scholarly journals Preclinical Evaluation of 11 C-Sarcosine as a Substrate of Proton-Coupled Amino Acid Transporters and First Human Application in Prostate Cancer

2017 ◽  
Vol 58 (8) ◽  
pp. 1216-1223 ◽  
Author(s):  
Morand Piert ◽  
Xia Shao ◽  
David Raffel ◽  
Mathew S. Davenport ◽  
Jeffrey Montgomery ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Amino Acid ◽  
Amino Acid Transporters ◽  
Preclinical Evaluation

scholarly journals Accumulation of Trans-1-Amino-3-[18F]Fluorocyclobutanecarboxylic Acid in Prostate Cancer due to Androgen-Induced Expression of Amino Acid Transporters

2014 ◽  
Vol 16 (6) ◽  
pp. 756-764 ◽  
Author(s):  
Hiroyuki Okudaira ◽  
Shuntaro Oka ◽  
Masahiro Ono ◽  
Takeo Nakanishi ◽  
David M. Schuster ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Amino Acid ◽  
Amino Acid Transporters ◽  
Induced Expression

scholarly journals Pictorial essay: incidental findings on 18F-Fluciclovine PET/CT scan

2021 ◽  
Author(s):  
Cinzia Romagnolo ◽  
Chiara Cottignoli ◽  
Andrea Palucci ◽  
Giuseppina Biscontini ◽  
Fabio Massimo Fringuelli ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Amino Acid ◽  
Rectal Wall ◽  
Pancreatic Head ◽  
Pulmonary Nodules ◽  
Prostatic Hyperplasia ◽  
Amino Acid Transporters ◽  
Pet Ct ◽  
Pictorial Essay ◽  
Pet Radiopharmaceutical

Abstract Introduction Fluorine-18 (18F) Fluciclovine (anti-1-amino-3-18F-fluorocyclobutane- 1-carboxylic acid [FACBC]) is a synthetic amino acid labeled with 18F, currently used as PET radiopharmaceutical to investigating prostate cancer, namely in the recurrent setting. Fluciclovine is transported to cell membranes by amino acid transporters, such as LAT1 and ASCT2. The upregulation of LAT-1 and ASCT2 activities is typical of prostate cancer but is also present in other pathological conditions such as non-prostatic neoplasms (e.g., lung cancer) and in benign inflammatory process (e.g., benign prostatic hyperplasia, chronic prostatitis, high-grade prostatic hyperplasia intraepithelial). Methods In this short essay we present a retrospective FACBC PET/CT analysis consisting of a selection of the five most relevant cases of patients referred in our centre to FACBC PET/CT for prostate cancer, with concomitant FACBC uptake in sites atyipical for prostate cancer. Results These five selected cases demonstrate FACBC uptake at the level of the pancreatic head, adrenal incidentalomas, pulmonary nodules, mediastinal lymph nodes and neoformative tissue of the rectal wall. Discussion Clinical cases selected in this pictorial essay have demonstrated that Fluciclovine is not an exclusive and specific radiotracer for prostate cancer and, therefore, can induce misdiagnosis. In fact, incidental benign and malignant uptake might occur and should be further evaluated with clinical correlation or other imaging.

scholarly journals 18F-Fluciclovine PET metabolic imaging reveals prostate cancer tumour heterogeneity associated with disease resistance to androgen deprivation therapy

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Gaurav Malviya ◽  
Rachana Patel ◽  
Mark Salji ◽  
Rafael S. Martinez ◽  
Peter Repiscak ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Amino Acid ◽  
Cancer Cells ◽  
Androgen Deprivation Therapy ◽  
Metabolic Imaging ◽  
Amino Acid Transporters ◽  
Human Prostate Cancer ◽  
Tumour Heterogeneity ◽  
Castration Resistant

Abstract Background Prostate cancer is highly prevalent worldwide. Androgen deprivation therapy (ADT) remains the treatment of choice for incurable prostate cancer, but majority of patients develop disease recurrence following ADT. There is therefore an urgent need for early detection of treatment resistance. Methods Isogenic androgen-responsive (CWR22Res) and castration-resistant (22Rv1) human prostate cancer cells were implanted into the anterior lobes of the prostate in CD-1 Nu mice to generate prostate orthografts. Castrated mice bearing CWR22Res and 22Rv1 orthografts mimic clinical prostate cancer following acute and chronic ADT, respectively. 18F-Fluciclovine (1-amino-3-fluorocyclobutane-1-carboxylic acid) with a radiochemical purity of > 99% was produced on a FASTlab synthesiser. Ki67 staining in endpoint orthografts was studied. Western blot, quantitative RT-PCR and next-generation sequencing transcriptomic analyses were performed to assess the expression levels of amino acid transporters (including LAT1 and ASCT2, which have been implicated for Fluciclovine uptake). Longitudinal metabolic imaging with 18F-Fluciclovine-based positron emission tomography (PET) was performed to study tumour response following acute and chronic ADT. Results Both immunohistochemistry analysis of endpoint prostate tumours and longitudinal 18F-Fluciclovine imaging revealed tumour heterogeneity, particularly following ADT, with in vivo 18F-Fluciclovine uptake correlating to viable cancer cells in both androgen-proficient and castrated environment. Highlighting tumour subpopulation following ADT, both SUVpeak and coefficient of variation (CoV) values of 18F-Fluciclovine uptake are consistent with tumour heterogeneity revealed by immunohistochemistry. We studied the expression of amino acid transporters (AATs) for 18F-Fluciclovine, namely LAT1 (SLC7A5 and SLC3A2) and ASCT2 (SLC1A5). SLC7A5 and SLC3A2 were expressed at relatively high levels in 22Rv1 castration-resistant orthografts following chronic ADT (modelling clinical castration-resistant disease), while SLC1A5 was preferentially expression in CWR22Res tumours following acute ADT. Additional AATs such as SLC43A2 (LAT4) were shown to be upregulated following chronic ADT by transcriptomic analysis; their role in Fluciclovine uptake warrants investigation. Conclusion We studied in vivo 18F-Fluciclovine uptake in human prostate cancer orthograft models following acute and chronic ADT. 18F-Fluciclovine uptakes highlight tumour heterogeneity that may explain castration resistance and can be exploited as a clinical biomarker.

scholarly journals Amino Acid Transporters on the Guard of Cell Genome and Epigenome

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 125
Author(s):  
Uğur Kahya ◽  
Ayşe Sedef Köseer ◽  
Anna Dubrovska
Keyword(s):  
Amino Acid ◽  
Cancer Metabolism ◽  
Tumor Imaging ◽  
Redox Homeostasis ◽  
Amino Acid Uptake ◽  
Metabolic Reprogramming ◽  
Tumor Evolution ◽  
Amino Acid Transporters ◽  
Acid Uptake ◽  
Growth And Survival

Tumorigenesis is driven by metabolic reprogramming. Oncogenic mutations and epigenetic alterations that cause metabolic rewiring may also upregulate the reactive oxygen species (ROS). Precise regulation of the intracellular ROS levels is critical for tumor cell growth and survival. High ROS production leads to the damage of vital macromolecules, such as DNA, proteins, and lipids, causing genomic instability and further tumor evolution. One of the hallmarks of cancer metabolism is deregulated amino acid uptake. In fast-growing tumors, amino acids are not only the source of energy and building intermediates but also critical regulators of redox homeostasis. Amino acid uptake regulates the intracellular glutathione (GSH) levels, endoplasmic reticulum stress, unfolded protein response signaling, mTOR-mediated antioxidant defense, and epigenetic adaptations of tumor cells to oxidative stress. This review summarizes the role of amino acid transporters as the defender of tumor antioxidant system and genome integrity and discusses them as promising therapeutic targets and tumor imaging tools.

scholarly journals Pichia pastoris and the Recombinant Human Heterodimeric Amino Acid Transporter 4F2hc-LAT1: From Clone Selection to Pure Protein

2021 ◽  
Vol 4 (3) ◽  
pp. 51
Author(s):  
Satish Kantipudi ◽  
Daniel Harder ◽  
Sara Bonetti ◽  
Dimitrios Fotiadis ◽  
Jean-Marc Jeckelmann
Keyword(s):  
Amino Acid ◽  
Pichia Pastoris ◽  
Protein Complexes ◽  
Amino Acid Transporter ◽  
Amino Acid Transporters ◽  
Expression Host ◽  
Amino Acids And Derivatives ◽  
Heterodimeric Complex ◽  
Acid Transporter ◽  
And Function

Heterodimeric amino acid transporters (HATs) are protein complexes composed of two subunits, a heavy and a light subunit belonging to the solute carrier (SLC) families SLC3 and SLC7. HATs transport amino acids and derivatives thereof across the plasma membrane. The human HAT 4F2hc-LAT1 is composed of the type-II membrane N-glycoprotein 4F2hc (SLC3A2) and the L-type amino acid transporter LAT1 (SLC7A5). 4F2hc-LAT1 is medically relevant, and its dysfunction and overexpression are associated with autism and tumor progression. Here, we provide a general applicable protocol on how to screen for the best membrane transport protein-expressing clone in terms of protein amount and function using Pichia pastoris as expression host. Furthermore, we describe an overexpression and purification procedure for the production of the HAT 4F2hc-LAT1. The isolated heterodimeric complex is pure, correctly assembled, stable, binds the substrate L-leucine, and is thus properly folded. Therefore, this Pichia pastoris-derived recombinant human 4F2hc-LAT1 sample can be used for downstream biochemical and biophysical characterizations.

scholarly journals LAT1 and ASCT2 Related microRNAs as Potential New Therapeutic Agents against Colorectal Cancer Progression

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 195
Author(s):  
Francisca Dias ◽  
Cristina Almeida ◽  
Ana Luísa Teixeira ◽  
Mariana Morais ◽  
Rui Medeiros
Keyword(s):  
Colorectal Cancer ◽  
Amino Acid ◽  
Cancer Progression ◽  
Cell Metabolism ◽  
Tumor Development ◽  
Amino Acid Transporters ◽  
Epigenetic Alterations ◽  
Therapeutic Approaches ◽  
Colorectal Cancer Progression ◽  
Made In

The development and progression of colorectal cancer (CRC) have been associated with genetic and epigenetic alterations and more recently with changes in cell metabolism. Amino acid transporters are key players in tumor development, and it is described that tumor cells upregulate some AA transporters in order to support the increased amino acid (AA) intake to sustain the tumor additional needs for tumor growth and proliferation through the activation of several signaling pathways. LAT1 and ASCT2 are two AA transporters involved in the regulation of the mTOR pathway that has been reported as upregulated in CRC. Some attempts have been made in order to develop therapeutic approaches to target these AA transporters, however none have reached the clinical setting so far. MiRNA-based therapies have been gaining increasing attention from pharmaceutical companies and now several miRNA-based drugs are currently in clinical trials with promising results. In this review we combine a bioinformatic approach with a literature review in order to identify a miRNA profile with the potential to target both LAT1 and ASCT2 with potential to be used as a therapeutic approach against CRC.

scholarly journals Dietary methionine level alters growth, digestibility, and gene expression of amino acid transporters in meat-type chickens

2020 ◽  
Vol 99 (1) ◽  
pp. 67-75 ◽  
Author(s):  
Naiara S. Fagundes ◽  
Marie C. Milfort ◽  
Susan M. Williams ◽  
Manuel J. Da Costa ◽  
Alberta L. Fuller ◽  
...  
Keyword(s):  
Gene Expression ◽  
Amino Acid ◽  
Amino Acid Transporters ◽  
Methionine Level ◽  
Meat Type
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