IDH1 R132H mutation generates a distinct phospholipid metabolite profile in glioma.

Many patients with glioma harbor specific mutations in the isocitrate dehydrogenase gene IDH1 that associate with a relatively better prognosis. IDH1-mutated tumors produce the oncometabolite 2-hydroxyglutarate. Because IDH1 also regulates several pathways leading to lipid synthesis, we hypothesized that IDH1-mutant tumors have an altered phospholipid metabolite profile that would impinge on tumor pathobiology.

Phospholipase D1 and choline kinase-α are interactive targets in breast cancer.

A consistent metabolic hallmark observed in multiple cancers is the increase of cellular phosphocholine (PC) and total choline-containing compounds (tCho), which is closely related to malignant transformation, invasion, and metastasis. Enzymes in choline phospholipid metabolism present attractive targets to exploit for treatment, but require a clear understanding of the mechanisms underlying the altered choline phospholipid metabolism observed in cancer. Choline kinase-α (Chk-α) is an enzyme in the Kennedy pathway that phosphorylates free choline (Cho) to PC, and its upregulation in several cancers is a major contributor to increased PC levels.

In vivo ³¹P magnetic resonance spectroscopic imaging (MRSI) for metabolic profiling of human breast cancer xenografts.

Purpose: To study cancer associated with abnormal metabolism of phospholipids, of which several have been proposed as biomarkers for malignancy or to monitor response to anticancer therapy. We explored 3D (31) P magnetic resonance spectroscopic imaging (MRSI) at high magnetic field for in vivo assessment of individual phospholipids in two patient-derived breast cancer xenografts representing good and poor prognosis (luminal- and basal-like tumors).

Materials And Methods: Metabolic profiles from luminal-like and basal-like xenograft tumors were obtained in vivo using 3D (31) P MRSI at 11.

Interplay of choline metabolites and genes in patient-derived breast cancer xenografts.

Introduction: Dysregulated choline metabolism is a well-known feature of breast cancer, but the underlying mechanisms are not fully understood. In this study, the metabolomic and transcriptomic characteristics of a large panel of human breast cancer xenograft models were mapped, with focus on choline metabolism.

Methods: Tumor specimens from 34 patient-derived xenograft models were collected and divided in two.

Low-molecular contrast agent dynamic contrast-enhanced (DCE)-MRI and diffusion-weighted (DW)-MRI in early assessment of bevacizumab treatment in breast cancer xenografts.

Purpose: To investigate the effect of bevacizumab treatment on vascular architecture and function in two xenograft models with different angiogenic properties using diffusion-weighted magnetic resonance imaging (DW-MRI) and dynamic contrast-enhanced MRI (DCE-MRI).

Materials And Methods: Mice carrying basal-like (MAS98.12) or luminal-like (MAS98.

Quantitative (31)P HR-MAS MR spectroscopy for detection of response to PI3K/mTOR inhibition in breast cancer xenografts.

Purpose: Phospholipid metabolites are of importance in cancer studies, and have been suggested as candidate metabolic biomarkers for response to targeted anticancer drugs. The purpose of this study was to develop a phosphorus ((31) P) high resolution magic angle spinning magnetic resonance spectroscopy protocol for quantification of phosphorylated metabolites in intact cancer tissue.

Methods: (31) P spectra were acquired on a 14.

Spermine and citrate as metabolic biomarkers for assessing prostate cancer aggressiveness.

Separating indolent from aggressive prostate cancer is an important clinical challenge for identifying patients eligible for active surveillance, thereby reducing the risk of overtreatment. The purpose of this study was to assess prostate cancer aggressiveness by metabolic profiling of prostatectomy tissue and to identify specific metabolites as biomarkers for aggressiveness. Prostate tissue samples (n = 158, 48 patients) with a high cancer content (mean: 61.

Feasibility of MR metabolomics for immediate analysis of resection margins during breast cancer surgery.

In this study, the feasibility of high resolution magic angle spinning (HR MAS) magnetic resonance spectroscopy (MRS) of small tissue biopsies to distinguish between tumor and non-involved adjacent tissue was investigated. With the current methods, delineation of the tumor borders during breast cancer surgery is a challenging task for the surgeon, and a significant number of re-surgeries occur. We analyzed 328 tissue samples from 228 breast cancer patients using HR MAS MRS.

Metabolic biomarkers for response to PI3K inhibition in basal-like breast cancer.

Introduction: The phosphatidylinositol 3-kinase (PI3K) pathway is frequently activated in cancer cells through numerous mutations and epigenetic changes. The recent development of inhibitors targeting different components of the PI3K pathway may represent a valuable treatment alternative. However, predicting efficacy of these drugs is challenging, and methods for therapy monitoring are needed.

Metabolic profiles of brain metastases.

Metastasis to the brain is a feared complication of systemic cancer, associated with significant morbidity and poor prognosis. A better understanding of the tumor metabolism might help us meet the challenges in controlling brain metastases. The study aims to characterize the metabolic profile of brain metastases of different origin using high resolution magic angle spinning (HR-MAS) magnetic resonance spectroscopy (MRS) to correlate the metabolic profiles to clinical and pathological information.

Spatially matched in vivo and ex vivo MR metabolic profiles of prostate cancer -- investigation of a correlation with Gleason score.

MR metabolic profiling of the prostate is promising as an additional diagnostic approach to separate indolent from aggressive prostate cancer. The objective of this study was to assess the relationship between the Gleason score and the metabolic biomarker (choline + creatine + spermine)/citrate (CCS/C) measured by ex vivo high-resolution magic angle spinning MRS (HR-MAS MRS) and in vivo MRSI, and to evaluate the correlation between in vivo- and ex vivo-measured metabolite ratios from spatially matched prostate regions. Patients (n = 13) underwent in vivo MRSI prior to radical prostatectomy.

Differentiating diffuse World Health Organization grade II and IV astrocytomas with ex vivo magnetic resonance spectroscopy.

Background: The prognosis and treatment of astrocytomas, which are primary brain tumors, vary depending on the grade of the tumor, necessitating a precise preoperative classification. Magnetic resonance spectroscopy (MRS) provides information about metabolites in tissues and is an emerging noninvasive tool to improve diagnostic accuracy in patients with intracranial neoplasia.

Objective: To investigate whether ex vivo MRS could differentiate World Health Organization grade II (A-II) and IV astrocytomas (glioblastomas; GBM) and to correlate MR spectral profiles with clinical parameters.

Subtype-specific response to bevacizumab is reflected in the metabolome and transcriptome of breast cancer xenografts.

Antiangiogenic therapy with bevacizumab has shown varying results in breast cancer clinical trials. Identifying robust biomarkers for selecting patients who may benefit from such treatment and for monitoring response is important for the future use of bevacizumab. Two established xenograft models representing basal-like and luminal-like breast cancer were used to study bevacizumab treatment response on the metabolic and gene expression levels.

Peripheral zone prostate cancer localization by multiparametric magnetic resonance at 3 T: unbiased cancer identification by matching to histopathology.

Objectives: The aim of this study was to assess the diagnostic accuracy of peripheral zone prostate cancer localization by multiparametric magnetic resonance (MR) at 3 T using segmental matching of histopathology and MR images to avoid bias by image features in selection of cancer and noncancer regions.

Materials And Methods: Forty-eight patients underwent multiparametric MR imaging (MRI) on a 3 T system using a phased array body coil and spine coil elements for signal detection before prostatectomy. The examination included T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), dynamic contrast-enhanced imaging (DCE-MRI), and MR spectroscopic imaging (MRSI).

Serum levels of choline-containing compounds are associated with aerobic fitness level: the HUNT-study.

Background: Cardiovascular disease (CVD) is a leading cause of death worldwide, and the number of people at risk is continuously growing. New methods for early risk prediction are therefore needed to actuate prevention strategies before the individuals are diagnosed with CVD. Several studies report that aerobic fitness level, measured as maximal oxygen uptake (VO(2max)), is the single best predictor of future CVD mortality in healthy people.

Intravascular targets for molecular contrast-enhanced ultrasound imaging.

Molecular targeting of contrast agents for ultrasound imaging is emerging as a new medical imaging modality. It combines advances in ultrasound technology with principles of molecular imaging, thereby allowing non-invasive assessment of biological processes in vivo. Preclinical studies have shown that microbubbles, which provide contrast during ultrasound imaging, can be targeted to specific molecular markers.

Quality control of prostate 1 H MRSI data.

MRSI of prostate cancer provides a potential clinical tool to aid in the detection and characterisation of this disease, but its clinical use is limited by the need for the specialist training of radiologists to read these datasets. An essential part of this reading is the assessment of the usability and reliability of MRSI spectra because they can be affected by artefacts such as poor signal to noise, lipid signal contamination and broad resonances that could cause errors of interpretation. We have developed an automated quality control algorithm that classifies every voxel of an MRSI dataset as either acceptable or unacceptable for further analysis, based on the spectral profile alone.

Lactate and glycine-potential MR biomarkers of prognosis in estrogen receptor-positive breast cancers.

Breast cancer is a heterogeneous disease with a variable prognosis. Clinical factors provide some information about the prognosis of patients with breast cancer; however, there is a need for additional information to stratify patients for improved and more individualized treatment. The aim of this study was to examine the relationship between the metabolite profiles of breast cancer tissue and 5-year survival.

Glycerophosphodiester phosphodiesterase domain containing 5 (GDPD5) expression correlates with malignant choline phospholipid metabolite profiles in human breast cancer.

Altered choline phospholipid metabolism is a hallmark of cancer, leading to malignant choline metabolite profiles consisting of low glycerophosphocholine (GPC) and high phosphocholine (PC) in human breast cancers. Glycerophosphocholine phosphodiesterase (GPC-PDE) catalyzes the degradation of GPC to free choline and glycerol-3-phosphate. The gene(s) encoding for the GPC-PDE(s) responsible for GPC degradation in breast cancers have not yet been identified.

Prognostic value of metabolic response in breast cancer patients receiving neoadjuvant chemotherapy.

Background: Today's clinical diagnostic tools are insufficient for giving accurate prognosis to breast cancer patients. The aim of our study was to examine the tumor metabolic changes in patients with locally advanced breast cancer caused by neoadjuvant chemotherapy (NAC), relating these changes to clinical treatment response and long-term survival.

Methods: Patients (n = 89) participating in a randomized open-label multicenter study were allocated to receive either NAC as epirubicin or paclitaxel monotherapy.

In vivo MRI and histopathological assessment of tumor microenvironment in luminal-like and basal-like breast cancer xenografts.

Purpose: To explore tumor pathophysiology with special attention to the microenvironment in two molecular subtypes of human breast cancer using in vivo magnetic resonance imaging (MRI) and histopathology. The impact of tumor growth, size, and the influence of estradiol were also investigated.

Materials And Methods: Two orthotopic and directly transplanted human breast cancer models representing luminal-like and basal-like molecular subtypes were characterized by dynamic contrast-enhanced MRI and diffusion-weighted MRI.

Diffusion-weighted and dynamic contrast-enhanced MRI in evaluation of early treatment effects during neoadjuvant chemotherapy in breast cancer patients.

Purpose: To use dynamic contrast-enhanced (DCE) and diffusion-weighted (DW) MRI at 3 Tesla (T) for early evaluation of treatment effects in breast cancer patients undergoing neoadjuvant chemotherapy (NAC), and assess the reliability of DW-MRI.

Materials And Methods: DW- and DCE-MRI acquisitions of 15 breast cancer patients were performed before and after one cycle of NAC. MRI tumor diameter and volume, apparent diffusion coefficient (ADC) and kinetic parameters (K(trans), v(e)) were derived.

In vivo MRS of locally advanced breast cancer: characteristics related to negative or positive choline detection and early monitoring of treatment response.

Object: To explore factors determining the detection of total choline (tCho) by in vivo MR spectroscopy (MRS) in locally advanced breast cancer and to evaluate the ability of in vivo tCho to predict treatment response after one cycle of neoadjuvant chemotherapy (NAC).

Materials And Methods: Breast cancer patients (N=40) scheduled for NAC were examined with an MR protocol including in vivo single voxel proton MRS, dynamic contrast enhanced MRI and diffusion weighted MRI. tCho was quantified based on the signal-to-noise ratio.

Predicting long-term survival and treatment response in breast cancer patients receiving neoadjuvant chemotherapy by MR metabolic profiling.

Purpose: This study aimed to evaluate whether MR metabolic profiling can be used for prediction of long-term survival and monitoring of treatment response in locally advanced breast cancer patients during neoadjuvant chemotherapy (NAC).

Methods: High resolution magic angle spinning (HR MAS) MR spectra of pre- and post-treatment biopsies from 33 patients were acquired. Tissue concentrations of choline-containing metabolites (tCho), glycine and taurine were assessed using electronic reference to access in vivo concentration (ERETIC) of the signal and receiver operating characteristic (ROC) curves was used to define their potential to predict patient survival and treatment response.