Fatty Acid Binding Protein 5 (FABP5) Promotes Aggressiveness of Gastric Cancer Through Modulation of Tumor Immunity

Shu Zhang,Mei-qing Qiu,Hui-jun Wang,Ya-fei Ju,Zhen Liu,Tao Wang,Shi-feng Kan,Zhen Yang,Ya-yun Cui,You-qiang Ke,Hong-min He,Li Sun 대한위암학회 2023 Journal of gastric cancer Vol.23 No.2

Purpose: Gastric cancer (GC) is the second most lethal cancer globally and is associated with poor prognosis. Fatty acid-binding proteins (FABPs) can regulate biological properties of carcinoma cells. FABP5 is overexpressed in many types of cancers; however, the role and mechanisms of action of FABP5 in GC remain unclear. In this study, we aimed to evaluate the clinical and biological functions of FABP5 in GC. Materials and Methods: We assessed FABP5 expression using immunohistochemical analysis in 79 patients with GC and evaluated its biological functions following in vitro and in vivo ectopic expression. FABP5 targets relevant to GC progression were determined using RNA sequencing (RNA-seq). Results: Elevated FABP5 expression was closely associated with poor outcomes, and ectopic expression of FABP5 promoted proliferation, invasion, migration, and carcinogenicity of GC cells, thus suggesting its potential tumor-promoting role in GC. Additionally, RNA-seq analysis indicated that FABP5 activates immune-related pathways, including cytokine-cytokine receptor interaction pathways, interleukin-17 signaling, and tumor necrosis factor signaling, suggesting an important rationale for the possible development of therapies that combine FABP5-targeted drugs with immunotherapeutics. Conclusions: These findings highlight the biological mechanisms and clinical implications of FABP5 in GC and suggest its potential as an adverse prognostic factor and/or therapeutic target.

Association of Dietary Intake of Folate, Vitamin B₆ and B₁₂ and MTHFR Genotype with Breast Cancer Risk

Liu, Ying,Zhou, Long-Shu,Xu, Xiao-Ming,Deng, Liang-Qing,Xiao, Qian-Kun Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.9

Aim: We aimed to investigate the associations of dietary intake of folate, vitamin $B_6$ and $B_{12}$ and MTHFR genotype with breast cancer in a Chinese population. Methods: A matched case-control study was conducted, and 435 patients with newly diagnosed and histologically confirmed breast cancer and 435 controls were collected. The folate intake, vitamin $B_6$ and vitamin $B_{12}$ were calculated, and MTHFR C665T, C677T and A1298C were analyzed by PCR-RFLP. Results: We found vitamin $B_{12}$ was likely to reduce the risk of breast cancer, and MTHFR 665TT was associated with increased risk of breast cancer. Folate intake, vitamin $B_{12}$ intake and variants of MTHFR C677T and MTHFR A1298C demonstrated no association with risk of breast cancer. However, we found patients with low intake of vitamin $B_6$ and MTHFR 665TT genotype had a higher risk of breast cancer (OR=1.87, 95% CI=1.29-2.77), the association being less pronounced among subjects with a moderate intake of vitamin $B_6$ and MTHFR 665TT genotype (OR=1.58, 95% CI=1.03-2.49, P=0.03). Conclusion: Our study indicated that the MTHFR C665T polymorphism and vitamin $B_6$ are associated with risk of breast cancer, which indicated roles for nutrients in developing breast cancer.

Synthesis and In Vitro Cytotoxicity of Cis-[Pt(NH3)(NH2OH)Cl2]

Qing-Song Ye,Xi-Zhu Chen,Yao Yu,Qiao-Wen Chang,Shu-Qian Hou,Wei-Ping Liu 대한약학회 2010 Archives of Pharmacal Research Vol.33 No.6

A novel mixed NH3/NH2OH platinum(II) complex cis-[Pt(NH3)(NH2OH)Cl2] was synthesized and characterized by elemental analysis, FAB-MS, FT-IR and 1H NMR spectroscopy. This complex was determined to have a good water-solubility and satisfactory stability. The pertinent complex was evaluated for its in vitro cytotoxicity against 3AO, HCT-116, LNcap, A549/ATCC and SGC-7901 human carcinoma cell lines. It shows appreciable cytotoxic activity that is comparable with cisplatin and is much more active than carboplatin.

Association of Single Nucleotide Polymorphisms in the Prostaglandin-endoperoxide Synthase 2 (PTGS2) and Phospholipase A₂ Group IIA (PLA2G2A) Genes with Susceptibility to Esophageal Squamous Cell Carcinoma

Liu, Fen,Wei, Wen-Qiang,Cormier, Robert T.,Zhang, Shu-Tian,Qiao, You-Lin,Li, Xin-Qing,Zhu, Sheng-Tao,Zhai, Yan-Chun,Peng, Xiao-Xia,Yan, Yu-Xiang,Wu, Li-Juan,He, Dian,He, Yan Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.4

Background: The prostaglandin-endoperoxide synthase 2 (PTGS2) and phospholipase A2 group IIA (PLA2G2A) genes encode enzymes that are involved in arachidonic acid and prostaglandin biosynthesis. Dysregulation of both genes is associated with inflammation and carcinogenesis, including esophageal squamous cell carcinoma (ESCC). We therefore hypothesized that there is an association between single nucleotide polymorphisms (SNPs) in these genes and susceptibility to ESCC. Methods: We performed a gene-wide tag SNP-based association study to examine the association of SNPs in PTGS2 and PLA2G2A with ESCC in 269 patients and 269 healthy controls from Taihangshan Mountain, Henan and Hebei Provinces, the rural area of China which has the highest incidence of esophageal cancer in the world. Thirteen tag SNPs in PLA2G2A and 4 functional SNPs in PTGS2 were selected and genotyped using a high-throughput Mass Array genotyping platform. Results: We found a modest increased risk of ESCC in subjects with the PTGS2 rs12042763 AA genotype (OR=1.23; 95% CI, 1.00-3.04) compared with genotype GG. For PLA2G2A, a decreased risk of ESCC was observed in subjects with the rs11677 CT (OR=0.51, 95%CI, 0.29-0.85) or TT genotype (OR=0.51, 95%CI, 0.17-0.96) or the T carriers (CT+TT) (OR=0.52, 95%CI, 0.31-0.85) when compared with the CC genotype. Also for PLA2G2A, rs2236771 C allele carriers were more frequent in the control group (P=0.02). Subjects with the GC (OR=0.55, 95%CI, 0.33-0.93) or CC genotype (OR=0.38, 95% CI, 0.16-0.94) or the C carriers (GC+CC) (OR=0.52, 95%CI, 0.32-0.85) showed a negative association with ESCC susceptibility. Conclusions: Our results suggest that PTGS2 and PLA2G2A gene polymorphisms may modify the risk of ESCC development.

Dietary Factors and Risk of Pancreatic Cancer: a Multi-Centre Case-Control Study in China

Liu, Shu-Zheng,Chen, Wan-Qing,Wang, Ning,Yin, Meng-Meng,Sun, Xi-Bin,He, Yu-Tong Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.18

Background: Pancreatic cancer is the sixth leading cause of cancer death with an increasing trend in China. Dietary intake is believed to play an important role in pancreatic cancer carcinogenesis. The aim of this paper was to evaluate associations between some dietary factors and risk of pancreatic cancer in a multi-centre case-control study conducted in China. Materials and Methods: Cases (n=323) were ascertained from four provincial cancer hospitals. Controls (n=323) were randomly selected from the family members of patients without pancreatic cancer in the same hospitals, 1:1 matched to cases by gender, age and study center. Data were collected with a questionnaire by personal interview. Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated using conditional logistic regression. Results: Tea intake (OR =0.49; 95%CI: 0.30-0.80) was associated with a half reduction in risk of pancreatic cancer. Reduced vegetable consumption (P trend: 0.04) was significant related to pancreatic cancer. Although no significant association was found for meat and fruit, ORs were all above or below the reference group. A protective effect was found for fruit (OR=1.73 for consumption of 1-2 times/week vs more than 3 times/week; 95%CI: 1.05-2.86). A high intake of meat was associated to a higher risk of pancreatic cancer (OR=0.59 for consumption of 1-2 times/week vs. more than 3 times/week; 95%CI: 0.35-0.97). Conclusions: The present study supports fruit consumption to reduce pancreatic cancer risk and indicates that high consumption of meat is related to an elevated risk. Direct inverse relations with tea and vegetable intake were also confirmed.

Enhanced ε-Poly-L-lysine Production from Streptomyces ahygroscopicus by a Combination of Cell Immobilization and In Situ Adsorption

( Liu Sheng Rong ),( Qing Ping Wu ),( Ju Mei Zhang ),( Shu Ping Mo ),( Xiao Juan Yang ),( Chun Xiao ) 한국미생물 · 생명공학회 2012 Journal of microbiology and biotechnology Vol.22 No.9

ε-Poly-L-lysine (ε-PL), produced by Streptomyces or Kitasatospora strains, is a homo-poly-amino acid of Llysine, which is used as a safe food preservative. The present study investigates the combined use of cell immobilization and in situ adsorption (ISA) to produce ε-PL in shaken flasks. Loofah sponge-immobilized Streptomyces ahygroscopicus GIM8 produced slightly more ε-PL than those immobilized on synthetic sponge, and sugarcane bagasse. Moreover, loofah sponge supported the maximum biomass. Hence, loofah sponge was chosen for cell immobilization. Meanwhile, the ion-exchange resin D152 was employed for ISA. The loofah sponge-immobilized cells produced 0.54 ± 0.1 g/l ε-PL, which significantly increased to 3.64 ± 0.32 g/l after combining with ISA through the addition of resin bags. The free cells with ISA using the dispersed resin yielded 2.73 ± 0.26 g/l of ε-PL, an increase from 0.82 ± 0.08 g/l. These data illustrate that the proposed combination method improved production most significantly compared with either immobilization or ISA only. Moreover, the immobilized cells could be repeatedly used and an ε-PL total amount of 8.05 ± 0.84 g/l was obtained. The proposed combination method offers promising perspectives for ε-PL production.

A Novel Multifocus Image Fusion Algorithm Based on Nonsubsampled Contourlet Transform

( Cuiyin Liu ),( Peng Cheng ),( Shu-qing Chen ),( Cuiwei Wang ),( Fenghong Xiang ) 한국인터넷정보학회 2013 KSII Transactions on Internet and Information Syst Vol.7 No.3

A novel multifocus image fusion algorithm based on NSCT is proposed in this paper. In order to not only attain the image focusing properties and more visual information in the fused image, but also sensitive to the human visual perception, a local multidirection variance (LEOV) fusion rule is proposed for lowpass subband coefficient. In order to introduce more visual saliency, a modified local contrast is defined. In addition, according to the feature of distribution of highpass subband coefficients, a direction vector is proposed to constrain the modified local contrast and construct the new fusion rule for highpass subband coefficients selection The NSCT is a flexible multiscale, multidirection, and shift-invariant tool for image decomposition, which can be implemented via the atrous algorithm. The proposed fusion algorithm based on NSCT not only can prevent artifacts and erroneous from introducing into the fused image, but also can eliminate `block effect` and `frequency aliasing` phenomenon. Experimental results show that the proposed method achieved better fusion results than wavelet-based and CT-based fusion method in contrast and clarity.

Prognostic Significance of Interactions Between ER Alpha and ER Beta and Lymph Node Status in Breast Cancer Cases

Han, Shu-Jing,Guo, Qing-Qing,Wang, Ting,Wang, You-Xin,Zhang, Yu-Xiang,Liu, Fen,Luo, Yan-Xia,Zhang, Jie,Wang, You-Li,Yan, Yu-Xiang,Peng, Xiao-Xia,Ling, Rui,He, Yan Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.10

Objective: Both estrogen receptors, ER alpha ($ER{\alpha}$) and ER beta ($ER{\beta}$), are expressed in 50-70% of breast cancer cases. The role of $ER{\alpha}$ as a prognostic marker in breast cancer has been well established as its expression is negative correlated with tumor size and lymph node metastasis. $ER{\beta}$ is also a favorable prognostic predictor although this is less well documented than for $ER{\alpha}$. Materials and Methods: To explore whether ERs independently or together might influence clinical outcome in breast cancer, the correlation between the ERs with the clinicopathological features was analyzed in 84 patients. Results: $ER{\alpha}$ expression negatively correlated with tumor stage (r=-0.246, p=0.028) and tended to be negatively correlated with lymph node status (r=-0.156, p=0.168) and tumor size (r=-0.246, p=0.099). Also, $ER{\beta}$ was negatively correlated with nodal status (r=-0.243, p=0.028), as was coexpression of $ER{\alpha}$ and $ER{\beta}$ (p=0.043, OR=0.194, 95% CI= 0.040-0.953). Conclusion: Coexpression of ERs might serve as an indicator of good prognosis in breast cancer patients.

Increased Serotonin Signaling Contributes to the Warburg Effect in Pancreatic Tumor Cells Under Metabolic Stress and Promotes Growth of Pancreatic Tumors in Mice

Jiang, Shu-Heng,Li, Jun,Dong, Fang-Yuan,Yang, Jian-Yu,Liu, De-Jun,Yang, Xiao-Mei,Wang, Ya-Hui,Yang, Min-Wei,Fu, Xue-Liang,Zhang, Xiao-Xin,Li, Qing,Pang, Xiu-Feng,Huo, Yan-Miao,Li, Jiao,Zhang, Jun-Feng Elsevier 2017 Gastroenterology Vol.153 No.1

<P><B>Background & Aims</B></P> <P>Desmoplasia and poor vascularity cause severe metabolic stress in pancreatic ductal adenocarcinomas (PDACs). Serotonin (5-HT) is a neuromodulator with neurotransmitter and neuroendocrine functions that contributes to tumorigenesis. We investigated the role of 5-HT signaling in the growth of pancreatic tumors.</P> <P><B>Methods</B></P> <P>We measured the levels of proteins that regulate 5-HT synthesis, packaging, and degradation in pancreata from Kras<SUP>G12D/+</SUP>/Trp53<SUP>R172H/+</SUP>/Pdx1-Cre (KPC) mice, which develop pancreatic tumors, as well as in PDAC cell lines and a tissue microarray containing 81 human PDAC samples. We also analyzed expression levels of proteins involved in 5-HT synthesis and degradation by immunohistochemical analysis of a tissue microarray containing 311 PDAC specimens, and associated expression levels with patient survival times. 5-HT level in 14 matched PDAC tumor and non-tumor tissues were analyzed by ELISA. PDAC cell lines were incubated with 5-HT and cell survival and apoptosis were measured. We analyzed expression of the 5-HT receptor HTR2B in PDAC cells and effects of receptor agonists and antagonists, as well as HTR2B knockdown with small hairpin RNAs. We determined the effects of 5-HT stimulation on gene expression profiles of BxPC-3 cells. Regulation of glycolysis by 5-HT signaling via HTR2B was assessed by immunofluorescence and immunoprecipitation analyses, as well as by determination of the extracellular acid ratio, glucose consumption, and lactate production. Primary PDACs, with or without exposure to SB204741 (a selective antagonist of HTR2B), were grown as xenograft tumors in mice, and SB204741 was administered to tumor-bearing KPC mice; tumor growth and metabolism were measured by imaging analyses.</P> <P><B>Results</B></P> <P>In immunohistochemical analysis of a tissue microarray of PDAC specimens, increased levels of TPH1 and decreased level of MAOA, which regulate 5-HT synthesis and degradation, correlated with stage and size of PDACs and shorter patient survival time. We found levels of 5-HT to be increased in human PDAC tissues compared with non-tumor pancreatic tissues, and PDAC cell lines compared with non-transformed pancreatic cells. Incubation of PDAC cell lines with 5-HT increased proliferation and prevented apoptosis. Agonists of HTR2B, but not other 5-HT receptors, promoted proliferation and prevented apoptosis of PDAC cells. Knockdown of HTR2B in PDAC cells, or incubation of cells with HTR2B inhibitors, reduced their growth as xenograft tumors in mice. We observed a correlation between 5-HT and glycolytic flux in PDAC cells; levels of metabolic enzymes involved in glycolysis, the phosphate pentose pathway, and hexosamine biosynthesis pathway increased significantly in PDAC cells following 5-HT stimulation. 5-HT stimulation led to formation of the HTR2B–LYN–p85 complex, which increased PI3K–Akt–mTOR signaling and the Warburg effect by increasing protein levels of MYC and HIF1A. Administration of SB204741 to KPC mice slowed growth and metabolism of established pancreatic tumors and prolonged survival of the mice.</P> <P><B>Conclusions</B></P> <P>Human PDACs have increased levels of 5-HT, and PDAC cells increase expression of its receptor, HTR2B. These increases allow for tumor glycolysis under metabolic stress and promote growth of pancreatic tumors and PDAC xenograft tumors in mice.</P>

Adherence to Cancer Prevention Guidelines and Endometrial Cancer Risk: Evidence from a Systematic Review and Dose-Response Meta-analysis of Prospective Studies

Hui Sun,Qing Chang,Ya-Shu Liu,Yu-Ting Jiang,Ting-Ting Gong,Xiao-Xin Ma,Yu-Hong Zhao,Qi-Jun Wu 대한암학회 2021 Cancer Research and Treatment Vol.53 No.1

Purpose The evidence of adherence to cancer prevention guidelines and endometrial cancer (EC) risk has been limited and controversial. This study summarizes and quantifies the relationship between adherence to cancer prevention guidelines and EC risk. Materials and Methods The online databases PubMed, Web of Science, and EMBASE were searched for relevant publications up to June 2, 2020. This study had been registered at PROSPERO. The registration number is CRD42020149966. Study quality evaluation was performed based on the Newcastle-Ottawa Scale. The I2 statistic was used to estimate heterogeneity among studies. Egger’s and Begg’s tests assessed potential publication bias. Summary hazard ratios (HRs) and 95% confi dence intervals (CIs) for the relationship between adherence to cancer prevention guidelines score was assigned to participants by summarizing individual scores for each lifestyle-related factor. The scores ranged from least healthy (0) to most healthy (20) and the EC risk was calculated using a random-effects model. Results Five prospective studies (four cohort studies and one case‑cohort study) consisted of 4,470 EC cases, where 597,047 participants were included. Four studies had a low bias risk and one study had a high bias risk. Summary EC HR for the highest vs. lowest score of adherence to cancer prevention guidelines was 0.54 (95% CI, 0.40 to 0.73) and had a high heterogeneity (I2=86.1%). For the dose-response analysis, an increment of 1 significantly reduced the risk of EC by 6%. No signifi cant publication bias was detected. Conclusion This study suggested that adherence to cancer prevention guidelines was negatively related to EC risk.