The use of rotation to fentanyl in cancer-related pain

Delia Dima,1 Ciprian Tomuleasa,1 Ioana Frinc,1 Sergiu Pasca,2 Lorand Magdo,2 Ioana Berindan-Neagoe,2–4 Mihai Muresan,5 Cosmin Lisencu,5 Alexandru Irimie,5,6 Mihnea Zdrenghea1,7 1Department of Hematology, Ion Chiricuta Oncology Institute, 2Faculty of Medicine, Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Iuliu Hatieganu, 3Department of Functional Genomics, The Oncology Institute Ion Chiricuta, 4Medfuture Research Center for Advanced Medicine, University of Medicine and Pharmacy, Iuliu Hatieganu, 5Department of Surgery, Ion Chiricuta Oncology Institute, 6Department of Oncology, University of Medicine and Pharmacy, Iuliu Hatieganu, 7Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania Abstract: Pain is commonly diagnosed with respect to cancer and heart diseases, being a major symptom in most neoplastic diseases. Uncontrolled pain leads to a decrease in the quality of life and an increase in the morbidity of the patient. Opioids represent the best analgetic supportive therapy and are frequently used in patients suffering from cancer and experiencing a high level of pain. Opioid treatment starts with a gradual titration of the dose until the minimum effective dose and the maximum tolerated dose are determined. Opioid rotation refers to the switch from one opioid to another in order to get a better response to analgetic therapy and reduce side effects. Fentanyl therapy is recommended to be continued during chemotherapy, radiotherapy, or in the case of surgical intervention. Rotation to fentanyl patches is an efficient and elegant solution for cancer patients, with reduced side effects. Opioid rotation, especially to fentanyl, was shown to increase the quality of life in patients with malignant disease. Finally, rotation to fentanyl is also advantageous from an economic point of view. Keywords: opioid rotation, cancer-related pain, fentany

Adult acute megakaryoblastic leukemia: rare association with cytopenias of undetermined significance and p210 and p190 BCR–ABL transcripts

Delia Dima,1,* Liana Oprita,2,* Ana-Maria Rosu,3,* Adrian Trifa,4 Cristina Selicean,1 Vlad Moisoiu,3 Ioana Frinc,1 Mihnea Zdrenghea,1,5 Ciprian Tomuleasa1,3,5 1Department of Hematology, Ion Chiricuta Oncology Institute, 2Department of Dentistry, 3Research Center for Functional Genomics and Translational Medicine, 4Department of Genetics, 5Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania *These authors contributed equally to this work Abstract: Acute megakaryocytic leukemia (M7-AML) is a rare form of acute myeloid leukemia (AML), which is associated with poor prognosis. The case presented in the current report is a statement for the difficult diagnosis and clinical management of M7-AML in the context of a previous hematologic disorder of undetermined significance and associated genetic abnormalities. Probably, following the complete hematologic remission and further with induction chemotherapy plus tyrosine kinase inhibitor therapy, the clinical management of this case will be followed by a allogeneic bone marrow transplantation, the only proven therapy to improve overall survival. Keywords: acute megakaryocytic leukemia, BCR–ABL transcript&nbsp

The use of rotation to fentanyl in cancer-related pain

Delia Dima,1 Ciprian Tomuleasa,1 Ioana Frinc,1 Sergiu Pasca,2 Lorand Magdo,2 Ioana Berindan-Neagoe,2–4 Mihai Muresan,5 Cosmin Lisencu,5 Alexandru Irimie,5,6 Mihnea Zdrenghea1,7 1Department of Hematology, Ion Chiricuta Oncology Institute, 2Faculty of Medicine, Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Iuliu Hatieganu, 3Department of Functional Genomics, The Oncology Institute Ion Chiricuta, 4Medfuture Research Center for Advanced Medicine, University of Medicine and Pharmacy, Iuliu Hatieganu, 5Department of Surgery, Ion Chiricuta Oncology Institute, 6Department of Oncology, University of Medicine and Pharmacy, Iuliu Hatieganu, 7Department of Hematology, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj Napoca, Romania Abstract: Pain is commonly diagnosed with respect to cancer and heart diseases, being a major symptom in most neoplastic diseases. Uncontrolled pain leads to a decrease in the quality of life and an increase in the morbidity of the patient. Opioids represent the best analgetic supportive therapy and are frequently used in patients suffering from cancer and experiencing a high level of pain. Opioid treatment starts with a gradual titration of the dose until the minimum effective dose and the maximum tolerated dose are determined. Opioid rotation refers to the switch from one opioid to another in order to get a better response to analgetic therapy and reduce side effects. Fentanyl therapy is recommended to be continued during chemotherapy, radiotherapy, or in the case of surgical intervention. Rotation to fentanyl patches is an efficient and elegant solution for cancer patients, with reduced side effects. Opioid rotation, especially to fentanyl, was shown to increase the quality of life in patients with malignant disease. Finally, rotation to fentanyl is also advantageous from an economic point of view. Keywords: opioid rotation, cancer-related pain, fentany

Small molecules against B-RAF (BRAF) Val600Glu (V600E) single mutation

Florin Zaharie,1,* Roxana Cojocneanu-Petric,1,* Mihai Muresan,1 Ioana Frinc,2 Delia Dima,2 Bobe Petrushev,3 Alina Tanase,4 Cristian Berce,1 Mariana Chitic,2 Ioana Berindan-Neagoe,1 Valentina Pileczki,1 Alexandru Irimie,5 Ciprian Tomuleasa2 1Iuliu Hatieganu University of Medicine and Pharmacy, 2Department of Hematology, Ion Chiricuta Oncology Institute, 3Department of Pathology, Emergency University Hospital, Cluj Napoca, 4Department of Stem Cell Transplantation, Fundeni Clinical Institute, Bucharest, 5Department of Surgery, Ion Chiricuta Oncology Institute, Cluj Napoca, Romania *These authors contributed equally to this communicationWe have read with great interest the paper by Tang and Chen1 published in the most recent issue of the International Journal of Nanomedicine, in which the authors describe the protocol by which scientists constructed the ideal BRAF (V600E)-modeled structure through homology modeling and introduced the method of structure-based docking or virtual screening from a large compound database. They concluded that BRAF (V600E) has a quite prominent structural or conformational variation when compared to the wild-type BRAF protein by matrix of root mean square fluctuation and principal component analysis. On the basis of structure-based virtual screening, ligand-based quantitative structure activity relationship models, and molecular dynamics simulation, we recommend aknadicine and 16beta-hydroxy-19s-vindolinine N-oxide as potent compounds for developing novel inhibitors in the future. Read the original article&nbsp

HLA Genotyping using Next Generation Sequencing

From an oncological perspective, the second most common malignancies in children are brain tumors. Despite the recent therapeutic breakthroughs in this field, concerning surgery, radiotherapy and chemotherapy alike, some cases still have poor outcomes in curability. This is especially the case in patients with high-risk histological types of tumors, and those suffering from residual, remitting and disseminated diseases. Due to the unique neuroanatomical emplacement of brain tumors and their aggressive infiltrative behavior, their total removal remains a demanding task. This can be perceived in the high rates of failure treatment and disease recurrence. Furthermore, the adjacent healthy brain tissue is inevitably damaged in the surgical process of effectively removing these tumors. Thus, stem cell transplantation may be a viable solution for the clinical management of these malignancies, as proven by various recent breakthroughs. In the current concise review, we present the role of next generation sequencing in HLA typing for stem cell transplantation in primary CNS pediatric malignancies

Gold nanoparticles enhance the effect of tyrosine kinase inhibitors in acute myeloid leukemia therapy

Bobe Petrushev,1,* Sanda Boca,2,* Timea Simon,2 Cristian Berce,3 Ioana Frinc,4 Delia Dima,4 Sonia Selicean,3 Grigore-Aristide Gafencu,3 Alina Tanase,5 Mihnea Zdrenghea,4,6 Adrian Florea,7 Sorina Suarasan,2 Liana Dima,8 Raluca Stanciu,3 Ancuta Jurj,1 Anca Buzoianu,9 Andrei Cucuianu,4,6,† Simion Astilean,2,10 Alexandru Irimie,11,12 Ciprian Tomuleasa,1,4 Ioana Berindan-Neagoe1,131Research Center for Functional Genomics and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 2Nanobiophotonics and Laser Microscopy Center, Babes Bolyai University, 3Department of Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 4Department of Hematology, Ion Chiricuta Oncology Institute, Cluj-Napoca, 5Department of Stem Cell Transplantation, Fundeni Clinical Institute, Bucharest, 6Department of Hematology, 7Department of Cell and Molecular Biology, 8School of Dentistry, 9Department of Pharmacology, Iuliu Hatieganu University of Medicine and Pharmacy, 10Faculty of Physics, Babes Bolyai University, 11Department of Surgery, Ion Chiricuta Oncology Institute, 12Department of Surgery, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania; 13Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA*These authors contributed equally to this work†This author passed away in February 2015Background and aims: Every year, in Europe, acute myeloid leukemia (AML) is diagnosed in thousands of adults. For most subtypes of AML, the backbone of treatment was introduced nearly 40 years ago as a combination of cytosine arabinoside with an anthracycline. This therapy is still the worldwide standard of care. Two-thirds of patients achieve complete remission, although most of them ultimately relapse. Since the FLT3 mutation is the most frequent, it serves as a key molecular target for tyrosine kinase inhibitors (TKIs) that inhibit FLT3 kinase. In this study, we report the conjugation of TKIs onto spherical gold nanoparticles.Materials and methods: The internalization of TKI-nanocarriers was proved by the strongly scattered light from gold nanoparticles and was correlated with the results obtained by transmission electron microscopy and dark-field microscopy. The therapeutic effect of the newly designed drugs was investigated by several methods including cell counting assay as well as the MTT assay.Results: We report the newly described bioconjugates to be superior when compared with the drug alone, with data confirmed by state-of-the-art analyses of internalization, cell biology, gene analysis for FLT3-IDT gene, and Western blotting to assess degradation of the FLT3 protein.Conclusion: The effective transmembrane delivery and increased efficacy validate its use as a potential therapeutic.Keywords: tyrosine kinase inhibitors, gold nanoparticles, acute myeloid leukemi