scholarly journals Systemic muscle wasting and coordinated tumour response drive tumourigenesis

2019 ◽  
Author(s):  
Holly Newton ◽  
Yi-Fang Wang ◽  
Laura Camplese ◽  
André E.X. Brown ◽  
Susumu Hirabayashi
Keyword(s):  
Amino Acid ◽  
Tumour Growth ◽  
Muscle Wasting ◽  
Human Cancer ◽  
Tumour Response ◽  
Human Kidney ◽  
Amino Acid Derivative ◽  
Database Analysis ◽  
Powerful Approach ◽  
Transporter Expression

SUMMARYCancer cells demand excess nutrients to support their proliferation, but how tumours exploit extracellular amino acids during systemic metabolic pertubations remain incompletely understood. Here we use a Drosophila model of obesity-enhanced tumourigenesis to uncover a systemic host-tumour nutrient circuit that supports tumour growth. We demonstrate coordinate induction of systemic cachexia-like muscle wasting with tumour-autonomous SLC36-family amino acid transporter expression as a proline-scavenging programme to drive tumourigenesis. This coordinated induction of cachexia and SLC36-transporters pertains to human kidney cancer and associates with significantly worse survival outcomes. We identify Indole-3-propionic acid as an optimal amino acid derivative to rationally target the proline-dependency of tumour growth. Combining insights from whole-animal Drosophila models and human cancer database analysis provides a powerful approach towards the identification and therapeutic exploitation of the amino acid vulnerabilities of tumourigenesis in the context of perturbed systemic metabolic network.

scholarly journals Systemic muscle wasting and coordinated tumour response drive tumourigenesis

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Holly Newton ◽  
Yi-Fang Wang ◽  
Laura Camplese ◽  
Joao B. Mokochinski ◽  
Holger B. Kramer ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Cancer Cells ◽  
Metabolic Network ◽  
Tumour Growth ◽  
Muscle Wasting ◽  
Tumour Response ◽  
Amino Acid Derivative ◽  
Powerful Approach ◽  
Transporter Expression

Abstract Cancer cells demand excess nutrients to support their proliferation, but how tumours exploit extracellular amino acids during systemic metabolic perturbations remain incompletely understood. Here, we use a Drosophila model of high-sugar diet (HSD)-enhanced tumourigenesis to uncover a systemic host-tumour metabolic circuit that supports tumour growth. We demonstrate coordinate induction of systemic muscle wasting with tumour-autonomous Yorkie-mediated SLC36-family amino acid transporter expression as a proline-scavenging programme to drive tumourigenesis. We identify Indole-3-propionic acid as an optimal amino acid derivative to rationally target the proline-dependency of tumour growth. Insights from this whole-animal Drosophila model provide a powerful approach towards the identification and therapeutic exploitation of the amino acid vulnerabilities of tumourigenesis in the context of a perturbed systemic metabolic network.

Cancer cachexia and diabetes: similarities in metabolic alterations and possible treatment,

2014 ◽  
Vol 39 (6) ◽  
pp. 643-653 ◽  
Author(s):  
Stéphanie Chevalier ◽  
Samaneh Farsijani
Keyword(s):  
Amino Acid ◽  
Cancer Cachexia ◽  
Muscle Wasting ◽  
Muscle Protein ◽  
Human Cancer ◽  
Muscle Protein Synthesis ◽  
Glucose Disposal ◽  
Muscle Loss ◽  
Amino Acid Availability ◽  
Age Related

Cancer cachexia is a metabolic syndrome featuring many alterations typical of type 2 diabetes (T2D). While muscle wasting is a hallmark of cachexia, epidemiological evidence also supports an accelerated age-related muscle loss in T2D. Insulin resistance manifests in both conditions and impairs glucose disposal and protein anabolism by tissues. A greater contribution of gluconeogenesis to glucose production may limit amino acid availability for muscle protein synthesis, further aggravating muscle loss. In the context of inter-dependence between glucose and protein metabolism, the present review summarizes the current state of knowledge on alterations that may lead to muscle wasting in human cancer. By highlighting the similarities with T2D, a disease that has been more extensively studied, the objective of this review is to provide a better understanding of the pathophysiology of cancer cachexia and to consider potential treatments usually targeted for T2D. Nutritional approaches aimed at stimulating protein anabolism might include specially formulated food with optimal protein and amino acid composition. Because the gradual muscle loss in T2D may be attenuated by diabetes treatment, anti-diabetic drugs might be considered in cachexia treatment. Metformin emerges as a choice candidate as it acts both on reducing gluconeogenesis and improving insulin sensitivity, and has demonstrated tumour suppressor properties in multiple cancer types. Such a multimodal approach to slow or reverse muscle wasting in cachexia warrants further investigation.

scholarly journals Systematic Review and Meta-Analysis of In Vitro Anti-Human Cancer Experiments Investigating the Use of 5-Aminolevulinic Acid (5-ALA) for Photodynamic Therapy

2021 ◽  
Vol 14 (3) ◽  
pp. 229
Author(s):  
Yo Shinoda ◽  
Daitetsu Kato ◽  
Ryosuke Ando ◽  
Hikaru Endo ◽  
Tsutomu Takahashi ◽  
...  
Keyword(s):  
Systematic Review ◽  
Photodynamic Therapy ◽  
Aminolevulinic Acid ◽  
Human Cancer ◽  
Meta Analysis ◽  
Protoporphyrin Ix ◽  
Cell Types ◽  
Amino Acid Derivative ◽  
Photodynamic Diagnosis

5-Aminolevulinic acid (5-ALA) is an amino acid derivative and a precursor of protoporphyrin IX (PpIX). The photophysical feature of PpIX is clinically used in photodynamic diagnosis (PDD) and photodynamic therapy (PDT). These clinical applications are potentially based on in vitro cell culture experiments. Thus, conducting a systematic review and meta-analysis of in vitro 5-ALA PDT experiments is meaningful and may provide opportunities to consider future perspectives in this field. We conducted a systematic literature search in PubMed to summarize the in vitro 5-ALA PDT experiments and calculated the effectiveness of 5-ALA PDT for several cancer cell types. In total, 412 articles were identified, and 77 were extracted based on our inclusion criteria. The calculated effectiveness of 5-ALA PDT was statistically analyzed, which revealed a tendency of cancer-classification-dependent sensitivity to 5-ALA PDT, and stomach cancer was significantly more sensitive to 5-ALA PDT compared with cancers of different origins. Based on our analysis, we suggest a standardized in vitro experimental protocol for 5-ALA PDT.

Synthesis of amino acid derivative Schiff base copper(II) complexes by microwave and wet mechanochemical methods

2021 ◽  
Vol 98 (1) ◽  
pp. 100004
Author(s):  
Nao Otani ◽  
Tetsundo Furuya ◽  
Natsuki Katsuumi ◽  
Tomoyuki Haraguchi ◽  
Takashiro Akitsu
Keyword(s):  
Schiff Base ◽  
Amino Acid ◽  
Acid Derivative ◽  
Amino Acid Derivative

Resolution of racemic mixture of α-amino acid derivative through composite membrane

2011 ◽  
Vol 378 (1-2) ◽  
pp. 531-540 ◽  
Author(s):  
Kripal Singh ◽  
Pravin G. Ingole ◽  
Jayesh Chaudhari ◽  
Harshad Bhrambhatt ◽  
Amit Bhattacharya ◽  
...  
Keyword(s):  
Amino Acid ◽  
Acid Derivative ◽  
Composite Membrane ◽  
Amino Acid Derivative ◽  
Racemic Mixture

scholarly journals Prognostic significance of amino-acid transporter expression (LAT1, ASCT2, and xCT) in surgically resected tongue cancer

2014 ◽  
Vol 110 (10) ◽  
pp. 2506-2513 ◽  
Author(s):  
M Toyoda ◽  
K Kaira ◽  
Y Ohshima ◽  
N S Ishioka ◽  
M Shino ◽  
...  
Keyword(s):  
Amino Acid ◽  
Tongue Cancer ◽  
Prognostic Significance ◽  
Amino Acid Transporter ◽  
Acid Transporter ◽  
Transporter Expression

Asymmetric Synthesis of an Amino Acid Derivative from Achiral Aroyl Acrylamide by Reversible Michael Addition and Preferential Crystallization

2016 ◽  
Vol 22 (46) ◽  
pp. 16429-16432 ◽  
Author(s):  
Yuki Kaji ◽  
Naohiro Uemura ◽  
Yoshio Kasashima ◽  
Hiroki Ishikawa ◽  
Yasushi Yoshida ◽  
...  
Keyword(s):  
Amino Acid ◽  
Asymmetric Synthesis ◽  
Acid Derivative ◽  
Michael Addition ◽  
Amino Acid Derivative

scholarly journals Liposomes Can Achieve Enantioselective C–C Bond Formation of an α-Amino Acid Derivative in Aqueous Media

ACS Omega ◽  
2017 ◽  
Vol 2 (1) ◽  
pp. 91-97 ◽  
Author(s):  
Fumihiko Iwasaki ◽  
Keishi Suga ◽  
Yukihiro Okamoto ◽  
Hiroshi Umakoshi
Keyword(s):  
Amino Acid ◽  
Acid Derivative ◽  
Bond Formation ◽  
Aqueous Media ◽  
Amino Acid Derivative

scholarly journals Comparative in vivo studying of potential antineoplastic properties among of amino-acid derivative glycosides of the indolocarbazole (detailed report)

2018 ◽  
Vol 17 (2) ◽  
pp. 71-77
Author(s):  
I. S. Golubeva ◽  
O. V. Goryunova ◽  
N. P. Yavorskaya
Keyword(s):  
Amino Acid ◽  
Computer Method ◽  
Antineoplastic Activity ◽  
Amino Acid Derivative ◽  
Optimum Dose ◽  
Tumor Growth Inhibition ◽  
Antineoplastic Effect ◽  
Significant Probability

Introduction.The existence of the active metabolite (amino acid) residue in the of an indolocarbazole molecule changes physical-chemical and pro-medicinal properties of aminoacid derivatives glycosides of indolocarbazole. The computer method has earlier foretold low probability of their cytotoxic activity in vitro that was confirmed in the MTT-test on 5 lines of tumor cells. The same computer method predicted significant probability of antineoplastic activity of aminoacid derivatives glycosides of indolocarbazole in vivo that demands the experimental check. Purpose of the study– assessment of aminoacid derivatives glycosides of indolocarbazole as potential antitumor medications.Materials and methods.The research of antineoplastic activity of aminoacid derivatives glycosides of indolocarbazole was performed on mice tumoral models – cervical cancer СС5. Abdominal injections were made to CBA/Lac mice 5 times a day with 24 h interval. Observation of animals was continued till their death. The antineoplastic effect of medicines was estimated according to tumor growth inhibition, increase in life expectancy of experiental mice in comparison with control animals.Results.The optimum dose for this number of compounds, equal to 100 mg/kg is titrated. The antineoplastic activity of aminoacid derivatives glycosides of indolocarbazole on the model СС5 is estimated.Conclusions.On the basis of the obtained data the expanded research of antineoplastic properties of the selected 5 aminoacid derivatives glycosides of indolocarbazole is supposed to perform in vivo.

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