In vivo MRS measurement of 2-hydroxyglutarate in patient-derived IDH-mutant xenograft mouse models versus glioma patients.
Javier
September 20, 2020
To produce a preclinical model isocitrate dehydrogenase (IDH) of the mutant glioma glioma patients and devise methods to test the compatibility MRS 2-hydroxyglutarate production (2HG) between preclinical models and patients.
Five patient-derived xenograft (PDX) rat glioma generated from two patients with IDH1 R132H mutation. A sequence PRESS adjusted at 9.4 T, with a phantom computer simulation and analysis, to improve the detection of 2HG in mice. 2HG and other metabolites in rats was measured using MRS optimized PDX at 9.4 T and compared with 3 T MRS measurements of metabolites in parent-tumor patients.
LCModel spectral fitting is done by using the home as a spectrum. metabolite levels were measured with reference to water.The PRESS TE optimized to 96 ms, which 2HG 2.25 ppm signal is narrow and overturned, causing a strict separation of resonance 2HG of adjacent signals from other metabolites. MRS optimized supplied precise detection 2HG in mice compared to short-TE MRS at 9.4 T. estimate of 2HG in PDX rats in good agreement with measurements of 2HG in 2HG production patients. The similarity between the model and parent PDX-tumor patients showed that the tumor PDX IDH maintain metabolic fingerprint parents and can serve as a preclinical model to improve our understanding of IDH mutations associated metabolic reprogramming.
Mutations start contributing to the development of cancer is sometimes present in premalignant cells. Is this mutation targeting therapy can eradicate premalignant cells is unclear. Acute myeloid leukemia (AML) is an interesting system to investigate the effects of preventive treatment for the disease is often preceded by premalignant state (clonal hematopoiesis or myelodysplastic syndromes).
In Npm1c / Dnmt3a mutant knock-in mice, the model of development of AML, leukemia preceded by an extended period of myeloid progenitor cell proliferation and self-renewal. We discovered that this self-renewal can be reversed with oral administration of small molecule (VTP-50 469) that targets MLL1-Menin chromatin complexes. The results of the preclinical support the hypothesis that high-risk individuals develop AML may benefit from targeted epigenetic therapy in the prevention setting.
In vivo MRS measurement of 2-hydroxyglutarate in patient-derived IDH-mutant xenograft mouse models versus glioma patients.
The acquisition of genetic mutations in a group A streptococcus at the site of infection and subsequent systemic spread of the mutant with a lethal mutation in a mouse model of streptococcal toxic shock syndrome.
Streptococcal toxic shock syndrome (STSS) is caused mainly by Streptococcus pyogenes (Group A Streptococcus, GAS), and has a mortality rate of 25%. Mutations in CsrRS and RopB, which suppresses the transcription of many virulence factors, was recently found in clinical isolates from STSS patients, but do not fully understand when and where GAS acquire a mutation in the host.
To resolve this question, we use our mouse models of human STSS GAS strains to recover from the injection sites, spleen and blood of mice dying with STSS-like symptoms, and analyzing sequence covR / covS genes and genes encoding ropB CsrRS and RopB. Fifteen of the twenty mice were inoculated transdermally into the muscle with GAS organisms become moribund with STSS-like symptoms after more than 20 days after the inoculation.
cDNA - Human Adult Normal Tissue: Skin
C1234218
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Brain
C1234035
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Colon
C1234090
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Heart
C1234122
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Ovary
C1234183
Biochain
40 reactions
EUR 1049
cDNA - Human Adult Normal Tissue: Theca
C1234261-10
Biochain
10 reactions
EUR 215
cDNA - Human Adult Normal Tissue: Breast
C1234086
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Kidney
C1234142
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Rectum
C1234206
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Spleen
C1234246
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Testis
C1234260
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Throat
C1234263-10
Biochain
10 reactions
EUR 215
cDNA - Human Adult Normal Tissue: Thymus
C1234264
Biochain
40 reactions
EUR 1049
cDNA - Human Adult Normal Tissue: Tongue
C1234267-10
Biochain
10 reactions
EUR 215
cDNA - Human Adult Normal Tissue: Tonsil
C1234268-10
Biochain
10 reactions
EUR 215
cDNA - Human Adult Normal Tissue: Uterus
C1234274
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Adipose
C1234003-10
Biochain
10 reactions
EUR 215
cDNA - Human Adult Normal Tissue: Adrenal
C1234004
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Bladder
C1234010
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Trachea
C1234160-10
Biochain
10 reactions
EUR 215
cDNA - Human Adult Normal Tissue: Stomach
C1234248
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Thyroid
C1234265
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Pancreas
C1234188
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Placenta
C1234200
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Prostate
C1234201
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Esophagus
C1234106
Biochain
40 reactions
EUR 385
Frozen Tissue Section - Human Adult Normal: Liver
T1234149
Biochain
5 slides
EUR 343
Total RNA - Human Adult Normal Tissue: Liver
R1234149-50
Biochain
50 ug
EUR 170
Paraffin Tissue Section - Human Adult Normal: Liver
T2234149
Biochain
5 slides
EUR 185
Total Protein - Human Adult Normal Tissue: Liver
P1234149
Biochain
1 mg
EUR 188
cDNA - Human Adult Normal Tissue: Whole Eye
C1234108-10
Biochain
10 reactions
EUR 468
cDNA - Human Adult Normal Tissue: Brain: Pons
C1234071-10
Biochain
10 reactions
EUR 215
cDNA - Human Adult Normal Tissue: Eye: Retina
C1234110-10
Biochain
10 reactions
EUR 468
cDNA - Human Adult Normal Tissue: Lymph Node
C1234161-10
Biochain
10 reactions
EUR 215
cDNA - Human Adult Normal Tissue: Bone Marrow
C1234024-10
Biochain
10 reactions
EUR 215
cDNA - Human Adult Normal Tissue: Spinal Cord
C1234234
Biochain
40 reactions
EUR 385
Membrane Protein - Human Adult Normal Tissue: Liver
P3234149
Biochain
0.1 mg
EUR 270
cDNA - Human Adult Normal Tissue: Colon Sigmoid
C1234095
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Uterus: Cervix
C1234275
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Uterus: Corpus
C1234276-10
Biochain
10 reactions
EUR 215
cDNA - Human Adult Normal Tissue: Uterus: Fundus
C1234278-10
Biochain
10 reactions
EUR 215
Human Adult Liver (Normal) Whole tissue lysate
HAL-1304
Alpha Diagnostics
1 mg
EUR 628.8
cDNA - Human Adult Normal Tissue: Brain: Amygdala
C1234036-10
Biochain
10 reactions
EUR 215
cDNA - Human Adult Normal Tissue: Fallopian Tube
C1234115-10
Biochain
10 reactions
EUR 215
cDNA - Human Adult Normal Tissue: Salivary Gland
C1234212-10
Biochain
10 reactions
EUR 215
cDNA - Human Adult Normal Tissue: Stomach: Cardia
C1234250-10
Biochain
10 reactions
EUR 215
cDNA - Human Adult Normal Tissue: Stomach: Corpus
C1234251-10
Biochain
10 reactions
EUR 215
cDNA - Human Adult Normal Tissue: Stomach: Fundus
C1234252-10
Biochain
10 reactions
EUR 215
FFPE Total RNA - Human Adult Normal Tissue: Liver
R2234149
Biochain
1 ug
EUR 689
cDNA - Human Adult Normal Tissue: Brain: Pituitary
C1234068-10
Biochain
10 reactions
EUR 261
cDNA - Human Adult Normal Tissue: Colon Ascending
C1234091
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Skeletal Muscle
C1234171
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Small Intestine
C1234226
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Stomach: Pylorus
C1234253-10
Biochain
10 reactions
EUR 215
cDNA - Rat Normal Tissue: Liver
C1434149
Biochain
40 reactions
EUR 385
cDNA - Dog Normal Tissue: Liver
C1734149
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Brain: Cerebellum
C1234039
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Colon Descending
C1234092
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Colon Transverse
C1234096
Biochain
40 reactions
EUR 385
FFPE Genomic DNA - Human Adult Normal Tissue: Liver
D2234149
Biochain
2 ug
EUR 684
cDNA - Human Adult Normal Tissue: Brain: Hippocampus
C1234052-10
Biochain
10 reactions
EUR 261
cDNA - Mouse Normal Tissue: Liver
C1334149
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Blood Vessel: Vein
C1234020-10
Biochain
10 reactions
EUR 215
cDNA - Human Adult Normal Tissue: Heart: Aorta Valve
C1234123-10
Biochain
10 reactions
EUR 215
cDNA - Human Adult Normal Tissue: Heart: Atrium (left)
C1234126
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Heart: Atrium (right)
C1234127
Biochain
40 reactions
EUR 385
Total RNA - Human Adult Normal Tissue: Liver: Left Lobe
R1234150-50
Biochain
50 ug
EUR 170
cDNA - Human Adult Normal Tissue: Blood Vessel: Artery
C1234013-10
Biochain
10 reactions
EUR 215
Total RNA - Human Adult Normal Tissue: Liver: Right Lobe
R1234151-50
Biochain
50 ug
EUR 170
cDNA - Human Adult Normal Tissue: Heart: Ventricle (left)
C1234138
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Brain: Cerebellum (left)
C1234040-10
Biochain
10 reactions
EUR 215
cDNA - Human Adult Normal Tissue: Brain: Cerebral Cortex
C1234042-10
Biochain
10 reactions
EUR 215
cDNA - Human Adult Normal Tissue: Brain: Corpus Callosum
C1234045-10
Biochain
10 reactions
EUR 215
cDNA - Human Adult Normal Tissue: Heart: Ventricle (right)
C1234139
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Small Intestine: Ileum
C1234227
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Brain: Cerebellum (right)
C1234041-10
Biochain
10 reactions
EUR 215
cDNA - Human Adult Normal Tissue: Brain: Olfactory (region)
C1234063-10
Biochain
10 reactions
EUR 215
cDNA - Human Adult Normal Tissue: Brain: Vermis Cerebelli
C1234082-10
Biochain
10 reactions
EUR 215
Total Protein - Human Adult Normal Tissue: Liver: Left Lobe
P1234150
Biochain
1 mg
EUR 188
cDNA - Human Adult Normal Tissue: Small Intestine: Jejunum
C1234230
Biochain
40 reactions
EUR 385
Total Protein - Human Adult Normal Tissue: Liver: Right Lobe
P1234151
Biochain
1 mg
EUR 188
cDNA - Human Adult Normal Tissue: Small Intestine: Duodenum
C1234101-10
Biochain
10 reactions
EUR 215
cDNA - Human Adult Normal Tissue: Lung: Left Lower Lobe
C1234155
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Lung: Left Upper Lobe
C1234156
Biochain
40 reactions
EUR 385
Membrane Protein - Human Adult Normal Tissue: Liver: Left Lobe
P3234150
Biochain
0.1 mg
EUR 270
cDNA - Human Adult Normal Tissue: Peripheral Blood Leukocyte
C1234148-10
Biochain
10 reactions
EUR 215
cDNA - Human Adult Normal Tissue: Lung: Right Lower Lobe
C1234157
Biochain
40 reactions
EUR 385
cDNA - Human Adult Normal Tissue: Lung: Right Upper Lobe
C1234159
Biochain
40 reactions
EUR 385
Total RNA - Human Adult Normal Tissue 5 Donor Pool: Liver
R1234149-P
Biochain
50 ug
EUR 370
cDNA - Human Adult Normal Tissue: Lung: Right Middle Lobe
C1234158
Biochain
40 reactions
EUR 385
cDNA - Monkey (Rhesus) Normal Tissue: Liver
C1534149
Biochain
40 reactions
EUR 385
cDNA - Monkey (Cynomolgus) Normal Tissue: Liver
C1534149-Cy
Biochain
40 reactions
EUR 385
Monkey (Cynomolgus) cDNA Normal Tissue: Liver
MC34-149
Alpha Diagnostics
10 rxn
EUR 498
Chicken (Normal/Adult) Universal (pool of tissue cDNA)
CHUC-565
Alpha Diagnostics
10 rxn
EUR 498
Genomic DNA - Human Adult Normal Tissue: Liver, from a single donor
D1234149
Biochain
100 ug
EUR 286
Total RNA - Human Adult Normal Tissue: Liver, Ambient temperature shipping
ATR1234149-50
Biochain
50 ug
EUR 185
FFPE and Frozen Matched Pair Total RNA: Human Adult Normal Tissue: Liver
R8234149-FP
Biochain
2x1 ug
EUR 1664
FFPE and Frozen Matched Pair Genomic DNA: Human Adult Normal Tissue: Liver
D8234149-FP
Biochain
2 x 2 ug
EUR 2099
Optimax First Strand cDNA Synthesis Kit
K4201100
Biochain
100 rnx
EUR 424
cDNA - Monkey (Rhesus) Normal Tissue: Liver: Left Lobe
C1534150
Biochain
40 reactions
EUR 385
cDNA - Monkey (Rhesus) Normal Tissue: Liver: Right Lobe
C1534151
Biochain
40 reactions
EUR 385
cDNA - Monkey (Cynomolgus) Normal Tissue: Liver: Left Lobe
C1534150-Cy
Biochain
40 reactions
EUR 385
cDNA - Monkey (Cynomolgus) Normal Tissue: Liver: Right Lobe
C1534151-Cy
Biochain
40 reactions
EUR 385
Matched Pair - cDNA - Human Primary Tumor and Normal Tissue: Liver
C8235149-PP
Biochain
10 reactions x2
EUR 530
igScript First Strand cDNA Synthesis Kit - 25 Reactions
4312
Intact Genomics
1/EA
EUR 178.8
igScript First Strand cDNA Synthesis Kit - 100 Reactions
4314
Intact Genomics
1/EA
EUR 453.6
Total RNA - Human Adult Normal Tissue: Lung
R1234152-50
Biochain
50 ug
EUR 170
Total RNA - Human Adult Normal Tissue: Skin
R1234218-50
Biochain
50 ug
EUR 284
Total RNA - Human Adult Normal Tissue: Brain
R1234035-50
Biochain
50 ug
EUR 170
Total RNA - Human Adult Normal Tissue: Cecum
R1234089-10
Biochain
10 ug
EUR 183
Total RNA - Human Adult Normal Tissue: Colon
R1234090-50
Biochain
50 ug
EUR 170
Total RNA - Human Adult Normal Tissue: Heart
R1234122-50
Biochain
50 ug
EUR 170
Total RNA - Human Adult Normal Tissue: Ovary
R1234183-10
Biochain
10 ug
EUR 643
Total RNA - Human Adult Normal Tissue: Penis
R1234194-50
Biochain
50 ug
EUR 170
Normal liver tissue array
LVN241
TissueArray
each
EUR 198
Description: Normal liver tissue array, 24 cases/24 cores, replaced by LVN241a
Normal liver tissue array
LVN241a
TissueArray
each
EUR 198
Description: Normal liver tissue array, 24 cases/24 cores, replacing LVN241
Total RNA - Human Adult Normal Tissue: Breast
R1234086-50
Biochain
50 ug
EUR 284
Total RNA - Human Adult Normal Tissue: Kidney
R1234142-50
Biochain
50 ug
EUR 170
Total RNA - Human Adult Normal Tissue: Rectum
R1234206-50
Biochain
50 ug
EUR 170
Total RNA - Human Adult Normal Tissue: Spleen
R1234246-50
Biochain
50 ug
EUR 170
Total RNA - Human Adult Normal Tissue: Testis
R1234260-50
Biochain
50 ug
EUR 170
Total RNA - Human Adult Normal Tissue: Throat
R1234263-10
Biochain
10 ug
EUR 191
Total RNA - Human Adult Normal Tissue: Thymus
R1234264-10
Biochain
10 µg
EUR 643
Total RNA - Human Adult Normal Tissue: Tongue
R1234267-50
Biochain
50 ug
EUR 170
Total RNA - Human Adult Normal Tissue: Tonsil
R1234268-10
Biochain
10 ug
EUR 191
Total RNA - Human Adult Normal Tissue: Uterus
R1234274-50
Biochain
50 ug
EUR 170
Total RNA - Human Adult Normal Tissue: Vagina
R1234283-10
Biochain
10 ug
EUR 191
Total RNA - Human Adult Normal Tissue: Adipose
R1234003-10
Biochain
10 ug
EUR 183
Total RNA - Human Adult Normal Tissue: Adrenal
R1234004-50
Biochain
50 ug
EUR 199
Total RNA - Human Adult Normal Tissue: Bladder
R1234010-50
Biochain
50 ug
EUR 170
Total RNA - Human Adult Normal Tissue: Trachea
R1234160-50
Biochain
50 ug
EUR 170
Total RNA - Human Adult Normal Tissue: Parotid
R1234190-50
Biochain
50 ug
EUR 199
Total RNA - Human Adult Normal Tissue: Stomach
R1234248-50
Biochain
50 ug
EUR 170
Total RNA - Human Adult Normal Tissue: Thyroid
R1234265-50
Biochain
50 ug
EUR 170
Frozen Tissue Array - Human Adult Normal Tissue, Multi-tissue I
T6234700-1
Biochain
1 slide
EUR 265
Frozen Tissue Array - Human Adult Normal Tissue, Multi-tissue I
T6234700-5
Biochain
5 slides
EUR 1004
Total Protein - Human Adult Normal Tissue: Lung
P1234152
Biochain
1 mg
EUR 188
Total Protein - Human Adult Normal Tissue: Skin
P1234218
Biochain
1 mg
EUR 188
Total RNA - Human Adult Normal Tissue: Appendix
R1234006-10
Biochain
10 ug
EUR 191
Total RNA - Human Adult Normal Tissue: Pancreas
R1234188-50
Biochain
50 ug
EUR 170
Total RNA - Human Adult Normal Tissue: Placenta
R1234200-50
Biochain
50 ug
EUR 170
Total RNA - Human Adult Normal Tissue: Prostate
R1234201-50
Biochain
50 ug
EUR 170
Total Protein - Human Adult Normal Tissue: Brain
P1234035
Biochain
1 mg
EUR 188
Total Protein - Human Adult Normal Tissue: Cecum
P1234089
Biochain
1 mg
EUR 188
Total Protein - Human Adult Normal Tissue: Colon
P1234090
Biochain
1 mg
EUR 188
Total Protein - Human Adult Normal Tissue: Heart
P1234122
Biochain
1 mg
EUR 188
Total Protein - Human Adult Normal Tissue: Ovary
P1234183
Biochain
1 mg
EUR 771
We found that all strains of GAS are propagated recovered from blood and spleen of mice dying have a good mutation in a gene or genes covR covS. Site mutations in the GAS strains recovered from blood and spleen identical in each mouse, while strains recovered from muscle strains including a mixture of disseminated, other mutant strains and the parent strain.