Article
Biochemistry & Molecular Biology
Jimena Alvarez Freile, Natasha Ustyanovska Avtenyuk, Macarena Gonzalez Corrales, Harm Jan Lourens, Gerwin Huls, Tom van Meerten, Ewa Cendrowicz, Edwin Bremer
Summary: This study investigates the expression and therapeutic effects of CD24 and CD47, two immune checkpoints, in B-cell lymphoma. The results show that CD24 is associated with poor survival in MCL patients, while CD47 is associated with survival in DLBCL patients. CD24 antibody treatment exhibits potent phagocytic effects in MCL, but not in DLBCL.
Review
Neurosciences
Henry Querfurth, Han-Kyu Lee
Summary: mTOR is involved in regulating energy metabolism, neuronal growth, insulin signaling, and autophagy, playing both beneficial and pathogenic roles in neurodegenerative diseases. Balanced actions of mTOR complexes may have implications for Alzheimer's disease, Parkinson's disease, Huntington's disease, Frontotemporal dementia, and Amyotrophic Lateral Sclerosis. Beyond rapamycin, rapalogs with improved tolerability and delivery modes hold promise in treating age-related conditions.
MOLECULAR NEURODEGENERATION
(2021)
Article
Medicine, Research & Experimental
Mohamed El-Tanani, Hamdi Nsairat, Alaa A. Aljabali, Angel Serrano-Aroca, Vijay Mishra, Yachana Mishra, Gowhar A. Naikoo, Walhan Alshaer, Murtaza M. Tambuwala
Summary: The mammalian target of rapamycin (mTOR), a signalling system, is necessary for various cell proliferation activities. It recognizes PI3KAKT stress signals as a serine-threonine kinase. The abnormal regulation of mTOR pathway has been proven to be crucial in cancer growth and advancement. This review primarily discusses the normal functions of mTOR as well as its abnormal roles in cancer development.
Article
Immunology
Junming He, Jun Zhao, Yuhe Quan, Xinlei Hou, Meixiang Yang, Zhongjun Dong
Summary: Complete phosphorylation of PKB by PDK1 and mTORC2 is essential for optimal NK cell development, regulating NK cell development by promoting E4BP4 expression and preventing cell apoptosis.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Marie Moosburner, Lamija Alibegovic, Korbinian Hasselmann, Anton Gaiderov, Johannes Hildebrand, Julia Philippou-Massier, Helmut Blum, Luca Fischer, Martin Dreyling, Elisabeth Silkenstedt
Summary: Constitutive activation of the PI3K/AKT/mTOR pathway is important in the development of mantle cell lymphoma (MCL), and the mTOR inhibitor temsirolimus is approved for treating relapsed or refractory MCL. However, early relapses have been observed despite favorable initial response rates. This study establishes a new temsirolimus-resistant MCL cell line and identifies upregulated pathways, such as PI3K/AKT/mTOR, RAS, and RTK-dependent PDGFR, FGFR, Met, and ALK signaling, in the resistant cells. MET overexpression is found to play a crucial role in mediating temsirolimus resistance, and combined treatment with temsirolimus and the RTK inhibitor crizotinib effectively restores sensitivity to temsirolimus.
HEMATOLOGICAL ONCOLOGY
(2023)
Article
Cell Biology
Sabrina Manni, Maria Pesavento, Zaira Spinello, Lara Saggin, Arash Arjomand, Anna Fregnani, Laura Quotti Tubi, Greta Scapinello, Carmela Gurrieri, Gianpietro Semenzato, Livio Trentin, Francesco Piazza
Summary: CK2 is an overexpressed kinase in many solid and blood-derived tumors. This study demonstrates that CK2 sustains MCL cell proliferation, survival, and anti-apoptotic ability, and is involved in BCR and Bcl-2 related signaling. CK2 inactivation enhances the cytotoxicity of Ibrutinib and Venetoclax, offering a potential strategy to overcome drug resistance.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Jessica Selig, H. Viviana Krug, Caroline Kueppers, D. Margriet Ouwens, Felix A. Kraft, Elena Adler, Sebastian J. Bauer, Artur Lichtenberg, Payam Akhyari, Mareike Barth
Summary: Diabetes and its key determinants, insulin resistance and hyperglycemia, contribute to calcific aortic valve disease (CAVD) by causing alterations in valvular interstitial cells (VIC) and extracellular matrix remodeling. The mTOR signaling pathway plays a crucial role in this process.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Oncology
Andrew J. Wagner, Vinod Ravi, Richard F. Riedel, Kristen Ganjoo, Brian A. Van Tine, Rashmi Chugh, Lee Cranmer, Erlinda M. Gordon, Jason L. Hornick, Heng Du, Berta Grigorian, Anita N. Schmid, Shihe Hou, Katherine Harris, David J. Kwiatkowski, Neil P. Desai, Mark A. Dickson
Summary: The study evaluated the efficacy and safety of nab-sirolimus in patients with malignant PEComa, showing an overall response rate of 39% with rapid and durable responses. Patients with TSC2 mutations were more likely to achieve a positive response. nab-sirolimus was considered an important new treatment option for this disease based on response rate, disease control, and safety profile.
JOURNAL OF CLINICAL ONCOLOGY
(2021)
Article
Immunology
Preeti Vyas, Rajkumar Tulsawani, Divya Vohora
Summary: Recent findings show that neuroinflammation is closely related to seizures, and the PI3K/Akt/mTOR pathway is speculated to be a potential target for treating neuroinflammation-mediated seizures and neurodegeneration. In a study on mice, PI3K inhibitors buparlisib and dactolisib were found to be effective in prolonging seizure latency and reducing neuronal loss, while rapamycin showed some resistance. The study suggests that targeting the PI3K pathway may offer new approaches for seizure therapies.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Oncology
Jiao Li, Hui Yu, Xing Wang, Yingying Ye, Wei Fang, Ning Ding, Lan Mi, Lingyan Ping, Xiaogan Wang, Yuqin Song, Jun Zhu
Summary: Inhibition of SGK1 shows potential therapeutic value in mantle cell lymphoma by significantly reducing cell proliferation, invasion and migration, inducing apoptosis, and blocking cell cycle progression. SGK1 inhibition also decreases the activation of multiple signaling pathways and has synergistic anti-tumor effects when used in combination with BTK inhibition. Further pre-clinical and clinical studies are necessary to explore the therapeutic potential of SGK1 inhibitor and its combination with BTK inhibitor.
Article
Oncology
Dongfeng Zeng, Yu Fang, Yue Fei, Rong Liang, Haige Ye, Yun Liang, Xiuhua Sun, Michael Wang, Huiqiang Huang, Lugui Qiu, Yuxuan Che, Panpan Liu, Yi Wang, Tao Pan, Yao Lv, Jintai Deng, Shuhua Yi, Yizi He, Ling Xiao, Huijuan Lv, Jiangfang Feng, Huilai Zhang, Hui Zhou, Dehui Zou, Qingqing Cai
Summary: A real-world multicenter study conducted in China evaluated treatment patterns and outcomes in newly diagnosed MCL patients treated with BTK inhibitors. The study found that non-HD-AraC chemotherapy combined with BTK inhibitors may be a viable therapeutic strategy for younger patients, and anti-HBV prophylaxis should be implemented in patients with resolved hepatitis B.
INTERNATIONAL JOURNAL OF CANCER
(2023)
Review
Oncology
Khalil Saleh, Morgane Cheminant, David Chiron, Barbara Burroni, Vincent Ribrag, Clementine Sarkozy
Summary: This article reviews the role of the tumor microenvironment (TME) in mantle cell lymphoma (MCL) and the different therapeutic strategies.
Article
Biochemistry & Molecular Biology
Alaa Abou Daher, Sahar Alkhansa, William S. Azar, Rim Rafeh, Hilda E. Ghadieh, Assaad A. Eid
Summary: Understanding the mechanisms behind diabetic nephropathy (DN) is crucial for developing effective treatments. The mTOR pathway has been identified as a key player in diabetes-induced kidney injury, through its involvement in insulin resistance, oxidative stress, and autophagy regulation.
ANTIOXIDANTS & REDOX SIGNALING
(2022)
Article
Ophthalmology
Nozomi Igarashi, Megumi Honjo, Makoto Aihara
Summary: Glaucoma, the second leading cause of blindness worldwide, is often treated with trabeculectomy, but this surgery can lead to excessive scarring and tissue fibrosis. Studies have shown that mTOR inhibitors may offer a new treatment modality for reducing fibrotic response in human conjunctival fibroblasts and improving bleb scarring after filtration surgery.
EXPERIMENTAL EYE RESEARCH
(2021)
Article
Cell Biology
Xianhuo Wang, Yue Fei, Xia Liu, Tingting Zhang, Wei Li, Xiaohui Jia, Xianming Liu, Lihua Qiu, Zhengzi Qian, Shiyong Zhou, Xiubao Ren, Qiongli Zhai, Bin Meng, Lanfang Li, Huilai Zhang
Summary: BGB-3111 demonstrates significant anti-cancer effects in BTK-expressing MCL cells, and when combined with bortezomib, it enhances these effects and improves safety. This combination therapy could be a potential therapeutic strategy for MCL patients.
Article
Oncology
Keenan T. Hartert, Kerstin Wenzl, Jordan E. Krull, Michelle Manske, Vivekananda Sarangi, Yan Asmann, Melissa C. Larson, Matthew J. Maurer, Susan Slager, William R. Macon, Rebecca L. King, Andrew L. Feldman, Anita K. Gandhi, Brian K. Link, Thomas M. Habermann, Zhi-Zhang Yang, Stephen M. Ansell, James R. Cerhan, Thomas E. Witzig, Grzegorz S. Nowakowski, Anne J. Novak
Summary: A study identified a high-risk subset of non-GCB DLBCL patients with genomic alterations and expression signatures affecting treatment outcomes, showing unfavorable prognoses with RCHOP therapy. However, these high-risk patients had better outcomes when lenalidomide was added to RCHOP treatment.
Review
Genetics & Heredity
Taylor M. Weiskittel, Cristina Correia, Grace T. Yu, Choong Yong Ung, Scott H. Kaufmann, Daniel D. Billadeau, Hu Li
Summary: Machine learning plays a crucial role in bridging the analytical gaps in single-cell studies and works synergistically with single-cell data. System biology algorithms have integrated machine learning with biological components to provide system-level analyses of single-cell omics data, shedding light on complex biological mechanisms.
Article
Oncology
Geffen Kleinstern, Melissa C. Larson, Stephen M. Ansell, Carrie A. Thompson, Grzegorz S. Nowakowski, Timothy G. Call, Dennis P. Robinson, Matthew J. Maurer, Raphael Mwangi, Andrew L. Feldman, Neil E. Kay, Anne J. Novak, Thomas M. Habermann, Susan L. Slager, James R. Cerhan
Summary: This study investigated the association between vaccinations and the risk of different lymphoma subtypes. The results showed that vaccinations against influenza and yellow fever were inversely associated with lymphoma risk. However, the association between hepatitis B vaccination and lymphoma risk was complex. These findings suggest that the vaccination-related lymphoma risk may vary depending on the time since vaccination and the type of vaccine.
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
(2022)
Article
Oncology
Yucai Wang, Shouhao Zhou, Xinyue Qi, Fang Yang, Matthew J. Maurer, Thomas M. Habermann, Thomas E. Witzig, Michael L. Wang, Grzegorz S. Nowakowski
Summary: This study conducted a network meta-analysis to compare the efficacy of different treatment regimens for follicular lymphoma. The results showed that G-Benda-G had the best progression-free survival, indicating that bendamustine is a better chemotherapy backbone for follicular lymphoma.
BLOOD CANCER JOURNAL
(2022)
Review
Oncology
Clifford M. Csizmar, Antoine N. Saliba, Elizabeth M. Swisher, Scott H. Kaufmann
Summary: PARP inhibitors have potential roles in the treatment of myeloid diseases, especially in acute myeloid leukemia (AML) with specific genetic characteristics. They may enhance the efficacy of other agents in AML but long-term use is associated with an increased risk of myelodysplastic syndrome (MDS) and AML.
Article
Hematology
Alessia Castellino, Yucai Wang, Melissa C. Larson, Matthew J. Maurer, Brian K. Link, Umar Farooq, Andrew L. Feldman, Sergei Syrbu, Thomas M. Habermann, Jonas Paludo, David J. Inwards, Thomas E. Witzig, Stephen M. Ansell, Cristine Allmer, Susan L. Slager, Jonathon B. Cohen, Peter Martin, James R. Cerhan, Grzegorz S. Nowakowski
Summary: By analyzing clinical characteristics, treatment, and clinical outcomes of MCL patients enrolled in a prospective cohort study, this study identified changes in frontline treatment patterns over the past years and found that these changes were associated with improved outcomes for patients.
Article
Oncology
Sanjal H. Desai, Levi D. Pederson, Betsy Laplant, Raphael Mwangi, Matthew J. Maurer, Jason R. Young, William R. Macon, Rebecca L. King, Yucai Wang, James R. Cerhan, Andrew L. Feldman, David J. Inwards, Ivana N. Micallef, Patrick B. Johnston, Luis F. Porrata, Stephen M. Ansell, Thomas M. Habermann, Thomas E. Witzig, Grzegorz S. Nowakowski
Summary: This study found that PET2 after two cycles of chemotherapy can predict the risk of disease progression and death in patients with diffuse large B cell lymphoma. PET2-guided risk-adapted strategies may improve outcomes for these patients.
BLOOD CANCER JOURNAL
(2022)
Article
Oncology
Christopher S. S. Strouse, Melissa C. C. Larson, Shawna L. L. Ehlers, Kathleen J. J. Yost, Matthew J. J. Maurer, Stephen M. M. Ansell, David J. J. Inwards, Patrick B. B. Johnston, Ivana N. N. Micallef, Brian K. K. Link, Umar Farooq, James R. R. Cerhan, Carrie A. A. Thompson
Summary: This study assessed the long-term quality of life of patients with aggressive lymphoma subtypes treated with autologous hematopoietic cell transplant compared with those without history of transplant. The results showed that patients remaining in remission at 3 and 6 years after diagnosis had a high level of quality of life, with no significant differences associated with history of treatment with autologous hematopoietic cell transplant.
JCO ONCOLOGY PRACTICE
(2022)
Review
Hematology
Grzegorz Nowakowski, Matthew J. Maurer, James R. Cerhan, Debarshi Dey, Laurie H. Sehn
Summary: Comparative effectiveness studies using real-world data can provide complementary evidence on treatment effectiveness. By balancing baseline covariates using propensity score methods, closely matched patient-level cohorts can be generated for robust comparative analyses.
AMERICAN JOURNAL OF HEMATOLOGY
(2023)
Letter
Hematology
Evandro D. Bezerra, Madiha Iqbal, Javier Munoz, Arushi Khurana, Yucai Wang, Matthew J. Maurer, Radhika Bansal, Matthew A. Hathcock, Nora Bennani, Hemant S. Murthy, Allison C. Rosenthal, Jonas Paludo, Jose C. Villasboas, Patrick B. Johnston, Thomas M. Habermann, Stephen M. Ansell, Januario E. Castro, Thomas E. Witzig, Mohamed A. Kharfan-Dabaja, Grzegorz S. Nowakowski, Yi Lin
Article
Hematology
Sanjal H. Desai, Raphael Mwangi, Wern Lynn Ng, Rebecca L. King, Matthew J. Maurer, James R. Cerhan, Andrew L. Feldman, Umar Farooq, Eric Mou, Thomas M. Habermann, Carrie A. Thompson, Yucai Wang, Thomas E. Witzig, Grzegorz S. Nowakowski
Summary: This observational study found that patients with DLBCL who underwent CNB had poor-risk features, worse outcomes, and inadequate tissue for molecular analyses compared to those who underwent EB. The increasing tissue requirements of biomarker-driven clinical trials may result in the exclusion of high-risk DLBCL patients who need novel agents.
Article
Oncology
Yucai Wang, Preetesh Jain, Frederick L. Locke, Matthew J. Maurer, Matthew J. Frank, Javier L. Munoz, Saurabh Dahiya, Amer M. Beitinjaneh, Miriam T. Jacobs, Joseph P. Mcguirk, Julie M. Vose, Andre Goy, Charalambos Andreadis, Brian T. Hill, Kathleen A. Dorritie, Olalekan O. Oluwole, Abhinav Deol, Jonas Paludo, Bijal Shah, Trent Wang, Rahul Banerjee, David B. Miklos, Aaron P. Rapoport, Lazaros Lekakis, Armin Ghobadi, Sattva S. Neelapu, Yi Lin, Michael L. Wang, Michael D. Jain
Summary: This study evaluated the efficacy and toxicity of Brexucabtagene autoleucel (brexu-cel) for relapsed/refractory mantle cell lymphoma (MCL) in the standard-of-care setting. The results showed that the efficacy and toxicity of brexu-cel were consistent with those reported in the ZUMA-2 trial. Tumor-intrinsic features of MCL, and possibly recent bendamustine exposure, may be associated with inferior efficacy outcomes.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Oncology
Cristina Correia, Matthew J. J. Maurer, Samantha J. J. McDonough, Paula A. A. Schneider, Paige E. E. Ross, Anne J. J. Novak, Andrew L. L. Feldman, James R. R. Cerhan, Susan L. L. Slager, Thomas E. E. Witzig, Bruce W. W. Eckloff, Hu Li, Grzegorz S. S. Nowakowski, Scott H. H. Kaufmann
Summary: The identification of follicular lymphoma (FL) patients with low disease burden but high risk for early progression is unclear. In a study on newly diagnosed FLs, BCL2 mutations with high variant allele frequency (VAF) were found to be associated with increased transformation risk and shorter event-free survival. However, other sequenced genes did not contribute significantly to the prognostic value of the panel. Nonsynonymous BCL2 mutations with VAF = 20% were consistently associated with decreased event-free survival and overall survival.
BLOOD CANCER JOURNAL
(2023)
Article
Hematology
Diego Villa, Aixiang Jiang, Carlo Visco, Nicola Crosbie, Rory Mcculloch, Michael J. Buege, Anita Kumar, David A. Bond, Jonas Paludo, Matthew J. Maurer, Gita Thanarajasingam, Katharine L. Lewis, Chan Y. Cheah, Joachim Baech, Tarec C. El-Galaly, Laveniya Kugathasan, David W. Scott, Alina S. Gerrie, David Lewis
Summary: This study evaluated the prognostic factors in patients with relapsed/refractory mantle cell lymphoma (MCL) exclusively initiating second-line Bruton's tyrosine kinase inhibitors (BTKis) after first-line rituximab-containing therapy. The results showed that time to progression of disease (POD), Ki67, and MCL International Prognostic Index (MIPI) were associated with survival outcomes in patients receiving second-line BTKis. The study also developed web/application-based calculators to predict progression-free survival and overall survival in this population.
Article
Oncology
Zhi-Zhang Yang, Hyo Jin Kim, Hongyan Wu, Xinyi Tang, Yue Yu, Jordan Krull, Daniel P. Larson, Raymond M. Moore, Matthew J. Maurer, Kevin D. Pavelko, Shahrzad Jalali, Joshua C. Pritchett, Rekha Mudappathi, Junwen Wang, Jose C. Villasboas, Patrizia Mondello, Anne J. Novak, Stephen M. Ansell
Summary: T-lymphocytes in the tumor microenvironment of follicular lymphoma (FL) show diverse phenotypes, which may influence tumor biology and patient survival. Our analysis of 82 FL patients revealed four immune subgroups with different T-cell phenotypes, and a higher prevalence of CD57(+) T-FH cells with a late-stage differentiation phenotype was associated with poor patient survival.
BLOOD CANCER JOURNAL
(2023)