Low heart and skin toxicity of a tetrahydropyranyl derivative of adriamycin (THP-ADM) as observed by electron and light microscopy.

Dantchev, D; Paintrand, M; Hayat, M.; Bourut, C.; Mathé, G

doi:10.7164/antibiotics.32.1085

Cited by 82 publications

(29 citation statements)

References 2 publications

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“…Although pirarubicin was chosen as an anthracyclin drug with less cardiotoxicity than DOX, it is unclear whether pirarubicin could reduce the incidence of cardiotoxicity without jeopardizing the overall outcome. 29,30 In fact, our observation period with a median of 13 years (range 8-22 years) after diagnosis is too short to estimate the true incidence of late adverse effects, because excess mortality continues at least as long as 25-30 years after treatment, for cancer survivors. 27 Therefore, establishment of a long-term, follow-up care system based on collaboration between clinical and laboratory investigators is our most urgent issue.…”

Section: Discussionmentioning

confidence: 99%

Long-term results of the Japanese Childhood Cancer and Leukemia Study Group studies 811, 841, 874 and 911 on childhood acute lymphoblastic leukemia

et al. 2009

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We analyzed the long-term outcomes of 1021 patients with acute lymphoblastic leukemia (ALL), enrolled in four successive clinical trials (ALL811, ALL841, ALL874 and ALL911) between 1981 and 1993. All patients received risk-adopted therapy according to leukocyte count and age at the time of diagnosis. The median follow-up durations of the four studies were 17.8 years in ALL811, 15.5 years in ALL841, 11.9 years in ALL874 and 15.8 years in ALL911. Patients' event-free survival (EFS) and overall survival (OS) rates at 12 years were 41.0 and 54.3% in ALL811, 50.2 and 60.2% in ALL841, 57.3 and 64.7% in ALL874, and 63.4 and 71.7% in ALL911, respectively. Thus, cure can become a reality for about 70% of children with ALL. There is, however, still a significant difference in survival outcomes according to risk group. Late effects were observed in 70 patients out of 834 (8.4%); hepatitis and short stature were most commonly reported. Reduction of late adverse effects for all patients and development of new treatment strategies for very-high-risk patients are major issues for upcoming trials to address.

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Section: Discussionmentioning

confidence: 99%

Long-term results of the Japanese Childhood Cancer and Leukemia Study Group studies 811, 841, 874 and 911 on childhood acute lymphoblastic leukemia

et al. 2009

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“…Additionally, some retrospective studies [25,26] have revealed that the overexpression of P-gp may be associated with poor prognosis. THP, a semisynthetic anthracycline glycoside, is a newer generation anthracycline anticancer agent that is reported to have a lower cardiotoxicity than ADM [11] . Changes in structure allow THP to be taken up by tumor cells approximately 170 times faster than ADM and increase the rates at which it distributes into the nucleus and Table 3).…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, THP has shown a greater antitumor activity [8][9][10] and lower cardiotoxicity [11] than ADM. This may be explained by the higher uptake of THP by tumor cells than ADM and its rapid distribution into the nucleus and subsequent incorporation into deoxyribonucleic acid (DNA) [12][13][14] .…”

Section: Introductionmentioning

confidence: 99%

Pirarubicin inhibits multidrug-resistant osteosarcoma cell proliferation through induction of G2/M phase cell cycle arrest

et al. 2012

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Aim: Pirarubicin (THP) is recently found to be effective in treating patients with advanced, relapsed or recurrent high-grade osteosarcoma. In this study, the effects of THP on the multidrug-resistant (MDR) osteosarcoma cells were assessed, and the underlying mechanisms for the disruption of cell cycle kinetics by THP were explored. Methods: Human osteosarcoma cell line MG63 and human MDR osteosarcoma cell line MG63/DOX were tested. The cytotoxicity of drugs was examined using a cell proliferation assay with the Cell Counting Kit-8 (CCK-8). The distribution of cells across the cell cycle was determined with flow cytometry. The expression of cell cycle-regulated genes cyclin B1 and Cdc2 (CDK1), and the phosphorylated Cdc2 and Cdc25C was examined using Western blot analyses. Results: MG63/DOX cells were highly resistant to doxorubicin (ADM) and gemcitabine (GEM), but were sensitive or lowly resistant to THP, methotrexate (MTX) and cisplatin (DDP). Treatment of MG63/DOX cells with THP (200-1000 ng/mL) inhibited the cell proliferation in time-and concentration-dependent manners. THP (50-500 ng/mL) induced MG63/DOX cell cycle arrest at the G 2 /M phase in time-and concentration-dependent manners. Furthermore, the treatment of MG63/DOX cells with THP (200-1000 ng/mL) downregulated cyclin B1 expression, and decreased the phosphorylated Cdc2 at Thr 161 . Conversely, the treatment increased the phosphorylated Cdc2 at Thr 14 /Tyr 15 and Cdc25C at Ser 216 , which led to a decrease in Cdc2-cyclin B1 activity. Conclusion: The cytotoxicity of THP to MG63/DOX cells may be in part due to its ability to arrest cell cycle progression at the G 2 /M phase, which supports the use of THP for managing patients with MDR osteosarcoma.

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“…Several experimental reports have shown that acute cardiotoxicity of pirarubicin is less than the cardiotoxicity of ADR (7,8). However objective studies concerning chronic cardiotoxic- ity of pirarubicin were not complete (13,14).…”

Section: Discussionmentioning

confidence: 99%

“…A new anthracycline derivative, 4'-O-tetrahydropyranydal (THP)-adriamycin (pirarubicin; Meiji Seika, Tokyo, Japan, and Nihonkayaku, Tokyo, Japan) was introduced in 1979 (3). Compared with ADR, pirarubicin has a similarly high antitumor efficacy (4 -6) and a much lower acute cardiotoxicity (7,8). However, it is unclear whether the chronic cardiotoxicity of pirarubicin is lower than that of ADR.…”

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confidence: 99%

Apoptosis in Young Rats with Adriamycin-Induced Cardiomyopathy—Comparison with Pirarubicin, a New Anthracycline Derivative

et al. 2002

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Low heart and skin toxicity of a tetrahydropyranyl derivative of adriamycin (THP-ADM) as observed by electron and light microscopy.

Cited by 82 publications

References 2 publications

Long-term results of the Japanese Childhood Cancer and Leukemia Study Group studies 811, 841, 874 and 911 on childhood acute lymphoblastic leukemia

Long-term results of the Japanese Childhood Cancer and Leukemia Study Group studies 811, 841, 874 and 911 on childhood acute lymphoblastic leukemia

Pirarubicin inhibits multidrug-resistant osteosarcoma cell proliferation through induction of G2/M phase cell cycle arrest

Apoptosis in Young Rats with Adriamycin-Induced Cardiomyopathy—Comparison with Pirarubicin, a New Anthracycline Derivative

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