Gene Summary

Gene:GAST; gastrin
Aliases: GAS
Summary:Gastrin is a hormone whose main function is to stimulate secretion of hydrochloric acid by the gastric mucosa, which results in gastrin formation inhibition. This hormone also acts as a mitogenic factor for gastrointestinal epithelial cells. Gastrin has two biologically active peptide forms, G34 and G17. [provided by RefSeq, Jul 2008]
Databases:OMIM, HGNC, Ensembl, GeneCard, Gene
Source:NCBIAccessed: 30 August, 2019


What does this gene/protein do?
Show (4)

Cancer Overview

Research Indicators

Publications Per Year (1994-2019)
Graph generated 31 August 2019 using data from PubMed using criteria.

Literature Analysis

Mouse over the terms for more detail; many indicate links which you can click for dedicated pages about the topic.

  • Haplotypes
  • Odds Ratio
  • Single Nucleotide Polymorphism
  • Skin Cancer
  • ets-Domain Protein Elk-4
  • Signal Transduction
  • Follow-Up Studies
  • Case-Control Studies
  • Acute Lymphocytic Leukaemia
  • Genotype
  • Cell Movement
  • Genetic Predisposition
  • Cell Line
  • Sweden
  • Alleles
  • Loss of Heterozygosity
  • BRAF
  • Adolescents
  • DNA-Binding Proteins
  • Promoter Regions
  • siRNA
  • Chromosome 17
  • Molecular Sequence Data
  • Neural Cell Adhesion Molecule L1
  • Zinc
  • Base Sequence
  • Protein Structure, Tertiary
  • Pedigree
  • Melanoma
  • Gene Expression
  • Germany
  • Cancer DNA
  • Gastrins
  • Immunohistochemistry
  • Childhood Cancer
  • Mutation
  • DNA Sequence Analysis
  • Cell Proliferation
  • Cancer Gene Expression Regulation
  • Ovarian Cancer
Tag cloud generated 30 August, 2019 using data from PubMed, MeSH and CancerIndex

Specific Cancers (4)

Data table showing topics related to specific cancers and associated disorders. Scope includes mutations and abnormal protein expression.

Note: list is not exhaustive. Number of papers are based on searches of PubMed (click on topic title for arbitrary criteria used).

Latest Publications: GAST (cancer-related)

Abolhassani M, Asadikaram G, Paydar P, et al.
Organochlorine and organophosphorous pesticides may induce colorectal cancer; A case-control study.
Ecotoxicol Environ Saf. 2019; 178:168-177 [PubMed] Related Publications
OBJECTIVES: Among the numerous agents, genetic factors and environmental elements such as pesticides have an important role in colorectal cancer (CRC) incidence. The present study aimed to investigate the probable-role of some organochlorine pesticides (OCPs) and organophosphorous pesticides (OPPs) in patients with CRC.
METHODS: In this case-control study, 42 patients with CRC and 30 healthy subjects were selected. The serum levels of some OCPs (α-HCH, β-HCH, γ-HCH, 2,4 DDE, 4,4 DDE, 2,4DDT and 4,4DDT) were measured by gas chromatography (GC) method. Serum levels of malondialdehyde (MDA), and total antioxidant capacity (TAC) as well as the enzyme activity of acetylcholinesterase (AChE) and arylesterase activity of Paraoxonase-1 (PON-1) were evaluated in all participants. The methylation specific PCR (MSP) assay was used for determining the methylation status of CpG island of p16 and MGMT genes in CRC patients.
RESULTS: The mean serum levels of each OCPs were significantly higher in the patient group compared to the control group (P < 0.001). The AChE and arylesterase activity of PON-1 in the patient group were significantly lower than the control group (P < 0.001). The mean serum levels of MDA and TAC in the serum of the patient group were significantly higher than the control group (P < 0.001 and P < 0.002, respectively). The current findings demonstrated significantly hypermethylation of p16 promoter in CRC patients.
CONCLUSION: Regarding the higher levels of OCPs in CRC patients, along with hypermethylation of the p16 promoter gene, diminishing in AChE and PON-1 activity and increasing in oxidative stress factors, the role of OCPs and OPPs in the CRC progression in the South-East of Iran may be assumed.

Nukii Y, Miyamoto A, Mochizuki S, et al.
Pneumatosis intestinalis induced by osimertinib in a patient with lung adenocarcinoma harbouring epidermal growth factor receptor gene mutation with simultaneously detected exon 19 deletion and T790 M point mutation: a case report.
BMC Cancer. 2019; 19(1):186 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Pneumatosis intestinalis is a rare adverse event that occurs in patients with lung cancer, especially those undergoing treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). Osimertinib is the most recently approved EGFR-TKI, and its usage is increasing in clinical practice for lung cancer patients who have mutations in the EGFR gene.
CASE PRESENTATION: A 74-year-old woman with clinical stage IV (T2aN2M1b) lung adenocarcinoma was determined to have EGFR gene mutations, namely a deletion in exon 19 and a point mutation (T790 M) in exon 20. Osimertinib was started as seventh-line therapy. Follow-up computed tomography on the 97th day after osimertinib administration incidentally demonstrated intra-mural air in the transverse colon, as well as intrahepatic portal vein gas. Pneumatosis intestinalis and portal vein gas improved by fasting and temporary interruption of osimertinib. Osimertinib was then restarted and continued without recurrence of pneumatosis intestinalis. Overall, following progression-free survival of 12.2 months, with an overall duration of administration of 19.4 months (581 days), osimertinib was continued during beyond-progressive disease status, until a few days before the patient died of lung cancer.
CONCLUSIONS: Pneumatosis intestinalis should be noted as an important adverse event that can occur with administration of osimertinib; thus far, such an event has never been reported. This was a valuable case in which osimertinib was successfully restarted after complete recovery from pneumatosis intestinalis, such that further extended administration of osimertinib was achieved.

Cao X, Zhang W, Moore PK, Bian J
Protective Smell of Hydrogen Sulfide and Polysulfide in Cisplatin-Induced Nephrotoxicity.
Int J Mol Sci. 2019; 20(2) [PubMed] Free Access to Full Article Related Publications
Though historically known as a toxic gas, hydrogen sulfide (H₂S) has displayed a new face as the third endogenous gaseous signaling molecule after nitric oxide (NO) and carbon monoxide (CO). Here in this review, we survey the role and therapeutic potential of H₂S in cisplatin-induced nephrotoxicity. Specifically, reduction of H₂S by cystathionine γ-lyase (CSE) downregulation upon cisplatin treatment may contribute to cisplatin-induced renal cell injury, possibly by augmentation of endogenous reactive oxygen species (ROS) production, while H₂S donation may prevent subsequent renal dysfunction by inhibiting NADPH oxidase activation. Intriguingly, H₂S slow-releasing compound GYY4137 seems to increase the anticancer activity of cisplatin, at least in several cancer cell lines, and this is probably due to its own anticancer effect. However, the efficacy of H₂S donors in tumor-bearing animals remains to be tested in terms of renal protection and cancer inhibition after receiving cisplatin. Furthermore, accumulative evidence regarding usage of polysulfide, a novel H₂S derived molecule, in the therapy of cisplatin-induced nephrotoxicity, was also summarized.

Chen H, Wang X, Guo F, et al.
Impact of p38γ mitogen-activated protein kinase (MAPK) on MDA-MB-231 breast cancer cells using metabolomic approach.
Int J Biochem Cell Biol. 2019; 107:6-13 [PubMed] Related Publications
BACKGROUND: The expression of p38 MAPK is high in breast cancer while its subunit p38γ had been rarely reported. We aimed to explain the effect of p38γ in breast cancer from the perspective of metabolomics.
METHODS: In this study, we detected the expression of p38γ in 28 breast carcinoma and para-tumor samples. Following MDA-MB-231 cell transfection with p38γ siRNAs and pc-DNA-3.1, cell viability, apoptosis, metastasis were determined through CCK-8, the cytometry analysis, transwell assay and wound healing assay. Finally, gas chromatograph-mass spectrometer (GC-MS) was used for analysis the differential metabolites.
RESULTS: The expression of p38γ was significantly up-regulated in breast cancer tissues. The transfection of si-p38γs could inhibit MDA-MB-231 cell propagation, metastasis, and induced cell apoptosis while overexpressed p38γ could promote the cell propagation, metastasis, and inhibit cell apoptosis. A total of 238 metabolites were identified and 72 of them differentially expressed in three groups (all P < 0.05, FDR < 0.05). Then the metabolites were enriched in the metabolism pathway, 85 pathways were included and 27 were significant (all P < 0.05, FDR < 0.05).
CONCLUSIONS: p38γ was up-regulated in breast cancer, which exerts a great influence on the cell growth, cell mobility, invasiveness, and apoptosis of MDA-MB-231 cells and also affected the metabolism.

Liljedahl ER, Wahlberg K, Lidén C, et al.
Genetic variants of filaggrin are associated with occupational dermal exposure and blood DNA alterations in hairdressers.
Sci Total Environ. 2019; 653:45-54 [PubMed] Related Publications
Hairdressers are exposed to high levels of chemicals, including possible carcinogens. For dermal exposure, the skin protects against the uptake of chemicals and the protein filaggrin (encoded by FLG) has a key role in skin barrier function. This study investigated if variants of FLG previously linked to impaired skin barrier function, i.e. null mutations and copy number variation (CNV) alleles (CNV10), are associated with cancer-related DNA changes. Blood and questionnaire data were collected from hairdressers (n = 295) and controls (n = 92). Exposure to aromatic amines was measured as hemoglobin adducts by gas chromatography tandem mass spectrometry. DNA from peripheral blood was used to test for FLG null mutations and CNV (10, 11, or 12 repeats), telomere length, and methylation of selected cancer-related genes. Hairdressers had a lower frequency of FLG null mutations (4.1 vs. 7.6%, P = 0.18) and CNV10 (43.2 vs. 56%, P = 0.0032) than controls. In hairdressers, CNV10 carriers had a decreased risk of high ortho-toluidine adducts in blood compared with non-carriers (odds ratio, OR = 0.49, 95% CI = 0.30-0.81). Further, telomere length was shorter for carriers of any FLG null allele (β = -0.18, 95% CI = -0.31 to -0.044) and CNV10 carriers (β = -0.054, 95% CI = -0.11 to -0.00051, linear regression adjusted for age, passive smoking, residence, and education) compared to non-carriers. Carriers of any FLG null allele showed higher methylation of the cyclin-dependent kinase inhibitor 2A gene CDKN2A (OR = 6.26, CI = 1.13-34.7), but not of the other genes analyzed. These associations were not found among the controls. Our study showed that the frequency of FLG CNV10 was lower among hairdressers than controls, which may indicate a healthy worker selection. Moreover, FLG null and CNV10 were associated with cancer-related DNA changes in hairdressers, which may influence their risk of cancer.

Tanaka H, Mizuno M, Ishikawa K, et al.
Molecular mechanisms of non-thermal plasma-induced effects in cancer cells.
Biol Chem. 2018; 400(1):87-91 [PubMed] Related Publications
Plasma is the fourth state of matter with higher energy than gas; non-thermal plasma (NTP) is currently available. As NTP is useful in sterilization, promoting wound healing and cancer treatments, the molecular mechanisms of plasma-induced effects in living cells and microorganisms are of significant interest in plasma medicine with medical-engineering collaboration. Molecular mechanisms of plasma-induced effects in cancer cells will be described in this minireview. Both direct and indirect methods to treat cancer cells with NTP have been developed. NTP interacts directly with not only cancer cells but also the liquids surrounding cancer cells and the immune cells that target them. Reactive oxygen and nitrogen species play key roles in NTP-induced effects; however, other mechanisms have been suggested. The complex interactions between NTP, cells and liquids have been extensively studied. In the future, details regarding NTP-induced effects on gene regulatory networks, signaling networks, and metabolic networks will be elucidated.

Choi JR, Koh SB, Kim HR, et al.
Radon Exposure-induced Genetic Variations in Lung Cancers among Never Smokers.
J Korean Med Sci. 2018; 33(29):e207 [PubMed] Free Access to Full Article Related Publications
Background: Lung cancer in never smokers (LCINS) differs etiologically and clinically from lung cancer attributed to smoking. After smoking, radon exposure is the second leading cause and the primary risk factor of lung cancer among never smokers. Exposure to radon can lead to genetic and epigenetic alterations in tumor genomes affecting genes and pathways involved in lung cancer development. The present study sought to explore genetic alterations associated with LCINS exposed to radon gas indoors.
Methods: Genetic associations were assessed via a case-control study of LCINS (39 cases and 30 controls) using next generation sequencing. Associations between genetic mutations and high exposure to radon were investigated by OncoPrint and heatmap graphs. Bioinformatic analysis was conducted using various tools. According radon exposure levels, we divided subjects in two groups of cases and controls.
Results: We found that ABL2 rs117218074, SMARCA4 rs2288845, PIK3R2 rs142933317, MAPK1 rs1803545, and androgen receptor (AR) rs66766400 were associated with LCINS exposed to high radon levels. Among these, Chromodomain helicase DNA-binding protein 4 (CHD4) rs74790047, TSC2 rs2121870, and AR rs66766408 were identified as common exonic mutations in both lung cancer patients and normal individuals exposed to high levels of radon indoor.
Conclusion: We identified that CHD4 rs74790047, TSC2 rs2121870, and AR rs66766408 are found to be common exonic mutations in both lung cancer patients and normal individuals exposed to radon indoors. Further analysis is needed to determine whether these genes are completely responsible for LCINS exposed to residential radon.

Nakamura A, Yamaguchi K, Minamiguchi S, et al.
Mucinous adenocarcinoma, gastric type of the uterine cervix: clinical features and HER2 amplification.
Med Mol Morphol. 2019; 52(1):52-59 [PubMed] Related Publications
Mucinous adenocarcinoma, gastric type (GAS) is difficult to diagnose and shows poor prognosis. Trastuzumab, an anti-human epidermal growth factor type 2 (HER2) monoclonal antibody, is effective in HER2-positive stomach cancer. The objectives of this study were to identify the clinicopathological characteristics of GAS and to evaluate HER2 expression in GAS. We retrospectively reviewed 322 cervical cancer cases diagnosed at the Kyoto University Hospital from 2010 to 2016. The incidence, clinical factors including age, stage, and lymph node status, tumor markers, immunoreactive expression of MUC6, HIK1083, and HER2, and HER2 amplification were evaluated. Of the 322 cases of cervical cancer, 13 cases of the adenocarcinoma cases were diagnosed as GAS. Watery discharge, lower abdominal pain, CA19-9 elevation, and lymph node metastasis were frequently observed in GAS (p = 0.0226, p = 0.0400, p = 0.0346, and p = 0.0274, respectively). Immunohistochemistry showed positive MUC6 status in all 13 cases and positive HIK1083 status in 8 cases. The HER2 expression status was equivocal in six cases by immunohistochemistry and HER2 amplification was identified in one case. GAS exhibits frequent lymph node metastasis and clinical symptoms such as watery discharge and lower abdominal pain, high levels of CA19-9. In addition, some parts of GAS exhibit HER2 amplification.

Riess JW, Gandara DR, Frampton GM, et al.
Diverse EGFR Exon 20 Insertions and Co-Occurring Molecular Alterations Identified by Comprehensive Genomic Profiling of NSCLC.
J Thorac Oncol. 2018; 13(10):1560-1568 [PubMed] Related Publications
INTRODUCTION: EGFR exon 20 insertions (EGFRex20ins) comprise an uncommon subset of EGFR-activating alterations relatively insensitive to first- and second-generation EGFR tyrosine kinase inhibitors (TKIs). However, recent early clinical data suggests these patients may benefit from newer-generation EGFR-TKIs. Comprehensive genomic profiling (CGP) identifies a broad spectrum of EGFRex20ins and associated co-occurring genomic alterations (GAs) present in NSCLC.
METHODS: Hybrid capture-based CGP was performed prospectively on 14,483 clinically annotated consecutive NSCLC specimens to a mean coverage depth of greater than 650X for 236 or 315 cancer-related genes.
RESULTS: Of 14,483 NSCLC cases, CGP identified 263 (1.8%) cases with EGFRex20ins, representing 12% (263 of 2251) of cases with EGFR mutations. Sixty-four unique EGFRex20ins were identified, most commonly D770_N771>ASVDN (21%) and N771_P772>SVDNP (20%). EGFR amplification occurred in 22% (57 of 263). The most common co-occurring GAs effected tumor protein p53 (TP53) (56%), cyclin dependent kinase inhibitor 2A (CDKN2A) (22%), cyclin dependent kinase inhibitor 2B (CDKN2B) (16%), NK2 homeobox 1 (NKX2-1) (14%) and RB transcriptional corepressor 1 (RB1) (11%); co-occurring GAs in other known lung cancer drivers were rare (5%). Average tumor mutational burden was low (mean 4.3, range 0 to 40.3 mutations/Mb). Clinical outcomes to first- and second-generation EGFR TKIs were obtained for five patients and none responded.
CONCLUSIONS: In the largest series of EGFRex20ins NSCLC, diverse EGFRex20ins were detected in 12% of EGFR-mutant NSCLC, a higher frequency than previously reported in smaller single-institution studies. Clinical outcomes showed lack of response to EGFR TKIs. Tumor mutational burden was low, consistent with non-smoking associated NSCLC. Comprehensive sequencing revealed increased proportion and wide variety of EGFRex20ins, representing a population of patients significant enough for focused efforts on effective interventions.

Rosenberger A, Hung RJ, Christiani DC, et al.
Genetic modifiers of radon-induced lung cancer risk: a genome-wide interaction study in former uranium miners.
Int Arch Occup Environ Health. 2018; 91(8):937-950 [PubMed] Article available free on PMC after 01/11/2019 Related Publications
PURPOSE: Radon is a risk factor for lung cancer and uranium miners are more exposed than the general population. A genome-wide interaction analysis was carried out to identify genomic loci, genes or gene sets that modify the susceptibility to lung cancer given occupational exposure to the radioactive gas radon.
METHODS: Samples from 28 studies provided by the International Lung Cancer Consortium were pooled with samples of former uranium miners collected by the German Federal Office of Radiation Protection. In total, 15,077 cases and 13,522 controls, all of European ancestries, comprising 463 uranium miners were compared. The DNA of all participants was genotyped with the OncoArray. We fitted single-marker and in multi-marker models and performed an exploratory gene-set analysis to detect cumulative enrichment of significance in sets of genes.
RESULTS: We discovered a genome-wide significant interaction of the marker rs12440014 within the gene CHRNB4 (OR = 0.26, 95% CI 0.11-0.60, p = 0.0386 corrected for multiple testing). At least suggestive significant interaction of linkage disequilibrium blocks was observed at the chromosomal regions 18q21.23 (p = 1.2 × 10
CONCLUSION: The well-established association of the genomic region 15q25 to lung cancer might be influenced by exposure to radon among uranium miners. Furthermore, lung cancer susceptibility is related to the functional capability of DNA damage signaling via ubiquitination processes and repair of radiation-induced double-strand breaks by the single-strand annealing mechanism.

Guo J, Qu H, Shan T, et al.
Tristetraprolin Overexpression in Gastric Cancer Cells Suppresses PD-L1 Expression and Inhibits Tumor Progression by Enhancing Antitumor Immunity.
Mol Cells. 2018; 41(7):653-664 [PubMed] Article available free on PMC after 01/11/2019 Related Publications
The RNA-binding protein tristetraprolin (TTP) binds to adenosine-uridine AU-rich elements in the 3'-untranslated region of messenger RNAs and facilitates rapid degradation of the target mRNAs. Therefore, it regulates the expression of multiple cancer and immunity-associated transcripts. Furthermore, a lack of TTP in cancer cells influences cancer progression and predicts poor survival. Although the functions of TTP on cancer cells have previously been researched, the mechanism of TTP on the interaction between cancer cells with their microenvironment remains undiscovered. In this study, we admed to determine the role of cancer cell TTP during the interaction between tumor and immune cells, specifically regulatory T cells (Tregs). We evaluate the capability of TTP to modulate the antitumor immunity of GC and explored the underlying mechanism. The overexpression of TTP in GC cells dramatically increased peripheral blood mononuclear lymphocyte (PBML) -mediated cytotoxicity against GC cells. Increased cytotoxicity against TTP-overexpressed GC cells by PBMLs was determined by Treg development and infiltration. Surprisingly, we found the stabilization of programmed death-ligand 1 (PD-L1) mRNA was declining while TTP was elevated. The PD-L1 protein level was reduced in TTP-abundant GC cells. PD-L1 gas been found to play a pivotal role in Treg development and functional maintenance in immune system. Taken together, our results suggest the overexpression of TTP in GC cells not only affects cell survival and apoptosis but also increases PBMLs -mediated cytotoxicity against GC cells to decelerate tumor progression. Moreover, we identified PD-L1 as a critical TTP-regulated factor that contributes to inhibiting antitumor immunity.

Plainvert C, Longo M, Seringe E, et al.
A clone of the emergent Streptococcus pyogenes emm89 clade responsible for a large outbreak in a post-surgery oncology unit in France.
Med Microbiol Immunol. 2018; 207(5-6):287-296 [PubMed] Related Publications
An outbreak of nosocomial infections due to Streptococcus pyogenes (Group A Streptococcus; GAS) occurred in a post-surgery oncology unit and concerned more than 60 patients and lasted 20 months despite enhanced infection control and prophylaxis measures. All GAS strains were characterized (emm genotype, toxin gene profile and pulse-field gel electrophoresis subtype). Selected strains were sequenced and phylogenetic relationship established. Capacity to form biofilm and interaction with human pulmonary epithelial cells and macrophages were determined. Twenty-six GAS strains responsible for invasive infections (II) and 57 for non-II or colonization were isolated from patients (n = 66) or healthcare workers (n = 13). Seventy strains shared the same molecular markers and 69 the same PFGE pattern; 56 were sequenced. They all belonged to the emerging emm89 clade 3; all but 1 were clonal. Whole genome sequencing identified 43 genetic profiles with sporadic mutations in regulatory genes and acquired mutations in 2 structural genes. Except for two regulatory gene mutants, all strains tested had the same biofilm formation capacity and displayed similar adherence and invasion of pulmonary epithelial cells and phagocytosis and survival in human macrophages. This large outbreak of GAS infection in a post-surgery oncology unit, a setting that contains highly susceptible patients, arose from a strain of the emergent emm89 clade. No relationship between punctual or acquired mutations, invasive status, and strain phenotypic characteristics was found. Noteworthy, the phenotypic characteristics of this clone account for its emergence and its remarkable capacity to elicit outbreaks.

Sp N, Kang DY, Kim DH, et al.
Nobiletin Inhibits CD36-Dependent Tumor Angiogenesis, Migration, Invasion, and Sphere Formation Through the Cd36/Stat3/Nf-Κb Signaling Axis.
Nutrients. 2018; 10(6) [PubMed] Article available free on PMC after 01/11/2019 Related Publications
Targeted cancer therapy with natural compounds is more effective than nontargeted therapy. Nobiletin is a flavonoid derived from citrus peel that has anticancer activity. Cluster of differentiation 36 (CD36) is a member of the class B scavenger receptor family that is involved in importing fatty acids into cells. CD36 plays a role in tumor angiogenesis by binding to its ligand, thrombospondin-1 (TSP-1), and then interacting with transforming growth factor beta 1 (TGFβ1). CD36 is implicated in tumor metastasis through its roles in fatty acid metabolism. This study investigated the molecular mechanisms underlying nobiletin's anticancer activity by characterizing its interactions with CD36 as the target molecule. We hypothesize that the anti-angiogenic activity of nobiletin involving its regulation of CD36 via signal transducer and activator of transcription 3 (STAT3) rather than through TSP-1. Gene analysis identified a Gamma interferon activation site (GAS) element in the CD36 gene promoter that acts as a STAT3 binding site, an interaction that was confirmed by ChIP assay. STAT3 interacts with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), suggesting that nobiletin also acts through the CD36/ (STAT3)/NF-κB signaling axis. Nobiletin inhibited CD36-dependent breast cancer cell migration and invasion as well as CD36-mediated tumor sphere formation. Taken together, these results suggest that nobiletin inhibits cancer stem cells in multiple ways.

Akkafa F, Koyuncu İ, Temiz E, et al.
miRNA-mediated apoptosis activation through TMEM 48 inhibition in A549 cell line.
Biochem Biophys Res Commun. 2018; 503(1):323-329 [PubMed] Related Publications
Lung has critic function in gas exchange, supplying oxygen to all cells. Rapid metastasis and the high rate of mortality characterises lung cancer. There are two types of this disease, small cell and non-small cell, which differs from each other according to histopathologic features. To date, many therapeutic approaches have been developed to destroy this deadly type of cancer, which one of them is mRNA targeted therapies through miRNA. miRNAs are 19-25 base paired molecules be able to suppress and destruct mRNA and found to be involved in development and progression of lung cancer. Transmembrane Protein 48 (TMEM48) is localised on nuclear pore complex and plays critic roles in nuclear traffic. Known that TMEM48 gene overexpressed in non-small lung cancer cells. Growing TMEM48 suppressed therapeutic studies indicated that decreased TMEM48 level might reveal a therapeutic effect for non-small cell lung cancers. TMEM48 studies based on the same strategy of gene-silencing, however, to our knowledge, any report has been published evaluates TMEM48's regulation by miRNAs. We aimed to clarify if miR-421 might be therapeutic player for non-small cancer cell lines (A549), hereby we suppressed TMEM48 by miR-421 and performed advanced molecular tests. Consequently, we recorded that while miR-421 is significantly suppressing TMEM48 expression; it increased apoptotic and tumor suppressor players CASPASE 3, PTEN and TP53 in A549 line, which is consistent with Annexin V - PI results: 30,6% of A549 observed to be apoptotic - 68,5% of A549 was in GO/G1. Our study indicated that miR-421 can suppress TMEM48 so that leads the cells to apoptosis. But it is not entirely clear how miR-421 triggers apoptosis and whether it interacts with the other cellular death pathways in A549.

Intlekofer AM, Joffe E, Batlevi CL, et al.
Integrated DNA/RNA targeted genomic profiling of diffuse large B-cell lymphoma using a clinical assay.
Blood Cancer J. 2018; 8(6):60 [PubMed] Article available free on PMC after 01/11/2019 Related Publications
We sought to define the genomic landscape of diffuse large B-cell lymphoma (DLBCL) by using formalin-fixed paraffin-embedded (FFPE) biopsy specimens. We used targeted sequencing of genes altered in hematologic malignancies, including DNA coding sequence for 405 genes, noncoding sequence for 31 genes, and RNA coding sequence for 265 genes (FoundationOne-Heme). Short variants, rearrangements, and copy number alterations were determined. We studied 198 samples (114 de novo, 58 previously treated, and 26 large-cell transformation from follicular lymphoma). Median number of GAs per case was 6, with 97% of patients harboring at least one alteration. Recurrent GAs were detected in genes with established roles in DLBCL pathogenesis (e.g. MYD88, CREBBP, CD79B, EZH2), as well as notable differences compared to prior studies such as inactivating mutations in TET2 (5%). Less common GAs identified potential targets for approved or investigational therapies, including BRAF, CD274 (PD-L1), IDH2, and JAK1/2. TP53 mutations were more frequently observed in relapsed/refractory DLBCL, and predicted for lack of response to first-line chemotherapy, identifying a subset of patients that could be prioritized for novel therapies. Overall, 90% (n = 169) of the patients harbored a GA which could be explored for therapeutic intervention, with 54% (n = 107) harboring more than one putative target.

Assmann CE, Cadoná FC, Bonadiman BDSR, et al.
Tea tree oil presents in vitro antitumor activity on breast cancer cells without cytotoxic effects on fibroblasts and on peripheral blood mononuclear cells.
Biomed Pharmacother. 2018; 103:1253-1261 [PubMed] Related Publications
The purpose of this study was to investigate some possible mechanisms underlying the in vitro antitumor activity of tea tree oil (TTO) on human and mouse breast cancer cells (MCF-7 and 4T1, respectively) and its cytotoxicity on fibroblasts (HFF-1) and on peripheral blood mononuclear cells (PBMCs). TTO High-Resolution Gas Chromatography (HRGC) showed seventeen main constituents, such as Terpinen-4-ol, γ-Terpinene, and α-Terpinene. High TTO concentrations (≥ 600 μg/mL) showed a remarkable antitumor activity, decreasing cell viability and cell proliferation of MCF-7 and 4T1 cells. TTO at 300 μg/mL increased the number of MCF-7 cells in the early stages of apoptosis and increased the BAX/BCL-2 genes ratio. TTO, mainly at 300 μg/mL, decreased cell growth and arrested MCF-7 cells in the S phase of the cell cycle. Lower antitumor concentrations (≤300 μg/mL) evaluated in MCF-7 and 4T1 cells were not cytotoxic to PBMCs and HFF-1. Also, TTO (300 μg/mL) was able to induce cell proliferation in fibroblasts after 72 h, indicating non-cytotoxic effect in these cells. TTO exhibited in vitro antitumor effect on MCF-7 and 4T1 cells by decreasing cell viability and modulating apoptotic pathways and cell cycle arrestment of MCF-7 cells. In this sense, our study provides new perspectives on the potential use of TTO for the development of new alternative therapies to treat topically locally advanced breast cancer (LABC).

Wang D, Wang L, Zhang Y, et al.
Hydrogen gas inhibits lung cancer progression through targeting SMC3.
Biomed Pharmacother. 2018; 104:788-797 [PubMed] Related Publications
Lung cancer is one of the most common lethal malignancies in the globe. The patients' prognoses are dim due to its high metastatic potential and drug resistance. Therefore, in the present study, we aim to find a more potent therapeutic approach for lung cancer. We mainly explored the function of hydrogen gas (H

Knuuttila M, Mehmood A, Mäki-Jouppila J, et al.
Intratumoral androgen levels are linked to TMPRSS2-ERG fusion in prostate cancer.
Endocr Relat Cancer. 2018; 25(9):807-819 [PubMed] Related Publications
Intratumoral androgen biosynthesis is one of the mechanisms involved in the progression of prostate cancer, and an important target for novel prostate cancer therapies. Using gas chromatography-tandem mass spectrometry and genome-wide RNA sequencing, we have analyzed androgen concentrations and androgen-regulated gene expression in cancerous and morphologically benign prostate tissue specimens and serum samples obtained from 48 primary prostate cancer patients. Intratumoral dihydrotestosterone (DHT) concentrations were significantly higher in the cancerous tissues compared to benign prostate (

Zhao R, Liang X, Zhao B, et al.
Ultrasound assisted gene and photodynamic synergistic therapy with multifunctional FOXA1-siRNA loaded porphyrin microbubbles for enhancing therapeutic efficacy for breast cancer.
Biomaterials. 2018; 173:58-70 [PubMed] Related Publications
To improve the non-invasive therapeutic efficacy for ER positive breast cancer (ER+ BC), we fabricated a multifunctional FOXA1 loaded porphyrin microbubble to combine photodynamic therapy (PDT) and gene therapy of FOXA1 knockdown (KD) with ultrasound targeted microbubble destruction (UTMD) technology under the guidance of contrast enhanced ultrasound (CEUS). Cationic porphyrin microbubbles (CpMBs) were firstly fabricated from a porphyrin grafted lipid with two cationic amino groups (PGL-NH2) and fluorocarbon inert gas of C

Stretch C, Aubin JM, Mickiewicz B, et al.
Sarcopenia and myosteatosis are accompanied by distinct biological profiles in patients with pancreatic and periampullary adenocarcinomas.
PLoS One. 2018; 13(5):e0196235 [PubMed] Article available free on PMC after 01/11/2019 Related Publications
INTRODUCTION: Pancreatic and periampullary adenocarcinomas are associated with abnormal body composition visible on CT scans, including low muscle mass (sarcopenia) and low muscle radiodensity due to fat infiltration in muscle (myosteatosis). The biological and clinical correlates to these features are poorly understood.
METHODS: Clinical characteristics and outcomes were studied in 123 patients who underwent pancreaticoduodenectomy for pancreatic or non-pancreatic periampullary adenocarcinoma and who had available preoperative CT scans. In a subgroup of patients with pancreatic cancer (n = 29), rectus abdominus muscle mRNA expression was determined by cDNA microarray and in another subgroup (n = 29) 1H-NMR spectroscopy and gas chromatography-mass spectrometry were used to characterize the serum metabolome.
RESULTS: Muscle mass and radiodensity were not significantly correlated. Distinct groups were identified: sarcopenia (40.7%), myosteatosis (25.2%), both (11.4%). Fat distribution differed in these groups; sarcopenia associated with lower subcutaneous adipose tissue (P<0.0001) and myosteatosis associated with greater visceral adipose tissue (P<0.0001). Sarcopenia, myosteatosis and their combined presence associated with shorter survival, Log Rank P = 0.005, P = 0.06, and P = 0.002, respectively. In muscle, transcriptomic analysis suggested increased inflammation and decreased growth in sarcopenia and disrupted oxidative phosphorylation and lipid accumulation in myosteatosis. In the circulating metabolome, metabolites consistent with muscle catabolism associated with sarcopenia. Metabolites consistent with disordered carbohydrate metabolism were identified in both sarcopenia and myosteatosis.
DISCUSSION: Muscle phenotypes differ clinically and biologically. Because these muscle phenotypes are linked to poor survival, it will be imperative to delineate their pathophysiologic mechanisms, including whether they are driven by variable tumor biology or host response.

Zhang B, Chen M, Zhang Y, et al.
An ultrasonic nanobubble-mediated PNP/fludarabine suicide gene system: A new approach for the treatment of hepatocellular carcinoma.
PLoS One. 2018; 13(5):e0196686 [PubMed] Article available free on PMC after 01/11/2019 Related Publications
OBJECTIVE: The purpose of this study is to generate an ultrasonic nanobubble (NB)-mediated purine nucleoside phosphorylase (PNP)/fludarabine suicide gene system for the treatment of human hepatocellular carcinoma (HCC).
METHODS: NBs were prepared from a mixture the phospholipids 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphate (DPPA), perfluoropropane gas and other materials using the high shear dispersion method. NBs treated with ultrasound irradiation functioned as a gene-transfer system, and a self-constructed suicide gene expression plasmid, pcDNA3.1(+)/PNP, treated with fludarabine functioned as a therapeutic gene. This system was used to determine the cytotoxic effects of PNP/fludarabine on HepG2 cells and SMMC7721 cells.
RESULTS: 1. NBs with a small diameter (208-416 nm) and at a high concentration and fine homogeneity were prepared under the optimal method. 2. The pcDNA3.1(+)/PNP plasmid was efficiently transfected into HCC cells using ultrasonic NBs. 3. At 0.75μg/ml fludarabine, PNP/fludarabine showed marked cytotoxic effects toward HepG2 and SMMC7721 cells. PNP/fludarabine achieved the same effect against both SMMC7721 and HepG2 cells but at a lower concentration of fludarabine for the latter. 4. Bystander effects: a 10-20% decrease in the cell survival rate was observed when only 5-10% of transfected cells were PNP positive.
CONCLUSIONS: NBs constitute a non-toxic, stable and effective gene-delivery platform. The PNP/fludarabine suicide gene system inhibited the growth of HCC cells, induced HCC cell apoptosis, and caused a notable bystander effect at a low fludarabine concentration. This study establishes an important new method for miniaturizing microbubbles and improving a new NB-mediated approach for gene therapy of HCC.

Liu HN, Wu H, Tseng YJ, et al.
Serum microRNA signatures and metabolomics have high diagnostic value in gastric cancer.
BMC Cancer. 2018; 18(1):415 [PubMed] Article available free on PMC after 01/11/2019 Related Publications
BACKGROUND: Many novel diagnostic biomarkers have been developed for gastric cancer (GC) recently. We chose two methods with high diagnostic value, the detection of serum microRNAs and metabolomics based on gas chromatography/mass spectrometry (GC/MS), and aimed to establish appropriate models.
METHODS: We reviewed the diagnostic accuracies of all microRNAs identified by previous diagnostic tests. Then appropriate microRNAs and their combinations were validated the diagnostic value. We included 80 patients with GC and 82 healthy controls (HCs) and detected the expression of the microRNAs. GC/MS analysis was conducted, and we used three multivariate statistical analyses to establish diagnostic models. The concentrations of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were detected for comparison with the novel models.
RESULTS: Sixty-seven published studies and 70 microRNAs were finally included in the systematic review. MiR-18a, miR-19a, miR-21, miR-92a, miR-199a and miR-421 were chosen to further validate their diagnostic efficiencies. Five of those microRNAs in GC patients had significantly different expression. The combination of miR-19a and miR-92a had the highest area under the curve (AUC) at 0.850 with a sensitivity of 91.3% and a specificity of 61.0%. The GC/MS analysis performed an excellent diagnostic value and the AUC reached 1.0.
CONCLUSION: There is a good potential for microRNAs and GC/MS analysis as new diagnostic methods in view of their high diagnostic value compared with traditional biomarkers.

Yan Y, Du C, Li G, et al.
CO suppresses prostate cancer cell growth by directly targeting LKB1/AMPK/mTOR pathway in vitro and in vivo.
Urol Oncol. 2018; 36(6):312.e1-312.e8 [PubMed] Related Publications
BACKGROUND: CO is a freely diffusible gas that acts as a physiological mediator of many biological and cellular processes, which has been shown to possess anticancer effect in many kinds of cancers. However, the effect of CO on prostate cancer has not been demonstrated. Therefore, we analyzed the antitumor activities and related mechanisms of CO on prostate cancer in vitro and in vivo.
METHODS: Cell viability of LNCaP and PC-3 cells after CORM-2 treatment was measured by CCK-8 assay, whereas the ATP production were detected by ATP detection assay. The early apoptosis induced by CO was evaluated by flow cytometry, and the expression level of apoptosis-related molecules (Caspases 3, 8, 9 and cleaved-Caspases 3, 8, 9) was detected using Western blot. Matrigel in vitro invasion assay was used to evaluate the effect of CO on cell invasion. We then evaluated the impact of CO on the expression of several key regulators involved in the LKB1 signaling pathway. At last, xenograft tumor in nude mice was used to further investigate the antitumor effect of CO in vivo.
RESULTS: Our results showed that CO could significantly inhibit proliferation and invasion, and induce apoptosis in human prostate cancer cell lines. The expression of LKB1 could be up-regulated after CO treatment, and CO also could increase p-AMPK levels and decrease p-mTOR. Furthermore, LKB1 knockdown could weaken the effect of CO on prostate cancer cells. In vivo, CO treatment significantly suppressed tumor growth and induced apoptosis in xenografts tumor in nude mice.
CONCLUSIONS: CO possesses striking anticancer effect in human prostate cancer cells in vitro and in vivo, which is largely mediated by LKB1-AMPK-mTOR axis.

Zhan Y, Shen L, Xu W, et al.
Functional improvements in patients with lymphangioleiomyomatosis after sirolimus: an observational study.
Orphanet J Rare Dis. 2018; 13(1):34 [PubMed] Article available free on PMC after 01/11/2019 Related Publications
BACKGROUND: Sirolimus has been shown to be effective in patients with lymphangioleiomyomatosis (LAM). We wish to summarize our experience using sirolimus and its effectiveness in LAM patients.
METHODS: We analyzed data from 98 patients who were diagnosed with definite or probable sporadic LAM based on the European Respiratory Society diagnosis criteria for LAM in 2010 at Peking Union Medical College Hospital and who had received sirolimus during January 2007 to June 2015. The data before and after the initiation of sirolimus therapy included pulmonary function tests, arterial blood gas analysis, 6-min walking distance (6MWD), size of chylous effusion and renal angiomyolipomas (AML), St. George's Respiratory Questionnaires (SGRQ) and vascular endothelial growth factor-D (VEGF-D) levels. Serum levels of sirolimus and adverse events were collected.
RESULTS: Median follow-up was 2.5 years. Most patients had forced expiratory volume in 1 s (FEV
CONCLUSION: Long-term use of sirolimus is safe in patients with LAM. LAM patients with FEV

Wu M, Xiong H, Zou H, et al.
A laser-activated multifunctional targeted nanoagent for imaging and gene therapy in a mouse xenograft model with retinoblastoma Y79 cells.
Acta Biomater. 2018; 70:211-226 [PubMed] Related Publications
Retinoblastoma (RB) is the most common intraocular malignancy of childhood that urgently needs early detection and effective therapy methods. The use of nanosized gene delivery systems is appealing because of their highly adjustable structure to carry both therapeutic and imaging agents. Herein, we report a folic acid (FA)-modified phase-changeable cationic nanoparticle encapsulating liquid perfluoropentane (PFP) and indocyanine green (ICG) (FA-CN-PFP-ICG, FCNPI) with good plasmid DNA (pDNA) carrying capacity, favorable biocompatibility, excellent photoacoustic (PA) and ultrasound (US) contrast, enhanced gene transfection efficiency and therapeutic effect. The liquid-gas phase transition of the FCNPI upon laser irradiation has provided splendid contrasts for US/PA dual-modality imaging in vitro as well as in vivo. More importantly, laser-mediated gene transfection with targeted cationic FCNPI nanoparticles demonstrated the best therapeutic effect compared with untargeted cationic nanoparticle (CN-PFP-ICG, CNPI) and neutral nanoparticle (NN-PFP-ICG, NNPI), both in vitro and in vivo. Such a multifunctional nanoagent is expected to combine dual-mode guided imaging with fewer side effects and proper therapeutic efficacy. These results establish an experimental foundation for the clinical detection of and therapy for RB.
STATEMENT OF SIGNIFICANCE: We successfully constructed a multifunctional targeted cationic nanoparticle (FCNPI) and meticulously compared the variations in the plasmid loading capacity and binding to Y79 cells with NNPI, CNPI, and FCNPI. FCNPI exhibited favorable plasmid loading capability, splendid ability for targeting and only it could provide optimal US and PA contrast to background during a considerable long time. The FCNPI/pDNA + Laser system also exhibited the best therapeutic effect in vivo; this finding proposes a potential strategy for the evaluation of an efficient gene delivery nanocarrier for gene targeting therapy of RB tumor. Our study showed that there are great advantages of targeting FCNPI to provide PA/US imaging and to enlighten laser-mediated gene transfection. FCNPI is a very helpful multifunctional agent with potential.

Shao Y, Ye G, Ren S, et al.
Metabolomics and transcriptomics profiles reveal the dysregulation of the tricarboxylic acid cycle and related mechanisms in prostate cancer.
Int J Cancer. 2018; 143(2):396-407 [PubMed] Related Publications
Genetic alterations drive metabolic reprograming to meet increased biosynthetic precursor and energy demands for cancer cell proliferation and survival in unfavorable environments. A systematic study of gene-metabolite regulatory networks and metabolic dysregulation should reveal the molecular mechanisms underlying prostate cancer (PCa) pathogenesis. Herein, we performed gas chromatography-mass spectrometry (GC-MS)-based metabolomics and RNA-seq analyses in prostate tumors and matched adjacent normal tissues (ANTs) to elucidate the molecular alterations and potential underlying regulatory mechanisms in PCa. Significant accumulation of metabolic intermediates and enrichment of genes in the tricarboxylic acid (TCA) cycle were observed in tumor tissues, indicating TCA cycle hyperactivation in PCa tissues. In addition, the levels of fumarate and malate were highly correlated with the Gleason score, tumor stage and expression of genes encoding related enzymes and were significantly related to the expression of genes involved in branched chain amino acid degradation. Using an integrated omics approach, we further revealed the potential anaplerotic routes from pyruvate, glutamine catabolism and branched chain amino acid (BCAA) degradation contributing to replenishing metabolites for TCA cycle. Integrated omics techniques enable the performance of network-based analyses to gain a comprehensive and in-depth understanding of PCa pathophysiology and may facilitate the development of new and effective therapeutic strategies.

Bourdeau RW, Lee-Gosselin A, Lakshmanan A, et al.
Acoustic reporter genes for noninvasive imaging of microorganisms in mammalian hosts.
Nature. 2018; 553(7686):86-90 [PubMed] Article available free on PMC after 01/11/2019 Related Publications
The mammalian microbiome has many important roles in health and disease, and genetic engineering is enabling the development of microbial therapeutics and diagnostics. A key determinant of the activity of both natural and engineered microorganisms in vivo is their location within the host organism. However, existing methods for imaging cellular location and function, primarily based on optical reporter genes, have limited deep tissue performance owing to light scattering or require radioactive tracers. Here we introduce acoustic reporter genes, which are genetic constructs that allow bacterial gene expression to be visualized in vivo using ultrasound, a widely available inexpensive technique with deep tissue penetration and high spatial resolution. These constructs are based on gas vesicles, a unique class of gas-filled protein nanostructures that are expressed primarily in water-dwelling photosynthetic organisms as a means to regulate buoyancy. Heterologous expression of engineered gene clusters encoding gas vesicles allows Escherichia coli and Salmonella typhimurium to be imaged noninvasively at volumetric densities below 0.01% with a resolution of less than 100 μm. We demonstrate the imaging of engineered cells in vivo in proof-of-concept models of gastrointestinal and tumour localization, and develop acoustically distinct reporters that enable multiplexed imaging of cellular populations. This technology equips microbial cells with a means to be visualized deep inside mammalian hosts, facilitating the study of the mammalian microbiome and the development of diagnostic and therapeutic cellular agents.

Falch CM, Sundaram AYM, Øystese KA, et al.
Gene expression profiling of fast- and slow-growing non-functioning gonadotroph pituitary adenomas.
Eur J Endocrinol. 2018; 178(3):295-307 [PubMed] Related Publications
OBJECTIVE: Reliable biomarkers associated with aggressiveness of non-functioning gonadotroph adenomas (GAs) are lacking. As the growth of tumor remnants is highly variable, molecular markers for growth potential prediction are necessary. We hypothesized that fast- and slow-growing GAs present different gene expression profiles and reliable biomarkers for tumor growth potential could be identified, focusing on the specific role of epithelial-mesenchymal transition (EMT).
DESIGN AND METHODS: Eight GAs selected for RNA sequencing were equally divided into fast- and slow-growing group by the tumor volume doubling time (TVDT) median (27.75 months). Data were analyzed by tophat2, cufflinks and cummeRbund pipeline. 40 genes were selected for RT-qPCR validation in 20 GAs based on significance, fold-change and pathway analyses. The effect of silencing
RESULTS: 350 genes were significantly differentially expressed (282 genes upregulated and 68 downregulated in the fast group,
CONCLUSIONS: Fast- and slow-growing GAs present different gene expression profiles, and genes related to EMT have higher expression in fast-growing tumors. In addition to

Jiménez-Garza O, Guo L, Byun HM, et al.
Aberrant promoter methylation in genes related to hematopoietic malignancy in workers exposed to a VOC mixture.
Toxicol Appl Pharmacol. 2018; 339:65-72 [PubMed] Related Publications
Occupational exposure to volatile organic compounds (VOCs) may cause hematopoietic malignancy, either by single exposure to benzene or possibly due to a concomitant exposure to several VOCs. Since oxidative stress, inflammation and DNA repair pathways are closely involved in cancer development, the effect of VOC exposure on expression of proteins involved in these pathways has been studied, but epigenetic changes have not been well described. Here, DNA methylation status following occupational exposure to a VOC mixture was assessed by bisulfite sequencing of the promoter regions of seven genes involved in the mentioned pathways. Peripheral blood samples and individual-level VOC exposure data were obtained from healthy leather shoe factory workers (LS, n=40) and gas station attendants (GS, n=36), as well as a reference group of university employees (C, n=66). Exposure levels for acetone, ethylbenzene, methyl ethyl ketone, n-hexane, toluene and xylene were higher in LS (p<0.001); benzene and methyl acetate levels were higher in GS (p<0.001). TOP2A, SOD1, and TNF-α promoter methylation status was increased in LS (p<0.05). In LS, we also found significant correlations between GSTP1 promoter methylation and both iNOS (r=0.37, p=0.008) and COX-2 (r=-0.38, p=0.007) methylation. In exposed groups, ethylbenzene exposure levels showed a significant correlation with TOP2A methylation (β=0.33). Our results show early, toxic effects at the epigenetic level caused by occupational exposure to high levels of a VOC mixture. These subcellular modifications may represent the initial mechanism of toxicity leading to hematopoietic malignancy, possibly due to a synergistic, hematotoxic effect of VOC mixtures.

Cattaneo ER, Prieto ED, Garcia-Fabiani MB, et al.
Glycerol-3-phosphate acyltransferase 2 expression modulates cell roughness and membrane permeability: An atomic force microscopy study.
PLoS One. 2017; 12(12):e0189031 [PubMed] Article available free on PMC after 01/11/2019 Related Publications
In mammalian cells, de novo glycerolipid synthesis begins with the acylation of glycerol-3-phosphate, catalyzed by glycerol-3-phosphate acyltransferases (GPAT). GPAT2 is a mitochondrial isoform primarily expressed in testis under physiological conditions, and overexpressed in several types of cancers and cancer-derived human cell lines where its expression contributes to the tumor phenotype. Using gene silencing and atomic force microscopy, we studied the correlation between GPAT2 expression and cell surface topography, roughness and membrane permeability in MDA-MB-231 cells. In addition, we analyzed the glycerolipid composition by gas-liquid chromatography. GPAT2 expression altered the arachidonic acid content in glycerolipids, and the lack of GPAT2 seems to be partially compensated by the overexpression of another arachidonic-acid-metabolizing enzyme, AGPAT11. GPAT2 expressing cells exhibited a rougher topography and less membrane damage than GPAT2 silenced cells. Pore-like structures were present only in GPAT2 subexpressing cells, correlating with higher membrane damage evidenced by lactate dehydrogenase release. These GPAT2-induced changes are consistent with its proposed function as a tumor-promoting gene, and might be used as a phenotypic differentiation marker. AFM provides the basis for the identification and quantification of those changes, and demonstrates the utility of this technique in the study of cancer cell biology.

Disclaimer: This site is for educational purposes only; it can not be used in diagnosis or treatment.

Cite this page: Cotterill SJ. GAST, Cancer Genetics Web: Accessed:

Creative Commons License
This page in Cancer Genetics Web by Simon Cotterill is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
Note: content of abstracts copyright of respective publishers - seek permission where appropriate.

 [Home]    Page last revised: 30 August, 2019     Cancer Genetics Web, Established 1999