ChemInform Abstract: Synthesis and Characterization of New 10-Acyl Derivatives of the Antipsoriatic Agent Dithranol: Coupling Products of Dithranol with all- trans-Retinoic Acid, 13-cis-Retinoid Acid, and an Aromatic Analogue of Retinoid Acid: all-trans-9

ChemInform ◽  
2010 ◽  
Vol 22 (5) ◽  
pp. no-no
Author(s):  
J.-D. BERSET ◽  
A. KREBS
Keyword(s):  
Retinoic Acid ◽  
Synthesis And Characterization ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Derivatives Of ◽  
Retinoid Acid ◽  
Acyl Derivatives

Presenting White Blood Cell Count and Kinetics of Molecular Remission Predict Prognosis in Acute Promyelocytic Leukemia Treated With All-Trans Retinoic Acid: Result of the Randomized MRC Trial

Blood ◽  
1999 ◽  
Vol 93 (12) ◽  
pp. 4131-4143 ◽  
Author(s):  
Alan K. Burnett ◽  
David Grimwade ◽  
Ellen Solomon ◽  
Keith Wheatley ◽  
Anthony H. Goldstone
Keyword(s):  
Retinoic Acid ◽  
Promyelocytic Leukemia ◽  
Rt Pcr ◽  
Blood Cell Count ◽  
Relapse Risk ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
To Receive ◽  
Risk Of Relapse

Abstract All-trans retinoic acid (ATRA) is an essential component of the treatment of acute promyelocytic leukemia (APL), but the optimal timing and duration remain to be determined. Molecular characterization of this disease can refine the diagnosis and could be potentially useful in monitoring response to treatment. Patients defined morphologically to have APL were randomized to receive a 5-day course of ATRA before commencing chemotherapy or to receive daily ATRA commencing with chemotherapy and continuing until complete remission (CR). The chemotherapy was that used in current MRC Leukaemia Trials. Outcome comparisons were by intention to treat with additional analysis for relevant risk factors. Patients were characterized by molecular techniques for the fusion products of the t(15;17) and monitored by reverse transcriptase-polymerase chain reaction (RT-PCR) during and after treatment. Two hundred thirty-nine patients were randomized. Treatment with extended ATRA resulted in a superior remission rate (87% v 70%, P < .001), due to fewer early and induction deaths (12% v 23%, P = .02), and less resistant disease (2% v 7%, P = .03), which was associated with a significantly more rapid recovery of neutrophils and platelets. Extended ATRA reduced relapse risk (20%v 36% at 4 years, P = .04) and resulted in superior survival (71% v 52% at 4 years, P = .005). Presenting white blood cell count (WBC) was a key determinant of outcome. The 70% of patients who presented with a WBC less than 10 × 109/L had a better CR (85% v62%, P = .0001) and reduced relapse risk (22% v42%, P = .002) and superior survival (69%v 43%, P < .0001). Within the low count group, extended ATRA resulted in a better CR (94% v 76%, P= .001), reduced relapse risk (13% v 35%, P = .04), and improved survival (80% v 57%, P = .0009). There was no evidence of benefit in patients presenting with a higher WBC (>10 × 109/L). Molecular monitoring after the third chemotherapy course had a correlation with risk of relapse. The relapse risk was 57% if the RT-PCR was positive versus 27% if the RT-PCR was negative (P = .006). APL patients who present with a low WBC derive substantial benefit from combining ATRA with induction chemotherapy until remission is achieved, whereas patients with a higher WBC did not benefit. Molecular characterization of disease can improve diagnostic precision and a positive RT-PCR after consolidation identifies patients at a higher risk of relapse.

scholarly journals Growth Inhibitory Effects of Ester Derivatives of Menahydroquinone-4, the Reduced Form of Vitamin K2(20), on All-Trans Retinoic Acid-Resistant HL60 Cell Line

Pharmaceutics ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 758
Author(s):  
Hirofumi Yamakawa ◽  
Shuichi Setoguchi ◽  
Shotaro Goto ◽  
Daisuke Watase ◽  
Kazuki Terada ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Adverse Effects ◽  
Vitamin K2 ◽  
Reduced Form ◽  
Inhibitory Effects ◽  
Hl60 Cells ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Growth Inhibitory ◽  
Derivatives Of

The first-choice drug for acute promyelocytic leukemia (APL), all-trans retinoic acid (ATRA), frequently causes drug-resistance and some adverse effects. Thus, an effective and safe agent for ATRA-resistant APL is needed. Menaquinone-4 (MK-4, vitamin K2(20)), used for osteoporosis treatment, does not have serious adverse effects. It has been reported that MK-4 has growth-inhibitory effects on HL60 cells by inducing apoptosis via the activation of Bcl-2 antagonist killer 1 (BAK). However, the effect of MK-4 on ATRA-resistant APL has not been reported. Here, we show that ester derivatives of menahydroquinone-4 (MKH; a reduced form of MK-4), MKH 1,4-bis-N,N-dimethylglycinate (MKH-DMG) and MKH 1,4-bis-hemi-succinate (MKH-SUC), exerted strong growth-inhibitory effects even on ATRA-resistant HL60 (HL-60R) cells compared with ATRA and MK-4. MKH delivery after MKH-SUC treatment was higher than that after MK-4 treatment, and the results indicated apoptosis induced by BAK activation. In contrast, for MKH-DMG, reconversion to MKH was slow and apoptosis was not observed. We suggest that the ester forms, including monoesters of MKH-DMG, exhibit another mechanism independent of apoptosis. In conclusion, the MKH derivatives (MKH-SUC and MKH-DMG) inhibited not only HL60 cells but also HL-60R cells, indicating a potential to overcome ATRA resistance.

Preparation and characterization of micelles of oligomeric chitosan linked to all-trans retinoic acid

2012 ◽  
Vol 87 (2) ◽  
pp. 1176-1184 ◽  
Author(s):  
Ali Fattahi ◽  
Mohammad-Ali Golozar ◽  
Jaleh Varshosaz ◽  
Hamid Mirmohammad Sadeghi ◽  
Mohammadhossein Fathi
Keyword(s):  
Retinoic Acid ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Presenting White Blood Cell Count and Kinetics of Molecular Remission Predict Prognosis in Acute Promyelocytic Leukemia Treated With All-Trans Retinoic Acid: Result of the Randomized MRC Trial

Blood ◽  
1999 ◽  
Vol 93 (12) ◽  
pp. 4131-4143 ◽  
Author(s):  
Alan K. Burnett ◽  
David Grimwade ◽  
Ellen Solomon ◽  
Keith Wheatley ◽  
Anthony H. Goldstone
Keyword(s):  
Retinoic Acid ◽  
Promyelocytic Leukemia ◽  
Rt Pcr ◽  
Blood Cell Count ◽  
Relapse Risk ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
To Receive ◽  
Risk Of Relapse

All-trans retinoic acid (ATRA) is an essential component of the treatment of acute promyelocytic leukemia (APL), but the optimal timing and duration remain to be determined. Molecular characterization of this disease can refine the diagnosis and could be potentially useful in monitoring response to treatment. Patients defined morphologically to have APL were randomized to receive a 5-day course of ATRA before commencing chemotherapy or to receive daily ATRA commencing with chemotherapy and continuing until complete remission (CR). The chemotherapy was that used in current MRC Leukaemia Trials. Outcome comparisons were by intention to treat with additional analysis for relevant risk factors. Patients were characterized by molecular techniques for the fusion products of the t(15;17) and monitored by reverse transcriptase-polymerase chain reaction (RT-PCR) during and after treatment. Two hundred thirty-nine patients were randomized. Treatment with extended ATRA resulted in a superior remission rate (87% v 70%, P < .001), due to fewer early and induction deaths (12% v 23%, P = .02), and less resistant disease (2% v 7%, P = .03), which was associated with a significantly more rapid recovery of neutrophils and platelets. Extended ATRA reduced relapse risk (20%v 36% at 4 years, P = .04) and resulted in superior survival (71% v 52% at 4 years, P = .005). Presenting white blood cell count (WBC) was a key determinant of outcome. The 70% of patients who presented with a WBC less than 10 × 109/L had a better CR (85% v62%, P = .0001) and reduced relapse risk (22% v42%, P = .002) and superior survival (69%v 43%, P < .0001). Within the low count group, extended ATRA resulted in a better CR (94% v 76%, P= .001), reduced relapse risk (13% v 35%, P = .04), and improved survival (80% v 57%, P = .0009). There was no evidence of benefit in patients presenting with a higher WBC (>10 × 109/L). Molecular monitoring after the third chemotherapy course had a correlation with risk of relapse. The relapse risk was 57% if the RT-PCR was positive versus 27% if the RT-PCR was negative (P = .006). APL patients who present with a low WBC derive substantial benefit from combining ATRA with induction chemotherapy until remission is achieved, whereas patients with a higher WBC did not benefit. Molecular characterization of disease can improve diagnostic precision and a positive RT-PCR after consolidation identifies patients at a higher risk of relapse.

Sign in / Sign up

Export Citation Format

Share Document