Category Archives: Hematology, cancer chemotherapy and related

Animation showing the Jak-Stat signalling pathway mechanism

The Jak-Stat pathway has recently attracted researchers’ attention. This has been motivated by the fact that this pathway is a potential target of future agents for the treatment of myeloproliferative disorders such as: polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis.

The animation below depicts the Jak-Stat signalling pathway mechanism:

As mentioned above, there are some expectations on the future of JAK STAT pathway in pharmacology:

JAK2 Inhibitors

Despite the success of imatinib mesylate in the treatment of CML, the genetic basis of the other major myeloproliferative disorders (polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis) has, until recently, remained obscure. It is now apparent that a common activating mutation in JAK2 (V617F) underlies the aberrant signaling and proliferation in most cases, although how one mutation leads to this spectrum of disorders remains unclear. The V617F mutation is found in the pseudokinase domain of JAK2, and disruption of this autoinhibitory region leads to unchecked activity of the kinase. Cells containing the JAK2 V617F mutation are growth inhibited and undergo apoptosis in response to specific JAK2 inhibitors in vitro. Thus, JAK2 inhibitors are under development for the treatment of polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis.

Source: Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy: D. Golan et al. LWW. 2007

Related links

Series Introduction: JAK-STAT signaling in human disease. Christian W. Schindler. J. Clin. Invest. 109(9): 1133-1137 (2002)

JAK-STAT signaling in asthma. Alessandra B. Pernis and Paul B. Rothman. J. Clin. Invest. 109(10): 1279-1283 (2002)

Thrombolytic agents: mechanism of action, indications, contraindications and side effects

Thrombolytic agents are used to lyse already formed blood clots in clinical settings where ischemia may be fatal ( acute mycardial infarction, pulmonary embolism, ischemic stroke, and arterial thrombosis). Very precise indications rule the use of these drugs, which are not free from serious side effects ( bleeding). Outline: Mechanism of action of thrombolytic therapy…

Cancer chemotherapy: PPT presentations

The PowerPoint files in this posts have been shared by R. Senthil Kumar M.D. ,  Dean of Basic Sciences and Pharmacology Professor at St. Matthew’s University School of Medicine. If you are interested in contributing to this blog, just send an e-mail to PPT 1: Introduction to cancer chemotherapy Download PPT file: Cancer Chemotherapy…

Serotonin 5-HT3-receptor antagonists: pharmacokinetics, MOA, indications and adverse effects

This posts overviews the general characteristics, pharmacokinetics, mechanism of action, dosing, indications and adverse effects profile of serotonin 5-HT3-receptor antagonists. These drugs are being increasingly used for the prevention of chemotherapy induced nausea and vomiting as well as antiemetic prophylaxis of post-operative and post-radiation nausea and vomiting. Continue Reading

PPIs reduce the effectiveness of clopidogrel (Plavix)

Pharmamotion has now a new page containing updates on  clopidogrel – PPI interactions. The latest edition of the monthly newsletter from the Medicines and Healthcare products Regulatory Agency has issued a drug safety advice on the interaction between the antiplatelet drug clopidogrel (Plavix) and PPIs. They conclude that available data supports a clinically significant interaction…

Overview on monoclonal antibody therapy: PPT, images and videos

This post intends to be a brief and readable overview on what monoclonal antibodies (mAbs) are and some examples of their clinical applications. The following slideshow is a clear and accurate introduction on the topic: (ignore the first slide error message and move to the second)Continue Reading

Vorinostat MSD for cutaneous T-cell lymphoma. MSD withdraws marketing application

Excerpts from the EMEA press release (dated 17th February) on the withdrawal of the marketing application for Vorinostat MSD: The European Medicines Agency (EMEA) has been formally notified by Merck Sharp & Dohme Ltd of its decision to withdraw its application for a centralised marketing authorisation for the medicine Vorinostat MSD (vorinostat), 100 mg hard…

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