Colorectal cancer (CRC) is a common malignancy that has the second highest incidence and mortality rate. Although there are many personalized treatment options for CRC, the therapeutic effects are ultimately limited by drug resistance. Studies have aimed to block the initiation and progression of CRC by inducing cell death to overcome this obstacle. Substantial evidence has indicated that both autophagy and ferroptosis play important regulatory roles in CRC. Autophagy, a lysosome-dependent process by which cellular proteins and organelles are degraded, is the basic mechanism for maintaining cell homeostasis. The duality and complexity of autophagy in cancer therapy is a hot topic of discussion. Ferroptosis, a regulated cell death pathway, is associated with iron accumulation-induced lipid peroxidation. The activation of ferroptosis can suppress CRC proliferation, invasion and drug resistance. Furthermore, recent studies have suggested an interaction between autophagy and ferroptosis. Autophagy can selectively degrade certain cellular contents to provide raw materials for ferroptosis, ultimately achieving antitumor and anti-drug resistance. Therefore, exploring the interaction between autophagy and ferroptosis could reveal novel ideas for the treatment of CRC. In this review, we describe the mechanisms of autophagy and ferroptosis, focusing on their roles in CRC and the crosstalk between them.

• Ferroptosis
• Autophagy
• Cell death
• Colorectal cancer
• Iron
• Lipid peroxidation

• Apoptosis
• Melanoma
• Metastasis
• Morusin
• Proliferation
• p53

• 81872071 he National Natural Science Foundation of China
• cstc2019jcyj-zdxmX0033 the Natural Science Foundation of Chongqing
• XYDS201912 the Fundamental Research Funds for the Central Universities
• CXTDX201601010 Chongqing University Innovation Team Building Program funded projects

• National Natural Science Foundation of China
• Suzhou City
• Zhejiang Province

• N-MYC
• miRNAs
• neuroblastoma
• p53 family proteins
• targeted anticancer therapy

• anticancer
• apoptotic protein
• deubiquitinating enzymes
• ubiquitin‑proteasome system

• antiproliferative
• molecular docking
• network pharmacology
• triple-negative breast cancer
• ursolic acid

Objective: We aimed to explore the prognostic value of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) genes in gastric cancer (GC). Methods: The RNA-sequencing (RNA-seq) expression data for 351 GC patients and other relevant clinical data were acquired from The Cancer Genome Atlas (TCGA). Survival analysis and a genome-wide gene set enrichment analysis (GSEA) were performed to define the underlying molecular value of the ADAMTS genes in GC development. Besides, qRT-PCR and immunohistochemistry were all employed to validate the relationship between the expression of these genes and GC patient prognosis. Results: The Log rank test with both Cox regression and Kaplan–Meier survival analyses showed that ADAMTS6 expression profile correlated with the GC patients clinical outcome. Patients with a high expression of ADAMTS6 were associated with poor overall survival (OS). Comprehensive survival analysis of the ADAMTS genes suggests that ADAMTS6 might be an independent predictive factor for the OS in patients with GC. Besides, GSEA demonstrated that ADAMTS6 might be involved in multiple biological processes and pathways, such as the vascular endothelial growth factor A (VEGFA), kirsten rat sarcoma viral oncogene (KRAS), tumor protein P53, c-Jun N-terminal kinase (JNK), cadherin (CDH1) or tumor necrosis factor (TNF) pathways. It was also confirmed by immunohistochemistry and qRT-PCR that ADAMTS6 is highly expressed in GC, which may be related to the prognosis of GC patients. Conclusion: In summary, our study demonstrated that ADAMTS6 gene could be used as a potential molecular marker for GC prognosis.

• ADAMTS
• gastric cancer
• mRNA
• prognosis

• BRCA1/2
• KRAS
• PIK3CA
• TP53
• gene mutation
• liquids biopsy
• ovarian cancer
• targeted therapy

• TP53
• glioblastoma
• prostate cancer
• rs1042522
• rs9895829 and rs2909430
• single nucleotide polymorphism
• Δ133p53

Cancer is one of the most common disease worldwide, with complex changes and certain traits which have been described as “The Hallmarks of Cancer.” Despite increasing studies on in-depth investigation of these hallmarks, the molecular mechanisms associated with tumorigenesis have still not yet been fully defined. Recently, accumulating evidence supports the observation that microRNAs and long noncoding RNAs (lncRNAs), two main classes of noncoding RNAs (ncRNAs), regulate most cancer hallmarks through their binding with DNA, RNA or proteins, or encoding small peptides. Reactive oxygen species (ROS), the byproducts generated during metabolic processes, are known to regulate every step of tumorigenesis by acting as second messengers in cancer cells. The disturbance in ROS homeostasis leads to a specific pathological state termed “oxidative stress”, which plays essential roles in regulation of cancer progression. In addition, the interplay between oxidative stress and ncRNAs is found to regulate the expression of multiple genes and the activation of several signaling pathways involved in cancer hallmarks, revealing a potential mechanistic relationship involving ncRNAs, oxidative stress and cancer. In this review, we provide evidence that shows the essential role of ncRNAs and the interplay between oxidative stress and ncRNAs in regulating cancer hallmarks, which may expand our understanding of ncRNAs in the cancer development from the new perspective.

• Cancer hallmarks
• Oxidative stress
• ROS
• ncRNAs

Genomic perturbations due to inaccurate DNA replication, including inappropriate chromosomal segregation often underlie the development of cancer and neurodegenerative diseases. The incidence of these two diseases increases with age and exhibits an inverse association. Therefore, elderly subjects with cancer exhibit a reduced risk of a neurodegenerative disease, and vice versa. Both of these diseases are associated with aging and share several risk factors. Cells have multiple mechanisms to repair DNA damage and inaccurate replication. Previous studies have demonstrated that tumor suppressor proteins serve a critical role in the DNA damage response, which may result in genomic instability and thus induction of cellular apoptosis. Tumor suppressor genes, such as phosphatase and tensin homologue deleted on chromosome 10 (PTEN), breast cancer susceptibility gene 1 (BRCA1) and TP53 reduce genomic susceptibility to cancer by repairing the damaged DNA. In addition, these genes work cooperatively to ensure the inhibition of the development of several types of cancer. PTEN, BRCA1 and TP53 have been recognized as the most frequently deleted and/or mutated genes in various types of human cancer. Recently, tumor suppressor genes have also been shown to be involved in the development of neurodegenerative diseases. The present review summarizes the recent findings of the functions of these tumor suppressors that are associated with genomic stability, and are involved in carcinogenic and neurodegenerative cell signaling. A summary is presented regarding the interactions of these tumor suppressors with their partners which results in transduction of downstream signals. The implications of these functions for cancer and neurodegenerative disease-associated biology are also highlighted.

• BRCA1
• DNA repair
• PTEN
• TP53
• aging
• carcinogenesis
• cell signaling
• genomic stability
• neurodegeneration
• reactive oxygen species

Purpose: To develop a triptolide (TP) self-microemulsifying drug delivery system and to investigate its anti-tumor effect on human gastric cancer line MGC80-3 xenografts in nude mice.

Methods: The medium chain triglyceride (MCT) was selected as oil phase; polyoxyethylene castor oil (EL) was selected as surfactant, and PEG-400 was selected as cosurfactant. The mass ratio of each phase was optimized by central composite design and response surface methodology to prepare TP-SMEDDS (self-microemulsifying drug delivery system). The quality of TP-SMEDDS was evaluated, and its inhibitory effect on tumor growth investigated in nude mice transplanted with MGC80-3 cells.

Results: The final prescription process was defined as follows: MCT mass ratio: 25.3%; EL mass ratio: 49.6%; PEG-400 mass ratio: 25.1%. The prepared TP-SMEDDS was a transparent liquid with a clear appearance (the theoretical particle size: 31.168 nm). On transmission electron microscopy, the microemulsion particles were spherical in size and uniformly distributed without adhesions. The in vitro release experiment showed complete release of the prepared TP-SMEDDS in PBS solution in 6 h. In vivo antitumor activity showed its inhibitory effect in the xenograft model.

Conclusion: The self-microemulsifying delivery system improved the oral bioavailability and the in vivo antitumor effect of TP.

• MGC80-3 cells
• anti-tumor effect
• central composite design and response surface methodology
• self-microemulsifying delivery system
• triptolide

• Renal cell cancer
• p53
• p53 isoforms
• p53 mutation

• Adult
• Aged
• Aged, 80 and over
• Carcinoma, Renal Cell/genetics
• Carcinoma, Renal Cell/metabolism
• Carcinoma, Renal Cell/pathology
• Female
• Humans
• Kidney Neoplasms/genetics
• Kidney Neoplasms/metabolism
• Male
• Middle Aged
• Mutation
• Prognosis
• Prospective Studies
• Protein Isoforms
• Tumor Suppressor Protein p53/biosynthesis
• Tumor Suppressor Protein p53/genetics

Hepatocellular carcinoma develops as a multistep process, in which cell cycle deregulation is a central feature, resulting in unscheduled proliferation. The PLAGL1 gene encodes a homonym zinc finger protein that is involved in cell-proliferation control. We determined the genomic profile and the transcription and expression level of PLAGL1, simultaneously with that of its molecular partners p53, PPARγ and p21, in cell-lines derived from patients with liver cancer, during in vitro cell growth. Our investigations revealed that genomic and epigenetic changes of PLAGL1 are also present in hepatoma cell-lines. Transcription of PLAGL1 in tumor cells is significantly lower than in normal fibroblasts, but no significant differences in terms of protein expression were detected between these two cell-types, indicating that there is not a direct relationship between the gene transcriptional activity and protein expression. RT-PCR analyses on normal fibroblasts, used as control, also showed that PLAGL1 and p53 genes transcription occurs as an apparent orchestrated process during normal cells proliferation, which gets disturbed in cancer cells. Furthermore, abnormal trafficking of the PLAGL1 protein may occur in hepatocarcinogenesis.

• PLAGL1
• cell proliferation
• chromosome
• hepatocellular carcinoma
• methylation

As tumor protein 53 (p53) isoforms have tumor‐promoting, migration, and inflammatory properties, this study investigated whether p53 isoforms contributed to glioblastoma progression. The expression levels of full‐length TP53α (TAp53α) and six TP53 isoforms were quantitated by RT‐qPCR in 89 glioblastomas and correlated with TP53 mutation status, tumor‐associated macrophage content, and various immune cell markers. Elevated levels of Δ133p53β mRNA characterised glioblastomas with increased CD163‐positive macrophages and wild‐type TP53. In situ‐based analyses found Δ133p53β expression localised to malignant cells in areas with increased hypoxia, and in cells with the monocyte chemoattractant protein C‐C motif chemokine ligand 2 (CCL2) expressed. Tumors with increased Δ133p53β had increased numbers of cells positive for macrophage colony‐stimulating factor 1 receptor (CSF1R) and programmed death ligand 1 (PDL1). In addition, cells expressing a murine ‘mimic’ of Δ133p53 (Δ122p53) were resistant to temozolomide treatment and oxidative stress. Our findings suggest that elevated Δ133p53β is an alternative pathway to TP53 mutation in glioblastoma that aids tumor progression by promoting an immunosuppressive and chemoresistant environment. Adding Δ133p53β to a TP53 signature along with TP53 mutation status will better predict treatment resistance in glioblastoma. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

• CSF1R
• PDL1
• TP53 isoform
• glioblastoma
• mutant TP53
• tumor-associated macrophages
• Δ133p53β

The effects of zerumbone on the proliferation and apoptosis of esophagus cancer cells and on the P53 and Bcl-2 expression levels were studied. The esophagus cancer EC-109 cells were cultured and inoculated. The effect of zerumbone on proliferation of EC-109 cells was detected via the Cell Counting Kit-8 (CCK-8) method. Cell apoptosis was detected via TdT-mediated dUTP nick end-labeling (TUNEL) staining. Moreover, the mRNA expression levels of P53 and Bcl-2 were detected via reverse transcription-polymerase chain reaction (RT-PCR), and the protein expression levels of P53 and Bcl-2 were evaluated via western blotting. CCK-8 detection results showed that compared with control group, zerumbone in different concentrations could inhibit the activity of EC-109, and the proliferation inhibition rate was significantly increased in a concentration-dependent manner with the increase of concentration. TUNEL staining showed that cell apoptosis gradually occurred in administration group, and the number of apoptotic cells was increased in a concentration-dependent manner with the increase of concentration. RT-PCR detection results showed that the mRNA expression level of P53 in administration group was significantly increased compared with that in control group, but that of Bcl-2 was significantly decreased. Western blotting showed that the protein expression level of Bcl-2 in administration group in different concentrations was significantly increased with the increase of zerumbone concentration, but that of Bcl-2 was significantly decreased in a concentration-dependent manner. Zerumbone can inhibit the proliferation and induce apoptosis of esophageal cancer EC-109 cells, and its induction of apoptosis may be realized through upregulating the mRNA expression of P53 and downregulating the mRNA expression of Bcl-2, and upregulating the protein expression of P53 and downregulating the protein expression of Bcl-2.

• Bcl-2
• EC-109
• P53
• apoptosis
• esophageal cancer
• proliferation
• zerumbone

• Antiviral responses
• Genomic organization
• Sc-p53I6
• Siniperca chuatsi

• Alternative Splicing
• Animals
• Cell Line
• DNA Virus Infections/immunology
• Fish Diseases/immunology
• Fish Proteins/genetics
• Fish Proteins/immunology
• Gene Expression Regulation
• Immunity, Innate
• Iridoviridae/physiology
• Perciformes/genetics
• Perciformes/immunology
• RNA, Messenger/genetics
• Rhabdoviridae/physiology
• Rhabdoviridae Infections/immunology
• Tissue Distribution
• Tumor Suppressor Protein p53/genetics
• Tumor Suppressor Protein p53/immunology

• chemosensitivity
• lung adenocarcinoma cell
• tumor protein p53α gene

Cancer stem cells (CSC) are responsible for cancer chemoresistance and metastasis formation. Here we report that Δ133p53β, a TP53 splice variant, enhanced cancer cell stemness in MCF-7 breast cancer cells, while its depletion reduced it. Δ133p53β stimulated the expression of the key pluripotency factors SOX2, OCT3/4, and NANOG. Similarly, in highly metastatic breast cancer cells, aggressiveness was coupled with enhanced CSC potential and Δ133p53β expression. Like in MCF-7 cells, SOX2, OCT3/4, and NANOG expression were positively regulated by Δ133p53β in these cells. Finally, treatment of MCF-7 cells with etoposide, a cytotoxic anti-cancer drug, increased CSC formation and SOX2, OCT3/4, and NANOG expression via Δ133p53, thus potentially increasing the risk of cancer recurrence. Our findings show that Δ133p53β supports CSC potential. Moreover, they indicate that the TP53 gene, which is considered a major tumor suppressor gene, also acts as an oncogene via the Δ133p53β isoform.

•

The Δ133p53β isoform promotes stemness of breast cancer cells

CD40 and CD40 ligand (CD40L) are costimulatory molecules that play a pivotal role in the proinflammatory immune response. Primarily expressed by activated CD4⁺ T cells, CD40L binds to CD40 on antigen presenting cells (APCs), thereby inducing APC activation. APCs, in turn, prime cytotoxic T lymphocytes (CTLs). Here, two tumor-associated antigen (TAA) animal models, p53-based and GP100-based, were utilized to examine the ability of CD40-CD40L to improve antigen-specific CTL-mediated antitumor immune responses. Although p53 and GP100 are self-antigens that generate low affinity antigen-specific CD8⁺ T cells, studies have shown that their functional avidity can be improved with CD40L-expressing APCs. Therefore, in the current study, we immunized mice with a DNA construct encoding a TAA in conjunction with another construct encoding CD40L via intramuscular injection followed by electroporation. We observed a significant increase in the antigen-specific CTL-mediated immune responses as well as the potent antitumor effects in both models. Antibody depletion experiments demonstrated that CD8⁺ T cells play a crucial role in eliciting antitumor effects in vaccinated mice. Furthermore, we showed that in vitro stimulation with irradiated tumor cells expressing both TAA and CD40L improved the functional avidity of antigen-specific CD8⁺ T cells. Thus, our data show that vaccination with TAA/CD40L DNA can induce potent antitumor effects against TAA-expressing tumors through the generation of better functioning antigen-specific CD8⁺ T cells. Our study serves as an important foundation for future clinical translation.

• Animals
• Antigen-Presenting Cells/immunology
• Antigen-Presenting Cells/pathology
• CD40 Ligand/genetics
• CD40 Ligand/immunology
• CD8-Positive T-Lymphocytes/immunology
• CD8-Positive T-Lymphocytes/pathology
• Cancer Vaccines/immunology
• Female
• Immune Tolerance
• Mice
• Mice, Transgenic
• Neoplasms, Experimental/genetics
• Neoplasms, Experimental/immunology
• Neoplasms, Experimental/therapy
• Tumor Suppressor Protein p53/genetics
• Tumor Suppressor Protein p53/immunology
• gp100 Melanoma Antigen/genetics
• gp100 Melanoma Antigen/immunology

• P50 CA098252 NCI NIH HHS
• R01 CA114425 NCI NIH HHS
• P50CA098252 NCI NIH HHS
• 2R01CA114425-06 NCI NIH HHS

P53作为转录因子，其转录激活功能维持了基因组的稳定性，对防止肿瘤的形成起着重要作用，是目前研究得最为广泛、深入的抑癌基因，被称为“基因卫士”。P53家族的成员p63、p73与p53在DNA结合结构域上有高度的同源性，某些p53家族亚型可以与p53-反应基因相结合起着转录激活的作用，另外一些则起着负性调节作用。肺癌是世界上患病率最高的恶性肿瘤之一，p53家族成员在肺癌中的异常表达与肺癌的发生有密切联系，并导致不良的预后及对放疗、化疗的抵抗。对p53家族成员在肺癌致病机制的深入研究可有助于为临床提供合理的化疗方案及靶向治疗策略。本文着重回顾总结p53家族成员在肺癌发生、化疗敏感性以及肺癌靶向治疗中的独特的作用。

• chemosensitivity
• methylation
• non-small cell lung cancer
• p73 gene

Expression of p53 appears to be correlated to prognosis in patients with malignancy, but its role in gastric carcinoma has remained controversial. Recently we reported that JWA, an ADP-ribosylation-like factor 6 interacting protein 5 (ARL6ip5), was both prognostic for overall survival and predictive for platinum-based treatment of gastric cancer. In this study, we aimed to investigate p53 expression as a prognostic and predictive marker in resectable gastric cancer, alone and in combination with JWA. Expression of p53 was examined in three large patient cohorts (total n = 1155) of gastric cancer. High expression of p53 was significantly correlated with unfavorable clinicopathologic parameters and decreased overall patient survival. Furthermore, patients with high p53 expression in tumors acquired remarkable survival benefit from adjuvant first-line platinum-based-chemotherapy. The synergy between p53 and JWA in predicting patient outcome was demonstrated, while no significantly elevated predictive value concerning chemotherapy was observed. Thus, p53 expression is a potent prognostic and predictive factor for resectable gastric cancer with adjuvant platinum-based chemotherapy. A combined effect of p53 with JWA as efficient prognostic indicators was found for the first time.

p53 is well known as a “guardian of the genome” for differentiated cells, in which it induces cell cycle arrest and cell death after DNA damage and thus contributes to the maintenance of genomic stability. In addition to this tumor suppressor function for differentiated cells, p53 also plays an important role in stem cells. In this cell type, p53 not only ensures genomic integrity after genotoxic insults but also controls their proliferation and differentiation. Additionally, p53 provides an effective barrier for the generation of pluripotent stem cell-like cells from terminally differentiated cells. In this review, we summarize our current knowledge about p53 activities in embryonic, adult and induced pluripotent stem cells.

• p53
• Embryonic stem cells
• Adult stem cells
• Induced pluripotent stem cells
• Cell differentiation

Testes-specific protease 50 (TSP50) is normally expressed in testes and abnormally expressed in breast cancer, but whether TSP50 is expressed in colorectal carcinoma (CRC) and its clinical significance is unclear. We aimed to detect TSP50 expression in CRC, correlate it with clinicopathological factors, and assess its potential diagnostic and prognostic value.

TSP50 mRNAs and proteins were detected in 7 CRC cell lines and 8 CRC specimens via RT-PCR and Western blot analysis. Immunohistochemical analysis of TSP50, p53 and carcinoembryonic antigen (CEA) with tissue microarrays composed of 95 CRCs, 20 colorectal adenomas and 20 normal colorectal tissues were carried out and correlated with clinicopathological characteristics and disease-specific survival for CRC patients. There was no significant correlation between the expression levels of TSP50 and p53 (P = 0.751) or CEA (P = 0.663). Abundant expression of TSP50 protein was found in CRCs (68.4%) while it was poorly expressed in colorectal adenomas and normal tissues (P<0.0001). Thus, CRCs can be distinguished from them with high specificity (92.5%) and positive predictive value (PPV, 95.6%). The survival of CRC patients with high TSP50 expression was significantly shorter than that of the patients with low TSP50 expression (P = 0.010), specifically in patients who had early-stage tumors (stage I and II; P = 0.004). Multivariate Cox regression analysis indicated that high TSP50 expression was a statistically significant independent risk factor (hazard ratio  = 2.205, 95% CI = 1.214–4.004, P = 0.009).

Our data demonstrate that TSP50 is a potential effective indicator of poor survival for CRC patients, especially for those with early-stage tumors.

• Adenoma/genetics
• Aged
• Biomarkers, Tumor/metabolism
• Carcinoembryonic Antigen/metabolism
• Cell Line, Tumor
• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/genetics
• Colorectal Neoplasms/metabolism
• Colorectal Neoplasms/pathology
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Middle Aged
• Multivariate Analysis
• Prognosis
• ROC Curve
• Regression Analysis
• Serine Endopeptidases/genetics
• Serine Endopeptidases/metabolism
• Tissue Array Analysis
• Tumor Suppressor Protein p53/metabolism

AIM: To investigate the correlation of P53 and Ki67 protein expression with the clinicopathological parameters in gastric cancer.

METHODS: A total of 1 107 surgical specimens of gastric cancer were collected from the Fuzhou General Hospital of Nanjing Military Command, The expression of P53 and Ki67 was examined by immunohistochemistry in 775 gastric cancer specimens taken from patients with complete clinical data.

RESULTS: The positive rates of P53 and Ki67 protein expression were 46.84% and 78.97%, respectively. Higher positive rates of P53 and Ki67 protein expression were noted in intestinal-type gastric cancer than in diffuse-type gastric cancer (54.7% vs 38.0%, 86.0% vs 70.0%, both P < 0.05) and in well-differentiated cancer than in poorly-differentiated cancer (54.7 vs 35.4%, 87.0% vs 67.2%, both P < 0.05). A higher positive rate of P53 protein expression was noted in gastroesophageal junction (GEJ) cancer than in gastric cancer (53.7% vs 41.9%, P < 0.05) and in cancer without distant metastasis than in that with distant metastasis (49.0% vs 30.3%, P < 0.05). A higher positive rate of Ki67 protein expression was noted in invasive cancer than in less invasive cancer ( 80.3% vs 60.4%, P < 0.05) and in cancer with lymph node metastasis than in that without lymph node metastasis (81.4% vs 72.6 %, P < 0.05).

CONCLUSION: P53 and Ki67 protein expression might be associated with the development, invasion, and metastasis of gastric cancer, and can be used to evaluate the malignant behavior and prognosis of gastric cancer.

• Gastric cancer
• P53
• Ki67
• Her-2
• Immunohistochemistry
• Clinicopathological parameter

• Animals
• CCAAT-Enhancer-Binding Proteins/metabolism
• Carcinoma, Hepatocellular/metabolism
• Disease Models, Animal
• Humans
• Intracellular Space/metabolism
• Liver Neoplasms/metabolism
• Mice
• Mice, Knockout
• Proteasome Endopeptidase Complex/metabolism
• RNA-Binding Proteins/genetics
• Retinoblastoma Protein/metabolism
• Signal Transduction
• Tumor Suppressor Protein p53/genetics
• Tumor Suppressor Protein p53/metabolism

• CA100070 NCI NIH HHS
• R01 GM055188-15 NIGMS NIH HHS
• AR044387 NIAMS NIH HHS
• R01 GM055188 NIGMS NIH HHS
• R01 CA159942 NCI NIH HHS
• R01 CA100070 NCI NIH HHS
• P01 AG020752 NIA NIH HHS
• AG20752 NIA NIH HHS
• AR052791 NIAMS NIH HHS
• R01 AR052791 NIAMS NIH HHS
• NS063298 NINDS NIH HHS
• GM55188 NIGMS NIH HHS
• R03 NS063298 NINDS NIH HHS
• R01 AR044387 NIAMS NIH HHS