Neural-cancer crosstalk: Reciprocal molecular circuits driving gastric tumorigenesis and emerging therapeutic opportunities.

The nervous system plays an important role in regulating physiological functions of the stomach, and its abnormal activity often impairs gastric homeostasis. In response to constant exposure to oncogenic stimuli that leads to gastric tumorigenesis, the neural system becomes an essential component of the tumor microenvironment via perineural infiltration, de novo neurogenesis, and axonogenesis, thereby driving cancer initiation and progression. In this review, we highlight emerging discoveries related to neural-cancer crosstalk and discuss how the nervous system is remodeled by tumor cells including neural components and modulators (including neurotransmitters and neuropeptides).

Altered expression of the Plexin-B2 system in tuberous sclerosis complex and focal cortical dysplasia IIb lesions.

Tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) type IIb are the predominant causes of drug-refractory epilepsy in children. Dysmorphic neurons (DNs), giant cells (GCs), and balloon cells (BCs) are the most typical pathogenic profiles in cortical lesions of TSC and FCD IIb patients. However, mechanisms underlying the pathological processes of TSC and FCD IIb remain obscure.

Novel combined endoscopic and laparoscopic surgery for advanced T2 gastric cancer: Two case reports.

Background: The standard treatment for advanced T2 gastric cancer (GC) is laparoscopic or surgical gastrectomy (either partial or total) and D2 lymphadenectomy. A novel combined endoscopic and laparoscopic surgery (NCELS) has recently been proposed as a better option for T2 GC. Here we describe two case studies demonstrating the efficacy and safety of NCELS.

Vascular endothelial growth factor-C modulates cortical NMDA receptor activity in cortical lesions of young patients and rat model with focal cortical dysplasia.

Emergence of dysmorphic neurons is the primary pathology in focal cortical dysplasia (FCD) associated pediatric intractable epilepsy; however, the etiologies related to the development and function of dysmorphic neurons are not fully understood. Our previous studies revealed that the expression of vascular endothelial growth factor-C (VEGF-C) and corresponding receptors VEGFR-2, VEGFR-3 was increased in the epileptic lesions of patients with tuberous sclerosis complex or mesial temporal lobe epilepsy. Here, we showed that the expression of VEGF-C, VEGFR-2, and VEGFR-3 was increased at both mRNA and protein levels in patients with cortical lesions of type I, IIa, and IIb FCD.

The landscape of immune microenvironment in lung adenocarcinoma and squamous cell carcinoma based on PD-L1 expression and tumor-infiltrating lymphocytes.

Aims: The aim of this study was to investigate the tumor microenvironment immune types (TMIT) based on tumor cell programmed cell death ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) distribution and whether distinct TMIT subtypes (TMIT I, PD-L1 /TIL ; TMIT II, PD-L1 /TIL ; TMIT III, PD-L1 /TIL ; and TMIT IV, PD-L1 /TIL ) differentially affect clinical outcomes of patients with lung adenocarcinoma (LAC) and squamous cell carcinoma (SCC).

Methods And Results: Immunohistochemistry (IHC) was applied to evaluate the expression of PD-L1 and the spatial distribution of programmed cell death 1 (PD-1) and CD8 TILs on the surgically resected specimens from 205 cases of LAC and 149 cases of SCC. PD-1 and CD8 TILs were more frequently distributed in SCC than those in LAC, regardless of their infiltrating in the tumor islets or stroma.

Author Correction: Invasion of white matter tracts by glioma stem cells is regulated by a NOTCH1-SOX2 positive-feedback loop.

The original and corrected figures are shown in the accompanying Author Correction.

Invasion of white matter tracts by glioma stem cells is regulated by a NOTCH1-SOX2 positive-feedback loop.

Early invasive growth along specific anatomical structures, especially the white matter tract, is regarded as one of the main causes of poor therapeutic outcome of people with gliomas. We show that some glioma stem cells (GSCs) are preferentially located along white matter tracts, which exhibit a demyelinated phenotype, at the invasive frontier of glioma tissues. These GSCs are CD133Notch1, whereas the nerve fibers express the Notch ligand Jagged1.

Kir2.1 Interaction with Stk38 Promotes Invasion and Metastasis of Human Gastric Cancer by Enhancing MEKK2-MEK1/2-ERK1/2 Signaling.

Potassium ion channels are emerging as promalignant factors involved in cancer progression. In this study, we found that invading human gastric cancer cells express high levels of inwardly rectifying potassium channel 2.1 (Kir2.

Lower MGMT expression predicts better prognosis in proneural-like glioblastoma.

Objective: To investigate the expression and significance of MGMT in different molecular subtypes of glioblastoma (GBM), and to evaluate the important role of MGMT and P53 in predicting the prognosis of GBM patients.

Methods: MGMT expression was detected by immunohistochemical staining in 72 cases of GBM which had been classified as three molecular subtypes. The relationship between MGMT and P53, an important molecule for identification of proneural-like GBM, were further analyzed.

Aldehyde dehydrogenase 1A1 circumscribes high invasive glioma cells and predicts poor prognosis.

Glioma is the most aggressive brain tumor with high invasiveness and poor prognosis. More reliable, sensitive and practical biomarkers to reveal glioma high invasiveness remain to be explored for the guidance of therapy. We herein evaluated the diagnostic and prognostic value of aldehyde dehydrogenase 1A1 (ALDH1A1) in the glioma specimens from 237 patients, and found that ADLH1A1 was frequently overexpressed in the high-grade glioma (WHO grade III-IV) as compared to the low-grade glioma (WHO grade I-II) patients.

SEMA3F prevents metastasis of colorectal cancer by PI3K-AKT-dependent down-regulation of the ASCL2-CXCR4 axis.

Semaphorin-3F (SEMA3F), an axonal repulsant in nerve development, has been shown to inhibit the progression of human colorectal cancer (CRC); however, the underlying mechanism remains elusive. In this study we found a negative correlation between the levels of SEMA3F and CXCR4 in CRC specimens from 85 patients, confirmed by bioinformatics analysis of gene expression in 229 CRC samples from the Cancer Genome Atlas. SEMA3F(high) /CXCR4(low) patients showed the lowest frequency of lymph node and distant metastasis and the longest survival.

Semaphorin-3F suppresses the stemness of colorectal cancer cells by inactivating Rac1.

Tumor cell stemness has been recognized as a key contributor to tumor initiation, progression and recurrence. Our previous studies have found that semaphorin-3F (SEMA3F), an axon guidance molecule in the development of central nervous system, inhibited the growth and metastasis of colorectal cancer (CRC). However, a possible role for SEMA3F in regulating cancer cell stemness remains unknown.

Metastatic consequences of immune escape from NK cell cytotoxicity by human breast cancer stem cells.

Breast cancer stem-like cells (BCSC) are crucial for metastasis but the underlying mechanisms remain elusive. Here, we report that tumor-infiltrating natural killer (NK) cells failed to limit metastasis and were not associated with improved therapeutic outcome of BCSC-rich breast cancer. Primary BCSCs were resistant to cytotoxicity mediated by autologous/allogeneic NK cells due to reduced expression of MICA and MICB, two ligands for the stimulatory NK cell receptor NKG2D.

Distinct patterns of ALDH1A1 expression predict metastasis and poor outcome of colorectal carcinoma.

Purpose: Aldehyde dehydrogenase 1A1 (ALDH1A1) has been proposed as a candidate biomarker for colorectal carcinoma (CRC). However, the heterogeneity of its expression makes it difficult to predict the outcome of CRC. The aim of this study was to evaluate the diagnostic and prognostic value of this molecule in CRC.

ALDH1A1 expression correlates with clinicopathologic features and poor prognosis of breast cancer patients: a systematic review and meta-analysis.

Background: Aldehyde dehydrogenase 1 family member A1 (ALDH1A1) has been identified as a putative cancer stem cell (CSC) marker in breast cancer. However, the clinicopathological and prognostic significance of this protein in breast cancer patients remains controversial.

Methods: This meta-analysis was conducted to address the above issues using 15 publications covering 921 ALDH1A1(+) cases and 2353 controls.

Increased pro-angiogenic factors, infiltrating neutrophils and CD163(+) macrophages in bronchoalveolar lavage fluid from lung cancer patients.

Infiltration of inflammatory cells and production of pro-angiogenic factors are important in lung cancer immunity. The distributions of those cells and their contributions to the production of pro-angiogenic factors and the activation phenotype of macrophages in bronchoalveolar lavage fluid (BALF) from lung cancer patients remain unclear. We analyzed the presence of distinct inflammatory cells and the macrophage activation phenotype together with the levels of vascular endothelial growth factor (VEGF) and interleukin 8 (IL-8) within BALF from 54 smoking lung cancer patients including 36 squamous cell carcinoma (SCC), 9 adenocarcinoma (AC), and 9 small cell lung cancer (SCLC) in comparison with those from 13 non-smoking and 7 smoking patients with nonspecific chronic inflammation and 8 non-smoking normal controls.

ALDH1A1 defines invasive cancer stem-like cells and predicts poor prognosis in patients with esophageal squamous cell carcinoma.

Invasion and metastasis are the major cause of deaths in patients with esophageal cancer. In this study, we isolated cancer stem-like cells from an esophageal squamous cell carcinoma cell line EC109 based on aldehyde dehydrogenase 1A1 (ALDH1A1), and found that ALDH1A1(high) cells possessed the capacities of self-renewal, differentiation and tumor initiation, indications of stem cell properties. To support their stemness, ALDH1A1(high) cells exhibited increased potential of invasion and metastasis as compared with ALDH1A1(low) cells.

Strategies for isolating and enriching cancer stem cells: well begun is half done.

Cancer stem cells (CSCs) constitute a subpopulation of cancer cells that have the potential for self-renewal, multipotent differentiation, and tumorigenicity. Studies on CSC biology and CSC-targeted therapies depend on CSC isolation and/or enrichment methodologies. Scientists have conducted extensive research in this field since John Dick's group successfully isolated CSCs based on the expression of the CD34 and CD38 surface markers.

β-Catenin/POU5F1/SOX2 transcription factor complex mediates IGF-I receptor signaling and predicts poor prognosis in lung adenocarcinoma.

Cancer stem-like cells (CSLC) are crucial in tumor initiation and progression; however, the underlying mechanism for the self-renewal of cancer cells remains undefined. In the study, immunohistochemical analysis of specimens freshly excised from patients with lung adenocarcinoma showed that high expression of insulin-like growth factor I receptor (IGF-IR) in lung adenocarcinoma cells was positively correlated with the expressions of cancer stem cell markers CD133 and aldehyde dehydrogenase 1 family member A1 (ALDH1A1). IGF-IR activation enhanced POU class 5 homeobox 1 (POU5F1) expression on human lung adenocarcinoma stem-like cells (LACSLC) through PI3K/AKT/GSK3β/β-catenin cascade.

Tumor-associated microglia/macrophages enhance the invasion of glioma stem-like cells via TGF-β1 signaling pathway.

The invasion of malignant glioma cells into the surrounding normal brain tissues is crucial for causing the poor outcome of this tumor type. Recent studies suggest that glioma stem-like cells (GSLCs) mediate tumor invasion. However, it is not clear whether microenvironment factors, such as tumor-associated microglia/macrophages (TAM/Ms), also play important roles in promoting GSLC invasion.

Connexin 43 reverses malignant phenotypes of glioma stem cells by modulating E-cadherin.

Malfunctioned gap junctional intercellular communication (GJIC) has been thought associated with malignant transformation of normal cells. However, the role of GJIC-related proteins such as connexins in sustaining the malignant behavior of cancer stem cells remains unclear. In this study, we obtained tumorspheres formed by glioma stem cells (GSCs) and adherent GSCs and then examined their GJIC.

Expression and cellular distribution of vascular endothelial growth factor-C system in cortical tubers of the tuberous sclerosis complex.

Cortical tubers are malformations of cortical development in patients with tuberous sclerosis complex (TSC), and highly associated with pediatric intractable epilepsy. Recent evidence has shown that signaling mediated through vascular endothelial growth factor-C (VEGF-C) and its receptors, VEGFR-2 and VEGFR-3, has direct effects on both neurons and glial cells. To understand the potential role of VEGF-C system in the pathogenesis of cortical tubers, we investigated the expression patterns of VEGF-C signaling in cortical tubers compared with age-matched normal control cortex (CTX).