Summary of Study ST001005

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000680. The data can be accessed directly via it's Project DOI: 10.21228/M8S684 This work is supported by NIH grant, U2C- DK119886.

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Study IDST001005
Study TitleAmino Acid Concentrations in Muscle Tissue of Muscle Wasting in Cancer Cachexia (part I)
Study SummaryAmino Acid Concentrations of Muscle Wasting in Cancer Cachexia. Muscle samples from 10 control patients, 10 weight stable pancreatic cancer patients, and 10 pancreatic cancer patients with significant weight loss. Samples are divided evenly between males and females.
Institute
Mayo Clinic
Last NameGuttridge
First NameDenis
Address520 Biomedical Research Tower 460 W. 12th Avenue Columbus, OH 43210
Emaildenis.guttridge@osumc.edu
Phone614-688-3137
Submit Date2018-07-12
Analysis Type DetailLC-MS
Release Date2019-07-17
Release Version1
Denis Guttridge Denis Guttridge
https://dx.doi.org/10.21228/M8S684
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR000680
Project DOI:doi: 10.21228/M8S684
Project Title:Mayo Pilot and Feasibility: Metabolomics of Muscle Wasting in Cancer Cachexia
Project Summary:Cachexia is a debilitating syndrome that results in severe, involuntary weight loss due to the depletion of skeletal muscle mass. This syndrome occurs in a majority of cancers and contributes to approximately one third of all cancer deaths. Currently, no effective therapy exists to combat this malignant disorder, and disappointing results from recent Phase III clinical trials indicate that a cachexia treatment is not likely to appear soon. Thus, it is clear that greater knowledge of the mechanisms driving muscle wasting in cachexia is needed in order to identify new therapeutic targets and stimulate new clinical trials. Our approach to gaining this knowledge has been to work with muscle biopsies from pancreatic cancer patients, since this population is highly prone to cachexia. We have also been expanding our studies beyond the classical mouse models of cancer cachexia in hopes of finding a new model that better recapitulates the human disease. We recently undertook RNA-Seq analysis comparing muscle biopsies from pancreatic cancer patients with and without cachexia, which has been exciting since this type of analysis has not yet been performed in patient samples. Preliminary results revealed that cachectic muscle was associated with alterations in metabolism. These data provide the rationale for performing metabolomics to ascertain whether specific metabolic pathways or metabolites can be identified as potential drivers of muscle wasting in cachexia or be used as biomarker of cachexia, which the field desperately needs. An additional need is a well-validated animal model of cancer cachexia that accurately reflects the human condition, which can be used to test mechanisms and pre-clinical compounds. We propose to perform these studies under the Mayo Clinic Metabolomics Resource Core Pilot and Feasibility Grant program to: 1) Identify metabolic alterations and biomarkers of pancreatic cancer-induced muscle wasting; and 2) Identify a suitable mouse model that recapitulates the metabolic imbalance of muscles from pancreatic cancer cachexia patients. By performing these studies, we will accelerate our understanding of the underlying causes of muscle wasting, which should translate to improving the current pipeline of anticachexia therapies.
Institute:Mayo Clinic
Last Name:Guttridge
First Name:Denis
Address:520 Biomedical Research Tower 460 W. 12th Avenue Columbus, OH 43210
Email:denis.guttridge@osumc.edu
Phone:614-688-3137

Subject:

Subject ID:SU001044
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Grouping
SA063348ms6644-25Control
SA063349ms6644-10Control
SA063350ms6644-17Control
SA063351ms6644-20Control
SA063352ms6644-22Control
SA063353ms6644-9Control
SA063354ms6644-12Control
SA063355ms6644-4Control
SA063356ms6644-5Control
SA063357ms6644-6Control
SA063358ms6644-18Weight Losing
SA063359ms6644-19Weight Losing
SA063360ms6644-24Weight Losing
SA063361ms6644-21Weight Losing
SA063362ms6644-2Weight Losing
SA063363ms6644-1Weight Losing
SA063364ms6644-28Weight Losing
SA063365ms6644-14Weight Losing
SA063366ms6644-27Weight Losing
SA063367ms6644-15Weight Losing
SA063368ms6644-30Weight Stable
SA063369ms6644-26Weight Stable
SA063370ms6644-29Weight Stable
SA063371ms6644-16Weight Stable
SA063372ms6644-7Weight Stable
SA063373ms6644-3Weight Stable
SA063374ms6644-8Weight Stable
SA063375ms6644-11Weight Stable
SA063376ms6644-13Weight Stable
SA063377ms6644-23Weight Stable
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Collection:

Collection ID:CO001038
Collection Summary:Tissue and blood donated from Cancer Cachexia Program at Ohio State University
Sample Type:Muscle

Treatment:

Treatment ID:TR001058
Treatment Summary:Cancer cachexia is a multi-factorial syndrome accompanying advanced cancer, with the most notable symptom being unintentional weight loss. Cachectic patients lose both adipose tissue and skeletal muscle, with skeletal muscle loss and its associated weakness contributing to the morbidity and mortality of these patients. Despite three decades of research into mechanisms driving muscle wasting due to cancer, to date, an approved pharmacological therapy to prevent or treat cancer cachexia is still lacking. Our laboratory focuses on cancer cachexia in patients with pancreatic cancer, as up to 85% of these patients experience weight loss. Cachexia often occurs early in the progression of pancreatic cancer, making clear that cachexia in these patients is not simply a result of end-stage disease. Further, with perhaps more than ΒΌ of all pancreatic cancer deaths resulting from muscle weakness as opposed to tumor burden, cachexia also significantly contributes to mortality due to pancreatic cancer. Because little progress has been made in improving treatment outcomes, addressing cancer-induced muscle wasting is perhaps the best strategy to prolong pancreatic cancer patient survival and increase patient quality of life. In an effort to better understand the mechanisms driving pancreatic cancer-induced muscle wasting, the Cancer Cachexia Program at Ohio State University has begun a Pancreatic Cancer Cachexia Tissue Bank. To date, over 130 patients undergoing attempted resection for pancreatic cancer or other abdominal surgeries have donated muscle and blood to our bank. A unique aspect of our tissue bank is our focus on patients eligible for resection. In contrast to other studies using patients with late-stage disease, our patients are not end-stage, as they are considered healthy enough to undergo a major operation.

Sample Preparation:

Sampleprep ID:SP001051
Sampleprep Summary:amino acids concentrations using muscle tissue

Combined analysis:

Analysis ID AN001647
Analysis type MS
Chromatography type Reversed phase
Chromatography system Waters Acquity
Column Waters Acquity BEH C18 (150 x 2.1mm,1.7um)
MS Type ESI
MS instrument type Triple quadrupole
MS instrument name Thermo Quantum Ultra
Ion Mode POSITIVE
Units nmoles/vial

Chromatography:

Chromatography ID:CH001159
Instrument Name:Waters Acquity
Column Name:Waters Acquity BEH C18 (150 x 2.1mm,1.7um)
Chromatography Type:Reversed phase

MS:

MS ID:MS001523
Analysis ID:AN001647
Instrument Name:Thermo Quantum Ultra
Instrument Type:Triple quadrupole
MS Type:ESI
Ion Mode:POSITIVE
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