Review
Biochemistry & Molecular Biology
Francisca Dias, Cristina Almeida, Ana Luisa Teixeira, Mariana Morais, Rui Medeiros
Summary: The development and progression of colorectal cancer are associated with changes in amino acid transporters, with tumor cells upregulating certain transporters to support increased amino acid intake for growth and proliferation. While therapeutic approaches targeting these transporters have been attempted, none have reached clinical application yet. MiRNA-based therapies are gaining attention, with several drugs in clinical trials showing promising results.
Article
Chemistry, Physical
Yufei Zhang, Qian Cheng, Yuhao Xue, Kai Yao, Madiha Zahra Syeda, Jian Xu, Jianheng Wu, Zhenjie Wang, Longguang Tang, Qingchun Mu
Summary: Glioma is a common brain tumor caused by glial cell growth. Current standard treatment involves surgery followed by radiation and chemotherapy, but the blood-brain barrier limits drug efficacy. L-type amino acid transporter 1 (LAT1) is highly expressed in glioma cells and facilitates drug transport across the blood-brain barrier. Temozolomide (TMZ) is a primary treatment for glioma, but resistance often occurs. Sorafenib, a multikinase inhibitor and inducer of ferroptosis, can enhance the effects of TMZ. Targeted nanoparticles loaded with TMZ and sorafenib increased cellular uptake, cytotoxicity, tumor accumulation, and anti-tumor efficacy compared to non-targeted nanoparticles.
Article
Biochemistry & Molecular Biology
Johanna Huttunen, Mahmoud Agami, Janne Tampio, Ahmed B. Montaser, Kristiina M. Huttunen
Summary: l-Type amino acid transporter 1 (LAT1) is widely expressed in the brain and placenta, with overexpression in several cancer cell types. While the structure and ligand interactions of LAT1 are well-known, its intracellular life cycle remains poorly understood. The functionality of LAT1 can be measured using different methods, but variations between laboratories make result comparison challenging. This study evaluates the usefulness of indirect cis-inhibition methods and direct cellular uptake methods in interpreting LAT1-ligand interactions, highlighting the importance of understanding intracellular kinetics and their impact on critical tissues like the brain.
Article
Biochemistry & Molecular Biology
Wenbin Wang, Haihua Pan, Feihua Ren, Hongxia Chen, Ping Ren
Summary: This study found that ASCT2 is highly expressed in pancreatic cancer and plays a significant role in regulating glutamine metabolism and maintaining redox homeostasis. Inhibition of ASCT2 can suppress the growth of pancreatic cancer cells and induce apoptosis, suggesting ASCT2 as a potential therapeutic target for pancreatic cancer.
BIOSCIENCE REPORTS
(2022)
Article
Gastroenterology & Hepatology
Cristina M. Hagen, Eva Roth, Theresia Reding Graf, Francois Verrey, Rolf Graf, Anurag Gupta, Giovanni Pellegrini, Nadege Poncet, Simone Mafalda Rodrigues Camargo
Summary: This study aimed to evaluate the role of LAT1 in the development and recovery of acute pancreatitis (AP). The results showed that LAT1 supports the regeneration of acinar cells after AP, with female mice lacking LAT1 exhibiting more pronounced alterations than male mice, indicating a sexual dimorphism in amino acid metabolism.
WORLD JOURNAL OF GASTROENTEROLOGY
(2022)
Article
Gastroenterology & Hepatology
Yunlong Sui, Namiko Hoshi, Ryuichi Ohgaki, Lingling Kong, Ryutaro Yoshida, Norihiro Okamoto, Masato Kinoshita, Haruka Miyazaki, Yuna Ku, Eri Tokunaga, Yuki Ito, Daisuke Watanabe, Makoto Ooi, Masakazu Shinohara, Kengo Sasaki, Yoh Zen, Takenori Kotani, Takashi Matozaki, Zibin Tian, Yoshikatsu Kanai, Yuzo Kodama
Summary: This study found that L-type amino acid transporter 1 (LAT1) is expressed constitutively in normal cells and plays an important role in tumor development and progression. The conditional deletion of LAT1 was shown to reduce the size and number of intestinal tumors and affect tumor initiation by reducing Wnt3 expression in Paneth cells. These findings partly explain how nutrient availability can influence the development of intestinal tumors.
JOURNAL OF GASTROENTEROLOGY
(2023)
Article
Oncology
Kazuko Kaneda-Nakashima, ZiJian Zhang, Yoshiyuki Manabe, Atsushi Shimoyama, Kazuya Kabayama, Tadashi Watabe, Yoshikatsu Kanai, Kazuhiro Ooe, Atsushi Toyoshima, Yoshifumi Shirakami, Takashi Yoshimura, Mitsuhiro Fukuda, Jun Hatazawa, Takashi Nakano, Koichi Fukase, Atsushi Shinohara
Summary: AMT has high affinity for LAT1, making At-211-AAMT a potential carrier for anti-cancer therapy by inhibiting tumor growth and inducing DNA double-stranded breaks. The accumulation of At-211-AAMT in vivo and its effectiveness in inhibiting tumor growth and metastasis suggest that At-211 could be useful for anti-cancer therapy, with LAT1 as a suitable target for radionuclide therapy.
Article
Biochemistry & Molecular Biology
Satish Kantipudi, Dimitrios Fotiadis
Summary: Studies have shown that 4F2hc-LAT1 is upregulated in cancer cells and serves as a potential anticancer target, while 4F2hc-LAT2 functions as a transporter in non-cancer cells. Cell assays are essential for determining the affinity and specificity of substrates and inhibitors for these transporters, providing valuable insights for drug development and disease research.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Oncology
Matthew L. Scarpelli, Debbie R. Healey, Shwetal Mehta, C. Chad Quarles
Summary: This study aimed to investigate the association between multiple biological factors and fluciclovine PET uptake in human glioblastoma, and found that fluciclovine PET uptake was significantly correlated with the level of the amino acid transporter ASCT2 in tumor cells, suggesting that fluciclovine PET may be useful for assessing amino acid metabolism in brain tumors.
FRONTIERS IN ONCOLOGY
(2022)
Review
Oncology
Catarina Lopes, Carina Pereira, Rui Medeiros
Summary: ASCT2 and LAT1 play crucial roles in cancer by impacting cell death resistance, proliferative signaling, cellular energetics regulation, angiogenesis, invasion, and metastasis. They are considered prognostic factors in various cancer types and potential therapeutic targets. Efforts have been made to develop inhibitors for these transporters, with JHP203 being the only compound in a Phase 1 clinical trial at present. Developing and testing novel inhibitors for ASCT2 and LAT1 could significantly improve cancer prognosis.
Article
Radiology, Nuclear Medicine & Medical Imaging
Anna Karlberg, Lars Kjelsberg Pedersen, Benedikte Emilie Vindstad, Anne Jarstein Skjulsvik, Hakon Johansen, Ole Solheim, Karoline Skogen, Kjell Arne Kvistad, Trond Velde Bogsrud, Kristin Smistad Myrmel, Guro F. Giskeodegard, Tor Ingebrigtsen, Erik Magnus Berntsen, Live Eikenes
Summary: This study aims to evaluate the correlation between anti-3-[F-18]FACBC PET combined with conventional MRI and histomolecular diagnosis in glioma diagnostics. The study found that anti-3-[F-18]FACBC PET has high uptake in the majority of gliomas and improves the accuracy of preoperatively predicted glioma diagnoses.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2023)
Article
Biochemistry & Molecular Biology
Jussi Karkkainen, Tuomo Laitinen, Magdalena Markowicz-Piasecka, Ahmed Montaser, Marko Lehtonen, Jarkko Rautio, Mikko Gynther, Antti Poso, Kristiina M. Huttunen
Summary: LAT1 is a crucial protein that can be utilized for improved or targeted drug delivery and restricting amino acid supply from cancer cells. The study found differences in transport efficiency and affinity of compounds for LAT1, important for designing effective drug delivery methods.
BIOORGANIC CHEMISTRY
(2021)
Article
Cell Biology
Sayuki Iwahashi, Jiajun Lyu, Kazuya Tokumura, Ryoma Osumi, Manami Hiraiwa, Takuya Kubo, Tetsuhiro Horie, Satoru Demura, Noriaki Kawakami, Taku Saito, Gyujin Park, Kazuya Fukasawa, Takashi Iezaki, Akane Suzuki, Akane Tomizawa, Hiroki Ochi, Hironori Hojo, Shinsuke Ohba, Eiichi Hinoi
Summary: This study identifies LAT1 in chondrocytes as an important regulator of postnatal spinal homeostasis. The results show that loss of LAT1 in chondrocytes leads to severe thoracic scoliosis with disorganization of chondrocytes, increased apoptosis, and decreased cell proliferation. Furthermore, the study reveals that LAT1 regulates the general amino acid control pathway, rather than the mechanistic target of rapamycin complex 1 pathway, in chondrocytes.
JOURNAL OF CELLULAR PHYSIOLOGY
(2022)
Article
Medicine, Research & Experimental
Katayun Bahrami, Juulia Järvinen, Tuomo Laitinen, Mika Reinisalo, Paavo Honkakoski, Antti Poso, Kristiina M. Huttunen, Jarkko Rautio
Summary: In this study, a series of LAT1-targeted drug-phenylalanine conjugates were evaluated. Through in vitro studies and induced-fit docking, it was concluded that smaller compounds were preferred for uptake by LAT1. The flexibility of the ligand played a crucial role in determining the transportability and interactions with LAT1. Introducing polar groups enhanced interactions, while compounds with a carbamate bond in the para-position of the aromatic ring displayed efficient transport efficiencies. The findings of this study have implications for designing CNS or antineoplastic drug candidates and discovering LAT1 inhibitors for cancer therapy.
MOLECULAR PHARMACEUTICS
(2023)
Review
Pharmacology & Pharmacy
Yoshikatsu Kanai
Summary: Cancer cells require a massive supply of nutrients, including amino acids. LAT1 is an amino acid transporter that is specifically expressed in cancer cells. High expression of LAT1 is associated with poor prognosis in patients. Inhibition of LAT1 can suppress cancer cell proliferation and tumor growth. LAT1 can also be used as a target for cancer diagnosis and specific delivery of anti-tumor drugs.
PHARMACOLOGY & THERAPEUTICS
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Ashesh B. Jani, Eduard Schreibmann, Peter J. Rossi, Joseph Shelton, Karen Godette, Peter Nieh, Viraj A. Master, Omer Kucuk, Mark Goodman, Raghuveer Halkar, Sherrie Cooper, Zhengjia Chen, David M. Schuster
JOURNAL OF NUCLEAR MEDICINE
(2017)
Article
Biochemistry & Molecular Biology
F. Tade, W. G. Wiles, G. Lu, B. Bilir, O. Akin-Akintayo, J. S. Lee, D. Patil, W. Yu, C. Ormenisan Gherasim, B. Fei, C. S. Moreno, A. O. Osunkoya, E. J. Teoh, S. Oka, H. Okudaira, M. M. Goodman, D. M. Schuster
Meeting Abstract
Oncology
E. Schreibmann, D. M. Schuster, P. R. Patel, J. W. Shelton, S. Cooper, H. Raghuveer, A. Jani
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2018)
Article
Radiology, Nuclear Medicine & Medical Imaging
Akinyemi A. Akintayo, O. A. Abiodun-Ojo, C. Weber, J. Sharma, C. Cohen, G. Sica, R. Halkar, M. M. Goodman, D. M. Schuster
MOLECULAR IMAGING AND BIOLOGY
(2019)
Article
Radiology, Nuclear Medicine & Medical Imaging
Tadashi Watabe, Kazuko Kaneda-Nakashima, Yuwei Liu, Yoshifumi Shirakami, Kazuhiro Ooe, Atsushi Toyoshima, Eku Shimosegawa, Mitsuhiro Fukuda, Atsushi Shinohara, Jun Hatazawa
JOURNAL OF NUCLEAR MEDICINE
(2019)
Meeting Abstract
Oncology
S. Tian, I. Sethi, X. Yang, A. Da Silva, J. Switchenko, T. K. Owonikoko, D. M. Schuster, W. J. Curran, K. A. Higgins
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2019)
Article
Radiology, Nuclear Medicine & Medical Imaging
Tadashi Watabe, Yuwei Liu, Kazuko Kaneda-Nakashima, Yoshifumi Shirakami, Thomas Lindner, Kazuhiro Ooe, Atsushi Toyoshima, Kojiro Nagata, Eku Shimosegawa, Uwe Haberkorn, Clemens Kratochwil, Atsushi Shinohara, Frederik Giesel, Jun Hatazawa
JOURNAL OF NUCLEAR MEDICINE
(2020)
Article
Oncology
Yuwei Liu, Tadashi Watabe, Kazuko Kaneda-Nakashima, Kazuhiro Ooe, Yoshifumi Shirakami, Atsushi Toyoshima, Eku Shimosegawa, Takashi Nakano, Atsushi Shinohara, Jun Hatazawa
TRANSLATIONAL ONCOLOGY
(2020)
Article
Biochemistry & Molecular Biology
Tadashi Watabe, Yuwei Liu, Kazuko Kaneda-Nakashima, Tatsuhiko Sato, Yoshifumi Shirakami, Kazuhiro Ooe, Atsushi Toyoshima, Eku Shimosegawa, Yang Wang, Hiromitsu Haba, Takashi Nakano, Atsushi Shinohara, Jun Hatazawa
Summary: This study compared the therapeutic effects of [At-211]NaAt and [I-131]NaI and found that [At-211]NaAt had superior efficacy against differentiated thyroid cancer. Dose-dependent therapeutic effects were observed in both treatments.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Kazuko Kaneda-Nakashima, Yoshifumi Shirakami, Tadashi Watabe, Kazuhiro Ooe, Takashi Yoshimura, Atsushi Toyoshima, Yang Wang, Hiromitsu Haba, Koichi Fukase
Summary: This study confirmed the impact of sodium/iodine symporter (NIS) expression on existing drugs through in vitro and in vivo tests. The results showed that sodium astatide ([At-211]NaAt) had a stronger tumor growth inhibitory effect compared to sodium iodide ([I-131]NaI), and the uptake rate correlated with NIS expression.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Yoshiharu Yonekura, Hiroshi Toki, Tadashi Watabe, Kazuko Kaneda-Nakashima, Yoshifumi Shirakami, Kazuhiro Ooe, Atsushi Toyoshima, Hiroo Nakajima, Noriyuki Tomiyama, Masako Bando
Summary: This study proposes a mathematical model for evaluating tumor response in an implanted tumor model, which was applied to data from a previous experiment on At-211 treatment in a thyroid cancer mouse model. The model can predict tumor response in other experimental settings and provide valuable information for planning the administration dose of radiopharmaceuticals in clinical trials.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Meeting Abstract
Oncology
A. Da Silva, P. Olcott, S. Tian, X. Yang, I. Sethi, S. M. Shirvani, S. Mazin, T. K. Owonikoko, J. D. Bradley, D. M. Schuster, K. A. Higgins
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2021)
Meeting Abstract
Oncology
V. R. Dhere, D. M. Schuster, S. Goyal, E. Schreibmann, B. Hershatter, P. J. Rossi, J. W. Shelton, P. R. Patel, A. Jani
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2021)
Meeting Abstract
Oncology
S. Tian, J. Switchenko, X. Yang, I. Sethi, A. Da Silva, C. Huntzinger, S. Shirvani, T. K. Owonikoko, D. M. Schuster, W. J. Curran, K. A. Higgins
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2020)
Meeting Abstract
Oncology
P. Olcott, S. M. Shirvani, S. Tian, I. Sethi, X. Yang, A. Da Silva, C. Huntzinger, S. Mazin, T. K. Owonikoko, D. M. Schuster, W. J. Curran, K. A. Higgins
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2020)
Article
Neurosciences
Xiaomei Lin, Tianyuyi Feng, Erheng Cui, Yunfei Li, Zhang Qin, Xiaohu Zhao
Summary: This study successfully established a rat model based on the genetic-environmental interaction, which exhibited phenotype characteristics similar to human AD in terms of cognitive function, brain microstructure, and immunohistochemistry. The genetic factor (APP mutation) and the environmental factor (acrolein exposure) accounted for 39.74% and 33.3% of the AD-like phenotypes in the model, respectively.
Article
Neurosciences
Gustavo Guimara Guerrero, Giovanna Bignoto Minhoto, Camilla dos Santos Tiburcio-Machado, Itza Amarisis Ribeiro Pinto, Claudio Antonio Federico, Marcia Carneiro Valera
Summary: The present study evaluated the influence of head and neck radiotherapy on the behavior and body weight gain in Wistar rats. The results demonstrated that different doses of radiation induced depressive behavior in the animals, and that the weight gain tended to be lower in the irradiated groups.
Article
Neurosciences
Ziwei Gao, Chao Lu, Yaping Zhu, Yuxin Liu, Yuesong Lin, Wenming Gao, Liyuan Tian, Lei Wu
Summary: This study reveals the underlying mechanisms of the rapid antidepressant effects of merazin hydrate (MH), which activates CaMKII to promote neuronal activities and proliferation in the hippocampus.
Article
Neurosciences
Kathleen E. Murray, Whitney A. Ratliff, Vedad Delic, Bruce A. Citron
Summary: Gulf War Illness (GWI) is a chronic disorder that affects approximately 30% of Veterans deployed to the Persian Gulf. This study found that exposure to toxicants during the Gulf War resulted in long-term changes in the morphology of dentate granule cells and that treatment with Nrf2 activator could improve neuronal health in the hippocampus.
Article
Neurosciences
Jing Li, Yan Zou, Xiangchuang Kong, Yangming Leng, Fan Yang, Guofeng Zhou, Bo Liu, Wenliang Fan
Summary: This study examines the functional connectivity changes in individuals with sudden sensorineural hearing loss (SSNHL) at the integrity, network, and edge levels. The findings reveal reduced intranetwork connectivity strength and increased internetwork connectivity in SSNHL patients. These alterations are associated with the duration of SSNHL and Tinnitus Handicap Inventory scores. The study provides crucial insights into the neural mechanisms of SSNHL and the brain's network-level responses to sensory loss.
Review
Neurosciences
Didier Majou, Anne-Lise Dermenghem
Summary: In the early stages of SAD, memory impairment is strongly correlated with cortical levels of soluble amyloid-beta peptide oligomers. A beta disrupts glutamatergic synaptic function and leads to cognitive deficits. This article describes the pathogenic mechanisms underlying cerebral amyloidosis, involving amyloid precursor protein synthesis, A beta residue clearance processes, and the role of specific molecules.
Article
Neurosciences
Jing Li, Yi Shan, Xiaojing Zhao, Guixiang Shan, Peng-Hu Wei, Lin Liu, Changming Wang, Hang Wu, Weiqun Song, Yi Tang, Guo-Guang Zhao, Jie Lu
Summary: This study investigates changes in brain anatomical structures and functional network connectivity after chronic complete thoracic spinal cord injury (cctSCI) and their impact on clinical outcomes. The findings reveal alterations in gray matter volume and functional connectivity in specific brain regions, indicating potential therapeutic targets and methods for tracking treatment outcomes.
Article
Neurosciences
Anllely Fernandez, Katherine Corvalan, Octavia Santis, Maxs Mendez-Ruette, Ariel Caviedes, Matias Pizarro, Maria -Teresa Gomez, Luis Federico Batiz, Peter Landgraf, Thilo Kahne, Alejandro Rojas-Fernandez, Ursula Wyneken
Summary: This study reveals the importance of SUMOylation in modulating the protein cargo of astrocyte-derived small extracellular vesicles (sEVs) and its potential impact on neurons.
Article
Neurosciences
Anika Luettig, Stefanie Perl, Maria Zetsche, Franziska Richter, Denise Franz, Marco Heerdegen, Ruediger Koehling, Angelika Richter
Summary: This study found that changes in c-Fos activity during short-term stimulation of the entopeduncular nucleus (EPN) are associated with improvement in dystonia, and also discovered that the cerebellum may be involved in the antidystonic effects.
Article
Neurosciences
Yanlin Tao, Wei Shen, Houyuan Zhou, Zikang Li, Ting Pi, Hui Wu, Hailian Shi, Fei Huang, Xiaojun Wu
Summary: Depression has a higher incidence in women compared to men, and this study investigated the impact of sex on depressive behaviors and underlying mechanisms using a corticosterone-induced depression model in mice. The results showed sex-specific anxiety and depression behaviors in the model group, as well as differences in protein expression and neurotransmitter levels between male and female mice. These findings enhance our understanding of sex-specific differences in depression and support tailored interventions.
Review
Neurosciences
Dnyandev G. Gadhave, Vrashabh V. Sugandhi, Chandrakant R. Kokare
Summary: This article discusses the characteristics and importance of the tight junctions of endothelial cells in the CNS, which act as a biological barrier known as the blood-brain barrier (BBB). It focuses on overcoming the challenges of delivering therapeutic agents to the brain in neurodegenerative disorders, particularly multiple sclerosis, through the use of biomaterials. The article also highlights the current limitations of animal models for studying multiple sclerosis and suggests a potential future research direction.
Article
Neurosciences
Li-Min Mao, Khyathi Thallapureddy, John Q. Wang
Summary: Propofol can enhance synapsin phosphorylation and modulate synaptic transmission in the mouse brain. The study reveals the potential role of synapsin as a substrate of propofol and its effects on neurotransmitter release machinery.
Article
Neurosciences
Syed Maaz Ahmed Rizvi, Abdul Baseer Buriro, Irfan Ahmed, Abdul Aziz Memon
Summary: This study explores the effects of prolonged mask usage on the human brain by analyzing EEG and physiological parameters. The results show that the mean EEG spectral power in alpha, beta, and gamma sub-bands of individuals wearing masks is smaller than those without masks. The performances on cognitive tasks and oxygen saturation level differ between the two groups, while blood pressure, body temperature, and heart rate are similar. The analysis also reveals that the occipital and frontal lobes exhibit the greatest variability in channel measurements.
Article
Neurosciences
Rui-Fang Ma, Lu-Lu Xue, Jin-Xiang Liu, Li Chen, Liu-Lin Xiong, Ting-Hua Wang, Fei Liu
Summary: This study observed changes in brain infarction and blood vessels in rats during neonatal hypoxic ischemic encephalopathy (NHIE) modeling using Transcranial Doppler Ultrasonography (TCD). Longer duration of hypoxia was associated with more severe nerve damage. TCD can dynamically monitor cerebral infarction after NHIE modeling, which may serve as a useful auxiliary method for evaluating animal experimental models.
Article
Neurosciences
Yuxiang Dai, Chen Yu, Lu Zhou, Longyang Cheng, Hongbin Ni, Weibang Liang
Summary: Overexpression of CXCR4 in glioma is correlated with patient survival, and its inhibition can reduce invasion and migration of glioma cells. Inhibiting Nur77 also decreases cancer progression associated with CXCR4.