Article
Biochemistry & Molecular Biology
Jang Mi Han, Hye Jin Jung
Summary: This study investigated the therapeutic effects of two natural compounds, berbamine and arcyriaflavin A, on glioblastoma stem-like cells (GSCs). The combined treatment synergistically inhibited GSC viability and tumorsphere formation and induced ROS- and calcium-dependent apoptosis. Furthermore, it downregulated the expression of key GSC markers and cell cycle regulatory proteins through inactivation of the CaMKII gamma-mediated signaling pathway.
Article
Biochemistry & Molecular Biology
Haibin Deng, Yanyun Gao, Verdiana Trappetti, Damian Hertig, Darya Karatkevich, Tereza Losmanova, Christian Urzi, Huixiang Ge, Gerrit Adriaan Geest, Remy Bruggmann, Valentin Djonov, Jean-Marc Nuoffer, Peter Vermathen, Nicola Zamboni, Carsten Riether, Adrian Ochsenbein, Ren-Wang Peng, Gregor Jan Kocher, Ralph Alexander Schmid, Patrick Dorn, Thomas Michael Marti
Summary: The study reveals the crucial role of lactate dehydrogenase B (LDHB) in regulating glucose and mitochondrial metabolism, and its impact on the survival and proliferation of non-small cell lung cancer (NSCLC) cells.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Michal Marcinkowski, Tomas Pilzys, Damian Garbicz, Jan Piwowarski, Kaja Przygonska, Maria Winiewska-Szajewska, Karolina Ferenc, Oleksandr Skorobogatov, Jaroslaw Poznanski, Elzbieta Grzesiuk
Summary: FTO is an N-6-methyladenosine demethylase which can remove methyl groups from nucleic acids, forming complexes with other proteins. Research indicates an interaction between FTO and calmodulin (CaM), influencing calcium-binding loops in CaM.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Tianyu Wang, Hui Wang, Fan Yang, Kuan Gao, Shuya Luo, Lichuan Bai, Ke Ma, Mei Liu, Shuwei Wu, Huijie Wang, Zaixing Chen, Qinghuan Xiao
Summary: This study revealed a new anticancer mechanism of honokiol by inhibiting cell proliferation through targeting Ano1 Ca2+-activated Cl- channels. Honokiol more potently inhibited Ano1 currents compared to Ano2 currents, with three critical amino acids (R429, K430, and N435) identified for honokiol-induced Ano1 inhibition.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Du-Hyong Cho, Hyeon-Ju Lee, Jee Young Lee, Jung-Hyun Park, Inho Jo
Summary: The study investigated the molecular mechanisms of FIR irradiation inhibiting breast cancer cell proliferation. Results demonstrated that FIR irradiation inhibited cell proliferation by activating the Ca2+/CaM/Chk2 signaling pathway without causing DNA damage.
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Anastasiia Bohush, Wieslawa Lesniak, Serge Weis, Anna Filipek
Summary: Parkinson's disease is a neurodegenerative disorder characterized by the formation of Lewy bodies and loss of dopaminergic neurons. Changes in intracellular Ca2+ levels can have serious consequences on cells, with calmodulin playing a crucial role in regulating neuronal plasticity. Therefore, alterations in the activity of calmodulin and its binding proteins may be linked to the development and progression of PD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Debarati Mukherjee, Rebecca A. Previs, Corinne Haines, Muthana Al Abo, Patrick K. Juras, Kyle C. Strickland, Binita Chakraborty, Sandeep Artham, Regina S. Whitaker, Katherine Hebert, Jake Fontenot, Steven R. Patierno, Jennifer A. Freedman, Frank H. Lau, Matthew E. Burow, Ching-Yi Chang, Donald P. McDonnell
Summary: Triple-negative breast cancers (TNBC) and high-grade serous ovarian cancer (HGSOC) are both aggressive and difficult to treat. This study found that the serine/threonine kinase CaMKK2 plays a significant role in promoting metastasis in these cancers, and inhibiting CaMKK2 can effectively block metastatic progression. The mechanism involves the CaMKK2- PDE1A-PKG1-VASP signaling pathway, which regulates actin cytoskeleton dynamics and cell motility. This research highlights CaMKK2 as a potential therapeutic target for restricting tumor invasiveness in TNBC and HGSOC patients.
Review
Oncology
Keigo Machida, Stanley M. Tahara
Summary: This review discusses the pharmacological and immune therapeutic targeting for hepatocellular carcinoma (HCC) and cholangiocarcinoma, as well as the role of immunotherapies and microbiota in tumor-initiating stem-like cells (TICs). Gut dysbiosis inhibits the efficacy of immunotherapies, and personalized medicine approaches targeting TIC/metastasis-initiating cells may be potential targets for HCC immunotherapy and microbiota modulation therapy.
Article
Multidisciplinary Sciences
Jiahui Xu, Xiaoli Yang, Qiaodan Deng, Cong Yang, Dong Wang, Guojuan Jiang, Xiaohong Yao, Xueyan He, Jiajun Ding, Jiankun Qiang, Juchuanli Tu, Rui Zhang, Qun-Ying Lei, Zhi-min Shao, Xiuwu Bian, Ronggui Hu, Lixing Zhang, Suling Liu
Summary: Enhanced neovasculogenesis, especially vasculogenic mimicry (VM), contributes to the development of triple-negative breast cancer (TNBC). We identified TEM8 as a functional marker for VM-forming BTICs in TNBC, providing a target for the development of effective therapies against TNBC targeting both BTIC self-renewal and neovasculogenesis simultaneously. TEM8 promotes stemness and VM differentiation capacity through a RhoC/ROCK1/SMAD5 axis.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Shayahati Bieerkehazhi, Ying Fan, Savannah J. West, Ritika Tewari, Junsuk Ko, Tingting Mills, Darren Boehning, Askar M. Akimzhanov
Summary: The study demonstrates the importance of the enzyme DHHC21 in T cell receptor signal transduction and protein acylation. DHHC21 is critical for the activation of CD4(+) T cells and plays a role in the differentiation of effector T helper lineages.
JOURNAL OF CELL SCIENCE
(2022)
Review
Oncology
Francesco Tamiro, Andrew P. Weng, Vincenzo Giambra
Summary: Leukemia-initiating cells (LIC) are unique cells in different types of leukemia that have self-renewing capabilities and produce tumors, which are functionally distinct from bulk leukemia cells. Current conventional treatments are not effective in eliminating LICs, hence innovative therapeutics targeting LICs hold promise for developing an effective cure for ALL.
Article
Oncology
Michael W. Caminear, Brittney S. Harrington, Rahul D. Kamdar, Michael J. Kruhlak, Christina M. Annunziata
Summary: The study found that disulfiram was more effective in reducing the viability of TICs compared to NCTs, affecting NF kappa B signaling, and was more suitable as a therapeutic to prevent EOC relapse.
FRONTIERS IN ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Premchand Rajeev, Nivedita Singh, Adel Kechkar, Cory Butler, Narendrakumar Ramanan, Jean-Baptiste Sibarita, Mini Jose, Deepak Nair
Summary: Synapse associated protein-97/Human Disk Large (SAP97/hDLG) is a conserved, alternatively spliced, modular, scaffolding protein critical in regulating the molecular organization of cell-cell junctions in vertebrates. The molecular determinants of first order phase transition of SAP97/hDLG is controlled by morpho-functional changes in its nanoscale organization. Additionally, the nanoscale molecular signatures of these signaling islands and phase transitions are altered in response to changes in cytosolic Ca2+, showing differential sensitivities to Ca2+ bound Calmodulin. SAP97/hDLG forms nanosized molecular domains in both heterologous cells and hippocampal pyramidal neurons, with molecular signatures and exchange kinetics being modulated by the availability of alternatively spliced isoforms.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Hyeong-Jae Kim, Peter C. W. Lee, Jeong Hee Hong
Summary: This study reveals the enhancing effect of histamine on lamin-A/C expression in lung cancer cells. This enhancement is dependent on histamine-mediated intracellular calcium signaling and Ca/CaMKII activation. Additionally, histamine stimulation attenuates lung cancer cell motility.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Shuhang Dai, Elisa Venturini, Saveg Yadav, Xiaoxuan Lin, Dylan Clapp, Martin Steckiewicz, Angela M. Gocher-Demske, Arthur M. Edelman, D. Grahame Hardie
Summary: This study reveals the important role of CaMKK2 in mediating EGFR signaling in cancer cells, with regulation mechanisms involving both calcium-dependent and calcium-independent pathways. Additionally, CaMKK2 regulates transcription of key genes, impacting cell survival and proliferation.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2022)
Article
Oncology
Xiaoqiong Wang, Verity Johnson, Laura Johnson, James R. Cook
Summary: RNA sequencing (RNAseq) was used to detect rearrangements of BCL2, BCL6, and MYC in aggressive B-cell lymphomas, complementing the role of FISH by identifying cryptic rearrangements and partner genes. Combined use of FISH and RNAseq may optimize the detection of clinically important translocations.
Letter
Oncology
Siba El Hussein, Wei Wang, Sa A. Wang, Sanam Loghavi, Xiaoqiong Wang, Lianqun Qiu, Hong Fang, L. Jeffrey Medeiros, Phyu Aung, Carlos Torres Cabala, Jeffrey L. Jorgensen, Naveen Pemmaraju, Joseph D. Khoury
LEUKEMIA & LYMPHOMA
(2021)
Article
Pathology
Mahsa Khanlari, Xiaoqiong Wang, Sanam Loghavi, Sa A. Wang, Shaoying Li, Beenu Thakral, Carlos E. Bueso-Ramos, C. Cameron Yin, Rashmi Kanagal-Shamanna, Joseph D. Khoury, Keyur P. Patel, Uday R. Popat, L. Jeffrey Medeiros, Sergej Konoplev
Summary: Allogeneic hematopoietic stem cell transplantation is a curative option for myelofibrosis, but the resolution of morphological changes following the transplant is gradual. This study compared bone marrow samples of patients who achieved molecular remission by day 100 post allo-HSCT with those who had persistent molecular evidence of disease. Results showed that certain morphological changes in the bone marrow, such as the disappearance of myelofibrosis, dense megakaryocyte clusters, and endosteal localization of megakaryocytes, may suggest disease response.
ANNALS OF DIAGNOSTIC PATHOLOGY
(2022)
Article
Medical Laboratory Technology
Sergej Konoplev, Xiaoqiong Wang, Guilin Tang, Shaoying Li, Wei Wang, Jie Xu, Sherry A. Pierce, Fuli Jia, Jeffrey L. Jorgensen, Farhad Ravandi, Ghayas C. Issa, L. Jeffrey Medeiros, Sa A. Wang
Summary: AML with KMT2A rearrangement exhibits diverse immunophenotypic spectrum, with a significant subset showing no monocytic differentiation. Major immunophenotype changes are common at the time of relapse.
CYTOMETRY PART B-CLINICAL CYTOMETRY
(2022)
Article
Biotechnology & Applied Microbiology
Diego Chowell, Seong-Keun Yoo, Cristina Valero, Alessandro Pastore, Chirag Krishna, Mark Lee, Douglas Hoen, Hongyu Shi, Daniel W. Kelly, Neal Patel, Vladimir Makarov, Xiaoxiao Ma, Lynda Vuong, Erich Y. Sabio, Kate Weiss, Fengshen Kuo, Tobias L. Lenz, Robert M. Samstein, Nadeem Riaz, Prasad S. Adusumilli, Vinod P. Balachandran, George Plitas, A. Ari Hakimi, Omar Abdel-Wahab, Alexander N. Shoushtari, Michael A. Postow, Robert J. Motzer, Marc Ladanyi, Ahmet Zehir, Michael F. Berger, Mithat Gonen, Luc G. T. Morris, Nils Weinhold, Timothy A. Chan
Summary: A machine learning model integrating genomic, molecular, demographic, and clinical data accurately predicts clinical response to immune checkpoint blockade in cancer patients. The model outperformed predictions based on tumor mutational burden and provides quantitative assessments of key model features. This approach is expected to substantially improve clinical decision-making in immunotherapy and inform future interventions.
NATURE BIOTECHNOLOGY
(2022)
Letter
Hematology
Xiaoqiong Wang, Guilin Tang, Zhihong Hu, Hong Fang, Wei Wang, Zhenya Tang, Gokce A. Toruner, Ting Zhou, Courtney D. DiNardo, Guillermo Garcia-Manero, Srdan Verstovsek, Carlos E. Bueso-Ramos, L. Jeffrey Medeiros, Shimin Hu
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Pathology
Kerri-Ann Latchmansingh, Xiaoqiong Wang, Ramiro E. Verdun, Mario L. Marques-Piubelli, Francisco Vega, M. James You, Jennifer Chapman, Izidore S. Lossos
Summary: This study reveals that LMO2 expression is associated with longer overall survival in T-lymphoblastic leukemia/lymphoma and could serve as a promising prognostic marker and potential target for novel therapies.
Article
Pathology
Anindita Ghosh, Mario L. Marques-Piubelli, Xiaoqiong Wang, Tiffany G. Sheu, Joanne Cheng, Khaja Khan, Wei Lu, John Manning, Guilin Tang, Luisa M. Solis, Francisco Vega
Summary: CD2 and CD58 play critical roles in immune cells, and decreased CD2 expression in lymphoma may lead to immune evasion.
Article
Multidisciplinary Sciences
Jiawei Zhang, Yichao Gan, Hongzhi Li, Jie Yin, Xin He, Liming Lin, Senlin Xu, Zhipeng Fang, Byung-Wook Kim, Lina Gao, Lili Ding, Eryun Zhang, Xiaoxiao Ma, Junfeng Li, Ling Li, Yang Xu, David Horne, Rongzhen Xu, Hua Yu, Ying Gu, Wendong Huang
Summary: CDK2 is over-activated in many cancers and is a potential target for cancer therapy. The authors identified a non-ATP competitive inhibitor, Homoharringtonine, that disrupts the interaction between CDK2 and cyclins and induces autophagic degradation of CDK2 protein. This study provides insights into a potential mechanism for treating CDK2-dependent cancers.
NATURE COMMUNICATIONS
(2022)
Article
Oncology
Sara Haddock, Tyler J. Alban, Sevin Turcan, Hana Husic, Eric Rosiek, Xiaoxiao Ma, Yuxiang Wang, Tejus Bale, Alexis Desrichard, Vladimir Makarov, Sebastien Monette, Wei Wu, Rui Gardner, Katia Manova, Adrienne Boire, Timothy A. Chan
Summary: Mutations in IDH1 and IDH2 drive the development of gliomas by inducing phenotypic reprogramming and stem-like properties. The CD24-positive cell population in IDH-mutant tumors possesses remarkable stem-like characteristics and shows enhanced tumor initiating potency. The induction of a CD24-positive population is one mechanism by which IDH-mutant tumors acquire stem-like properties.
Article
Multidisciplinary Sciences
Zhipeng Meng, Fu-Long Li, Cao Fang, Benjamin Yeoman, Yunjiang Qiu, Ying Wang, Xiaomin Cai, Kimberly C. Lin, Di Yang, Min Luo, Vivian Fu, Xiaoxiao Ma, Yarui Diao, Filippo G. Giancotti, Bing Ren, Adam J. Engler, Kun-Liang Guan
Summary: This study reveals that class 3 Semaphorins (SEMA3s) activate the Hippo pathway to regulate tissue growth, angiogenesis, and tumorigenesis, highlighting the critical role of Hippo signaling in SEMA3 physiological function.
Article
Genetics & Heredity
Xiaoxiao Ma, Nadeem Riaz, Robert M. Samstein, Mark Lee, Vladimir Makarov, Cristina Valero, Diego Chowell, Fengshen Kuo, Douglas Hoen, Conall W. R. Fitzgerald, Hui Jiang, Jonathan Alektiar, Tyler J. Alban, Ivan Juric, Prerana Bangalore Parthasarathy, Yu Zhao, Erich Y. Sabio, Richa Verma, Raghvendra M. Srivastava, Lynda Vuong, Wei Yang, Xiao Zhang, Jingming Wang, Lawrence K. Chu, Stephen L. Wang, Daniel W. Kelly, Xin Pei, Jiapeng Chen, Rona Yaeger, Dmitriy Zamarin, Ahmet Zehir, Mithat Gonen, Luc G. T. Morris, Timothy A. Chan
Summary: Defects in pathways governing genomic fidelity are linked to improved response to immune checkpoint blockade therapy. Mutations in POLE/POLD1, specifically function-associated signatures, can enhance antitumor immunity and sensitivity to ICB. A mutant POLE/D1 function-associated signature-based model outperforms traditional approaches in identifying patients who benefit from ICB. The spectrum of mutational signatures correlates with biochemical features of neoantigens and aids in T cell recognition.
Article
Oncology
Phillip M. Rappold, Lynda Vuong, Josef Leibold, Nicholas H. Chakiryan, Michael Curry, Fengshen Kuo, Erich Sabio, Hui Jiang, Briana G. Nixon, Ming Liu, Anders E. Berglund, Andrew W. Silagy, Eduardo A. Mascareno, Mahdi Golkaram, Mahtab Marker, Albert Reising, Alexander Savchenko, John Millholland, Ying-Bei Chen, Paul Russo, Jonathan Coleman, Ed Reznik, Brandon J. Manley, Irina Ostrovnaya, Vladimir Makarov, Renzo G. DiNatale, Kyle A. Blum, Xiaoxiao Ma, Diego Chowell, Ming O. Li, David B. Solit, Scott W. Lowe, Timothy A. Chan, Robert J. Motzer, Martin H. Voss, A. Ari Hakimi
Summary: This study identifies myeloid inflammation as a key driver of disease recurrence in localized clear-cell renal cell carcinoma (ccRCC) and suggests that effector T-cell gene signatures are not associated with disease recurrence. Targeting immunosuppressive myeloid inflammation significantly reduces metastatic development in an immunocompetent mouse model.
Article
Oncology
Jia Li, Tingting Hong, Yue Wei, Lei Guo, Minjung Lee, Hui Yang, Caleb Class, Yaling Yang, Xiaoqiong Wang, Hua He, Stefan Siwko, M. James You, Yubin Zhou, Guillermo Garcia-Manero, Yun Huang
Summary: Epigenetic abnormalities in DNA hydroxymethylation (5hmC) have been found in patients with myeloid neoplasms, and these abnormalities can act as valuable markers for the disease. The study also shows that dynamic changes in 5hmC can affect the binding of transcription factors, altering transcriptional outputs and impacting cell survival and stemness.
CLINICAL EPIGENETICS
(2022)
Review
Oncology
Xiaoxiao Ma, Timothy A. Chan
Summary: This article discusses the demand and opportunities brought about by the rapid adoption of immune checkpoint blockade therapy. It presents new biomarker candidates and investigates their biological mechanisms and how they fit into the existing landscape of ICB biomarkers. Additionally, the article discusses the challenges of using biomarker-derived models to facilitate the development of new immunotherapies.
