Wyniki wyszukiwania - Biblioteka Nauki

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The Outcome of Targeted Therapy in Advanced Gastrointestinal Stromal Tumors (Gist) with Non-Exon 11 Kit Mutations

100%

Osuch C. , Rutkowski P. , Brzuszkiewicz K. , Bylina E. , Limon J. , Siedlecki J. A.

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2015

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tom 86

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nr 7

325-332

EN

GIST is the most common mesenchymal tumour of gastrointestinal tract arising from mutation of KIT or PDGFRA gene. Surgery is the primary method of treatment, however a targeted therapy with imatinib is necessary due to recurrence. The aim of the study was to evaluate efficacy of the targeted chemotherapy in advanced gastrointestinal stromal tumours with non-exon 11 KIT mutations. Material and methods. Data from 279 patients with advanced GIST treated with imatinib between 2001 and 2011 were analysed in the study. Exon 11 KIT mutation was found in 192 patients (68.7%), non-exon 11 KIT mutation was found in 87 patients (31.3%): this group included lack of mutation - wild-type, exon 9 KIT mutations, exon 18 PDGFRA D842V mutations, non-D842V PDGFRA mutations as well as non-exon 9 and 11 KIT mutations. Analysis of progression-free survival and overall survival were done for the entire group of patients and for patients with particular mutations, and then effects on progression-free survival and overall survival of such factors as sex, age, imatinib dose were evaluated. Results. Occurrence of non-exon 11 KIT mutation increases the risk of disease progression by 20% in comparison to the presence of exon 11 KIT mutation, however it does not increase the risk of patient’s death. Percentage of 5-year progression-free survivals is the greatest in the case of PDGFRA mutation other than D842V mutation. Percentage of 5-year survivals in case of the presence of D842V PDGFRA mutation is more than twice worse than in the case of the other mutations. Lesion location in the gastrointestinal tract affected the risk of death, with the greatest percentage of 5-year survival for lesions located in the stomach. Such factors as sex, age at diagnosis (<50, ≥50 years) and imatinib dose did not affect the risk of disease progression and the risk of patient’s death. Conclusions. The ratio of overall survival of patients with advanced GIST with a mutation other than exon 11 KIT mutation treated with imatinib is similar to the ratio of overall survival of patients with GIST with exon 11 KIT mutation. An exception is the group of patients with GIST in whom the presence of D842V PDGFRA mutation was found. In general, longer survival has been found in patients with GIST located in the stomach in comparison to the small intestine or other less frequent locations. Percentage of 5-year progression-free survivals is the greatest in the case of PDGFRA mutation other than D842V mutation.

2

Original vs generic drugs in treatment of chronic myeloid leukaemia

88%

Rusicka P.

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nr 3

A126-131

EN

The beginning of the twenty-first century saw a breakthrough in haematology, oncology and general medicine driven by the introduction of imatinib (Glivec) to the treatment of chronic myeloid leukaemia. For the first time, a neoplastic disease was successfully treated by a therapy targeting the genetic cause of the disease. At present, targeted therapy based on imatinib is the first one to enter a new stage which is the launch of generic drugs. Poland is the first country in the European Union which, from the beginning of July 2014, introduced generic imatinib. Hence, there is no reliable data on its use except for results from bioequivalence tests. The only data available comes from developing countries where other preparations are used, without reliable bioequivalence studies. However, all generic drugs of imatinib registered in Poland have successfully passed such tests. Undoubtedly, it is necessary to appropriately monitor patients with chronic myeloid leukaemia receiving generic drugs in order to ensure their safety and provide information to other countries where therapy based on generic drugs will be introduced in the following years.

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Imatinib inhibits the renewal and tumorigenicity of CT-26 colon cancer cells after cytoreductive treatment with doxorubicin

75%

Przybyszewska M. , Miloszewska J. , Kotlarz A. , Swoboda P. , Pysniak K. , Szczepek W. , Kaczmarek L. , Markowicz S.

Archivum Immunologiae et Therapiae Experimentalis

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2017

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tom 65

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nr 1

4

Role of anti-apoptotic pathways activated by BCR/ABL in the resistance of chronic myeloid leukemia cells to tyrosine kinase inhibitors

75%

Danisz K. , Blasiak J.

Acta Biochimica Polonica

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2013

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tom 60

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nr 4

503-514

EN

Chronic myeloid leukemia (CML) is a hematological stem cell disorder characterized by the excessive proliferation of the myeloid lineage. In its initial chronic phase, the myeloid progenitor cells expand and demonstrate apparently normal differentiation. The disease may then transform into the accelerated phase, usually associated with resistance to therapy, and finally, into acute leukemic progression phase - blast crisis. Abnormal myeloid cells produce progenitors, which have lost their ability to differentiate, but retain the capacity to proliferate. The molecular hallmark of CML is the Philadelphia chromosome, resulting from reciprocal chromosome translocation, t(9;22)(q34;q11), and containing the BCR/ABL fusion gene, producing the BCR/ABL protein with a constitutive tyrosine kinase activity. BCR/ABL-positive cells have faster growth and proliferation over their normal counterparts and are resistant to apoptosis. Introduction of imatinib (IM), a tyrosine kinase inhibitor, revolutionized the therapy of CML, changing it from a fatal disease into a chronic disorder. However, some patients show a primary resistance to IM, others acquire such resistance in the course of therapy. Therefore, a small number of leukemic stem cells retains self-renewal capacity under IM treatment. Because BCR/ABL is involved in many signaling pathways, some of them may be essential for resistance to IM-induced apoptosis. The PI3K/AKT, Ras and JAK/STAT signaling pathways are involved in resistance to apoptosis and can be activated by BCR/ABL. Therefore, they can be candidates for BCR/ABL-dependent pro-survival pathway(s), allowing a fraction of CML cells to withstand treatment with tyrosine kinase inhibitors.

5

Liposomal imatinib: an EPR and DSC study

51%

Beni S. , Budai M. , Noszal B. , Grof P.

Cellular and Molecular Biology Letters

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2005

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tom 10

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nr Suppl.