CD57 defines a novel cancer stem cell that drive invasion of diffuse pediatric-type high grade gliomas.

Background: Diffuse invasion remains a primary cause of treatment failure in pediatric high-grade glioma (pHGG). Identifying cellular driver(s) of pHGG invasion is needed for anti-invasion therapies.

Methods: Ten highly invasive patient-derived orthotopic xenograft (PDOX) models of pHGG were subjected to isolation of matching pairs of invasive (HGG) and tumor core (HGG) cells.

Targeting Erbin-mitochondria axis in platelets/megakaryocytes promotes B cell-mediated antitumor immunity.

The roles of platelets/megakaryocytes (MKs), the key components in the blood system, in the tumor microenvironment and antitumor immunity are unclear. In patients with colorectal cancer, the number of platelets was significantly increased in patients with metastasis, and Erbin expression was highly expressed in platelets from patients with metastases. Moreover, Erbin knockout in platelets/MKs suppressed lung metastasis in mice and promoted aggregations of platelets.

Targeting GBM with an Oncolytic Picornavirus SVV-001 alone and in combination with fractionated Radiation in a Novel Panel of Orthotopic PDX models.

Background: Animal models representing different molecular subtypes of glioblastoma multiforme (GBM) is desired for developing new therapies. SVV-001 is an oncolytic virus selectively targeting cancer cells. It's capacity of passing through the blood brain barrier makes is an attractive novel approach for GBM.

EphB6 deficiency in intestinal neurons promotes tumor growth in colorectal cancer by neurotransmitter GABA signaling.

EphB6 belongs to the receptor tyrosine kinase, whose low expression is associated with shorter survival of colorectal cancer (CRC) patients. But the role and mechanism of EphB6 in the progression of CRC need further study. In addition, EphB6 was mainly expressed in intestinal neurons.

Inclusion of the Number of Metastatic Lymph Nodes in the Staging System for Medullary Thyroid Cancer: Validating a Modified American Joint Committee on Cancer Tumor-Node-Metastasis Staging System.

The current American Joint Committee on Cancer (AJCC) staging system (8th edition) for medullary thyroid cancer (MTC) was originally extrapolated from the staging system for differentiated thyroid cancer. However, the current staging system does not accurately predict the prognosis of patients with MTC. The present study was based on data from the Surveillance, Epidemiology, and End Results (SEER) database and validated by multicenter data from the Shanghai Tenth People's Hospital, Tongji University School of Medicine, Xuzhou City Central Hospital, and Suzhou Ninth People's Hospital.

Synergistic anti-tumor efficacy of mutant isocitrate dehydrogenase 1 inhibitor SYC-435 with standard therapy in patient-derived xenograft mouse models of glioma.

Clinical outcomes in patients with WHO grade II/III astrocytoma, oligodendroglioma or secondary glioblastoma remain poor. Isocitrate dehydrogenase 1 (IDH1) is mutated in > 70% of these tumors, making it an attractive therapeutic target. To determine the efficacy of our newly developed mutant IDH1 inhibitor, SYC-435 (1-hydroxypyridin-2-one), we treated orthotopic glioma xenograft model (IC-BT142AOA) carrying R132H mutation and our newly established orthotopic patient-derived xenograft (PDX) model of recurrent anaplastic oligoastrocytoma (IC-V0914AOA) bearing R132C mutation.

Comprehensive analysis of suppressor of cytokine signaling proteins in human breast Cancer.

Background: Abnormal expression of suppressor of cytokine signaling (SOCS) proteins regulates tumor angiogenesis and development in cancers. In this study, we aimed to perform a comprehensive bioinformatic analysis of SOCS proteins in breast invasive carcinoma (BRCA).

Methods: The gene expression, methylation level, copy number, protein expression and patient survival data related to SOCS family members in BRCA patients were obtained from the following databases: Oncomine, The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Human Protein Atlas (HPA), Gene Expression Profiling Interactive Analysis (GEPIA), PCViz, cBioPortal and Kaplan-Meier plotter.

Myristoylation-mediated phase separation of EZH2 compartmentalizes STAT3 to promote lung cancer growth.

N-myristoylation is a crucial signaling and pathogenic modification process that confers hydrophobicity to cytosolic proteins. Although different large-scale approaches have been applied, a large proportion of myristoylated proteins remain to be identified. EZH2 is overexpressed in lung cancer cells and exerts oncogenic effects via its intrinsic methyltransferase activity.

Targeting Erbin in B cells for therapy of lung metastasis of colorectal cancer.

The mechanisms and key factors involved in tumor environments for lung metastasis of CRC are still unclear. Here, using clinical samples from lung metastases of CRC patients, we found that intestinal immune network for IgA production was significantly dysregulated in lung metastases of CRC. Single-cell RNA sequencing discovered a subtype of B cells positive for Erbin, one member of the leucine-rich repeat and PDZ domain (LAP) family, was involved in the lung metastases.

Circadian Clock Disruption Suppresses PDL1 Intraepithelial B Cells in Experimental Colitis and Colitis-Associated Colorectal Cancer.

Background & Aims: The circadian clock is crucial for physiological homeostasis including gut homeostasis. Disorder of the circadian clock may contribute to many diseases including inflammatory bowel disease (IBD). However, the role and the mechanisms of circadian clock involvement in IBD still are unclear.

DNA Methylation-Reprogrammed Ang II (Angiotensin II) Type 1 Receptor-Early Growth Response Gene 1-Protein Kinase C ε Axis Underlies Vascular Hypercontractility in Antenatal Hypoxic Offspring.

As the most common clinical stress during mid and late pregnancy, antenatal hypoxia has profound adverse effects on individual's vascular health later in life, but the underlying mechanisms are still not understood. The purpose of this study was to reveal the mechanisms of the acquired vascular dysfunction in offspring imposed by antenatal hypoxia. Pregnant rats were housed in a normoxic or hypoxic (10.

The circular RNA circ-ERBIN promotes growth and metastasis of colorectal cancer by miR-125a-5p and miR-138-5p/4EBP-1 mediated cap-independent HIF-1α translation.

Background: Circular RNA (circRNAs) and hypoxia have been found to play the key roles in the pathogenesis and progression of cancer including colorectal cancer (CRC). However, the expressions and functions of the specific circRNAs in regulating hypoxia-involved CRC metastasis, and the circRNAs that are relevant to regulate HIF-1α levels in CRC remain elusive.

Methods: qRT-PCR was used to detect the expression of circRNAs and mRNA in CRC cells and tissues.

Lymph Node Ratio-Based Staging System for Gallbladder Cancer With Fewer Than Six Lymph Nodes Examined.

Purpose: The 8th edition of the American Joint Committee on Cancer (AJCC) tumor-lymph node-metastasis (TNM) staging system for gallbladder cancer (GBC) recommended that at least six lymph nodes (LNs) should be examined. But most patients with GBC had fewer than six LNs resected. This study aimed to establish an alternative index for assessing the LN status during the staging system for GBC patients with fewer than six LNs retrieved.

Asperolide A prevents bone metastatic breast cancer via the PI3K/AKT/mTOR/c-Fos/NFATc1 signaling pathway.

Background: Breast cancer is the leading cause of death among women with malignant tumors worldwide. Bone metastasis is the main factor affecting the prognosis of breast cancer. Therefore, both antitumor and anti-breast-cancer-induced osteolysis agents are urgently needed.

Impact of SCID mouse gender on tumorigenicity, xenograft growth and drug-response in a large panel of orthotopic PDX models of pediatric brain tumors.

Brain tumor is the leading cause of cancer related death in children. Clinically relevant animals are critical for new therapy development. To address the potential impact of animal gender on tumorigenicity rate, xenograft growth and in vivo drug responses, we retrospectively analyzed 99 of our established patient derived orthotopic xenograft mouse models (orthotopic PDX or PDOX).

The gut microbiota regulates autism-like behavior by mediating vitamin B homeostasis in EphB6-deficient mice.

Background: Autism spectrum disorder (ASD) is a developmental disorder, and the effective pharmacological treatments for the core autistic symptoms are currently limited. Increasing evidence, particularly that from clinical studies on ASD patients, suggests a functional link between the gut microbiota and the development of ASD. However, the mechanisms linking the gut microbiota with brain dysfunctions (gut-brain axis) in ASD have not yet been full elucidated.

Incidence, prevalence, and outcomes of systemic malignancy with bone metastases.

Purpose: Evidence on the incidence, prevalence, and outcomes of bone metastases among patients with systemic malignancy is limited. This study aimed to evaluate it using the Surveillance, Epidemiology, and End Results (SEER) database.

Methods: We collected patients diagnosed with solid malignant tumors deriving outside of the bone, hematologic malignancies, Kaposi sarcoma, lymphoma, and myeloma from the SEER database (from 2010 to 2013).

Racial/Ethnic Disparities and Survival in Pediatrics with Gliomas Based on the Surveillance, Epidemiology, and End Results Database in the United States.

Background: Gliomas are the most common type of primary central nervous system tumor for both children and adults. However, the influence of racial/ethnic disparities on the survival of children with gliomas has not been fully evaluated yet.

Methods: Baseline characteristics of patients, including sex, year of diagnosis, surgery, grade, radiation, histology, and races, were collected.

NSD2 circular RNA promotes metastasis of colorectal cancer by targeting miR-199b-5p-mediated DDR1 and JAG1 signalling.

Liver metastasis is the main cause of death in patients with colorectal cancer (CRC). Here, we searched for CRC metastasis-associated circular RNA in a mouse model of liver metastasis of CRC by using RNA (transcriptome)-sequencing. We identified a novel and conserved circular RNA, circ-NSD2, functioning as a promoter of CRC metastasis.

Ube2v1-mediated ubiquitination and degradation of Sirt1 promotes metastasis of colorectal cancer by epigenetically suppressing autophagy.

Background: Ubiquitination is a basic post-translational modification for cellular homeostasis, and members of the conjugating enzyme (E2) family are the key components of the ubiquitin-proteasome system. However, the role of E2 family in colorectal cancer (CRC) is largely unknown. Our study aimed to investigate the role of Ube2v1, one of the ubiquitin-conjugating E2 enzyme variant proteins (Ube2v) but without the conserved cysteine residue required for the catalytic activity of E2s, in CRC.

Satb2 ablation decreases PTZ-induced seizure susceptibility and pyramidal neuronal excitability.

Special AT-rich sequence-binding protein 2 (Satb2) is a transcriptional regulator and people with SATB2 mutation or duplication could display epilepsy. However, whether Satb2 is related with epilepsy and its mechanisms are largely unexplored. Here we found that the expression of Satb2 was decreased following the neuronal hyperactivities.

Erbin exerts a protective effect against inflammatory bowel disease by suppressing autophagic cell death.

The pathogenesis and key functional molecules involved in inflammatory bowel disease (IBD) including Crohn's disease (CD) and ulcerative colitis (UC) remain unclear. Here, we reported that Erbin, a protein required for the polarity of epithelial cells, is conserved across species and highly expressed in the intestinal mucosa in mice and zebrafish. Pathologically, Erbin expression in the intestinal mucosa was significantly decreased in DSS induced acute colitis mice, IL-10 deficient mice and clinical biopsy specimens from patients with ulcerative colitis.

Dicer suppresses cytoskeleton remodeling and tumorigenesis of colorectal epithelium by miR-324-5p mediated suppression of HMGXB3 and WASF-2.

Emerging evidence indicates that microRNAs, a class of small and well-conserved noncoding RNAs, participate in many physiological and pathological processes. RNase III endonuclease DICER is one of the key enzymes for microRNA biogenesis. Here, we found that DICER was downregulated in tumor samples of colorectal cancer (CRC) patients at both mRNA and protein levels.

Satb2 Ablation Impairs Hippocampus-Based Long-Term Spatial Memory and Short-Term Working Memory and Immediate Early Genes (IEGs)-Mediated Hippocampal Synaptic Plasticity.

Special AT-rich sequence-binding protein 2 (Satb2) is a protein binding to the matrix attachment regions of DNA and important for gene regulation. Patients with SATB2 mutation usually suffer moderate to severe mental retardation. However, the mechanisms for the defects of intellectual activities in patients with SATB2 mutation are largely unclear.