Micturition defects and altered bladder function in the klotho mutant mouse model of aging

Introduction and objectives: Symptoms associated with detrusor underactivity (DU) or an underactive bladder (UAB) can greatly affect a person’s quality of life and growing old is a major etiologic factor DU and UAB. Klotho gene has been associated with suppression several phenotypes of aging, and there is a moderate klotho expression in the bladder. Considering this, we hypothesized that klotho gene involved in the regulation of bladder function. Thus, we examined the genetic model of premature aging rodents with hypomorphic klotho expression to changes in bladder function.

Methods: Klotho mutant mice designated as a preclinical model of aging. Men and women have urinary klotho mice were measured at weeks 4, 6, and 8 through metabolic cages and test place void. Histology is rated at 4, 6, and 8 weeks. Lastly, the contraction of the bladder was assessed using bladder tissue bath lines. All the animals are gender- and age-matched wild-type littermates for analysis.

Result: the Void and bladder contraction test klotho mutant mice revealed that, similar to other aging models, has risen to cancel the frequency and decreased urinary volume per micturition event. In vitro contractile response to electrical stimulation is weaker and subtypes of muscarinic receptor expression is reduced in the mutant mice klotho bladder. These data suggest that bladder klotho mutant mice have impaired bladder function.

cDNA - Monkey (Cynomolgus) Normal Tissue: Cecum
C1534089-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Colon
C1534090-Cy	Biochain	40 reactions	EUR 385

cDNA - Monkey (Cynomolgus) Normal Tissue: Heart
C1534122-Cy	Biochain	40 reactions	EUR 385

cDNA - Monkey (Cynomolgus) Normal Tissue: Liver
C1534149-Cy	Biochain	40 reactions	EUR 385

cDNA - Monkey (Cynomolgus) Normal Tissue: Ovary
C1534183-Cy	Biochain	40 reactions	EUR 1049

cDNA - Monkey (Cynomolgus) Normal Tissue: Penis
C1534194-Cy	Biochain	40 reactions	EUR 578

Monkey (Cynomolgus) cDNA Normal Tissue: Liver
MC34-149	Alpha Diagnostics	10 rxn	EUR 498

cDNA - Monkey (Cynomolgus) Normal Tissue: Kidney
C1534142-Cy	Biochain	40 reactions	EUR 385

cDNA - Monkey (Cynomolgus) Normal Tissue: Spleen
C1534246-Cy	Biochain	40 reactions	EUR 385

cDNA - Monkey (Cynomolgus) Normal Tissue: Testis
C1534260-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Throat
C1534263-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Thymus
C1534264-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Tongue
C1534267-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Tonsil
C1534268-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Ureter
C1534273-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Uterus
C1534274-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Vagina
C1534283-Cy	Biochain	40 reactions	EUR 578

Monkey (Cynomolgus) cDNA Normal Tissue: Spleen
MC34-246	Alpha Diagnostics	10 rxn	EUR 498

cDNA - Monkey (Cynomolgus) Normal Tissue: Adipose
C1534003-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Adrenal
C1534004-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Bladder
C1534010-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Trachea
C1534160-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Parotid
C1534190-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Stomach
C1534248-Cy	Biochain	40 reactions	EUR 385

cDNA - Monkey (Cynomolgus) Normal Tissue: Thyroid
C1534265-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Appendix
C1534006-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Pancreas
C1534188-Cy	Biochain	40 reactions	EUR 385

cDNA - Monkey (Cynomolgus) Normal Tissue: Placenta
C1534200-Cy	Biochain	40 reactions	EUR 385

cDNA - Monkey (Cynomolgus) Normal Tissue: Prostate
C1534201-Cy	Biochain	40 reactions	EUR 578

Monkey (Cynomolgus) cDNA Normal Tissue: Pancreas
MC34-188	Alpha Diagnostics	10 rxn	EUR 498

cDNA - Monkey (Cynomolgus) Normal Tissue: Esophagus
C1534106-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Diaphragm
C1534169-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Epididymis
C1534105-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Gallbladder
C1534118-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Parathyroid
C1534189-Cy	Biochain	40 reactions	EUR 1180

cDNA - Monkey (Cynomolgus) Normal Tissue: Whole Eye
C1534108-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Brain: Pons
C1534071-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Brain:Cerebellum
C1534039-Cy	Biochain	40 reactions	EUR 385

cDNA - Monkey (Cynomolgus) Normal Tissue: Spinal Cord
C1534234-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Brain: Insula
C1534055-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Uterus: Cervix
C1534275-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Brain: Amygdala
C1534036-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Brain: Olfactory
C1534063-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Brain: Pituitary
C1534068-Cy	Biochain	40 reactions	EUR 715

cDNA - Monkey (Cynomolgus) Normal Tissue: Skeletal Muscle
C1534171-Cy	Biochain	40 reactions	EUR 385

cDNA - Monkey (Cynomolgus) Normal Tissue: Small Intestine
C1534226-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Brain: Hippocampus
C1534052-Cy	Biochain	40 reactions	EUR 715

cDNA - Monkey (Cynomolgus) Normal Tissue: Heart: Pericardium
C1534133-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Liver: Left Lobe
C1534150-Cy	Biochain	40 reactions	EUR 385

cDNA - Monkey (Cynomolgus) Normal Tissue: Brain: Diencephalon
C1534049-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Liver: Right Lobe
C1534151-Cy	Biochain	40 reactions	EUR 385

cDNA - Monkey (Cynomolgus) Normal Tissue: Brain: Frontal Lobe
C1534051-Cy	Biochain	40 reactions	EUR 385

cDNA - Monkey (Cynomolgus) Normal Tissue: Brain: Pineal Gland
C1534067-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Brain: Parietal Lobe
C1534066-Cy	Biochain	40 reactions	EUR 385

cDNA - Monkey (Cynomolgus) Normal Tissue: Brain: Temporal Lobe
C1534078-Cy	Biochain	40 reactions	EUR 385

cDNA - Monkey (Cynomolgus) Normal Tissue: Brain: Choroid Plexus
C1534044-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Brain: Occipital Lobe
C1534062-Cy	Biochain	40 reactions	EUR 385

cDNA - Monkey (Cynomolgus) Normal Tissue: Brain: Cerebral Cortex
C1534042-Cy	Biochain	40 reactions	EUR 385

cDNA - Monkey (Cynomolgus) Normal Tissue: Brain: Corpus Callosum
C1534045-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Small Intestine: Ileum
C1534227-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Brain: Precentral Gyrus
C1534073-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Brain: Medulla Oblongata
C1534057-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Brain: Postcentral Gyrus
C1534072-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Small Intestine: Jejunum
C1534230-Cy	Biochain	40 reactions	EUR 578

cDNA - Monkey (Cynomolgus) Normal Tissue: Small Intestine: Duodenum
C1534101-Cy	Biochain	40 reactions	EUR 578

cDNA - Human Adult Normal Tissue: Rectum
C1234206	Biochain	40 reactions	EUR 385

Total RNA - Monkey (Cynomolgus) Normal Tissue: Lung
R1534152-Cy	Biochain	50 ug	EUR 191

Total RNA - Monkey (Cynomolgus) Normal Tissue: Brain
R1534035-Cy	Biochain	50 ug	EUR 191

Total RNA - Monkey (Cynomolgus) Normal Tissue: Colon
R1534090-Cy	Biochain	50 ug	EUR 191

Total RNA - Monkey (Cynomolgus) Normal Tissue: Heart
R1534122-Cy	Biochain	50 ug	EUR 191

Total RNA - Monkey (Cynomolgus) Normal Tissue: Liver
R1534149-Cy	Biochain	50 ug	EUR 191

Total RNA - Monkey (Cynomolgus) Normal Tissue: Artery
R1534013-Cy	Biochain	50 ug	EUR 353

Total RNA - Monkey (Cynomolgus) Normal Tissue: Kidney
R1534142-Cy	Biochain	50 ug	EUR 191

Total RNA - Monkey (Cynomolgus) Normal Tissue: Bladder
R1534010-Cy	Biochain	50 ug	EUR 353

Total RNA - Monkey (Cynomolgus) Normal Tissue: Stomach
R1534248-Cy	Biochain	50 ug	EUR 191

Total RNA - Monkey (Cynomolgus) Normal Tissue: Pancreas
R1534188-Cy	Biochain	50 ug	EUR 191

Total RNA - Monkey (Cynomolgus) Normal Tissue: Diaphragm
R1534169-Cy	Biochain	50 ug	EUR 191

cDNA - Monkey (Rhesus) Normal Tissue: Rectum
C1534206	Biochain	40 reactions	EUR 385

Membrane Protein - Monkey (Cynomolgus) Normal Tissue: Brain
P3534035-Cy	Biochain	0.1 mg	EUR 270

FDA normal organ tissue array of cynomolgus monkey
CyFDA1h	TissueArray	each	EUR 354
Description: FDA normal organ tissue array of cynomolgus monkey, 20 cases/32 types/99 cores (core size 1.0mm), replacing CyFDA1g

Total RNA - Monkey (Cynomolgus) Normal Tissue: Colon Sigmoid
R1534095-Cy	Biochain	50 ug	EUR 353

Total RNA - Monkey (Cynomolgus) Normal Tissue: Colon Ascending
R1534091-Cy	Biochain	50 ug	EUR 353

Total RNA - Monkey (Cynomolgus) Normal Tissue: Skeletal Muscle
R1534171-Cy	Biochain	50 ug	EUR 191

Total RNA - Monkey (Cynomolgus) Normal Tissue: Small Intestine
R1534226-Cy	Biochain	50 ug	EUR 191

Total RNA - Monkey (Cynomolgus) Normal Tissue: Colon descending
R1534092-Cy	Biochain	50 ug	EUR 353

Total RNA - Monkey (Cynomolgus) Normal Tissue: Colon Transverse
R1534096-Cy	Biochain	50 ug	EUR 353

Frozen Tissue Section Panel - Monkey (Cynomolgus) Normal Tissue, Multi-tissue I
T6534448-Cy	Biochain	5 slides	EUR 504

Frozen Tissue Section Panel - Monkey (Cynomolgus) Normal Tissue, Multi-tissue III
T6534423-Cy	Biochain	5 slides	EUR 504

Paraffin Tissue Section Panel - Monkey (Cynomolgus) Normal Tissue, Multi-tissue II
T8534608-Cy	Biochain	5 slides	EUR 242

FDA multiple organ normal tissue array of cynomolgus monkey
CyFDA241	TissueArray	each	EUR 216
Description: FDA multiple organ normal tissue array of cynomolgus monkey, 6 cases/ 23 organs/ 24 cores

Total RNA - Monkey (Cynomolgus) Normal Tissue: Small Intestine: Duodenum
R1534101-Cy	Biochain	50 ug	EUR 353

Paraffin Tissue Section Panel - Monkey (Cynomolgus) Normal Tissue, Multi-tissue I, 8 different tissues
T8534448-Cy	Biochain	5 slides	EUR 242

Paraffin Tissue Section Panel - Monkey (Cynomolgus) Normal Tissue, Multi-tissue III, 8 different tissues
T8534423-Cy	Biochain	5 slides	EUR 242

Monkey (Cyno.) Normal Rectum Whole tissue lysate
MCL-1203	Alpha Diagnostics	1 mg	EUR 927.6

cDNA - Rat Normal Tissue: Rectum
C1434206	Biochain	40 reactions	EUR 578

cDNA - Dog Normal Tissue: Rectum
C1734206	Biochain	40 reactions	EUR 385

Frozen Tissue Section - Human Adult Normal: Rectum
T1234206	Biochain	5 slides	EUR 343

Total RNA - Human Adult Normal Tissue: Rectum
R1234206-50	Biochain	50 ug	EUR 170

cDNA - Mouse Normal Tissue: Rectum
C1334206	Biochain	40 reactions	EUR 578

Paraffin Tissue Section - Human Adult Normal: Rectum
T2234206	Biochain	5 slides	EUR 185

Total Protein - Human Adult Normal Tissue: Rectum
P1234206	Biochain	1 mg	EUR 188

Membrane Protein - Human Adult Normal Tissue: Rectum
P3234206	Biochain	0.1 mg	EUR 270

Human Adult Rectum (Normal) Whole tissue lysate
HAL-1373	Alpha Diagnostics	1 mg	EUR 628.8

Cynomolgus Monkey: Rectum (single section per slide) (5 slides/pack)
CyFPT021	TissueArray	5 slides	EUR 150

cDNA - Human Adult Normal Tissue: Lung
C1234152	Biochain	40 reactions	EUR 385

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: Liver
C1234149	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

Monkey (Rhesus) Normal Rectum Whole tissue lysate
MRL-1314	Alpha Diagnostics	1 mg	EUR 927.6

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: 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

Genomic DNA - Human Adult Normal Tissue: Rectum, from a single donor
D1234206	Biochain	100 ug	EUR 286

cDNA - Human Adult Normal Tissue: Esophagus
C1234106	Biochain	40 reactions	EUR 385

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

Monkey (Cynomolgus) control (non-immunized) serum, Adult mixed sex
NMCS-1	Alpha Diagnostics	1 ml	EUR 169.2

Monkey (Cynomolgus) control (non-immunized) serum, Adult mixed sex
NMCS-5	Alpha Diagnostics	5 ml	EUR 416.4

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

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

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 - 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

cDNA - Human Adult Normal Tissue: Brain: Hippocampus
C1234052-10	Biochain	10 reactions	EUR 261

cDNA - Human Adult Normal Tissue: Liver: Left Lobe
C1234150	Biochain	40 reactions	EUR 385

cDNA - Human Adult Normal Tissue: Liver: Right Lobe
C1234151	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

Conclusion: Klotho mutant mice recapitulate many of the characteristics of a dysfunctional bladder older, including bladder function changes. Given the short timeframe for bladder dysfunction and robustness of the model, this model will provide new insight to encourage the study of aging bladder.

Landscape metabolism of Genetically Engineered Mutant Rat Glioma Model IDH1

Understanding metabolic reprogramming aggressive brain tumor has potential applications for the treatment and imaging biomarkers. However, little is known about the nutritional requirements of isocitrate dehydrogenase 1 (IDH1) mutant glioma.

The IDH1 mutation involve acquisitions neomorphic enzymatic activity that produces D-2-hydroxyglutarate of α-ketoglutarate. In order to gain insight into this metabolism of malignant brain tumor, we performed metabolic profiling orthotopic tumor and contralateral area for glioma IDH1 mutant mouse model; as well as to test the use of glucose and glutamine in supplying major metabolic pathways such as glycolysis and the tricarboxylic acid (TCA).

We also revealed that the main substrate 2-hydroxyglutarate is glutamine in this model, and how the re-routing of this destructive utilization in the TCA. Our 13C tracing analysis, along with hyperpolarized magnetic resonance experiments, expressing the same glycolytic pathway active in both areas (tumor and contralateral) of the brain. Therefore, we describe the reprogramming of the central carbon metabolism associated with IDH1 mutations in genetically engineered mouse models that reflect tumor biology encountered in patients with glioma.

Bone is one of the sites most frequently in lung cancer metastatic non-small cell (NSCLC). Osimertinib, with and without bevacizumab (BV), has been studied in patients with advanced NSCLC. However, the efficacy of drugs on bone metastases of NSCLC has not been studied. H1975 human NSCLC cell lines, expressing red fluorescent protein (H1975-RFP), it orthotopically injected into the tibia of nude mice. established mouse models were randomized into four treatment groups of nine rats: Control; BV only; osimertinib only; osimertinib and BV combination.