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Chinese Pharmacological Bulletin ; (12): 325-329, 2022.
Article Dans Chinois | WPRIM | ID: wpr-1014129

Résumé

Aim Amyotrophic lateral sclerosis (Alii) is a neurodegenerative disease caused by the selective loss of upper and lower motor neurons.Its pathogenesis is complex and not yet fully understood.Accumulating evidences show that energy metabolism defieits and homeostasis imbalance lead to selective degeneration of motor neurons in ALS.Adenosine phosphate-activated protein kinase ( AMPK) and silent information regulator-1 (SIRT1) are known to sense energy metabolism at the cellular level, playing an essential part in regulating the energy homeostasis and autophagy by activating downstream pathways.AMPK activates SIRT1 to activate the deaeetylation and activation of downstream genes involved in energy metabolism such as peroxisome proliferator-aetivated receptor 7 ( PPAR-y) and eoaetivator la ( PGC-la) , thereby increasing the level of mitochondrial biosynthesis.Therefore, the mechanism by which AMPK/SIRT1 participates in the regulation of energy metabolism is highly likely to be a potential target for ALS treatment.Here we first review the important role of energy metabolism defects and mitochondrial abnormalities in the pathogenesis of ALS, and briefly address the therapeutic potential of AMPK/SIRT1/PGC-1 a pathway as a treatment target in ALS, and how targeted regulation of this signaling pathway makes it an effective therapeutic strategy for ALS.

2.
Acta Academiae Medicinae Sinicae ; (6): 421-423, 2010.
Article Dans Chinois | WPRIM | ID: wpr-322759

Résumé

<p><b>OBJECTIVE</b>To evaluate the efficacy,clinical benefits and toxicities of gemcitabine combined with erlotinib for advanced pancreatic cancer.</p><p><b>METHOD</b>Clinical data of 20 patients with advanced pancreatic cancer treated with gemcitabine 1000 mg/m2 on day 1 and day 8 (repeated every 21 days) plus erlotinib 100-150 mg/d at Peking Union Medical College Hospital was reviewed retrospectively.</p><p><b>RESULTS</b>No patient achieved complete remission or partial remission, 11 patients (55%) had stable disease, and 9 patients (45%) experienced disease progression. The disease control rate was 55%, and clinical benefit rate was 30%. The median progression free survival was 4.0 months, and the median overall survival was 8 months. The total incidence of hematologic toxicity was 70%, including 15% of grade 3-4 leucopenia and 5% of grade 3-4 thrombocytopenia. Eleven patients (55%) had rash, which were all grade 1-2. One patient had grade 2 diarrhea and five had grade 1 transaminase elevation. No chemotherapy-related death occurred.</p><p><b>CONCLUSIONS</b>Gemcitabine combined with erlotinib is an effective regimen for pancreatic cancer with good clinical tolerance. The most common adverse events are hematologic toxicities and rash.</p>


Sujets)
Adulte , Sujet âgé , Femelle , Humains , Mâle , Adulte d'âge moyen , Protocoles de polychimiothérapie antinéoplasique , Utilisations thérapeutiques , Désoxycytidine , Chlorhydrate d'erlotinib , Études de suivi , Tumeurs du pancréas , Traitement médicamenteux , Quinazolines , Études rétrospectives , Résultat thérapeutique
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