Advances and challenges in neuroimaging-based pain biomarkers.

Identifying neural biomarkers of pain has long been a central theme in pain neuroscience. Here, we review the state-of-the-art candidates for neural biomarkers of acute and chronic pain. We classify these potential neural biomarkers into five categories based on the nature of their target variables, including neural biomarkers of (1) within-individual perception, (2) between-individual sensitivity, and (3) discriminability for acute pain, as well as (4) assessment and (5) prospective neural biomarkers for chronic pain. For each category, we provide a synthesized review of candidate biomarkers developed using neuroimaging techniques including functional magnetic resonance imaging (fMRI), structural magnetic resonance imaging (sMRI), and electroencephalography (EEG). We also discuss the conceptual and practical challenges in developing neural biomarkers of pain. Addressing these challenges, optimal biomarkers of pain can be developed to deepen our understanding of how the brain represents pain and ultimately help alleviate patients' suffering and improve their well-being.

Long noncoding RNA high expression in hepatocellular carcinoma facilitates tumor growth through enhancer of zeste homolog 2 in humans.

UNLABELLED: In recent years, long noncoding RNAs (lncRNAs) have been shown to have critical regulatory roles in cancer biology. However, the contributions of lncRNAs to hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remain largely unknown. Differentially expressed lncRNAs between HBV-related HCC and paired peritumoral tissues were identified by microarray and validated using quantitative real-time polymerase chain reaction. Liver samples from patients with HBV-related HCC were analyzed for levels of a specific differentially expressed lncRNA High Expression In HCC (termed lncRNA-HEIH); data were compared with survival data using the Kaplan-Meier method and compared between groups by the log-rank test. The effects of lncRNA-HEIH were assessed by silencing and overexpressing the lncRNA in vitro and in vivo. The expression level of lncRNA-HEIH in HBV-related HCC is significantly associated with recurrence and is an independent prognostic factor for survival. We also found that lncRNA-HEIH plays a key role in G(0) /G(1) arrest, and further demonstrated that lncRNA-HEIH was associated with enhancer of zeste homolog 2 (EZH2) and that this association was required for the repression of EZH2 target genes. CONCLUSIONS: Together, these results indicate that lncRNA-HEIH is an oncogenic lncRNA that promotes tumor progression and leads us to propose that lncRNAs may serve as key regulatory hubs in HCC progression.

Synergistic effects of amorphous OSA-modified starch, unsaturated lipid-carrier, and sonocavitation treatment in fabricating of Lavandula angustifolia essential oil nanoparticles.

This investigation aims to evaluate the synergistic effects of amorphous OSA-modified starch, unsaturated lipid-carrier (RBD-SFO), and high-energy microfluidization in synergy with the ultrasonic techniques in fabricating of Lavandula angustifolia essential oil (LAF-EO) nanoparticle. GC-MS and SEM techniques were employed to investigate the LAF-EO isolation method used. DLS analysis was employed along with CLSM and TEM techniques to investigate the physicochemical properties of nanoemulsion formulation (NE) matrices. The NE achieved the optimal spherical and size distributions of droplets (125.7 nm), Poly Dispersity Index (PdI) (0.183), and ζ-potential (-40.3 mV) when the contents of the formulation matrix were as follows: OSA-MS (2%), LAF-EO (1%), RBD-SFO (1%), and Tween-80 (1%). The findings of this work provide a new concept about the synergistic effects of amorphous OSA-modified starch and unsaturated lipid carrier as safe-grade macromolecules in the fabricating of LAF-EO nanoparticles. Besides, the application of the ultrasound cavitation phenomenon has been shown to have effective effect in reducing the droplet hydrodynamic diameter along with enhancing the distribution (PdI) and electrokinetic potential of the LAF-EO nanoparticles.

Expression of vascular endothelial growth factors A and C in human pancreatic cancer.

AIM: To study the expression of vascular endothelial growth factor A (VEGF-A) and VEGF-C and to determine whether the presence of VEGF-A and VEGF-C was associated with the clinicopathologic characteristics of pancreatic cancer. METHODS: VEGF-A and VEGF-C mRNA transcripts were examined by Northern blot in 6 human pancreatic cancer cell lines and 8 normal pancreatic tissues and 8 pancreatic carcinoma specimens. The expression of VEGF-A and VEGF-C proteins was examined by Western blot in the tested cell lines and by immunohistochemical stain in 50 pancreatic carcinoma samples. RESULTS: VEGF-A and VEGF-C mRNA transcripts were present in all the 6 human pancreatic cancer cell lines. Immunoblotting revealed the presence of VEGF-A and VEGF-C proteins in all the cell lines. Northern blot analysis of total RNA revealed 3.0-fold and 3.6-fold increase in VEGF-A and VEGF-C mRNA transcript in the cancer samples, respectively. Immunohistochemical analysis confirmed the expression of VEGF-A and VEGF-C in cancer cells within the tumor mass. Immunohistochemical analysis of 50 pancreatic cancer tissue samples revealed the presence of VEGF-A and VEGF-C immunoreactivity in 50% and 80% of the cancer tissue samples, respectively. The presence of VEGF-A in these cells was associated with larger tumor size and enhanced local spread (c2 = 6.690, P = 0.035<0.05) but was not associated with decreased patient survival. However, the presence of VEGF-C in the cancer cells was associated with increased lymph node metastasis (c2 = 5.710, P = 0.017 < 0.05), but was not associated with decreased patient survival. There was no correlation between the expression of VEGF-A and VEGF-C in the same cancer cells. CONCLUSION: VEGF-A and VEGF-C are commonly overexpressed in human pancreatic cancer and may contribute to tumor growth and lymph node metastasis. There is no relationship between the expression of VEGF-A and VEGF-C in pancreatic cancer.

Interleukin-1alpha, 6 regulate the secretion of vascular endothelial growth factor A, C in pancreatic cancer.

BACKGROUND: Vascular endothelial growth factor (VEGF, namely VEGF-A) is an angiogenic polypeptide and VEGF-C is a lymphangiogenic polypeptide that has been implicated in cancer growth, invasion and metastasis. Several cytokines and growth factors play an important part in cancer progression. These cytokines and growth factors are the principal mediators of cancer cells--stromal cell interaction, which is critical for invasion of cancer cells to the surrounding tissues and metastatic dissemination to distant organs. In this study, we studied VEGF-A, C expression in cultured human pancreatic cancer cell lines and whether the presence of VEGF-A, C in the cell lines is regulated by cytokines interleukin-1alpha(IL-1alpha), and interleukin-6 (IL-6). METHODS: We used Northern blot and Western blot methods to analyze expression of the gene and protein of VEGF-A, C in all 6 tested cell lines (ASPC-1, CAPAN-1, MIA-PaCa-2, PANC-1, COLO-357 and T3M4) respectively. To analyze what is the regulator for this VEGF-A, C expression in pancreatic cancer, we used the reverse transcription-polymerase chain reaction (RT-PCR) method to analyze VEGF-A, C expression in cultured human pancreatic cancer cell lines (CAPAN-1 and COLO-357) under the stimulation with IL-1alpha(10 microg/L) or IL-6 (100 microg/L). RESULTS: Northern blot analysis revealed the presence of the 4.1 kb VEGF-A mRNA transcript and 2.4-kb VEGF-C mRNA transcript in all 6 tested cell lines. Immunoblotting with highly specific anti-VEGF-A, anti-VEGF-C antibody revealed the presence of a molecular weight of 43-kDa VEGF-A protein and 55-kDa VEGF-C protein in all the cell lines. RT-PCR analysis revealed the levels of the VEGF-A and VEGF-C gene were 1-2 fold and a 1-fold increase in the COLO-357 cell line by stimulation with IL-1alpha, however, no effect was found in the CAPAN-1 cell line. The levels of the VEGF-A and VEGF-C gene were 2-5 fold and a 1-fold increase in the CAPAN-1 cell line by stimulation with IL-6, but no effect was found in the COLO-357 cell line. CONCLUSION: These findings suggested that the expression of VEGF-A, C and their regulation by IL-1alpha, IL-6 in pancreatic cancer contributes to the lymphatic and distant metastasis and the disease progression.

[Exogenous expression of SOCS box-deficient mutant ASB-8 suppresses the growth of lung adenocarcinoma SPC-A1 cells].

ASB-8 is a new member of the human ankyrin repeat and SOCS box containing protein family (ASB). This report deals with the expression of ASB-8 protein in lung carcinoma tissue, as well as its biological effect on the proliferation and growth of lung cancer cell line SPC-A1. ASB-8 was expressed in pT7-450 expression vector, and an anti-ASB-8 rabbit polyclonal antibody was prepared. The expression of ASB-8 protein in lung carcinoma tissue was detected using immunohistochemistry. The growth characteristics of the lung adenocarcinoma SPC-A1 cells expressing either exogenous ASB-8 or ASB-8 SB (SOCS box-deficient) was studied by both in vitro cell growth curve and in vivo nude mouse tumor formation assay. Immunohistochemical staining detected positive reaction of 96.8% (30/31) showing that ASB-8 was highly expressed in lung cancer tissues; however, the expression of ASB-8 was lower, or even no expression in noncancerous lung tissues. Significant growth inhibition was observed in SPC-A1 cell line expressing ASB-8 SB on day 4 and persisted to day 6, compared with mock transfected cells (P<0.01). No difference in the growth properties was observed between ASB-8 and mock transfected cells. In vivo study also showed that tumor formation of ASB-8 SB expressing cells was significantly inhibited as compared with that of the control group (P<0.01). Therefore, ASB-8 may play an important role in growth and proliferation of lung cancer, possibly as positive regulator.

[The expression and imprinting status of insulin-like growth factor 2 gene in colorectal cancer].

OBJECTIVE: To study the imprinting status and expression level of insulin-like growth factor 2 (IGF2) gene in colorectal cancer and to provide a clue for the mechanism of carcinogenesis of colorectal cancer. METHODS: The expression levels of IGF2 in the paired colorectal cancer and adjacent normal tissue were examined and compared by use of semi-quantitative reverse transcription-polymerase chain reaction. The imprinting status of IGF2 was detected by restriction fragment length polymorphism. The relationships between the expression level of IGF2, its imprinting status, and the carcinogenesis of colorectal cancer were analyzed. RESULTS: IGF2 was overexpressed in 82.4% (28/34) of colorectal cancer tissues which was significantly higher than those of the matched normal tissues (P<0.01, t=3.01). 87.5% (14/16) of colorectal cancer showed loss of imprinting(LOI), while 71.4%(10/14) of normal tissues also displayed LOI of IGF2. CONCLUSION: Overexpression of IGF2 was found to play an important role in carcinogenesis of colorectal cancer. LOI of IGF2 may be a prophase manifestation of colorectal cancer.

[Expression of human novel gene CT120 in lung cancer and its effects on cell growth].

BACKGROUND & OBJECTIVE: A novel membrane-associated gene CT120 was isolated from chromosome 17p13.3 locus in our laboratory. Its mRNA was not expressed in human normal lung tissues, but was abundant in human lung cancer cell line SPC-A-1. This study was designed to investigate the differential expression patterns of CT120 in different lung cancer and noncancerous tissues using immunohistochemistry and to explore the effects of ectopic expression and overexpression of CT120 on cell growth in vitro and in vivo. METHODS: A polypeptide at the C-terminus of CT120 was selected by bioinformatics, then was synthesized and conjugated to KLH (a high molecular carrier). The chicken anti-CT120 antibody IgY was prepared with the synthesized antigen and was used to determine the different expression patterns of CT120 in various tumor cell lines and in lung cancer and noncancerous tissues. The effects of ectopic expression of CT120 on NIH/3T3 cell growth were investigated through colony formation analysis. The effect of overexpression of CT120 on the cell growth of A549 was analyzed using growth curve assay and tumor formation assay of transfected cells in nude mice. RESULTS: The novel gene CT120 expressed in various tumor cell lines and expressed remarkably higher in lung cancers than in noncancerous tissues as well as normal lung tissues. Also, it promoted the proliferation of NIH/3T3 and A549 cells in vitro and in vivo. CONCLUSION: CT120 gene may be a novel candidate gene closely related to lung carcinogenesis.