Summary of Study ST001016

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 IDST001016
Study TitleSphingolipid Concentrations in Muscle Tissue of Muscle Wasting in Cancer Cachexia (part-III)
Study SummarySphingolipid 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 Date2018-07-15
Analysis Type DetailLC-MS
Release Date2020-07-15
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:SU001055
Subject Type:Human
Subject Species:Homo sapiens
Taxonomy ID:9606
Species Group:Mammals

Factors:

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

mb_sample_id local_sample_id Grouping Gender
SA063672ms6646-12Control Female
SA063673ms6646-5Control Female
SA063674ms6646-4Control Female
SA063675ms6646-17Control Female
SA063676ms6646-22Control Female
SA063677ms6646-20Control Male
SA063678ms6646-9Control Male
SA063679ms6646-10Control Male
SA063680ms6646-25Control Male
SA063681ms6646-6Control Male
SA063682ms6646-19Weight Losing Female
SA063683ms6646-18Weight Losing Female
SA063684ms6646-2Weight Losing Female
SA063685ms6646-28Weight Losing Female
SA063686ms6646-15Weight Losing Female
SA063687ms6646-24Weight Losing Male
SA063688ms6646-27Weight Losing Male
SA063689ms6646-21Weight Losing Male
SA063690ms6646-14Weight Losing Male
SA063691ms6646-1Weight Losing Male
SA063692ms6646-8Weight Stable Female
SA063693ms6646-26Weight Stable Female
SA063694ms6646-29Weight Stable Female
SA063695ms6646-13Weight Stable Female
SA063696ms6646-3Weight Stable Female
SA063697ms6646-30Weight Stable Male
SA063698ms6646-16Weight Stable Male
SA063699ms6646-7Weight Stable Male
SA063700ms6646-11Weight Stable Male
SA063701ms6646-23Weight Stable Male
Showing results 1 to 30 of 30

Collection:

Collection ID:CO001049
Collection Summary:Tissue and blood donated from Cancer Cachexia Program at Ohio State University
Sample Type:Muscle

Treatment:

Treatment ID:TR001069
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:SP001062
Sampleprep Summary:sphingolipid concentrations using muscle tissue

Combined analysis:

Analysis ID AN001658
Analysis type MS
Chromatography type Reversed phase
Chromatography system Waters Acquity
Column Waters Acquity BEH C8 (150 x 2mm,1.7um)
MS Type ESI
MS instrument type Triple quadrupole
MS instrument name Thermo Quantum Ultra
Ion Mode POSITIVE
Units ug/vial

Chromatography:

Chromatography ID:CH001169
Instrument Name:Waters Acquity
Column Name:Waters Acquity BEH C8 (150 x 2mm,1.7um)
Chromatography Type:Reversed phase

MS:

MS ID:MS001533
Analysis ID:AN001658
Instrument Name:Thermo Quantum Ultra
Instrument Type:Triple quadrupole
MS Type:ESI
Ion Mode:POSITIVE
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