Article
Biochemistry & Molecular Biology
Sylwester Glowacki, Ewelina Synowiec, Marzena Szwed, Monika Toma, Tomasz Skorski, Tomasz Sliwinski
Summary: Chronic myeloid leukemia (CML) is caused by the BCR-ABL1 protein, inducing oxidative stress and leading to resistance to imatinib (IM). Research shows increased ROS accumulation in BCR-ABL1 positive cells, heightened DNA damage in IM-sensitive cells, and alterations in antioxidant enzyme activity and mitochondrial potential in IM-resistant cells.
Article
Hematology
Hagop M. Kantarjian, Elias Jabbour, Michael Deininger, Elisabetta Abruzzese, Jane Apperley, Jorge Cortes, Charles Chuah, Daniel J. DeAngelo, John DiPersio, Andreas Hochhaus, Jeffrey Lipton, Franck E. Nicolini, Javier Pinilla-Ibarz, Delphine Rea, Gianantonio Rosti, Philippe Rousselot, Neil P. Shah, Moshe Talpaz, Shouryadeep Srivastava, Xiaowei Ren, Michael Mauro
Summary: Ponatinib has demonstrated deep and durable responses in patients with chronic-phase chronic myeloid leukemia, especially in those resistant to second-generation TKI treatment, and has shown good safety and survival outcomes.
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Article
Pharmacology & Pharmacy
Hyacinthe Johnson-Ansah, Benjamin Maneglier, Francoise Huguet, Laurence Legros, Martine Escoffre-Barbe, Martine Gardembas, Pascale Cony-Makhoul, Valerie Coiteux, Laurent Sutton, Wajed Abarah, Camille Pouaty, Jean-Michel Pignon, Bachra Choufi, Sorin Visanica, Benedicte Deau, Laure Morisset, Emilie Cayssials, Mathieu Molimard, Stephane Bouchet, Francois-Xavier Mahon, Franck Nicolini, Philippe Aegerter, Jean-Michel Cayuela, Marc Delord, Heriberto Bruzzoni-Giovanelli, Philippe Rousselot
Summary: This study evaluated the value of therapeutic drug monitoring (TDM) in imatinib treatment for patients with chronic myelogenous leukemia. The results showed that TDM strategy significantly increased the plasma concentration of imatinib and improved the treatment outcome for patients.
Article
Biochemistry & Molecular Biology
Rachid Lahlil, Anne Aries, Maurice Scrofani, Celine Zanetti, Desline Hennequin, Bernard Drenou
Summary: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disease characterized by the presence of the BCR-ABL fusion gene. Treatment with tyrosine kinase inhibitors (TKIs) such as imatinib mesylate (IM) has significantly improved clinical outcomes for CML patients, but IM resistance remains a major challenge. The cause of IM resistance in CML cells is unclear, but additional genetic alterations in leukemic stem cells (LSCs) are a common cause of relapse. A study found that a rare subpopulation of stem cells called very small embryonic-like stem cells (VSELs) in adult CML patients is resistant to IM and less sensitive to apoptosis compared to leukemic hematopoietic stem cells (HSCs). The expression levels of certain miRNAs are also affected in these IM-resistant VSELs, including miR-126 and miR-21, which are involved in LSC leukemia-initiating capacity and growth.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Frederic Millot, Meinolf Suttorp, Stephanie Ragot, Guy Leverger, Jean-Hugues Dalle, Caroline Thomas, Nathalie Cheikh, Brigitte Nelken, Marilyne Poiree, Genevieve Plat, Birgitta Versluys, Birgitte Lausen, Marina Borisevich
Summary: The study evaluated the rate of children with childhood chronic myeloid leukemia who remained in molecular response after discontinuing imatinib following sustained deep molecular response (DMR). The findings showed fluctuating molecular free remission rates at different time points post-discontinuation, with no significant influencing factors identified.
Article
Medicine, General & Internal
Ik-Chan Song, Sang-Noon Yeon, Myeong-Won Lee, Hyewon Ryu, Hyo-Jin Lee, Hwan-Jung Yun, Byung Joo Sun, Jae-Hyeong Park, Jin-Ok Jeong, Deog-Yeon Jo
Summary: This study retrospectively analyzed the prevalence of pulmonary hypertension (PH) among Korean chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKIs), such as dasatinib, imatinib, and nilotinib. The results showed that not only dasatinib, but also imatinib and nilotinib could induce PH in CML patients. Risk factors for developing PH included age over 60, dasatinib treatment, and positive cardiopulmonary symptoms/signs at the time of transthoracic echocardiography.
Editorial Material
Oncology
Eda Nuhoglu Kantarci, Ece Tolgay, Ahmet Emre Eskazan
Summary: This editorial discusses the search for the best patient-based treatment option as well as evaluates a recent study by Tiribelli et al., published in Cancer.
Article
Genetics & Heredity
Hossam Hodeib, Dina Abd El Hai, Mohamed A. Tawfik, Alzahraa A. Allam, Ahmed F. Selim, Mohamed E. Sarhan, Amal Selim, Nesreen M. Sabry, Wael Mansour, Amira Youssef
Summary: This study aimed to explore the impact of SKP2 gene expression on the early treatment response in first-line IM-treated CML patients. The results showed that SKP2 gene and protein levels were upregulated in CML patients. SKP2 gene expression level can be used for diagnosing CML patients and predicting early treatment response.
Article
Hematology
Fadi G. Haddad, Koji Sasaki, Ghayas C. Issa, Guillermo Garcia-Manero, Farhad Ravandi, Tapan Kadia, Jorge Cortes, Marina Konopleva, Naveen Pemmaraju, Yesid Alvarado, Musa Yilmaz, Gautam Borthakur, Courtney DiNardo, Nitin Jain, Naval Daver, Nicholas J. Short, Elias Jabbour, Hagop Kantarjian
Summary: This study evaluated the outcome of TKI discontinuation in CML patients and identified factors associated with success rates of treatment-free remission (TFR). The study found that TFR is safe and feasible in patients with Ph-positive CML on TKI therapy. Achieving MR4 or MR4.5 for at least 5 years was correlated with a better outcome.
AMERICAN JOURNAL OF HEMATOLOGY
(2022)
Article
Oncology
Kendra L. Sweet, Jorge E. Cortes, Jane F. Apperley, Mel Mann, Michael J. Mauro, Vivian G. Oehler, Cristina Ruiz, Charles A. Schiffer, Lori A. Ehrlich, Gulsum E. Pamuk, Joseph Wynne, Gautam U. Mehta, R. Angelo de Claro, Marc R. Theoret, B. Douglas Smith, Kelly J. Norsworthy
Summary: The FDA has an accelerated approval program for potentially promising drugs in treating serious conditions. All available treatments for chronic myeloid leukemia (CML) have undergone this program. A group consisting of CML experts, patient panelists, and FDA members gathered to discuss the utility of the accelerated approval program in CML and its future role in drug development, and the results are summarized here.
CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Fang Cheng, Guolin Yuan, Qiang Li, Zheng Cui, Weiming Li
Summary: This study confirmed the long-term efficacy and safety of imatinib for treating Chinese CML patients. Additionally, it demonstrated the feasibility of imatinib dose reduction and treatment-free remission attempts in patients with sustained stable deep molecular response after years of imatinib treatment in real-life settings.
FRONTIERS IN ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Raquel Alves, Ana Cristina Goncalves, Joana Jorge, Antonio M. Almeida, Ana Bela Sarmento-Ribeiro
Summary: This study evaluated the therapeutic potential of elacridar, a P-glycoprotein and BCRP inhibitor, in CML cell lines. The results showed that elacridar as monotherapy was not effective, but when combined with imatinib, it could overcome resistance. This provides a new treatment option for overcoming TKI resistance.
Article
Biochemistry & Molecular Biology
Giordana Feriotto, Paolo Marchetti, Riccardo Rondanin, Federico Tagliati, Serena Aguzzi, Simone Beninati, Fabio Casciano, Claudio Tabolacci, Carlo Mischiati
Summary: In this study, the bis-ketone moiety of curcumin (CUR) was replaced to obtain more stable derivatives 2 and 22. The evaluation of their chemical-physical characteristics and cell experiments showed that derivatives 2 and 22 had better bioavailability and stability than CUR, and exhibited significant cytotoxicity and pro-apoptotic effects on chronic myeloid leukemia (CML) cells. Moreover, derivative 22 was able to reverse drug resistance in CML cells resistant to imatinib (IM).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Fang Cheng, Fang Zeng, Qiang Li, Zheng Cui, Yilin Chen, Weiming Li, Yu Zhang
Summary: This study explores the optimization of imatinib dose in CML patients based on therapeutic drug monitoring (TDM). The results show that imatinib concentration is closely associated with clinical response and adverse reactions. Dose reduction based on TDM is feasible and safe for patients exhibiting optimal response, improving adverse reactions without affecting molecular relapse-free survival rate.
Article
Medicine, Research & Experimental
Jani Huuhtanen, Mette Ilander, Bhagwan Yadav, Olli M. J. Dufva, Hanna Lahteenmaki, Tiina Kasanen, Jay Klievink, Ulla Olsson-Stromberg, Jesper Stentoft, Johan Richter, Perttu Koskenvesa, Martin Hoglund, Stina Soderlund, Arta Dreimane, Kimmo Porkka, Tobias Gedde-Dahl, Bjorn T. Gjertsen, Leif Stenke, Kristina Myhr-Eriksson, Berit Markevarn, Anna Lubking, Andreja Dimitrijevic, Lene Udby, Ole Weis Bjerrum, Henrik Hjorth-Hansen, Satu Mustjoki
Summary: In patients with chronic myeloid leukemia, combination therapy with dasatinib and IFN-alpha can improve deep molecular remission and restore immune function.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Biochemistry & Molecular Biology
Yuki Narita, Kana Hamamura, Mami Kashiyama, Sara Utsumi, Yutaka Kakizoe, Yuki Kondo, Yoichi Ishitsuka, Hirofumi Jono, Tetsumi Irie, Masashi Mukoyama, Hideyuki Saito, Daisuke Kadowaki, Sumio Hirata, Kenichiro Kitamura
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Article
Infectious Diseases
Kazutaka Oda, Tomomi Katanoda, Yumi Hashiguchi, Shoji Kondo, Yuki Narita, Koji Iwamura, Kisato Nosaka, Hirofumi Jono, Hideyuki Saito
JOURNAL OF INFECTION AND CHEMOTHERAPY
(2020)
Article
Infectious Diseases
Kazutaka Oda, Toshikazu Miyakawa, Tomomi Katanoda, Yumi Hashiguchi, Koji Iwamura, Kisato Nosaka, Ayami Yamaguchi, Hirofumi Jono, Hideyuki Saito
JOURNAL OF INFECTION AND CHEMOTHERAPY
(2020)
Article
Oncology
Yuki Shirakawa, Takuichiro Hide, Michiko Yamaoka, Yuki Ito, Naofumi Ito, Kunimasa Ohta, Naoki Shinojima, Akitake Mukasa, Hideyuki Saito, Hirofumi Jono
Article
Infectious Diseases
Kazutaka Oda, Hirofumi Jono, Katsuyuki Sagishima, Hideyuki Saito
JOURNAL OF INFECTION AND CHEMOTHERAPY
(2020)
Article
Chemistry, Multidisciplinary
Kazutaka Oda, Hirofumi Jono, Hidenobu Kamohara, Kazuhiko Nishi, Naomi Tanoue, Hideyuki Saito
PHARMACEUTICAL RESEARCH
(2020)
Article
Biochemistry & Molecular Biology
Nozomi Yabuuchi, Huixian Hou, Nao Gunda, Yuki Narita, Hirofumi Jono, Hideyuki Saito
Summary: SULT1A1 plays toxico-pathological roles in the progression of cisplatin-induced acute kidney injury, while the IS/AhR/ROS axis brings about oxidative stress.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Yukako Yamakawa, Motohiro Morioka, Tetsuya Negoto, Kimihiko Orito, Munetake Yoshitomi, Yukihiko Nakamura, Nobuyuki Takeshige, Masafumi Yamamoto, Yasuharu Takeuchi, Kazutaka Oda, Hirofumi Jono, Hideyuki Saito
Summary: The study investigated a novel step-down infusion method of barbiturates under normothermia for controlling intracranial pressure in patients with severe traumatic brain injury or severe cerebrovascular disease. The method successfully maintained stable thiamylal concentrations and kept intracranial pressure below 20 mmHg in all patients, while also maintaining cerebral perfusion pressure above 65 mmHg without any serious side effects. This approach may provide a new and effective treatment option for patients with increased intracranial pressure.
PHARMACOLOGY RESEARCH & PERSPECTIVES
(2021)
Article
Chemistry, Multidisciplinary
Kazutaka Oda, Yumi Hashiguchi, Toshimi Kimura, Yasuhiro Tsuji, Kensuke Shoji, Yoshiko Takahashi, Kazuaki Matsumoto, Hideki Kawamura, Hideyuki Saito, Yoshio Takesue
Summary: This study validated a newly developed web application, PAT, for estimating AUC of vancomycin. PAT showed the least bias when using two concentrations for estimation, with only 6% of estimations falling outside the acceptable range. Compared to evaluated software, PAT's AUC estimation was unbiased.
PHARMACEUTICAL RESEARCH
(2021)
Article
Oncology
Yuki Fujimoto, Shikiko Ueno, Kazutaka Oda, Nao Gunda, Yumi Shimomura, Yuka Nishimura, Ayami Yamaguchi, Akari Kuwano, Yuki Ito, Yusuke Baba, Aina Nishigaki, Natsumi Michiwaki, Shota Uchino, Kayo Kurogi, Yawara Kawano, Masao Matsuoka, Hideyuki Saito, Yutaka Okuno, Hirofumi Jono
Summary: This study verified that serum bortezomib concentration may be associated with the emergence of diarrhea in multiple myeloma patients receiving bortezomib therapy. Patients with a bortezomib concentration higher than 0.857 ng/mL are more likely to experience diarrhea.
Article
Cell Biology
Yuki Shirakawa, Kunimasa Ohta, Shunsuke Miyake, Ayumi Kanemaru, Akari Kuwano, Kou Yonemaru, Shota Uchino, Michiko Yamaoka, Yuki Ito, Naofumi Ito, Takuichiro Hide, Naoki Shinojima, Akitake Mukasa, Hideyuki Saito, Hirofumi Jono
Summary: This study aimed to investigate the mechanisms underlying GSCs development by focusing on extrinsic ribosome incorporation into GBM cells. The results showed that ribosome incorporation promoted the formation of GSC-like cells, with implications for the potential biological and clinical significance of extrinsic ribosomal proteins in GSC development.
Article
Pharmacology & Pharmacy
Kazutaka Oda, Shota Uchino, Kayo Kurogi, Mai Horikawa, Naoya Matsumoto, Kou Yonemaru, Hitomi Arakaki, Taiki Katsume, Kaho Matsuyama, Tomomi Katanoda, Yuki Narita, Koji Iwamura, Hirofumi Jono, Hideyuki Saito
Summary: Therapeutic drug monitoring for voriconazole is crucial for optimal pharmacotherapy, and the newly developed LM1010 equipment showed acceptable clinical performance when compared with outsourcing measurement using liquid chromatography-tandem mass spectrometry.
JOURNAL OF PHARMACEUTICAL HEALTH CARE AND SCIENCES
(2021)
Article
Medicine, Research & Experimental
Kazutaka Oda, Tomoyuki Yamada, Kazuaki Matsumoto, Yuki Hanai, Takashi Ueda, Masaru Samura, Akari Shigemi, Hirofumi Jono, Hideyuki Saito, Toshimi Kimura
Summary: This study aimed to demonstrate the potential of the Bayesian forecasting approach for achieving the target AUC rapidly. It concluded that early sampling could improve the probability of AUC(0-24) and AUC(24-48), but it was not sufficient for predicting AUC(SS). Further research is needed to apply early sampling-based model-informed precision dosing in clinical settings.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Huixian Hou, Mai Horikawa, Yuki Narita, Hirofumi Jono, Yutaka Kakizoe, Yuichiro Izumi, Takashige Kuwabara, Masashi Mukoyama, Hideyuki Saito
Summary: Renal fibrosis, the final manifestation of chronic kidney disease (CKD), can be controlled and prevented by targeting the enzyme SULT1A1 to decrease the accumulation of indoxyl sulfate (IS). In a study with Sult1a1-KO mice, it was found that the exacerbation of inflammation and renal fibrosis in WT mice was significantly suppressed in Sult1a1-KO mice. Expression of CD206(+) was upregulated and β-catenin expression was downregulated in Sult1a1-KO mice. Additionally, the study confirmed the beneficial effect of erythropoietin (EPO) in attenuating renal fibrosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Infectious Diseases
Yumi Hashiguchi, Kazutaka Oda, Tomomi Katanoda, Kisato Nosaka, Hirofumi Jono, Hideyuki Saito
JOURNAL OF INFECTION AND CHEMOTHERAPY
(2020)