides. Read More

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Epigenetic modifier gene mutations-positive AML patients with intermediate-risk karyotypes benefit from decitabine with CAG regimen.

Int J Cancer 2020 03 14;146(5):1457-1467. Epub 2019 Aug 14.

Department of Hematology and BMT center, Chinese PLA General Hospital, Beijing, China.

It remains unclear whether there is a relationship between therapeutic effects of hypomethylating agents (HMAs) and epigenetic modifier gene mutations (EMMs) in patients with cytogenetically intermediate-risk acute myeloid leukemia (IR-AML). Based on targeted-capture sequencing, we retrospectively analyzed the correlation between EMMs and prognosis in 83 IR-AML patients treated with decitabine in combination with cytarabine, aclarubicin hydrochloride and granulocyte colony-stimulating factor (DCAG, n = 35) or "7 + 3" induction regimens (n = 48). In the multivariate analyses, EMM (+) patients did not show any statistically significant difference in remission rates from EMM (-) patients in the DCAG group (p > 0. Read More

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Minimal residual disease may be an early prognostic indicator for newly diagnosed acute myeloid leukemia patients induced by decitabine-based chemotherapy.

Hematology 2019 Dec;24(1):552-558

a Department of Hematology , The First Hospital of Jilin University , Changchun , People's Republic of China.

To analyze the efficacy and safety of decitabine combined with low/reduced-dose chemotherapy in newly diagnosed acute myeloid leukemia (AML) patients unfit for intensive therapy and to investigate the early prognostic indicators for these patients. The eligible patients treated with decitabine-based chemotherapy were retrospectively analyzed. Responses and long-term survival were calculated and their correlation with clinical characteristics was analyzed. Read More

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December 2019

Clinical efficacy of decitabine in combination with standard-dose cytarabine, aclarubicin hydrochloride, and granulocyte colony-stimulating factor in the treatment of young patients with newly diagnosed acute myeloid leukemia.

Onco Targets Ther 2019 28;12:5013-5023. Epub 2019 Jun 28.

Department of Hematology, Chinese PLA General Hospital, Beijing 100853, People's Republic of China.

The chemotherapeutic regimen DCAG (decitabine with cytarabine, aclarubicin hydrochloride, and granulocyte colony-stimulating factor) is effective for elderly patients with acute myeloid leukemia, but recommendations for young patients remain controversial. This study investigated the tolerance and efficacy of DCAG for patients with newly diagnosed acute myeloid leukemia (aged 14-60 years). The clinical features or molecular markers that may predict response to DCAG were identified. Read More

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Influence of DNMT3A R882 mutations on AML prognosis determined by the allele ratio in Chinese patients.

J Transl Med 2019 07 10;17(1):220. Epub 2019 Jul 10.

Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People's Republic of China.

Background: The influence of DNMT3A R882 mutations on adult acute myeloid leukemia (AML) prognosis is still controversial presently. The influence of R882 allele ratio on drug response and prognosis of AML is unknown yet. Besides, it is obscure whether anthracyclines are involved in chemoresistance resulted from R882 mutations. Read More

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Oxidative DNA Damage and Apoptosis Induced by Aclarubicin, an Anthracycline: Role of Hydrogen Peroxide and Copper.

Anticancer Res 2019 Jul;39(7):3443-3451

Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Japan.

Background/aim: This study aimed to investigate aclarubicin (ACR)-induced oxidative DNA damage and apoptosis.

Materials And Methods: ACR-induced apoptosis was analyzed using HL-60 leukemia cells and HP100 cells, hydrogen peroxide (HO)-resistant cells derived from HL-60 cells. ACR-induced DNA damage was analyzed using plasmid DNA. Read More

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Concentration-response studies of the chromosome-damaging effects of topoisomerase II inhibitors determined in vitro using human TK6 cells.

Mutat Res 2019 05 15;841:49-56. Epub 2019 May 15.

Environmental Toxicology Graduate Program and Department of Molecular, Cell and Systems Biology, University of California, Riverside, CA, 92521, USA. Electronic address:

Topoisomerase II (topo II) inhibitors are commonly used as chemotherapy to treat multiple types of cancer, though their use is also associated with the development of therapy related acute leukemias. While the chromosome-damaging effects of etoposide, a topo II poison, have been proposed to act through a threshold mechanism, little is known about the chromosome damaging effects and dose responses for the catalytic inhibitors of the enzyme. The current study was designed to further investigate the potencies and concentration-response relationships of several topoisomerase II inhibitors, including the topoisomerase II poison etoposide, as well as catalytic inhibitors aclarubicin, merbarone, ICRF-154 and ICRF-187 using both a traditional in vitro micronucleus assay as well as a flow-cytometry based version of the assay. Read More

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