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Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Aclarubicin is produced by Streptomyces galilaeus, and its general structure and properties are similar to those of doxorubicin, although there are differences to the substitution pattern in the A- and D-rings, and two additional sugar moieties are joined in a linear fashion to the D-ring amino sugar, which is itself modified through demethylation. It is sometimes referred to as an oligosaccharide intercalating agent due to the multiple sugars. No longer prescribed in the UK, aclarubicin is used in some countries for acute nonlymphocytic leukemia in patients who have relapsed or are resistant or refractory to first-line chemotherapy.
Microparticulate Carriers as a Therapeutic Option in Regional Cancer Therapy: Clinical Considerations
Published in Neville Willmott, John Daly, Microspheres and Regional Cancer Therapy, 2020
J. H. Anderson, Colin S. McArdle, T. G. Cooke
Polylactic acid microspheres (mean diameter 200 μm) containing 10% by weight of aclarubicin were used for embolization following administration via the hepatic artery in 62 patients with hepatocellular carcinoma, resulting in a 42.6% partial response rate (<50% pretreatment tumor size) and 19.2% 3-year survival.31 Side effects were transient and subsided with conservative treatment. Plasma pharmacokinetics of aclarubicin in dogs and humans indicated prolonged continuous drug release up to 72 h after administration; yet systemic exposure was significantly less than that experienced by patients receiving free drug in solution as a bolus by the same route.
Mass Spectrometric Analysis
Published in Adorjan Aszalos, Modern Analysis of Antibiotics, 2020
Intact anthracyclines have also been successfully characterized by positive and negative ion modes of desorption CI. Nogalamycin (3) and several analogs gave protonated molecular ions and several structurally significant fragment ions using isobutane [205]. Positive and negative ion desorption CI spectra were compared for 10 naturally occurring and semisynthetic anthracyclines using methane [52]. Formation of negative ions were found to be highly favored, presumably due to the facile reduction of quinones to radical anions by resonance electron capture. The negative ion spectra exhibit molecular and aglycone ions. These ions were readily detected using 1—10 ng. Aclarubicin (4), an anthracycline with a trisaccharide side chain, exhibits negative anthraquinone-containing ions representing the sequential loss of the saccharide groups. These principles were applied to characterize seven analogs of aclarubicin, two of which were found in the plasma of a patient being treated with this drug [206]. In another study the urinary metabolites of aclarubicin were also identified with the help of EI, FD, and negative ion FAB mass spectrometry [207],
Optimal timing to retrieve oocytes for fertility preservation in patients with acute myeloid leukemia: two cases of controlled ovarian stimulation using DuoStim with a literature review
Published in Gynecological Endocrinology, 2023
Mami Sekiguchi, Ayumu Ito, Yusuke Fukuda, Masato Yoneyama, Mayuko Furui, Kentaro Nakaoka, Nahomi Umemura, Yuko Hayashi, Yuko Tamaki, Yukiko Katagiri, Masahiko Nakata
Important questions exist regarding the strengths and limitations of FP in patients with AML because of the low gonadotoxicity of standard chemotherapy for AML [3,16]. Although there is little information regarding the gonadotoxicity of idarubicin and aclarubicin, which were administered in our cases, some studies have reported on the ovarian toxicity of doxorubicin used to treat Hodgkin lymphoma, which belongs to the same anthracycline family and has a similar chemical structural formula. It accumulates in the nucleus and mitochondria of cancer cells; however, it also induces apoptosis of oocytes and granulosa cells of the follicle by generating oxidative stress, causing cell death of the postovulatory MII oocytes and preovulatory GV oocytes and primitive ovarian follicles [12,17]. Moreover, after doxorubicin administration, blood flow to the ovaries and vessel wall constriction is decreased. Therefore, the mechanism of doxorubicin-related ovarian toxicity is believed to be ischemia-induced acute ovarian injury [12,18]. The low peak E2 values during all OR cycles in Case 2 and the large number of degenerated oocytes in the luteal phase OR of the DuoStim cycle in Case 1 suggest that idarubicin induces apoptosis of granulosa cells and primordial follicles by a similar mechanism.
Normal Absolute Monocyte Count in Combination with Normal/High Absolute Lymphocyte Count at the Time of Relapse is Associated with Improved Survival in Patients with Early Relapsed Acute Myeloid Leukemia
Published in Cancer Investigation, 2021
Yu Zhang, Kanchun Dai, Qianying Zhang, Yisha Huang, Yiyun Feng, Deeksha Bhardwaj, Kang Yu, Jianhua Feng
Reinduction therapies for AML in early relapse included one of the followings (Table 1): (i) CLAG (cladribine, high-dose cytarabine and G-CSF) alone in 6 patients, or combined with mitoxantrone in 4 patients, (ii) high-dose cytarabine (2000 mg/m2 every 12 hours) in 2 patients, (iii) FLAG (fludarabine, high-dose cytarabine, and G-CSF) alone in 1 patient, or combined with idarubicin in 3 patients, or mitoxantrone in 4 patients, (iv) EA (etoposide and cytarabine) only in 1 patient, or combined with mitoxantrone in 9 patients, idarubicin in 3 patients, or aclarubicin in 2 patients, (v) low-dose cytarabine and G-CSF in combination with idarubicin (CIG) in 3 patients, homoharringtonine (CHG) in 2 patients, aclarubicin (CAG) in 1 patient, or mitoxantrone (CNG) in 1 patient, (vi) homoharringtonine combined with cytarabine (HA) in 3 patients, aclarubicin and etoposide in 1 patient, (vii) conventional doses of cytarabine (50–200 mg/m2 per day) combined with idarubicin in 7 patients, mitoxantrone in 1 patient, or aclarubicin in 1 patient, (viii) HAA (homoharringtonine, aclarubicin and cytarabine) combined with cladribine in 1 patient, (ix) VICP (vincristine, idarubicin, cyclophosphamide and prednisone) in 1 patient due to the expression of lymphoid-associated antigens in blast cells.
Therapeutic strategies, including allogeneic stem cell transplantation, to overcome relapsed/refractory adult T-cell acute lymphoblastic leukemia
Published in Expert Review of Hematology, 2021
Dong Won Baek, Jung Min Lee, Juhyung Kim, Hee Jeong Cho, Joon Ho Moon, Sang Kyun Sohn
Combination therapy with cytarabine (10 mg/m2 every 12 hours on days 1–14), aclarubicin (5–7 mg/m2 on days 1–8), plus concurrent granulocyte colony-stimulating factor (200 μg/m2/day) (CAG regimen) was administered to 11 T-ALL and 14 B-ALL patients for R/R disease. One course of the CAG regimen showed a 56% CR rate and a 64% ORR, without severe adverse effects. Furthermore, an overall response was reported in all 11 T-ALL patients, but only in 35.7% of the B-ALL patients, suggesting a significant treatment potential, especially for patients with R/R T-ALL [27]. Based on these results, a multicenter retrospective study of 41 patients with R/R T-ALL who received the CAG regimen was conducted; 33 (80.5%) achieved CR, and 35 (84.9%) showed an overall response after one course of the CAG regimen. In addition, 12 (29.2%) patients had MRD <0.1%. Among the 41 patients, 27 (66%) successfully bridged to allogeneic transplantation, 22 received transplantation after achieving CR, and five did not achieve CR status. The estimated two-year OS rates of transplanted and chemotherapy alone patients were 84.2% and 58.3%, respectively, and the rates of two-year event-free survival were 78.7% and 58.3%, respectively [28]. Augmented hyper-CVAD, clofarabine, FLAM or FLAG-Ida regimens can also be considered before transplantation for R/R T-ALL patients (Table 2) [29–33].